Developing a workplace resilience instrument.
Resilience benefits from the use of protective factors, as opposed to risk factors, which are associated with vulnerability. Considerable research and instrument development has been conducted in clinical settings for patients. The need existed for an instrument to be developed in a workplace setting to measure resilience of employees. This study developed and tested a resilience instrument for employees in the workplace. The research instrument was distributed to executives and nurses working in the United States in hospital settings. Five-hundred-forty completed and usable responses were obtained. The instrument contained an inventory of workplace resilience, a job stress questionnaire, and relevant demographics. The resilience items were written based on previous work by the lead author and inspired by Weick's [1] sense-making theory. A four-factor model yielded an instrument having psychometric properties showing good model fit. Twenty items were retained for the resulting Workplace Resilience Instrument (WRI). Parallel analysis was conducted with successive iterations of exploratory and confirmatory factor analyses. Respondents were classified based on their employment with either a rural or an urban hospital. Executives had significantly higher WRI scores than nurses, controlling for gender. WRI scores were positively and significantly correlated with years of experience and the Brief Job Stress Questionnaire. An instrument to measure individual resilience in the workplace (WRI) was developed. The WRI's four factors identify dimensions of workplace resilience for use in subsequent investigations: Active Problem-Solving, Team Efficacy, Confident Sense-Making, and Bricolage.


Structural characterisation of a water-soluble polysaccharide from tissue-cultured Dendrobium huoshanense C.Z. Tang et S.J. Cheng.
A water-soluble polysaccharide TC-DHPA4 with a molecular weight of 8.0 × 105 Da was isolated from tissue-cultured Dendrobium huoshanense by anion exchange and gel permeation chromatography. Monosaccharide analysis revealed that the homogeneous polysaccharide was made up of rhamnose, arabinose, mannose, glucose, galactose and glucuronic acid with a molar ratio of 1.28:1:1.67:4.71:10.43:1.42. The sugar residue sequence analysis based on the GC-MS files and NMR spectra indicated that the backbone of TC-DHPA4 consisted of the repeated units:→6)-β-Galp-(1→6)-β-Galp-(1→4)-β-GlcpA-(1→6)-β-Glcp-(1→6)-β-Glcp-(→. The sugar residue sequences β-Glcp-(1→)-α-Rhap-(1→3)-β-Galp-(1→, β-Glcp-(1→4)-α-Rhap-(1→3)-β-Galp-(1→, β-Galp-(1→6)-β-Manp-(1→3)-β-Galp-(1→, and α-l-Araf-(1→2)-β-Manp-(1→3)-β-Galp-(1→ were identified as the branches attached to the C-3 position of (1→6)-linked galactose in the backbone.


Reversible control of free energy and topography of nanostructured surfaces.
We describe a facile method for the formation of dynamic nanostructured surfaces based on the modification of porous anodic aluminum oxide with poly(N-isopropyl acrylamide) (PNIPAAm) via surface-initiated atom transfer radical polymerization. The dynamic structure of these surfaces was investigated by atomic force microscopy (AFM), which showed dramatic changes in the surface nanostructure above and below the aqueous lower critical solution temperature of PNIPAAm. These changes in surface structure are correlated with changes in the macroscopic wettability of the surfaces, which was probed by water contact angle measurements. Principal component analysis was used to develop a quantitative correlation between AFM image intensity histograms and macroscopic wettability. Such correlations and dynamic nanostructured surfaces may have a variety of uses.


Quantification of the uptake of silver nanoparticles and ions to HepG2 cells.
The toxic mechanism of silver nanoparticles (AgNPs) is still debating, partially because of the common co-occurrence and the lack of methods for separation of AgNPs and Ag(+) in biological matrices. For the first time, Triton-X 114-based cloud point extraction (CPE) was proposed to separate AgNPs and Ag(+) in the cell lysates of exposed HepG2 cells. Cell lysates were subjected to CPE after adding Na2S2O3, which facilitated the transfer of AgNPs into the nether Triton X-114-rich phase by salt effect and the preserve of Ag(+) in the upper aqueous phase through the formation of hydrophilic complex. Then the AgNP and Ag(+) contents in the exposed cells were determined by ICP-MS after microwave digestion of the two phases, respectively. Under the optimized conditions, over 67% of AgNPs in cell lysates were extracted into the Triton X-114-rich phase while 94% of Ag(+) remained in the aqueous phase, and the limits of detection for AgNPs and Ag(+) were 2.94 μg/L and 2.40 μg/L, respectively. This developed analytical method was applied to quantify the uptake of AgNPs to the HepG2 cells. After exposure to 10 mg/L AgNPs for 24 h, about 67.8 ng Ag were assimilated per 10(4) cells, in which about 10.3% silver existed as Ag(+). Compared to the pristine AgNPs (with 5.2% Ag(+)) for exposure, the higher ratio of Ag(+) to AgNPs in the exposed cells (10.3% Ag(+)) suggests the transformation of AgNPs into Ag(+) in the cells and/or the higher uptake rate of Ag(+) than that of AgNPs. Given that the toxicity of Ag(+) is much higher than that of AgNPs, the substantial content of Ag(+) in the exposed cells suggests that the contribution of Ag(+) should be taken into account in evaluating the toxicity of AgNPs to organisms, and previous results obtained by regarding the total Ag content in organisms as AgNPs should be reconsidered.


Abnormal patterns of tongue-palate contact in the speech of individuals with cleft palate.
Individuals with cleft palate, even those with adequate velopharyngeal function, are at high risk for disordered lingual articulation. This article attempts to summarize current knowledge of abnormal tongue-palate contact patterns derived from electropalatographic (EPG) data in speakers with cleft palate. These data, which have been reported in 23 articles published over the past 20 years, have added significantly to our knowledge about cleft palate speech. Eight abnormal patterns of tongue-palate contact are described and illustrated with data from children and adults with repaired cleft palate. The paper also discusses some of the problems in interpreting EPG data from speakers with abnormal craniofacial anatomy and emphasizes the importance of quantifying relevant aspects of tongue-palate contact data. Areas of research requiring further investigation are outlined.


Immune activation markers and AIDS prognosis.
Four assays for serum levels of cellular products of immune activation were examined as prognostic markers for AIDS in a prospective study of asymptomatic HIV-seropositive homosexual men. Baseline serum values of beta 2-microglobulin (beta 2M), neopterin, soluble CD8 (sCD8), and soluble interleukin-2 receptor (sIL-2R) for 185 men were examined univariately and multivariately as predictors of AIDS during 36 months of follow-up. Thirty-three cases of AIDS (18%) were diagnosed during the follow-up period. All four assays correlated highly with each other (r = 0.48-0.63), and all four were good univariate predictors of AIDS and comparable to CD4 lymphocyte count. beta 2M, neopterin, and sCD8 predicted AIDS independently of both CD4 count and HIV p24 antigen or p24 antibody in multivariate analysis. Within the range of CD4 count 200-499 x 10(6) cells/l, an immune activation marker used in combination with an assay for p24 antigen identifies those at 3-6% risk of AIDS over 36 months (low risk on both assays) and those at 63-86% risk (high risk on both assays). These results can be used to guide physicians and patients making decisions about treating asymptomatic HIV infection with zidovudine in individuals with CD4 lymphocyte count of 200-499 x 10(6) cells/l.


Using peer-assisted learning and role-playing to teach generic skills to dental students: the health care simulation model.
Increasing importance is attached to teaching generic skills to undergraduate students in various disciplines. This article describes an extracurricular, student-led activity for teaching generic skills using the Model United Nations over three months. The activity used the Health Care Simulation Model (HCSM) with peer learning and role-playing to accomplish its objectives. An interview was used to select from undergraduate and postgraduate dental students at Alexandria University, Alexandria, Egypt, to develop a group of staff to act as peer teachers after receiving training (n=77). These peer teachers provided training for 123 undergraduate dental students to serve as delegates who acted as trainees or peer learners. At the end of the training sessions, a conference was held in which the students played the roles of delegates representing officials responsible for health care systems in ten countries. The students reported improvement in generic skills, enjoyed several aspects of the experience, and disliked other aspects of the model to a lesser extent. In multivariate analysis, perceived usefulness of the HCSM was significantly greater for staff than delegates and increased as self-reported improvement in knowledge of health care systems increased. This study suggests that innovative, student-centered educational methods can be effective for teaching generic skills and factual information.


Remote physiological ischemic training promotes coronary angiogenesis via molecular and cellular mobilization after myocardial ischemia.
This study was designed to explore the mechanism of physiological ischemic training (PIT) on remote limbs, with a special focus on the potential role of endothelial progenitor cells (EPCs), vascular endothelial growth factor (VEGF), and nitric oxide (NO) in local ischemic myocardium. Myocardial ischemia (MI) rabbit models were randomly assigned to sham-operated group (SO), training-only group (TO), MI group, PIT group, VEGF inhibitor group (VEGF-), NO inhibitor group (NO-), VEGF and NO inhibitor group (VEGF-/NO-), and EPC inhibitor group (EPC-). A constrictor was implanted around the left ventricular branch to induce controlled MI. The PIT procedure consisted of three cycles of a 3-minutes cuff inflation on the hindlimbs with a reperfusion of 5 minutes. Plasma and myocardial EPC numbers, VEGF level, and NO concentration, as well as capillary density (CD), coronary blood flow (CBF), and coronary collateral blood flow (CCBF) in myocardium, were measured. Nonparametric statistical techniques were applied to identify the differences between groups, and regression models were used to detect correlations between agents. VEGF levels, NO concentrations, and also EPC counts in both plasma and myocardium were highest in the PIT group. Capillary density, CCBF, and CCBF/CBF were also statistically elevated in the PIT group. VEGF explained 74% of variance in NO. NO explained 65% of variance in EPCs. EPCs explained 68% of variance in capillary density. Capillary density explained 78% of variance in CCBF and CCBF/CBF. PIT mobilized EPCs and promoted revascularization through upregulating VEGF and NO level.


Immunometric Antibody Sandwich Enzyme-Linked Immunosorbent Assay.
The antibody sandwich enzyme-linked immunosorbent assay (ELISA) is the most commonly used assay for rapid and accurate detection of antigens. It displays greater sensitivity compared with the indirect ELISA and can be used to determine absolute antigen concentrations in unknown samples provided purified antigen standards are available, although it requires the use of two different antibodies. Briefly, wells are coated with antigen-specific capture antibody then incubated with samples containing unknown antigen. Washing removes unbound antigen and exogenous sample protein before incubation with a second antigen-specific detection antibody, washing, and reincubation with a reporter-labeled tertiary antibody. After tertiary antibody is washed off, substrate is added and hydrolysis is measured spectrophotometrically. The signal intensity is directly proportional to the concentration of the antigen in the test sample.


Sediment Resuspension and Deposition on Seagrass Leaves Impedes Internal Plant Aeration and Promotes Phytotoxic H2S Intrusion.
HIGHLIGHTS: Sedimentation of fine sediment particles onto seagrass leaves severely hampers the plants' performance in both light and darkness, due to inadequate internal plant aeration and intrusion of phytotoxic H2S. Anthropogenic activities leading to sediment re-suspension can have adverse effects on adjacent seagrass meadows, owing to reduced light availability and the settling of suspended particles onto seagrass leaves potentially impeding gas exchange with the surrounding water. We used microsensors to determine O2 fluxes and diffusive boundary layer (DBL) thickness on leaves of the seagrass Zostera muelleri with and without fine sediment particles, and combined these laboratory measurements with in situ microsensor measurements of tissue O2 and H2S concentrations. Net photosynthesis rates in leaves with fine sediment particles were down to ~20% of controls without particles, and the compensation photon irradiance increased from a span of 20-53 to 109-145 μmol photons m-2 s-1. An ~2.5-fold thicker DBL around leaves with fine sediment particles impeded O2 influx into the leaves during darkness. In situ leaf meristematic O2 concentrations of plants exposed to fine sediment particles were lower than in control plants and exhibited long time periods of complete meristematic anoxia during night-time. Insufficient internal aeration resulted in H2S intrusion into the leaf meristematic tissues when exposed to sediment resuspension even at relatively high night-time water-column O2 concentrations. Fine sediment particles that settle on seagrass leaves thus negatively affect internal tissue aeration and thereby the plants' resilience against H2S intrusion.


The growth of polio virus in human diploid fibroblasts grown with cellulose microcarriers in suspension cultures.
Human diploid fibroblasts have been successfully grown with cellulose fiber microcarriers in suspension giving values of between 1 to 2 X 10(6) cells/ml. When infected with polio virus type 1 titers were obtained which were at least as good or better than those obtained with monkey kidney cells and similar to that obtained with Vero cells. Good results were also obtained using conventional microcarriers such as Cytodex, Biosilon and Gelibeads. Our results suggest that many of the technical difficulties in growing human diploid fibroblasts on microcarriers can be overcome allowing these cells to be a favourable alternative to heteroploid cells as a substrate for viral vaccine production.


The Socioeconomic Impact of Surgical Site Infections.
Précis: Surgical site infections are an ever-increasing phenomenon worldwide due to different factors. This brief report aimeds to highlight at a glance, for both physicians and political and institutional leaders, the economic burden of surgical site infections. Objectives: This brief report aimed to highlight the economic burden of surgical site infections (SSIs). Methods: A narrative review focusing on this subject has been carried out. Results: Surgical site infections are responsible for generating important costs. In 2017, a French cohort highlighted a mean cost of each SSI treatment to be around €1,814; the same year, the Centers for Disease Control and Prevention guidelines evaluated the mean cost caused by SSI treatment to be from $10,443 to $25,546 per SSI. This cost depends on many factors including the patient himself and the type of surgery. Conclusions: Prevention of the risk of infection is, therefore, a profitable concept for surgery that must be integrated within all healthcare managements worldwide.


Peripheral sensory nerve dysfunction in children and adolescents with type 1 diabetes mellitus.
The aim of the present study was to investigate peripheral sensory nerve function in diabetic children and adolescents without neurological symptoms. Ninety-two children and adolescents with Type 1 (insulin-dependent) diabetes mellitus (mean +/- SD age: 14.2 +/- 2.1 years, diabetes duration: 5.8 +/- 3.0 years) and 80 healthy control subjects (age: 13.8 +/- 2.2 years) matched for age, sex, body mass index, and height standard deviation score were involved in the study. Using a sine-wave transcutaneous stimulator, current perception threshold (CPT) testing at 2000, 250 and 5 Hz was performed on the left median and peroneal nerves. Diabetic children had increased CPT at 2000 Hz on both nerves as compared to the control group (median (interquartile range), median nerve: 2.43 (2.20-3.43) vs 1.80 (1.51-2.60) mA, p = 0.02; peroneal nerve: 3.51 (2.81-4.82) vs 2.70 (2.04-3.70) mA, p = 0.01). Twenty-one (23%) of patients had CPT values higher than that of any healthy individual. Of these, elevated CPT was observed in 9 (9.8%) patients on the median nerve, in 8 (8.7%) patients on the peroneal nerve, and in 4 (4.3%) patients on both median and peroneal nerves. Using multiple logistic regression analysis, worse long-term metabolic control and advanced puberty were independently predictive of peripheral sensory nerve dysfunction as the dependent variable (adjusted OR (95% CI): 3.4 (1.2-6.2), p = 0.01, and 2.8 (1.1-5.6), p = 0.03, respectively). In conclusion, evidence of peripheral sensory nerve dysfunction is not rare in children and adolescents with diabetes and can be demonstrated by CPT testing in asymptomatic patients. Poor metabolic control is a risk factor for such subclinical neuropathy, and pubertal development may be involved in the pathogenesis of diabetic peripheral neuropathy.


HIV preferentially infects HIV-specific CD4+ T cells.
HIV infection is associated with the progressive loss of CD4(+) T cells through their destruction or decreased production. A central, yet unresolved issue of HIV disease is the mechanism for this loss, and in particular whether HIV-specific CD4(+) T cells are preferentially affected. Here we show that HIV-specific memory CD4(+) T cells in infected individuals contain more HIV viral DNA than other memory CD4(+) T cells, at all stages of HIV disease. Additionally, following viral rebound during interruption of antiretroviral therapy, the frequency of HIV viral DNA in the HIV-specific pool of memory CD4(+) T cells increases to a greater extent than in memory CD4(+) T cells of other specificities. These findings show that HIV-specific CD4(+) T cells are preferentially infected by HIV in vivo. This provides a potential mechanism to explain the loss of HIV-specific CD4(+) T-cell responses, and consequently the loss of immunological control of HIV replication. Furthermore, the phenomenon of HIV specifically infecting the very cells that respond to it adds a cautionary note to the practice of structured therapy interruption.


Treatment of localized gingival recessions. Part I. Lateral sliding flap.
This study was undertaken to evaluate biometrically the changes that occur on the recipient as well as on the donor tooth with regard to gingival recession, sulcus depth and width of keratinized gingiva after performing a lateral sliding flap in the treatment of localized denuded roots. Fourteen teeth with gingival recession were treated using a lateral sliding flap. Measurements were recorded preoperatively and 1, 3 and 6 months after surgery. A mean gain of 2.69 mm of soft tissue coverage over the denuded root was found 6 months postoperatively which represents 69% of coverage. The mean gain in width of keratinized gingiva averaged 3.15 mm. On the donor tooth an average gingival recession of 1.1o mm was found after 6 months, and the width of keratinized gingiva decreased an average of 1.25 mm. Results remained stable after 30 days postsurgery.


Understanding binding selectivity toward trypsin and factor Xa: the role of aromatic interactions.
A congeneric series of four bis-benzamidine inhibitors sharing a dianhydrosugar isosorbide scaffold in common has been studied by crystal structure analysis and enzyme kinetics with respect to their binding to trypsin and factor Xa. Within the series, aromatic interactions are an important determinant for selectivity discrimination among both serine proteases. To study the selectivity-determining features in detail, we used trypsin mutants in which the original binding site is gradually substituted to finally resemble the factor Xa binding pocket. The influence of these mutations has been analyzed on the binding of the closely related inhibitors. We present the crystal structures of the inhibitor complexes obtained by co-crystallizing an "intermediate" trypsin mutant. They could be determined to a resolution of up to 1.2 A, and we measured the inhibitory activity (K(i)) of each ligand against factor Xa, trypsin, and the various mutants. From these data we were able to derive a detailed structure-activity relationship which demonstrates the importance of aromatic interactions in protein-ligand recognition and their role in modulating enzyme selectivity. Pronounced preference is experienced to accommodate the benzamidine anchor with meta topology in the S(1) specificity pocket. One ligand possessing only para topology deviates strongly from the other members of the series and adopts a distinct binding mode addressing the S(1)' site instead of the distal S(3)/S(4) binding pocket.


Myocardial death and dysfunction after ischemia-reperfusion injury require CaMKIIδ oxidation.
Reactive oxygen species (ROS) contribute to myocardial death during ischemia-reperfusion (I/R) injury, but detailed knowledge of molecular pathways connecting ROS to cardiac injury is lacking. Activation of the Ca2+/calmodulin-dependent protein kinase II (CaMKIIδ) is implicated in myocardial death, and CaMKII can be activated by ROS (ox-CaMKII) through oxidation of regulatory domain methionines (Met281/282). We examined I/R injury in mice where CaMKIIδ was made resistant to ROS activation by knock-in replacement of regulatory domain methionines with valines (MMVV). We found reduced myocardial death, and improved left ventricular function 24 hours after I/R injury in MMVV in vivo and in vitro compared to WT controls. Loss of ATP sensitive K+ channel (KATP) current contributes to I/R injury, and CaMKII promotes sequestration of KATP from myocardial cell membranes. KATP current density was significantly reduced by H2O2 in WT ventricular myocytes, but not in MMVV, showing ox-CaMKII decreases KATP availability. Taken together, these findings support a view that ox-CaMKII and KATP are components of a signaling axis promoting I/R injury by ROS.


[Selective neck dissection for node-positive necks (N1, N2) in patients with head and neck squamous cell carcinoma].
To evaluate therapeutic effect in a consecutive series of patients with node-positive of N1 and N2 head and neck squamous cell carcinoma (HNSCC) who underwent selective neck dissection as part of their treatment in a single institution. Retrospectively analyzed 36 patients with node positive head and neck squamous cell carcinoma, which had undergone 40 selective neck dissection (SND) and 16 radical neck dissections (RND) and the therapeutic effects of the SND in HNSCC patients with node positive. Kaplan-Meier method was used to estimate the survival analysis among the different levels, and log-rank method for comparison of the different distribution of the several influential factors of the survival; the fisher's exact test was used to test the difference of the neck recurrence between the groups that with or without lymph node extracapsular spread. Cox proportional hazard model was applied to screen the potentially significant prognostic factors. The 3 and 5 years survival rate of this group were 76.8% and 54.3% retrospectively. The 3 and 5 years' survival rate were both 100% in the N1 + N2a group, while 59.4% and 32.0% in the N2b + N2c group correspondingly. With log-rank test between the two groups above, significant statistical difference was revealed (P = 0.003) in the 5 years' survival rates. To the groups that with or without extracapsular spread (ECS), the recurrence rate were 36.4% and 3.4% respectively and significant statistical difference existed (P = 0.015). In the groups that with or without ECS, the 3 years' survival rate were 45.5% and 81.8% , and 5 years' survival rate were 39.7% and 65.5% respectively, also the significant statistical difference (P = 0.0148 and P = 0.0423 respectively) had presented. SND is appropriate for treatment of N1 neck of the patient with HNSCC; However, SND should be taken very cautious to the N2 neck and node-positive neck with extracapsular spread, MRND or RND might be a better choice to prevent the recurrence in the neck.


Value-added processing of peanut meal: aflatoxin sequestration during protein extraction.
The efficacy of a bentonite clay, Astra-Ben 20A (AB20A), to sequester aflatoxin from contaminated (approximately 110 ppb) peanut meal during protein extraction was studied. Aqueous peanut meal dispersions (10% w/w) were prepared by varying the pH, temperature, enzymatic hydrolysis conditions, and concentrations of AB20A. After extraction, dispersions were centrifuged and filtered to separate both the water-soluble and the water-insoluble fractions for subsequent testing. Inclusion of AB20A at 0.2 and 2% reduced (p < 0.05) aflatoxin concentrations below 20 ppb in both fractions; however, the higher concentration of AB20A also reduced (p < 0.05) the water-soluble protein content. Inclusion of 0.2% AB20A did not affect protein solubility, total soluble solids, or degree of hydrolysis. Peanut meal adsorption isotherms measured the AB20A capacity to sequester aflatoxin. These results are discussed in the context of a process designed to sequester aflatoxin from contaminated peanut meal, which could enable derivatives of this high protein material to be utilized in enhanced feed and/or food applications.


Ethical controversies in prenatal microarray.
Chromosome microarray (CMA) analysis enables genome interrogation at a much higher resolution than is possible with conventional karyotyping. CMA is considered 'standard of care' for postnatal genetic testing, yet its introduction into the prenatal setting has been delayed, in part because of ethical concerns about possible psychosocial harm and deficits in informed consent. The findings of several large trials have now been reported, allowing preliminary quantification of the relative benefits and harms of CMA in prenatal diagnosis. Qualitative studies have also provided insights into the patient experience particularly in cases in which results of uncertain significance are provided. In an attempt to minimize potential harms, some professional guidelines have suggested limiting access to CMA to patients with fetal abnormality on ultrasound, limiting the diagnostic power of CMA by using targeted platforms or limiting reporting. We provide an overview of the relative benefits and harms of prenatal CMA, and critically examine the strategies proposed to minimize harms in the context of other important ethical issues such as patient autonomy, justice and equity of access. We advocate for improved patient consent, counselling and support so that patients can fully benefit from the improved diagnostic yield of CMA despite the challenges that are intrinsic to the prenatal setting.


Quantitative analysis of retinal glycerolipid molecular species acetylated by acetolysis.
A method for the quantitative analysis of molecular species of 1,2-diacylglycerol acetates (1,2-DGAC) containing polyunsaturated fatty acids is described. Phosphatidylethanolamine (PE) isolated from frog retina was used to test the method. PE was converted to 1,2-DGAC by acetolysis. The molecular species of the 1,2-DGAC were resolved by reverse-phase high performance liquid chromatography (HPLC), detected by UV absorption spectroscopy at 210 nm, and identified by gas-liquid chromatography (GLC) of the fatty acid methyl esters (FAME). Molar response curves were generated for each DGAC molecular species that eluted as a single entity from HPLC by determining the moles of fatty acids in the molecular species collected and the response (peak area unit) of the UV detector. Each molecular species response curve was linear from about 10 pmoles to 4-8 nmoles, allowing the slope of each curve to be used as a molar absorptivity. This method provides a means for quantification of most of the molecular species of all glycerolipid classes.


Review of criterion-referenced standards for cardiorespiratory fitness: what percentage of 1 142 026 international children and youth are apparently healthy?
To identify criterion-referenced standards for cardiorespiratory fitness (CRF); to estimate the percentage of children and youth that met each standard; and to discuss strategies to help improve the utility of criterion-referenced standards for population health research. A search of four databases was undertaken to identify papers that reported criterion-referenced CRF standards for children and youth generated using the receiver operating characteristic curve technique. A pseudo-dataset representing the 20-m shuttle run test performance of 1 142 026 children and youth aged 9-17 years from 50 countries was generated using Monte Carlo simulation. Pseudo-data were used to estimate the international percentage of children and youth that met published criterion-referenced standards for CRF. Ten studies reported criterion-referenced standards for healthy CRF in children and youth. The mean percentage (±95% CI) of children and youth that met the standards varied substantially across age groups from 36%±13% to 95%±4% among girls, and from 51%±7% to 96%±16% among boys. There was an age gradient across all criterion-referenced standards where younger children were more likely to meet the standards compared with older children, regardless of sex. Within age groups, mean percentages were more precise (smaller CI) for younger girls and older boys. There are several CRF criterion-referenced standards for children and youth producing widely varying results. This study encourages using the interim international criterion-referenced standards of 35 and 42 mL/kg/min for girls and boys, respectively, to identify children and youth at risk of poor health-raising a clinical red flag.


The pio operon is essential for phototrophic Fe(II) oxidation in Rhodopseudomonas palustris TIE-1.
Phototrophic Fe(II)-oxidizing bacteria couple the oxidation of ferrous iron [Fe(II)] to reductive CO(2) fixation by using light energy, but until recently, little has been understood about the molecular basis for this process. Here we report the discovery, with Rhodopseudomonas palustris TIE-1 as a model organism, of a three-gene operon, designated the pio operon (for phototrophic iron oxidation), that is necessary for phototrophic Fe(II) oxidation. The first gene in the operon, pioA, encodes a c-type cytochrome that is upregulated under Fe(II)-grown conditions. PioA contains a signal sequence and shares homology with MtrA, a decaheme c-type cytochrome from Shewanella oneidensis MR-1. The second gene, pioB, encodes a putative outer membrane beta-barrel protein. PioB is a homologue of MtrB from S. oneidensis MR-1. The third gene, pioC, encodes a putative high potential iron sulfur protein (HiPIP) with a twin-arginine translocation (Tat) signal sequence and is similar to the putative Fe(II) oxidoreductase (Iro) from Acidithiobacillus ferrooxidans. Like PioA, PioB and PioC appear to be secreted proteins. Deletion of the pio operon results in loss of Fe(II) oxidation activity and growth on Fe(II). Complementation studies confirm that the phenotype of this mutant is due to loss of the pio genes. Deletion of pioA alone results in loss of almost all Fe(II) oxidation activity; however, deletion of either pioB or pioC alone results in only partial loss of Fe(II) oxidation activity. Together, these results suggest that proteins encoded by the pio operon are essential and specific for phototrophic Fe(II) oxidation in R. palustris TIE-1.


Management of bile duct stones in the era of laparoscopic cholecystectomy.
The development of laparoscopic cholecystectomy has transformed many aspects of gallstone disease management, particularly the care of patients with known or suspected bile duct stones. New obstacles to operative access to the bile duct have stressed the importance of accurate clinical prediction and detection of bile duct stones and led to increased reliance on nonsurgical approaches, especially pre- or postoperative endoscopic retrograde cholangiopancreatography and sphincterotomy, as well as spurring the development of new techniques such as laparoscopic common bile duct exploration. This work reviews the key features and rational usage of the endoscopic, laparoscopic and open surgical procedures, as well as other adjunct techniques, employed in the treatment of bile duct stones, emphasizing current options in the approach to this problem in the perilaparoscopic cholecystectomy setting. Management of bile duct stones in other special clinical circumstances and the potential future role of emerging technologies are also discussed.


Metabolic pathway catalyzed by Vanin-1 pantetheinase plays a suppressive role in influenza virus replication in human alveolar epithelial A549 cells.
Our previous analysis of gene expression profiles in the peripheral blood from patients with influenza A (H1N1) pdm09 pneumonia revealed elevated transcription levels of the vanin-1 (vascular non-inflammatory molecule 1, VNN1) gene, which encodes an epithelial ectoenzyme with pantetheinase activity involved in recycling coenzyme A. Here, to elucidate the role of VNN1 in influenza A virus (IAV) H1N1 infection, we investigated the change of VNN1 expression in the context of IAV infection and the effects of its related substances, i.e., its direct substrate pantetheine and its two metabolites pantothenic acid and cysteamine on the replication of IAV in the human alveolar epithelial carcinoma cell line A549. The messenger RNA expression of VNN1 in A549 cells was significantly increased (by 4.9-fold) after IAV infection under an elevated concentration of pantetheine. Moreover, VNN1 mRNA levels were elevated by > 100-fold in response to pro-inflammatory cytokines, especially TNF-α and IL-1β. Pantetheine significantly reduced the IAV replication and IAV Matrix 1 (M1) mRNA levels when it was administered prior to and during infection. In addition, cysteamine treatment during IAV infection significantly reduced the viral replication and IAV M1 mRNA levels, whereas pantothenic acid did not. These findings suggest that the metabolic pathway catalyzed by VNN1 pantetheinase plays a suppressive role in IAV infection in the respiratory tract, especially in severe conditions under hypercytokinemia.


Microelastic gradient gelatinous gels to induce cellular mechanotaxis.
The understanding and realization of directional cell movement towards a harder region of a cell culture substrate surface, so-called mechanotaxis, might provide a solid basis for a functional artificial extracellular matrix, enabling manipulation and elucidation of cell motility. The photolithographic surface microelasticity patterning method was developed for fabricating a cell-adhesive hydrogel with a microelasticity gradient (MEG) surface using photocurable styrenated gelatin to investigate the condition of surface elasticity to induce mechanotaxis as a basis for such substrate-elasticity-dependent control of cell motility. Patterned MEG gels consisting of different absolute surface elasticities and elasticity jumps were prepared. Surface elasticity and its two-dimensional distribution were characterized by microindentation tests using atomic force microscopy (AFM). From analyses of trajectories of 3T3 cell movement on each prepared MEG gel, two critical criteria of the elasticity jump and the absolute elasticity to induce mechanotaxis were identified: (1) a high elasticity ratio between the hard region and the soft one, and (2) elasticity of the softer region to provide medium motility. Design of these conditions was found to be necessary for fabricating an artificial extracellular matrix to control or manipulate cell motility.


[Characteristics of contraction force of bovine ciliary muscles caused by cholinergic agent].
We studied the contractions caused by the cholinergic agent carbachol on bovine ciliary muscles. Ciliary muscle strips (width 4 mm x length 6 mm) were prepared in the directions of the longitudinal and circular muscles. Contractions were measured with an isometric tension recorder. The concentration for 50% effective dose was 10(-7) M carbachol, and maximum contraction was obtained at 3 x 10(-6) M. Also, maximum contraction was obtained at a resting tension of 600 mg for the longitudinal direction and 400 mg for the circular direction. At a resting tension of 400 mg and concentration of 10(-5) M, average contraction for the longitudinal direction (L) was 335 +/- 106 mg (mean +/- SD, n = 20) and 104 +/- 52 mg (mean +/- SD, n = 20) for the circular direction (C). The ratio between L and C was about 3:1. The results suggest that bovine ciliary muscles have more ability to perform accommodation than in previous reports, and that the magnitude of contractions depends on the direction of the ciliary muscle fibers.


Biosynthesis of proteases by Rhizopus oligosporus IHS13 in low-cost medium by solid-state fermentation.
The present study describes the biosynthesis of proteases by a locally isolated mould culture of Rhizopus oligosporus IHS13 in a low-cost medium by solid-state fermentation technique. The fermentation was carried out in a low-cost medium such as sunflower meal, wheat bran and rice bran. Sunflower meal and wheat bran in a ratio of 1:1 and moistened with distilled water was found to be the best substrate for protease synthesis. All the three substrates are very cheap agricultural by-products found in Pakistan. The production of proteases in sunflower meal and rice bran was also investigated but the results were unsatisfactory. Different cultural conditions such as rate of fermentation, effect of incubation temperature, effect of pH and depth of the fermentation medium were also optimized. The maximum enzyme synthesis was found after 72 h of fermentation at a temperature of 30 degrees C. The optimum pH and depth of the medium for protease synthesis were found to be 5.0 and 20 mm respectively. The maximum enzyme biosynthesis found during the course of present studies was 7.0 U ml(-1).


Engineered DNAzyme Enables Homogeneous Detection of Cereulide via Polychromic Fluorescence Modality.
Cereulide, the exotoxin of emetic Bacillus cereus, has garnered considerable attention due to its capacity to produce foodborne poisonings and great chemical stability. Herein, a G-quadruplex-hemin DNAzyme-based biosensor was developed to detect cereulide in the homogeneous solution. Due to the special ring structure and high affinity to K+, cereulide can be attracted and intercalated into the G-quadruplex; thus, the properties of the G4 DNAzyme can be altered. The melting temperature (Tm) of the G4 DNAzyme in the presence or absence of cereulide was 58.75 and 50.10 °C, respectively, proving the intercalation of cereulide into the G4 DNAzyme. By using the polychromic fluorescence modality of CdTe quantum dots and o-phenylenediamine to assess the variation in the catalytic activity of the DNAzyme, the intercalation of cereulide had bidirectional effects in G4 DNAzyme-mediated reactions, showing that the fluorescence intensity of CdTe quantum dots displayed a linear relationship with the concentration of cereulide from 0.16 to 40 μg/mL with the limit of detection (LOD) of 0.10 μg/mL, while the fluorescence intensity of DAP exhibited a linear relationship with the concentration of cereulide from 0.02 to 40 μg/mL with the LOD of 0.01 μg/mL. It will be a perspective step of controlling cereulide as a hazardous material in food or the environment.


Effectiveness of technology-based interventions in detection, prevention, monitoring and treatment of patients at risk or diagnosed with mild cognitive impairment: protocol for a systematic review.
The gradual changes over the decades in the longevity and ageing of European society as a whole can be directly related to the prolonged decline in the birth rate and increase in the life expectancy. According to the WHO, there is an increased risk of dementia or other cognitive disorders as the population ages, which have a major impact on public health. Mild cognitive impairment (MCI) is described as a greater than expected cognitive decline for an individual's age and level of education, but that does not significantly interfere with activities of daily living. Patients with MCI exhibit a higher risk of dementia compared with others in the same age group, but without a cognitive decline, have impaired walking and a 50% greater risk of falling.The urban lifestyle and advent of smartphones, mobility and immediate access to all information via the internet, including health information, has led to a totally disruptive change in most general aspects.This systematic review protocol is aimed at evaluating the effectiveness of technology-based interventions in the detection, prevention, monitoring and treatment of patients at risk or diagnosed with MCI. This review protocol follows the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols reporting guidelines. The search will be performed on MEDLINE (PubMed), CENTRAL, CINAHL Plus, ISI Web of Science and Scopus databases from 2010 to 2020. Studies of interventions either randomised clinical trials or pre-post non-randomised quasi-experimental designs, published in English and Spanish will be included. Articles that provide relevant information on the use of technology and its effectiveness in interventions that assess improvements in early detection, prevention, follow-up and treatment of the patients at risk or diagnosed with MCI will be included. Ethics committee approval not required. The results will be disseminated in publications and congresses.


Interleukin-1alpha, interleukin-1beta, and interleukin-1Ra polymorphisms in febrile seizures.
Febrile seizures are the most common form of childhood seizures. The exact mechanism promoting convulsions during a common febrile illness remains unknown, but it is accepted that genetic influences are likely to account for at least some of the cases. Previous studies reported high interleukin-1beta levels in the cerebrospinal fluid of patients with febrile seizures. Recently, an association between a regulatory polymorphism in the genes encoding interleukin-1beta and interleukin-1Ra and febrile seizures was reported. In this study, we attempted to confirm these findings. We analyzed the cytokine gene polymorphisms of interleukin-1beta, interleukin-1alpha, and interleukin-1Ra of 73 children with febrile seizure and 152 healthy controls. The distribution of interleukin-1beta -511, interleukin-1alpha -889, and interleukin-1Ra genotypes and alleles did not differ significantly between cases and controls. Our data suggest that the studied gene polymorphisms of interleukin-1beta, interleukin-1alpha, and interleukin-1Ra do not have a significant role in the pathogenesis of febrile seizures.


Neurological aspects of hyperinsulinism-hyperammonaemia syndrome.
Hyperinsulinism-hyperammonaemia syndrome (HHS) is a rare cause of congenital hyperinsulinism, due to missense mutations in the GLUD1 gene, resulting in glutamate dehydrogenase (GDH) overactivity. The aim of this study was to document the spectrum of neurological disturbances associated with HHS and to identify possible phenotype-genotype correlations. We retrospectively analyzed the neurological outcomes of 22 consecutive patients (12 males, 10 females) aged from 18 months to 40 years and diagnosed with HHS. We analyzed demographic and clinical features and neuroradiological, biochemical, and genetic findings. Fourteen patients had childhood-onset epilepsy. Learning disability was found in 17 patients. Two patients had pyramidal involvement and one had generalized dystonia. Seizures were observed in 11 of 19 patients with documented GLUD1 mutations, and nine of these 11 patients had a mutation in the guanosine triphosphate (GTP) binding site. Our data demonstrate that neurological disorders in HHS are more frequent than previously thought and might suggest that mutations in the GTP binding site of GDH could be associated with more frequent epilepsy.


Directing and Boosting of Cell Migration by the Entropic Force Gradient in Polymer Solution.
Noncontact manipulation of nano/micromaterials presents a great challenge in fields ranging from biotechnology to nanotechnology. In this study we developed a new strategy for the manipulation of molecules and cells based on diffusiophoresis driven by a concentration gradient of a polymer solute. By using laser focusing in a microfluidic device, we created a sharp concentration gradient of poly(ethylene glycol) (PEG) in a solution of this polymer. Because diffusiophoresis essentially depends on solute gradients alone, PEG solute contrast resulted in trapping of DNA and eukaryotic cells with little material dependence. Furthermore, quantitative analysis revealed that the motility of migrating cells was enhanced with the PEG concentration, consistent with a theoretical model of boosted cell migration. Our results support that a solute contrast of polymer can exert an interfacial force gradient that physically propels objects and may have application for the manipulation of soft materials.


Induction of Low-Level Hydrogen Peroxide Generation by Unbleached Cotton Nonwovens as Potential Wound Dressing Materials.
Greige cotton is an intact plant fiber. The cuticle and primary cell wall near the outer surface of the cotton fiber contains pectin, peroxidases, superoxide dismutase (SOD), and trace metals, which are associated with hydrogen peroxide (H₂O₂) generation during cotton fiber development. Traditionally, the processing of cotton into gauze involves scouring and bleaching processes that remove the components in the cuticle and primary cell wall. The use of unbleached, greige cotton fibers in dressings, has been relatively unexplored. We have recently determined that greige cotton can generate low levels of H₂O₂ (5-50 micromolar). Because this may provide advantages for the use of greige cotton-based wound dressings, we have begun to examine this in more detail. Both brown and white cotton varieties were examined in this study. Brown cotton was found to have a relatively higher hydrogen peroxide generation and demonstrated different capacities for H₂O₂ generation, varying from 1 to 35 micromolar. The H₂O₂ generation capacities of white and brown nonwoven greige cottons were also examined at different process stages with varying chronology and source parameters, from field to nonwoven fiber. The primary cell wall of nonwoven brown cotton appeared very intact, as observed by transmission electron microscopy, and possessed higher pectin levels. The levels of pectin, SOD, and polyphenolics, correlated with H₂O₂ generation.


Influence of muscle activity on the actions of chloride channel blockers in the mouse skeletal muscle.
The purpose of this work was to investigate the effect of channel blockers in the presence and absence of nerve and/or muscle activity. 9-Anthracenecarboxylic acid (0.03 mM), a chloride channel blocker, increased both the amplitude and duration of the contractile response to direct stimulation in the mouse soleus muscle in either low Ca2+ Krebs (0.25 mM) or normal Ca2+ Krebs (2.5 mM) containing 0.1 mM 4-aminopyridine (potassium channel blocker). In addition, spontaneous contractions were induced by 9-anthracenecarboxylic acid in low Ca2+ Krebs. On the other hand, the combination of two potassium channel blockers, 4-aminopyridine (0.3 mM) plus tetraethylammonium ion (10 mM), increased the twitch amplitude but only slightly increased the contractile duration in the mouse soleus muscle in normal Krebs. The contraction-potentiating actions of 9-anthracenecarboxylic acid were inhibited by denervation, while those of 4-aminopyridine plus tetraethylammonium were not. Chronic exposure to the sciatic nerve to a lidocaine-cuff, but not to a colchicine-cuff, exhibited similar effects as denervation. Direct electrical stimulations were applied for 2 days to the soleus muscle through implanted teflon-coated multistranded electrodes in vivo, beginning immediately after denervation or cuff treatments. The contraction-potentiating effects of 4-aminopyridine plus 9-anthracenecarboxylic acid or 9-anthracenecarboxylic acid in low Ca2+ Krebs were restored in the denervated or lidocaine-cuff-treated soleus muscle by chronic direct stimulations. The membrane potential and input resistance of muscle fibres and the effects of 9-anthracenecarboxylic acid, which were altered by denervation or cuff treatment, were also partially restored by this measure. When sciatic nerves had been treated with lidocaine-cuff for 4 days and the cuff was then removed for 7 days, the contraction-potentiating effects of 9-anthracenecarboxylic acid were also restored. Four days after Achilles tenotomy, the contraction-potentiating effects of 9-anthracenecarboxylic acid were markedly inhibited. It was concluded that muscle activity controls the properties of chloride channels and that neural activity may affect the properties of chloride channels via enhancement of the muscle contraction.


The expression of P-glycoprotein in leukemia cells is associated with the upregulated expression of nestin, a class 6 filament protein.
Multidrug resistance (MDR) is a serious obstacle to the effective chemotherapeutic treatment of leukemia. Expression of plasma membrane P-glycoprotein (P-gp), a transporter involved in drug efflux, is the most frequently observed molecular causality of MDR. We observed the coexpression of P-gp and the filament protein nestin in the acute myeloid leukemia (AML) cell lines SKM-1 and MOLM-13 following the induction of P-gp expression using vincristine. Nestin is considered a marker of neural stem cells and neural progenitor cells. The aim of this study was to determine whether there is causal relationship between the expression of P-glycoprotein and the expression of nestin in both of these AML cell lines. The expression of P-gp was induced in SKM-1 cells by selective pressure using vincristine (VCR), mitoxantrone (MTX), azacytidine (AzaC) and lenalidomide (LEN). Whereas the selective pressure of VCR, MTX and AzaC also induced P-gp expression in MOLM-13 cells, LEN was found to be ineffective in this regard. In all cases in which P-gp expression was induced in SKM-1 and MOLM-13 cells, its expression was associated with the induction of nestin mRNA expression and the presence of a 200-220kDa nestin-immunoreactive protein band in western blots. Silencing P-gp expression using s10418 siRNA (known as the P-gp silencer) was associated with the downregulation of the nestin transcript level, demonstrated using RT-PCR. Nestin mRNA was also observed in two P-gp-positive variants of L1210 cells that were obtained either by selection with VCR or by transfection with a retrovirus encoding human P-gp. Detectable levels of nestin transcripts were not observed in P-gp-negative parental L1210 cells. Taken together, these results indicated that the induction of P-gp expression is causally associated with the expression of nestin in leukemia cells.


Formaldehyde toxicity. Part I. Occupational exposure and a report of 5 cases.
Formaldehyde is ubiquitous in the occupational, domestic and general environment, and in manufactured and consumer goods. The clinical and radiological findings in 5 shop employees exposed to formaldhyde are presented. Two features are of interest: (i) 1 of the workers developed vomiting, a symptom previously unreported in adults exposed to formaldehyde; and (ii) all 5 victims developed turbinate swelling, apparent clinically and radiologically. The swelling was marked, causing obstruction of the nasal passages, and persisted for some time after most of the sources of exposure had been dealt with. This phenomenon is also previously undocumented.


Tissue depletion of quinocetone and its five major metabolites in pigs, broilers, and carp fed quinocetone premix.
A residue depletion study was performed to investigate the tissue kinetics of quinocetone (1) and its major metabolites. Quinocetone and its major metabolites were simultaneously quantitated with a high-performance liquid chromatography-ultraviolet (HPLC-UV) method. A total of 25 pigs, 30 broilers, and 50 carp were fed 100 mg/kg quinocetone for 90, 42, and 60 days, respectively. Liver, kidney, muscle, and fat (skin) tissues were collected at five different withdrawal times for analysis. Results revealed that quinocetone, 1-desoxyquinocetone (2), carbonyl-reduced 4-desoxyquinocetone (4), 3-methylquinoxaline-2-carboxylic acid (5), and carbonyl-reduced dideoxyquinocetone (6) could be depleted quickly in tissues; by contrast, dideoxyquinocetone, 3, persisted for a long time in the liver. Therefore, the liver is possibly the target tissue of quinocetone, and 3 is the residual marker; the recommended withdrawal times (WDTs) are 0 days in pigs and carp and 3 days in broilers. These results provided clear monitoring tools and technical standards to evaluate the food safety of quinocetone.


Population histamine burden assessed using wastewater-based epidemiology: The association of 1,4‑methylimidazole acetic acid and fexofenadine.
Systematic sampling and analysis of wastewater has become an important tool for monitoring consumption of drugs and other substances, and has been proposed as a method to evaluate aspects of population health using endogenous biomarkers. 1,4‑methylimidazoleacetic acid (MIAA) is an endogenous biomarker and metabolite of histamine turnover. Its urinary excretion is elevated in conditions such as mastocytosis, hay fever, hives, food allergies and anaphylaxis. The aim of this study was to develop and apply methods for MIAA in wastewater and compare its occurrence with antihistamine use in wastewater. Consecutive daily samples were collected from seven catchments serving populations from 3000 to 2 million and covering rural and urban communities during the 2016 Census in Australia. MIAA and the antihistamines (ranitidine, fexofenadine, cetirizine) were quantified consistently. Per capita excretion of MIAA (mg/d/capita) estimated from the WW concentrations were consistent with findings from previous clinical studies. We found significant positive correlations between loads of MIAA and fexofenadine (R2 = 0.68, p < 0.0001) and cetirizine (R2 = 0.25, p = 0.03) across the various catchments. Sewer reactor experiments on the degradation of MIAA and the antihistamines found that fexofenadine is stable for at least 24 h while MIAA, ranitidine and cetirizine are subject to degradation, and this should be considered in interpretations. To the best of our knowledge, this study is the first wastewater study to introduce and monitor an endogenous metabolite of histamine, and the first study to monitor and relate proxies of disease and treatment of disease.


Phyllotaxis, disk packing, and Fibonacci numbers.
We consider the evolution of the packing of disks (representing the position of buds) that are introduced at the top of a surface which has the form of a growing stem. They migrate downwards, while conforming to three principles, applied locally: dense packing, homogeneity, and continuity. We show that spiral structures characterized by the widely observed Fibonacci sequence (1, 1, 2, 3, 5, 8, 13, ...), as well as related structures, occur naturally under such rules. Typical results are presented in an animation.


Comparative efficacy and acceptability of antiepileptic drugs for classical trigeminal neuralgia: a Bayesian network meta-analysis protocol.
Trigeminal neuralgia (TN) affects 4 to 28.9/100 000 people worldwide, and antiepileptic drugs such as carbamazepine and oxcarbazepine are the firstline treatment options. However, the efficacy and safety of other antiepileptic drugs remain unclear due to insufficient direct comparisons. To compare the efficacy and acceptability of all currently available antiepileptic agents for the treatment of patients with classical TN. We will search the PubMed, EMBASE, Cochrane Library and Web of Science databases for unpublished or undergoing research listed in registry platforms. We will include all randomised controlled trials comparing two different antiepileptic drugs or one antiepileptic drug with placebo in patients with classical TN. The primary outcomes will be the proportion of responders and the number of subjects who dropout during the treatment. The secondary outcomes will include the two primary outcomes but in the follow-up period, changes in the self-reporting assessment scale for neuralgia and quality of life assessment. In terms of network meta-analysis, we will fit our model to a Bayesian framework using the JAGS and pcnetmeta packages of the R project. This protocol will not disseminate any private patient data. The results of this review will be disseminated through peer reviewed publication. CRD42016048640.


Total Thyroidectomy Versus Lobectomy for the Treatment of Follicular Thyroid Microcarcinoma.
To compare the effectiveness of total thyroidectomy versus thyroid lobectomy for the treatment of follicular thyroid microcarcinoma. Data were extracted from the Surveillance, Epidemiology, and End Results 18 Database. The study cohort included patients diagnosed with follicular thyroid microcarcinoma between 1988 and 2009, treated with either total thyroidectomy or thyroid lobectomy. Propensity-score analysis using inverse probability weighting was used to control for allocation bias. A total of 203 patients were identified. The 5-year overall survival was 98% for patients treated with lobectomy and 99% for those treated with total thyroidectomy; this difference was not statistically significant (p=0.13). Unadjusted analysis and propensity-score analysis revealed no difference in overall survival between the two treatment groups (p=0.15 and p=0.49, respectively). Total thyroidectomy does not appear to offer any survival advantage over thyroid lobectomy for patients with follicular thyroid microcarcinoma.


Aortic pathophysiology by cardiovascular magnetic resonance in patients with clinical suspicion of coronary artery disease.
To correlate cardiovascular magnetic resonance (CMR)-based measurement of aortic pulse wave velocity (PWV) with serum markers for atherosclerosis and plaque burden in the thoracic aorta. Individuals with risk factors for coronary atherosclerosis underwent CMR pulse wave velocity examination of the descending thoracic aorta and computed tomography for coronary calcium scoring. Inversion recovery images allowed quantification of aortic plaque. Serum lipids and c-reactive protein levels were measured. Mean PWV did not correlate with presence of aortic plaque (p = 0.55). Subgroup analysis showed no significant correlation with PWV and total plaque. PWV and pulse pressure correlated (PP) (R2 0.38, p = 0.0003), but PWV and other predictor variables did not. Total plaque area correlated with aortic diameter (p = 0.0066). In patients with suspected coronary artery disease, aortic pulse wave velocity reflects increased aortic stiffness demonstrated by elevated pulse pressure, but does not directly correlate with aortic plaque or serum markers for arterial disease.


Influence of cyclic dimer formation on the phase behavior of carboxylic acids.
A new thermodynamic approach based on the Sear and Jackson association theory for doubly bonded dimers [Mol. Phys.1994, 82, 1033] is proposed to describe the thermodynamic properties of carboxylic acids. The new model is able to simultaneously represent the vapor pressures, saturated densities, and vaporization enthalpies of the shortest acids and is in a much better agreement with experimental data than other approaches that do no consider the formation of cyclic dimers. The new model is applied to mixtures of carboxylic acids with nonassociating compounds, and a very good description of the vapor-liquid equilibria in mixtures of alkanes + carboxylic acids is obtained.


Meta-analysis of dose selection for budesonide in the treatment of Chinese patients with AECOPD.
To systematically observe the curative efficacy and safety of budesonide inhalation in the treatment of acute exacerbation of chronic obstructive pulmonary disease, and to find a suitable dose of aerosolized budesonide for Chinese patients. The meta-analysis study was conducted at Wenjiang District People's Hospital, Chengdu City, Sichuan Province, China from May 2019 to August 2019 and comprised randomised controlled trials of glucocorticoids for acute exacerbation of chronic obstructive pulmonary disease on the databases of the China National Knowledge Infrastructure, Wanfang Medical Network, PubMed, Medline, Embase, Cochrane Library and Google Scholar. Data extraction and quality evaluation of the studies was done and meta-analysis was then performed using RevMan 5.3. There were 25 studies identified that comprised 1959 patients. When the budesonide dose was 6mg/d and the methylprednisolone dose was 40mg/d, no significant difference was found in partial pressure of carbon dioxide and oxygen post-treatment (p>0.05). When the nebulized budesonide dose was <6mg/d, methylprednisolone was more effective than budesonide (p<0.05), while >6mg/d was not significantly more effective (p>0.05). At 4mg/d, the difference in the dyspnoea score post-treatment was significant (p<0.05). No significant difference was found in dyspnoea scores after intravenous glucocorticoid treatment when the dose was greater than or equal to 4mg/d. In terms of adverse reactions, the response rate of blood glucose, blood pressure, excitement, insomnia and stomach discomfort in the intravenous group was higher than that in the nebulised group (p<0.05). Oropharyngeal discomfort in the nebulized group was higher than that the intravenous group (p<0.05). The optimal dose for the inhalation of budesonide in Chinese patients was between 4mg/d and 6mg/d. The adverse reactions of nebulised budesonide were lower than those of intravenous methylprednisolone.


Burden of disease and increasing prevalence of inflammatory bowel disease in a population-based cohort in the Netherlands.
Reported epidemiology and phenotype distributions vary widely and disease burden of inflammatory bowel disease (IBD) is poorly described. Our aim was to establish these features in a population-based cohort covering 319 976 inhabitants. Furthermore, differences between tertiary referral and peripheral hospital patients were quantified. IBD patients in the adherence area of three peripheral hospitals (2004-2012) were included. Medical and surgical treatment data were obtained. Quality of life and disease activity were evaluated. An outpatient cohort from a tertiary referral centre was accrued. A total of 1461 patients were included: 761 (52.1%) with ulcerative colitis (UC), 579 (39.5%) with Crohn's disease (CD) and 121 (8.3%) with IBD-unspecified. Point prevalence of IBD was 432.1 per 100 000 inhabitants in 2010, which increased significantly over time, P-value of less than 0.0001. The mean annual incidence was 17.2 for UC, 10.5 for CD and 2.2 for IBD-unspecified. Tertiary referral Crohn's patients used thiopurines and biological therapy and underwent surgery significantly more often than patients in peripheral hospitals (P<0.0001). Disease activity correlated negatively with quality of life (P<0.0001) in UC and CD. The prevalence of IBD is still increasing. Burden of disease was significantly more severe, mainly in Crohn's patients, in the referral centre, highlighting the importance of population-based studies to accurately describe phenotype distribution and disease burden.


[Molecular pathogenesis of peripheral T-cell lymphoma (1): angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified and anaplastic large cell lymphoma].
Peripheral T-cell lymphomas (PTCL) belong to the group of non-Hodgkin lymphoma and particularly that of mature T/NK cells lymphoproliferative neoplasms. The 2008 WHO classification describes different PTCL entities with varying prevalence. With the exception of the histological subtype "ALK positive anaplastic large cell lymphoma", PTCL are characterized by a poor prognosis. The mechanisms underlying the pathogenesis of these lymphomas are not yet fully understood, but development of genomic high-throughput analysis techniques now allows to extensively identify the molecular abnormalities present in tumor cells. This review aims to summarize the current knowledge and recent advances about the molecular events occurring at the origin or during the natural history of main entities of PTCL. It will be published in two parts : the first is focused on the three more frequent entities, angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, and anaplastic large cell lymphoma. The second (which will appear in the november issue) will describe other subtypes less frequent and of poor prognosis : extranodal NK/T-cell lymphoma, nasal type, adult T-cell leukemia/lymphoma, and enteropathy-associated T-cell lymphoma. T or NK cell lymphoproliferative disorders with leukemic presentation, primary cutaneous T-cell lymphoma and very rare subtypes of PTCL whose prevalence is less than 5% (hepatosplenic T-cell lymphoma and subcutaneous panniculitis-like T cell lymphoma) will not be discussed herein.


3D Magnetic Metal-Organic Frameworks Current Collectors Accelerate the Lithium-Ion Diffusion Rate for Superlong Cyclic Lithium Metal Anode.
Lithium, is the most ideal anode material for lithium-based batteries. However, the overgrowth of lithium dendrites and the low lithium-ion diffusion rate at low temperatures limit the further application of lithium metal anodes. Here, the applied magnetic field is introduced inside the lithium metal anode by using a novel magnetic metal-organic framework as a current collector. The magnetic field can improve the conductivity of this novel current collector, thus accelerating the diffusion of lithium ions in the battery, an advantage that is particularly prominent at low temperatures. In addition, the current collector can stabilize the solid electrolyte interface and inhibit the growth of lithium dendrites, resulting in excellent electrochemical performance. The symmetrical cell at room temperature can exceed 4600 h with a hysteresis voltage of only 9 mV. After 300 cycles at room temperature, the capacity of full cell is still 142 mA h g-1 , and it remains stable for 380 cycles at 5 °C (capacity above 120 mA h g-1 ). The strategy of constructing novel current collector with magnetic field can promote the further application of lithium batteries in extreme conditions such as low temperatures.


Technique of functional and motility test: how to perform antroduodenal manometry.
Antroduodenal manometry is one of the methods to evaluate stomach and duodenal motility. This test is a valuable diagnostic tool for gastrointestinal motility disorders especially small intestinal pseudo-obstruction which is difficult to make definite diagnosis by clinical manifestations or radiologic findings. Manometric findings that have no evidence of mechanical obstruction and suggestive of pseudo-obstruction with neuropathy or myopathy can avoid unnecessary surgery and the treatment can be directly targeted. Moreover, among patients who have clinically suspected small intestinal pseudo-obstruction but with normal manometric findings, the alternative diagnosis including psychiatric disorder or other organic disease should be considered. The application of this test to the patients with functional gastrointestinal symptoms especially to find the association of motor abnormalities to the symptom has less impressive yield. Antroduodenal manometry is now readily available only in some tertiary care centers. The aim of this review is to describe the antroduodenal manometry technique, interpretation and clinical utility.


Mediating Photochemical Reaction Rates at Lewis Acidic Rare Earths by Selective Energy Loss to 4f-Electron States.
Manifesting chemical differences in individual rare earth (RE) element complexes is challenging due to the similar sizes of the tripositive cations and the corelike 4f shell. We disclose a new strategy for differentiating between similarly sized Dy3+ and Y3+ ions through a tailored photochemical reaction of their isostructural complexes in which the f-electron states of Dy3+ act as an energy sink. Complexes RE(hfac)3(NMMO)2 (RE = Dy (2-Dy) and Y (2-Y), hfac = hexafluoroacetylacetonate, and NMMO = N-methylmorpholine-N-oxide) showed variable rates of oxygen atom transfer (OAT) to triphenylphosphine under ultraviolet (UV) irradiation, as monitored by 1H and 19F NMR spectroscopies. Ultrafast transient absorption spectroscopy (TAS) identified the excited state(s) responsible for the photochemical OAT reaction or lack thereof. Competing sensitization pathways leading to excited-state deactivation in 2-Dy through energy transfer to the 4f electron manifold ultimately slows the OAT reaction at this metal cation. The measured rate differences between the open-shell Dy3+ and closed-shell Y3+ complexes demonstrate that using established principles of 4f ion sensitization may deliver new, selective modalities for differentiating the RE elements that do not depend on cation size.


Relationship between Plasma Albumin Concentration and Plasma Volume in 5 Inbred Rat Strains.
Using the Evans Blue procedure, we previously found strain-related differences in plasma volumes in 5 inbred rat strains. Because albumin binds strongly with Evans blue, this protein is important in the Evans blue method of plasma volume determination. Therefore, we speculated that interstrain differences in plasma albumin concentration (PAC) could distort calculated plasma volumes. To address this concern, we used ELISA techniques to measure PAC in these inbred rat strains. In study A, the blood volume was measured by using Evans blue dye, and albumin was measured at the start of hemorrhage. In study B, blood volume was not measured, and albumin was measured twice, near the start and end of hemorrhage (approximately 14 min apart). Neither study revealed any interstrain differences in PAC, which decreased after hemorrhage in all 5 strains. No correlation was found between PAC and plasma volume, survival time, blood lactate, or blood base excess. Percentage changes in PAC during hemorrhage were greater in salt-sensitive compared with Lewis rats. Moreover, these percentage changes were associated with survival time in Fawn hooded hypertensive rats. Our data show that the plasma volumes we measured previously were not misrepresented due to variations in PAC.


Metabolomic and transcriptomic analyses identify external conditions and key genes underlying high levels of toxic glycoalkaloids in tubers of stress-sensitive potato cultivars.
High levels of toxic steroidal glycoalkaloids (SGAs) in potato tubers constitute a recognized food quality problem. Tuber SGA levels vary between potato cultivars and can increase after post-harvest stresses such as wounding and light exposure. A few cultivars, e.g., 'Magnum Bonum' and 'Lenape,' have been withdrawn from commercial sales due to excessive SGA levels during some cultivation years. However, these sudden SGA increases are diffucult to predict, and their causes are not understood. To identify external and genetic factors that underlie sudden SGA increases in certain potato cultivars, we have here in a 2-year study investigated 'Magnum Bonum' and five additional table potato cultivars for their SGA levels after wounding and light exposure. Results showed that 'Magnum Bonum' has an unusual strong SGA response to light exposure, but not to wounding, whereas 'Bintje' displayed an opposite regulation. Levels of calystegine alkaloids were not significantly altered by treatments, implicating independent metabolic regulation of SGA and calystegine levels also under conditions of high SGA accumulation. Metabolomic and transcriptomic analyses identified a small number of key genes whose expression correlated with SGA differences between cultivars. Overexpression of two key genes in transgenic low-SGA potato cultivars increased their leaf SGA levels significantly. The results show that a strong response to light can underlie the SGA peaks that occasionally occur in certain potato cultivars and indicate that a between-cultivar variation in the expression of single SGA key genes can account for cultivar SGA differerences. We propose that current attempts to mitigate the SGA hazard will benefit from an increased consideration of cultivar-dependent SGA responses to post-harvest conditions, particularly light exposure. The identified key SGA genes can now be used as a molecular tool in this work.


Amplitude of low frequency fluctuations during resting state predicts social well-being.
Social well-being represents primarily public phenomena, which is crucial for mental and physical health. However, little is known about the neural basis of this construct, especially how it is maintained during resting state. To explore the neural correlates of social well-being, this study correlated the regional fractional amplitude of low frequency fluctuations (fALFF) with social well-being of healthy individuals. The results revealed that the fALFF in the bilateral posterior superior temporal gyrus (pSTG), right anterior cingulate cortex (ACC), right thalamus and right insula positively predicted individual differences in social well-being. Furthermore, we demonstrated the different role of three pursuits of human well-being (i.e., pleasure, meaning and engagement) in these associations. Specifically, the pursuits of meaning and engagement, not pleasure mediated the effect of the fALFF in right pSTG on social well-being, whereas the pursuit of engagement mediated the effect of the fALFF in right thalamus on social well-being. Taken together, we provide the first evidence that spontaneous brain activity in multiple regions related to self-regulatory and social-cognitive processes contributes to social well-being, suggesting that the spontaneous activity of the human brain reflects the efficiency of social well-being.


[Symptomatology, differential diagnosis and treatment of bacterial meningitis of newborns and infants (author's transl)].
Bacterial meningitis in our hospital too shows its maximal frequence with 30.5% in the first month of life, 25.2% of these cases being newborns. The frequent difficulties of diagnosis in this period of life are demonstrated. Predisposing factors and possible complications of meningitis are named. The principles of modern therapy are summarized.


Nanoimprint lithography of Al nanovoids for deep-UV SERS.
Deep-ultraviolet surface-enhanced Raman scattering (UV-SERS) is a promising technique for bioimaging and detection because many biological molecules possess UV absorption lines leading to strongly resonant Raman scattering. Here, Al nanovoid substrates are developed by combining nanoimprint lithography of etched polymer/silica opal films with electron beam evaporation, to give a high-performance sensing platform for UV-SERS. Enhancement by more than 3 orders of magnitude in the UV-SERS performance was obtained from the DNA base adenine, matching well the UV plasmonic optical signatures and simulations, demonstrating its suitability for biodetection.


ERP-pupil size correlations reveal how bilingualism enhances cognitive flexibility.
A bilingual upbringing has been shown to enhance executive control, but the neural mechanisms underpinning such effect are essentially unknown. Here, we investigated whether monolingual and bilingual toddlers differ in semantic processing efficiency and their allocation of attention to expected and unexpected visual stimuli. We simultaneously recorded event-related brain potentials (ERPs) and pupil size in monolingual and bilingual toddlers presented with (spoken) word-picture pairs. Although ERP effects elicited by semantic relatedness were indistinguishable between the two children groups, pictures unrelated to the preceding word evoked greater pupil dilation than related pictures in bilinguals, but not in monolinguals. Furthermore, increasing pupil dilation to unrelated pictures was associated with decreasing N400 amplitude in bilinguals, whereas the monolingual toddlers showed the opposite association. Hence, attention to unexpected stimuli seems to hamper semantic integration in monolinguals, but to facilitate semantic integration in bilinguals, suggesting that bilingual toddlers are more tolerant to variation in word-referent mappings. Given the link between pupil dilation and norepinephrine-driven cognitive efficiency, correlations between ERP amplitude and concurrent pupil dilation provide new insights into the neural bases of the bilingual cognitive advantage.


A Real-Time Arrhythmia Heartbeats Classification Algorithm Using Parallel Delta Modulations and Rotated Linear-Kernel Support Vector Machines.
Real-time wearable electrocardiogram monitoring sensor is one of the best candidates in assisting cardiovascular disease diagnosis. In this paper, we present a novel real-time machine learning system for Arrhythmia classification. The system is based on the parallel Delta modulation and QRS/PT wave detection algorithms. We propose a patient dependent rotated linear-kernel support vector machine classifier that combines the global and local classifiers, with three types of feature vectors extracted directly from the Delta modulated bit-streams. The performance of the proposed system is evaluated using the MIT-BIH Arrhythmia database. According to the AAMI standard, two binary classifications are performed and evaluated, which are supraventricular ectopic beat (SVEB) versus the rest four classes, and ventricular ectopic beat (VEB) versus the rest. For SVEB classification, the preferred SkP-32 method's F1 score, sensitivity, specificity, and positive predictivity value are 0.83, 79.3%, 99.6%, and 88.2%, respectively, and for VEB classification, the numbers are 0.92%, 92.8%, 99.4%, and 91.6%, respectively. The results show that the performance of our proposed approach is comparable to that of published research. The proposed low-complexity algorithm has the potential to be implemented as an on-sensor machine learning solution.


Antidepressant-Like Effect of the Endogenous Neuroprotective Amine, 1MeTIQ in Clonidine-Induced Depression: Behavioral and Neurochemical Studies in Rats.
Biogenic amines such as norepinephrine, dopamine, and serotonin play a well-described role in the treatment of mood disorders especially depression. Animal models are widely used to study antidepressant-like effect in rodents; however, it should be taken into account that pharmacological models do not always answer to the complexity of the disease processes. This study verified the behavioral (forced swim test (FST), locomotor activity test) and neurochemical effects (monoamines metabolism) of a low dose of clonidine (0.1 mg/kg i.p.) which was used as an experimental model of depression. In such pharmacological model, we investigated the antidepressant-like effect of an endogenous neuroprotective amine, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) administered in a dose of 25 mg/kg (i.p.) before clonidine in the behavioral and neurochemical tests carried out in rats. The behavioral study has shown that clonidine produced depression in the locomotor activity test but did not cause pro-depressive effect in the FST. 1MeTIQ produced antidepressant-like effect in the FST and completely antagonized clonidine-induced sedation in the locomotor activity test. Neurochemical data demonstrated that clonidine produced a significant inhibition of monoamine metabolism in the central nervous system. The release of dopamine, noradrenaline, and serotonin as well as the rate of their metabolism were diminished in the investigated brain structures (frontal cortex, hypothalamus, and striatum). 1MeTIQ completely antagonized the clonidine-induced depression of monoaminergic systems and restored their levels to the control values. 1MeTIQ as an endogenous neuroprotective compound with a distinct antidepressant-like activity in rodents produces hope on the efficiency of antidepressant medicines for future practical clinical use.


Biodegradation of all stereoisomers of the EDTA substitute iminodisuccinate by Agrobacterium tumefaciens BY6 requires an epimerase and a stereoselective C-N lyase.
Biodegradation tests according to Organization for Economic Cooperation and Development standard 301F (manometric respirometry test) with technical iminodisuccinate (IDS) revealed ready biodegradability for all stereoisomers of IDS. The IDS-degrading strain Agrobacterium tumefaciens BY6 was isolated from activated sludge. The strain was able to grow on each IDS isomer as well as on Fe(2+)-, Mg(2+)-, and Ca(2+)-IDS complexes as the sole carbon, nitrogen, and energy source. In contrast, biodegradation of and growth on Mn(2+)-IDS were rather scant and very slow on Cu(2+)-IDS. Growth and turnover experiments with A. tumefaciens BY6 indicated that the isomer R,S-IDS is the preferred substrate. The IDS-degrading enzyme system isolated from this organism consists of an IDS-epimerase and a C-N lyase. The C-N lyase is stereospecific for the cleavage of R,S-IDS, generating d-aspartic acid and fumaric acid. The decisive enzyme for S,S-IDS and R,R-IDS degradation is the epimerase. It transforms S,S-IDS and R,R-IDS into R,S-IDS. Both enzymes do not require any cofactors. The two enzymes were purified and characterized, and the N-termini were sequenced. The purified lyase and also the epimerase catalyzed the transformation of alkaline earth metal-IDS complexes, while heavy metal-IDS complexes were transformed rather slowly or not at all. The observed mechanism for the complete mineralization of all IDS isomers involving an epimerase offers an interesting possibility of funneling all stereoisomers into a catabolic pathway initiated by a stereoselective lyase.


Surface State Tunneling Signatures in the Two-Component Superconductor UPt_{3}.
Quasiparticle interference (QPI) imaging of Bogoliubov excitations in quasi-two-dimensional unconventional superconductors has become a powerful technique for measuring the superconducting gap and its symmetry. Here, we present the extension of this method to three-dimensional superconductors and analyze the expected QPI spectrum for the two-component heavy-fermion superconductor UPt_{3} whose gap structure is still controversial. Starting from a 3D electronic structure and the three proposed chiral gap models E_{1g,u} or E_{2u}, we perform a slab calculation that simultaneously gives extended bulk states and topologically protected in-gap dispersionless surface states. We show that the number of Weyl arcs and their hybridization with the line node provides a fingerprint that may finally determine the true nodal structure of the UPt_{3} superconductor.


Repeat motions and backbone flexibility in designed proteins with different numbers of identical consensus tetratricopeptide repeats.
The tetratricopeptide repeat (TPR) is a 34-residue helix-turn-helix motif that occurs as three or more tandem repeats in a wide variety of proteins. We have determined the repeat motions and backbone fluctuations of proteins containing two or three consensus TPR repeats (CTPR2 and CPTR3, respectively) using 15N NMR relaxation measurements. Rotational diffusion tensors calculated from these data for each repeat within each TPR protein indicate that there is a high degree of motional correlation between different repeats in the same protein. This is consistent with the prevailing view that repeat proteins, such as CTPR2 and CTPR3, behave as single cooperatively folded domains. The internal motions of backbone NH groups were determined using the Lipari-Szabo model-free formalism. For most residues, there was a clear separation between the influence of internal motion and the influence of global rotational tumbling on the observed magnetic relaxation. The local internal motions are highly restricted in most of the helical elements, with slightly greater flexibility in the linker elements. Comparisons between CTPR2 and CTPR3 indicate that an addition of a TPR repeat to the C-terminus (before the solvation helix) of CTPR2 slightly reduces the flexibility of the preceding helix.


The efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of endometriosis: A protocol for systematic review and meta-analysis.
Endometriosis (EMS) is one of the common diseases in women, which seriously affects the quality of life of women. Leuprorelin acetate can control the development of EMS, but long-term use can cause perimenopausal symptoms in women. Clinical studies have shown that Kuntai capsule combined with leuprorelin acetate is effective in the treatment of EMS, which can relieve perimenopausal symptoms, but it lacks of evidence-based medical evidence. Therefore, this study aims to systematically evaluate the efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS. CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, PubMed, The Cochrance Library, Embase, Web of Science, and other databases were searched by computer to collect randomized controlled trials of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS. The retrieval time was from the establishment of the database to February 2021. Two researchers screened the literatures and extracted the data and meta-analysis was performed using RevMan 5.3 software. This study evaluated the efficacy and safety of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS by clinical effective rate, serum sex hormone levels estradiol, follicle-stimulating hormone, luteinizing hormone, visual analogue scale, Kupperman score and incidence of adverse reactions. This study will provide reliable evidence-based evidence for the clinical application of Kuntai capsule combined with leuprorelin acetate in the treatment of EMS. Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. DOI 10.17605/OSF.IO/AZU47.


Micro/Nanoscale 3D Assembly by Rolling, Folding, Curving, and Buckling Approaches.
The miniaturization of electronics has been an important topic of study for several decades. The established roadmaps following Moore's Law have encountered bottlenecks in recent years, as planar processing techniques are already close to their physical limits. To bypass some of the intrinsic challenges of planar technologies, more and more efforts have been devoted to the development of 3D electronics, through either direct 3D fabrication or indirect 3D assembly. Recent research efforts into direct 3D fabrication have focused on the development of 3D transistor technologies and 3D heterogeneous integration schemes, but these technologies are typically constrained by the accessible range of sophisticated 3D geometries and the complexity of the fabrication processes. As an alternative route, 3D assembly methods make full use of mature planar technologies to form predefined 2D precursor structures in the desired materials and sizes, which are then transformed into targeted 3D mesostructures by mechanical deformation. The latest progress in the area of micro/nanoscale 3D assembly, covering the various classes of methods through rolling, folding, curving, and buckling assembly, is discussed, focusing on the design concepts, principles, and applications of different methods, followed by an outlook on the remaining challenges and open opportunities.


Effect of culture conditions on cathepsin B inhibitor production by a marine bacterium, Pseudomonas sp. strain PB01.
A novel cathepsin B inhibitor-producing bacterium was isolated from marine sediments and identified based on its 16S rDNA sequence as Pseudomonas sp. strain PB01 (Accession No. EU126129). The growth and enzyme inhibitor production were investigated under various culture conditions. A mixture of organic nitrogen source was required for the optimal production, whereas both glucose and maltose proved to be the effective carbon sources for cathepsin B inhibitor production. Other optimal culture conditions included temperature range between 25 and 28 degrees, initial medium pH of 6.6, and shaking speed of 200 rpm. Under these optimal conditions, the maximum inhibitory activity from culture broth was approximately 50% after 30 h of cultivation. Additionally, kinetic study revealed that inhibitor production paralleled with cell growth, which suggested that the inhibitor may be a primary metabolite of that bacterium.


High-level expression of an Aspergillus niger endo-beta-1,4-glucanase in Pichia pastoris through gene codon optimization and synthesis.
To improve the expression efficiency of recombinant endo-beta-1,4-glucanase in P. pastoris, the endo-beta-1,4-glucanase (egI) gene from Aspergillus niger was synthesized using optimized codons. Fourteen pairs of oligonucleotides with 15 bp overlap were designed and the full-length syn-egI gene was generated by two-step PCR-based DNA synthesis. In the synthesized endo-beta-1,4-glucanase gene syn-egI, 193 nucleotides were changed, and the G+C content was decreased from 54% to 44.2%. The syn-egI gene was inserted into pPIC9K and transformed into P. pastoris GS115 by electroporation. The enzyme activity of recombinant P. pastoris stain 2-7# reached 20.3 U/ml with 1% barley beta-glucan and 3.3 U/ml with 1% carboxymethylcellulose (CMC) as substrate in shake flasks versus 1270.3 U/ml and 220.7 U/ml for the same substrates in 50 l fermentors. The molecular mass of the recombinant protein was approximately 40 kDa as determined by SDS-PAGE analysis, the optimal temperature for recombinant enzyme activity was 70 degrees C and the optimal pH was 5.0 when CMC was used as the substrate.


Formation of epsilon-hydroxycaproate and epsilon-aminocaproate from N-nitrosohexamethyleneimine: evidence that microsomal alpha-hydroxylation of cyclic nitrosamines may not always involve the insertion of molecular oxygen into the substrate.
The formation of the products of microsomal metabolism of the cyclic nitrosamine, nitrosohexamethyleneimine (NO-HEX) were studied. Information on the origins of the oxygen atoms in four major metabolites of NO-HEX was obtained by metabolizing this compound in an 18O2 atmosphere using microsomes and cytosol, beta- and gamma-Hydroxy-NO-HEX are formed as a result of the insertion of a hydroxyl group derived from molecular oxygen into NO-HEX. All of the oxygen atoms in epsilon-aminocaproate (EAC) were derived from water. Approximately half of the molecules of epsilon- hydroxycaproate ( EHC ) contain an 18O atom; thus, half of the alpha-hydroxy-NO-HEX formed incorporates a hydroxyl group derived from molecular oxygen with the remainder of the hydroxyls being from water. To account for the above data and the related metabolic origins of EAC and EHC ( Hecker and McClusky , Cancer Res., 42 (1982) 59; Hecker et al., Teratogen. Carcinogen. Mutagen (1982) in press), we have proposed a mechanism for the formation of these compounds from cyclic nitrosamines catalyzed by microsomal and cytosolic enzymes.


A tale of two tragedies.
When the World Trade Center and the Pentagon were attacked on September 11, Americans were stunned by the tragedy unfolding before them on television. Thousands of lives were lost in the outcome, resulting in an unprecedented outpouring of sympathy, support and demands for action. Most people felt they had never seen or experienced anything like it before. To a smaller portion of the population, however, the shock of sudden and unforeseen disaster was strangely reminiscent of what we experienced in the onset of the AIDS epidemic. There were many similarities to what people were feeling then and now. Little more than a month after the terrorist attacks, however, it was clear that there were also some striking dissimilarities that added to the pain felt by all those who have lost someone to AIDS. Those dissimilarities became clearer with each passing month.


Two Cases of Congenital Chylethorax: A Successful Story of Medical Management.
Congenital chylothorax (CC) is one of the most common causes of pleural effusions in neonates. Associated ipsilateral pulmonary aplasia in CC results in neonatal respiratory distress. Here, we report 2 cases of CC who were managed in the Teaching Hospital Karapitiya, Sri Lanka, between 2017 and 2019. Both babies were males who presented with respiratory distress within a few hours of birth. Their antenatal ultrasound scans failed to detect CC. Chest radiographs showed left-sided pleural effusions. Pleural fluid was milky yellowish suggestive of chylothorax, and the analysis revealed elevated triglycerides, high lymphocyte counts, and low cholesterol levels compatible with CC. They were managed in the neonatal intensive care unit and kept nil by mouth for initial 48 hours. Intravenous octeotride infusion was started on day one and was continued for 7 and 10 days, respectively. The maximum dose of octeotride was 2 μg/kg/hour. Both babies needed intercostal tube placement for 5 and 6 days, respectively. None of them required invasive ventilation. They were started on a medium-chain fatty acid formula, which was continued for about one week. Both babies were commenced on breast milk by day 7 of life and continued with exclusive breastfeeding. Within two weeks, they were discharged home and followed up in the paediatric respiratory clinic for another year. None of them was found to have long-term respiratory complications during the follow-up.


Distinctiveness of management in a university psychiatric hospital as a public health institution.
The distinctiveness of management of a university psychiatric hospital which has the status of a public health institution is manifested in the following ways: * Distinctive features and characteristics of managing service provider organizations compared to those whose operational results involve tangible products; * Distinctive features of management which originate from its role as a regional hospital and a tertiary research and educational institution in the field of psychiatry, with special importance for the Republic of Slovenia as a whole; * Distinctive features of management that are defined by the social and legal framework of operation of public health institutions and their special social mission. This paper therefore discusses the specific theoretical and practical findings regarding management of service provider organizations from the viewpoint of their social mission and significance, as well as their legal organization, internal structure and values.


Mathematical modelling of schistosomiasis japonica: comparison of control strategies in the People's Republic of China.
We present the first mathematical model on the transmission dynamics of Schistosoma japonicum. The work extends Barbour's classic model of schistosome transmission. It allows for the mammalian host heterogeneity characteristic of the S. japonicum life cycle, and solves the problem of under-specification of Barbour's model by the use of Chinese data we are collecting on human-bovine transmission in the Poyang Lake area of Jiangxi Province in China. The model predicts that in the lake/marshland areas of the Yangtze River basin: (1) once-yearly mass chemotherapy of humans is little better than twice-yearly mass chemotherapy in reducing human prevalence. Depending on the heterogeneity of prevalence within the population, targeted treatment of high prevalence groups, with lower overall coverage, can be more effective than mass treatment with higher overall coverage. Treatment confers a short term benefit only, with prevalence rising to endemic levels once chemotherapy programs are stopped; (2) depending on the relative contributions of bovines and humans, bovine treatment can benefit humans almost as much as human treatment. Like human treatment, bovine treatment confers a short-term benefit. A combination of human and bovine treatment will dramatically reduce human prevalence and maintains the reduction for a longer period of time than treatment of a single host, although human prevalence rises once treatment ceases; (3) assuming 75% coverage of bovines, a bovine vaccine which acts on worm fecundity must have about 75% efficacy to reduce the reproduction rate below one and ensure mid-term reduction and long-term elimination of the parasite. Such a vaccination program should be accompanied by an initial period of human treatment to instigate a short-term reduction in prevalence, following which the reduction is enhanced by vaccine effects; (4) if the bovine vaccine is only 45% efficacious (the level of current prototype vaccines) it will lower the endemic prevalence, but will not result in elimination. If it is accompanied by an initial period of human treatment and by a 45% improvement in human sanitation or a 30% reduction in contaminated water contact by humans, elimination is then possible.