Parametric waveform synthesis: a scalable approach to generate sub-cycle optical transients.
The availability of electromagnetic pulses with controllable field waveform and extremely short duration, even below a single optical cycle, is imperative to fully harness strong-field processes and to gain insight into ultrafast light-driven mechanisms occurring in the attosecond time-domain. The recently demonstrated parametric waveform synthesis (PWS) introduces an energy-, power- and spectrum-scalable method to generate non-sinusoidal sub-cycle optical waveforms by coherently combining different phase-stable pulses attained via optical parametric amplifiers. Significant technological developments have been made to overcome the stability issues related to PWS and to obtain an effective and reliable waveform control system. Here we present the main ingredients enabling PWS technology. The design choices concerning the optical, mechanical and electronic setups are justified by analytical/numerical modeling and benchmarked by experimental observations. In its present incarnation, PWS technology enables the generation of field-controllable mJ-level few-femtosecond pulses spanning the visible to infrared range.


Palladium-Catalyzed Regioselective C3-Allylic Alkylation of 2-Aryl Imidazopyridines with MBH Carbonates.
Imidazopyridine is an important framework that constitutes several pharmaceutical drugs and biologically active molecules. Herein, we present the palladium-catalyzed regioselective C3-allylic alkylation of 2-aryl imidazopyridines with MBH carbonates. This strategy furnishes a broad spectrum of C3-allylated imidazopyridines, and their structures have been unequivocally established using X-ray analysis. Besides, the reaction can be easily scaled up on a gram scale, and the ensuing product can be smoothly manipulated into synthetically useful entities.


Transformational experience of a student nurse with diabetes: a case study.
The current study was aimed to investigate the transformational experience of a female student nurse living with type 1 diabetes. A case study of a 24-year-old diabetes patient was conducted, with interviews concerning the evolving process she had lived through during the period from her later high school years to her graduation from nursing college. Followings were identified as 5-transformation process: With her diabetes-related limitation, the participant experienced 'conflict involving choosing a college and major'. The participant tried to be in charge of managing her diabetes and stepped forward to 'adaptation to college life as a new environment', and she learned more about the process of 'evolving awareness of caring' and developed herself further through the process of 'integration of the nurse identity into self-identity', and finally through the process of 'progression and preparation for getting a job' she achieved her goals, being positive about the future. The results of the study can provide individuals with diabetes a way of self-management and help the patients and their families in diabetes education. Further research will be needed to refine the results of this study and to learn more about the experiences of patients with type I diabetes in college years.


T cell activation via CD2 [T, gp50] molecules: accessory cells are required to trigger T cell activation via CD2-D66 plus CD2-9.6/T11(1) epitopes.
Binding monoclonal antibodies (MAb) both to D66 and 9.6/T11(1) epitopes on the CD2 [T,gp50]-defined molecule produces a high level of T cell mitosis. This was observed with a battery of MAb of different isotypes. In contrast, none of the anti-D66 or anti-9.6/T11(1)Ab could trigger T cell proliferation in combination with anti-T11(3). Moreover, all anti-D66-9.6/T11(1) pairs of MAb tested required monocytes to activate T cells which were recruited through their Fc receptors. Variations among normal individuals were observed in the level of response to anti-D66-9.6/T11(1) pairs of Ab, 75% of a population of French Caucasians giving a high response. The level of response of a given individual was determined by his accessory cells. However, the level of response of an individual appeared to be minimally influenced by the isotype of a peculiar anti-D66 or anti-9.6/T11(1) Ab. The addition of exogeneous IL 2 could overcome the removal of accessory cells or the modulation of CD3 molecules. In contrast, IL 2 receptor appearance was not overcome by removal of monocytes. Thus, T cell activation via CD2 seems to be produced by "touching" several definite regions of this molecule which trigger a cascade of events similar to those produced by mitogenic lectins. One can assume that the appropriate conformational changes of the CD2 molecule induced by anti-D66-9.6/T11(1) pairs of Ab are solely produced when they are presented by accessory cells. This leaves open the question of whether accessory cells would also play a more active role.


The cooperative binding of chromosomal protein HMG-14 to nucleosome cores is reduced by single point mutations in the nucleosomal binding domain.
Mutants of human chromosomal protein HMG-14 were generated by site directed mutagenesis and used to study functional domains in this protein. A replacement of serine by cysteine at position 7 did not affect the binding of the protein to nucleosome cores. The sulfhydryl group in the nucleosome-bound protein is accessible to modifying agents suggesting that position 7 in the protein is not in close contact with either the DNA or the histones in the core particles. Under cooperative binding conditions, replacements of alanine by proline at position 21, or of lysine by cysteine at position 26, decreased the affinity of the protein for nucleosome cores 6.7- and 3-fold respectively. In contrast, the non-cooperative mode of binding was only minimally affected. A replacement of glutamic acid by glutamine at position 76 caused only minor changes in the binding of the protein to the cores. The results indicate that single point mutations, which change either the conformation or change in the nucleosomal binding domain of the protein, significantly reduce the ability of the HMG-14 protein to bind to nucleosome cores. We suggest that in chromatin the protein binds to nucleosomes in a cooperative manner and that upon binding to nucleosomes the protein acquires a distinct conformation.


Ordering of V2+, Mn2+, and Fe3+ Ions in Zoisite, Ca2Al3Si3O12(OH).
The presence of very small amounts of Mn(2+), V(2+), and Fe(3+) ions in zoisite can be easily detected by the electron paramagnetic resonance technique at room temperature. The Mn(2+) and Fe(3+) ions are completely ordered and are probably located in the Ca(1)- and Al(II)-sites, respectively, whereas the V(2+) ions probably occupy both Ca(1)- and Ca(2)-sites, with a preference for the Ca(1)-site.


Memory CD8 T cell inflation vs tissue-resident memory T cells: Same patrollers, same controllers?
The induction of long-lived populations of memory T cells residing in peripheral tissues is of considerable interest for T cell-based vaccines, as they can execute immediate effector functions and thus provide protection in case of pathogen encounter at mucosal and barrier sites. Cytomegalovirus (CMV)-based vaccines support the induction and accumulation of a large population of effector memory CD8 T cells in peripheral tissues, in a process called memory inflation. Tissue-resident memory (TRM ) T cells, induced by various infections and vaccination regimens, constitute another subset of memory cells that take long-term residence in peripheral tissues. Both memory T cell subsets have evoked substantial interest in exploitation for vaccine purposes. However, a direct comparison between these two peripheral tissue-localizing memory T cell subsets with respect to their short- and long-term ability to provide protection against heterologous challenge is pending. Here, we discuss communalities and differences between TRM and inflationary CD8 T cells with respect to their development, maintenance, function, and protective capacity. In addition, we discuss differences and similarities between the transcriptional profiles of TRM and inflationary T cells, supporting the notion that they are distinct memory T cell populations.


Effect of homologous delayed hypersensitivity testing on specific and non-specific lymphoblastic transformation in cattle latently infected with bovine rhinotracheitis virus (bovine herpesvirus 1, BHV 1).
Two cattle latently infected with infectious bovine rhinotracheitis virus (Bovine herpesvirus 1, BHV 1) were intradermally injected with inactivated BHV 1 antigen (delayed hypersensitivity test, DHT, skin test). Another animal, free of BHV 1 infection was similarly treated. Two latent carriers of the virus, intradermally injected with Phosphate-Buffered Saline solution were used as control. The evolution of spontaneous multiplication of lymphocytes and lymphoblastic transformation in vitro induced by three phytomitogens (con A, PHA, PWM) and BHV 1 antigen was followed in all animals. The delayed hypersensitivity test provoked an increase in spontaneous lymphocyte multiplication in latent carriers as well as an increase in mitogen- and antigen-induced blastogenesis on the 2nd and the 9th day following the treatment. A similar increase occurred on the 9th day in the BHV 1-free animal. Therefore, in latent carriers of BHV 1, delayed hypersensitivity testing induces an anamnestic lymphocyte reaction corresponding to the cutaneous one. This first lymphocyte activity is followed, one week later, by a new reaction which occurs both in infected and uninfected animals.


Coherent optical power spectra of photographic materials.
Measurements of the light scattering properties of nine films and plates commonly used in holography and optical processing were made using a calibrated coherent optical Fourier transform computer. On the basis of the magnitude and shape of the scattered light power spectrum, the measured films are divided into two classes, the first of which includes the low resolution films with high scattering, and the second of which includes the high resolution, low noise, films, and plates. Film spectra of the first category decrease rapidly with spatial frequency to about 25 cycles/mm and are constant to 200 cycles/mm, the maximum frequency to which measurements were made. Spectra in the second category were typically more than 10 dB lower in intensity than those of the first at any given spatial frequency, and these spectra decreased monotonically throughout the region of measurement. On the basis of both the spectral measurements and measurements of the specular and diffuse densities, the Callier Q coefficient is evaluated as one figure of merit for predicting the signal-to-noise properties of materials for optical processing.


Susceptibility to SIV Infection After Adenoviral Vaccination in a Low Dose Rhesus Macaque Challenge Model.
Vaccination with the Merck human adenovirus serotype-5 (HAdV-5) vectored HIV-1 subtype B gag/pol/nef vaccine was unexpectedly associated with enhanced susceptibility to HIV-1 infection in uncircumcised HAdV-5 seropositive men. It has been hypothesized that vaccination may have resulted in activated CD4+ T lymphocytes trafficking to mucosal sites thereby increasing targets for HIV infection. We have previously shown that AdV-vector vacci-nation in rhesus macaques resulted in an increase in the frequency of activated mucosal CD4+ T cells. However, whether this increase in activation is sufficient to increase susceptibility to HIV/SIV infection is unclear. To examine this scenario, we developed a preliminary, proof-of-concept vaccination-challenge model in order to examine vaccine-induced SIV susceptibility in rhesus macaques. Rhesus macaques (n = 10/group) were vaccinated with a simian AdV-7 (SAdV-7)-vector encoding an irrelevant insert (SARS spike) and challenged 5 weeks post-prime in an escalating dosing regimen starting with sub-infectious doses (1:10,000 or 2TCID50) of SIVmac251. In contrast to our previous study, the SAdV-7 vaccine regimen did not induce detectable mucosal CD4+ T cell activation at the time points assessed in animals obtained from a different vendor and housed in a different facility. Within the power of the study, we did not observe significantly increased SIV acquisition in SAdV-7-vaccinated (5/10) versus placebo-vaccinated (3/10) macaques after repeated low-dose intra-rectal SIVmac251 challenge (P < 0.2). These results lay groundwork for future experiments to assess vaccine-induced SIV susceptibility in rhesus macaques. Further larger-scale studies are necessary to confirm the AdV-vector vaccination associated trend towards increased SIV/HIV acquisition and clarify associated mechanisms.


ACE ID genotype and the muscle strength and size response to unilateral resistance training.
To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05). ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.


Worldwide trends in penile implantation surgery: data from over 63,000 implants.
Penile prosthesis implantation represents the gold standard of treatment for severe or medically refractory erectile dysfunction (ED). We sought to address the paucity of currently available literature about global penile prosthesis usage in regard to geography, patient age, surgical approach, implanter volume, and etiology of ED. From device manufacturer information, we compiled data on over 63,000 implants performed worldwide. Data was grouped and then analyzed to examine trends in penile implantation between the years of 2005-2012. The number of implants was seen to steadily increase over the study period. Of the 63,013 total procedures recorded, 85.9% were performed within the United States. 60-78% of procedures were done using the penoscrotal (PS) approach, with only Belgium/Netherlands as an outlier with an infrapubic (INF) majority. The US was notable for having an increasing number of implanters doing 16-30, 31-50, or >100 implants yearly. Etiology of ED worldwide was variable, but "organic," post-prostatectomy, and diabetes accounted for the vast majority of cases worldwide. Penile prosthesis implantation is an increasing practice, as evidenced by a steady increase in the number of implants performed over a 7-year study period. Acceptance of this treatment option for ED is variable by region with the US leading the annual number of implantations by a wide margin. Worldwide, there appears to be a predominance of surgeons placing implants via the PS approach.


A physical map of the hyperthermophilic bacterium Aquifex pyrophilus chromosome.
A genomic map of the hyperthermophilic hydrogen-oxidizing bacterium Aquifex pyrophilus was established with NotI (GC/GGCCGC), SpeI (A/CTAGT), and XbaI (T/CTAGA). Linking clones and cross-hybridization of restriction fragments revealed a single circular chromosome of 1.6 Mbp. A single flagellin gene and six rRNA gene units were located on this map by Southern hybridization.


Genetic diversity and antifungal susceptibility of Candida albicans isolated from Iranian patients.
A total of 105 independent Candida albicans strains isolated from patients in Iran were investigated. According to CLSI documents M27-A3 and M27-S4, the 24 h geometric mean MICs of caspofungin, itraconazole, and fluconazole were 0.27, 3.19, and 11.91 μg/ml, respectively. Microsatellites analysis of CEF3, CAIII, LOC4 Loci identified 93 different allelic genotypes clustered apart into six different clades. Antifungal susceptibility was not linked with the source of isolation and the corresponding genotype of C. albicans strains.


Preservation of myocardial oxygen balance and functional reserve by coronary vasodilators.
Reduced myocardial function at very high heart rates may be due to limited coronary blood supply. The effects of the vasodilators nitroglycerin (10 micrograms kg-1 min-1) and elevated CO2 upon regional function during tachycardia were studied. In open-chest anaesthetized dogs, regional contractile force, epicardial tissue blood flow and local NADH redox level were recorded during graded ventricular pacing. It was found that the vasodilating action of nitroglycerin in the unpaced heart was much lower than produced by CO2 (23.6 +/- 5.8% vs. 137.6 +/- 33.5%). Maximal pacing at 275 bpm caused only a moderate flow elevation in control (20 +/- 6.8%) and CO2 conditions (20.3 +/- 4.03%), but marked vasodilation during nitroglycerin infusion (85.2 +/- 14.6%). Regional function during tachycardia was improved similarly by both vasodilators. NADH levels increased with heart rates under all experimental conditions, but the absolute NADH levels were consistently lower following vasodilator treatments. The lowest NADH levels were observed during nitroglycerin treatment at all heart rates. It is suggested that nitroglycerin augments myocardial functional reserve by preserving oxygen balance more than predicted by its vasodilatory effect alone.


MSCALE: A General Utility for Multiscale Modeling.
The combination of theoretical models of macromolecules that exist at different spatial and temporal scales has become increasingly important for addressing complex biochemical problems. This work describes the extension of concurrent multiscale approaches, introduces a general framework for carrying out calculations, and describes its implementation into the CHARMM macromolecular modeling package. This functionality, termed MSCALE, generalizes both the additive and subtractive multiscale scheme (e.g. QM/MM ONIOM-type), and extends its support to classical force fields, coarse grained modeling (e.g. ENM, GNM, etc.), and a mixture of them all. The MSCALE scheme is completely parallelized with each subsystem running as an independent, but connected calculation. One of the most attractive features of MSCALE is the relative ease of implementation using the standard MPI communication protocol. This allows external access to the framework and facilitates the combination of functionality previously isolated in separate programs. This new facility is fully integrated with free energy perturbation methods, Hessian based methods, and the use of periodicity and symmetry, which allows the calculation of accurate pressures. We demonstrate the utility of this new technique with four examples; (1) subtractive QM/MM and QM/QM calculations; (2) multi-force field alchemical free energy perturbation; (3) integration with the SANDER module of AMBER and the TINKER package to gain access to potentials not available in CHARMM; and (4) mixed resolution (i.e. coarse grain / all-atom) normal mode analysis. The potential of this new tool is clearly established and in conclusion an interesting mathematical problem is highlighted and future improvements are proposed.


The survival outcomes of neoadjuvant sintilimab combined with chemotherapy in patients with locally advanced esophageal squamous cell carcinoma.
Neoadjuvant programmed death receptor-1 (PD-1) inhibitor combined with chemotherapy has been reported to improve the pathological response of locally advanced esophageal squamous cell carcinoma (ESCC), but the systematic report on survival follow-up is quite few. This study we will report the survival follow-up outcomes after a median follow-up of 21.1 months. This was a real-world retrospective study. Locally advanced ESCC patients treated with neoadjuvant sintilimab combined with albumin-bound paclitaxel and nedaplatin followed by surgery and completed at least 1-year follow-up were reviewed. The primary outcome was disease-free survival (DFS) at 24 months. The secondary outcome was overall survival (OS) at 24 months. Ninety eligible patients were included in the analysis between July 2019 and October 2021. The median number of neoadjuvant cycles was 3 (range 2-4). All patients achieved R0 resection. With a median follow-up of 21.1 months (range 14.0-39.0), the median DFS and median OS had not reached, 2-year DFS rate was 78.3% (95%CI 68.8%-89.1%) and 2-years OS rate was 88.0% (95%CI 80.6%-96.0%). Postoperative pathological stage, pCR, MPR, tumor down-staging were significantly correlated with favorable survival outcome. Univariable and multivariable Cox regression analysis identified cycle number of neoadjuvant treatment as independent predictor of DFS. Our results preliminarily show a survival benefit of neoadjuvant sintilimab combined with chemotherapy in locally advanced ESCC.


Growth of Azotobacter vinelandii on Soil Nutrients.
Azotobacter vinelandii cells grew well in a medium made from soil and distilled water which contained little or no carbohydrate. They utilized p-hydroxybenzoic acid and other phenolic acids, soil nitrogen, and water-soluble mineral substances. Seventeen soils which supported excellent growth of A. vinelandii contained 11 to 18 different phenolic acids each, including p-hydroxybenzoic, m-hydroxybenzoic, vanillic, p-coumeric, syringic, cis- and trans-ferrulic, and other unidentified aromatic acids. Three white, chalky "caliche" soils which were taken from areas where no plants grew failed to support the growth of A. vinelandii, and these contained no, two, and three phenolic acids, respectively. A. vinelandii did not fix nitrogen when growing in dialysates of soils which contained numerous phenolic acids. Growth was ample and rapid in most of the soils tested, but cell morphology was different from that usually seen in chemically defined, nitrogen-free media which contain glucose.


Recurrent Cough and Expectoration for 10 Years: A Case Report.
Rationale. Most cases of cystic fibrosis occur in Europe, with only a few occurring in Asia. Pulmonary cystic fibrosis is not a rare disease, but in children it is a potentially life-threatening condition. Children suffering from pulmonary cystic fibrosis rarely survive to adulthood, and responses to treatment are generally poor. The most common cause of cystic fibrosis is a genetic mutation on chromosome 7. Patient concerns. A 15-year-old boy with healthy parents suffered from a recurrent cough and expectoration for nearly 10 years. Six years previously, a definitive diagnosis of pulmonary cystic fibrosis and hepatic cirrhosis was made at the Beijing Children's Hospital. The first occurrence of hematemesis occurred 1 year ago. The main symptoms, which caused this period of hospitalization, were cough, expectoration, and hematemesis. Diagnoses. The underlying cause was finally determined to be the cystic fibrosis transmembrane conductance regulator gene (p.G970D). After genetic and sweat testing performed at the Beijing Children's Hospital in 2012, a definitive diagnosis of cystic fibrosis was made. Interventions. The patient was administered hemostatic treatment, antibiotics, and cough relief and sputum reduction therapy. Outcomes. The patient's condition rapidly improved and continued to remain stable, though future relapse is possible following respiratory tract infections. Lessons. This case indicates that in the case of any child that presents a recurrent cryptogenic cough and expectoration, whether accompanied by hematemesis or not, pulmonary cystic fibrosis should be considered. In order to determine underlying causes and prepare for cystic fibrosis transmembrane conductance regulator modulator therapy, genetic and sweat testing are recommended to be conducted if available.


Delayed onset of midline netrin expression in Artemia franciscana coincides with commissural axon growth and provides evidence for homology of midline cells in distantly related arthropods.
Although many similarities in arthropod central nervous systems (CNS) development exist, differences in midline cell formation and ventral nerve cord axonogenesis have been noted in arthropods. It is possible that changes in the expression of axon guidance molecules such as Netrin, which functions during commissural axon guidance in Drosophila and many other organisms, may parallel these differences. In this investigation, we analyze this hypothesis by examining Netrin accumulation during development of the brine shrimp Artemia franciscana, a branchiopod crustacean. An Artemia franciscana netrin (afrnet) orthologue was cloned. An antibody to the afrNet protein was generated and used to examine the pattern of afrNet accumulation during Artemia development. Despite differences between Drosophila and Artemia nerve cord development, examination of afrNet accumulation suggests that this protein functions to regulate commissure formation during Artemia CNS development. However, detection of afrNet at the midline and on commissural axons occurs at a relatively later time point in Artemia as compared with Drosophila. Detection of afrNet in a subset of midline cells that closely resemble Netrin-expressing cells at the Drosophila midline provides evidence for homology of midline cells in arthropods. Expression of Netrins in many other tissues is comparable, suggesting that Netrin proteins may play many conserved roles during arthropod development.


Purification of Neisseria gonorrhoeae surface L-antigen.
A purified preparation of the L-antigen of Neisseria gonorrhoeae with a 40-fold increase of antigenic activity over the crude extract was prepared. The antigen was extracted from the cell envelope by mild treatment with sodium dodecyl sulfate and purified by Sepharose 4B, diethylaminoethyl-cellulose, and diethyl-(2-hydroxypropyl)aminoethyl (QAE)-Sephadex column chromatography. The purified antigen was heat labile and trypsin sensitive. The smallest antigenically active subunit appeared to have a molecular weight of 38,500, as shown by polyacrylamide gel electrophoresis of the product incubated with sodium dodecyl sulfate.


Patient-nominated supporters as facilitators for engagement in HIV care in a referral hospital in Peru: A retrospective cohort study.
Patient-nominated supporters can potentially improve the continuum of HIV care. We retrospectively determined factors associated with having a patient-nominated supporter among people living with HIV (PLWH), and its association with retention in care and viral suppression. We analysed registries of adults evaluated by social workers (n = 1345) at a referral hospital in Peru between 2011-2014. Nondisclosure of HIV status was associated with lacking supporters (aPR: 5.41, 95% CI: 3.83-7.64). Retention in care was 76.4% and 34.2% after one and two years of enrolment, respectively. PLWH with supporters were more likely to be retained in care after two years (aRR = 1.36, 95% CI: 1.02-1.81), but not after one year (aRR = 1.10, 95% CI: 0.98-1.23) compared to PLWH without supporters. Having supporters who were parents or friends was associated with an increased probability of being retained in care after one and two years of enrolment. Viral suppression after one year of enrolment was 58.7%. Having a supporter was not associated with viral suppression (aRR = 1.18, 95% CI: 0.99-1.41), but PLWH with supporters were more likely to have viral load measurements (p = 0.005). Patient-nominated supporters appear beneficial for engagement in HIV care; these benefits may be related to the nature of their relationship with PLWH.


The expressions of matrix metalloproteinase-9, estrogen receptor, and progesterone receptor in thin endometrial tissue and their significance.
This study aims to investigate the expressions of matrix metalloproteinase-9 (MMP-9), estrogen receptor (ER), and progesterone receptor (PR) in thin endometrium. Patients who received treatment in our hospital between January 2018 and September 2020 were enrolled. Endometrial thickness was measured using transvaginal ultrasound; in patients with a midluteal phase endometrial thickness of <7 mm, a sample of endometrial tissue was obtained using a hysteroscope, and the MMP-9, ER, and PR expressions were detected using immunohistochemistry. In addition, the number of endometrial glands was calculated in a complete field of view under a low-power (100×) microscope, and the serum estrogen and progesterone levels were determined. Following hormone therapy, the midluteal phase endometrial thickness was measured again using transvaginal ultrasound, and the patients were divided into two groups: the thin endometrium group and the normal endometrium group (n = 50, each). Patients in the thin endometrium group had an endometrial thickness of <7 mm, while patients in the normal endometrium group had an endometrial thickness of 7-10 mm. The number of endometrial glands as well as the ER and MMP-9 expressions were lower in the thin endometrium group than in the normal endometrium group; the differences were statistically significant (p < .05). The receiver operator characteristic curve revealed that ER and MMP-9 had a high prediction accuracy in patients with refractory thin endometrium, while the number of endometrial glands was moderately predictive. Compared with other patients with thin endometrium, patients with refractory thin endometrium had a reduced the number of endometrial glands and significantly lower ER and MMP-9 expressions.


Exploring Optimized Spiking Neural Network Architectures for Classification Tasks on Embedded Platforms.
In recent times, the usage of modern neuromorphic hardware for brain-inspired SNNs has grown exponentially. In the context of sparse input data, they are undertaking low power consumption for event-based neuromorphic hardware, specifically in the deeper layers. However, using deep ANNs for training spiking models is still considered as a tedious task. Until recently, various ANN to SNN conversion methods in the literature have been proposed to train deep SNN models. Nevertheless, these methods require hundreds to thousands of time-steps for training and still cannot attain good SNN performance. This work proposes a customized model (VGG, ResNet) architecture to train deep convolutional spiking neural networks. In this current study, the training is carried out using deep convolutional spiking neural networks with surrogate gradient descent backpropagation in a customized layer architecture similar to deep artificial neural networks. Moreover, this work also proposes fewer time-steps for training SNNs with surrogate gradient descent. During the training with surrogate gradient descent backpropagation, overfitting problems have been encountered. To overcome these problems, this work refines the SNN based dropout technique with surrogate gradient descent. The proposed customized SNN models achieve good classification results on both private and public datasets. In this work, several experiments have been carried out on an embedded platform (NVIDIA JETSON TX2 board), where the deployment of customized SNN models has been extensively conducted. Performance validations have been carried out in terms of processing time and inference accuracy between PC and embedded platforms, showing that the proposed customized models and training techniques are feasible for achieving a better performance on various datasets such as CIFAR-10, MNIST, SVHN, and private KITTI and Korean License plate dataset.


[Hormones and tumor therapy: current clinical status and future developments in endocrine therapy of breast cancer].
Postoperative adjuvant hormone therapy and hormone therapy in disseminated breast cancer will be discussed systematically. The classical ablative and additive endocrine therapeutic measures--with the exception of ovarectomy and gestagen therapy--are increasingly being replaced by antagonists. Individual chapters discuss recent experience with combined hormone-radiotherapy or hormone-chemotherapy. In addition, a successful therapy scheme for the treatment of disseminated breast cancer will be presented.


Orexin receptors couple to Ca2+ channels different from store-operated Ca2+ channels.
We have investigated Ca2+ release and receptor- and store-operated Ca2+ influxes in Chinese hamster ovary-K1 cells expressing human OX1 orexin receptor. Receptor-operated Ca2+ influx-response to 3 nM orexin-A was not affected by Gd3+ or 2-APB (2-aminoethoxydiphenyl borate), but was inhibited by Ni2+. Store-operated Ca2+ influx was blocked by Ni2+, Gd3+ and 2-APB, whereas the thapsigargin-induced release was unaffected. 2-APB did not block inositol-1,4,5- trisphosphate-dependent Ca2+ release in these cells. Thus, low concentrations of orexin-A cause activation of two Ca2+ influxes in the cells: primarily, a receptor-operated Ca2+ influx, and secondarily, a store-depletion activated Ca2+ influx, which is subsequent to receptor-activated Ca2+ influx and the therewith-caused IP3 production. The results show that these two rely on different molecular entities.


Defining disease: determining practice.
Management of patients traditionally starts with establishing a diagnosis, a process that relies heavily on how diseases are defined. But definitions of disease vary with time and are influenced by, amongst other things, culture, politics, sociology and economics. The ninth annual Drug and Therapeutics Bulletin symposium, 'Defining disease: determining practice', explored the ways disease is defined and how this might affect practice. Here, we summarise the key points raised in the presentations and subsequent discussion.


Bacterial Endophytes: The Hidden Actor in Plant Immune Responses against Biotic Stress.
Bacterial endophytes constitute an essential part of the plant microbiome and are described to promote plant health by different mechanisms. The close interaction with the host leads to important changes in the physiology of the plant. Although beneficial bacteria use the same entrance strategies as bacterial pathogens to colonize and enter the inner plant tissues, the host develops strategies to select and allow the entrance to specific genera of bacteria. In addition, endophytes may modify their own genome to adapt or avoid the defense machinery of the host. The present review gives an overview about bacterial endophytes inhabiting the phytosphere, their diversity, and the interaction with the host. Direct and indirect defenses promoted by the plant-endophyte symbiont exert an important role in controlling plant defenses against different stresses, and here, more specifically, is discussed the role against biotic stress. Defenses that should be considered are the emission of volatiles or antibiotic compounds, but also the induction of basal defenses and boosting plant immunity by priming defenses. The primed defenses may encompass pathogenesis-related protein genes (PR family), antioxidant enzymes, or changes in the secondary metabolism.


Low-dose alfacalcidol controls secondary hyperparathyroidism in predialysis chronic kidney disease.
In the long term, secondary hyperparathyroidism (sHPT) causes severe osseous and non-osseous problems in patients with chronic kidney disease (CKD). Active vitamin D metabolites, i.e. calcitriol and alfacalcidol, have been utilized for sHPT treatment for more than 20 years. Yet, data on predialysis CKD patients are rather sparse. We monitored alfacalcidol therapy in 1,159 patients with CKD and sHPT in a 12-month multicenter observational study. Virtually all patients were in CKD stages 3-5 at study begin. The patients were recruited from 241 German nephrological centers. The mean alfacalcidol dose at study begin was 0.28 microg per day and 61.8% of patients received alfacalcidol daily (mean dose 0.34 microg); the remainder of the patients received intermittent therapy (mostly 3 times weekly, mean dose 0.19 microg/day). The initial alfacalcidol dose was maintained in 67.5% of patients; it was increased in 22% and decreased in 10.6%. At study end, the mean alfacalcidol dose was 0.32 microg/day. The mean calculated glomerular filtration rate decreased by 2.8 ml/min during the study (p < 0.001). The mean parathyroid hormone (PTH) concentration decreased from 27.5 to 23.1 pmol/l (p < 0.01) in the whole patient group. In the subgroup with intact PTH (iPTH) >20 pmol/l (48.3% of patients), the mean iPTH decreased from 41.3 to 30.9 pmol/l (p < 0.001). In the subgroups with iPTH <20 pmol/l at study begin, iPTH remained constant. The mean serum calcium increased from 2.23 to 2.31 mmol/l (p < 0.001) and 7.7% of patients had at least one serum calcium value above the normal range. Serum phosphate increased from 1.50 to 1.57 mmol/l (p < 0.001) and phosphate rose above 1.8 mmol/l in 21.5% of patients. Serum calcitriol increased significantly from 20.6 ng/l at baseline to 31.1 ng/l during the last quarter of the study (p < 0.001). iPTH was correlated negatively with kidney function, serum calcium and calcitriol and positively with serum phosphate. The frequency of side effects attributed to alfacalcidol was very low. Taken together, low-dose alfacalcidol prevented progression or caused regression of sHPT in a large cohort of CKD 3-5 patients. There were little effects on serum calcium and phosphate. Due to non-calciotropic activities of calcitriol, the alfacalcidol-induced rise in serum calcitriol could be clinically beneficial. The data support the concept that sHPT should be treated rather early in the course of CKD.


Case-Mix for Performance Management: A Risk Algorithm Based on ICD-10-CM.
Accurate risk adjustment is the key to a reliable comparison of cost and quality performance among providers and hospitals. However, the existing case-mix algorithms based on age, sex, and diagnoses can only explain up to 50% of the cost variation. More accurate risk adjustment is desired for provider performance assessment and improvement. To develop a case-mix algorithm that hospitals and payers can use to measure and compare cost and quality performance of their providers. All 6,048,895 patients with valid diagnoses and cost recorded in the US Veterans health care system in fiscal year 2016 were included in this study. The dependent variable was total cost at the patient level, and the explanatory variables were age, sex, and comorbidities represented by 762 clinically homogeneous groups, which were created by expanding the 283 categories from Clinical Classifications Software based on ICD-10-CM codes. The split-sample method was used to assess model overfitting and coefficient stability. The predictive power of the algorithms was ascertained by comparing the R, mean absolute percentage error, root mean square error, predictive ratios, and c-statistics. The expansion of the Clinical Classifications Software categories resulted in higher predictive power. The R reached 0.72 and 0.52 for the transformed and raw scale cost, respectively. The case-mix algorithm we developed based on age, sex, and diagnoses outperformed the existing case-mix models reported in the literature. The method developed in this study can be used by other health systems to produce tailored risk models for their specific purpose.


Distinct comparative genomic hybridisation profiles in gastric mucosa-associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21).
t(11;18)(q21;q21) occurs specifically in mucosa-associated lymphoid tissue (MALT) lymphoma and the translocation generates a functional API2-MALT1 fusion product that activates nuclear factor (NF)kappaB. t(11;18) positive lymphomas usually lack the chromosomal aberrations and microsatellite alterations frequently seen in the translocation-negative MALT lymphomas. To further understand their genetic differences, we investigated gastric MALT lymphomas with and without t(11;18) by comparative genomic hybridisation. In general, both chromosomal gains and losses were far more frequent in t(11;18)-negative (median = 3.4 imbalances) than t(11;18)-positive cases (median = 1.6 imbalances), with gains being more frequent than losses. Recurrent chromosomal gains involving whole or major parts of a chromosome were seen for chromosomes 3, 12, 18 and 22 (23%, 19%, 19% and 27% respectively). Discrete recurrent chromosomal gains were found at 9q34 (11/26 = 42%). Bioinformatic analysis of genes mapping to 9q34 revealed potential targets. Among them, TRAF2 and CARD9 are known interaction partners of BCL10, playing a role in NFkappaB activation. Interphase fluorescent in situ hybridisation confirmed genomic gain of the TRAF2, CARD9 and MALT1 loci in 5/6 and 2/2 cases showing chromosomal gains at 9q34 and 18q21 respectively. The results further highlight the genetic difference between MALT lymphomas with and without t(11;18). Moreover, our findings suggest that genomic gain of genes that modulate NFkappaB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation-negative MALT lymphoma.


Pontine supranuclear facial palsy.
Two patients presented with a unilateral supranuclear facial palsy. Additional dysarthria was attributed to the pontine origin documented by magnetic resonance imaging on the contralateral side. The pontine disorder also was indicated by an isolated delay of the blink reflex R1 component or of the masseter reflex. We attribute the facial palsy to a lesion of a supranuclear fiber bundle supplying the facial nucleus. The location of the lesions favors these fibers taking a separate course from the main pyramidal tract at the mid- to upper pontine level.


Assessing knowledge of Sudden Infant Death Syndrome among African American women in two Mississippi communities.
Sudden Infant Death Syndrome (SIDS) is the third leading cause of Mississippi infant mortality with nonwhite infants dying of SIDS at two to three times the rate of white infants. The purpose of this study was to assess the level of SIDS related knowledge among African American women in two geographical areas of Mississippi and gain insight on improving methods for SIDS education and outreach. An African American faculty was contracted to conduct six focus groups among African American women (n = 57) in two geographical areas of the state. Themes were common among participants from both the metropolitan and rural Delta communities. Participants in both geographical areas were familiar with [or at least had previously heard] the term SIDS. Unfortunately, there was inconsistency among participants as to the source of information. Given the inconsistencies, it is not surprising that overall knowledge related to SIDS was incomplete and in some cases inaccurate. Some information regarding SIDS is available in the various communities. Unfortunately, the information is not fully understood and is not consistently distributed resulting in a lack of knowledge among these women and thus, a continued risk for high rates of SIDS events in Mississippi.


Comparing diagnostic tests: a simple graphic using likelihood ratios.
The diagnostic abilities of two or more diagnostic tests are traditionally compared by their respective sensitivities and specificities, either separately or using a summary of them such as Youden's index. Several authors have argued that the likelihood ratios provide a more appropriate, if in practice a less intuitive, comparison. We present a simple graphic which incorporates all these measures and admits easily interpreted comparison of two or more diagnostic tests. We show, using likelihood ratios and this graphic, that a test can be superior to a competitor in terms of predictive values while having either sensitivity or specificity smaller. A decision theoretic basis for the interpretation of the graph is given by relating it to the tent graph of Hilden and Glasziou (Statistics in Medicine, 1996). Finally, a brief example comparing two serodiagnostic tests for Lyme disease is presented. Published in 2000 by John Wiley & Sons, Ltd.


High glucose: activating autophagy and affecting the biological behavior of human lens epithelial cells.
To clarify the effect of autophagy on human lens epithelial cells (HLECs) under high glucose conditions. HLECs were cultured with different concentrations of glucose and 3-methyladenine (3-MA); the expression of autophagy-related protein LC3B was detected by Western blotting and immunofluorescence histochemistry. The migration of HLECs was quantified by scratch wound assay and the expression of transforming growth factor-β (TGF-β) was measured by real-time polymerase chain reaction. Compared with 5 mmol/L normal glucose treatment, 40 mmol/L glucose treatment can significantly increase the generation of autophagosome in HLECs, which could be inhibited by 0.375 mmol/L 3-MA treatment. The migration of HLECs and the expression of TGF-β in HLECs induced by high glucose were significantly suppressed by 0.375 mmol/L 3-MA treatment. Autophagy promotes HLECs cell migration and increases the expression of TGF-β after exposed to high glucose, which may relate to the development of diabetic cataract.


Suicide trends in Wisconsin 1984-1998: good news for young and old.
In Wisconsin, suicide is the eighth leading cause of death. Subgroups identified as being at higher risk are the elderly (> age 65) and young adults (aged 15-24). 1) To compare overall national trends in suicide rates to Wisconsin trends in suicide rates from 1984 to 1998; 2) to examine suicide rates in Wisconsin sub-groups (age, gender and race) 1984-1998; and 3) to assess progress toward Wisconsin's Public Health Agenda for the Year 2000 suicide mortality goals. National Center for Injury Control and Prevention data on suicide mortality were accessed for the United States and Wisconsin using WISQARS data extraction system. Mean suicide rates were calculated for two 5-year spans (1984-1988 and 1994-1998). Average numbers of deaths and percent change between mortality rates were calculated for the two 5-year spans. From 1984-1998, mean suicide mortality rates decreased 8% nationally and 14% in Wisconsin. Various trends are occurring between genders and ages. The current declines in teens 15-19 and elderly 75-84 may indicate reversals of previous trends. Rates for women decreased for nearly all age groups, continuing previously documented declines. While it appears progress has been made toward Wisconsin Public Health Agenda goals, it appears unlikely the overall objective of 8 per 100,000 will be met.


Sex differences in the developing brain as a source of inherent risk.
Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics. Markedly distinct signaling pathways direct differentiation in specific brain regions, resulting in mosaicism of relative maleness, femaleness, and sameness through-out the brain, while canalization both exaggerates and constrains sex differences. Non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains. This higher baseline of inflammation is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation.


Large post-hysterectomy and post-radiation vesicovaginal fistulas: repair by ileocystoplasty.
We devised a technique for simultaneous closure of large post-hysterectomy and post-radiation vesicovaginal fistulas, and augmentation of the concomitant shrunken bladder by ileocystoplasty as a 1-step procedure. Between 1989 and 2000, 4 patients with large vesicovaginal fistulas after radical hysterectomy and radiotherapy for spinocellular cancer of the uterine cervix underwent fistula repair according to the technique described. The premise of utmost importance in the proposed technique is a healthy and not radiation damaged distal ileum. Fistula closure was achieved in 3 patients, while in 1 a 3 mm residual fistula was repaired 5 years later by a Martius skin flap. In all patients the augmented bladder allowed good quality of life with spontaneous voiding, and daytime and nighttime continence. The technique described seems to have certain advantages. Wide dissection of the bladder from the vagina and pelvic walls is avoided. The bladder defect is closed with a well vascularized ileal segment. Bladder capacity is enlarged simultaneously with good functional results. The procedure can be adapted to cases with concomitant damaged distal ureters.


Psychological aspects of awake brain surgery in children-interests and risks.
Awake brain surgery (ABS) in children remains a subject of controversial debate for the potential psychological limitations that are related to this type of procedure. However, the tolerance and benefits of ABS in adults advocate for increased application of ABS in children. In this study, we report the psychological assessment, evaluation algorithm, and outcome of pediatric patients, who underwent ABS for surgical treatment of lesions in eloquent areas. Psychological selection criteria and the specifications of psychological support are described. A retrospective review and analysis of psychological assessment and psychological outcome of pediatric patients, who underwent ABS between 2005 and 2018 at the Department of pediatric neurosurgery, University of Lyon, France, was performed. Long-term psychological outcomes are reported. ABS was proposed to 18 children aged between 9 and 17 years and their families. After psychological evaluation of the individual patient and their familial surrounding, five boys and 12 girls (n = 17) were accounted eligible for ABS. They underwent asleep-awake-asleep brain surgery with intraoperative testing. In 16 cases, ABS could be performed as planned. Psychological alterations were postoperatively observed in 3 patients, symptoms of a post-traumatic stress disorder in 1 patient. The precise preoperative evaluation of the risk-benefit ratio in children plays a crucial role in anticipating a good psychological outcome. Professional psychological preparation and support of the child and his or her family are the key elements for successful completion of ABS.


Psychotherapy with intercultural couples: a contemporary psychodynamic approach.
Although the number of intercultural marriages has dramatically increased in the last three decades, few articles have been published on the counseling of intercultural couples. The authors propose a methodology for working with these couples using intersubjectivity and self-psychology as theoretical perspectives. The role of culture in the construction of the individual's subjectivity is seen as central to understanding the psychodynamics of the intercultural couple. Two case studies are presented in order to highlight the theoretical assumptions underlying the authors' perspectives.


Potential biomarkers of ductal carcinoma in situ progression.
Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk. In this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies. The results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis. We propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.


Postmenopausal hormone use, screening, and breast cancer: characterization and control of a bias.
Previous investigators have suggested that screening-related biases may explain associations between postmenopausal hormone use and breast cancer. To investigate these biases, we studied postmenopausal women in the Nurses' Health Study from 1988 to 1994. Hormone use is associated with increased subsequent screening. Among women not screened in the previous 2 years, the probability difference, comparing current hormone users with others, for having mammography in the following 2 years is 19.5%; among women previously screened, the difference is 4.9%. These differences persist after control for other factors. If the increase in screening is causal, screening by mammogram could be intermediate in the causal pathway to breast cancer diagnosis. To deal with this problem, we restrict attention to a subset of the cohort in which the effect of postmenopausal hormone use on screening is small (women previously screened). In this subset, the rate ratio comparing breast cancer rates among current postmenopausal hormone users with others is 1.28. In a sensitivity analysis, the bias could not by itself plausibly account for the associations in our data. Our data provide evidence of an association between postmenopausal hormone use and breast cancer that is not solely the product of a detection bias.


Linear morphea overlying site of previous lichen aureus in a pediatric patient.
Lichen aureus is a pigmented purpuric dermatosis that tends to occur on the lower extremities, and linear morphea is an inflammatory disease of the dermis and subcutaneous fat that leads to a scarlike induration. We present a pediatric case of linear morphea developing in the same anatomic distribution as prior lichen aureus. Due to the possible progression of lichen aureus to morphea described herein and the difficulty in diagnosing early morphea, close follow-up may be considered for pediatric patients who present with this pigmented purpuric dermatosis.


Inhibiting effects of low-molecular weight heparin and adrenocortical hormone on hemolysis of red cells in patients with paroxysmal nocturnal hemoglobinuria in vitro.
To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.


Naturally occurring subclinical Corynebacterium kutscheri infection in laboratory rats: strain and age related antibody response.
Naturally occurring subclinical Corynebacterium kutscheri infection was analyzed by antibody response related to the strain of rats. Wistar-Lewis, Wistar and Spraque-Dawley rats were high responders in seroconversion rates and antibody titers, while Brown Norway and Fischer rats were low responders. The antibody response was related to age also. Some young rats had maternal antibody to C. kutscheri, but antibody disappeared before 8 weeks of age. Rats were antibody-negative for several months thereafter and became antibody-positive after 6 months of age. The antibody response was highest at 8 to 9 months of age in subclinical C. kutscheri infection. This antibody response was very late, compared to the antibody response to Sendai virus and Mycoplasma infections.


[Simultaneous characterization of two types of major active components in Kushen by high performance liquid chromatography coupled to multi-stage mass spectrometry].
In this study, a high performance liquid chromatography coupled with multi-stage mass spectrometry method was developed for simultaneous characterization of alkaloids and flavonoids, the main active components, in Kushen with diverse physical and chemical properties. Forty-two major constituents, including sixteen Kushen alkaloids and twenty-six Kushen flavonoids were tentatively identified. Additionally, useful and characteristic fragmentation pathways of two types of Kushen alkaloids, namely cytisine-type and sparteine-type, in positive ions mode were proposed and summarized, which would lay a foundation for the rapid identification of the active ingredients in traditional Chinese medicine Kushen.


Changes in Clinical Presentation and Epidemiology of Respiratory Pathogens Associated With Acute Respiratory Illness in Military Trainees After Reintroduction of Adenovirus Vaccine.
Background. Adenovirus (Ad) has long been the predominant cause of acute respiratory illness (ARI) in military trainees. In 2011, live oral Ad vaccines for serotypes 4 and 7 were reintroduced into US basic military training populations. This study evaluated the impact on clinical presentations and other respiratory pathogens. Methods. The Center for Advanced Molecular Detection at Joint Base San Antonio-Lackland prospectively collects demographic, clinical, and polymerase chain reaction data from respiratory specimens (throat swab and nasal wash) among Air Force trainees presenting for care of ARI. Results. From June 2008 to August 2013, 2660 trainees enrolled and were tested for selected respiratory pathogens. Post-vaccine introduction (VI), reported systemic symptoms were less frequent, including fever (38% vs 94%) and myalgia (37% vs 67%; P < .01). Median temperature and heart rate decreased (98.4 vs 101.3°F, 81 vs 96 beats per minute; P < .01). Ad detection decreased for all Ad (3% vs 68%), Ad4 (1% vs 70%), 7 (0% vs 8%), 14 (0% vs 5%), and 3 (0.1% vs 2%); P < .01). Rhinovirus and cases with no pathogen identified increased in frequency (35% vs 18%, 51% vs 14%; P < .01). Conclusions. Acute respiratory illness in military trainees post-VI is associated with decreased severity of systemic symptoms and reduced fever and heart rate. Marked reductions in frequency of Ad serotypes are seen, including those in the vaccine, with no serotype shift. However, detection of several other respiratory pathogens, most notably rhinovirus, is observed in increasing proportions, and a majority are now undiagnosed clinical syndromes.


The Effect of Bimaxillary Surgery on the Airway Morphology in Class III Patients: Taking Into Account the Head Posture During Walking.
To assess changes in head and neck posture, airway, hyoid, tongue, and soft palate in skeletal class III individuals whose cephalograms were taken using dynamic natural head positioning method with an inclinometer. This study was conducted on 20 class III patients operated with double jaw surgery. Natural head positions were determined before and 6 months after the surgery. Craniocervical, pharyngeal airway, tongue, and hyoid positions were measured. In the analysis of the data, paired t test, independent sample t test and correlation tests were used. There was a statistically significant change in the craniocervical measurements with the operation and the head position was further extended (P < 0.05). Significant changes were observed in the soft palate angles upon surgery (P < 0.026) and the increase in oropharyngeal airway area was statistically significant (P < 0.001). There was a statistically significant increase in tongue length (TL) and distance from vertical reference plane to tongue tip (TTi/VRP) measurements (P < 0.001 and P < 0.012, respectively). There was a statistically significant decrease in distance from horizontal reference plane to tongue tip (TTi/HRP) and tongue dorsum (TD/HRP) measurements (P < 0.033 and P < 0.003, respectively). The only significant change among the hyoid bone position-related measurements was distance between hyoidale and epiglottis (P < 0.013). Hyoid bone location, tongue measurements, and posterior pharyngeal airway were found to be related to each other and they have been found to be effective on the head and neck posture. Head position will be affected by possible surgical alternatives.


[The effect of PTC1 transfection on the growth and apoptosis of human pulmonary adenocarcinoma cell A549].
To investigate the effects of the tumor suppressor gene PTC on the growth inhibition and down-regulation of epidermal growth factor receptors (EGFR) in pulmonary adenocarcinoma cell A549. Pulmonary adenocarcinoma cell A549 were divided into wild type group, mutant type group, blank group and control group. They were transfected with wild-type PTC1 plasmids, mutant-PTC1 plasmids and blank plasmids, respectively. After transfection, the cell growth curve was drown every day for a week. The expression of PTC1 and EGFR were detected by western blot. Flow cytometry was used to analyze apoptosis and cell cycle of the transfected cells. After transfected with wild-type PTC1, the growth rates of A549 cells were slow down, but the other groups of cells had no change. Compared with the control group, the expression of EGFR were down-regulated. The apoptosis rates in wild type group was 24.5%, and the mutant type group was 8.3% (P < 0.01). But the apoptosis rate of blank group has no change. Wild-type PTC1 could induce apoptosis and inhibitory effect on A549 cells.


Transfusion in Haemoglobinopathies: Review and recommendations for local blood banks and transfusion services in Oman.
Sickle cell disease and homozygous β-thalassaemia are common haemoglobinopathies in Oman, with many implications for local healthcare services. The transfusions of such patients take place in many hospitals throughout the country. Indications for blood transfusions require local recommendations and guidelines to ensure standardised levels of care. This article summarises existing transfusion guidelines for this group of patients and provides recommendations for blood banks and transfusion services in Oman. This information is especially pertinent to medical professionals and policy-makers developing required services for the standardised transfusion support of these patients.


Two Tier Hox Collinearity Mediates Vertebrate Axial Patterning.
A two tier mechanism mediates Hox collinearity. Besides the familiar collinear chromatin modification within each Hox cluster (nanocollinearity), there is also a macrocollinearity tier. Individual Hox clusters and individual cells are coordinated and synchronized to generate multiscale (macro and nano) collinearity in the early vertebrate embryo. Macro-collinearity is mediated by three non-cell autonomous Hox-Hox interactions. These mediate temporal collinearity in early NOM (non-organizer mesoderm), time space translation where temporal collinearity is translated to spatial collinearity along the early embryo's main body axis and neural transformation, where Hox expression is copied monospecifically from NOM mesoderm to overlying neurectoderm in the late gastrula. Unlike nanocollinearity, which is Hox cluster restricted, axial macrocollinearity extends into the head and EAD domains, thus covering the whole embryonic anterior-posterior (A-P) axis. EAD: extreme anterior domain, the only A-P axial domain anterior to the head. The whole time space translation mechanism interacts with A-P signaling pathways via "decision points," separating different domains on the axis.


Enhancing the focal-resolution of aeroacoustic time-reversal using a point sponge-layer damping technique.
This letter presents the Point-Time-Reversal-Sponge-Layer (PTRSL) technique to enhance the focal-resolution of aeroacoustic Time-Reversal (TR). A PTRSL is implemented on a square domain centered at the predicted source location and is based on damping the radial components of the incoming and outgoing fluxes propagating toward and away from the source, respectively. A PTRSL is shown to overcome the conventional half-wavelength diffraction-limit; its implementation significantly reduces the focal spot size to one-fifth of a wavelength for a monopole source. Furthermore, PTRSL reduces the focal spots of a dipole source to three-tenths of a wavelength, as compared to three-fifths without its implementation.


Unique pitch evolution in the smectic-C+alpha phase.
Employing resonant x-ray diffraction, we observed unique pitch evolutions in the smectic-C*(alpha) phase in mixtures of two antiferroelectric liquid crystals. Our results show that the pitch in this phase continuously evolves across 4 layers, contradicting a theoretical model that predicts that the smectic-C*(FI2) phase intervenes in the smectic-C*(alpha) phase. The phase sequences we found can be explained by another model that includes one type of long-range interaction among smectic layers.


A simplified technique for transtympanic electrocochleography.
Recently, electrocochleography (ECochG) has enjoyed a resurgence in clinical use, particularly in the preoperative and intraoperative evaluation of Meniere's disease patients. With a transtympanic electrode, large amplitude, repeatable waveforms can be easily recorded. Despite this fact, transtympanic ECochG has not been widely adopted in the United States, primarily because of the technical difficulties in securing the electrode and then delivering a stimulus. We have developed a simplified transtympanic electrode placement, using a standard subdermal needle held in place by a foam plug earphone. The foam plug earphone not only secures the electrode, but also delivers the stimulus. We have used this technique in a series of cases, both intraoperatively as well as in the outpatient clinic. The advantages of this approach are discussed and illustrated with individual and group data.


Receptor-associated protein interacts with amyloid-beta peptide and promotes its cellular uptake.
Brain amyloid-beta (Abeta) peptide accumulation and aggregation are critical events in the pathogenesis of Alzheimer disease. Increasing evidence has demonstrated that LRP1 is involved in Alzheimer disease pathogenesis. The physiological ligands of LRP1, including apoE, play significant roles in the cellular clearance of Abeta. The receptor-associated protein (RAP) is a specialized chaperone for members of the low density lipoprotein receptor family. RAP shares structural and receptor-binding properties with apoE. Here, we show that RAP binds to both Abeta40 and Abeta42 in a concentration-dependent manner and forms complexes with them. Fluorescence-activated cell sorter analysis showed that RAP significantly enhances the cellular internalization of Abeta in different cell types, including brain vascular smooth muscle, neuroblastoma, glioblastoma, and Chinese hamster ovary cells. This effect of RAP was confirmed by fluorescence microscopy and enzyme-linked immunosorbent assay. RAP binds to both LRP1 and heparin; however, the ability of RAP to enhance Abeta cellular uptake was blocked by heparin and heparinase treatment but not by LRP1 deficiency. Furthermore, the effects of RAP were significantly decreased in heparan sulfate proteoglycan-deficient Chinese hamster ovary cells. Our findings reveal that RAP is a novel Abeta-binding protein that promotes cellular internalization of Abeta.


TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.
Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination.


Special Issues in Epilepsy: The Elderly, the Immunocompromised, and Bone Health.
This article discusses targeted special issues in epilepsy, including epilepsy in the elderly and immuncompromised populations and bone health in epilepsy. Although this is a broad and diverse set of topics, common themes can be identified by focusing on elderly patients and patients who are immunocompromised that provide a valuable framework for other groups. An increasing incidence of epilepsy has been reported in patients 65 years of age and older. As people age, physiologic changes can alter antiepileptic drug metabolism, which can significantly impact dosing requirements and tolerability. Side effects of antiepileptic drugs may pose a significant challenge given the relatively high frequency of comorbid illnesses. When evaluating and treating immunocompromised patients, a broad range of potential etiologies for new-onset or worsening seizures must be considered. When choosing an antiepileptic drug, drug-drug interactions, the potential for increased side effects, and the overall impact of treatments on the underlying illness must be considered. The most recent findings and recommendations pertaining to bone health assessment and maintenance in various populations with epilepsy are summarized. Treating epilepsy and seizures in special populations requires taking a broad view of patients' overall health status, including potentially complex treatment regimens and a unique predisposition to adverse events.


Complete Genome Sequence of Herbiconiux sp. Strain L3-i23 Isolated from Soil in Japan.
This study describes the complete genome sequence of Herbiconiux sp. strain L3-i23, acquired from an assembly of long reads and subsequently polished using short reads. The complete genome comprises a 3,139,863-bp chromosome with a GC content of 69.51% and a circular plasmid (39,507 bp).


Probing the photoreaction mechanism of phytochrome through analysis of resonance Raman vibrational spectra of recombinant analogues.
Resonance Raman spectra of native and recombinant analogues of oat phytochrome have been obtained and analyzed in conjunction with normal mode calculations. On the basis of frequency shifts observed upon methine bridge deuteration and vinyl and C(15)-methine bridge saturation of the chromophore, intense Raman lines at 805 and 814 cm(-)(1) in P(r) and P(fr), respectively, are assigned as C(15)-hydrogen out-of-plane (HOOP) wags, lines at 665 cm(-)(1) in P(r) and at 672 and 654 cm(-)(1) in P(fr) are assigned as coupled C=C and C-C torsions and in-plane ring twisting modes, and modes at approximately 1300 cm(-)(1) in P(r) are coupled N-H and C-H rocking modes. The empirical assignments and normal mode calculations support proposals that the chromophore structures in P(r) and P(fr) are C(15)-Z,syn and C(15)-E,anti, respectively. The intensities of the C(15)-hydrogen out-of-plane, C=C and C-C torsional, and in-plane ring modes in both P(r) and P(fr) suggest that the initial photochemistry involves simultaneous bond rotations at the C(15)-methine bridge coupled to C(15)-H wagging and D-ring rotation. The strong nonbonded interactions of the C- and D-ring methyl groups in the C(15)-E,anti P(fr) chromophore structure indicated by the intense 814 cm(-1) C(15) HOOP mode suggest that the excited state of P(fr) and its photoproduct states are strongly coupled.


Calibration of mobile manipulators using 2D positional features.
Robotic manipulators are increasingly being attached to Automatic Ground Vehicles (AGVs) to aid in the efficiency of assembly for manufacturing systems. However, calibrating these mobile manipulators is difficult as the offset between the robotic manipulator and the AGV is often unknown. This paper provides a novel, simple, and low-cost method for calibrating and measuring the performance of mobile manipulators by using data collected from a laser retroreflector that digitally detects the horizontal two-dimensional (2D) position of reflectors on an artifact as well as a navigation system that provides the heading angle and 2D position of the AGV. The method is mathematically presented by providing a closed form solution to the positional component of the 2D robotworld/hand-eye calibration problem AX Y= B. The method is then applied to simulated data as well as data collected in a laboratory setting and compared to other methods.


Palladium-Catalyzed Decarboxylative ortho-C(sp2 )-H Aroylation of N-Sulfoximine Benzamides at Room Temperature.
A palladium-catalyzed method for the decarboxylative ortho C-H acylation of N-sulfoximine benzamides is developed at room temperature. The catalytic method enables easy access to various functionalized 2-aroylaromatic carboxylic acid derivatives in good isolated yields. Based on our mechanistic studies, a Pd(II)/Pd(IV) catalytic cycle that involves aroyl radical intermediate is proposed for the reaction.


A stopped-flow study of the dual chemiluminescence for the luminol-KIO4-Mn(2+) system in strong alkaline solutions.
A novel phenomenon of dual chemiluminescence (CL) was observed for the KIO4-luminol-Mn(2+) system in strong alkaline solutions using the stopped-flow technique. Scavenging study of the reactive oxygen species (ROS) suggested that the two CL peaks originated from different CL pathways precipated by distinct ROS (O2(-) and •OH for the first peak, mainly 1O2 for the second peak). Generation of these ROS at different time intervals from the reactions involving IO4(-), O2, and Mn(2+) and their subsequent reactions with luminol induced the intense CL emission. The relative intensity of the two CL peaks can be tuned over a wide range by varying the concentrations of Mn(2-), luminol and KIO4. Because of the involvement of different ROS in each pathway, the two CL peaks could respond quite differently to various substances. Moreover, variation of the intensity ratio of the two CL peaks altered the relative proportions of the corresponding ROS, thereby changing their responses to a given substance. The dual CL emission acts like a pair of tunable probes and it is believed that this CL system has great potential in analytical applications.


Sensitive colorimetric assay using insulin G-quadruplex aptamer arrays on DNA nanotubes coupled with magnetic nanoparticles.
Described here is a methodology for fabrication of a sensitive colorimetric nanoassay for measurement of insulin using G-quadruplex aptamer arrays on DNA nanotubes (DNTs) coupled with magnetic nanoparticles. The spectroscopic findings (e.g. visible spectra, velocity assay and limit of detection determination) indicated a highly sensitive performance of this new nanoassay in comparison to those results obtained from the insulin assay with non-arrayed aptamers. The clinical performance statistics (i.e. paired sample t-test, Bland-Altman plot and scatter diagram) from the newly developed assay and the enzyme-linked immunosorbent assay suggested its reliable precision and its acceptable repeatability for measurement of insulin in human sera. This is, to our knowledge, the first study for the application of magnetic nanoparticle-coupled DNTs for carrying G-quadruplex aptamers for detection of biomolecules (such as insulin) in human serum.


NEURO-ONCOLOGIC PHYSICAL THERAPY FOR THE OLDER PERSON.
Due to the uncertainty of the course of diagnoses, patients with neuro-oncological malignancies present challenges to the physical therapist. At times, the presentation of impairments and disabilities of these patients with neuro-oncological diagnoses do not necessarily coincide with the involved area of the brain or spinal cord. It is our intention to provide guidance to the physical therapist who will be working with these patients with neuro-oncological diagnoses, in hopes that their encounters will be more productive and meaningful. This article describes a brief overview of common central nervous system malignancies, its medical treatment, as well as possible complications and side effects that would need to be considered in rehabilitating these patients. Special consideration is given to the elderly patients with neuro-oncological diagnoses. Pertinent physical therapy assessments and interventions are discussed.


Effect of chronic alcohol administration on transketolase in the brain and the liver of rats.
To estimate the nutritional and the pathological states in thiamin-deficiency-related diseases, especially Wernicke-Korsakoff syndrome, we studied the relationship among transketolase activity, transketolase concentration, and thiamin phosphate esters in rats chronically fed alcohol. In the brain of alcohol-fed rats, the enzyme activity and concentration decreased although there was no positive correlation between the two. On the contrary, transketolase activity in the liver correlated positively with concentration, and both transketolase activity and concentration were decreased in the thiamin-deficient groups. These findings suggest that transketolase in the brain may be different from that in the liver and that the alteration of the enzyme activity in the brain may be based on the conformational change of the protein molecule caused by chronic alcohol administration.


Ciliary ultrastructure and nasal mucociliary clearance in chronic and allergic rhinitis.
The authors have studied nasal specimens collected by means of nasal brushing in eight patients affected by allergic rhinitis and in eight affected by chronic rhinitis, while in other four patients affected by allergic rhinitis a lower turbinate biopsy was performed. All twenty patients showed an increased mucociliary clearance time and a reduced velocity regardless to the pathology during a previously performed saccharin test. Different ultrastructural alterations have been observed, such as: both central and peripheral microtubules alterations; absence of dynein arms; absence of radial spokes; ciliary membrane alterations; "compound" cilia; disorientation of central tubules. These alterations have been observed variously associated in both allergic and chronic rhinitis patients groups. Basing on their data, the authors state that ciliary abnormalities cannot be considered specific of a particular pathology but they can coexist in different situations. They also think that the mucociliary clearance parameters determination represents the only method to evaluate, even if in an indirect fashion, the percentage of ciliary abnormalities, as no direct quantitative method has been described. Ciliary ultrastructural alterations can be of diagnostic value only if associated with mucociliary clearance time and velocity determination.


Male urinary incontinence: prevalence, risk factors, and preventive interventions.
Urinary incontinence (UI) in community-dwelling men affects quality of life and increases the risk of institutionalization. Observational studies and randomized, controlled trials published in English from 1990 to November 2007 on the epidemiology and prevention of UI were identified in several databases to abstract rates and adjusted odds ratios (OR) of incontinence, calculate absolute risk difference (ARD) after clinical interventions, and synthesize evidence with random-effects models. Of 1083 articles identified, 126 were eligible for analysis. Pooled prevalence of UI increased with age to 21% to 32% in elderly men. Poor general health, comorbidities, severe physical limitations, cognitive impairment, stroke (pooled OR 1.54; 95% confidence interval [CI], 1.14-2.1), urinary tract infections (pooled OR 3.49; 95% CI, 2.33-5.23), prostate diseases, and diabetes (pooled OR 1.36; 95% CI, 1.14-1.61) were associated with UI. Treatment with tolterodine alone (ARD 0.17; 95% CI, 0.02-0.32) or combined with tamsulosin (ARD 0.17; 95% CI, 0.08-0.25) resulted in greater self-reported benefit compared with placebo. Radical prostatectomy or radiotherapy for prostate cancer compared with watchful waiting increased UI. Short-term prevention of UI with pelvic floor muscle rehabilitation after prostatectomy was not consistently seen across randomized, controlled trials. The prevalence of incontinence increased with age and functional dependency. Stroke, diabetes, poor general health, radiation, and surgery for prostate cancer were associated with UI in community-dwelling men. Men reported overall benefit from drug treatments. Limited evidence of preventive effects of pelvic floor rehabilitation requires future investigation.


Prevalence and Characteristics of Campylobacter Throughout the Slaughter Process of Different Broiler Batches.
Handling and consumption of chicken meat are risk factors for human campylobacteriosis. This study was performed to describe the Campylobacter population in broiler carcasses and environmental samples throughout the slaughter process. Moreover, the genetic diversity and antimicrobial resistance of the Campylobacter strains were evaluated. Cloacal swabs, samples from carcasses at different stages, and environmental samples were collected thrice from the different flocks at the same abattoir located in Central Jiangsu, China. Campylobacter isolated from the three batches (n = 348) were identified as Campylobacter jejuni (n = 117) and Campylobacter coli (n = 151) by multiplex PCR. Characterization by multilocus sequence typing revealed a specific genotype of Campylobacter for each batch. Antimicrobial sensitivity to 18 antibiotics were analyzed for all selected strains according to the agar diffusion method recommended by the Clinical and Laboratory Standards Institute. Antibiotic susceptibility tests indicated that the majority of the tested isolates were resistant to quinolones (>89.7%). Less resistance to macrolide (59.8%), gentamicin (42.7%), amikacin (36.8%) was observed. Results showed that 94.0% of the tested strains demonstrated multidrug resistance.


Hallux Valgus Bunion Splint: Surgical Dressing Technique.
Hallux valgus is a common condition with a complex etiology resulting in numerous treatment options. Recurrence of the deformity can occur following correction. Surgical technique and possibly also postoperative care play a role in reducing recurrence rates. This article highlights a postoperative surgical dressing technique which allows for semirigid support during the immediate postoperative period. A wooden tongue depressor placed along the medial border of the hallux comprises the primary support for the dressing. The rigidity of the tongue depressor allows for the hallux to be drawn toward the depressor, encouraging neutral alignment of the hallux. Dressings are removed 2 weeks postoperatively, with new dressings applied in similar fashion and maintained in place until 6 weeks postoperatively. Based upon our observations, our surgical dressing technique provides sufficient support following hallux valgus correction surgery while being straightforward to replicate without the need for frequent dressing changes. The dressing materials are of negligible cost and are typically readily available. No associated wound complications have been observed. We present an easily replicable and affordable option for postoperative hallux valgus correction surgical dressings. Level V: Expert Opinion.


Evaluation of a prevention program to address body focus and negative affect among children.
The current study evaluated a program to improve the body image and positive and negative affect of children. Participants were 368 children aged 8-12 years. The results demonstrated that boys placed more importance on and were less satisfied with their muscles; girls were less satisfied with their weight and the importance of weight increased with increasing age. Children with a large BMI were less satisfied with their weight. Boys in the intervention group showed reduced levels of negative affect over time. Further research is required to develop prevention and intervention programs to lower the effects of body dissatisfaction and negative affect among children.


Map-Matching-Based Localization Using Camera and Low-Cost GPS for Lane-Level Accuracy.
For self-driving systems or autonomous vehicles (AVs), accurate lane-level localization is a important for performing complex driving maneuvers. Classical GNSS-based methods are usually not accurate enough to have lane-level localization to support the AV's maneuvers. LiDAR-based localization can provide accurate localization. However, the price of LiDARs is still one of the big issues preventing this kind of solution from becoming wide-spread commodity. Therefore, in this work, we propose a low-cost solution for lane-level localization using a vision-based system and a low-cost GPS to achieve high precision lane-level localization. Experiments in real-world and real-time demonstrate that the proposed method achieves good lane-level localization accuracy, outperforming solutions based on only GPS.


Flow enhances photosynthesis in marine benthic autotrophs by increasing the efflux of oxygen from the organism to the water.
Worldwide, many marine coastal habitats are facing rapid deterioration due in part to human-driven changes in habitat characteristics, including changes in flow patterns, a factor known to greatly affect primary production in corals, algae, and seagrasses. The effect of flow traditionally is attributed to enhanced influx of nutrients and dissolved inorganic carbon (DIC) across the benthic boundary layer from the water to the organism however, here we report that the organism's photosynthetic response to changes in the flow is nearly instantaneous, and that neither nutrients nor DIC limits this rapid response. Using microelectrodes, dual-pulse amplitude-modulated fluorometry, particle image velocimetry, and real time mass-spectrometry with the common scleractinian coral Favia veroni, the alga Gracilaria cornea, and the seagrass Halophila stipulacea, we show that this augmented photosynthesis is due to flow-driven enhancement of oxygen efflux from the organism to the water, which increases the affinity of the RuBisCO to CO(2). No augmentation of photosynthesis was found in the absence of flow or when flow occurred, but the ambient concentration of oxygen was artificially elevated. We suggest that water motion should be considered a fundamental factor, equivalent to light and nutrients, in determining photosynthesis rates in marine benthic autotrophs.


Spindle cell rhabdomyosarcoma of the anterior mandible manifesting as a periapical lesion of pulpal origin: Case report.
A 25-year-old male patient presented with swelling and pain in the mandibular anterior region for the previous 6 months. He had a history of repeated traumatic episodes associated with his lower incisors. A periapical radiograph revealed a radiolucent lesion involving the apices of the lower incisors, whereas cone beam computed tomography revealed a large osteolytic lesion involving all mandibular incisors and loss of labial and lingual cortical plates. Histological, immunohistochemical and bone scan examination of the curetted tissue established a differential diagnosis of spindle cell rhabdomyosarcoma of the anterior mandible. Such rare but life-threatening oral cancers can be correctly diagnosed and treated only through systematic analysis of clinical findings and examining the diseased tissue with histological and other diagnostic procedures.


Selenium and trace element mobility affected by periodic displacement of stratification in the Great Salt Lake, Utah.
The Great Salt Lake (GSL) is a unique ecosystem in which trace element activity cannot be characterized by standard geochemical parameters due to the high salinity. Movement of selenium and other trace elements present in the lake bed sediments of GSL may occur due to periodic stratification displacement events or lake bed exposure. The water column of GSL is complicated by the presence of a chemocline persistent over annual to decadal time scales. The water below the chemocline is referred to as the deep brine layer (DBL), has a high salinity (16.5 to 22.9%) and is anoxic. The upper brine layer (UBL) resides above the chemocline, has lower salinity (12.6 to 14.7%) and is oxic. Displacement of the DBL may involve trace element movement within the water column due to changes in redox potential. Evidence of stratification displacement in the water column has been observed at two fixed stations on the lake by monitoring vertical water temperature profiles with horizontal and vertical velocity profiles. Stratification displacement events occur over periods of 12 to 24h and are associated with strong wind events that can produce seiches within the water column. In addition to displacement events, the DBL shrinks and expands in response to changes in the lake surface area over a period of months. Laboratory tests simulating the observed sediment re-suspension were conducted over daily, weekly and monthly time scales to understand the effect of placing anoxic bottom sediments in contact with oxic water, and the associated effect of trace element desorption and (or) dissolution. Results from the laboratory simulations indicate that a small percentage (1%) of selenium associated with anoxic bottom sediments is periodically solubilized into the UBL where it potentially can be incorporated into the biota utilizing the oxic part of GSL.


Genetic Association Study and Machine Learning to Investigate Differences in Platelet Reactivity in Patients with Acute Ischemic Stroke Treated with Aspirin.
Aspirin resistance (AR) is a pressing problem in current ischemic stroke care. Although the role of genetic variations is widely considered, the data still remain controversial. Our aim was to investigate the contribution of genetic features to laboratory AR measured through platelet aggregation with arachidonic acid (AA) and adenosine diphosphate (ADP) in ischemic stroke patients. A total of 461 patients were enrolled. Platelet aggregation was measured via light transmission aggregometry. Eighteen single-nucleotide polymorphisms (SNPs) in ITGB3, GPIBA, TBXA2R, ITGA2, PLA2G7, HMOX1, PTGS1, PTGS2, ADRA2A, ABCB1 and PEAR1 genes and the intergenic 9p21.3 region were determined using low-density biochips. We found an association of rs1330344 in the PTGS1 gene with AR and AA-induced platelet aggregation. Rs4311994 in ADRA2A gene also affected AA-induced aggregation, and rs4523 in the TBXA2R gene and rs12041331 in the PEAR1 gene influenced ADP-induced aggregation. Furthermore, the effect of rs1062535 in the ITGA2 gene on NIHSS dynamics during 10 days of treatment was found. The best machine learning (ML) model for AR based on clinical and genetic factors was characterized by AUC = 0.665 and F1-score = 0.628. In conclusion, the association study showed that PTGS1, ADRA2A, TBXA2R and PEAR1 polymorphisms may affect laboratory AR. However, the ML model demonstrated the predominant influence of clinical features.


Small Molecules of Marine Origin as Potential Anti-Glioma Agents.
Marine organisms are able to produce a plethora of small molecules with novel chemical structures and potent biological properties, being a fertile source for discovery of pharmacologically active compounds, already with several marine-derived agents approved as drugs. Glioma is classified by the WHO as the most common and aggressive form of tumor on CNS. Currently, Temozolomide is the only chemotherapeutic option approved by the FDA even though having some limitations. This review presents, for the first time, a comprehensive overview of marine compounds described as anti-glioma agents in the last decade. Nearly fifty compounds were compiled in this document and organized accordingly to their marine sources. Highlights on the mechanism of action and ADME properties were included. Some of these marine compounds could be promising leads for the discovery of new therapeutic alternatives for glioma treatment.


Pantoyl-gamma-aminobutyric acid facilitates cholinergic function in the central nervous system.
Pantoyl-gamma-aminobutyric acid (P-GABA) administered i.p. inhibited scopolamine- and atropine-induced locomotor activities in mice, but did not inhibit methamphetamine- and apomorphine-induced locomotor activities. In radiolabeled ligand binding experiments, P-GABA did not inhibit the bindings of [3H]quinuclidinyl benzilate, [3H]spiroperidol and [3H]apomorphine to rat brain membranes, but inhibited that of [3H]muscimol. GABA and P-GABA enhanced K+ (25 mM)-induced release of [3H]acetylcholine from slices of the cerebral cortex and hippocampus dose-dependently, and their effects were antagonized by bicuculline but not by tetrodotoxin. These results suggest that P-GABA binds to GABA receptors causing enhanced cholinergic neurotransmission in the central nervous system. The results are discussed in relation to the clinical use of P-GABA in treatment of Alzheimer's disease and senile dementia of the Alzheimer type.


Public perspectives on informed consent for biobanking.
The National Institutes of Health and other federal health agencies are considering establishing a national biobank to study the roles of genes and environment in health. We assessed the public's attitudes toward the proposed biobank, including preferences for providing informed consent. Sixteen focus groups were conducted, and themes arising from the focus groups were tested in a large, representative survey (n=4659) of the general population. Our research demonstrates that when considering participating in a genomic biobank, individuals want ongoing choices and control over access to their samples and information.


A comparison of light spot hydrophone and fiber optic probe hydrophone for lithotripter field characterization.
The performance of a newly developed light spot hydrophone (LSHD) in lithotripter field characterization was compared to that of the fiber optic probe hydrophone (FOPH). Pressure waveforms produced by a stable electromagnetic shock wave source were measured by the LSHD and FOPH under identical experimental conditions. In the low energy regime, focus and field acoustic parameters matched well between the two hydrophones. At clinically relevant high energy settings for shock wave lithotripsy, the measured leading compressive pressure waveforms matched closely with each other. However, the LSHD recorded slightly larger |P_| (p < 0.05) and secondary peak compressive pressures (p < 0.01) than the FOPH, leading to about 20% increase in total acoustic pulse energy calculated in a 6 mm radius around the focus (p = 0.06). Tensile pulse durations deviated ~5% (p < 0.01) due to tensile wave shortening from cavitation activity using the LSHD. Intermittent compression spikes and laser light reflection artifacts have been correlated to bubble activity based on simultaneous high-speed imaging analysis. Altogether, both hydrophones are adequate for lithotripter field characterization as specified by the international standard IEC 61846.