Amyl acetate: an alternative technique to dry mount Chalcidoidea (Hymenoptera) from alcohol, faster and inexpensively.
Ethanol (EtOH) 70% is commonly used in collections to preserve and store many unprepared soft-bodied Chalcidoidea. Specimens air-dried directly from alcohol, however, often suffer from collapse of some body parts, making subsequent observation of their morphology difficult or even impossible. We propose an inexpensive method for processing and dry-mounting specimens of Chalcidoidea, using a chemical process including amyl acetate. Four treatments using amyl acetate at different concentrations and exposure times were evaluated for specimens of Eulophidae, Mymaridae, Encyrtidae, Aphelinidae, Pteromalidae, and Trichogrammatidae. Treatment with amyl acetate resulted in specimens of consistently higher quality. Based on our results, treatment of specimens for 1 h with 50:50 amyl acetate and ethanol mixture, followed by treatment for 1 h with 100% amyl acetate, yielded specimens adequate for morphological observations for most of the families. Further experiments are required, however, to optimize this approach for Trichogrammatidae and Eulophidae. This method is a relatively simple, inexpensive, and safe alternative to other methods commonly used for restoring Chalcidoidea preserved in alcohol.


Dominant-negative interference of the transforming growth factor beta type II receptor in mammary gland epithelium results in alveolar hyperplasia and differentiation in virgin mice.
Transforming growth factor (TGF)-beta1 and TGF-beta3 are normally expressed at high levels in the mammary gland during quiescence and at all stages of development, except lactation. Exogenously added TGF-beta1, -beta2, and -beta3 have been shown to regulate growth and differentiation of mammary epithelial cells in vitro and in vivo. TGF-betas signal through a heteromeric complex of type I and type II serine/threonine kinases. The type II receptor is necessary for ligand binding and growth suppression by TGF-betas. Deletions of the cytoplasmic domains of several kinase receptors known to function in multimeric complexes have been shown to act as dominant-negative mutations. To evaluate the role of endogenous TGF-betas in the growth and differentiation of the mammary gland in vivo, we have targeted expression of a truncated, kinase-defective TGF-beta type II receptor to mammary epithelial cells in transgenic mice using the mouse mammary tumor virus promoter/enhancer. Transgene expression was localized to the epithelial cells of terminal ducts and alveolar buds. At approximately 20 weeks of age, virgin female transgenic mice demonstrated varying degrees of mammary epithelial hyperplasia. Mammary glands from transgenic, virgin animals exhibited alveolar development and expression of the milk protein, beta-casein. The data suggest that impaired responsiveness in the epithelium to endogenous TGF-betas results in inappropriate alveolar development and differentiation in the mammary gland. We conclude that endogenous TGF-betas signal to the epithelium to maintain quiescence in the mammary glands of virgin animals.


GaN-based metamaterial terahertz bandpass filter design: tunability and ultra-broad passband attainment.
Engineering metamaterial-based devices such as terahertz bandpass filters (BPFs) play a definitive role in advancement of terahertz technology. In this article, we propose a design procedure to obtain a considerably broadband terahertz BPF at a normal incidence; it shows promising filtering characteristics, including a wide passband of ∼1.34 THz at a central frequency of 1.17 THz, a flat top in a broad band, and high transmission, compared to previous reports. Then, exploiting the voltage-dependent carrier density control in an AlGaN/GaN heterostructure with a Schottky gate configuration, we investigate the tuning of the transmission properties in a narrow-band terahertz filter. A combination of the ultra-wide, flat-top BPF in series with the tunable, narrow band filter designed in the current study offers the ability to tune the desired resonance frequency along with high out-of-band rejection and the suppression of unwanted resonances in a large spectral range. The proposed structure exhibits a frequency tunability of 103 GHz for a voltage change between -8 and 2 V, and a transmission amplitude change of ∼0.51. This scheme may open up a route for the improved design of terahertz filters and modulators.


Datura stramonium Flowers as a Potential Natural Resource of Bioactive Molecules: Identification of Anti-Inflammatory Agents and Molecular Docking Analysis.
The present study investigated the antioxidant, antibacterial, antiviral and anti-inflammatory activities of different aerial parts (flowers, leaves and seeds) of Datura stramonium. The plant material was extracted with 80% methanol for about 24 h. The sensitivity to microorganisms analysis was performed by the microdilution technique. Antioxidant tests were performed by scavenging the DPPH and ABTS radicals, and by FRAP assay. Anti-inflammatory activity was evaluated through the inhibition of nitric oxide production in activated macrophage RAW 264.7 cells. Cell viability was assessed with an MTT assay. Results show that the flower extract revealed a powerful antimicrobial capacity against Gram-positive bacteria and strong antioxidant and anti-inflammatory activities. No significant cytotoxicity to activated macrophages was recorded. High resolution electrospray ionization mass spectrometry and nuclear magnetic resonance analysis identified two molecules with important anti-inflammatory effects: 12α-hydroxydaturametelin B and daturametelin B. Molecular docking analysis with both pro-inflammatory agents tumor necrosis factor alpha and interleukin-6 revealed that both compounds showed good binding features with the selected target proteins. Our results suggest that D. stramonium flower is a promising source of compounds with potential antioxidant, antibacterial, and anti-inflammatory activities. Isolated withanolide steroidal lactones from D. stramonium flower extract with promising anti-inflammatory activity have therapeutic potential against inflammatory disorders.


Epac and PKA: a tale of two intracellular cAMP receptors.
cAMP-mediated signaling pathways regulate a multitude of important biological processes under both physiological and pathological conditions, including diabetes, heart failure and cancer. In eukaryotic cells, the effects of cAMP are mediated by two ubiquitously expressed intracellular cAMP receptors, the classic protein kinase A (PKA)/cAMP-dependent protein kinase and the recently discovered exchange protein directly activated by camp (Epac)/cAMP-regulated guanine nucleotide exchange factors. Like PKA, Epac contains an evolutionally conserved cAMP binding domain that acts as a molecular switch for sensing intracellular second messenger cAMP levels to control diverse biological functions. The existence of two families of cAMP effectors provides a mechanism for a more precise and integrated control of the cAMP signaling pathways in a spatial and temporal manner. Depending upon the specific cellular environments as well as their relative abundance, distribution and localization, Epac and PKA may act independently, converge synergistically or oppose each other in regulating a specific cellular function.


Frenkel-exciton decomposition analysis of circular dichroism and circularly polarized luminescence for multichromophoric systems.
Recently, a method to calculate the absorption and circular dichroism (CD) spectra based on the exciton coupling has been developed. In this work, the method was utilized for the decomposition of the CD and circularly polarized luminescence (CPL) spectra of a multichromophoric system into chromophore contributions for recently developed through-space conjugated oligomers. The method which has been implemented using rotatory strength in the velocity form and therefore it is gauge-invariant, enables us to evaluate the contribution from each chromophoric unit and locally excited state to the CD and CPL spectra of the total system. The excitonic calculations suitably reproduce the full calculations of the system, as well as the experimental results. We demonstrate that the interactions between electric transition dipole moments of adjacent chromophoric units are crucial in the CD and CPL spectra of the multichromophoric systems, while the interactions between electric and magnetic transition dipole moments are not negligible. © 2018 Wiley Periodicals, Inc.


Adaptive scatter kernel deconvolution modeling for cone-beam CT scatter correction via deep reinforcement learning.
Scattering photons can seriously contaminate cone-beam CT (CBCT) image quality with severe artifacts and substantial degradation of CT value accuracy, which is a major concern limiting the widespread application of CBCT in the medical field. The scatter kernel deconvolution (SKD) method commonly used in clinic requires a Monte Carlo (MC) simulation to determine numerous quality-related kernel parameters, and it cannot realize intelligent scatter kernel parameter optimization, causing limited accuracy of scatter estimation. Aiming at improving the scatter estimation accuracy of the SKD algorithm, an intelligent scatter correction framework integrating the SKD with deep reinforcement learning (DRL) scheme is proposed. Our method firstly builds a scatter kernel model to iteratively convolve with raw projections, and then the deep Q-network of the DRL scheme is introduced to intelligently interact with the scatter kernel to achieve a projection adaptive parameter optimization. The potential of the proposed framework is demonstrated on CBCT head and pelvis simulation data and experimental CBCT measurement data. Furthermore, we have implemented the U-net based scatter estimation approach for comparison. The simulation study demonstrates that the mean absolute percentage error (MAPE) of the proposed method is less than 9.72% and the peak signal-to-noise ratio (PSNR) is higher than 23.90 dB, while for the conventional SKD algorithm, the minimum MAPE is 17.92% and the maximum PSNR is 19.32 dB. In the measurement study, we adopt a hardware-based beam stop array algorithm to obtain the scatter-free projections as a comparison baseline, and our method can achieve superior performance with MAPE < 17.79% and PSNR > 16.34 dB. In this paper, we propose an intelligent scatter correction framework that integrates the physical scatter kernel model with DRL algorithm, which has the potential to improve the accuracy of the clinical scatter correction method to obtain better CBCT imaging quality.


Physical evidence of rape against children and adolescents in Brazil: Analysis of 13,870 reports of sexual assault in 2017.
The medical literature reports child and adolescent maltreatment since the 8th century. Unfortunately, even today, the incomplete knowledge of this event persists. Several forms of violence are applied to children and adolescents, mainly sexual violence including rape and sexual assault. Forensic medical examinations routinely include the genital area, anus, and the body of the victims for signs of a recent or old injury. The main goal of this study is to show the results of physical and sexual examinations regarding confirmation of rape in children and adolescents, based on the medicolegal reports. We made a descriptive cross-sectional study conducted by collecting data from Medicolegal Institute (IML-São Paulo, Brazil) in 2017. We examined 13,870 reports of sexological examinations of victims of the alleged rape. The variables analyzed were age; sex; physical examination; sexological examination; and direct search for sperm in the vaginal, anal, or oral cavity. We selected 11,725 reports from victims under 18 years. As for the medical-legal findings, only 1735 reports (14.8%) confirmed sexual abuse. The most affected ages were between 3 and 5 years in the male group and 11 to 14 years in the female group. The most frequent injuries were bruises and abrasions, fissures in the anal region. In 96.2% of the examined males and 85.8% of the females under 14 years old, the examination was inconclusive, and somebody cannot prove the alleged rape. Only 1735 reports (113 from men and 1622 from women) concluded beyond any doubt the alleged rape (14.8%). The search for sperm was positive in only 1582 cases (13.5%). This study shows that the results of the medicolegal examinations were quite limited in recording evidence. Sexual violence against children and adolescents reaches mostly females under 13 years of age. Besides, it is a complicated crime to prove, as 85.8% of female examinations and 96.2% of male exams revealed: "no supporting elements" or "undetermined" to characterize the felony. Therefore, to prevent it, the communication of the alleged rape must be made as quickly as possible.


Platelet reactivity in vivo in dogs with arterial prostheses seeded with endothelial cells.
This study was designed to assess platelet activity in vivo with vascular prostheses seeded with endothelial cells to determine the time course for development of thromboresistance and to test the ability of prostheses to produce prostacyclin. Sixteen dogs were randomly allocated to receive seeded (experimental group) or unseeded (control group) velour Dacron aortic prostheses. Serial measurements of platelet survival were performed to assess platelet interaction with prostheses in vivo, and platelet serotonin was monitored as an index of platelet release in vivo. After placement of prostheses, dogs in the experimental group had rapid normalization of platelet survival, with most having normal platelet survival at 4 to 8 weeks after surgery. In contrast, most control animals had reduced platelet survival throughout the 12 week period of study. Significant differences between groups in mean platelet survival were noted at 8 weeks after surgery (p less than .005) and in mean platelet serotonin at 12 weeks after surgery (p less than .05). Luminal surface production of 6-keto-PGF1 alpha from seeded prostheses was similar to aortic production and significantly greater (p less than .05) than that of control prostheses. Gross thrombus was present on 6.0 +/- 3.4% of the prosthetic surface in experimental animals in comparison to 26.6 +/- 19.2% in controls (p less than .005). The results of these studies document accelerated nonreactivity with platelets of seeded prostheses due to rapid coverage with endothelium possessing a normal ability to produce prostacyclin.


Thermodynamic perturbation theory for fused sphere hard chain fluids using nonadditive interactions.
A model is developed for the equation of state of fused chains based on Wertheim thermodynamic perturbation theory and nonadditive size interactions. The model also assumes that the structure (represented by the radial distribution function) of the fused chain fluid is the same as that of the touching hard sphere chain fluid. The model is completely based on spherical additive and nonadditive size interactions. The model has the advantage of offering good agreement with simulation data while at the same time being independent of fitted parameters. The model is most accurate for short chains, small values of Delta (slightly fused spheres) and at intermediate (liquidlike) densities.


Treatment of femoral shortness due to nonunion or malunion by distraction device and Huckstep instrumentation.
Eighteen adult patients with nonunion or malunion of the femur and leg length discrepancy were treated with Wagner's distraction device and Huckstep instrumentation in one or two-staged operations. The Huckstep nail is introduced into the medullary cavity. Screws are transfixed to one segment before distraction. After completion of distraction, screws are transfixed to the other segment. Autogenous bone graft or allograft is also transfixed to fill up the gap. Continuous passive motion of the knee is conducted between operations and after operation. Postoperative protection is not necessary. All 12 patients who were operated for more than nine months had united and are reported here. Both patients with previous infection of the bone had flare up of the infection which was controlled medically. Both healed and united finally. No patient had contracture of the knee. This method corrects deformity and prevents angulation during distraction. Postoperative care is simple. The patient can return to his work soon after he is discharged. This method is not recommended for infection, bone of small caliber and desired lengthening for more than 6 centimeters.


Case report of a bilateral adrenal myelolipoma associated with Cushing disease.
Adrenal myelolipomas are rare benign tumors, composed of a variable mixture of mature adipose tissue and hematopoietic tissue. These tumors are frequently detected incidentally and are usually asymptomatic, and hormonally inactive. During a routine health checkup, a 52-year-old man was found to have a tumor on the bilateral adrenal glands. Abdominal computed tomography revealed a well-defined, heterogeneously enhanced bilateral adrenal mass, suggesting a myelolipoma. The hormonal evaluation revealed adrenocorticotropic hormone (ACTH) dependent Cushing syndrome. The patient underwent left adrenalectomy, and transsphenoidal resection of a pituitary mass. The final diagnosis was adrenal myelolipoma associated with Cushing disease. Growth of right adrenal myelolipoma was detected during the 7-year follow-up. There were enhancing pituitary lesions in repeat magnetic resonance imaging of the sellar region, which implies persistent or recurrent pituitary adenoma. This case reinforces relationship between Cushing disease and adrenal myelolipoma. To the best of our knowledge, this is the first reported pathologically confirmed bilateral adrenal myelolipoma associated with Cushing disease. This report supports the idea that ACTH is associated with the development of adrenal myelolipoma.


Gait Analysis for Early Detection of Motor Symptoms in the 6-OHDA Rat Model of Parkinson's Disease.
Computer-supported gait analysis has proven to be effective for the comprehensive assessment of gait changes in rodent models of neurodegenerative and neurological disorders. However, full characterization of individual gait parameters is required for specific neurological or neurodegenerative disorders such as Parkinson's disease (PD). Gait disturbances in particular present as the most constraining set of symptoms in PD, finally depriving patients from most activities of normal daily living. In this study, we have characterized the gait pattern abnormalities observed in two rat models of PD: the medial forebrain bundle (MFB) 6-OHDA lesion model and the striatal 6-OHDA lesion model. Our data indicates significant changes in 21 different gait parameters in the MFB lesion cohort. We observed a steady decline in the overall walking speed and cadence, as well as significant alterations in the gait parameters stride length, initial dual stance, paw print position, step cycle, swing phase of the step cycle, stand index, phase dispersion, print length, and print area in at least one of the paws. These alterations correlated with the extent of tyrosine hydroxylase (TH) neuronal loss observed in this group. These alterations were detected as early as 1 week post lesion. In contrast, limited gait dysfunction was detected in the striatal lesion cohort related to the low level of TH neuronal loss detected in this group. In this study we have demonstrated that gait analysis is a reliable method for the detection of motor deficiencies in a MFB 6-OHDA lesion model of PD and may prove a clinically relevant, low impact method of testing functional impairment as early as 1 week post lesion.


Viruses, Immunity and Unusual Lymphoproliferative Disorders of the Chest: Integrating Imaging With Pathogenesis and Clinical Presentations.
Unusual lymphoproliferative diseases result from the stimulation of intrathoracic lymphoid tissue by viruses and immune dysfunction, ranging from benign hyperplasia to malignant transformation. We review the clinical, radiological, and histopathological findings of unusual lymphoproliferative disorders, which have been linked to viruses or immune dysfunction, focusing on thoracic manifestations. Understanding these advances in science enhances the radiologist's skills in integrating the imaging findings to the clinical scenario to suggest the correct diagnosis.


Solid-phase synthesis of polymers using the ring-opening metathesis polymerization.
We report a general method for the solid-phase synthesis of polymers via the ring-opening metathesis polymerization (ROMP). The method involves polymerization in solution to form a block copolymer, immobilization of the polymer via reaction of one block with a resin-bound functional group, modification of the other block, and liberation of the polymer from the resin. We demonstrated the utility of this approach by generating a block copolymer with an N-hydroxysuccinimidyl ester-substituted block (for on-resin functionalization) and a maleimide-substituted block (for conjugation to the resin). We showed that the Diels-Alder reaction can be employed to immobilize the polymers and that amines of diverse structure can be used to modify the resin-bound polymers. The reversibility of the furan-maleimide Diels-Alder adduct was exploited to liberate the polymer from the support. Specifically, treatment of the resin with cyclopentadiene resulted in complete polymer release. The resulting polymers are functional: they were as potent in assays with the lectin concanavalin A as polymers generated by traditional solution routes. We anticipate that this method can be used for the rapid synthesis of diverse polymers via ROMP.


The effectiveness of group-purchasing organizations.
The prices paid for routine medical supply items by six hospital group-purchasing systems and a control group of 24 nonaffiliated hospitals were compared to determine the effects of group purchasing. Each of the six group-purchasing systems obtained lower prices for supply items used in the study, ranging from 12 to 26 percent average savings. The enforcement of written contracts among the plan's members and the percentage of plan member participation appeared to explain effectiveness. Size of the plan and volume of purchases did not influence the percentage of saving realized among the groups.


Endurance and contest: women's narratives of endometriosis.
Endometriosis is an often painful medical condition in which, in response to hormones associated with the menstrual cycle, the uterine lining grows in the peritoneum and other organs, bleeding into the surrounding organs and tissues. Diagnosis is not always straightforward, and women and health professionals alike may have difficulties recognizing period pain as a sign of anomaly, considering it instead as an inevitable part of menstruation. This article describes the illness narratives of Australian women with endometriosis, drawing on data collected during a study conducted in Victoria in 2004-5. Thirty women (aged 20-78 years) from various socio-demographic backgrounds participated in in-depth interviews. We explore the influence of socio-demographic background and social and family norms on women's illness narratives of endurance and contest. Narratives of endurance are characterized by the normalization of period pain by young women, their families and health professionals, and, with diagnosis, long-term exposure to biomedical treatments. In contrast, narratives of contest are dominated by how women's subjective experience is challenged by doctors, their requirements for a patient-centered approach, and their desire to have access to complementary treatments.


Effects of decompression on pain, range of motion and function in patients with acute vs chronic lumbar radiculopathy.
The purpose of this study was to determine the effects of manual lumbar decompression on pain, range of motion, and function in patients with acute vs chronic lumbar radiculopathy. Thirty patients fulfilling the eligibility criteria at Tehsil Headquarter Civil Hospital Daska were randomly placed into three groups: acute group (n=10), chronic group (n=10), and control group (n=10). Mean age of the participants was 33.3±8.5 years and the mean body mass index was 25.0±4.4. There were 12 males and 21 female participants. Group A and Group B were 18 treated with decompression, lumbar mobilisation, hot packs, TENS and exercise therapy, while the patients in Group C were treated with lumbar mobilisation, hot packs and exercise therapy. Total duration of the treatment was four weeks at three sessions per week and the outcomes were measured at baseline and at the completion of four-week treatment with Visual Analogue Scale, Modified Oswestry Disability index, Straight Leg Raise, and Inclinometer. Data was analysed by using SPSS version 25. One Way ANOVA and Kruskal-Wallis Test were used to compare the means across the groups. It was concluded that manual lumbar decompression decreases pain, and increases range of motion and function in Group A (acute) as compared to Group B (chronic) and Group C (control).


Transcatheter aortic valve thrombosis: the relation between hypo-attenuated leaflet thickening, abnormal valve haemodynamics, and stroke.
The presence of hypo-attenuated leaflet thickening (HALT) and/or reduced leaflet motion on multi-detector row computed tomography (MDCT) has been proposed as a possible marker for early transcatheter aortic valve thrombosis. However, its association with abnormal valve haemodynamics on echocardiography (another potential marker of thrombosis) and clinical outcomes (stroke) remains unclear. The present study evaluated the prevalence of HALT on MDCT and abnormal valve haemodynamics on echocardiography. In addition, the occurrence of ischemic stroke and/or transient ischemic attack (TIA) was assessed. A total of 434 patients (mean age 80 ± 7 years, 51% male) who underwent transcatheter aortic valve replacement (TAVR) were evaluated. Transcatheter valve haemodynamics were assessed on echocardiography at discharge, 6 months, and thereafter yearly (up to 3 years post-TAVR). The presence of HALT and/or reduced leaflet motion was assessed on MDCT performed 35 days [interquartile range 19-210] after TAVR in 128 of these 434 patients. Possible TAVR valve thrombosis was defined by mean transvalvular gradient ≥20 mmHg and aortic valve area (AVA) ≤1.1cm2 on echocardiography or by the presence of HALT or reduced leaflet motion on MDCT. The occurrence of ischemic stroke/TIA at follow-up was recorded. HALT and/or reduced leaflet motion was present in 12.5% of 128 patients undergoing MDCT, and was associated with a slightly higher mean transvalvular gradient (12.4 ± 8.0 mmHg vs. 9.4 ± 4.3 mmHg; P = 0.026) and smaller AVA (1.49 ± 0.39 cm2 vs. 1.78 ± 0.45 cm2, P = 0.017). Only one patient with HALT on MDCT revealed abnormal valve haemodynamics on echocardiography. At 3-year follow-up, abnormal valve haemodynamics on echocardiography were observed in 3% of patients. HALT on MDCT and abnormal valve haemodynamics on echocardiography were not associated with increased risk of ischemic stroke/TIA. On MDCT, 12.5% of patients showed HALT or reduced leaflet motion, whereas only one of these patients had abnormal valve haemodynamics on echocardiography. Neither HALT nor increased transvalvular gradient were associated with stroke/TIA.


A Novel System for Correction of Relative Angular Displacement between Airborne Platform and UAV in Target Localization.
This paper provides a system and method for correction of relative angular displacements between an Unmanned Aerial Vehicle (UAV) and its onboard strap-down photoelectric platform to improve localization accuracy. Because the angular displacements have an influence on the final accuracy, by attaching a measuring system to the platform, the texture image of platform base bulkhead can be collected in a real-time manner. Through the image registration, the displacement vector of the platform relative to its bulkhead can be calculated to further determine angular displacements. After being decomposed and superposed on the three attitude angles of the UAV, the angular displacements can reduce the coordinate transformation errors and thus improve the localization accuracy. Even a simple kind of method can improve the localization accuracy by 14.3%.


2DProts: database of family-wide protein secondary structure diagrams.
Secondary structures provide a deep insight into the protein architecture. They can serve for comparison between individual protein family members. The most straightforward way how to deal with protein secondary structure is its visualization using 2D diagrams. Several software tools for the generation of 2D diagrams were developed. Unfortunately, they create 2D diagrams based on only a single protein. Therefore, 2D diagrams of two proteins from one family markedly differ. For this reason, we developed the 2DProts database, which contains secondary structure 2D diagrams for all domains from the CATH and all proteins from PDB databases. These 2D diagrams are generated based on a whole protein family, and they also consider information about the 3D arrangement of secondary structure elements. Moreover, 2DProts database contains multiple 2D diagrams, which provide an overview of a whole protein family's secondary structures. 2DProts is updated weekly and is integrated into CATH. Freely accessible at https://2dprots.ncbr.muni.cz. The web interface was implemented in JavaScript. The database was implemented in Python. Supplementary data are available at Bioinformatics online.


Rate and complications of adult epilepsy surgery in North America: Analysis of multiple databases.
Epilepsy surgery is under-utilized, but recent studies reach conflicting conclusions regarding whether epilepsy surgery rates are currently declining, increasing, or remaining steady. However, data in these prior studies are biased toward high-volume epilepsy centers, or originate from sources that do not disaggregate various procedure types. All major epilepsy surgery procedures were extracted from the Centers for Medicare and Medicaid Services Part B National Summary Data File and the American College of Surgeons National Surgical Quality Improvement Program. Procedure rates, trends, and complications were analyzed, and patient-level predictors of postoperative adverse events were identified. Between 2000-2013, 6200 cases of epilepsy surgery were identified. Temporal lobectomy was the most common procedure (59% of cases), and most did not utilize electrocorticography (63-64%). Neither temporal nor extratemporal lobe epilepsy surgery rates changed significantly during the study period, suggesting no change in utilization. Adverse events, including major and minor complications, occurred in 15.3% of temporal lobectomies and 55.6% of hemispherectomies. Our findings suggest stagnant rates of both temporal and extratemporal lobe epilepsy surgery across U.S. surgical centers over the past decade. This finding contrasts with prior reports suggesting a recent dramatic decline in temporal lobectomy rates at high-volume epilepsy centers. We also observed higher rates of adverse events when both low- and high-volume centers were examined together, as compared to reports from high-volume centers alone. This is consistent with the presence of a volume-outcome relationship in epilepsy surgery.


A starter's guide to preclinical teeth arrangement: simplified clinometer.
Arrangement of artificial teeth in a bilaterally symmetrical fashion with proper inclinations of teeth had been a challenging task for beginners. A variety of tools and guiding equipment have been developed to help students to learn teeth arrangement. Unfortunately, those tools were either costly or unsuitable for use with mean value articulators. This article attempts to introduce a simplified clinometer which can be attached to mean value articulator and can be used as a guide to arrange teeth in a bilaterally symmetrical manner by the undergraduates in both clinical and preclinical set-up. Training of the future dentists in sound esthetic principles in a preclinical environment, using this device, will increase the final clinical efficacy of their work. The aim of this article is to provide a simple but effective device to undergraduate students to help them learn teeth arrangement easily and systematically.


The effects of dietary flaxseed on cardiac arrhythmias and claudication in patients with peripheral arterial disease 1.
Patients with peripheral artery disease (PAD) are at increased risk for cardiovascular events, and higher susceptibility for cardiac arrhythmias may be involved. The objectives of this double-blinded randomized controlled FLAX-PAD trial were to determine whether daily consumption of a diet supplemented with 30 g of milled flaxseed (or placebo) over 1 year by PAD patients has effects on the prevalence of cardiac arrhythmias and exercise capacity. Cardiac arrhythmias were assessed on a cardiac stress test and at rest. At baseline, the PAD patients had a high incidence of cardiac arrhythmias (48% in the flaxseed group and 32% in the placebo group). After 1 year, the presence of cardiac arrhythmias in the flaxseed group decreased by 2% and increased by 12% in the placebo group (P > 0.05). Electrocardiographic variables (P, PR, QRS, QT, and QTc) did not change in either group during the trial. Patients from both groups improved initial and absolute claudication distances but the intergroup difference was also not statistically significant. In summary, the prevalence of cardiac arrhythmias and physical capacity trended in a positive direction for patients ingesting flaxseed but either a larger sample size or a longer intervention with flaxseed may be required to show statistically significant differences.


Real-time optical wireless transmissions of digital TV signals using white InGaN LEDs grown with an asymmetric quantum barrier.
The feasibility of using InGaN LEDs grown with asymmetric barrier layer (ABL) as transmitters in visible light communications is investigated experimentally. Compared with normal LEDs, the improvement in the spontaneous emission rate due to enhanced carrier localization and better uniformity of carrier distribution in ABL-containing MQWs leads to the fabricated LEDs can exhibit a 32.6% (@ 350 mA) increase in emission intensity and a 10.5% increase in modulation bandwidth. After eliminating the slow-responding phosphorescent components emitting from the phosphor-converted white LEDs, an open eye-diagram at 180 Mb/s is demonstrated over a distance of 100 cm in directed line-of-sight optical links. With the use of proposed LEDs, real-time transmissions of digital TV signals over a moderate distance (~100 cm) in free space is shown to be available in a 150 Mbit/s white LED-based optical link with conventional on-off keying modulation.


RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4.
Pancreatic adenocarcinoma patients have low survival rates due to late-stage diagnosis and high rates of cancer recurrence even after surgical resection. It is important to understand the molecular characteristics associated with survival differences in pancreatic adenocarcinoma tumors that may inform patient care. RNA sequencing was performed for 51 patient tumor tissues extracted from patients undergoing surgical resection, and expression was associated with overall survival time from diagnosis. Our analysis uncovered 323 transcripts whose expression correlates with survival time in our pancreatic patient cohort. This genomic signature was validated in an independent RNA-seq dataset of 68 additional patients from the International Cancer Genome Consortium. We demonstrate that this transcriptional profile is largely independent of markers of cellular division and present a 19-transcript predictive model built from a subset of the 323 transcripts that can distinguish patients with differing survival times across both the training and validation patient cohorts. We present evidence that a subset of the survival-associated transcripts is associated with resistance to gemcitabine treatment in vitro, and reveal that reduced expression of one of the survival-associated transcripts, Angiopoietin-like 4, impairs growth of a gemcitabine-resistant pancreatic cancer cell line. Gene expression patterns in pancreatic adenocarcinoma tumors can distinguish patients with differing survival outcomes after undergoing surgical resection, and the survival difference could be associated with the intrinsic gemcitabine sensitivity of primary patient tumors. Thus, these transcriptional differences may impact patient care by distinguishing patients who would benefit from a non-gemcitabine based therapy.


LDL receptor and ApoE are involved in the clearance of ApoM-associated sphingosine 1-phosphate.
Sphingosine 1-phosphate (S1P) is a vasoactive lipid mediator that is speculated to be involved in various aspects of atherosclerosis. About 70% of circulating plasma S1P is carried on HDL, and several pleiotropic properties of HDL have been ascribed to S1P. In the previous study with human subjects, however, LDL cholesterol or apoB, but not HDL cholesterol or apoA-I, had a significant positive correlation with the plasma S1P level, suggesting that the metabolic pathway for LDL might have some roles in the metabolism of S1P. In this study, we analyzed the association between LDL receptor, an important protein in the clearance of LDL, and circulating S1P. We observed that in LDL receptor-overexpressing mice, the plasma S1P levels as well as apolipoprotein M (apoM), a carrier of S1P, were decreased and that exogenously administered C17S1P bound to apoM-containing lipoproteins was cleared more rapidly. Unlike the situation in wild-type mice, LDL receptor overexpression in apoE-deficient mice did not reduce the plasma S1P or apoM levels, suggesting that apoE might be a ligand for the LDL receptor during the clearance of these factors. The present findings clarify the novel roles of the LDL receptor and apoE in the clearance of S1P, a multifunctional bioactive phospholipid.


Radiation effects on soluble metabolites in cultured HeLa cells examined by 1H MRS: changes in concentration of glutathione and of lipid catabolites induced by gamma rays and proton beams.
Cultured HeLa cells were irradiated with a single acute dose of either gamma rays (40 Gy) or low-energy proton beams (20 Gy). (1)H magnetic resonance spectra of intact cells harvested at different times after irradiation and of the correspondent perchloric acid (PCA) extracts prepared at different times after irradiation were run. Selected signals from glutathione and lactate were examined with the aim of investigating effects of irradiation on antioxidative stores and on mitochondrial activity. An increase of signal intensity of glutathione (GSH) takes place at 15 and 24 hr after irradiation, while a decrease of its signal intensity, accompanied by an increase of that of free glutamate, starts appearing 48 hr after irradiation. Lactate signal increases 48 hr after irradiation. Signals from lipid catabolites were also examined to explore their sensitivity in predicting the response to radiotherapy. Intensity ratios of signals of glycerophosphorylcholine and choline to that of phosphorylcholine increase with time after irradiation. Irradiating cells with gamma rays or proton beams at half a dose produces effects comparable to the metabolic variations presented here. The present experiments allow more insight into the complex pattern of the changes of GSH by irradiation and indicate that magnetic resonance spectroscopy signals from GSH, glutamate, lactate, and lipid catabolites are affected by irradiation. Finally, these data represent a first indication that the relative biological efficiency for some metabolic damage of low-energy proton beams with respect to gamma rays can reach a value of 2.


The Incidence of Benzodiazepine and Related Drug Use in Persons with and without Alzheimer's Disease.
Benzodiazepines and related drugs (BZDR) are occasionally used to treat certain symptoms of Alzheimer's disease (AD). However, the risks related to BZDR use are high in older persons. Although frequent BZDR use has been reported in persons with AD, no previous study has focused specifically on the incidence of BZDR use in this population. We investigated the incidence of BZDR use in persons with and without AD during a five-year follow-up. The Finnish nationwide, register-based MEDALZ cohort includes all AD cases who received a clinically verified AD diagnosis in 2005-2011 (n = 70,718) and their matched comparison persons. Incidence of BZDR, including benzodiazepines (lorazepam, oxazepam, temazepam, alprazolam, chlordiazepoxide, diazepam, and nitrazepam) and Z-drugs (zolpidem and zopiclone), use was investigated in the cohort from two years before to three years after the diagnosis of AD. Further, initial BZDRs were investigated. The incidence of BZDR use was higher in persons with AD starting from 12 months before the diagnosis and peaked at six months after the diagnosis of AD (incidence rate ratio [IRR] = 2.6, 95% confidence interval [CI] = 2.5-2.8). Benzodiazepines were more frequently initiated by persons with AD, with the incidence peaking at six months after the diagnosis (IRR = 4.5, 95% CI = 4.1-4.9) and remaining over three times higher than in comparison persons until three years after the diagnosis. Early symptomatic treatment with BZDRs is contrary to AD treatment guidelines. As BZDRs impair cognition, the observed early treatment with BZDRs may complicate the monitoring of AD treatment effectiveness.


An allosteric receptor by simultaneous "casting" and "molding" in a dynamic combinatorial library.
Allosteric synthetic receptors are difficult to access by design. Herein we report a dynamic combinatorial strategy towards such systems based on the simultaneous use of two different templates. Through a process of simultaneous casting (the assembly of a library member around a template) and molding (the assembly of a library member inside the binding pocket of a template), a Russian-doll-like termolecular complex was obtained with remarkable selectivity. Analysis of the stepwise formation of the complex indicates that binding of the two partners by the central macrocycle exhibits significant positive cooperativity. Such allosteric systems represent hubs that may have considerable potential in systems chemistry.


Longevity in male and female joggers: the Copenhagen City Heart Study.
Since 1970, jogging has become an increasingly popular form of exercise, but concern about harmful effects has been raised following reports of deaths during jogging. The purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women. Jogging habits were recorded in a random sample of 17,589 healthy men and women aged 20-98 years, invited between 1976 and 2003 to the Copenhagen City Heart Study. The expected lifetime was calculated by integrating the predicted survival curve estimated in the Cox model. In this study 1,878 persons (1,116 men and 762 women) were classified as joggers. During the 35-year maximum follow-up period, we registered 122 deaths among joggers and 10,158 deaths among nonjoggers. The age-adjusted hazard ratio of death among joggers was 0.56 (95% confidence interval: 0.46, 0.67) for men and 0.56 (95% confidence interval: 0.40, 0.80) for women. The age-adjusted increase in survival with jogging was 6.2 years in men and 5.6 years in women. This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women.


The pathogenesis of dermatomyositis.
This review looks at the many different factors thought to play a role in idiopathic inflammatory myopathies (IIM), concentrating mainly on the dermatomyositis (DM) subtype. Subject areas addressed include looking at the different clinical features of IIM, paying particular attention to the skin manifestations. There is a discussion around investigations needed with their perceived value, followed by a description of the immunohistochemical findings of DM. This review goes on to address other attributing factors such as genetic associations with the different subtypes of IIM, and environmental factors including infections, ultraviolet radiation and vitamin D deficiency and drugs. Finally, the potential immunopathogenesis of DM is summarized, looking at T cells, B cells, autoantibodies, dendritic cells, cytokines and nonimmune-mediated endoplasmic reticulum stress.


Ranitidine-enhanced 99mtechnetium pertechnetate imaging in children improves the sensitivity of identifying heterotopic gastric mucosa in Meckel's diverticulum.
Meckel's diverticulum is the most common congenital gastrointestinal anomaly. (99m )Technetium pertechnetate imaging (Meckel's scan) is the best noninvasive method used to diagnose this condition when heterotopic gastric mucosa (HGM) is present. Although cimetidine enhancement has been shown to improve sensitivity of the Meckel's scan, ranitidine enhancement has also been advocated; however, this recommendation is based on unpublished data. Thirty-seven children with confirmed Meckel's diverticulum were reviewed retrospectively. Of eight children with HGM in the Meckel's diverticulum who presented with profuse rectal bleeding and underwent the conventional Meckel's scan, three of them (37.5%) had a false negative study. Ranitidine, when administered either intravenously or orally for 24 h prior to the Meckel's scan, enhanced the sensitivity of this test to 87.5% in our patient cohort.


Prognostic value of histopathological findings in aneurysmal subarachnoid hemorrhage.
Aneurysmal subarachnoid hemorrhage (SAH) carries a severe prognosis, which is often related to the development of cerebral vasospasm. Even though several clinical and radiological predictors of vasospasm and functional outcome have been established, the prognostic value of histopathological findings remains unclear. Histopathological findings in resected distal aneurysm walls were examined, as were the clinical and radiological factors in a series of 91 patients who had been neurosurgically treated for aneurysmal SAH. The impact of the histological, clinical, and radiological factors on the occurrence of vasospasm and functional outcome at discharge was analyzed. Histopathological findings frequently included lymphocytic infiltrates (60%), fibrosis (60%), and necrosis (50%) of the resected aneurysm wall. On univariate analysis, clinical (Hunt and Hess grade) and radiological (aneurysm size) factors as well as histopathological features-namely, lymphocytic infiltrates and necrosis of the aneurysm wall-were significantly associated with the occurrence of vasospasm. On multivariate analysis, lymphocytic infiltrates (OR 6.35, 95% CI 2.32-17.36, p = 0.0001) and aneurysm size (OR 1.22, 95% CI 1.05-1.42, p = 0.009) remained the only factors predicting the development of vasospasm. A poor functional outcome at discharge was significantly associated with vasospasm, other clinical factors (Hunt and Hess grade, alcohol consumption, hyperglycemia, and elevated white blood cell count [WBC] at admission), and radiological factors (Fisher grade and aneurysm size), as well as with histopathological features (lymphocytic infiltrates [p = 0.0001] and necrosis of the aneurysm wall [p = 0.0015]). On multivariate analysis taking into account all clinical, radiological, and histological factors; vasospasm (OR 9.82, 95% CI 1.83-52.82, p = 0.008), Hunt and Hess grade (OR 5.61, 95% CI 2.29-13.74, p = 0.0001), patient age (OR 1.09, 95% CI 1.02-1.16, p = 0.0013), elevated WBC (OR 1.29, 95% CI 1.01-1.64, p = 0.04), and Fisher grade (OR 4.35, 95% CI 1.25-15.07, p = 0.015) best predicted functional outcome at discharge. The demonstration of lymphocytic infiltrates in the resected aneurysm wall is of independent prognostic value for the development of vasospasm in patients with neurosurgically treated aneurysmal SAH. Thus, histopathology might complement other clinical and radiological factors in the identification of patients at risk.


Relationship Between Weightbearing Ankle Dorsiflexion Passive Range of Motion and Ankle Kinematics During Gait.
Measurement of weightbearing ankle dorsiflexion (DF) passive range of motion (PROM) has been suggested as a way to estimate ankle kinematics during gait; however, no previous study has demonstrated the relationship between ankle DF during gait and ankle DF PROM with knee extension. We examine the relationship between maximum ankle DF during gait and nonweightbearing and weightbearing ankle DF PROM with knee extension. Forty physically active individuals (mean ± SD age, 21.63 ± 1.73 years) participated in this study. Ankle DF PROM with knee extension was measured in the nonweightbearing and weightbearing conditions; maximum ankle DF during gait was assessed using a three-dimensional motion analysis system. The relationship between each variable was calculated using the Pearson product moment correlation coefficient, and the difference in ankle DF PROM between the nonweightbearing and weightbearing conditions was analyzed using a paired t test. The weightbearing measurement (r = 0.521; P < .001) for ankle DF PROM showed a greater correlation with maximum ankle DF during gait than did the nonweightbearing measurement (r = 0.245; P = .029). Ankle DF PROM was significantly greater in the weightbearing than in the nonweightbearing condition (P < .001) despite a significant correlation between the two measurements (r = 0.402; P < .001). These findings indicate that nonweightbearing and weightbearing measurements of ankle DF PROM with knee extension should not be used interchangeably and that weightbearing ankle DF PROM with the knee extended is more appropriate for estimating ankle DF during gait.


Routine amnioscopy at term.
A controlled study for the management of antepartum meconium-stained amniotic fluid (MSAF) detected by amnioscopy performed in a total of 508 patients is presented. The incidence of antepartum MSAF was 2.2%, while intrapartum MSAF was found in 15% of cases. A significant incidence of depressed neonates was found in the latter group. Patients with antepartum MSAF had no perinatal losses, whether managed expectantly or by oxytocin induction. Immediate operative intervention (ie, cesarean section) is not warranted. Observations on FHR patterns, fetal pH, and Apgar scores of these patients are presented.


Twenty-four hours abstinence and the quality of sperm parameters.
Patients with abnormal basic parameters and mainly low concentration can be expected to have improved parameters on the second consecutive day. As the number of abnormal basic parameters increases, the more significant improvement can be expected. On the other hand, patients with normal or few abnormal basic semen parameters show a decrease after 24 h. Furthermore, the magnitude of change to both directions in TMC and TNMC values in these patients emphasises these conclusions. Based on the type and mainly the combined number of abnormal basic semen parameters, insemination strategy can be tailored to male fertility patients. Those with abnormal concentration or multiple abnormal semen parameters may benefit from 2 consecutive day intercourses or inseminations or a short period of abstinence due to a significant improvement in the semen parameters on second day insemination. In those with normal basic semen parameters, a reduction in semen quality is expected after 24 h, and a single-timed insemination and longer abstinence can be recommended.


[A Case of Strangulated Bowel Obstruction after a Laparoscopic Hartmann's Operation for Rectal Cancer].
A 98-year-old woman presented with hematochezia and a circumferential type 2 tumor in the rectum Rb identified on fiberoscopy. We a performed laparoscopic Hartmann's operation and D2 lymphadenectomy for advanced rectal cancer. A sigmoid colostomy was created via the intraperitoneal route. On the postoperative day 12, the patient experienced abdominal pain. Computed tomography showed that the small intestine formed a closed loop in the pelvic space. The patient was diagnosed with a strangulated bowel obstruction of the small intestine for which an emergency exploratory laparotomy was performed. The small intestine, which had passed through a defect between the lifted sigmoid colon and the left abdominal wall, was strangulated by the lifted sigmoid colon. We performed partial resection of the small intestine. The patient died on postoperative day 32 of acute deterioration of aortic valve stenosis. There have been few reports of strangulated bowel obstruction resulting from internal hernia associated with colostomy. These findings demonstrate that it is important to select the appropriate route for colostomy creation in each case.


Novel regulatory effect of angiotensin II type 1 receptor-interacting molecule on vascular smooth muscle cells.
We have recently cloned a novel molecule that interacts with the angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP). In this study, we tested the hypothesis that ATRAP modulates angiotensin II-induced responses in vascular smooth muscle cells. The results of immunoprecipitation and bioluminescence resonance energy transfer assay demonstrated a direct interaction between ATRAP and AT1R at baseline and showed that angiotensin II enhanced the interaction of these proteins >2-fold. The results of immunofluorescence analysis also demonstrated that >65% of ATRAP constitutively colocalized with an endosome marker. Although only 36% of ATRAP colocalized with AT1R at baseline, angiotensin II enhanced the colocalization of these molecules and made 92% of ATRAP colocalize with AT1R on a quantitative fluorescence analysis. Overexpression of ATRAP by adenoviral transfer decreased the cell surface AT1R number from 4.33 to 2.13 fmol/10(6) cells at baseline and from 3.04 to 1.26 fmol/10(6) cells even after removal of angiotensin II. ATRAP also suppressed angiotensin II-mediated increases in c-fos gene transcription and transforming growth factor-beta production. Furthermore, this suppression was accompanied by inhibition of angiotensin II-induced activation of 5-bromodeoxyuridine incorporation. Finally, ATRAP knockdown by small-interference RNA activated angiotensin II-induced c-fos gene expression, which was effectively inhibited by valsartan, an AT1R-specific antagonist. These results indicate that ATRAP promotes internalization of AT1R and attenuates the angiotensin II-mediated c-fos-transforming growth factor-beta pathway and proliferative response in vascular smooth muscle cells, suggesting a novel strategy to inhibit vascular fibrosis and remodeling through a novel and specific blockade of AT1R signaling.


Quantifying forearm muscle activity during wrist and finger movements by means of multi-channel electromyography.
The study of hand and finger movement is an important topic with applications in prosthetics, rehabilitation, and ergonomics. Surface electromyography (sEMG) is the gold standard for the analysis of muscle activation. Previous studies investigated the optimal electrode number and positioning on the forearm to obtain information representative of muscle activation and robust to movements. However, the sEMG spatial distribution on the forearm during hand and finger movements and its changes due to different hand positions has never been quantified. The aim of this work is to quantify 1) the spatial localization of surface EMG activity of distinct forearm muscles during dynamic free movements of wrist and single fingers and 2) the effect of hand position on sEMG activity distribution. The subjects performed cyclic dynamic tasks involving the wrist and the fingers. The wrist tasks and the hand opening/closing task were performed with the hand in prone and neutral positions. A sensorized glove was used for kinematics recording. sEMG signals were acquired from the forearm muscles using a grid of 112 electrodes integrated into a stretchable textile sleeve. The areas of sEMG activity have been identified by a segmentation technique after a data dimensionality reduction step based on Non Negative Matrix Factorization applied to the EMG envelopes. The results show that 1) it is possible to identify distinct areas of sEMG activity on the forearm for different fingers; 2) hand position influences sEMG activity level and spatial distribution. This work gives new quantitative information about sEMG activity distribution on the forearm in healthy subjects and provides a basis for future works on the identification of optimal electrode configuration for sEMG based control of prostheses, exoskeletons, or orthoses. An example of use of this information for the optimization of the detection system for the estimation of joint kinematics from sEMG is reported.


Survival Strategies for Tsunami of ICD-10-CM for Interventionalists: Pursue or Perish!
The unfunded mandate for the implementation of International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) is scheduled October 1, 2015. The development of ICD-10-CM has been a complicated process. We have endeavored to keep Interventional Pain Management doctors apprised via a variety of related topical manuscripts. The major issues relate to the lack of formal physician participation in its preparation. While the American Health Information Management Association (AHIMA) and American Hospital Association (AHA) as active partners in its preparation. Centers for Medicare and Medicaid Services (CMS) and Centers for Disease Control and Prevention (CDC) are major players; 3M and Blue Cross Blue Shield Association are also involved. The cost of ICD-10-CM implementation is high, similar to the implementation of electronic health records (EHRs), likely consuming substantial resources. While ICD-10, utilized worldwide, includes 14,400 different codes, ICD-10-CM, specific for the United States, has expanded to 144,000 codes, which also includes procedural coding system. It is imperative for physicians to prepare for the mandatory implementation. Conversion from ICD-9-CM to ICD-10-CM coding in interventional pain management is not a conversion of one to one that can be easily obtained from software packages. It is a both a difficult and time-consuming task with each physician, early on, expected to spend on estimation at least 10 minutes per visit on extra coding for established and new patients. For interventional pain physicians, there have been a multitude of changes, including creation of new codes and confusing conversion of existing codes. This manuscript describes a variety of codes that are relevant to interventional pain physicians and often utilized in daily practices. It is our objective that this manuscript will provide coding assistance to interventional pain physicians.


Increased utilization of constraint in total knee arthroplasty following anterior cruciate ligament and multiligament knee reconstruction.
Anterior cruciate ligament (ACL) and multiligament knee (MLK) injuries increase the risk of development of knee osteoarthritis and eventual need for total knee arthroplasty (TKA). There are limited data regarding implant use and outcomes in these patients. The aim of this study was to compare the use of constrained implants and outcomes among patients undergoing TKA with a history of prior knee ligament reconstruction (PKLR) versus a matched cohort of patients undergoing TKA with no history of PKLR. Patients with a history of ACL or MLK reconstruction who underwent TKA between 2007 and 2017 were identified in a single-institution registry. There were 223 patients who met inclusion criteria (188 ACL reconstruction patients, 35 MLK reconstruction patients). A matched cohort, also of 223 patients, was identified based on patient age, body mass index (BMI), sex, and year of surgery. There were 144 male patients and 79 female patients in both cohorts. Mean age at the time of TKA was 57.2 years (31 to 88). Mean BMI was 29.7 kg/m2 (19.5 to 55.7). There was a significantly higher use of constrained implants among patients with PKLR (76 of 223, 34.1%) compared with the control group (40 of 223, 17.9%; p < 0.001). Subgroup analysis showed a higher use of constrained implants among patients with prior MLK reconstruction (21 of 35, 60.0%) compared with ACL reconstruction (55 of 188, 29.3%; p < 0.001). Removal of hardware was performed in 69.5% of patients with PKLR. Mean operative time (p < 0.001) and tourniquet time (p < 0.001) were longer in patients with PKLR compared with controls. There were no significant differences in rates of deep vein thrombosis, pulmonary embolism, infection, transfusion, postoperative knee range of movement (ROM), or need for revision surgery. There was no significant difference in preoperative or postoperative Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS, JR) scores between groups. Results of this study suggest a history of PKLR results in increased use of constrained implants but no difference in postoperative knee ROM, patient-reported outcomes, or incidence of revision surgery. Cite this article: Bone Joint J 2019;101-B(7 Supple C):77-83.


Prevalence and heritability of alcohol use disorders in 18-year old Swedish twins.
Background: Heritability of alcohol use disorders (AUDs) varies widely, with reported estimates of 30-78% in twin studies. This variation might be due to methodological differences (e.g., using different thresholds for AUDs, age differences between samples). Aim: To investigate the heritability of AUDs in a nation-wide sample of male and female twins in late adolescence (18 years). Participants: The study is based on data from 8,330 18-year-old Swedish monozygotic (MZ) and dizygotic (DZ) twins from the Child and Adolescent Twin Study (Sweden). Method: Univariate sex-limitation twin analyses were performed using (a) total AUDIT score, (b) different AUDIT cut-offs (AUDIT-10: potentially harmful alcohol use and most likely alcohol dependent ; AUDIT-C: potential hazardous alcohol consumption/active alcohol use disorders), and (c) a risk-group classification for alcohol dependence based on AUDIT total score. Results: Prevalence of potential hazardous alcohol consumption/active alcohol use was 57.1%, and for potentially harmful alcohol use prevalence was 26.5%. Prevalence was higher among females (59.0% and 31.1% respectively) than males (54.4% and 20.0% respectively). Overall, the results of the univariate model fitting indicated that there were qualitative sex differences in the genetic and environmental influences on AUDs, with generally moderate heritability estimates ranging between 0.37 and 0.50. Discussion: At odds with previous research, a harmful/hazardous drinking pattern was more common in this age group among females than a low-risk drinking pattern (where males were overrepresented). Heritability estimates were moderate throughout all measures and cut-offs, with equally high contributions from shared and non-shared environment. Sex-limitation models revealed qualitative sex differences for AUDs, suggesting that different genetic and/or environmental factors influence variation in AUDs in males and females.


Multi-institution prospective trial of reduced-dose craniospinal irradiation (23.4 Gy) followed by conformal posterior fossa (36 Gy) and primary site irradiation (55.8 Gy) and dose-intensive chemotherapy for average-risk medulloblastoma.
Limiting the neurocognitive sequelae of radiotherapy (RT) has been an objective in the treatment of medulloblastoma. Conformal RT to less than the entire posterior fossa (PF) after craniospinal irradiation might reduce neurocognitive sequelae and requires evaluation. Between October 1996 and August 2003, 86 patients, 3-21 years of age, with newly diagnosed, average-risk medulloblastoma were treated in a prospective, institutional review board-approved, multi-institution trial of risk-adapted RT and dose-intensive chemotherapy. RT began within 28 days of definitive surgery and consisted of craniospinal irradiation (23.4 Gy), conformal PF RT (36.0 Gy), and primary site RT (55.8 Gy). The planning target volume for the primary site included the postoperative tumor bed surrounded by an anatomically confined margin of 2 cm that was then expanded with a geometric margin of 0.3-0.5 cm. Chemotherapy was initiated 6 weeks after RT and included four cycles of high-dose cyclophosphamide, cisplatin, and vincristine. At a median follow-up of 61.2 months (range, 5.2-115.0 months), the estimated 5-year event-free survival and cumulative incidence of PF failure rate was 83.0% +/- 5.3% and 4.9% +/- 2.4% (+/- standard error), respectively. The targeting guidelines used in this study resulted in a mean reduction of 13% in the volume of the PF receiving doses >55 Gy compared with conventionally planned RT. The reductions in the dose to the temporal lobes, cochleae, and hypothalamus were statistically significant. This prospective trial has demonstrated that irradiation of less than the entire PF after 23.4 Gy craniospinal irradiation for average-risk medulloblastoma results in disease control comparable to that after treatment of the entire PF.


Why Patients Fall Through the Cracks: Assessment of Patients' Overactive Bladder Treatment.
Objective: Despite an established treatment algorithm for overactive bladder (OAB), it is unclear how many patients proceed through each step. Our objective was to evaluate the percentage of patients receiving each step of care and identify reasons why patients did not receive certain treatments. Methods: This was a retrospective cohort study with cross-sectional survey of new OAB patients. The medical record was queried for relevant patient characteristics and documentation of conservative, medical, and third-line therapies. In the survey, patients were asked about current bladder symptoms and reasons why they did not use certain treatments. Descriptive statistics were used for analysis. Results: One hundred eleven patients met the inclusion criteria; the most common diagnosis was mixed incontinence (40%, n = 45). The median number of visits for OAB was 2 (range 1-8). On retrospective analysis, 64% (71) of patients had documented attempts at conservative therapy. Seventy-six percent (84) of patients attempted medical therapy, and only 11% (12) progressed to any third-line therapy. Fifty-nine percent (64) of eligible patients responded to the survey. Fifty-three percent (34) of respondents reported persistent moderate to very severe bother due to bladder symptoms. Thirty percent to fifty percent of patients who did not attempt one or more of the three levels of OAB therapy reported that they were never offered that treatment option. Conclusions: Many patients do not progress to the next steps in OAB therapy despite failure of more conservative treatments. Barriers to care included limited follow-up and education about other therapy options. A formalized institutional care pathway may lead to improved OAB treatment.


Tetrahedral n-type materials: efficient quenching of the excitation of p-type polymers in amorphous films.
Tetrahedral naphthalenediimide compound 1 has been synthesized as an example of a new class of amorphous n-type materials, in which the nondirectionality obtained by its shape is decoupled from its optoelectronic properties. 1 forms bicontinuous films with p-type polymers and effectively quenches the excited state, yielding long-lived mobile charge carriers on pulsed illumination.


Genome-wide association and transcriptional studies reveal novel genes for unsaturated fatty acid synthesis in a panel of soybean accessions.
The nutritional value of soybean oil is largely influenced by the proportions of unsaturated fatty acids (FAs), including oleic acid (OA, 18:1), linoleic acid (LLA, 18:2), and linolenic acid (LNA, 18:3). Genome-wide association (GWAS) studies along with gene expression studies in soybean [Glycine max (L.) Merr.] were leveraged to dissect the genetics of unsaturated FAs. A association panel of 194 diverse soybean accessions were phenotyped in 2013, 2014 and 2015 to identify Single Nucleotide Polymorphisms (SNPs) associated with OA, LLA, and LNA content, and determine putative candidate genes responsible for regulating unsaturated FAs composition. 149 SNPs that represented 73 genomic regions were found to be associated with the unsaturated FA contents in soybean seeds according to the results of GWAS. Twelve novel genes were predicted to be involved in unsaturated FA synthesis in soybean. The relationship between expression pattern of the candidate genes and the accumulation of unsaturated FAs revealed that multiple genes might be involved in unsaturated FAs regulation simultaneously but work in very different ways: Glyma.07G046200 and Glyma.20G245500 promote the OA accumulation in soybean seed in all the tested accessions; Glyma.13G68600 and Glyma.16G200200 promote the OA accumulation only in high OA germplasms; Glyma.07G151300 promotes OA accumulation in higher OA germplasms and suppresses that in lower OA germplasms; Glyma.16G003500 has the effect of increasing LLA accumulation in higher LA germplasms; Glyma.07G254500 suppresses the accumulation of LNA in lower OA germplasms; Glyma.14G194300 might be involved in the accumulation of LNA content in lower LNA germplasms. The beneficial alleles and candidate genes identified might be valuable for improving marker-assisted breeding efficiency and exploring the molecular mechanisms underlying unsaturated fatty acid of soybean.


Depth and frequency dependence of geoacoustic properties on the New England Mud Patch from reflection coefficient inversiona).
Muddy sediments cover significant portions of continental shelves, but their physical properties remain poorly understood compared to sandy sediments. This paper presents a generally applicable model for sediment-column structure and variability on the New England Mud Patch (NEMP), based on trans-dimensional Bayesian inversion of wide-angle, broadband reflection-coefficient data in this work and in two previously published reflection-coefficient inversions at different sites on the NEMP. The data considered here include higher frequencies and larger bandwidth and cover lower reflection grazing angles than the previous studies, hence, resulting in geoacoustic profiles with significantly better structural resolution and smaller uncertainties. The general sediment-column structure model includes an upper mud layer in which sediment properties change slightly with depth due to near-surface processes, an intermediate mud layer with nearly uniform properties, and a geoacoustic transition layer where properties change rapidly with depth (porosity decreases and sound speed, density, and attenuation increase) due to increasing sand content in the mud above a sand layer. Over the full frequency band considered in the new and two previous data sets (400-3125 Hz), there is no significant sound-speed dispersion in the mud, and attenuation follows an approximately linear frequency dependence.


Light-induced self-written waveguide fabrication using 1550 nm laser light.
Light-induced self-written (LISW) optical waveguides were fabricated for the first time, to the best of our knowledge, using a photopolymerizable resin system formed by 1550 nm pulse laser light. A two-photon absorption (TPA) chromophore with a TPA cross section of several hundred Goeppert-Mayer (GM) at 1550 nm was used. Furthermore, the optical interconnection between a single-mode fiber and a fiber Bragg grating was demonstrated by the present technique, using one-way irradiation of 1550 nm laser light through the single-mode fiber. The LISW waveguide formation using 1550 nm laser light offers a new and promising alternative route for optical interconnection in silicon photonics technology.


Effects of calcitonin gene-related peptide on bone resorption mediated by interleukin-1.
We examined the effects of calcitonin gene-related peptide CGRP on the bone resorption stimulated by IL-1 alpha after neonatal mouse calvaria were cultured in vitro and bone resorption was determined by measuring the release of calcium into the medium after alpha 48-hour incubation. CGRP (10(-9)-10(-8) M) blocked completely the IL1 alpha-mediated increase in bone resorption and inhibited the basal bone resorption. In accordance with the effects of calcitonin on osteoclasts, CGRP caused cessation of lamellipodia activity and gradual retraction of lamellipodia when added into the culture medium. Quantitative analysis showed that CGRP (10(-6) M) caused a gradual reduction of osteoclastic surface area and convex perineum. These data show that CGRP inhibits IL1 alpha mediated bone resorption because of its direct regulation of osteoclast activity.


Limitation of the augmentation index for evaluating arterial stiffness.
Although the augmentation index (AIx) is widely used to evaluate arterial stiffness in clinics and research, some conflicting data exist in regard to its validity. We therefore performed a series of studies to test the validity of AIx. The first study in 196 peritoneal dialysis patients showed that AIx in diabetics was lower than that in non-diabetic patients (p<0.05), which was in contradiction with the previous studies. Further analysis showed that AIx was just weakly correlated with pulse pressure (PP)-a known index of arterial stiffness. We also found that the increase of augmentation pressure (AP) was usually accompanied with increased central PP (C-PP). As AP and C-PP are used as the numerator and denominator in the AIx formula, an increase in the numerator (AP) would not necessarily result in an increase of the quotient (AIx) unless the denominator (C-PP) was stable. We then conducted a second study trying to test the validity of AIx through mathematical ratiocination. The increases in the central second peak (P2) and AP were assumed to represent increased arterial stiffness. Different values of AIx were obtained by varying the central initial systolic peak (P1) and diastolic pressure (DP). Mathematical ratiocination showed that AIx was dependent on multiple factors, F=(DeltaSP-DeltaDP)x(P1-P2)+(DeltaP2-DeltaP1)x(SP-DP), which suggested that a change of AIx would not always be attributable to changes in P2 and AP. This speculation was further proved by clinical data in our third study. In conclusion, through a series of studies and ratiocination, we showed that the augmentation index (AIx or AIx@75bpm) might not be a sensitive surrogate for a change in central pressure waveforms, which is a manifestation of change in large artery function. The limitation of AIx as an index of arterial stiffness is rooted in its formula, which has a clear mathematical flaw.


Asthma. The states' challenge.
At the national level, asthma is increasingly being recognized as an important public health problem. Because of the significant role of environmental exposure in asthma morbidity, public health agencies have a critical role to play in the surveillance and prevention of the disease. In April 1996, the Council of State and Territorial Epidemiologists, with assistance from the Centers for Disease Control and Prevention, surveyed state and territorial public health departments to determine the status of their asthma surveillance and intervention programs. Of the 51 health departments that responded, only eight reported that they had implemented an asthma control program within the previous 10 years. Reasons cited for not having programs included lack of funds, shortage of personnel, and asthma not being a priority. Most states were unable to assess the burden of asthma because they lack data or face barriers to using existing data. Removing barriers to the use of data is a first step toward defining the scope of the asthma problem.


Towards a Computer Aided Prognosis for Brain Glioblastomas Tumor Growth Estimation.
Bridging the gap between mathematical and biological models and clinical applications could be considered as one of the new challenges of medical image analysis over the ten last years. This paper presents an advanced and convivial algorithm for brain glioblastomas tumor growth modelization. The brain glioblastomas tumor region would be extracted using a fast distribution matching developed algorithm based on global pixel wise information. A new model to simulate the tumor growth based on two major elements: cellular automata and fast marching method (CFMM) has been developed and used to estimate the brain tumor evolution during the time. On the basis of this model, experiments were carried out on twenty pathological MRI selected cases that were carefully discussed with the clinical part. The obtained simulated results were validated with ground truth references (real tumor growth measure) using dice metric parameter. As carefully discussed with the clinical partner, experimental results showed that our proposed algorithm for brain glioblastomas tumor growth model proved a good agreement. Our main purpose behind this research was of course to make advances and progress during clinical explorations helping therefore radiologists in their diagnosis. Clinical decisions and guidelines would be hence so more focused with such an advanced tool that could help clinicians and ensuring more accuracy and objectivity.


Promoting supportive parenting in new mothers with substance-use problems: a pilot randomized trial of residential treatment plus an attachment-based parenting program.
This pilot randomized trial tested the feasibility and efficacy of supplementing residential substance-abuse treatment for new mothers with a brief, yet rigorous, attachment-based parenting program. Twenty-one predominantly (86%) White mothers and their infants living together in residential substance-abuse treatment were randomly assigned to the program (n = 11) or control (n = 10) group. Program mothers received 10 home-based sessions of Dozier's Attachment and Biobehavioral Catch-up (ABC) intervention. Postintervention observations revealed more supportive parenting behaviors among the randomly assigned ABC mothers.


Novel missense mutations in the TRPS1 transcription factor define the nuclear localization signal.
Deletion or mutation of the TRPS1 gene leads to the tricho-rhino-phalangeal syndromes (TRPS). The gene encodes a zinc-finger transcription factor, which contains two regions with basic amino acids LRRRRG (NLS1) and RRRTRKR (NLS2) that resemble potential nuclear localization signals (NLSs). Here, we describe the identification of novel TRPS1 mutations in patients with TRPS type I (TRPS I) and provide, by reconstructing the mutant TRPS1 proteins and subcellular localization studies, evidence that only the RRRTRKR motif functions as a NLS. Two different mutations affect the last arginine residue of this motif. The exchanges of arginine to histidine, found in two unrelated patients with TRPS I, as well as the exchange of arginine to cysteine, found in another unrelated patient, prevent the translocation of the mutant TRPS1 to the nucleus when ectopically expressed in COS 7 cells. In contrast, a mutant that lacks the conserved GATA-type zinc-finger domain and most of the LRRRRG motif is able to enter the nucleus.


Paired Opposite 4 mm Clear Corneal Incisions on Steep Meridian during Phacoemulsification.
To evaluate the effect of opposite clear corneal incisions (OCCI) with 4 mm incisions on the steep meridian on postoperative astigmatism. This study was performed on 64 eyes of 55 patients with keratometric astigmatism of ≥ 1 diopter (D) undergoing phacoemulsification. Patients were divided into two groups, with-the-rule (WTR) astigmatism and against-the-rule (ATR) astigmatism. Initial incisions in the WTR group were performed on the temporal side with 3.2 mm keratome and paired stab incisions were performed on the steep meridian. At the end of the surgery, stab incisions were enlarged to 4 mm. Follow-up visits were scheduled at 1, 3, 6, and 12 months postoperatively, which included refraction and keratometry. It was found that the mean preoperative keratometric astigmatism was 2.06 ± 0.86 D. The postoperative mean keratometric astigmatism was 1.3 ± 0.7 D after 1 month and 1.2 ± 0.7 D after 12 months. The mean astigmatism correction between the preoperative measure and that taken at 1 month was statistically significant (P = 0.001), but there was no significant change in the severity of astigmatism afterward. The mean surgically-induced astigmatism was found to be 1.99 ± 0.9 D. The 12-month changes of mean absolute astigmatism were: 1.06 ± 0.7 D in the WTR group, and 0.53 ± 0.7 D in the ATR group. The difference between the two groups was statistically significant (P = 0.02). Based on our findings, we posit that paired OCCI on the steep axis, using 4 mm incisions is an effective technique to correct preoperative astigmatism.


Long-term Follow-up of MEN1 Patients Who Do Not Have Initial Surgery for Small ≤2 cm Nonfunctioning Pancreatic Neuroendocrine Tumors, an AFCE and GTE Study: Association Francophone de Chirurgie Endocrinienne & Groupe d'Etude des Tumeurs Endocrines.
To report long-term follow-up of patients with multiple endocrine neoplasia type 1 (MEN1) and nonfunctioning pancreatic neuroendocrine tumors (NF-PET). Pancreaticoduodenal tumors occur in almost all patients with MEN1 and are a major cause of death. The natural history and clinical outcome are poorly defined, and management is still controversial for small NF-PET. Clinical outcome and tumor progression were analyzed in 46 patients with MEN1 with 2 cm or smaller NF-PET who did not have surgery at the time of initial diagnosis. Survival data were analyzed using the Kaplan-Meier method. Forty-six patients with MEN1 were followed prospectively for 10.7 ± 4.2 (mean ± standard deviation) years. One patient was lost to follow-up and 1 died from a cause unrelated to MEN1. Twenty-eight patients had stable disease and 16 showed significant progression of pancreaticoduodenal involvement, indicated by increase in size or number of tumors, development of a hypersecretion syndrome, need for surgery (7 patients), and death from metastatic NF-PET (1 patient). The mean event-free survival was 13.9 ± 1.1 years after NF-PET diagnosis. At last follow-up, none of the living patients who had undergone surgery or follow-up had evidence of metastases on imaging studies. Our study shows that conservative management for patients with MEN1 with NF-PET of 2 cm or smaller is associated with a low risk of disease-specific mortality. The decision to recommend surgery to prevent tumor spread should be balanced with operative mortality and morbidity, and patients should be informed about the risk-benefit ratio of conservative versus aggressive management when the NF-PET represents an intermediate risk.


Antibiotic resistance: Italian awareness survey 2016.
Antimicrobial resistance has become a public health priority worldwide. The WHO conducted a survey concerning the personal use of antibiotics, knowledge of appropriate use and awareness of the issue of resistance. A similar survey was conducted in Italy involving 666 young university students and 131 seniors attending courses of the University of the third age. Antibiotics seem to be taken with moderate frequency and appropriately: 30% of respondents took them in the past six months and 94% took these drugs only prescribed by a doctor, in the correct dose and for the proper duration. Notable confusion concerning the conditions treatable with antibiotics was detected (only 30% indicated gonorrhea, and 30-40% believed that antibiotics should be employed for fever, cold, and flu), while 94% of participants seemed aware of the problem of antibiotic resistance. Most of the respondents identified the behaviors that can reduce the phenomenon of resistance (regular handwashing and use of antibiotics only when prescribed and needed). The results of our survey, that involved people of high level of instruction and living in urban areas of northern regions, cannot be extended to all the Italian population. However, they provide valid elements to promote initiatives aimed to a more aware use of antibiotics.


[Concentric left ventricular hypertrophy in patients with hypertension. When should ventricular hyperexcitability be searched for?].
The main objective is to determine when concentric left ventricular hypertrophy (LVH) increased ventricular ectopic activity in essential hypertension. Twenty-four hours Holter monitoring was recorded in 56 patients with essential hypertension: 20 without LVH and 36 with concentric LVH determined by echocardiography (left ventricular mass greater than 215 g). According the degree of septal thickness (ST), patients were classed in 4 groups: (formula; see text) This study allows to conclude that mean and severe concentric LVH (ST greater than or equal to 12) detected by echo are associated with a greater PVC and a higher Lown's class ventricular ectopy. The degree of ST was strong correlated with the Lown's classification (r = 0.6, p less than .0001).


Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk.
Matrix metalloproteinase (MMP) 2, MMP7 and MMP9 are important members of the MMP family. Four polymorphisms in the promoter region of these MMPs, which are MMP2 -1306 C>T, MMP2 -735 C>T, MMP7 -181 A>G and MMP9 -1562 C>T, have been reported to be functional and may contribute to genetic susceptibility to cancers. However, the associations between these polymorphisms and cancer risk remain inconclusive due to conflicting results from different case-control studies. To better evaluate the role of these polymorphisms in cancer development, we conducted a meta-analysis that included 51 studies, with more than 40,000 subjects. The results showed that under dominant genetic model, MMP2 -1306 T was associated with lower susceptibility to lung cancer [odds ratio (OR) = 0.50, 95% confidence interval (CI) 0.43-0.59, P(heterogeneity) = 0.147, I(2) = 44.1%], head and neck cancer (OR = 0.53, 95% CI 0.41-0.69, P(heterogeneity) = 0.974, I(2) = 0.0%) and oesophageal cancer (OR = 0.67, 95% CI 0.55-0.80, P(heterogeneity) = 0.593, I(2) = 0.0%); MMP2-735T was associated with lower risk in lung cancer (OR = 0.65, 95%CI 0.53-0.79, P(heterogeneity) = 0.42, I(2) = 0.0%) and oesophageal cancer (OR = 0.84, 95% CI 0.70-0.99, P(heterogeneity) = 0.206, I(2) = 37.4%); MMP7 -181 AG and GG genotype carriers had an increased gastric cancer risk (OR = 1.90, 95% CI 1.43-2.51, P(heterogeneity) = 0.992, I(2) = 0.0%) and MMP9 -1562 C>T was not associated with cancer risk in the whole group analysis (OR = 0.99, 95% CI 0.91-1.08, P(heterogeneity) = 0.419, I(2) = 3.0%) and subgroup analyses. In all, our meta-analysis suggests that MMP2 -1306 C>T, MMP2 -735 C>T and MMP7 -181 A>G may play allele-specific roles in cancer development, while MMP9 -1562 C>T may not be a major risk factor for most cancer types. Large case-control studies should be performed to clarify the possible roles of these four polymorphisms in different kinds of cancer in more detail.


Timely Identified Early Migration of Peripherally Inserted Central Catheter by Focused Ultrasound.
A peripherally inserted central venous catheter (PICC) has been widely applied to central venous assess. There were some known complications such as phlebitis, leakage, blockage, dislodgment, breakage, or malposition of PICC. Catheter migration was assessed by using chest radiograph or administering contrast medium. Herein, we report a 77-year-old woman presenting to emergency department with odynophagia and left neck swelling of 3 days duration. The initial impression was deep neck infection. Focused ultrasound identified a hyperechoic tube with thrombosis in left jugular vein, which indicated migration of PICC. Clinical symptoms immediately resolved after removal of PICC and anticoagulation therapy.


Cloning of deoxynucleoside monophosphate kinase genes and biosynthesis of deoxynucleoside diphosphates.
The genes encoding four deoxynucleoside monophosphate kinase (dNMP kinase) enzymes, including ADK1 for deoxyadenylate monophosphate kinase (AK), GUK1 for deoxyguanylate monophosphate kinase (GK), URA6 for deoxycytidylate monophosphate kinase (CK), and CDC8 for deoxythymidylate monophosphate kinase (TK), were isolated from the genome of Saccharomyces cerevisiae ATCC 2610 strain and cloned into E. coli strain BL21(DE3). Four recombinant plasmids, pET17b-JB1 containing ADK1, pET17b-JB2 containing GUK1, pET17b-JB3 containing URA6, and pET17b-JB4 containing CDC8, were constructed and transformed into E. coli strain for over-expression of AK, GK, CK, and TK. The amino acid sequences of these enzymes were analyzed and a putative conserved peptide sequence for the ATP active site was proposed. The four deoxynucleoside diphosphates (dNDP) including deoxyadenosine diphosphate (dADP), deoxyguanosine diphosphate (dGDP), deoxycytidine diphosphate (dCDP), and deoxythymidine diphosphate (dTDP), were synthesized from the corresponding deoxynucleoside monophosphates (dNMP) using the purified AK, GK, CK, and TK, respectively. The effects of pH and magnesium ion concentration on the dNDP biosynthesis were found to be important. A kinetic model for the synthetic reactions of dNDP was developed based on the Bi-Bi random rapid equilibrium mechanism. The kinetic parameters including the maximum reaction velocity and Michaelis-Menten constants were experimentally determined. The study on dNDP biosynthesis reported in this article are important to the proposed bioprocess for production of deoxynucleoside triphosphates (dNTP) that are used as precursors for in vitro DNA synthesis. There is a significant advantage of using enzymatic biosyntheses of dNDP as compared to the chemical method that has been in commercial use.


[Managment of the suicidal patient in the out-patient practice].
Appropriate handling of suicidal tendencies is for certain one of the most important duties within ambulant treatment. As various examples show, occurrence of a suicidal tendency can be chronical as well as acute. Well-known risk factors including current psychopathology and psychodynamics help to identify and assess a suicidal tendency and to take necessary therapeutic options. Some of these can be applied in general, others have to be tailored specifically with respect to the mental disorder in question. Suicide often occurs in an interpersonal context. This fact underlines on one hand the importance and the therapeutic potential of the relationship between the patient and the therapist, on the other hand it results in many cases in a highly stressful situation for the therapist. Significant attention has to be paid to counter transference and its control. Development of an emergency plan and challenges of a "non-suicidal-contract" are discussed. We recommend an agreement with the patient to contact the therapist in case of not feeling able to control his/her own actions. This agreement includes our guarantee of permanent reachability.


First Report of Aphanomyces euteiches Race 1 and Race 2 Causing Aphanomyces Root Rot on Alfalfa (Medicago sativa) in South Dakota.
Aphanomyces euteiches causes Aphanomyces root rot (ARR) in alfalfa (Medicago sativa), along with root rot on many other legumes, including pea, clover, and lentil (Malvick et al., 2009). In 2020, South Dakota (SD) planted the most acres of alfalfa in the United States, which demonstrates the importance of alfalfa to the state. Several SD growers reported alfalfa establishment problems likely to be associated with ARR. Soil samples were collected from 16 fields under commercial alfalfa production in Lake County, SD in June 2020. Composite soil samples based on 24 subsamples were collected in a W-shaped pattern at a depth of 15 cm. Collected soil was sieved, and 80 cm3 was placed in plastic pots (6 cm x 6 cm). Each pot was planted with 25 seeds, covered with an additional 15 cm3 soil, and placed in a growth chamber with a 16-hour photoperiod at temperatures of 24 and 19 ℃ (day and night). Alfalfa seedlings, including Saranac (susceptible to races R1 and R2), WAPH-1 (resistant only to R1), WAPH-5 (resistant to both R1 and R2), and Mustang 625 (resistant to both R1 and R2 and coated with mefenoxam) grew in collected soil for 7 days, followed by 4 days under flooded conditions. Trays were drained, and at 21 days after planting (DAP), roots were removed from soil, washed in distilled water, and rated to measure severity of disease symptoms (Samac et al., 2015). The average severity index (ASI) used a 1-5 disease severity scale, 5 being a dead plant and 1 being no symptoms present (http://www.naaic.org/stdtests/Aphano.html). Race was based on ASI where R1 included an ASI of ≥3 for Saranac and <3 for WAPH-1, and R2 included an ASI of >3.0 for Saranac and WAPH-1 and <3.0 for WAPH-5 (Malvick and Grau, 2001). Race-typing experiments were repeated twice with six replicate pots per alfalfa cultivar per experiment and determined the presence of both R1 and R2 in Lake County, SD. ASI values for Mustang 625 and WAPH-5 were similar across all fields evaluated, which indicates limited confounding effects of other root rotting pathogens. DNA was extracted from three symptomatic roots from each field and was PCR amplified using A. euteiches specific primers (Vandemark et al., 2002). A PCR product was observed in all 16 fields evaluated, and the absence of a product was observed when DNA was extracted from alfalfa roots grown in vermiculite. Following race-typing, infected alfalfa roots were surfaced sterilized and placed on Aphanomyces selective media consisting of mefenoxam and benomyl in cornmeal agar (CMA) (Pfender et al., 1984). Isolates were identified as A. euteiches based on hyphal morphology (Malvick and Grau, 2001). Alfalfa seedlings (Saranac) were grown in vermiculite under growth conditions used for the race-typing assay and inoculated 6 DAP with two isolates of A. euteiches. Inoculation was completed using half plates of one week old A. euteiches mycelium on CMA blended with one liter of water (Samac et al., 2015). At 35 DAP, control alfalfa seedlings inoculated with blended CMA and water remained asymptomatic, and alfalfa infected with A. euteiches displayed symptoms including honey-brown colored lesions. For confirmation of Koch's postulates, DNA from three re-infected seedlings was again PCR amplified using A. euteiches specific primers and confirmed our previous work. This is the first report of either R1 or R2 of A. euteiches causing ARR on alfalfa in SD. To avoid future yield loss, SD growers should consider planting available alfalfa cultivars that have resistance to both races of A. euteiches.


Participants strengthen clinical trial research: the vital role of participant advisors in the Breast Cancer Prevention Trial.
Views regarding the rights and roles of participants in clinical trial research have changed extensively over the past several decades. Such changes have included moving from paternalistic views, in which human subjects often were totally uninformed of research participation, to a perspective that recognized certain rights of human subjects. In recent years, the consumer rights movement, a growing customer service perspective in health care, and the growth of a variety of advocacy groups have brought further change in attitudes and efforts to include consumer representatives and research participants in a variety of advisory roles. The BCPT PAB is a model for a way to involve research study participants in an expanded role. Members of the board initiate efforts to promote participation and inform potential participants about the trial. They help establish outreach efforts to recruit individuals from underrepresented populations. They serve as effective spokespersons for the trial to the media at both local and national levels, and they give highly useful guidance to the NSABP and the NCI regarding a variety of aspects of clinical trials. Beyond the formal responsibilities that were outlined when the board was established, the trial participants serving on the advisory board also have provided inspiration and motivation for other participants as well as for the clinicians, researchers, and administrators conducting the BCPT. The extensive contributions of the advisory board members confirm and add to the understanding of the variety of ways that clinical research participants can play a role in strengthening such research efforts. Further, the BCPT PAB may serve as a model strategy for drawing on the unique resource represented by the participants in clinical trial studies.


Tb(III)-doped silica nanoparticles for sensing: effect of interfacial interactions on substrate-induced luminescent response.
The present work introduces the easy modification of the water-in-oil microemulsion procedure aimed at the doping of the Tb(III) complexes within core or shell zones of the silica nanoparticles (SNs), which are designated as "core-shell", "shell", and "core". The dye molecules, chelating ligands, and copper ions were applied as the quenchers of Tb(III)-centered luminescence through dynamic or/and static mechanisms. The binding of the quenchers at the silica/water interface results in the quenching of the Tb(III) complexes within SNs, which, in turn, is greatly dependent on the synthetic procedure. The luminescence of "core" SNs remains unchanged under the binding of the quenchers at the silica/water interface. The quenching through dynamic mechanism is more significant for "core-shell" and "shell" than for "core" SNs. Thus, both "core-shell" and "shell" SNs have enough percentage of the Tb(III) complexes located close to the interface for efficient quenching through the energy transfer. The quenching through the ion or ligand exchange is most efficient for "core-shell" SNs due to the greatest percentage of the Tb(III) complexes at the silica/water interface, which correlates with the used synthetic procedure. The highlighted regularities introduce the applicability of "core-shell" SNs used as silica beads for phosphatidylcholine bilayers in sensing their permeability toward the quenching ions.