The effects of the irregular sample and missing data in time series analysis.
Human self-report time series data are typically marked by irregularities in sampling rates; furthermore, these irregularities are typically natural outcomes of the data generation process. Relatively little has been published to assist the analysis of irregularly sampled data. We report the results of a series of computational experiments on synthetic data sets designed to assess the utility of techniques for handling irregular time series data. The behavior of a conservative quasiperiodic, a dissipative chaotic, and a self-organized critical dynamics were sampled regularly in time and the regular sampling was disrupted by data point removal or by stochastic shifts in time. Missing data segments were then patched by means of segment concatenation, by segment filling with average data values, or by local interpolation in phase space. We compared results of nonlinear analytical tools such as autocorrelations and correlation dimensions using complete and patched sets, as well as power spectra with Lomb periodograms of the decimated sets. Local interpolation in phase space was particularly successful at preserving key features of the original data, but required potentially impractical quantities of intact data as a primer. While the other patching methods are not limited by the need for intact data, they distort results relative to the intact series. We conclude that irregularly sampled data sets with as much as 15 percent missing data can potentially be re-sampled or repaired for analysis with techniques that assume regular sampling without introducing substantial errors.


Effects of Rab27A and Rab27B on Invasion, Proliferation, Apoptosis, and Chemoresistance in Human Pancreatic Cancer Cells.
Rab family members are key regulatory factors that function as molecular switches in multiple phases of vesicular trafficking. Our previous study demonstrated that Rab27A and Rab27B overexpression may predict a poor outcome of pancreatic ductal adenocarcinoma. The purpose of this study was to investigate the role of Rab27A and Rab27B in the progression of pancreatic cancer. We down-regulated Rab27A and Rab27B expression in pancreatic cancer cell lines. The regulatory effects of knockdown Rab27A and Rab27B on pancreatic cancer cell were measured by cisplatin assay, invasion assay, proliferation assay, and Western blot assay. Rab27A and Rab27B down-regulation enhances sensitivity to cisplatin and induces apoptosis in ASPC-1 and PANC-1 cells. In addition, down-regulation of Rab27A reduced the invasive and proliferative ability of ASPC-1 cells, and Rab27B knockdown significantly prevented cancer invasion and proliferation in PANC-1 cells. Our findings provide evidence that Rab27A and Rab27B play significant roles in cell invasion, proliferation, and apoptosis, as well as in chemotherapy resistance.


Effect of 12-month treatment with metformin and/or oral contraceptives on health-related quality of life in polycystic ovary syndrome.
Health-related quality of life (HRQoL) is impaired in polycystic ovary syndrome (PCOS), but the effect of treatment with metformin (M) and/or oral contraceptives (OCP) is undetermined. To assess changes in HRQoL during 12-month randomized treatment with M, OCP or M + OCP in PCOS. Ninety women with PCOS were randomized to treatment with M, OCP or M + OCP. HRQoL was evaluated by a PCOS-specific visual analog scale (PCOS-VAS) regarding 1: Facial hair, 2: Body hair, 3: Acne, 4: Irregular menses, 5: Weight and 6: PCOS in general, and Short Form 36 (SF-36). PCOS-VAS1(facial hair) improved during treatment with OCP (n = 23) compared to M (n = 19), and during M + OCP (n = 23) compared to M treatment, whereas changes in PCOS-VAS2-6 and SF-36 scores were comparable between the three medical intervention groups. Pooled data (n = 65) showed improved PCOS-VAS scores during treatment (all p < .05), but changes in PCOS-VAS were unassociated with changes in BMI or FG-scores despite significant weight-loss during treatment with M (-3.0 kg (-10.3; 0.6)) and M + OCP (-1.9 kg (-4.9; 0.1)) and decreased FG-score during M + OCP treatment (median (quartiles)). PCOS-VAS scores improved significantly and to the same extent during treatment with M, OCP or M + OCP.


Diazocinones: synthesis and conformational analysis.
1,2,4,5-Tetrazines (prepared from aryl nitriles) condense with isoxazolylcyclobutanones (prepared from 3-benzenesulfonyl-3-vinylcyclobutanol) in methanolic KOH to give conformationally restricted 6-isoxazol-5-yl-6,7-dihydro-5H-[1,2]diazocin-4-ones. The solution 1H NMR spectra of dihydrodiazocinone 1a with phenyl moieties at C3 and C8 reveal two conformations of the eight-membered heterocycle that are non-interconverting on the NMR time scale at ambient temperature. The kinetics of the conversion process, followed by 1H NMR between 21 and 70 degrees C in DMSO solution, yield an activation energy of approximately 21 kcal/mol relative to the kinetic conformer and show an equilibrated ratio of approximately 5:1 of the thermodynamic to the kinetic conformers. The electronic structure calculations on a model dihydrodiazocinone predict geometries for the two conformations. One of these geometries agrees with the X-ray crystallographic analysis of the thermodynamic conformation of 1a.


Kidney dosimetry in 777 patients during 177Lu-DOTATATE therapy: aspects on extrapolations and measurement time points.
Fractionated peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is increasingly applied as an effective treatment for patients with disseminated neuroendocrine tumors. In parallel to dose planning before external beam radiation therapy, dosimetry is also needed to optimize PRRT to the individual patient. Accordingly, absorbed doses to organs at risk need to be calculated during PRRT, based on serial measurements of radioactivity distribution utilizing SPECT/CT. The dosimetry should be based on as few measurements as possible, while still retaining reliable results. The main aim of the present work was to calculate the fractional contribution of the extrapolations of the curve fits for the absorbed dose calculations to the kidneys. The secondary aim was to study agreement between absorbed dose (AD) and the effective half-life (teff) for the kidneys, estimated by means of measurements at one or two time points, in comparison to our current method employing three time points. In 777 patients with disseminated neuroendocrine tumors undergoing PRRT, SPECT/CT over the abdomen was acquired at 1, 4, and 7 days after 177Lu-DOTATATE infusion. The absorbed dose to the kidneys was calculated from SPECT/CT radioactivity distribution data, and the teff and fractional contributions of the extrapolations were estimated, utilizing data from one, two, and three time points, respectively. The fractional contributions from extrapolations before day 1 measurement and after day 7 measurement were approximately 26% and 11%, respectively. The mean differences in absorbed dose, based on one, two, and three time points were small, but with high method dependence for individual patients. The differences in estimated teff were small when it was based on measurements at days 1 and 7, but high for days 1 and 4 time points. When assessing simplifications of methods for calculation of the absorbed dose to the kidneys, it was of the uttermost importance to incorporate the fractional contribution for the extrapolations included in the reference method. Measurements at an early and a late time point were found most important. An intermediate measurement contributes with an idea of the goodness of the fit.


Modeling of the sorption and diffusion processes of volatile organic air pollutants in grape fruits.
A mathematical model for the description of the sorption and diffusion processes of gaseous toluene and p-xylene in fruits of grape has been proposed. This model is based on the Fick's II low regarding a particle with a spherical shape (such as the berry of grapevine) and describes changes of air pollutant concentrations in different layers of the fruit, that is, the wax, peel, and pulp, during an exposure to contaminated air. The mass transfer coefficient and diffusion coefficients in the respective layers can be estimated using the experimental values. The theoretical data and the results from the exposure under steady-state laboratory conditions were compared and showed a good applicability of the proposed model for the prediction of volatile air pollutant partitioning in grape berries.


From data processing to mental organs: an interdisciplinary path to cognitive neuroscience.
Human brain is a highly evolved coordinating mechanism in the species Homo sapiens. It is only in the last 100 years that extensive knowledge of the intricate structure and complex functioning of the human brain has been acquired, though a lot is yet to be known. However, from the beginning of civilisation, people have been conscious of a 'mind' which has been considered the origin of all scientific and cultural development. Philosophers have discussed at length the various attributes of consciousness. At the same time, most of the philosophical or scientific frameworks have directly or indirectly implied mind-body duality. It is now imperative that we develop an integrated approach to understand the interconnection between mind and consciousness on one hand and brain on the other. This paper begins with the proposition that the structure of the brain is analogous, at least to certain extent, to that of the computer system. Of course, it is much more sophisticated and complex. The second proposition is that the Chomskyean concept of 'mental organs' is a good working hypothesis that tries to characterise this complexity in terms of an innate cognitive framework. By following this dual approach, brain as a data processing system and brain as a superstructure of intricately linked mental organs, we can move toward a better understanding of 'mind' within the framework of empirical science. The one 'mental organ' studied extensively in Chomskyean terms is 'language faculty' which is unique in its relation to brain, mind and consciousness.


The effects of garlic supplementation on weight loss: A systematic review and meta-analysis of randomized controlled trials.
Obesity is related to increase in the incidence of morbidity and mortality. Studies have suggested anti-obesity properties of garlic; however, results are inconsistent. This systematic review and meta-analysis is done to summarize the data obtained from available randomized clinical trials on the effect of garlic supplementation on body weight, Body Mass Index (BMI), and Waist Circumference (WC). The online databases of Scopus, PubMed, Google Scholar and Cochrane library were searched until March 2018 for related publications using relevant keywords. Effect sizes of eligible studies were pooled using random-effects models. Cochran's Q-test and I2 index were used for assessing heterogeneity. We found 1241 records in our initial search, of which 13 randomized clinical trials (RCTs) with 15 treatment arms were included. Pooled analysis showed that garlic administration might significantly decrease WC (Weighed Mean Difference (WMD): -1.10 cm, 95% CI: -2.13, -0.07, P = 0.03, I2 = 0%). However, garlic intervention had no significant effect on body weight (WMD): -0.17 kg, 95% CI: -0.75 to 0.39, P = 0.54, I2 = 0%) and BMI (WMD: -0.17 kg/m2, 95% CI: -0.52, 0.16, P = 0.30, I2 = 44.5%) as compared to controls. From Subgroup analysis, it was ascertained that the effect of garlic supplementation on BMI was significant in trials with duration < 12 weeks (WMD: -0.58 kg/m2, 95% CI: -1.08, -0.08, I2 = 19.8%, P = 0.02) compared to those with higher duration (>12 weeks). The current meta-analysis results suggest that garlic supplementation seems to reduce waist circumference unlike body weight and BMI.


Effects of phenytoin and flunarizine on the rise in extracellular potassium induced by repetitive stimulation of rat cerebral cortex.
At a critical intensity of repetitive stimulation, [K+]0 in cerebral cortex increases rapidly to a "ceiling" value of 10-12 mM. Phenomena related to this rapid regenerative increase in [K+]0 were investigated using K+-sensitive microelectrodes. The critical intensity required to induce this rise was found to be increased by phenytoin (90 mg/kg preload + 30 mg/kg presurgery) but not by flunarizine (30 mg/kg preload + 10 mg/kg presurgery), when the stimulus (20 Hz, 0.4 ms pulse duration, 5 or 40 s train duration) was applied to a 1 mm2 area of parietal neocortex in alfentanil-anesthesized rats. Flunarizine and phenytoin appear to differ in their mechanisms of anti-epileptic action.


Recurrent network dynamics reconciles visual motion segmentation and integration.
In sensory systems, a range of computational rules are presumed to be implemented by neuronal subpopulations with different tuning functions. For instance, in primate cortical area MT, different classes of direction-selective cells have been identified and related either to motion integration, segmentation or transparency. Still, how such different tuning properties are constructed is unclear. The dominant theoretical viewpoint based on a linear-nonlinear feed-forward cascade does not account for their complex temporal dynamics and their versatility when facing different input statistics. Here, we demonstrate that a recurrent network model of visual motion processing can reconcile these different properties. Using a ring network, we show how excitatory and inhibitory interactions can implement different computational rules such as vector averaging, winner-take-all or superposition. The model also captures ordered temporal transitions between these behaviors. In particular, depending on the inhibition regime the network can switch from motion integration to segmentation, thus being able to compute either a single pattern motion or to superpose multiple inputs as in motion transparency. We thus demonstrate that recurrent architectures can adaptively give rise to different cortical computational regimes depending upon the input statistics, from sensory flow integration to segmentation.


Liver regeneration during the associating liver partition and portal vein ligation for staged hepatectomy procedure in Sus scrofa is positively modulated by stem cells.
This present study investigated the impact of the application of stem cells to liver regeneration following the first stage of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). The experiment was conducted on a pig model (n=6, 3 that did not receive application of stem cells, 3 that received application stem cells). Collected samples of liver (day 0 and 9 following surgery) were subjected to complete transcriptome sequencing. In total, 39 differentially expressed genes were found in the group without the application of the stem cells (genes of unwanted processes such as fibrosis and inflammation). In the group that did receive application of stem cells, no significantly differentially expressed genes were found, indicating a properly regenerated liver remnant. The present study therefore demonstrated, to the best of our knowledge for the first time, the positive effect of stem cells application in the liver regeneration process during ALPPS procedure in the pig model.


11 Beta-hydroxysteroid dehydrogenase type 1 is induced in human monocytes upon differentiation to macrophages.
11beta-hydroxysteroid dehydrogenases (11beta-HSD) perform prereceptor metabolism of glucocorticoids through interconversion of the active glucocorticoid, cortisol, with inactive cortisone. Although the immunosuppressive and anti-inflammatory activities of glucocorticoids are well documented, the expression of 11beta-HSD enzymes in immune cells is not well understood. Here we demonstrate that 11beta-HSD1, which converts cortisone to cortisol, is expressed only upon differentiation of human monocytes to macrophages. 11beta-HSD1 expression is concomitant with the emergence of peroxisome proliferator activating receptor gamma, which was used as a surrogate marker of monocyte differentiation. The type 2 enzyme, 11beta-HSD2, which converts cortisol to cortisone, was not detectable in either monocytes or cultured macrophages. Incubation of monocytes with IL-4 or IL-13 induced 11beta-HSD1 activity by up to 10-fold. IFN-gamma, a known functional antagonist of IL-4 and IL-13, suppressed the induction of 11beta-HSD1 by these cytokines. THP-1 cells, a human macrophage-like cell line, expressed 11beta-HSD1 and low levels of 11beta-HSD2. The expression of 11beta-HSD1 in these cells is up-regulated 4-fold by LPS. In summary, we have shown strong expression of 11beta-HSD1 in cultured human macrophages and THP-1 cells. The presence of the enzyme in these cells suggests that it may play a role in regulating the immune function of these cells.


The Friedreich ataxia region: characterization of two novel genes and reduction of the critical region to 300 kb.
Friedreich ataxia is a severe neurodegenerative autosomal recessive disorder of unknown biochemical defect. The Friedreich ataxia locus (FRDA) is tightly linked to the centromeric side of the D9S5 locus. We have used 'exon-trapping' to identify two new genes, approximately 100 and 200 kb centromeric to D9S5, respectively. One gene appears ubiquitously expressed while the other is prominently expressed in muscle. The ubiquitous transcript codes for a protein containing a 20 aa repeat reminiscent of simple repeats found in several ribonucleoproteins. Using the single-strand conformation polymorphism (SSCP) procedure, we searched for mutations in affected patients in the coding sequence of the two genes, as well as in a gene that we had previously identified in the same region. Eight polymorphic DNA changes but no causative mutations were found, suggesting that the genes are not candidates for Friedreich ataxia. The discovery of a simple sequence repeat polymorphism in the most centromeric gene allowed the localization within that gene of the breakpoint of a previously described recombination in a Friedreich ataxia family, therefore excluding the two distal genes from the FRDA region. The lack of causative mutations in the three genes and the position of the recombination further delineate the FRDA locus to a 300 kb interval.


Effect of cadmium on the roots of beetroot (Beta vulgaris L.).
The article dwells upon identifying the effect of cadmium on the roots of beetroot. The exposure effects of various concentrations of cadmium were studied at different levels of the plant organization (tissue pieces, organelles, membrane vesicles). The effect was noted only at a concentration of 100 μm. The negative effect of cadmium on the roots tissues of beetroot appeared with an increase in permeability and a decrease in the stability of cell membranes due to a change in the composition of fatty acids of membrane lipids and an increase in oxidation processes. The effect of cadmium in model experiments on the activity of the proton pumps of the vacuolar membrane has been evaluated. The pumps provide for the transport of heavy metals into the vacuole, which is one of the effective mechanisms for phytoremediation. The influence of cadmium in model experiments on the activity of the proton pump of a vacuolar membrane was evaluated. Under the influence of cadmium, a decrease in the activity of V-ATPase was observed, while the activity of V-PPase did not change. The results obtained complement our understanding of the damaging effects that occur in plant cells under cadmium stress.


[A new horizon of tuberculosis control and research].
In the 1990s, tuberculosis (TB) came to be recognized as one of re-emerging diseases and as a serious health issue worldwide. This has brought about many innovations for TB control and care. These include a series of bacteriological examination methods based on the nucleic acid amplification, immunological diagnostics for TB infection or active disease. The completion of the whole genome analysis of Mycobacterium tuberculosis opened the way to the development of novel modalities for therapeutics, diagnostics and vaccines. For TB control, WHO developed the DOTS strategy as a standard TB treatment programme that has been being expanded globally, in both developed and developing nations. Japan's TB control programme is being revised drastically in order to meet the change in the TB epidemiology, aiming at realization of the DOTS concept adapted into the Japanese setting of patient care.


[The optimizing design and experiment for a MOEMS micro-mirror spectrometer].
A MOEMS micro-mirror spectrometer, which uses micro-mirror as a light switch so that spectrum can be detected by a single detector, has the advantages of transforming DC into AC, applying Hadamard transform optics without additional template, high pixel resolution and low cost. In this spectrometer, the vital problem is the conflict between the scales of slit and the light intensity. Hence, in order to improve the resolution of this spectrometer, the present paper gives the analysis of the new effects caused by micro structure, and optimal values of the key factors. Firstly, the effects of diffraction limitation, spatial sample rate and curved slit image on the resolution of the spectrum were proposed. Then, the results were simulated; the key values were tested on the micro mirror spectrometer. Finally, taking all these three effects into account, this micro system was optimized. With a scale of 70 mm x 130 mm, decreasing the height of the image at the plane of micro mirror can not diminish the influence of curved slit image in the spectrum; under the demand of spatial sample rate, the resolution must be twice over the pixel resolution; only if the width of the slit is 1.818 microm and the pixel resolution is 2.2786 microm can the spectrometer have the best performance.


The X factor: A robust and powerful approach to X-chromosome-inclusive whole-genome association studies.
The X-chromosome is often excluded from genome-wide association studies because of analytical challenges. Some of the problems, such as the random, skewed, or no X-inactivation model uncertainty, have been investigated. Other considerations have received little to no attention, such as the value in considering nonadditive and gene-sex interaction effects, and the inferential consequence of choosing different baseline alleles (i.e., the reference vs. the alternative allele). Here we propose a unified and flexible regression-based association test for X-chromosomal variants. We provide theoretical justifications for its robustness in the presence of various model uncertainties, as well as for its improved power when compared with the existing approaches under certain scenarios. For completeness, we also revisit the autosomes and show that the proposed framework leads to a more robust approach than the standard method. Finally, we provide supporting evidence by revisiting several published association studies. Supporting Information for this article are available online.


Fully automated, high speed, tomographic phase object reconstruction using the transport of intensity equation in transmission and reflection configurations.
While traditional transport of intensity equation (TIE) based phase retrieval of a phase object is performed through axial translation of the CCD, in this work a tunable lens TIE is employed in both transmission and reflection configurations. These configurations are extended to a 360° tomographic 3D reconstruction through multiple illuminations from different angles by a custom fabricated rotating assembly of the phase object. Synchronization circuitry is developed to control the CCD camera and the Arduino board, which in its turn controls the tunable lens and the stepper motor to automate the tomographic reconstruction process. Finally, a MATLAB based user friendly graphical user interface is developed to control the whole system and perform tomographic reconstruction using both multiplicative and inverse radon based techniques.


Comparison of the Memory Foam Pad Versus the Bean Bag with Shoulder Braces in Preventing Patient Displacement during Gynecologic Laparoscopic Surgery.
To compare the amount of patient displacement when a memory foam pad is used versus a bean bag with shoulder braces. The secondary aim was to evaluate for postoperative extremity symptoms including pain, numbness, and weakness. A prospective randomized pilot study (Canadian Task Force classification I). A single academic institution. Women ≥18 years of age undergoing laparoscopic or robotic gynecologic surgery. Patients were randomized to be positioned on the memory foam pad (group A) or the bean bag with shoulder braces (group B) preoperatively. The patients' positions were measured before and after the procedure, and the displacement was recorded. Patients were followed postoperatively and questioned regarding upper extremity or lower extremity weakness, numbness, and pain. Demographic characteristics were collected using the electronic medical record. Forty-three patients were included in the study (22 in group A and 21 in group B). The demographic and intraoperative characteristics of the patients were similar in both groups. The patients in group A moved a mean distance of 3.80 ± 3.32 cm, whereas those in group B moved a mean distance of 1.07 ± 1.93 cm (p = .002). A Pearson correlation coefficient did not yield a correlation between patient displacement and age, body mass index, length of surgery, or pathology weight. In group A, 2 patients had lower extremity numbness, and 1 patient had upper extremity numbness. In group B, 1 patient had upper extremity pain, and 1 patient had both upper and lower extremity numbness. These patients had complete resolution of their symptoms within the first 2 weeks postoperatively, with the exception of 1 patient in group A whose lower extremity numbness resolved 3 months postoperatively. Positioning patients on the bean bag with shoulder braces resulted in significantly less displacement during gynecologic laparoscopic surgery when compared with the memory foam pad. All postoperative extremity numbness, weakness, and pain were temporary and resolved completely in our cohort. A larger study would be necessary to determine the true incidence of peripheral nerve injuries because these are rare complications of laparoscopic surgeries.


The role of fibrin sealants in hepatic surgery.
The repair of all tissue disruption begins with hemostasis and tissue sealing. Fibrin sealant is a concentrated mix of the factors required for the body to initiate this process. By applying this mixture directly to the site of injury, clotting and wound healing can be facilitated. Studies have demonstrated that fibrin sealant is effective in controlling bleeding and inducing tissue sealing in many organs. It is particularly useful in hepatobiliary surgery due to the soft nature of liver parenchyma and its propensity to bleed and leak bile. This chapter will discuss the basic science foundation of fibrin sealants and their applications in hepatic surgery.


Structural basis for L-lysine feedback inhibition of homocitrate synthase.
The alpha-aminoadipate pathway of lysine biosynthesis is modulated at the transcriptional and biochemical levels by feedback inhibition. The first enzyme in the alpha-aminoadipate pathway, homocitrate synthase (HCS), is the target of the feedback regulation and is strongly inhibited by l-lysine. Here we report the structure of Schizosaccharomyces pombe HCS (SpHCS) in complex with l-lysine. The structure illustrates that the amino acid directly competes with the substrate 2-oxoglutarate for binding within the active site of HCS. Differential recognition of the substrate and inhibitor is achieved via a switch position within the (alpha/beta)(8) TIM barrel of the enzyme that can distinguish between the C5-carboxylate group of 2-oxoglutarate and the epsilon-ammonium group of l-lysine. In vitro and in vivo assays demonstrate that mutations of the switch residues, which interact with the l-lysine epsilon-ammonium group, abrogate feedback inhibition, as do substitutions of residues within the C-terminal domain that were identified in a previous study of l-lysine-insensitive HCS mutants in Saccharomyces cerevisiae. Together, these results yield new insights into the mechanism of feedback regulation of an enzyme central to lysine biosynthesis.


Palliative limb salvage using a retrograde nail-cement composite after intercalary resection of a distal femoral osteosarcoma: a case report.
Malignant lower-limb metaphyseal and diaphyseal bone tumours that have not yet invaded the epiphysis can usually be managed with limb-sparing surgery. Reconstructions using intercalary allografts, autoclaved autografts, extracorporeally irradiated autografts, vascularised autografts, and distraction osteogenesis have all achieved favourable results. In patients with metastatic disease and a short life expectancy, reconstruction with allografts or autografts should be carefully considered because a long recovery period is needed. An intercalary endoprosthesis provides immediate stability, a short recovery period and a low implant failure rate. Nonetheless, it may be expensive when there is inadequate space for stem insertion, necessitating a custom-made endoprosthesis. We present a 12-year-old boy with stage-III osteosarcoma of the metaphysis and diaphysis of the femur who underwent knee joint salvage and reconstruction with a retrograde, locked, intramedullary nail surrounded with methylmethacrylate. At the one-month follow-up, the patient could walk unassisted. At the 2-year follow-up, his Musculoskeletal Tumor Society score was 83%. The patient died from lung metastases at 31 months. He had not experienced any complications with the reconstruction.


Fine-root turnover patterns and their relationship to root diameter and soil depth in a 14C-labeled hardwood forest.
Characterization of turnover times of fine roots is essential to understanding patterns of carbon allocation in plants and describing forest C cycling. We used the rate of decline in the ratio of 14C to 12C in a mature hardwood forest, enriched by an inadvertent 14C pulse, to investigate fine-root turnover and its relationship with fine-root diameter and soil depth. Biomass and Delta14C values were determined for fine roots collected during three consecutive winters from four sites, by depth, diameter size classes (< 0.5 or 0.5-2 mm), and live-or-dead status. Live-root pools retained significant 14C enrichment over 3 yr, demonstrating a mean turnover time on the order of years. However, elevated Delta14C values in dead-root pools within 18 months of the pulse indicated an additional component of live roots with short turnover times (months). Our results challenge assumptions of a single live fine-root pool with a unimodal and normal age distribution. Live fine roots < 0.5 mm and those near the surface, especially those in the O horizon, had more rapid turnover than 0.5-2 mm roots and deeper roots, respectively.


Higher Serum Vitamin D Levels have a Positive Association with the Incidence of Recidivans Form of Cutaneous Leishmaniasis; A Cross-Sectional Study.
Several manifestations of cutaneous leishmaniasis are related to the host's immune system and the species of parasite. There have been some studies on the relationship between vitamin D statuses in infectious diseases including cutaneous leishmaniasis. However, the results of these studies have been inconsistent. In this cross-sectional study, 147 patients with leishmaniasis were recruited and divided into the following categories: acute cutaneous leishmaniasis (<1 year) (n = 51), chronic cutaneous leishmaniasis (more than 1 year) (n = 26), and leishmaniasis recidivans (the appearance of new papular lesions around a previous scar) (n = 20), and a group of participants without leishmaniasis (n = 50), as a control group. Serum 25-hydroxyvitamin D [25(OH) D] level was analyzed. There were significant differences in serum 25(OH) D between the groups with acute or chronic leishmaniasis and those with recidivans leishmaniasis (P = 0.013 and P = 0.022, respectively). The median serum level of vitamin D in the acute group was 13.7 ng/mL, in the chronic group was 16.05 ng/mL, in the recidivans group was 21.75 ng/mL, and in the control group was 17.97 ng/mL. Higher serum concentrations of 25(OH) vitamin D levels being associated with leishmaniasis recidivans.


Helical structure of phospholamban in membrane bilayers.
The regulation of calcium levels across the membrane of the sarcoplasmic reticulum involves the complex interplay of several membrane proteins. Phospholamban is a 52 residue integral membrane protein that is involved in reversibly inhibiting the Ca(2+) pump and regulating the flow of Ca ions across the sarcoplasmic reticulum membrane during muscle contraction and relaxation. The structure of phospholamban is central to its regulatory role. Using homonuclear rotational resonance NMR methods, we show that the internuclear distances between [1-(13)C]Leu7 and [3-(13)C]Ala11 in the cytoplasmic region, between [1-(13)C]Pro21 and [3-(13)C]Ala24 in the juxtamembrane region and between [1-(13)C]Leu42 and [3-(13)C]Cys46 in the transmembrane domain of phospholamban are consistent with alpha-helical secondary structure. Additional heteronuclear rotational-echo double-resonance NMR measurements confirm that the secondary structure is helical in the region of Pro21 and that there are no large conformational changes upon phosphorylation. These results support the model of the phospholamban pentamer as a bundle of five long alpha-helices. The long extended helices provide a mechanism by which the cytoplasmic region of phospholamban interacts with residues in the cytoplasmic domain of the Ca(2+) pump.


Telomere DNA G-quadruplex folding within actively extending human telomerase.
Telomerase reverse transcribes short guanine (G)-rich DNA repeat sequences from its internal RNA template to maintain telomere length. G-rich telomere DNA repeats readily fold into G-quadruplex (GQ) structures in vitro, and the presence of GQ-prone sequences throughout the genome introduces challenges to replication in vivo. Using a combination of ensemble and single-molecule telomerase assays, we discovered that GQ folding of the nascent DNA product during processive addition of multiple telomere repeats modulates the kinetics of telomerase catalysis and dissociation. Telomerase reactions performed with telomere DNA primers of varying sequence or using GQ-stabilizing K+ versus GQ-destabilizing Li+ salts yielded changes in DNA product profiles consistent with formation of GQ structures within the telomerase-DNA complex. Addition of the telomerase processivity factor POT1-TPP1 altered the DNA product profile, but was not sufficient to recover full activity in the presence of Li+ cations. This result suggests GQ folding synergizes with POT1-TPP1 to support telomerase function. Single-molecule Förster resonance energy transfer experiments reveal complex DNA structural dynamics during real-time catalysis in the presence of K+ but not Li+, supporting the notion of nascent product folding within the active telomerase complex. To explain the observed distributions of telomere products, we globally fit telomerase time-series data to a kinetic model that converges to a set of rate constants describing each successive telomere repeat addition cycle. Our results highlight the potential influence of the intrinsic folding properties of telomere DNA during telomerase catalysis, and provide a detailed characterization of GQ modulation of polymerase function.


Stepping molecular motor amid Lévy white noise.
We consider a model of a stepping molecular motor consisting of two connected heads. Directional motion of the stepper takes place along a one-dimensional track. Each head is subject to a periodic potential without spatial reflection symmetry. When the potential for one head is switched on, it is switched off for the other head. Additionally, the system is subject to the influence of symmetric, white Lévy noise that mimics the action of external random forcing. The stepper exhibits motion with a preferred direction which is examined by analyzing the median of the displacement of a midpoint between the positions of the two heads. We study the modified dynamics of the stepper by numerical simulations. We find flux reversals as noise parameters are changed. Speed and direction appear to very sensitively depend on characteristics of the noise.


Chitosan-covered liposomes as a promising drug transporter: nanoscale investigations.
Liposomes are small artificial vesicles spherical shaped of 50-1000 nm in diameter. They are created from natural non-toxic phospholipids membranes. Externally, they are decorated with biocompatible polymers. Chitosan, a natural polymer, demonstrates exceptional advantages in drug delivery, in particular, as liposome cover. In this paper, Molecular Dynamics simulations (MD) are performed in the coupled NPT-NPH and NVT-NVE statistical ensembles to study the static and dynamic properties of DPPC membrane-bilayer with grafted cationic chitosan chains, with added Cl- anions to neutralize the environment, using the Martini coarse-grained force-field. From the NPT-NPH MD simulations we found a chitosan layer L DM ranging from 3.2 to 6.6 nm for graft chains of a degree of polymerization n p = 45 and different grafting molar fractions X p = 0.005, X p = 0.014 and X p = 0.1. Also, the chitosan chains showed three essential grafting regimes: mushroom, critic, and brush depending on X p. The DPPC bilayer thickness D B and the area per lipid A l increased proportionally to X p. From the NVT-NVE MD simulations, the analysis of the radial distribution function showed that the increase of X p gives a more close-packed and rigid liposome. The analysis of the mean square displacement revealed that the diffusion of lipids is anomalous. In contrast, the diffusion of chitosan chains showed a normal diffusion, just after 100 ps. The diffusion regime of ions is found to be normal and independent of time. For the three identified regimes, the chitosan showed a tendency to adhere to the membrane surface and therefore affect the properties of the liposomal membrane.


Membrane Localization of HspA1A, a Stress Inducible 70-kDa Heat-Shock Protein, Depends on Its Interaction with Intracellular Phosphatidylserine.
HspA1A is a cytosolic molecular chaperone essential for cellular homeostasis. HspA1A also localizes at the plasma membrane (PM) of tumor and stressed cells. However, it is currently unknown how this cytosolic protein translocates to the PM. Taking into account that HspA1A interacts with lipids, including phosphatidylserine (PS), and that lipids recruit proteins to the PM, we hypothesized that the interaction of HspA1A with PS allows the chaperone to localize at the PM. To test this hypothesis, we subjected cells to mild heat-shock and the PM-localized HspA1A was quantified using confocal microscopy and cell surface biotinylation. These experiments revealed that HspA1A's membrane localization increased during recovery from non-apoptotic heat-shock. Next, we selectively reduced PS targets by overexpressing the C2 domain of lactadherin (Lact-C2), a known PS-biosensor, and determined that HspA1A's membrane localization was greatly reduced. In contrast, the reduction of PI(4,5)P2 availability by overexpression of the PLCδ-PH biosensor had minimal effects on HspA1A's PM-localization. Implementation of a fluorescent PS analog, TopFluor-PS, established that PS co-localizes with HspA1A. Collectively, these results reveal that HspA1A's PM localization and anchorage depend on its selective interaction with intracellular PS. This discovery institutes PS as a new and dynamic partner in the cellular stress response.


[Clinical analysis of postoperative recurrent nerve palsy in patients undergoing operation of carcinoma of the thoracic esophagus].
From January 1976 to April 1987, 325 cases of carcinoma of the thoracic esophagus were resected in our department. Among these cases, 25 cases were not included because of direct operative deaths or early hospital deaths, and 300 cases were selected for clinical analysis of postoperative recurrent nerve palsy, which occurred in 75 cases (25.0%). The rate of occurrence of this palsy in the last 6-year period was higher than that in the first 6-year period (34.0% and 15.3%, respectively). It was suggested that the extension of surgical procedures to the cervix and upper mediastinum had contributed to this increase in rate. The sides affected by palsy were as follows: left, 56.0%, right 12.0%, bilateral, 24.0%; unknown, 8.0%. The importance of gentle handling of the left recurrent nerve during operation should be emphasized. The rate of occurrence of palsy in the cases of "Iu" was higher than in cases of "Im" and "Ei" (53.3%, 31.6%, 26.8%, respectively). The rate of occurrence of this palsy was significantly higher in the cases in which cervical anastomosis was performed than in cases in which intrathoracic anastomosis was performed (31.9% and 2.8%, respectively; p less than 0.01). Of the cases complicated by this palsy (Group A), tracheostomy was done in 12.0% of the cases and long-term transnasal tracheal tube cannulation or tube reinsertion done in 29.3%. These rates were significantly higher than the rates for cases who did not develop this palsy (Group B). The rates of occurrence of postoperative pulmonary complications within one month after surgery in Group A and Group B were almost same (24.3% and 21.8%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Drugs in Development for Acute Kidney Injury.
The care of patients with acute kidney injury (AKI) has been limited due to the lack of effective therapeutics that can either prevent AKI during high-risk situations or treat AKI once established. A revolution in the scientific understanding of the pathogenesis of AKI has led to the identification of potential therapeutic targets. These targets include pathways involved in inflammation, cellular repair and fibrosis, cellular metabolism and mitochondrial function, oxidative stress, apoptosis, and hemodynamics and oxygen delivery. Many compounds are entering early-phase clinical trials. In addition, efforts to better describe sub-categories of AKI (through endo-phenotyping) hold promise to target therapies more effectively based upon pathways that are operative in the pathogenesis. These advances bring optimism that the care of patients with AKI will be transformed with the hope of better outcomes.


Leptospiral uveitis - there is more to it than meets the eye!
Leptospirosis, caused by pathogenic species of genus Leptospira, is a highly prevalent zoonotic disease throughout many parts of the world, and an important emerging disease within the United States. Uveitis is a common complication of systemic infection in humans. A similar condition in horses is characterized by recurrent bouts of inflammation. In this article, we review advances in our understanding of leptospiral uveitis and its pathogenic mechanisms.


Determining the Association Between Emergency Department Crowding and Debriefing After Pediatric Trauma Resuscitations.
Debriefing in the pediatric emergency department (PED) is an invaluable tool to improve team well-being, communication, and performance. Despite evidence, surveys have reported heavy workload as a barrier to debriefing leading to missed opportunities for improvement in an already busy ED. The study aims to determine the association between the incidence of debriefing after pediatric trauma resuscitations and PED crowding. A total of 491 Trauma One activations in Riley Children's Hospital Pediatric Emergency Department that presented between April 2018 to December 2019 were included in the study. Debriefing documentations, patient demographics, time and date of presentation, mechanism of injury, injury severity score, disposition from PED, and length of stay (LOS) were collected and analyzed. The National Emergency Department Overcrowding Scale score at arrival, Average LOS, total PED census, total PED waiting room census, and rates of left without being seen were compared between groups. Of 491 Trauma One activations presented to our PED, 50 (10%) trauma evaluations had documented debriefing. The National Emergency Department Overcrowding Scale score at presentation was significantly lower in those with debriefing versus without debriefing. In addition, the PED hourly census, waiting room census, average LOS, and left without being seen were also significantly lower in the group with debriefing. In addition, trauma cases with debriefing had a higher proportion of patients with profound injuries and discharges to the morgue. Pediatric emergency department crowding is a significant barrier to debriefing after trauma resuscitations. However, profound injuries and traumatic pediatric deaths remain the strongest predictors in conducting debriefing regardless of PED crowding status.


Increased excitability of cortical neurons induced by associative learning: an ex vivo study.
In adult mice, classical conditioning in which whisker stimulation is paired with an electric shock to the tail results in a decrease in the frequency of head movements, induces expansion of the cortical representation of stimulated vibrissae and enhances inhibitory synaptic interactions within the 'trained' barrels. We investigated whether such a simple associative learning paradigm also induced changes in neuronal excitability. Using whole-cell recordings from ex vivo slices of the barrel cortex we found that layer IV excitatory cells located in the cortical representation of the 'trained' row of vibrissae had a higher frequency of spikes recorded at threshold potential than neurons from the 'untrained' row and than cells from control animals. Additionally, excitatory cells within the 'trained' barrels were characterized by increased gain of the input-output function, lower amplitudes of fast after-hyperpolarization and decreased effect of blocking of BK channels by iberiotoxin. These findings provide new insight into the possible mechanism for enhanced intrinsic excitability of layer IV excitatory neurons. In contrast, the fast spiking inhibitory cells recorded in the same barrels did not change their intrinsic excitability after the conditioning procedure. The increased excitability of excitatory neurons within the 'trained' barrels may represent the counterpart of homeostatic plasticity, which parallels enhanced synaptic inhibition described previously. Together, the two mechanisms would contribute to increase the input selectivity within the conditioned cortical network.


Discovery of 2-pyridylureas as glucokinase activators.
Glucokinase (GK) is the rate-limiting step for insulin release from the pancreas in response to high levels of glucose. Flux through GK also contributes to reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can allosterically activate GK may address this issue. Herein we report the identification and initial optimization of a novel series of glucokinase activators (GKAs). Optimization led to the identification of 33 as a compound that displayed activity in an oral glucose tolerance test (OGTT) in normal and diabetic mice.


Frontal white matter microstructure and treatment response of late-life depression: a preliminary study.
This study tested the hypothesis that microstructural abnormalities in white matter areas of the brain containing frontostriatal tracts are associated with a low rate of remission of geriatric depression. Thirteen older patients with major depression received open, but controlled, treatment with citalopram at a target daily dose of 40 mg for 12 weeks. Diffusion tensor imaging was used to determine fractional anisotropy in preselected white matter regions. Survival analysis with Cox's proportional hazards model revealed that lower fractional anisotropy of the right and the left frontal white matter regions 15 mm above the anterior commissure-posterior commissure plane was associated with a low remission rate after age was considered. Remission was not significantly associated with fractional anisotropy of lower frontal regions or a temporal region. Microstructural white matter abnormalities lateral to the anterior cingulate may be associated with a low rate of remission of geriatric depression.


Nigrostriatal denervation does not affect glutamate transporter mRNA expression but subsequent levodopa treatment selectively increases GLT1 mRNA and protein expression in the rat striatum.
There is growing evidence that the loss of the nigrostriatal dopaminergic neurones induces an overactivity of the corticostriatal glutamatergic pathway which seems to be central to the physiopathology of parkinsonism. Moreover, glutamatergic mechanisms involving NMDA receptors have been shown to interfere with the therapeutical action of levodopa. Given the key role played by uptake processes in glutamate neurotransmission, this study examined the effects of nigrostriatal deafferentation and of levodopa treatment on the striatal expression of the glutamate transporters GLT1, GLAST and EAAC1 in the rat. No significant changes in striatal mRNA levels of these transporters were detected after either levodopa treatment (100 mg/kg; i.p., twice a day for 21 days) or unilateral lesion of the nigrostriatal pathway by intranigral 6-hydroxydopamine injection. In contrast, animals with the lesion subsequently treated with levodopa showed a selective increase (36%) in GLT1 mRNA levels in the denervated striatum versus controls. These animals also showed increased GLT1 protein expression, as assessed by immunostaining and western blotting. These data provide the first evidence that levodopa therapy may interfere with striatal glutamate transmission through change in expression of the primarily glial glutamate transporter GLT1. We further suggest that levodopa-induced GLT1 overexpression may represent a compensatory mechanism preventing neurotoxic accumulation of endogenous glutamate.


Solvent effects on the reaction coordinate of the hydrolysis of phosphates and sulfates: application of Hammond and anti-Hammond postulates to understand hydrolysis in solution.
The mechanism of the alkaline hydrolysis of phosphate and sulfate esters is of great interest. Ab initio quantum mechanical calculations and dielectric continuum methods are used to investigate the effect of the solvent on the associative/dissociative and the in-line/sideways character of the hydrolysis reaction of ethylene sulfate (ES) and ethylene phosphate (EP(-)), and their acyclic counterparts, dimethyl sulfate (DMS) and dimethyl phosphate (DMP(-)). The gas-phase reaction coordinates are determined by Hartree-Fock and density functional theory. For ES, the reaction coordinate in solution is determined; for the other three reactions only the transition state in solution is obtained. The alterations in the reaction induced by solvent are interpreted by use of the Hammond and anti-Hammond postulates.


The private sector role in HIV/AIDS in the context of an expanded global response: expenditure trends in five sub-Saharan African countries.
Global financing for the HIV response has reached unprecedented levels in recent years. Over US$10 billion were mobilized in 2007, an effort credited with saving the lives of millions of people living with HIV (PLHIV). A relatively unexamined aspect of the global HIV response is the role of the private sector in financing HIV/AIDS services. As the nature of the response evolves from emergency relief to long-term sustainability, understanding current and potential contributions from the private sector is critical. This paper examines trends in private sector financing, management and resource consumption related to HIV/AIDS in five sub-Saharan African countries, with a particular emphasis on the effects of recently scaled-up donor funding on private sector contributions. We analysed National Health Accounts HIV/AIDS subaccount data for Kenya, Malawi, Rwanda, Tanzania and Zambia between 2002 and 2006. HIV subaccounts provide comparable data on the flow of HIV/AIDS funding from source to use. Findings indicate that private sector contributions decreased in all countries except Tanzania. With regards to managing HIV/AIDS funds, non-governmental organizations are increasingly controlling the largest share of resources relative to other stakeholders, whereas private for-profit entities are managing fewer HIV/AIDS resources since the donor influx. The majority of HIV/AIDS funds were spent in the public sector, although a considerable amount was spent at private facilities, largely fuelled by out-of-pocket (OOP) payments. On the whole, OOP spending by PLHIV decreased over the 4-year period, with the exception of Malawi, demonstrating that PLHIV have increased access to free or subsidized HIV/AIDS services. Our findings suggest that the influx of donor funding has led to decreased private contributions for HIV/AIDS. The reduction in private sector investment and engagement raises concerns about the sustainability of HIV/AIDS programmes over the long term, particularly in light of current global economic crisis and emerging competing priorities.


The impact of nutritional status and changes of body composition on the prognosis of metastatic renal cell carcinoma patients.
This study aimed to analyze the impact of patients' nutritional status and changes in body composition on the prognosis of metastatic renal cell carcinoma (mRCC) patients who received systemic therapy with tyrosine kinase inhibitors (TKIs). A total of 57 mRCC patients who received systemic therapy with TKIs as first-line therapy at our facility between November 2004 and October 2018 were included. The Prognostic Nutritional Index (PNI) was used to evaluate their nutritional status. The volumes of skeletal muscle mass and fat tissue were calculated using the SYNAPSE VINCENT system. The effects of nutritional status and body composition of mRCC patients on progression-free survival (PFS) and overall survival (OS) were analyzed using Cox regression methods. Low PNI at the start of systemic therapy was a significant prognostic predictor for OS (HR 3.807 [95% CI 1.205-12.027], P=0.046), and it was related to loss of muscle mass three months after systemic therapy. Although the loss of muscle mass at the start of systemic therapy was not associated with OS, loss of muscle mass during treatment predicted worse OS. Nutritional status of mRCC patients may predict changes in body composition and be associated with their prognosis. J. Med. Invest. 70 : 80-87, February, 2023.


Effect of fasting on dopamine neurotransmission in subregions of the nucleus accumbens in male and female mice.
Diets high in saturated fat (HFD) disrupt dopamine neurotransmission, whereas fasting alters tonic and phasic dopamine release to drive motivation and food consumption. However, functional compartments in the nucleus accumbens (NAc) influencing these effects are not well characterized, and sex comparisons have not been made. This study sought to determine whether consumption of a HFD, sex, or being fed versus fasted altered baseline dopamine release and reuptake throughout NAc subregions. Male and female C57BL/6 mice were fed a control diet or nutrient matched HFD for six weeks. Ex-vivo fast-scan cyclic voltammetry revealed females had significantly slower dopamine reuptake in the NAc core than males when fed ad lib control diet. Fasting enhanced dopamine release and reuptake in the NAc core but not the medioventral shell. Further, being fasted versus fed significantly increased dopamine release throughout the NAc core in control males but specifically promoted release and reuptake in only the ventrolateral core of HF-fed males, effects which were lacking in females. Finally, fasting promoted dopamine release and reuptake in the rostral NAc core of controls and more caudally in HFD groups. These data support that dopamine neurotransmission is heterogeneous in NAc subregions and suggest the ventrolateral core is responsive to energy state. Furthermore, a rostrocaudal gradient in the NAc core might control valence responses to fasting that could promote overeating after chronic HFD consumption.


FBXO32, a new TGF-β/Smad signaling pathway target gene, is epigenetically inactivated in gastric cardia adenocarcinoma.
FBXO32 has recently been identified as a TGF-β/Smad signaling pathway target gene, involved in regulating cell survival and may be transcriptionally silenced by epigenetic mechanisms in some kind of carcinomas. The present study was to investigate the role and promoter methylation status of FBXO32 in gastric cardia adenocarcinoma (GCA), and determine the prognostic significance of FBXO32 in GCA. Bisulfite Conversion-Specific and Methylation-Specific PCR, real-time RT-PCR and immunohistochemical staining methods were used to detect the methylation status and expression of FBXO32 in GCA samples. The frequency of FBXO32 methylation in GCA tumor tissues (44.6%) was significantly higher than that in corresponding normal tissues (3.6%) and was associated with TNM stage, pathological differentiation, distant metastasis or recurrence and upper gastrointestinal cancers (UGIC) family history. Decreased mRNA and protein expression of FBXO32 was observed in GCA tumor tissues and was associated with FBXO32 promoter methylation status. A positive correlation between FBXO32 and p-Smad2/3, Smad4 protein expression was also found in clinical specimens. GCA patients in stage III and IV, with positive UGIC family history, and hypermethylation and down-expression of FBXO32 were most likely to develop metastatic disease and also showed the worse survival. In all, aberrant hypermethylation of FBXO32 may be one of the mechanisms that lead to loss or down expression of the gene in GCA, FBXO32 may be a functional tumor suppressor and reactivation of FBXO32 gene may has therapeutic potential and may be used as a prognostic marker for GCA patients.


Psychogenic parkinsonism: clinical spectrum and diagnosis.
Patients with psychogenic parkinsonism (PP), like those with Parkinson's disease (PD), may have tremor, bradykinesia, rigidity, and gait disturbances. Unusual features predominate in PP, but clear psychogenic signs may not be obvious. Because PP may be difficult to diagnose, identifying a wider spectrum of disease manifestations that point toward psychogenic rather than organic parkinsonism could be useful for clinicians. We retrospectively reviewed the charts and clinical data for all patients referred for parkinsonism to a single physician at our movement disorders clinic from 1980 to 2012. Patients with PP represented 1.5% of all patients referred for parkinsonism. Among 36 patients with PP, the most common complaints were tremor (31), gait disturbance (18), fatigue (12), and diminished balance (10). Neurologic examination revealed 12 patients with unusual (functional) postures, 5 with a normal exam, and none with micrographia, hypophonia, or hypomimia. Seven of 36 patients improved, 6 of these with antidepressant therapy. PP is not rare in a movement disorders practice. Leg tremor is more likely in PP than in PD, whereas falls are rare. Unusual (nonphysiologic) postures may be present. The outcome generally is not favorable, although antidepressants are beneficial in some patients with disease duration of <2 years. The presence of micrographia, hypophonia, or hypomimia strongly suggests an organic cause of parkinsonism rather than PP.


[Clinical validation of the 2020 diagnostic approach for pediatric autoimmune encephalitis in a single center].
Objective: To evaluate the value of the 2020 diagnostic criteria (Cellucci criteria) for pediatric autoimmune encephalitis (AE) in children with suspected AE in a single center. Methods: The clinical data of 121 children hospitalized at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2021, with a diagnosis of suspected AE, were retrospectively collected and analyzed. The children were divided into definite antibody-positive AE (dAPAE), probable antibody-negative AE (prANAE), possible AE (pAE) and non-AE groups according to the Chinese expert consensus and the Graus criteria. A new diagnosis was made according to the Cellucci criteria which was compared with the clinical diagnosis to evaluate the diagnostic value of the Cellucci criteria. The Mann-Whitney U test, Kruskal-Wallis test, and χ2 test were used to compare the differences among groups. The sensitivity and specificity were used to evaluate efficacy of the Cellucci criteria. Results: Among the 121 children, 72 were males and 49 were females, with an age of 10.3 (6.5, 14.0) years at disease onset. There were 99 cases diagnosed as AE according the clinical diagnosis (58 males and 41 females), of which 43 cases were diagnosed as dAPAE, 14 cases as prANAE and 42 cases as pAE, and the other 22 cases were not AE (14 males and 8 females). The top 2 initial symptoms in the 99 children with AE were seizures (53 cases, 53.5%) and abnormal mental behaviors (35 cases, 35.4%). And the most common symptoms during the course of the disease were abnormal mental behaviors (77 cases, 77.8%) and seizures (64 cases, 64.6%). There were statistically differences in the incidence of consciousness disorders, autonomic dysfunctions during the course of the disease and the length of hospitalization among the 4 groups (χ2=21.63, 13.74, H=22.60, all P<0.05). Ninety-six of the 121 children were tested for AE-related antibodies, of which 45 cases (46.9%) were antibody-positive. According to the Cellucci criteria, 42 cases were diagnosed as dAPAE, 34 cases as prANAE and 14 cases as pAE. Compared with the clinical diagnosis, the sensitivity of the Cellucci criteria for the diagnosis of the 3 types of AE were 93.02%, 92.86% and 87.88%, and the specificity were 96.23%, 74.39% and 86.36%, respectively. Conclusions: The Cellucci criteria has a high sensitivity and specificity for the diagnosis of pAE and dAPAE in the clinical management of children with suspected AE, while a high sensitivity but low specificity for the diagnosis of prANAE. Therefore, it is recommended to apply the Cellucci criteria selectively in clinical practice according to the actual situation, especially in the diagnosis of prANAE.


[Completion pneumonectomy for pulmonary aspergillosis with hyper immunoglobulin-E syndrome].
A 22-year-old man was admitted to the department of pediatrics of our institute in February 2005, because of pulmonary aspergillosis. He had been diagnosed as hyper immunoglobulin-E syndrome in infancy, and repeated pulmonary infectious desease, such as pulmonary aspergillosis. He received art of right upper lobectomy by pulmonary aspergillosis at the age of 17. In February 2005, he had hemosputum and the chest X-ray showed a giant cavity with niveau in the right lung. In spite of medical treatment by antibiotics and antimycotics, the lesion rapidly increased in size. Therefore, right completion pneumonectomy and omentopexy around the bronchial stump was done. His postoperative course was uneventful.


Statistical optimization of glyphosate adsorption by biochar and activated carbon with response surface methodology.
The introduction of glyphosate, found in herbicides, to waterbodies is of concern due to its toxicity and hence potential threat to public health and ecological systems. The present study has compared glyphosate removal from aqueous solution with activated carbon and biochar. Box-Behnken design, and percent contribution with Pareto analysis techniques were used in surface response and efficiency calculations modelled the process conditions and their effects. The adsorption data better fitted the Freundlich isotherm model than the Langmuir model. The rate of glyphosate adsorption was found to follow a pseudo-second-order model. pH of the solutions was regulated by buffering during the adsorption process. Higher efficacy of glyphosate removal was obtained by optimising parameters such as operating pH, initial glyphosate concentration, temperature, adsorbent dose, and contact time. The conditions yielding the best removals were pH 8.0, 0.2 mg/L, 50.0 °C, 11.4 g/L, 1.7 h for activated carbon and pH 5.0, 0.7 mg/L, 50.0 °C, 12.3 g/L, 1.9 h for biochar, for the aforementioned parameters respectively. The maximum removal capacity and efficiency were 0.0173 mg/g and 98.45% for activated carbon, and 0.0569 mg/g and 100.00% for biochar. The test results indicated biochar could be important from the perspective of performance and affordability.


Occupational asthma.
This article will serve as a guide to the diagnosis of occupational asthma. It contains few particulars about the substances known to cause the illness, and these omissions are intentional. The recommended approach begins with the patient and sometimes, but not always, ends with identification of the offending agent.


CH/π-interaction-driven self-assembly of tetraphenylethylene derivatives into the face to face arrangement.
For tetraphenylethene (TPE) derivatives, it is difficult to determine the arrangement of the molecules in the aggregation state because disordered aggregation usually occurs. To solve the problem, we have explored a novel and facile strategy to investigate the aggregation mode of a TPE derivative framework in which the two neighboring ortho carbons of two phenyl moieties at the same ethylene carbon were linked with an alkoxyl chain (C4) (denoted as TPEC4). The XRD measurements on the particles obtained in a DMSO/H2O mixture (f w = 60%) showed sharp peaks which is consistent with the simulated XRD patterns on the basis of a single crystal structure of TPEC4, indicating well-ordered molecular packing in the aggregated state. The CH/π-interaction and solvophobicity driven self-assembly behaviour of the compound was observed in the DMSO/H2O mixture. A face to face molecular packing structure that arises from quadruple intermolecular CH/π-interactions of the tetraphenylethylenes is the key motif for self-assembly in solution. The unique blue-red shifted emission in the DMSO/H2O mixture associated with aggregated behaviour of the compound was also investigated. This discovery will provide the basis for theoretical research and the rational design of TPE-based luminogens.


Lessons from computer simulations of ablation of atrial fibrillation.
This paper reviews the simulations of catheter ablation in computer models of the atria, from the first attempts to the most recent anatomical models. It describes how postulated substrates of atrial fibrillation can be incorporated into mathematical models, how modelling studies can be designed to test ablation strategies, what their current trade-offs and limitations are, and what clinically relevant lessons can be learnt from these simulations. Drawing a parallel between clinical and modelling studies, six ablation targets are considered: pulmonary vein isolation, linear ablation, ectopic foci, complex fractionated atrial electrogram, rotors and ganglionated plexi. The examples presented for each ablation target illustrate a major advantage of computer models, the ability to identify why a therapy is successful or not in a given atrial fibrillation substrate. The integration of pathophysiological data to create detailed models of arrhythmogenic substrates is expected to solidify the understanding of ablation mechanisms and to provide theoretical arguments supporting substrate-specific ablation strategies.


First trimester screening for preeclampsia.
Aspirin therapy from the first trimester of pregnancy may benefit women at high risk for preeclampsia. We review publications from the past year that examine first-trimester screening studies for preeclampsia. For a false positive rate of 5%, first-trimester uterine artery Doppler studies will detect 50-65% of women who will develop severe preeclampsia (i.e. needing delivery before 35 weeks). Measurement of placental volume with three-dimensional ultrasound at 11-14 weeks detected 20% for a false positive rate of 10% in one study and further evaluation of this technique is needed. Maternal serum placental growth factor, vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 have shown initial promise, but recent studies have shown no improvement in screening compared with using uterine artery Doppler alone. Placental protein 13 is the most promising serum marker and in combination with uterine Doppler may predict up to 90% of cases of severe preeclampsia for a false positive rate of 9%. First-trimester uterine artery Doppler can identify over half of women who will develop preeclampsia. Detection rates may be increased by a combination of uterine artery Doppler with first-trimester maternal serum markers, especially placental protein 13. Such high-risk women may be the most likely to benefit from pharmacological intervention in future trials.


A cross-national study on adolescent substance use: Intentions, peer substance use, and parent-adolescent communication.
This longitudinal two-wave cross-national study investigated whether intentions, friends' substance use, and parent-adolescent substance-use specific communication predict adolescent alcohol and cannabis use 1 year later, while estimating reversed links. The temporal order between these two substances was also examined. We used multi-group cross-lagged panel modeling on data from 2 ethnically and socioeconomically diverse samples: Sint Maarten (N = 350; Mage = 14.19) and the Netherlands (N = 602; Mage = 13.50). Results showed that in the Netherlands, cannabis use predicts more subsequent problems (alcohol use, intention to use cannabis, and affiliation with cannabis-using friends). But for Sint Maarten, alcohol use predicts more subsequent problems (cannabis use, intention to use alcohol, and affiliation with alcohol-using friends). These opposing results demonstrate that caution is warranted when generalizing results across countries.


Uncertainty in weather and climate prediction.
Following Lorenz's seminal work on chaos theory in the 1960s, probabilistic approaches to prediction have come to dominate the science of weather and climate forecasting. This paper gives a perspective on Lorenz's work and how it has influenced the ways in which we seek to represent uncertainty in forecasts on all lead times from hours to decades. It looks at how model uncertainty has been represented in probabilistic prediction systems and considers the challenges posed by a changing climate. Finally, the paper considers how the uncertainty in projections of climate change can be addressed to deliver more reliable and confident assessments that support decision-making on adaptation and mitigation.


Anatomic Considerations Guiding Single Versus Multiportal Endoscopic Approaches for Resection of Juvenile Nasopharyngeal Angiofibroma: Cases Series With Graded Multicorridor Resections.
Juvenile nasopharyngeal angiofibromas (JNAs) are characterized by expansive and destructive growth, often invading the midline/paranasal sinuses, pterygopalatine fossa, and infratemporal fossa and can extend into the orbit, cavernous sinus, or intracranially. To evaluete the major benefits of the extended endoscopic endonasal approach (EEA) for JNA resection as compared with more traditional and invasive transpalatal and transfacial approaches. When JNAs extend into lateral anatomic compartments, the optimal operative trajectory often requires additional approach strategies or surgical staging. We retrospectively reviewed 8 cases of large JNAs arising in symptomatic adolescent boys (University of Pittsburgh Medical Center Stages II, III, and V) and discuss anatomic and tumor considerations guiding the decision of a pure EEA vs combined EEA and sublabial transmaxillary approach (Caldwell-Luc). A pure extended EEA was used in 6 JNA cases (UPMC Stages II-III); a multiportal EEA + Caldwell-Luc maxillotomy was used in 2 cases. One of the 2 patients (UPMC Stage V) previously treated with multiportal EEA + Caldwell-Luc maxillotomy underwent staged left temporal/transzygomatic craniotomy, obtaining gross total resection. Seven patients ultimately underwent complete removal without recurrence. One patient with a small residual JNA (UPMC II) underwent stereotactic radiosurgery without progression to date. JNAs with lateral extension into the infratemporal fossa often benefited from additional lateral exposure using a Caldwell-Luc maxillotomy. Cases with significant skull base and/or dural involvement may undergo staged surgical treatment; temporalis + transzygomatic craniotomy is often useful for second-stage approaches for residual tumor in these lateral infratemporal or intracranial regions. SRS should be considered for residual tumor if additional surgery is not warranted.


Analgesic efficacy of an ibuprofen-codeine combination.
Subjects who had undergone dental impaction surgery and who had moderate to severe postoperative pain were given, under double-blind, randomized conditions, a single dose of either codeine 60 mg, aspirin 650 mg, ibuprofen 400 mg, aspirin 650 mg + codeine 60 mg, ibuprofen 400 mg + codeine 60 mg, or placebo. A total of 249 subjects were included in the statistical analysis. On a report form, subjects recorded pain intensity, pain relief, and side effects hourly for four hours. They also gave an overall impression at the end of the observation period. Analysis of variance and pairwise contrasts were used to analyze the data. For the sum of pain intensity differences, the total of the hourly pain relief scores, and overall impression, there was a significant analgesic effect for codeine, aspirin, and ibuprofen and no significant interaction when they were used in combination. Ibuprofen alone was statistically superior to aspirin and also achieved higher mean scores than the aspirin-codeine combination. The ibuprofen-codeine combination was the most effective treatment for every analgesic parameter, but it was not statistically superior to ibuprofen alone. The possibility exists that the ibuprofen-codeine combination peaked out the sensitivity of the model. There was no notable difference in the frequency or intensity of side effects among the treatment groups, and no subject had to withdraw due to an adverse effect. This study again confirms the superiority of ibuprofen to aspirin and suggests that ibuprofen is at least as effective as an aspirin-codeine combination. Codeine added a small amount of additional analgesia when used in combination with ibuprofen.


A phase II trial of a transmucosal herbal patch for the treatment of gingivitis.
Systemic treatments for gingivitis frequently are inadequate for controlling specific sites of severe gingival inflammation. The authors conducted a study to test site-specific therapy using a transmucosal herbal periodontal patch (THPP) that was impregnated with plant extracts reported to reduce inflammatory response. The study was a single-center, randomized, placebo-controlled, double-masked, longitudinal phase II trial involving participants with clinically diagnosed gingivitis. Participants who were enrolled in the study received either THPPs or placebo patches (PP) for three days. The authors evaluated gingival inflammation visually using the gingival index (GI) and by measuring gingival crevicular fluid β-glucuronidase (BG) enzymatic activity at baseline (day one) and on days two, four, eight and 15. The authors randomly assigned 53 participants to receive the THPP or the PP. Participants who received the THPPs had a greater reduction in mean GI scores than did those who received the PPs. This finding was significant on days four and 15. The percentage of participants whose GI scores decreased by one or more was higher among those receiving the THPP than among those receiving the PP, as assessed on days four and 15. The average decrease in BG levels (fluorescence units) for participants receiving the THPP was significantly greater on days four and eight than they were for those receiving the PP. No serious adverse events were associated with the use of the THPP. Topical treatment by means of the THPP may be effective and safe in reducing topical gingival inflammation. Further studies are needed to confirm these findings and determine the best method for administering the THPP and the appropriate dosing. Site-specific treatment of gingival inflammation is feasible and could be used as an adjunct for systemic therapeutic interventions.


The prevalence of perioperative iron deficiency anaemia in women undergoing caesarean section-a retrospective cohort study.
Caesarean section is a common surgery, with almost 23 million procedures performed globally each year. Postpartum haemorrhage, in association with caesarean section surgery, is a leading global cause of maternal morbidity and mortality. Perioperative iron deficiency anaemia is a risk factor for intraoperative bleeding. Therefore, anaemia is an important and modifiable risk factor for bleeding during caesarean section surgery. Recent recommendations advise that all preoperative patients with anaemia (defined as haemoglobin concentration (Hb) < 130 g/L), regardless of sex, be assessed and treated to normalise haemoglobin levels. It is unclear how this recommendation translates to pregnant women where the World Health Organization (WHO) defines anaemia at a much lower threshold (Hb < 110 g/L). We aimed to determine the prevalence, and characterization, of Hb levels < 130 g/L perioperatively in women undergoing caesarean section. We conducted a retrospective cohort study of 489 consecutive women who underwent caesarean section over a 12-week period, in a single-centre tertiary referral maternity unit in Australia. We calculated the proportion of women who were anaemic (Hb < 130 g/L) at four time points-first hospital appointment, third trimester, preoperatively and on discharge from hospital. The proportion of women who were iron deficient (ferritin level < 30 μg/L) at their first hospital appointment was determined. Haemoglobin was measured in 479 women. Ferritin was measured in 437 of these women. The mean (SD) Hb at the first hospital appointment, third trimester, preoperatively, and postoperatively on discharge was 126.7 (11.4) g/L, 114.6 (10.6) g/L, 124.1 (12.4) g/L, and 108.0 (13.6) g/L respectively. Iron deficiency was present in 148 (33.9%) women at their first hospital appointment; 107 of 248 (43.1%) women with anaemia and 41 of 189 (21.7%) with no anaemia. 29 women were found to have moderate anaemia (Hb 80-109 g/L) with 18 of these 29 (62.1%) women having iron deficiency. Only 68 (45.9%) women with iron deficiency at their first hospital appointment received treatment. The prevalence of anaemia classified as Hb < 130 g/L versus the WHO classification of Hb < 110 g/L from all causes was 57.4% versus 6.1% at first hospital appointment, 94% versus 26.1% in third trimester, and 66.0% versus 12.2% preoperatively. Postoperatively at least 40% of women had Hb < 130 g/L on hospital discharge versus at least 23% of women using WHO definition of Hb < 110 g/L. Of the 112 women with hospital discharge Hb < 110 g/L, 35 (31.3%) women were iron deficient at their first hospital appointment. Over one in three women were iron deficient at their first hospital appointment. 62% of women with moderate anaemia (Hb 80-109 g/L) also had iron deficiency. At least four in 10 women were anaemic (Hb < 130 g/L) on hospital discharge. Less than half of the women with anaemia were treated. Our data suggests that 30% of postoperative anaemia may be prevented with intensive treatment of iron deficiency in early pregnancy. Large prospective studies, are needed to determine outcomes after caesarean section in women, stratified by preoperative Hb and ferritin levels. The prevalence of anaemia in our data suggests it is a moderate public health problem.


Microinjection of dsRNA into fully-grown mouse oocytes.
RNA interference (RNAi) is a suitable method for sequence-specific post-transcriptional gene silencing in a number of model systems. The following protocol describes delivery of a double-stranded RNA (dsRNA) of choice into fully-grown, germinal vesicle-intact (GV) mouse oocytes by microinjection. Microinjected oocytes can be cultured for up to 2 d or they can be matured to metaphase II. The metaphase II eggs can be fertilized in vitro and cultured up to the blastocyst stage. The efficiency of knockdown by RNAi can be assayed by quantitative reverse transcriptase (RT)-PCR (qPCR).


Hepatoprotective activity of a phytotherapeutic formula on thioacetamide--induced liver fibrosis model.
Hepatic fibrosis is a widespread alteration in the liver that primarily consists of increased collagen deposition in the tissue. The aim of the present study was to evaluate the protective effects of poly-phytocompound EH-1501 containing small amounts of silymarin but also other potentially effective substances on thioacetamide (TTA)-induced liver fibrosis and to elucidate the mechanisms underlying these protective effects in rats. Forty rats were randomly divided into four groups. Liver fibrosis was induced by intraperitoneal injection of 200 mg/kg body weight. TAA dissolved in saline was administered thrice a week, for 8 weeks. Groups 1 (normal healthy control) and 2 (liver injury model) received water for 8 weeks or silymarin (50 mg/kg p.o. daily) for 8 weeks (group 3) or a poly-phytocompound EH-1501 (containing grape leaf, wild strawberry, dandelion and milk thistle, EuroHealth, Italy) (200 mg/kg, daily respectively) for 8 weeks (group 4). Biochemistry and serum fibrosis markers were AST, ALT, GGT, bilirubin, thiobarbituric acid reactive substances (TBARs), hyaluronic acid and type IV collagen 7s. Liver tissue was used to assay glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), TBARs, hydroxyproline and gene expression of collagen alpha1 (col alpha1) and transforming growth factor-beta1 (TGF-beta1). Silymarine and EH-1501 were equally effective in reducing serum markers of liver damage and fibrosis as well as oxidative stress. However, as compared to silymarine, EH-1501 was significantly more effective in improving tissue level of GPx while decreasing TBARs and hydroproline content (p < 0.05). When looking at gene expression of col alpha1 and TGF-beta1, EH-1501 showed a significantly higher degree of gene down-regulation as compared to silymarine (p < 0.05). Taken altogether, these data suggest that a natural antioxidant-containing phytocompound EH-1501 exerts an effective hepatoprotective property in experimental chronic fibrotizing liver injury to a significantly higher degree than silymarin.


Physiological Correlates and Predictors of Functional Recovery After Chiasmal Decompression.
The intrinsic abilities and limits of the nervous system to repair itself after damage may be assessed using a model of optic chiasmal compression, before and after a corrective surgical procedure. Visual fields (VFs), multifocal visual evoked potentials (mfVEP), retinal nerve fiber layer (RNFL) thickness, and diffusion tensor imaging were used to evaluate a patient before and after removal of a meningioma compressing the chiasm. Normally sighted individuals served as controls. The advantage of each modality to document visual function and predict postoperative outcome (2-year follow-up) was evaluated. Postsurgery visual recovery was best explained by critical mass of normally conducting fibers and not associated with average conduction amplitudes. Recovered VF was observed in quadrants in which more than 50% of fibers were identified, characterized by intact mfVEP latencies, but severely reduced amplitudes. Recovery was evident despite additional reduction of RNFL thickness and abnormal optic tract diffusivity. The critical mass of normally conducting fibers was also the best prognostic indicator for functional outcome 2 years later. Our results highlight the ability of the remaining normally conductive axons to predict visual recovery after decompression of the optic chiasm. The redundancy in anterior visual pathways may be explained, neuroanatomically, by overlapping receptive fields.


Does the follow-your-passions ideology cause greater academic and occupational gender disparities than other cultural ideologies?
Five preregistered studies (N = 1934) demonstrate that the prevalent U.S. ideology to "follow your passions" perpetuates academic and occupational gender disparities compared to some other cultural ideologies. Study 1 shows that the follow-your-passions ideology is commonly used by U.S. students in making academic choices. Studies 2-5 find that making the follow-your-passions ideology salient causes greater academic and occupational gender disparities compared to the resources ideology (i.e., the idea that one should pursue a field that leads to high income and job security). In Study 4, the follow-your-passions ideology causes greater gender disparities even when compared to a cultural ideology that aligns more with the female gender role (i.e., communal ideology). In Study 5, a moderated mediation analysis supports the hypothesis that gender disparities are explained by women's versus men's greater tendency to draw upon female role-congruent selves when the follow-your-passions ideology is salient compared to when the resources ideology is salient. Drawing upon female role-congruent selves remains a significant mediator even when accounting for alternative mediators (e.g., appropriateness of ideology for one's gender). The follow-your-passions ideology may not seem explicitly gendered, but it causes greater academic and occupational gender disparities compared to some other cultural ideologies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Meconium aspiration stimulates cyclooxygenase-2 and nitric oxide synthase-2 expression in rat lungs.
To study the impact of meconium aspiration on the biosynthesis of prostaglandins and nitric oxide, we investigated the effects of intratracheal meconium instillation on the expression of cyclooxygenase-1 (COX-1) and -2 (COX-2) and endothelial (NOS-3) and inducible (NOS-2) nitric oxide synthase in rat lungs. Anesthetized, tracheotomized, and ventilated rats received 3 mL/kg human meconium suspension intratracheally (n = 19), and 14 control rats received an equal volume of saline. Ten rats were pretreated with indomethacin, and 13 rats were pretreated with dexamethasone. The lungs were ventilated with 70% oxygen for 3 h after the insult, and the level of COX-1, COX-2, NOS-2, and NOS-3 mRNA in lung tissue was analyzed by Northern blot hybridization. Furthermore, the expression and localization of the enzyme proteins was analyzed by immunohistochemistry. COX-1 and NOS-3 were clearly expressed in the lungs of control rats, whereas the level of COX-2 and NOS-2 expression was minimal. Meconium administration did not affect the expression of COX-1, but COX-2 expression was up-regulated in the respiratory epithelium and alveolar macrophages. Meconium also induced up-regulation of NOS-2 in the pulmonary epithelium, vascular endothelium, and macrophages. Indomethacin pretreatment did not affect the enzyme expressions, whereas dexamethasone administration significantly inhibited the meconium-induced COX-2 and NOS-2 up-regulation. Our data thus indicate that intrapulmonary meconium up-regulates lung COX-2 and NOS-2 gene expression, suggesting an important role for prostaglandins and nitric oxide in the meconium aspiration-induced pulmonary inflammation and hemodynamic changes.


Profiling of Long Non-coding RNAs and mRNAs by RNA-Sequencing in the Hippocampi of Adult Mice Following Propofol Sedation.
Propofol is a frequently used intravenous anesthetic agent. The impairment caused by propofol on the neural system, especially the hippocampus, has been widely reported. However, the molecular mechanism underlying the effects of propofol on learning and memory functions in the hippocampus is still unclear. In the present study we performed lncRNA and mRNA analysis in the hippocampi of adult mice, after propofol sedation, through RNA-Sequencing (RNA-Seq). A total of 146 differentially expressed lncRNAs and 1103 mRNAs were identified. Bioinformatics analysis, including gene ontology (GO) analysis, pathway analysis and network analysis, were done for the identified dysregulated genes. Pathway analysis indicated that the FoxO signaling pathway played an important role in the effects of propofol on the hippocampus. Finally, four lncRNAs and three proteins were selected from the FoxO-related network for further validation. The up-regulation of lncE230001N04Rik and the down-regulation of lncRP23-430H21.1 and lncB230206L02Rik showed the same fold change tendencies but changes in Gm26532 were not statistically significant in the RNA-Seq results, following propofol sedation. The FoxO pathway-related proteins, PI3K and AKT, are up-regulated in propofol-exposed group. FoxO3a is down-regulated at both mRNA and protein levels. Our study reveals that propofol sedation can influence the expression of lncRNAs and mRNAs in the hippocampus, and bioinformatics analysis have identified key biological processes and pathways associated with propofol sedation. Cumulatively, our results provide a framework for further study on the role of lncRNAs in propofol-induced or -related neurotoxicity, particularly with regards to hippocampus-related dysfunction.


Analysis of a binary composite endpoint with missing data in components.
Composite endpoints are often used in clinical trials in order to increase the overall event rates, reduce the sizes of the trials and achieve desired power. For example, in a trial to study the effect of a treatment on the prevention of venous thromboembolic events after a major orthopaedic surgery of the lower limbs, the primary endpoint is usually a composite endpoint consisting of any deep vein thrombosis identified by systematic venography of lower limbs, symptomatic and well-documented non-fatal pulmonary embolism, and death from all causes. Just as any endpoints, missing data can occur in the components of the composite endpoint. If a patient has missing data on some of the components but not all the components, this patient may not have complete data but partial data for the composite endpoint. To be consistent with the intention-to-treat principle, the patient should not be discarded from the analysis. In this research, we propose an approach for the analysis of a composite endpoint with missing data in components. The main idea is to first derive the probabilities of all possible study outcomes based on the appropriate model and then to construct the overall rate for the composite endpoint. Simulations are conducted to compare the approach with several naïve methods. A data example is used to illustrate the application of the approach.


Deposition and clearance of chrysotile asbestos.
Studies of human lungs indicate that, for virtually all types of exposure, the relative proportion of amphibole asbestos retained in the lung far exceeds the proportion in the original dust and, conversely, the relative proportion of chrysotile is far less than that in the original dust. Although amphiboles appear to accumulate in lung in proportion to exposure and chrysotile does not, failure of chrysotile deposition is probably not the reason for the disproportionate retention of amphibole fibres. The available data suggest that chrysotile is deposited in the parenchyma but is cleared extremely rapidly, with the vast bulk of fibres removed from human lungs within weeks to months after inhalation; by comparison, amphibole clearance half-lives are of the order of years to decades. The mechanisms of preferential chrysotile clearance remain uncertain, but fragmentation of chrysotile into short fibres, possibly accompanied by extremely rapid dissolution of such fibres, appears to be important in this process. Chrysotile fibres do penetrate to the periphery of the lung, so that differences in mesothelial pathogenicity of chrysotile and amphiboles in regard to mesothelioma are not caused by failure of chrysotile to reach the pleura. The theory that the tremolite contaminant rather than the chrysotile itself is the cause of 'chrysotile-induced' disease (especially mesothelioma) is consistent with the available human data, but the contrary ideas that disease is caused either by the total transient burden of inhaled chrysotile fibres or by a small, sequestered, long-retained fraction of chrysotile fibres still need to be excluded.


Adenosine is inherently favored as the branch-site RNA nucleotide in a structural context that resembles natural RNA splicing.
We previously used in vitro selection to identify the 7S11 deoxyribozyme, which catalyzes formation of 2',5'-branched RNA using a branch-site adenosine nucleophile and a 5'-triphosphate electrophile. An unanswered question is whether the use of branch-site adenosine is inherently preferred or a chance event during the particular selection experiment. Here we have found that deoxyribozymes newly selected to use uridine as the branch-site RNA nucleotide in a structural context that resembles natural RNA splicing instead prefer a branch-site adenosine, although adenosine was never available during the selection itself. Our results support a chemical basis for nature's choice of the branch-site nucleotide, which is almost always adenosine in group II introns and the spliceosome.


Sub-60 nm periodic grating feature patterning by immersion based 364 nm laser interference.
In this paper, we report a methodology to fabricate high resolution periodic grating features using high index prism based interferometer and i-line laser source. Features with sub-60 nm half pitch size were fabricated on i-line resist in an immersion medium using a prism of high index 1.939.


Microheterogeneity and preanalytical stability of protein biomarkers of inflammation and renal function.
Protein biomarker microheterogeneity has attracted increasing attention in epidemiological and clinical research studies. Knowledge concerning the preanalytical stability of proteins is paramount to assess the biological significance of their proteoforms. We investigated the stability of the inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and calprotectin (S100A8/9), and the renal function marker, cystatin C (CnC). In total 16 proteoforms were quantified by immuno-MALDI-TOF MS in EDTA plasma and serum samples from 15 healthy volunteers. Prior to analysis blood samples were stored at either room temperature from 1 h up to 8 days, or underwent up to 9 consecutive freeze/thaw cycles. Pearson's correlation coefficient and t-test, intra-class correlation coefficient (ICC), and Autoregressive Integrated Moving-Average (ARIMA) models were used to investigate the stability of proteoform concentrations and distributions in blood. Plasma and serum concentrations of CRP and SAA proteoforms were highly stable during room temperature exposure and repeated freeze/thaw cycles, demonstrating excellent reproducibility (ICC > 0.75), no serial dependency in ARIMA models, and stable distribution of proteoforms. Stability analyses for proteoforms of S100A8/9 and CnC identified only minor preanalytical changes in concentrations and distributions, and none of the proteoforms were produced during prolonged exposure to room temperature or repeated freezing/thawing. The four proteins and their proteoforms are stable during sub-optimal sample handling, and represent robust biomarker candidates for future biobank studies aimed at investigating the microheterogeneity of SAA, S100A8/9, and CnC in relation to inflammation, renal dysfunction and various clinical outcomes.


Mobility during the post-partum period and viraemia in women living with HIV in South Africa.
We investigated the association between travel and viraemia in post-partum women with human immunodeficiency virus on antiretroviral therapy (ART). Data are from a trial of post-partum ART delivery strategies. Women who initiated ART during pregnancy, were clinically stable with a viral load (VL) <400 copies/ml and were <10 weeks post-partum were enrolled at a primary care antenatal clinic in Cape Town, South Africa. Study visits at 3, 6, 12, 18 and 24 months post-partum included questions about travel, defined as ≥1 night spent outside of the city, and VL testing. Generalised mixed effects models assessed the association between travel and subsequent VL ≥400 copies/ml. Among 402 women (mean age 29 y, 35% born in the Western Cape), 69% reported one or more travel events over 24 months. Being born beyond the Western Cape (adjusted odds ratio [aOR] 2.03 [95% confidence interval {CI} 1.49 to 2.77]), duration post-partum in months (aOR 1.03 [95% CI 1.02 to 1.05]) and living with the child (aOR 0.60 [95% CI 0.38 to 0.93]) were associated with travel. In multivariable analyses, a travel event was associated with a 92% increase in the odds of a VL ≥400 copies/ml (aOR 1.92 [95% CI 1.19 to 3.10]). Interventions to support women on ART who travel are urgently required.


Relationship between measures of inhibitory processes in patients with schizophrenia: role of substance abuse disorders.
Disruption of prepulse inhibition of the startle response (PPI) has been widely identified in patients with schizophrenia, as well as impairment in many domains of cognitive functioning. However, there is some controversy regarding the relationship between PPI and the different neuropsychological tasks assessing inhibition. This controversy may be due to the influence of other variables, such as substance abuse. We aimed to determine whether differences in inhibition in schizophrenia subjects were related to their pattern of substance use and whether there was a correlation between the changes in each process. PPI and neuropsychological functioning were studied in three groups of subjects with schizophrenia (N=73): tobacco dependents (ToD; n=22), multiple substance abusers (MSUD; n=31) and non-substance abusers (non-SUD; n=20). All subjects were assessed using PPI and neuropsychological tests (Stroop and Wisconsin Card Sorting Test [WCST]). ToD showed better pre-attentive inhibitory function compared to the other two groups, and MSUD showed lower resistance to interference. Furthermore, significant correlations were found between PPI, Stroop, and WCST. Our data suggest that there is a relationship between the different tasks assessing inhibition in schizophrenia, being affected by substance abuse history. We also found differences in inhibition capacity depending on substance abuse in patients with schizophrenia.