Does season alter responsiveness of the reproductive neuroendocrine axis to the suppressive actions of cortisol in ovariectomized ewes?
Season can profoundly influence activity of the hypothalamic-pituitary-adrenal axis and alter reproductive neuroendocrine responsiveness to stress and gonadal steroids. Here we tested the hypothesis that the inhibitory effect of a stress-like increment in plasma concentration of the adrenal steroid cortisol on pulsatile LH secretion varies with season. LH pulse patterns were monitored prior to and during the administration of cortisol in the same seven ovariectomized ewes during three stages of the yearly breeding cycle: breeding season, transition to anestrus, and midanestrus. The elevation in cortisol mimicked the rise in plasma level of cortisol in response to an immune/inflammatory stress. During all three seasons, cortisol acutely suppressed the pulsatile release of LH. This inhibition reflected a marked reduction of LH pulse amplitude and a minimal suppression of LH pulse frequency. Of interest, the suppressive effect of this physiologic increment in cortisol did not vary across seasons. This provides initial evidence that, in ovariectomized ewes, cortisol-induced suppression of pulsatile LH secretion differs from that of gonadal steroids in that it is not profoundly influenced by season.


Efficacy of alprazolam in reducing fluoxetine-induced jitteriness in patients with major depression.
Serotonin selective reuptake inhibitors (SSRIs) have become the most widely prescribed antidepressants in the United States. The selective influence of SSRIs on serotonin neurotransmission has resulted in a specific constellation of adverse effects termed "jitteriness" syndrome, which occurs in at least 30% of patients taking SSRIs. Because there have been no systematic studies examining treatment of SSRI-induced jitteriness, we conducted a prospective study of the efficacy of adjunctive alprazolam therapy for fluoxetine-induced jitteriness symptoms. Fifty-four subjects with major depression were treated with fluoxetine 20 mg/day. Subjects experiencing an increase in jitteriness symptoms within 2 weeks of starting fluoxetine were given adjunctive alprazolam 0.5 mg to 4.0 mg daily for 2 weeks followed by a 2-week taper period. Eighteen (33.3%) of 54 patients experienced jitteriness symptoms during fluoxetine treatment. We observed a statistically significant reduction in the severity and number of jitteriness symptoms with adjunctive alprazolam. Moreover, in most cases jitteriness symptoms did not reappear during the alprazolam taper period or after alprazolam was discontinued. These observations suggest that a brief course of adjunctive alprazolam treatment may be efficacious in reducing the duration and severity of jitteriness symptoms resulting from antidepressants that are selective for serotonin.


[Plasma renin activity (PRA), angiotensin II (AII), atrial natriuretic peptide (ANP) and AII/ANP ratio in severely burned patients].
Plasma renin activity (PRA), angiotensin II (AII), atrial natriuretic peptide (ANP) and AII/ANP were determined by radioimmunoassay in samples of blood from 59 burn patients. The results demonstrated that PRA, AII, ANP, AII/ANP increased significantly postburn. The increased level of AII/ANP correlated positively with the extent of burn injury as well as the severity of postburn renal dysfunction suggesting that the imbalance of AII and ANP played an important role in the pathogenesis of postburn renal damage.


Sperm-based contraceptive vaccines: current status, merits and development.
At the present growth rate, the world population is estimated to reach a phenomenal 8.9 billion people by the year 2050, posing a great risk of overpopulation. Therefore, new strategies of contraception are required. A novel contraceptive strategy that is receiving considerable attention is that of immunocontraception. Spermatozoa have proteins that are unique, cell specific, immunogenic and accessible to antibodies. The targeting of antibodies to gamete-specific antigens implicated in sperm function, sperm-egg binding and fertilisation could block sperm binding and thus fertilisation. The present review highlights the current status, relative merits and future directions for various sperm-based candidate antigens with regard to the development of a contraceptive vaccine.


Dual-dispersion-regime dual-comb mode-locked laser.
We report on the first, to the best of our knowledge, solid-state dual-comb mode-locked laser that simultaneously operates in different dispersion regimes. Due to the intrinsic polarization multiplexing in a birefringent Yb:Ca3NbGa3Si2O14 (Yb:CNGS) gain medium, the laser emits two cross-polarized pulse trains with a repetition rate offset of ∼ 4.8 kHz from a single cavity. We obtain dual pulse generation with a 20-fold difference in duration by setting the net cavity group delay dispersion to cross zero across the emission band of the employed gain medium. While the duration of the soliton-like pulses experiencing anomalous dispersion amounts to 117 fs, the second laser output, which is spectrally located in the normal dispersion region, is strongly chirped with a pulse duration of 2360 fs.


Objective scaling of facial nerve function based on area analysis (OSCAR).
An objective scaling of facial nerve function based on area analysis (OSCAR) was developed using the variations of luminance produced by changes of facial expression. The presented method of scaling facial motions has the advantage of being continuous, objective, and reproducible. It is fast and simple to use.


Tunable upconversion in a nanocrystal-organic molecule hybrid: reabsorption vs. resonant energy transfer.
Organic semiconductors, such as polycyclic aromatic hydrocarbons, are typically not responsive to near infrared (NIR) light due to their relatively large bandgaps. Here, we show that the NIR light at 980 nm can be efficiently converted to broadband visible upconversion (UC) emission by rubrene molecules in a solution dispersed with upconversion nanoparticles (UCNPs). Spectroscopic characterizations indicate that the sensitization of emission by rubrene molecules strongly depends on the location of the 4f levels of Er3+ ions and the interplay between reabsorption and Förster-type energy transfer. Even for the solution with the highest rubrene concentration (>1 mg mL-1), energy transfer by reabsorption of UC emission from the UCNPs is the dominant process, and the radiationless resonant energy transfer process is weak, as the separation between most rubrene molecules and NCs is far larger than the Förster distance. The results of this work could be of particular interest for the development of organic-inorganic hybrid systems for NIR light harvesting and detection.


A hybrid classifier for characterizing motor unit action potentials in diagnosing neuromuscular disorders.
The time and frequency features of motor unit action potentials (MUAPs) extracted from electromyographic (EMG) signal provide discriminative information for diagnosis and treatment of neuromuscular disorders. However, the results of conventional automatic diagnosis methods using MUAP features is not convincing yet. The main goal in designing a MUAP characterization system is obtaining high classification accuracy to be used in clinical decision system. For this aim, in this study, a robust classifier is proposed to improve MUAP classification performance in estimating the class label (myopathic, neuropathic and normal) of a given MUAP. The proposed scheme employs both time and time-frequency features of a MUAP along with an ensemble of support vector machines (SVMs) classifiers in hybrid serial/parallel architecture. Time domain features includes phase, turn, peak to peak amplitude, area, and duration of the MUAP. Time-frequency features are discrete wavelet transform coefficients of the MUAP. Evaluation results of the developed system using EMG signals of 23 subjects (7 with myopathic, 8 with neuropathic and 8 with no diseases) showed that the system estimated the class label of MUAPs extracted from these signals with average of accuracy of 91% which is at least 5% higher than the accuracy of two previously presented methods. Using different optimized subsets of features along with the presented hybrid classifier results in a classification accuracy that is encouraging to be used in clinical applications for MUAP characterization.


Outcomes of Latarjet Versus Distal Tibia Allograft for Anterior Shoulder Instability Repair: A Matched Cohort Analysis.
Anterior glenoid reconstruction with fresh distal tibia allograft (DTA) has been described for management of recurrent shoulder instability, with encouraging early outcomes; however, no comparative data with the Latarjet procedure are available. The purpose of this study was to compare the clinical outcomes between patients undergoing DTA and a matched cohort of patients undergoing Latarjet. Cohort study; Level of evidence, 3. A review was conducted of prospectively collected data for patients with a minimum 15% anterior glenoid bone loss who underwent shoulder stabilization via either the DTA or Latarjet procedure and had a minimum follow-up of 2 years. Consecutive patients undergoing DTA were matched in a 1-to-1 format to patients undergoing Latarjet by age, body mass index, history of contact sports, and number of previous shoulder operations. Patients were evaluated pre- and postoperatively with a physical examination and the following outcome assessments: Simple Shoulder Test, visual analog scale, American Shoulder and Elbow Surgeons, Western Ontario Shoulder Instability Index, and Single Assessment Numeric Evaluation. Complications, reoperations, and episodes of recurrent instability were analyzed. Statistical analysis was performed with Student t tests, with P < .05 considered significant. A total of 100 patients (50 Latarjet, 50 DTA) with a mean ± SD age of 25.6 ± 6.1 years were analyzed at 45 ± 20 months (range, 24-111) after surgery. Thirty-two patients (64%) in each group underwent prior ipsilateral shoulder surgery (range, 1-3). Patients undergoing DTA had significantly greater glenoid bone loss defects when compared with patients undergoing Latarjet (28.6% ± 7.4% vs 22.4% ± 10.3%, P = .001). Patients in both groups experienced significant improvements in all outcome scores after surgery ( P < .05 for all). No significant differences were found in postoperative scores between the Latarjet and DTA groups: visual analog scale (0.67 ± 0.97 vs 1.83 ± 2.31), American Shoulder and Elbow Surgeons (91.06 ± 8.78 vs 89.74 ± 12.66), Western Ontario Shoulder Instability Index (74.30 ± 21.84 vs 89.69 ± 5.50), or Single Assessment Numeric Evaluation (80.68 ± 7.21 vs 90.08 ± 13.39) ( P > .05 for all). However, patients in the Latarjet group had superior Simple Shoulder Test outcomes ( P = .011). There were 10 complications (10%) for the entire cohort, including 5 in the Latarjet group (3 of which required reoperation) and 5 in the DTA group (3 of which required reoperation). The overall recurrent instability rate was 1% (1 patient). Fresh DTA reconstruction for recurrent anterior shoulder instability results in a clinically stable joint with similar clinical outcomes as the Latarjet procedure. Longer-term studies are needed to determine if these results are maintained over time.


A mutant human proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway.
A coding mutation in the human insulin gene (His-B10----Asp) is associated with familial hyperproinsulinemia. To model this syndrome, we have produced transgenic mice that express high levels of the mutant prohormone in their islets of Langerhans. Strain 24-6 mice, containing about 100 copies of the mutant gene, were normoglycemic but had marked increases of serum human proinsulin immunoreactive components. Biosynthetic studies on isolated islets revealed that approximately 65% of the proinsulin synthesized in these mice was the human mutant form. Unlike the normal endogenous mouse proinsulin, which was almost exclusively handled via a regulated secretory pathway, up to 15% of the human [Asp10]proinsulin was rapidly secreted after synthesis via an unregulated or constitutive pathway, and approximately 20% was degraded within the islet cells. The secreted human [Asp10]proinsulin was not processed proteolytically. However, the processing of the normal mouse and human mutant proinsulins within the islets from transgenic mice was not significantly impaired. These findings suggest that the hyperproinsulinemia of the patients is the result of the continuous secretion of unprocessed mutant prohormone from the islets via this alternative unregulated pathway.


Wall-Eyed Bilateral Internuclear Ophthalmoplegia by Ischemic Stroke: Case Report and Literature Review.
Wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) is a rare symptom. Several studies have reported that a small brainstem lesion could cause WEBINO. The authors present the case of an 88-year-old female individual who developed sudden-onset diplopia and gait disturbance. Neurological examination revealed WEBINO with convergence impairment, gaze-evoked upward nystagmus on upward gaze, and bilateral limb ataxia. Brain magnetic resonance imaging revealed a small paramedian pontine tegmentum infarction, responsible for the symptoms. A literature review of WEBINO in ischemic stroke revealed that most patients exhibited impaired convergence and other neurological symptoms. Gaze-evoked upward nystagmus on upward gaze and bilateral limb ataxia accompanied by WEBINO due to a small brainstem lesion were the characteristic findings of our case.


Pharmacological blockade of small conductance Ca2+-activated K+ channels by ICA reduces arrhythmic load in rats with acute myocardial infarction.
Acute myocardial infarction (AMI) with development of ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD). At present, no pharmacological treatment has successfully been able to prevent VF in the acute stage of AMI. This study investigates the antiarrhythmic effect of inhibiting small conductance Ca2+-activated K+ (SK) channels using the pore blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) in AMI rats. Acute coronary ligation was performed in 26 anesthetized rats, and ECG, monophasic action potentials (MAPs), and ventricular effective refractory period (vERP) were recorded. Rats were randomized into four groups: (i) 3 mg/kg i.v. ICA with AMI (AMI-ICA-group, n = 9), (ii) vehicle with AMI (AMI-vehicle-group, n = 9), (iii) vehicle with sham operation (sham-vehicle-group, n = 8), and (iv) 3 mg/kg i.v. ICA with sham operation (sham-ICA-group, n = 6). At the end of experiments, hearts were stained for the non-perfused area at risk (AAR). AMI resulted in the development of ventricular tachycardia (VT) in all AMI-vehicle and AMI-ICA rats; however, ICA significantly decreased VT duration. VF occurred in 44% of AMI-vehicle rats but not in AMI-ICA rats. Monophasic action potential duration at 80% repolarization (MAPD80) in the ischemic area decreased rapidly in both AMI-vehicle and AMI-ICA rats. However, 5 min after occlusion, MAPD80 returned to baseline in AMI-ICA rats but not in AMI-vehicle rats. The vERP was prolonged in the AMI-ICA group compared to AMI-vehicle after ligation. AAR was similar between the AMI-vehicle group and the AMI-ICA group. In rats with AMI, ICA reduces the burden of arrhythmia.


Psychiatric Comorbidities Modify the Association Between Childhood ADHD and Risk for Suicidality: A Population-Based Longitudinal Study.
The objective of this study was to evaluate the effect of psychiatric comorbidities on the association between childhood ADHD and suicidality among adults. Subjects were recruited from a population-based birth cohort. Participating adult subjects with childhood ADHD and non-ADHD controls were administered a structured psychiatric interview to assess suicidality and psychiatric comorbidities. Associations were assessed using logistic regression. Compared with controls, ADHD cases were significantly more likely to meet criteria for suicidality. Subjects with childhood ADHD who met criteria for generalized anxiety disorder had a higher than expected risk of suicidality with an observed odds ratio of 10.94 (95% confidence interval [4.97, 24.08]) compared with an expected odds ratio of 4.86, consistent with a synergistic interaction effect. Significant synergistic interactions were also observed for hypomanic episode and substance-related disorders. Childhood ADHD is significantly associated with adult suicidal risk. Comorbidity between ADHD and some psychiatric disorders is associated with a higher suicidal risk than expected.


Single-monthly-dose vitamin D supplementation in elderly patients.
To determine the serum levels of calcidiol and calcitriol in 2 men and in 21 postmenopausal, primarily elderly women receiving hormone replacement therapy, orally administered calcium citrate, and an additional supplement of 50,000 IU of vitamin D (1.25 mg of cholecalciferol) once monthly for various periods. We determined plasma calcidiol and calcitriol levels at various times, ranging from -1 to +60 days after intake of a single dose of 1.25 mg of vitamin D in 10 initial or short-term users (1 to 6 months) and in 13 women who had been using this monthly regimen for several years. The primary concerns were the safety and adequacy of the blood levels achieved with a regimen that encouraged compliance. In long-term users of monthly vitamin D regimens, calcidiol levels were usually slightly in excess of the upper limit of normal (that is, >52 ng/mL [>130 nmol/L]) at all times throughout the month; in contrast, calcitriol levels exceeded the normal range (8 to 52 pg/mL [19 to 125 pmol/L]) only once in 18 samplings. In short-term users, calcidiol levels exceeded the normal range only once shortly after intake, and no calcitriol level exceeded the normal range. Once-a-month dosage of 50,000 IU (1.25 mg) of vitamin D in elderly women receiving hormone replacement therapy plus supplemental calcium and uncontrolled generic multivitamin intake yields calcitriol levels within the normal range, even after years of use of this regimen. Calcidiol levels exceeded the normal range at all times in long-term users but only once in short-term users. Calcidiol concentrations, however, were found to be far below levels (>150 ng/mL [>375 nmol/L]) that might produce hypercalciuria or hypercalcemia.


Meta-analysis of radiocesium contamination data in Japanese forest trees over the period 2011-2013.
The fate and dispersion of radiocesium in forests affected by the Fukushima atmospheric fallouts have been efficiently characterized by Japanese scientists thanks to monitoring surveys of radioactive contents in contaminated soil, water, and vegetation samples at numerous sites. In this paper, we carry out a meta-analysis of the field surveys conducted over the period 2011-2013 in evergreen coniferous and deciduous broadleaf forests of Fukushima or neighboring prefectures. The review focuses on contamination data acquired in tree vegetation - about 1500 spatio-temporal measurements of concentrations, inventories and depuration fluxes - with a particular interest for organs that were directly exposed to the atmospheric fallouts and subjected to depuration mechanisms (foliage, branches and outer bark). To reduce the spatial variability between the sites, radioactive data were normalized by the total deposit estimated at each site. Our analysis highlights the overall consistency of field observations despite the variety of experimental protocols, disparate sampling periods, differences in the forest stand characteristics and variability of the atmospheric deposition conditions. Assuming that the sites conformed to the same dynamics (within the range of residual variability), we then derive, discuss, and compare the mean representative evolutions of radiocesium contamination in the two categories of forest. Thanks to a simple mass balance approach, we finally demonstrate that: (i) about 90% of the radiocesium deposit was intercepted by evergreen coniferous vegetation, (ii) 80% of the deposit was gradually transferred to the forest floor in 3years, according to a well characterized depuration kinetics, and (iii) about 4% was readily absorbed by the foliage and translocated to internal organs (inner bark, stem wood and roots) at a rate of about 10-4d-1.


The status of stem cell transplantation for rheumatoid arthritis: a rheumatologist's view.
Stem cell transplantation (SCT) for rheumatoid arthritis will only be appropriate for a very small proportion of patients--those with aggressive disease who have had inadequate responses to several disease modifying antirheumatic drug regimens, including tumor necrosis factor blockers. The presence of biopsy proven T cell infiltrates in the synovium may be a way to improve appropriate patient selection. While there is general agreement regarding patient selection, the specifics of these criteria are not yet delineated. As for patient selection, the most appropriate SCT regimen has not yet been agreed upon and further pilot studies in this area will be required. In contrast to the above areas in which there is a distinct lack of consensus, outcome measures are better defined in RA and should include remission rate, Disease Activity Scale or American College of Rheumatology 50 (ACR 50) and ACR 70 responses, as well as longterm benefit/risk ratios (or utilities). It would be appropriate to convene a 2-3 day conference in 1-2 years to decide on the above, after more pilot data have been developed.


BF3.Et2O-catalyzed direct carbon-carbon bond formation of alpha-EWG Ketene-(S,S)-acetals and alcohols and synthesis of unsymmetrical biaryls.
A highly efficient BF3.OEt2-catalyzed formal dehydration C-C coupling reaction between readily available alpha-EWG ketene-(S,S)-acetals and various alcohols via direct substitution of the hydroxy group in alcohols has been developed. On the basis of this C-C coupling reaction, a series of alkylated alpha-EWG ketene-(S,S)-acetals and functionalized 1,4-pentanedienes were prepared in high to excellent yields and the unsymmetrical biaryls were synthesized in good yields from the generated 1,4-pentanedienes and nitroalkanes through a one-pot annulation-aromatization process.


District nurses' experiences with a caseload profiling tool: a service evaluation.
Caseload profiling is being advocated as a method to measure, manage and evidence increasingly complex caseloads in district nursing. However, there is no qualitative work on district nurses' experiences of applying caseload profiling to their caseloads. The aim of the service evaluation presented in this paper was to explore a working group's experiences of implementing a caseload-profiling tool to caseloads in district nursing in one community setting. As part of the service evaluation, three semi-structured interviews were conducted during meetings of the working group. Following data collection, thematic analysis supported the identification of three themes: barriers, facilitators and significance of data collected from caseload profiling. Subthemes were identified and compared with available literature and policy to enable new insights from practitioners to be gained. The service evaluation concluded that caseload profiling is a simple process that yields rich, complex data, with the data generated from the caseload profiles providing a method to evidence the complexity of district nursing caseloads and information to support proactive caseload management and identification of service delivery priorities.


A possible role for selenoprotein glutathione peroxidase (GPx1) and thioredoxin reductases (TrxR1) in thyroid cancer: our experience in thyroid surgery.
Oxidative stress is responsible for some alterations in the chemical structure and, consequently, in the function of proteins, lipids, and DNA. Recent studies have linked oxidative stress to cancers, particularly thyroid cancer, but the mechanisms remain unclear. Here, we further characterize the role of oxidative stress in thyroid cancer by analyzing the expression of two selenium antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase (TrxR1) in thyroid cancer cells. Samples of both healthy thyroid tissue and thyroid tumor were taken for analysis after total thyroidectomy. The expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified by densitometric analyses, while the evaluation of free radicals was performed by Electron Paramagnetic Resonance (EPR)-spin trapping technique. Our results show a decrease in the expression of GPx1 and TrxR1 (- 45.7 and - 43.2% respectively, p < 0.01) in the thyroid cancer cells compared to the healthy cells. In addition, the EPR technique shows an increase of free radicals in tumor tissue, significantly higher than that found in healthy thyroid tissue (+ 116.3%, p < 0.01). Our findings underscore the relationship between thyroid cancer and oxidative stress, showing the imbalance of the oxidant/antioxidant system in thyroid cancer tissue. These results suggest that either the inability to produce adequate antioxidant defense or an increased consumption of antioxidants, due to the hyper-production of free radicals, may play a crucial role in thyroid cancer.


Laser-treated substrate with nanoparticles for surface-enhanced Raman scattering.
A rapid and simple approach to fabricate a large area of nanostructured substrate for surface-enhanced Raman scattering (SERS) is reported. Gold nanoparticles ranging from 10 to 40 nm in diameter uniformly distributed on a silicon substrate were obtained by annealing the gold film precoated on the silicon substrate with UV nanosecond (ns) laser pulses. The gold nanoparticles were formed by surface tension of the melted gold layer heated by ns laser pulses. The enhancement factor of the SERS substrate for Rhodamine 6G at 632.8 nm excitation was measured to be higher than 10(5). The proposed technique provides the opportunity to equip a functional microchip with SERS capability of high sensitivity and chemical stability.


Administration of mAb against alpha E beta 7 prevents and ameliorates immunization-induced colitis in IL-2-/- mice.
We previously demonstrated that 2,4,6-trinitrophenol (TNP)-OVA immunization leads to a transmural colitis in the IL-2-/- mouse that is caused by IL-12-driven CD4+ Th1 T cells and resembles human Crohn's disease. The integrin alpha E beta 7 is highly expressed on colonic intraepithelial lymphocytes and has been suggested to function as a homing or retention molecule for intraepithelial lymphocytes. To evaluate the role of alpha E beta 7 in colitis, we administered a mAb against alpha E beta 7 to IL-2-/- mice that were immunized at the same time with TNP-OVA in CFA. To our surprise, this treatment resulted in a significantly reduced colitis severity score, 0-2 vs 3-4, that was associated with a significant reduction in CD4+ lamina propria lymphocyte subpopulation (p < 0.01). In contrast, the total number of splenic CD4+ T cells of treated animals was significantly elevated compared with that of untreated animals (3.2 +/- 0.6 x 107 vs 1.2 +/- 0.2 x 107; p < 0.05). Similarly, functional studies revealed that IFN-gamma production by lamina propria lymphocytes isolated from IL-2-/- TNP-OVA-immunized mice treated with anti-alpha E beta 7 was significantly lower than in untreated IL-2-/- TNP-OVA-immunized mice. In contrast, IFN-gamma production by splenic cells isolated from treated IL-2-/- TNP-OVA-immunized mice was significantly higher than in untreated mice. Finally, TNP-OVA-immunized IL-2-/- mice that were treated after the colitis had been established also showed a significant decrease in mucosal inflammation after alpha E beta 7 mAb administration. Thus, the above findings demonstrate that the onset and maintenance of inflammatory bowel disease depends on the colonic localization of lamina propria CD4+ lymphocytes expressing alpha E beta 7.


A case study from the interaction of strawberry and Botrytis cinerea highlights the benefits of comonitoring both partners at genomic and mRNA level.
Strawberry Fragaria x ananassa (cv. Korona) was inoculated with Botrytis cinerea by dipping berries in a conidial suspension. Colonization by the pathogen was monitored using real-time PCR, ELISA and ergosterol assays, the first showing the highest sensitivity. The expression of pathogen beta-tubulin and six polygalacturonases (Bcpg1-6) and three host defence genes (polygalacturonase-inhibiting protein (FaPGIP) and two class II chitinases) were monitored using real-time RT-PCR. The maximum transcript levels of the host defence genes occurred at 16 h postinoculation (hpi) at the presumed initial penetration stage. The unique transcript profile of Bcpg2 over the 96-h incubation time and its high transcript levels relative to those of the other Bcpgs at 8-24 hpi suggest that the gene has a specific role in the penetration stage. Bcpg1 was expressed constitutively at a relatively high level in actively growing mycelia throughout the experimental period. Comparison of the transcript profiles indicated that Bcpg1 and Bcpg3-6 were coordinately regulated.


Sensitivity analysis of Markov models for communities of competing sessile organisms.
1. Communities of competing sessile organisms are often modelled using Markov chains. Sensitivity analysis of the stationary distribution of these models tells us how we expect the abundance of each organism to respond to changes in interactions between species. This is important for conservation and management. 2. Markov models for such communities have usually been formulated in discrete time. Each column of the discrete-time transition matrix must sum to 1 (column stochasticity). Sensitivity analysis therefore involves defining a pattern of compensation that maintains column stochasticity as a single transition probability changes. There is little biological theory about the appropriate compensation pattern, but the usual choices involve changing only the elements of a single column of the transition matrix. 3. I argue that if the underlying dynamics occur in continuous time, each transition probability is the net outcome of direct and many indirect interactions. 4. Determining the consequences of changing a single direct interaction will often be of interest. I show how this can be achieved using a continuous-time model. The resulting discrete-time compensation pattern is quite different from those that have been considered elsewhere, with changes occurring in many columns. 5. I also show how to determine which direct interactions are being changed under any discrete-time compensation pattern.


BioQuant: Data Processing Software for Simultaneous Imaging Analysis for Elements and Molecules Using Two Mass Spectrometers.
Simultaneous imaging analysis for both elements and molecules was conducted by introducing laser-induced sample particles into two separate mass spectrometers (i.e., an inorganic spectrometer and an organic mass spectrometer) through the split-flow protocol. The timing of ion detections for elements and molecules can be different, reflecting the differences in mass scan rates, lengths for transport tubing, and flow rates of carrier gases, and thus, the timing of ion detections must be carefully aligned to discuss abundance correlations between elements and molecules. To achieve this, a new data processing software "BioQuant" was developed to correct the time difference of the signal intensities for components obtained by the two mass spectrometers. With the BioQuant software, signal intensity data obtained from several unit cells were merged into a newly defined unit cell, calculated by the common time intervals from both mass spectrometers. With the newly defined unit cells, correlation analysis between the elements and molecules can be conducted. Combination of the BioQuant software and laser ablation system connected to two separated mass spectrometers can become a benchmark technique for simultaneous imaging analysis for both the elements and molecules from single sample material.


Chronic hepatitis B in children: Therapeutic challenges and perspectives.
Chronic hepatitis B virus (HBV) infection and HBV-related hepatitis in children remains an unmet medical need, as current treatments are only partially effective, and only in a limited number of affected children. So-called "immunotolerant" children have not shown increased serological responses to available treatments. In cases involving more active disease, serological response has only been obtained in approximately one-third of patients when using interferon, while other cases exhibited virological response solely under continuous treatment with nucleoside analogs. Guidelines have recently been established to aid pediatricians in effectively managing this condition. With the available medications, no treatment is so far indicated for immunotolerant children, but only for cases presenting increased alanine aminotransferase levels to over 1.5-2 times the upper limit of normal for over 6 months, and without spontaneous HB envelope antigen to antibody seroconversion. The therapeutic arsenal approved by the Food and Drugs Administration and European Medicines Agency for children remains limited because of the lack of large-scale clinical trials validating treatments already approved for the adult population. Yet, the recent discovery of a specific HBV-cell surface receptor, NTCP, allows for new treatment perspectives regarding the future.


Alterations of markers during hepatocarcinogenesis in rats.
Fischer 344 male rats were treated with N-nitrosodiethylamine, and two weeks later promotion was effected by treatment with N-2-acetylaminofluorene for 14 days. At midpoint of the promotion protocol, one group of rats was subjected to partial hepatectomy (model A); others were treated with either carbon tetrachloride (model B) or thioacetamide (model C). Alterations in the activities of marker enzymes (glucose-6-phosphatase, gamma-glutamyl transpeptidase, cytochrome P-450, N-demethylase) during hepatocarcinogenesis were followed biochemically. The highest incidences of liver foci and of hepatocellular carcinomas were observed in model A, and these showed a good correlation with long-lasting elevated gamma-glutamyl transpeptidase activity. Analysis of the marker alterations suggests that there are three stages in hepatocarcinogenesis: (1) depression resulting from the toxic action of the initiator; (2) recovery and adaptation to cellular injury; and (3) long-lasting adverse alterations in the activities of the marker enzymes after promotion. The loss of certain non-histone proteins soon after promotion was also observed. Comparative studies of the individual actions of initiators and promoters on marker enzymes indicated that both contribute to the marker changes during hepatocarcinogenesis.


Arcanobacterium haemolyticum and streptococcal pharyngitis.
Arcanobacterium haemolyticum was recovered from 0.5% of throat cultures of 3,922 patients seeking medical attention because of sore throat. Most of the patients positive for A. haemolyticum were 15-25 years old, and had fever (80%), lymphadenopathy (67%), pharyngeal exudate (69%) or skin rash (23%). In this age group, 2% of the throat cultures proved positive for A. haemolyticum. All A. haemolyticum strains were susceptible to penicillin, erythromycin, cephalexin and clindamycin, but resistant to trimethoprim/sulphamethoxazole. In half of the patients with A. haemolyticum it was the only bacterial pathogen isolated, while in the remainder, beta-haemolytic streptococci were also detected. As expected, beta-haemolytic streptococci were much more frequent than A. haemolyticum in the throat cultures.


Use of a platelet-fibrinogen-thrombin mixture as a corneal adhesive: experiments with sutureless lamellar keratoplasty in the rabbit.
A platelet-fibrinogen-thrombin mixture utilizing autologous platelets was studied for its potential as a corneal adhesive. In the rabbit it demonstrated sufficient adhesive properties to allow 50 per cent of lamellar keratoplasties (autotransplants) to remain in place without the use of sutures. The mixture retains significant adhesive properties for four to six days. It is simple to prepare and apply. It also appears nonantigenic and nontoxic to the cornea; it does not incite inflammation, nor interfere with corneal clarity or the regrowth of corneal epithelium.


[A comparison of maternal psychosocial adaptation among pregnant women with different gravidity].
The purpose of this study was to examine women's psychosocial adaptation during different trimesters of pregnancy and to compare maternal psychosocial adaptation between primigravida and multigravida. A cross-sectional and comparative research design was conducted. A convenience sample consisting of 717 pregnant women who made a prenatal clinical visit in southern Taiwan were recruited for this study. The sample included 369 primigravida and 348 multigravida. A Demographic Inventory and the Chinese version of the Prenatal Self-Evaluation Questionnaire (PSEQ) were used to collect data. Results found that (1) the subscale "relationship with husband" for multigravida showed statistically significant differences between the three trimesters, with scores for the third trimester higher than those for the first. Also, multigravida had poorer adaptation on "relationship with husband" in the third trimester than in the first; (2) Analysis of covariance was used to adjust for age, marital status and planned pregnancy, as the distribution of such variables was significantly different between primigravida and multigravida. Results showed significant differences between the two sample groups in terms of PSEQ total scores and scores for "concern for well-being of self and baby," "preparation for labor," and "fear of helplessness, and loss of control in labor." This indicates that primigravida had poorer maternal psychosocial adaptation than multigravida and worried more about "concern for well-being of self and baby," "preparation for labor," and "fear of helplessness, and loss of control in labor." The findings of this study provide evidence-based data to help nursing professionals provide more suitable nursing care to pregnant women. Nurses should assess pregnant women's psychosocial adaptation during their prenatal visiting and then assist them to better understand the process of childbirth and enhance their level of control during labor. In addition, nurses should appraise women's relationships with their husbands during the third trimester and supply appropriate nursing care to pregnant women for a more pleasant pregnancy and labor experience.


The effects of acute exercise intensity on episodic and false memory among young adult college students.
Background: Previous experimental work demonstrates that acute exercise may enhance episodic memory performance. However, limited research has examined the extent to which acute exercise influences false episodic memory production, and no studies, to date, have examined whether there is an intensity-specific effect of acute exercise on both true episodic and false episodic memories. Thus, the present experiment evaluated the effects of intensity-specific acute exercise on episodic memory and false episodic memory. Methods: A three-arm, parallel, between-group randomized controlled trial was employed in the University setting, with participants (N=60; Mage= 20.8 years) randomized into a moderate intensity exercise group (15-minute bout of treadmill exercise at 50% heart rate reserve), a high intensity exercise group (15-minute bout of treadmill exercise at 80% heart rate reserve), or a control group (time-matched period of sitting). True episodic and false episodic memory were both assessed using 6 word-lists from the Deese-Roediger-McDermott (DRM) paradigm, including both a short-term recall and a delayed memory recognition assessment. Results: For the number of words recalled across each of the 6 lists, there was a significant main effect for list (P<0.001, η2 p=0.15), marginally significant main effect for group (P=0.07, η2 p=0.09), but no list by group interaction effect (P=0.44, η2 p=0.03). Those in the high-intensity exercise group recalled significantly (P<0.05) more words than the control group. For the false episodic word recall, across various lists, high-intensity acute exercise was associated with a greater rate of false episodic memories. For the memory recognition task, there was no main effect for word type (P=0.46, η2 p=0.01), group (P=0.4443, η2 p=.03), word type by group interaction (P=0.44,η2 p=0.03), recall by group interaction (P=0.4441, η2 p=0.04), or word type by recall by group interaction (P=0.32, η2 p=0.04). However, there was a main effect for recall (P<0.001, η2 p=.54)and a word type by recall interaction (P<0.001, η2 p=0.77). Conclusion: These findings suggest that acute high-intensity exercise may enhance true episodic memories, and, possibly, also increase the rate of false episodic memories. We discuss these findings in the context of how different acute exercise intensities may have unique and differential effects on underlying mechanistic processes related to true and false episodic memory.


A Speech Recognition Method Based on Domain-Specific Datasets and Confidence Decision Networks.
This paper proposes a speech recognition method based on a domain-specific language speech network (DSL-Net) and a confidence decision network (CD-Net). The method involves automatically training a domain-specific dataset, using pre-trained model parameters for migration learning, and obtaining a domain-specific speech model. Importance sampling weights were set for the trained domain-specific speech model, which was then integrated with the trained speech model from the benchmark dataset. This integration automatically expands the lexical content of the model to accommodate the input speech based on the lexicon and language model. The adaptation attempts to address the issue of out-of-vocabulary words that are likely to arise in most realistic scenarios and utilizes external knowledge sources to extend the existing language model. By doing so, the approach enhances the adaptability of the language model in new domains or scenarios and improves the prediction accuracy of the model. For domain-specific vocabulary recognition, a deep fully convolutional neural network (DFCNN) and a candidate temporal classification (CTC)-based approach were employed to achieve effective recognition of domain-specific vocabulary. Furthermore, a confidence-based classifier was added to enhance the accuracy and robustness of the overall approach. In the experiments, the method was tested on a proprietary domain audio dataset and compared with an automatic speech recognition (ASR) system trained on a large-scale dataset. Based on experimental verification, the model achieved an accuracy improvement from 82% to 91% in the medical domain. The inclusion of domain-specific datasets resulted in a 5% to 7% enhancement over the baseline, while the introduction of model confidence further improved the baseline by 3% to 5%. These findings demonstrate the significance of incorporating domain-specific datasets and model confidence in advancing speech recognition technology.


Tuberculin skin test conversion in patients under treatment with anti-tumor necrotizing factor alpha agents.
Despite successful clinical outcomes of biologic medications in patients with chronic rheumatic diseases, some considerable adverse effects such as infections remain a major concern. Possibility of tuberculosis (TB) reactivation over treatment with anti-tumor necrotizing factor (TNF) alpha agents has necessitated a screening test before initiation of treatment. However, screening over the course of treatment is not recommended in those patients with negative baseline screening tests. This study aimed to evaluate the efficacy of tuberculin skin test (TST) before treatment in patients with chronic rheumatologic diseases who were indicated to receive anti-TNF-alpha therapy and the necessity of repeating this test over the course of treatment. In this prospective study, patients with chronic rheumatologic diseases receiving anti-TNF-alpha agents were studied in a two-year period. TST was performed before treatment and those with positive results were excluded from the study. Thereafter, treatment with anti-TNF-alpha agents was initiated with the indicated dose. TST was repeated before administration of biologic treatment until TST became positive or 16 weeks after the initiation of treatment with anti-TNF-alpha. A total of 51 cases were studied, of whom one patient (1.9%) was excluded due to positive TST before treatment. All participants received infliximab and the TST test became positive in one patient (2%) 2 weeks after receiving the first dose. Also, the results of further tests at weeks 6, 10, and 14 were all negative for the remaining patients. Due to the possibility of TST conversion after administration of anti-TNF-alpha therapy, it is important to consider TB monitoring in patients under treatment with these agents using available methods such as TST.


Masking of irregular corneal topography with contact lenses.
We examined the effectiveness of various types of contact lenses in masking irregular corneal topography using videokeratoscopy, residual aberrations, and measurement of visual acuity. Thirteen subjects with differing degrees of keratoconus were recruited. Four types of soft lenses were used that varied in both thickness and water content, along with a rigid gas permeable (RGP) and a flexible gas permeable contact lens. RGP contact lenses provided the best visual acuity and the least residual aberrations. Flexible gas permeable lenses showed a reasonable masking of corneal distortion but did not provide the expected improvement in visual acuity. Soft contact lenses provided marginally better visual acuity than spectacle correction, but the level of residual aberrations was still high, even for relatively thick soft lenses (up to 0.2 mm). A significant correlation existed between the regularity of the front surface of the contact lenses on the eye and visual acuity in low illumination. Among the currently available contact lens materials, RGP lenses provide the best visual performance for subjects with keratoconus.


Rupture of Abdominal Aortic Aneurysm Caused by Combined Type IIIb and Type Ia Endoleak with the Endurant II Endograft: A Case Report.
We report a case of combined types IIIb and Ia endoleak that developed 6 years after endovascular aneurysm repair (EVAR) with the Endurant II® endograft for abdominal aortic aneurysm (AAA). The patient presented with post-EVAR AAA rupture and underwent emergency open repair. We observed types IIIb and Ia endoleak and successfully performed felt banding to preserve the stent graft. Type IIIb endoleak with the Endurant® endograft is rare, and treatments have not been fully established. We summarized the case reports regarding type IIIb endoleak with the Endurant® endograft and mainly discussed the treatments.


Long-term feeding of various fat diets modulates azoxymethane-induced colon carcinogenesis through Wnt/beta-catenin signaling in rats.
The Wnt signaling pathway plays an essential role in carcinogenesis, and the amount of fat intake and composition of dietary fatty acids are crucial factors for colon carcinogenesis. We investigated whether various dietary fats affected the Wnt signaling pathway of colon tumorigenesis in azoxymethane (AOM)-treated rats. Male Sprague-Dawley rats were given intraperitoneal injections of AOM and supplemented with 10% corn, olive, beef, and fish oil for 44 wk. Aberrant crypt foci (ACF) and tumors were examined at 12 and 44 wk. Normal appearing colon mucosal proliferation and apoptosis were evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation and percentages of fragmented DNA, respectively. Expressions of beta-catenin, cyclin D(1), Wnt2, Wnt3, and Wnt5a of normal appearing colon mucosa were analyzed by Western blot analysis. Long-term dietary corn oil and beef tallow increased ACF, tumor incidence, and tumor numbers in AOM-treated rats. In contrast, both olive and fish oil inhibited them. Dietary corn oil and beef tallow increased BrdU incorporation and the expression of cytosolic beta-catenin and cyclin D(1) and decreased apoptosis in the colon mucosa. Expressions of Wnt2 and Wnt3 in rats fed with beef tallow and Wnt5a in rats fed with corn oil increased with or without AOM-treatment. BrdU-incorporated cells were often observed at the tops of crypts in rats fed with beef tallow, whereas this was not observed in rats fed with the other diet. Long-term high intake of corn oil and beef tallow enhanced cell proliferation through Wnt signaling and modulated the distribution of proliferating cells, which might contribute to promoting effects in colon tumorigenesis.


Amputee skin condition: occlusion, stratum corneum hydration and free amino acid levels.
Patients with a prosthetic limb report negative skin effects, including irritation, rash and chafing, which can lead to infection, discomfort and reduced wear time to significantly impact normal activities. The aims were to examine the epidermal integrity (transepidermal water loss, TEWL), stratum corneum (SC) hydration [moisture accumulation rate (MAT)], friction and biomechanical properties in active below the knee amputees and to determine the effects of an inert sock liner on skin condition. The liner reduced hydration, TEWL and friction and increased elasticity versus the amputee's conventional skin care methods. Residual limb TEWL was increased and MAT was reduced versus the contralateral normal skin. In a second study, we hypothesized that complete occlusion would decrease free amino acids (FAA) and quantified them by high performance liquid chromatography in an adult volar forearm model. Occlusion with a water vapor impermeable wet dressing led to increased TEWL, erythema and dryness and reduced MAT versus normal skin, comparable to the results in the amputees. The FAA levels were significantly reduced for the occluded sites. The results suggest that residual limb occlusion in amputees may block the formation of FAA in the upper SC. Therapies based on replacement of water binding FAAs, may alleviate the consequences of long-term occlusion.


Multifunctional 3D cationic starch/nanofibrillated cellulose/silver nanoparticles nanocomposite cryogel: Synthesis, adsorption, and antibacterial characteristics.
We report a new 3D nanocomposite cryogel combines the advantages of cationic starch (Cs), nanofibrillated cellulose (NFC) and silver nanoparticles (Ag NPs). Cs was the main component of the cryogel while NFC was used as a filling agent to enhance the mechanical properties of the produced cryogel. Both Cs and NFC endow the cryogel with adsorption properties while Ag NPs enhances its antibacterial properties. Ag NPs was green synthesized with the aid of microwave radiation using NFC as reducing and stabilizing agent. The prepared Ag particles were free of impurities with sizes <10 nm and good stability in solution. Two different concentrations of the prepared Ag NPs were added to a mixture of Cs and NFC and subjected to freeze drying to get porous cryogel (3D microstructure). The Ag NPs free cryogel has highly porosity smooth surface with large surface area. Adding Ag NPs decreased these features and increased the 3D roughness. Optimum adsorption of reactive blue 49 was observed after 30 min of contact with 1.5 g/L of the cryogel at pH 1. The adsorption kinetics and isotherm were best described by the pseudo-first-order and Freundlich equations, respectively. All prepared cryogels have notable antibacterial properties that were significantly improved by adding Ag NPs. Overall, the new 3D composite cryogel can efficiently remove dyes and bacteria from wastewater.


Differentiation antigens on mouse eosinophils and neutrophils identified by monoclonal antibodies.
A panel of hybridomas secreting monoclonal antibodies (mAb) reacting with antigens on mouse eosinophils and neutrophils has been selected. It is shown that four mAb bind preferentially to eosinophils, recognizing antigens expressed between 5 and 25 times more densely on these cells than on neutrophils. One mAb reacts preferentially with neutrophils, binding an antigen about 12 times more common on these cells than on eosinophils. Four mAb are shown to react with both eosinophils and neutrophils, and also macrophages. These mAb confirm the presence of different differentiation antigens on both eosinophils and neutrophils, and show that the myeloid series express antigens not expressed on lymphocytes.


Interobserver variation in assessment of gastroduodenal lesions associated with non-steroidal anti-inflammatory drugs.
Video endoscopic images were used to investigate whether gastroenterologists could agree on the definition of lesions within the stomach seen at endoscopy, with particular reference to those seen in patients taking non-steroidal anti-inflammatory drugs. Seven experienced endoscopists, unaware of the patients' clinical history or drug consumption, recorded their classification for 93 randomised video images of gastric lesions. There was complete agreement in the diagnosis of ulceration for nine images from patients who were not taking non-steroidal anti-inflammatory drugs; eight of nine were classified as deep ulcers, with 86% agreement for this subclassification. By contrast, the overall agreement for lesions in patients taking non-steroidal anti-inflammatory drugs was only 55%. Only nine of 44 ulcers were subclassified as deep, and there was considerable cross classification of non-haemorrhagic erosions and ulcers. In conclusion, ulcers that occur in patients taking non-steroidal anti-inflammatory drugs differ from those in patients who are not taking these drugs in that they are often more superficial and difficult to distinguish from erosions. The prognostic importance of these lesions is, therefore, uncertain.


[Pharmaceutical Regulations in the Japanese Hospitals in 1880s and the Case of a Scholar of Pharmacology in Oita Prefecture].
In the 1870s, various provisions existed regarding pharmacists working at Japanese military hospitals. And in the decade of the 1880s, some hospitals in Tokyo and Oita implemented them. These provisions gave pharmacists the right to challenge doctors' prescriptions and provide patients with medicine-related information. In Oita Prefecture, patients could have their prescriptions filled outside of the hospital. This paper examines the case of one scholar of pharmacology who worked in Oita Medical School Hospital.


Long-term on-farm participatory maize breeding by stratified mass selection retains molecular diversity while improving agronomic performance.
Modern maize breeding programs gave rise to genetically uniform varieties that can affect maize's capacity to cope with increasing climate unpredictability. Maize populations, genetically more heterogeneous, can evolve and better adapt to a broader range of edaphic-climatic conditions. These populations usually suffer from low yields; it is therefore desirable to improve their agronomic performance while maintaining their valuable diversity levels. With this objective, a long-term participatory breeding/on-farm conservation program was established in Portugal. In this program, maize populations were subject to stratified mass selection. This work aimed to estimate the effect of on-farm stratified mass selection on the agronomic performance, quality, and molecular diversity of two historical maize populations. Multilocation field trials, comparing the initial populations with the derived selection cycles, showed that this selection methodology led to agronomic improvement for one of the populations. The molecular diversity analysis, using microsatellites, revealed that overall genetic diversity in both populations was maintained throughout selection. The comparison of quality parameters between the initial populations and the derived selection cycles was made using kernel from a common-garden experiment. This analysis showed that the majority of the quality traits evaluated progressed erratically over time. In conclusion, this breeding approach, through simple and low-cost methodologies, proved to be an alternative strategy for genetic resources' on-farm conservation.


Incorporating evidence-based practice into the macro practice curriculum.
Considerable attention has been directed in preparing social work students to understand the paradigm of evidence-based practice (EBP). The infusion of EBP through training, course instruction, and assignments has the potential to enhance EBP knowledge acquisition in the macro practice curriculum. This article examines an approach to integrating EBP into the curriculum through a training model that is linked with the practice, research, and practicum courses. A preliminary study based on student satisfaction ratings reveals that the approach was effective in helping students to acquire knowledge about the process of EBP and in using evidence to make practice decisions.


[Refractive aspects of modern cataract surgery].
Modern cataract surgery is a refractive procedure whereby one basically can achieve the targeted postoperative refraction. To achieve this goal, according to the patient's wishes, biometry, mathematical calculation of IOL power and astigmatism management are important factors. On the other hand, multifarious developments in intraocular lens technology also contribute to this target. The individual choice of incision (on axis surgery: incision in the steeper meridian, length, shape and location concerning cornea or sclera) reduces the preoperatively existing astigmatism. Biometry with personalised data and formulas of the third generation are important factors to achieve the targeted refraction. In addition to this, the development of manifold lens designs in the last years to improve intraocular lens quality has enabled progress within various domains, for example, the use of optimised intraocular lenses to compensate corneal aberration, the implantation of toric lenses for corrections of higher pre-existing corneal astigmatism or the use of phacic intraocular lenses to correct higher ametropia. Patient satisfaction postoperatively depends on the precise refractive result as desired. With our current operative and technical possibilities we are able to achieve this with high probability and safety.


Prenatal antibiotics and atopic dermatitis among 18-month-old children in the Danish National Birth Cohort.
Despite extensive research, the aetiology of atopic dermatitis remains largely unknown, but reduced intestinal microbiota diversity in neonates has been linked to subsequent atopic dermatitis. Consequently, postnatal antibiotics have been proposed as a risk factor, but a potential association between prenatal antibiotics and atopic dermatitis is not well studied. Overall, the current evidence suggests a positive association between exposure to prenatal antibiotics and atopic dermatitis. To investigate the association between prenatal antibiotics and atopic dermatitis among 18-month-old children. This study conducted within the Danish National Birth Cohort included 62 560 mother-child pairs. Data on maternal prenatal antibiotics were collected in the 30th gestation week and 6 months post-partum, and offspring atopic dermatitis 18 months post-partum through telephone interviews. Antibiotic use was categorized by the timing of exposure as 1st-2nd trimester (gestation week 0-29), 3rd trimester (gestation week 30-birth), all three trimesters or none. Data were analysed by logistic regression analyses adjusting for potential confounders. Exposure to antibiotics prenatally was associated with increased odds of atopic dermatitis among children born by atopic mothers but only when used in both 1st-2nd and 3rd trimester (ORadj 1.45, 95% CI: 1.19-1.76). The findings were consistent using different definitions of atopic dermatitis. Prenatal exposure to antibiotics throughout pregnancy was associated with an increased risk of atopic dermatitis but only within the first 18 months of life among children born by atopic mothers. The clinical usefulness of this finding must rest on corroboration in independent data sources.


Cholinergic synapses in human cerebral cortex: an ultrastructural study in serial sections.
Cholinergic axons in the human cerebral cortex were analyzed by electron microscopy. Choline acetyltransferase (ChAT) immunoreactivity was used to identify cholinergic axons in samples of anterior temporal lobe removed at surgery. A systematic survey of labeled axon varicosities, visualized in complete serial sections, showed that 67% of all varicosities formed identifiable synaptic specializations. These synapses were usually symmetric and quite small, often present in only one to two serial sections. However, an occasional synapse was asymmetric and larger, seen in five to seven serial sections. The postsynaptic processes at cholinergic synapses were often identified as spiny dendrites or spines. The existence of cholinergic axons in the human cerebral cortex has been demonstrated in numerous studies. Our findings provide the first ultrastructural evidence that these axons make synaptic contact with cortical neurons in the human brain.


Biosynthesis of lysine in plants: the putative role of meso-diaminopimelate dehydrogenase.
Extracts from Chlamydomonas, corn, soybean and tobacco were tested for enzymes of the lysine biosynthetic pathway. Dihydrodipicolinic acid (DHD) synthase, DHD reductase, diaminopimelate (DAP) epimerase and DAP decarboxylase were present in all. However, in contrast to the report of Wenko et al., meso-DAP dehydrogenase could not be detected in extracts prepared from soybean. Moreover, it was not found in Chlamydomonas, corn and tobacco as well. In order to set an upper limit to the amount of meso-DAP dehydrogenase that might be present, reconstruction experiments were performed with soybean and corn extracts in which the conversion of dihydrodipicolinate to lysine was made dependent on the addition of limited amounts of the meso-DAP dehydrogenase purified from Bacillus sphaericus. The presence of DAP epimerase and the absence of meso-DAP dehydrogenase indicates that the meso-DAP dehydrogenase abbreviated pathway for lysine synthesis is not operative in plants.


Mechanism of spermidine uptake in cultured mammalian cells and its inhibition by some polyamine analogues.
Transport pathways for spermidine (Spd) were characterized in mammalian cells in culture of different origin, i.e. L 1210, P 388, C 6, U 251, Balb/c 3T3 normal and transformed by virus SV40 (SV40/3T3). The kinetic constants (Km and Vmax) for 14C-Spd uptake were found to be different in these cells. Spd uptake was inhibited by spermine and putrescine in all cells. Preloading of these cells with system A and other amino acids, including ornithine, usually did not affect Spd uptake, except in L 1210 and C 6 cells, where Spd uptake was accelerated by 2-aminoisobutyric acid, demonstrating that in these two cell lines the polyamines share the system A pathway. Iso-osmotic replacement of Na+ by choline chloride in the assay medium resulted in a decrease in Spd uptake which suggests that Spd uptake is Na+ activated. In all cells, Spd uptake was inhibited by gramicidin and the Ca2+ ionophore A 23187. The degree of inhibition varied among the cells. Valinomycin (K+ ionophore) inhibited Spd uptake by C 6, P 388, Balb/c 3T3 and SV40/3T3 but not by L 1210 and U 251 cells. Treatment with N-ethylmaleimide or p-L 1210, C 6, Balb/c 3T3 and SV40/3T3 cells did not affect appreciably the uptake process. Some newly synthesized polyamine analogues inhibited the Spd uptake of all cells.


Staged repair of transposition of the great arteries with anomalous coronary anatomy and complete atrioventricular canal.
The association of complete atrioventricular canal with transposition of the great arteries is rare, with a prevalence of less than 3-5%. We present an 18-month-old patient with a complete atrioventricular canal, side-by-side transposition of the great arteries, and anomalous coronary anatomy, managed initially with pulmonary banding and then by arterial switch with complete atrioventricular canal repair at early infancy.


Postoperative Autologous Reinfusion in Total Knee Replacement.
Surgeries for total knee replacement (TKR) are increasing and in this context there is a need to develop new protocols for management and use of blood transfusion therapy. Autologous blood reduces the need for allogeneic blood transfusion and the aim of the present study was to verify the safety and the clinical efficacy. An observational retrospective study has been conducted on 124 patients, undergoing cemented total knee prosthesis replacement. Observed population was stratified into two groups: the first group received reinfusion of autologous blood collected in the postoperative surgery and the second group did not receive autologous blood reinfusion. Analysis of data shows that patients undergoing autologous blood reinfusion received less homologous blood bags (10.6% versus 30%; p = 0.08) and reduced days of hospitalization (7.88 ± 0.7 days versus 8.96 ± 2.47 days for the control group; p = 0.03). Microbiological tests were negative in all postoperatively salvaged and reinfused units. Our results emphasize the effectiveness of this procedure and have the characteristics of simplicity, low cost (€97.53 versus €103.79; p < 0.01), and easy reproducibility. Use of autologous drainage system postoperatively is a procedure that allows reducing transfusion of homologous blood bags in patients undergoing TKR.


The neurobiology of visual-saccadic decision making.
Over the past two decades significant progress has been made toward understanding the neural basis of primate decision making, the biological process that combines sensory data with stored information to select and execute behavioral responses. The most striking progress in this area has been made in studies of visual-saccadic decision making, a system that is becoming a model for understanding decision making in general. In this system, theoretical models of efficient decision making developed in the social sciences are beginning to be used to describe the computations the brain must perform when it connects sensation and action. Guided in part by these economic models, neurophysiologists have been able to describe neuronal activity recorded from the brains of awake-behaving primates during actual decision making. These recent studies have examined the neural basis of decisions, ranging from those made in predictable sensorimotor tasks to those unpredictable decisions made when animals are engaged in strategic conflict. All of these experiments seem to describe a surprisingly well-integrated set of physiological mechanisms that can account for a broad range of behavioral phenomena. This review presents many of these recent studies within the emerging neuroeconomic framework for understanding primate decision making.


[Carotid artery ultrasound and intravascular ultrasound].
Lipid lowering therapy is associated with a significant reduction in cardiocerebral events. But, additional studies are necessary to identify patients in whom atheroma may results in developing coronary events. Intravascular ultrasound(IVUS) and carotid artery echocardiography have significantly contributed to the understanding of nature of atherosclerosis and have validated the concepts of vascular remodeling and vulnerable plaque. Actually, intimal-medial thickness(IMT) in carotid echo is good predictors of cardiovascular events. Positive remodeled plaque with soft characteristics is more likely to rupture and cause acute coronary syndrome. Thus, studies using IVUS and carotid echo may lead to important insights into how risk factor reduction stabilizes plaque and reduces the risk of acute coronary events.


[Time and narrative: the psychic character of history].
The thesis developed here is that of the "psychic character of history", following Simmel's terminology. Psychic character must not, however, be understood as a lack of objectivity. On the contrary, it is an instrument of investigation, which indicates the conditions of objectification in the human and social sciences. If the historian always reconstructs a past time, it is because the past form is the mode, specific to history, of distancing/objectification. Anthropology and sociology make use of other modes of distancing. The reconstruction that takes place during psychoanalysis is thus, on three points of comparison, clarified by the narrative process proper to history.


Evaluation of the Head and Neck Surgery During the Pandemic COVID-19: A Tertiary Care Center Study.
There is a notable shift in the attitude of the admission, review, diagnostics, and follow-up of patients for all the medical sectors and of particular interest of cancer patients. The present study aimed to elaborate on the identification of patients with head and neck cancers (HNCs); the diagnostics, the triage, and the best treatment plan were all evaluated and at the same time compared with the years before the pandemic at a tertiary care center that caters to various other patients also. A retrospective observational clinical study was conducted at the tertiary care center that catered to all the medical specialties. The demographics, the patient characteristics, the surgeries performed, complications, mortality, and readmissions were evaluated and compared with the pre-coronavirus disease (COVID) time. There was a significant difference in the complications for the pre-COVID time when the groups were compared for the matched pair. The proper screening and triaging of the patients will help in the early intervention of the patients with the HNCs.


An alternative mechanism for the methylation of phosphoethanolamine catalyzed by Plasmodium falciparum phosphoethanolamine methyltransferase.
The phosphobase methylation pathway catalyzed by the phosphoethanolamine methyltransferase in Plasmodium falciparum (PfPMT), the malaria parasite, offers an attractive target for anti-parasitic drug development. PfPMT methylates phosphoethanolamine (pEA) to phosphocholine for use in membrane biogenesis. Quantum mechanics and molecular mechanics (QM/MM) calculations tested the proposed reaction mechanism for methylation of pEA involving the previously identified Tyr-19-His-132 dyad, which indicated an energetically unfavorable mechanism. Instead, the QM/MM calculations suggested an alternative mechanism involving Asp-128. The reaction coordinate involves the stepwise transfer of a proton to Asp-128 via a bridging water molecule followed by a typical Sn2-type methyl transfer from S-adenosylmethionine to pEA. Functional analysis of the D128A, D128E, D128Q, and D128N PfPMT mutants shows a loss of activity with pEA but not with the final substrate of the methylation pathway. X-ray crystal structures of the PfPMT-D128A mutant in complex with S-adenosylhomocysteine and either pEA or phosphocholine reveal how mutation of Asp-128 disrupts a hydrogen bond network in the active site. The combined QM/MM, biochemical, and structural studies identify a key role for Asp-128 in the initial step of the phosphobase methylation pathway in Plasmodium and provide molecular insight on the evolution of multiple activities in the active site of the PMT.


Evaluation of brewers' spent grain as a novel media for yeast growth.
Brewers' spent grain (BSG) is a by-product generated from the beer manufacturing industry, which is extremely rich in protein and fiber. Here we use low cost BSG as the raw material for the production of a novel growth media, through a bioconversion process utilizing a food grade fungi to hydrolyze BSG. The novel fermentation media was tested on the yeast Rhodosporidium toruloides, a natural yeast producing carotenoid. The yeast growth was analysed using the growth curve and the production of intracellular fatty acids and carotenoids. Untargeted GCMS based metabolomics was used to analyse the constituents of the different growth media, followed by multivariate data analysis. Growth media prepared using fermented BSG was found to be able to support the growth in R. toruloides (21.4 mg/ml) in comparable levels to YPD media (24.7 mg/ml). Therefore, the fermented BSG media was able to fulfill the requirement as a nitrogen source for R. toruloides growth. This media was able to sustain normal metabolomics activity in yeast, as indicated by the level of fatty acid and carotenoid production. This can be explained by the fact that, in the fermented BSG media metabolites and amino acids were found to be higher than in the unfermented media, and close to the levels in YPD media. Taken together, our study provided evidence of a growth media for yeast using BSG. This should have potential in replacing components in the current yeast culture media in a sustainable and cost effective manner.


[Brachial plexopathy after breast cancer].
Neoplastic plexopathy is an unusual, but known cause of neuropathy. This is a case report of a patient, who developed brachial plexopathy years after completing treatment for breast cancer. The patient presented with pain in one arm and, subsequently, developed sensory deficits and muscle atrophy, resulting in severely impaired hand function. Repeated magnetic resonance imaging and positron emission tomography scans were necessary before the final diagnosis could be made. The case report illustrates the importance of a thorough and repeated diagnostic work-up, when metastatic cancer is a perhaps unlikely but possible cause of plexopathy.


A Novel and More Efficient Oscillating Foil for Wave-Driven Unmanned Surface Vehicles.
In the wave-driven unmanned surface vehicles (WUSVs), oscillating-foils are the most straightforward and widely used wave energy conversion mechanism, like the wave glider. However, WUSVs usually sail slowly compared with other types of USVs. Improving the thrust of the oscillating foil to increase its speed can help WUSVs improve their maneuverability and shorten the completion of ocean missions. This paper proposed a novel method to enhance oscillating foils' thrust force using asymmetric cross-section shape and asymmetric oscillating motion. The thrust enhancement effect is verified by CFD simulation and pool experiment. The experimental results show that the asymmetric wing can enhance the propulsive force by at least 13.75%. The speed enhancement of WUSVs brought by this enhanced thrust is at least 7.6%, which has also been verified by simulation and sea experiment. The asymmetric foil only needs to make low-cost modifications on the traditional rigid symmetric foil to achieve the desired thrust enhancement effect.


Stereoselective glucuronidation of carvedilol in human liver and intestinal microsomes.
Carvedilol is used clinically as a β-adrenoceptor antagonist for the treatment of chronic heart failure and is primarily metabolized into glucuronides by UDP-glucuronosyltransferase (UGT). In this study, the stereoselective glucuronidation of carvedilol by the human liver and intestinal microsomes was examined using racemate and enantiomers. Carvedilol glucuronidation activities at substrate concentrations of 1-1,000 µmol/l in human liver and intestinal microsomes were determined by high-performance liquid chromatography with fluorescence detection, and the kinetic parameters were estimated. The activities of S-glucuronidation toward racemic and enantiomeric carvedilol in liver microsomes were higher than those of R-glucuronidation at all substrate concentrations examined. In intestinal microsomes, the activities of S-glucuronidation from racemic and enantiomeric carvedilol at ≤100 µmol/l substrates were higher than those of R-glucuronidation, whereas the glucuronidation activities at ≥200 µmol/l substrates exhibited the opposite stereoselectivity (R > S) compared with those at ≤100 µmol/l substrates. The activities of R- and S-calvedilol glucuronidation from racemate and enantiomers in the liver and intestinal microsomes were decreased at substrate concentrations of ≥100 or 200 µmol/l, and the kinetics at substrate concentrations of 1-100 and 1-1,000 µmol/l fitted with Michaelis-Menten and substrate inhibition models, respectively. The stereoselectivities of CL(int) values for carvedilol glucuronidation followed by Michaelis-Menten and substrate inhibition models were R < S for liver microsomes and R ≈ S for intestinal microsomes. These findings demonstrate that the stereoselectivity of carvedilol glucuronidation was different between human liver and intestinal microsomes, and suggest that the difference is due to the tissue-specific expression of UGT isoforms involved in the glucuronidation of carvedilol.


The alpha-aminoadipate pathway for lysine biosynthesis is widely distributed among Thermus strains.
We previously reported that lysine is synthesized through the alpha-aminoadipate pathway in Thermus thermophilus HB27 (T. Kosuge and T. Hoshino, FEMS Microbiol. Lett., 169, 361-367, 1998), which was the first report demonstrating the synthesis of lysine through the alpha-aminoadipate pathway in Bacteria. LYS20 and LYS4, which respectively encode homocitrate synthase and homoaconitate hydratase have already been identified as the lysine biosynthetic genes in T. thermophilus HB27. In the present work, we examined eight other Thermus strains for the existence of genes belonging to the alpha-aminoadipate pathway. BamHI- or BglII-digested total DNAs from the eight strains were analyzed by Southern hybridization using LYS20 or LYS4 as a DNA probe. DNA fragments that hybridized with one or both of the genes were detected in seven of the Thermus strains but not in T. ruber. The sizes of the fragments that hybridized with the LYS20 and LYS4 probes were the same among T. thermophilus HB27, T. thermophilus HB8, "T. caldophilus" GK24, and four "T. flavus" strains. For example, a similar 4.3-kb fragment was detected in each of the above seven strains. In this fragment, four open reading frames were found downstream of the LYS4 gene in T. thermophilus HB27. Gene disruption experiments revealed that three open reading frames are involved in lysine biosynthesis in T. thermophilus HB27. These results strongly suggest that the lysine biosynthetic gene cluster for the alpha-aminoadipate pathway is widely distributed in the genus Thermus.


Completeness of revascularization for multivessel coronary artery disease and its effect on one-year outcome: a report from the NHLBI Dynamic Registry.
When percutaneous coronary intervention (PCI) is performed in patients with multivessel coronary disease, a targeted revascularization (TR) of diseased vessels is performed more often than complete revascularization (CR). We compared baseline characteristics and 1-year outcomes of patients undergoing TR by operator choice (n = 1,091), TR because CR was unachievable (n = 375), and CR (n = 315) in the National Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry. Patients receiving TR because CR was unachievable were older, had more comorbidities, worse ejection fraction, less often received 2b/3a inhibitors and stents, and less frequently achieved complete angiographic success than either patients receiving TR by choice or CR. Despite these considerable differences, cumulative rates of 1-year mortality, the need for repeat PCI, or coronary bypass surgery were similar in patients who received CR, TR by choice, or TR because CR was unachievable. In multivariable models, after adjustment for clinical characteristics and propensity to receive CR, the hazard ratio for CR versus TR was 1.10 (95% CI: 0.58-2.10) for 1-year mortality; 0.89 (0.60-1.32) for repeat PCI, and 0.92 (0.66-1.29) for repeat PCI or coronary bypass surgery. In conclusion, despite the presence of more unfavorable characteristics, patients undergoing TR demonstrate 1-year outcomes equivalent to those having CR, supporting its continued use in selected patients.


Involvement of nitric oxide in depolarization-induced suppression of inhibition in hippocampal pyramidal cells during activation of cholinergic receptors.
Several types of neurons are able to regulate their synaptic inputs via releasing retrograde signal molecules, such as endocannabinoids or nitric oxide (NO). Here we show that, during activation of cholinergic receptors, retrograde signaling by NO controls CB1 cannabinoid receptor (CB1R)-dependent depolarization-induced suppression of inhibition (DSI). Spontaneously occurring IPSCs were recorded in CA1 pyramidal neurons in the presence of carbachol, and DSI was induced by a 1-s-long depolarization step. We found that, in addition to the inhibition of CB1Rs, blocking the NO signaling pathway at various points also disrupted DSI. Inhibitors of NO synthase (NOS) or NO-sensitive guanylyl cyclase (NO-sGC) diminished DSI, whereas a cGMP analog or an NO donor inhibited IPSCs and partially occluded DSI in a CB1R-dependent manner. Furthermore, an NO scavenger applied extracellularly or postsynaptically also decreased DSI, whereas L-arginine, the precursor for NO, prolonged it. DSI of electrically evoked IPSCs was also blocked by an inhibitor of NOS in the presence, but not in the absence, of carbachol. In line with our electrophysiological data, double immunohistochemical staining revealed an NO-donor-induced cGMP accumulation in CB1R-positive axon terminals. Using electron microscopy, we demonstrated the postsynaptic localization of neuronal NOS at symmetrical synapses formed by CB1R-positive axon terminals on pyramidal cell bodies, whereas NO-sGC was found in the presynaptic terminals. These electrophysiological and anatomical results in the hippocampus suggest that NO is involved in depolarization-induced CB1R-mediated suppression of IPSCs as a retrograde signal molecule and that operation of this cascade is conditional on cholinergic receptor activation.


Understanding polygenic models, their development and the potential application of polygenic scores in healthcare.
The use of genomic information to better understand and prevent common complex diseases has been an ongoing goal of genetic research. Over the past few years, research in this area has proliferated with several proposed methods of generating polygenic scores. This has been driven by the availability of larger data sets, primarily from genome-wide association studies and concomitant developments in statistical methodologies. Here we provide an overview of the methodological aspects of polygenic model construction. In addition, we consider the state of the field and implications for potential applications of polygenic scores for risk estimation within healthcare.


The Candida albicans agglutinin-like sequence family of adhesins: functional insights gained from structural analysis.
Candida albicans colonizes many host sites suggesting its interaction with diverse ligands. Candida albicans adhesion is mediated by a number of proteins including those in the Als (agglutinin-like sequence) family, which have been studied intensively. The recent solution of the Als binding domain structure ended years of speculation regarding the molecular mechanism for Als adhesive function. Als adhesins bind flexible C termini from a broad collection of proteins, providing the basis for adhesion to various cell types and perhaps for C. albicans broad tissue tropism. Understanding adhesive functions at the molecular level will reveal the sequence of events in C. albicans pathogenesis, from host recognition to complex interactions such as development of polymicrobial biofilms or disseminated disease.


Post hoc analysis of plasma amino acid profiles: towards a specific pattern in autism spectrum disorder and intellectual disability.
Objectives Autism spectrum disorders and intellectual disability present a challenge for therapeutic and dietary management. We performed a re-analysis of plasma amino acid chromatography of children with autism spectrum disorders ( n = 22) or intellectual disability ( n = 29) to search for a metabolic signature that can distinguish individuals with these disorders from controls ( n = 30). Methods We performed univariate and multivariate analyses using different machine learning strategies, from the raw data of the amino acid chromatography. Finally, we analysed the metabolic pathways associated with discriminant biomarkers. Results Multivariate analysis revealed models to discriminate patients with autism spectrum disorders or intellectual disability and controls from plasma amino acid profiles ( P < 0.0003). Univariate analysis showed that autism spectrum disorder and intellectual disability patients shared similar differences relative to controls, including lower glutamate ( P < 0.0001 and P = 0.0002, respectively) and serine ( P = 0.002 for both) concentrations. The multivariate model ( P < 6.12.10-7) to discriminate between autism spectrum disorders and intellectual disability revealed the involvement of urea, 3-methyl-histidine and histidine metabolism. Biosigner analysis and univariate analysis confirmed the role of 3-methylhistidine ( P = 0.004), histidine ( P = 0.003), urea ( P = 0.0006) and lysine ( P = 0.002). Conclusions We revealed discriminant metabolic patterns between autism spectrum disorders, intellectual disability and controls. Amino acids known to play a role in neurotransmission were discriminant in the models comparing autism spectrum disorders or intellectual disability to controls, and histidine and b-alanine metabolism was specifically highlighted in the model.


Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study.
Extended-release injectable naltrexone (XR-NTX) is an effective treatment for opioid use disorder (OUD), but initiation remains a barrier to implementation. Standard practice requires a 10- to 15-day inpatient admission prior to XR-NTX initiation and involves a methadone or buprenorphine taper followed by a 7- to 10-day washout, as recommended in the Prescribing Information for XR-NTX. A 5- to 7-day rapid induction approach was developed that utilizes low-dose oral naltrexone and non-opioid medications. The CTN-0097 Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT) study was a hybrid type I effectiveness-implementation trial that compared the effectiveness of the standard procedure (SP) to the rapid procedure (RP) for XR-NTX initiation across six community inpatient addiction treatment units, and evaluated the implementation process. Sites were randomized to RP every 14 weeks in an optimized stepped wedge design. Participants (target recruitment = 450) received the procedure (SP or RP) that the site was implementing at time of admission. The hypothesis was RP will be non-inferior to SP on proportion of inpatients who receive XR-NTX, with a shorter admission time for RP. Superiority testing of RP was planned if the null hypothesis of inferiority of RP to SP was rejected. If RP for XR-NTX initiation is shown to be effective, the shorter inpatient stay could make XR-NTX more feasible and have an important public health impact expanding access to OUD pharmacotherapy. Further, a better understanding of facilitators and barriers to RP implementation can help with future translatability and uptake to other community programs. NCT04762537 Registered February 21, 2021.


Broad photoelectron spectrum and lowered electron affinity due to hydrogen in ZnOH: a joint experimental and theoretical study.
We report a combined experimental and theoretical photoelectron spectroscopy study of ZnOH(-). We find that the electron binding energy spectrum of ZnOH(-) reveals a broad and featureless peak between 1.4 and 2.4 eV in energy. The vertical detachment energy (VDE) of ZnOH(-) is determined to be 1.78 eV, which is lower than the 2.08 eV VDE of ZnO(-). Our theoretical calculations match the VDE of ZnOH(-) accurately, but we find that the broadness of the peak cannot be explained by rotational or vibrational state excitation. The broadness of this peak is in strong contrast to the narrow and easily understood first peak of the ZnO spectrum, which features a well-resolved vibrational progression that can be readily explained by calculating the Franck-Condon transition factors. This study provides spectroscopic evidence of the effect of hydrogen on diatomic ZnO.


Expression of bone morphogenetic protein in the course of osteoinduction by recombinant human bone morphogenetic protein-2.
To clarify the mechanism of osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2), we examined the time-course localization of bone morphogenetic proteins (BMPs) immunostained by an anti-BMP-2 monoclonal antibody after implantation of pellets consisting of rhBMP-2 and collagen in rat calf muscle pouch. On day 3 after implantation, BMP was detected in the entire lump, and the intensity of staining for BMP around the implant on day 7 was weaker than that on day 3. The staining for BMP decreased with time and the region of staining for BMP remained more centralized in the implant. On day 10 after implantation, BMP was observed in part of the newly induced cartilage, especially around chondrocytes. On day 14 after implantation, BMP was localized in the newly induced woven bone. On day 21, BMP staining was found in osteoblasts at the surface of the newly induced bone. Especially, the staining for BMP decreased from day 10 to day 21. These results indicate that the woven bone was replaced with mature lamellar bone from day 14 to day 21. The present findings suggest that rhBMP-2 plays an important role in osteoinduction, especially at the early stage.


Abnormalities of antibody production after thermal injury. An association with reduced interleukin 2 production.
Antibody (Ab) production was studied in 25 burned patients who were immunized with 0.5 mg of tetanus toxoid adsorbed. Anti-tetanus toxoid (TT) Ab was measured by hemagglutination, radial immunodiffusion, and an enzyme-linked immunosorbent assay, and the results for the patients were compared with those for five similarly immunized healthy controls. As measured by hemagglutination, 12 (63%) of 19 patients had lower Ab responses than all five controls (P less than .05 by chi 2), and the median Ab response during the period of maximum response was significantly less than that in controls (8 vs 15.5 log2 maximum dilution; P = .014). After the initial response, serum Ab levels were not maintained in patients, in contrast to controls. This pattern was demonstrated by all three assays; enzyme-linked immunosorbent assay demonstrated that IgG anti-TT Ab was the major class of Ab produced. In nine patients interleukin 2 production by T lymphocytes was measured simultaneously; it was significantly depressed throughout the study except during the period from 36 to 45 days. The Ab response was also impaired in this patient group. Since maintained antibody production in response to TT is known to be T-cell dependent, these results suggest that inadequate interleukin 2 production leading to reduced T-cell help may be responsible for the lack of a persistent Ab response in these burned patients.


Industrial and wildfire aerosol pollution over world heritage Lake Baikal.
Lake Baikal is the biggest reservoir of fresh water with unique flora and fauna; presently it is negatively affected by climate change, water warming, industrial emissions, shipping, touristic activities, and Siberian forest fires. The assessment of air pollution - related Baikal's ecosystem damage is an unsolved problem. Ship, based expedition exploring the Baikal atmospheric aerosol loading, was performed over the lake area in July 2018. We combine the aerosol near - water and vertical distributions over the Lake Baikal basin with meteorological observations and air mass transportation simulations. Lidar sounding of aerosol fields in the troposphere assesses the atmospheric background in the pristine areas and the pollution during fire-affected periods. Aerosol optical properties (scattering and spectral absorption) converted to the particle number size, black carbon (BC) mass, and Absorption Angstrom Exponent (AAE) provide the inside into aerosol characterization. Transport of industrial emissions from Krasnoyarsk and Irkutsk regions, and wildfire plumes from Republic of Yakutia relates the pollution sources to the increased concentrations of fine particle numbers, PM10 and BC mass over Southern and Northern/Central Baikal, respectively. The highest PM10 and BC are associated to the harbor and touristic areas of intensive shipping and residential biomass burning. Deposition estimates applied to aerosol data exhibit the pollution fluxes to water surface over the whole Baikal area. AAE marks the impact of coal combustion, residential biomass burning, and wildfires indicating the high pollution level of the Lake Baikal ecological system .


Management of cancer of the nasal cavity and paranasal sinuses.
Cancer involving the antrum can be cured in a greater percentage of cases if the lesions are detected earlier, specifically diagnosed histologically, and radically managed at the time of the initial treatment. The procedure of choice is, first, surgical removal (with a scalpel) of as much of the tumor as is possible without risk of operative death, then limited but specific cancerocidal radiation as indicated by operative findings or regular postoperative observation. The period of convalescence will be less distressing and shorter with this procedure than with others; and, in those cases in which cure is not effected, palliation will be more satisfactory. The cured patients are cosmetically acceptable without functional disability except for unilateral loss of vision in cases in which exenteration of the orbit is necessary.


Understanding Biological Regulation Through Synthetic Biology.
Engineering synthetic gene regulatory circuits proceeds through iterative cycles of design, building, and testing. Initial circuit designs must rely on often-incomplete models of regulation established by fields of reductive inquiry-biochemistry and molecular and systems biology. As differences in designed and experimentally observed circuit behavior are inevitably encountered, investigated, and resolved, each turn of the engineering cycle can force a resynthesis in understanding of natural network function. Here, we outline research that uses the process of gene circuit engineering to advance biological discovery. Synthetic gene circuit engineering research has not only refined our understanding of cellular regulation but furnished biologists with a toolkit that can be directed at natural systems to exact precision manipulation of network structure. As we discuss, using circuit engineering to predictively reorganize, rewire, and reconstruct cellular regulation serves as the ultimate means of testing and understanding how cellular phenotype emerges from systems-level network function.


[A case of unresectable biliary tract cancer with liver metastasis that exhibited an effective response to chemotherapy].
Surgical resection is the only curative treatment for biliary tract cancer; however, it is only feasible if the cancer is detected at an early stage. Since early diagnoses are difficult, most patients are diagnosed when the cancer is at an unresectable, advanced stage. Current treatments for unresectable cases include radiotherapy and chemotherapy, although it remains difficult to achieve long-term survival. We herein present our experience with a case of unresectable biliary tract cancer that exhibited an effective response to chemotherapy with gemcitabine plus cisplatin (GEM+CDDP). The patient was a 76- year-old man with biliary tract cancer( T2N1M0, cStage III). Multiple liver metastases were detected during laparotomy. We judged the tumor to be unresectable and placed a biliary tract metallic stent. After surgery, we initiated chemotherapy with GEM+CDDP. No liver metastases were visualized on computed tomography (CT) after 5 courses of chemotherapy. We considered surgical resection; however, the patient chose to continue chemotherapy. Currently, the patient is alive and well without any recurrence of liver metastasis, 26 months after surgery.


Charge carrier relaxation in InGaAs-GaAs quantum wire modulation-doped heterostructures.
The time dependencies of the carrier relaxation in modulation-doped InGaAs-GaAs low-dimensional structures with quantum wires have been studied as functions of temperature and light excitation levels. The photoconductivity (PC) relaxation follows a stretched exponent with decay constant, which depends on the morphology of InGaAs epitaxial layers, presence of deep traps, and energy disorder due to inhomogeneous distribution of size and composition. A hopping model, where electron tunnels between bands of localized states, gives appropriate interpretation for temperature-independent PC decay across the temperature range 150-290 K. At low temperatures (T < 150 K), multiple trapping-retrapping via 1D states of InGaAs quantum wires (QWRs), sub-bands of two-dimensional electron gas of modulation-doped n-GaAs spacers, as well as defect states in the GaAs environment are the dominant relaxation mechanism. The PC and photoluminescence transients for samples with different morphologies of the InGaAs nanostructures are compared. The relaxation rates are found to be largely dependent on energy disorder due to inhomogeneous distribution of strain, nanostructure size and composition, and piezoelectric fields in and around nanostructures, which have a strong impact on efficiency of carrier exchange between bands of the InGaAs QWRs, GaAs spacers, or wetting layers; presence of local electric fields; and deep traps.