Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats.
Charcot-Marie-Tooth type 1A (CMT1A) is the most common type of hereditary motor and sensory neuropathies (HMSN), caused by the duplication of the 17p11.2 region that includes the PMP22 gene. Reciprocal deletion of the same region is the main cause of hereditary neuropathy with liability to pressure palsies (HNPP). CMT1A accounts for approximately 50% of HMSN patients. Diagnostics of CMT1A and HNPP are based on quantitative analysis of the affected region or RFLP detection of breakage points. The aim of this study was to improve the sensitivity and efficiency of CMT1A and HNPP genetic diagnostics by introducing analysis of six STR markers (D17S261-D17S122-D17S839-D17S1358-D17S955-D17S921) spanning the duplicated region. Forty-six CMT1A and seven HNPP patients, all genetically diagnosed by RFLP analysis, were tested for duplication or deletion using six STR markers. In all CMT1A and HNPP patients, microsatellite analysis comprising six STR markers confirmed the existence of a duplication or deletion. In 89% (41/46) CMT1A patients the confirmation was based on detecting three alleles on at least one locus. In the remaining 11% (5) CMT1A patients, duplication was also confirmed based on two peaks with clear dosage difference for at least two different markers. All HNPP patients (7/7) displayed only one allele for each analyzed locus. Microsatellite analysis using six selected STR loci showed a high level of sensitivity and specificity for genetic diagnostics of CMT1A and HNPP. The results here strongly suggest STR marker analysis as a method of choice in PMP22 duplication/deletion testing.


Posterior composite resins.
A quarter of a century ago, composite resin was introduced and quickly outmoded silicate cement and acrylic resin as a restorative material. Although composite resin cannot replace amalgam, it has a strong foothold in dentistry, most notably for its superior color-matching ability. This article contrasts many properties of composite resin to amalgam, and takes a look at new developments in posterior esthetic materials.


Darbepoetin alfa: a new therapeutic agent for renal anemia.
Darbepoetin alfa is a super-sialylated analog of human erythropoietin that has a longer circulating half-life in vivo compared to both native and recombinant hormone. It has the same mechanism of action as erythropoietin, stimulating the same surface membrane receptor and triggering the same intracellular chain of events. An extra two N-linked carbohydrate chains, however, gives darbepoetin alfa greater metabolic stability in vivo, and its terminal half-life after intravenous administration is approximately three times longer than for intravenous erythropoietin. This in turn allows injections of the drug to be given less frequently, and studies have shown that once-weekly and once-every-other-week dosing can maintain the hemoglobin concentration in patients with renal anemia. The recommended starting dose for darbepoetin alfa is 0.45 microg/kg once weekly for both IV and SC administration, with subsequent titration based on the hemoglobin concentration. The adverse event profile is very similar to that seen with rHuEPO, and no antibodies have been detected in several thousand patients exposed to the drug, some of whom have been treated for up to five years now. Following a clinical research program that began in November 1996, darbepoetin alfa was finally approved by the European Commission in June 201, and by the FDA in September 201.


Gene map of the cow: conservation of linkage with mouse and man.
Cattle-hamster hybrid somatic cells segregating cattle chromosomes have been analyzed by cellulose-acetate electrophoresis for 28 enzyme gene products including the previously unassigned loci for GAPD, ITPA, ADA, ACO1, GDH, GUK, CAT, and GLO1. These 28 loci are organized into 21 independent syntenic groups bringing the composite bovine gene map to 35 loci on 24 syntenic groups. Thirty-two homologous genes now have been mapped in humans, mice, and cattle. Conservation of cattle and human linkage groups is evidenced by only three linkage discordancies among these 32 loci as contrasted to nine discordancies among the same loci in the human and mouse maps.


Transplantation of oligodendrocyte precursor cells improves locomotion deficits in rats with spinal cord irradiation injury.
Demyelination contributes to the functional impairment of irradiation injured spinal cord. One potential therapeutic strategy involves replacing the myelin-forming cells. Here, we asked whether transplantation of Olig2(+)-GFP(+)-oligodendrocyte precursor cells (OPCs), which are derived from Olig2-GFP-mouse embryonic stem cells (mESCs), could enhance remyelination and functional recovery after spinal cord irradiation injury. We differentiated Olig2-GFP-mESCs into purified Olig2(+)-GFP(+)-OPCs and transplanted them into the rats' cervical 4-5 dorsal spinal cord level at 4 months after irradiation injury. Eight weeks after transplantation, the Olig2(+)-GFP(+)-OPCs survived and integrated into the injured spinal cord. Immunofluorescence analysis showed that the grafted Olig2(+)-GFP(+)-OPCs primarily differentiated into adenomatous polyposis coli (APC(+)) oligodendrocytes (54.6±10.5%). The staining with luxol fast blue, hematoxylin & eosin (LFB/H&E) and electron microscopy demonstrated that the engrafted Olig2(+)-GFP(+)-OPCs attenuated the demyelination resulted from the irradiation. More importantly, the recovery of forelimb locomotor function was enhanced in animals receiving grafts of Olig2(+)-GFP(+)-OPCs. We concluded that OPC transplantation is a feasible therapy to repair the irradiated lesions in the central nervous system (CNS).


Distinct roles for the small GTPases Cdc42 and Rho in endothelial responses to shear stress.
Shear stress, the tangential component of hemodynamic forces, plays an important role in endothelial remodeling. In this study, we investigated the role of Rho family GTPases Cdc42 and Rho in shear stress-induced signal transduction and cytoskeleton reorganization. Our results showed that shear stress induced the translocation of Cdc42 and Rho from cytosol to membrane. Although both Cdc42 and Rho were involved in the shear stress-induced transcription factor AP-1 acting on the 12-O-tetradecanoyl-13-phorbol-acetate-responsive element (TRE), only Cdc42 was sufficient to activate AP-1/TRE. Dominant-negative mutants of Cdc42 and Rho, as well as recombinant C3 exoenzyme, attenuated the shear stress activation of c-Jun NH2-terminal kinases (JNKs), suggesting that Cdc42 and Rho regulate the shear stress induction of AP-1/TRE activity through JNKs. Shear stress-induced cell alignment and stress fiber formation were inhibited by the dominant-negative mutants of Rho and p160ROCK, but not by the dominant-negative mutant of Cdc42, indicating that the Rho-p160ROCK pathway regulates the cytoskeletal reorganization in response to shear stress.


Lifestyle medicine course for family medicine residents: preliminary assessment of the impact on knowledge, attitudes, self-efficacy and personal health.
The WHO estimates that by 2020 two-thirds of the diseases worldwide will be the result of unhealthy lifestyle habits. Less than half of primary care physician graduates feel prepared to give lifestyle behaviour counselling. Our objective was to evaluate the impact of lifestyle medicine (LM) course on self-reported knowledge, attitudes, self-efficacy and health behaviour of family medicine residents. Based on the Israeli syllabus for the study of LM, we delivered five face to face 20 H courses. Pre/post data were collected by knowledge, attitudes, self-efficacy and personal health survey: RESULTS: A total of 112 family medicine residents participated in one of the five courses, of which 91 (81.3%) filled both pre and post surveys. Participates showed an improvement in self-reported knowledge and capacity to manage patients in regard to smoking, weight management and physical activity. An improvement was noted in personal health behaviour of overweight participant's in regard to self-reported physical activity. A comprehensive LM syllabus based course has a positive impact on family medicine residents LM counselling abilities. We suggest that LM course should be considered as a potential permanent addition to the family medicine residency programme.


Statistical performance of local attractor dimension estimators in non-Axiom A dynamical systems.
We investigate various estimators based on extreme value theory (EVT) for determining the local fractal dimension of chaotic dynamical systems. In the limit of an infinitely long time series of an ergodic system, the average of the local fractal dimension is the system's global attractor dimension. The latter is an important quantity that relates to the number of effective degrees of freedom of the underlying dynamical system, and its estimation has been a central topic in the dynamical systems literature since the 1980s. In this work, we propose a framework that combines phase space recurrence analysis with EVT to estimate the local fractal dimension around a particular state of interest. While the EVT framework allows for the analysis of high-dimensional complex systems, such as the Earth's climate, its effectiveness depends on robust statistical parameter estimation for the assumed extreme value distribution. In this study, we conduct a critical review of several EVT-based local fractal dimension estimators, analyzing and comparing their performance across a range of systems. Our results offer valuable insights for researchers employing the EVT-based estimates of the local fractal dimension, aiding in the selection of an appropriate estimator for their specific applications.


Multiple components of blood group A and B antigens in human erythrocyte membranes and their difference between A1 and A2 status.
Human type O erythrocyte membranes were converted to type A1 by purified human A1-enzyme, to type A2 by purified human A2-enzyme, and to type B by purified human B-enzyme in the presence of radioactive sugar donors (i.e., UDP-N-acetylgalactosamine for A-enzyme and UDP-galactose for B-enzyme, respectively). Type A2 erythrocyte membranes were also converted to type A1 by purified A1-enzyme A1-enzyme. The labeled blood group antigens (A1, A2, and B) thus produced were analyzed by sodium dodecyl sulfate gel electrophoresis and by isoelectric focusing. It was demonstrated that blood group antigens on erythrocyte membranes are mostly (greater than 80%) glycolipid, not glycoprotein. The blood group glycolipids were presumably conjugated with other membrane materials and formed three major components in type A1 and type B erythrocyte membranes. However, two of the three components were absent in type O erythrocyte membranes converted to type A2. These results indicate the heterogeneity of blood group components in erythrocytes membranes and the qualitative difference between A1 and A2 antigens on these membranes.


The isolation and characterization of enriched microvascular endothelial cells from mouse adipose tissue. The induction of class II molecules of the major histocompatibility complex (MHC) by interferon-gamma (IFN-gamma).
Collagenase digestion and selective filtration have been used to establish primary cultures from mouse omentum of cells enriched for microvascular endothelium. In culture these cells exhibit a cobblestone morphology characteristic of endothelial cells, metabolize an acetylated low-density lipoprotein, and exhibit trace levels of angiotensin-converting enzyme activity. In primary cultures, the cells are negative for class II molecules (Ia) of the major histocompatibility complex (MHC) but can be induced to express these molecules by exposure to a supernatant from concanavalin A (ConA)-treated rat spleen cells or by recombinant interferon-gamma (rIFN-gamma). This procedure can provide a readily available source of enriched endothelial cells which can be used to understand the interactions between these cells and cells of the immune system.


Influence of the sulfation degree of glycosaminoglycans on their multilayer assembly with poly-l-lysine.
We report on the build-up and the intrinsic properties of polyelectrolyte multilayer films from poly-l-lysine and glycosaminoglycans (GAGs) with different sulfation degree, i.e. different charge. We used three complementary techniques, namely electrokinetic analysis (EKA), quartz-crystal microbalance with dissipation (QCM-D) and surface plasmon resonance (SPR), to characterize the assembly process and to assess the properties of the obtained films. EKA elucidated the contribution of the polymers charged groups to the net surface charge of the films and suggested that the assembly process is not solely driven by electrostatic interactions. The combined analysis of QCM-D and SPR data demonstrated that the mechanical properties of the films are dependent on the polymer charge: sulfated GAGs (heparin and chondroitin sulfate) form elastic films while hyaluronan (no sulfation) assembles into multilayer constructs with viscous behavior. The contribution of the water content to these distinct regimes is also discussed. Finally, we show that rather complete characterization of the film properties is possible by SPR employing the two-wavelength and two-media approach: thickness, adsorbed mass, refractive index, and interaction kinetics of the assembly process can be studied by SPR alone.


Factors influencing wound healing after surgery for metastatic disease of the spine.
The study group consisted of 53 patients who underwent 75 operations for spine metastases. Patient and tumor demographic factors, preoperative nutritional status, and perioperative adjunctive therapy were retrospectively reviewed. To determine the risk factors for wound breakdown and infection in patients undergoing surgery for spinal metastases. Spinal fusion using spine implants may be associated with an infection rate of 5% or more. Surgery for spine metastases is associated with an infection rate of more than 10%. Factors other than the type of surgery performed may account for the greater infection rate. Data were obtained by reviewing patient records. Age, sex, and neurologic status of the patient; tumor type and site; and surgical details were noted. Adjunctive treatment with corticosteroids and radiotherapy was recorded. Nutritional status was evaluated by determining serum protein and serum albumin concentrations and by total lymphocyte count. Wound breakdown and infection occurred in 15 of 75 wounds. No patient or tumor demographic factors other than intraoperative blood loss (P < 0.1) were statistically associated with infection. The correlation between preoperative protein deficiency (P < 0.01) or perioperative corticosteroid administration (P < 0.10) and wound infection was significant. There was no statistical correlation between lymphocyte count or perioperative radiotherapy and wound infection. The results indicate that preoperative protein depletion and perioperative administration of corticosteroids are risk factors for wound infection in patients undergoing surgery for spine metastases. Perioperative correction of nutritional depletion and cessation of steroid therapy may reduce wound complications.


Serum calcium as an indicator of persistent organ failure in acute pancreatitis.
Decreased level of serum calcium was commonly seen in critical illness. Hypocalcemia was significantly more frequent in patients with severe form of acute pancreatitis (AP), and a negative correlation was observed between endotoxemia and serum calcium in AP. AP patients with persistent organ failure (POF) show an extremely high mortality. The association underlying calcium and POF in AP has not been characterized. We conducted a retrospective cohort study of adult patients who presented within 72hours from symptom onset of AP at our center between January 2014 and May 2015. Demographic parameters on admission, organ failure assessment, laboratory data and in-hospital mortality were compared between patients with and without POF. Uni-and multi-variate logistic regression analyses were utilized to evaluated the predictive ability of serum calcium. A total of 128 consecutive AP patients, including 29 with POF, were included. Compared to patients without POF, patients with POF showed a significantly lower value of serum calcium on admission (2.11±0.46 vs. 1.55±0.36mmol/L, P<0.001). After multivariate logistic analysis, serum calcium remained an independent risk factor for POF (Hazard ratio 0.21, 95% confident interval: 0.08-0.58; P=0.002). A calcium value of 1.97mmol/L predicted POF with an area under the curve (AUC) of 0.888, a sensitivity with 89.7% and specificity with 74.8%, respectively. Our results indicate that serum calcium on admission is independently associated with POF in AP and may serve as a potential prognostic factor.


Clinical trials with 5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide (NSC-82196) given intravenously.
Clinical trials with 5-[3,3-bis(2-chloroethyl)-1-triazeno]imidazole-4-carboxamide (NSC-82196) given intravenously to 32 patients with various tumors suggest that the maximum tolerated dose is 5 g/m2 divided into five consecutive daily injections and repeated at 5-6-week intervals. The principal dose-limiting toxic effect was severe nausea and vomiting. Pain and flushing after administration were often severe. The time of onset and the degree of severity of delayed bone marrow toxicity (nadir, 31-35 days) were erratic, but the toxicity was reversible and usually tolerable. One patient with lymphosarcoma had an objective response. Phase II trials with NSC-82196 in patients with lymphoma and melanoma appear warranted.


Colloidal polymer-coated Zn-doped iron oxide nanoparticles with high relaxivity and specific absorption rate for efficient magnetic resonance imaging and magnetic hyperthermia.
Colloidally stable nanoparticles-based magnetic agents endowed with very high relaxivity and specific absorption rate are extremely desirable for efficient magnetic resonance imaging and magnetic hyperthermia, respectively. Here, we report a water dispersible magnetic agent consisting of zinc-doped superparamagnetic iron oxide nanoparticles (i.e., Zn-SPIONs) of 15 nm size with high saturation magnetization coated with an amphiphilic polymer for effective magnetic resonance imaging and magnetic hyperthermia of glioblastoma cells. These biocompatible polymer-coated Zn-SPIONs had 24 nm hydrodynamic diameter and exhibited high colloidal stability in various aqueous media, very high transverse relaxivity of 471 mM-1 s-1, and specific absorption rate up to 743.8 W g-1, which perform better than most iron oxide nanoparticles reported in the literature, including commercially available agents. Therefore, using these polymer-coated Zn-SPIONs even at low concentrations, T2-weighted magnetic resonance imaging and moderate magnetic hyperthermia of glioblastoma cells under clinically relevant magnetic field were successfully implemented. In addition, the results of this in vitro study suggest the superior potential of Zn-SPIONs as a theranostic nanosystem for brain cancer treatment, simultaneously acting as a contrast agent for magnetic resonance imaging and a heat mediator for localized magnetic hyperthermia.


Vitamin K prophylaxis: leaving the old route for the new one?
Oral or parenteral administration of vitamin K is the accepted practice for prevention of early vitamin K deficiency bleeding (VKDB) in the newborn. However, vitamin K prophylaxis in the newborn continues to be a worldwide health concern, particularly in breastfed infants. This paper reviews the current status of the use of vitamin K for the prevention of early and late VKDB.


Influence of processing procedure on the quality of Radix Scrophulariae: a quantitative evaluation of the main compounds obtained by accelerated solvent extraction and high-performance liquid chromatography.
An improved high-performance liquid chromatography with diode array detection combined with accelerated solvent extraction method was used to simultaneously determine six compounds in crude and processed Radix Scrophulariae samples. Accelerated solvent extraction parameters such as extraction solvent, temperature, number of cycles, and analysis procedure were systematically optimized. The results indicated that compared with crude Radix Scrophulariae samples, the processed samples had lower contents of harpagide and harpagoside but higher contents of catalpol, acteoside, angoroside C, and cinnamic acid. The established method was sufficiently rapid and reliable for the global quality evaluation of crude and processed herbal medicines.


Prior oral contraceptive use is associated with higher blood pressure in older women.
Studies of young, premenopausal women suggest that changes in coronary risk factors do not persist after discontinuation of oral contraceptive use. However, little is known about longterm effects of past oral contraceptive use in older, postmenopausal women, who typically have a more atherogenic profile. This study examines the relation of past oral contraceptive use (including duration) to heart disease risk factors in postmenopausal women. Subjects were 517 women aged 50-69 from the Rancho Bernardo Study who attended follow-up clinic visits. Past oral contraceptive use was reported by 24.2% and two thirds had used oral contraceptives < or = 5 years. After adjustment for covariates, the only significant difference was that past users had higher diastolic blood pressures than never users (p < 0.01). Among older women, the diastolic blood pressure of past users was 3.9 mm Hg higher than that of never users (p < 0.01). Women who used oral contraceptives for < or = 5 years had diastolic blood pressures 3.6 mm Hg higher than those of never users (p < 0.01). No differences were found among younger women or those who used oral contraceptives > or = 6 years. Past oral contraceptive users may be at increased risk for heart disease because of a small but significant elevation in diastolic blood pressure that persists many years after discontinuing oral contraceptive use.


Paradoxical benefits of dual-task contexts for visuomotor memory.
It is generally thought that increased attention helps when one is learning a new task. However, using a dual-task paradigm, we showed that the rate of visuomotor learning was the same regardless of attentional distraction caused by a secondary task. Yet, when participants were tested later, a motor skill learned under distraction was remembered only when a similar distraction was present; when participants were tested without the distracting task, their performance reverted to untrained levels. This paradoxical result, in which the level of performance decreases when more attentional resources are available, suggests that the dual-task context, or the lack thereof, acts as a vital context for learning. This task-context-dependent "savings" was evident even when the specific secondary task or sensory modality differed between learning and recall; thus, the dual tasking, rather than the specific stimuli, provides context. This discovery suggests that the success of learning and rehabilitation programs may be diminished if they are developed without consideration of the role of task contexts.


A comparative randomized trial of intermittent intrahepatic arterial carboplatin- versus doxorubicin-lipiodol emulsion in advanced hepatocellular carcinoma (stage IV).
The study was performed to investigate the anti-tumor effect, survival rate, and toxicity of intermittent intrahepatic infusion chemotherapy with carboplatin suspended in lipiodol. We conducted a randomized controlled study containing either doxorubicin or carboplatin in 65 patients with advanced hepatocellular carcinoma. The results observed in the carboplatin- and doxorubicin-lipiodol groups included: response rates, 29.0 and 20.6% respectively, 1-year survival rates of, 60.4% and 40.4%, respectively, and the difference achieved statistical significance (p=0.025). The median survival of 31 patients who received carboplatin emulsified with lipiodol was 16.9 months, 34 patients who received doxorubicin was 12.1 months. The difference achieved statistical significance. Compared with doxorubicin, carboplatin caused neither cardiotoxicity nor nephrotoxicity, and side effects of nausea and vomiting were less severe. Therefore, carboplatin is effective and preferable for repeated intrahepatic arterial administration to treat advanced hepatocellular carcinoma over a relatively long period.


Orthodontic and orthopedic treatment for a growing patient with Tessier number 0 cleft.
The purpose of this case report was to introduce the concept of orthodontic and orthopedic treatment for a growing patient with Tessier number 0 cleft. A 5-year-old boy patient with Tessier number 0 cleft presented congenitally missing maxillary central incisors (MXCI), a bony defect at the premaxilla, a constricted maxillary arch, an anterior openbite, and maxillary hypoplasia. His treatment was divided into three stages: management of the bony defect at the premaxilla and the congenitally missing MXCIs using a fan-type expansion plate, iliac bone grafting, and eruption guidance of the maxillary lateral incisors into the graft area for substitution of MXCIs; management of the maxillary hypoplasia using sequential facemask therapy with conventional and skeletal anchorage; and management of the remaining occlusal problems using fixed orthodontic treatment. The total treatment duration was 15 years and 10 months. Class I canine and Class II molar relationships and normal overbite and overjet were achieved at the end of treatment. Although the long-term use of facemask therapy resulted in significant protraction of the retrusive maxilla, the patient exhibited Class III profile because of continued mandibular growth. However, the treatment result was well maintained after 2 years of retention. The findings from this case suggest that interdisciplinary and customized approaches are mandatory for successful management of maxillary hypoplasia, bony defect, and dental problems in Tessier number 0 cleft. Moreover, considering the potential of orthognathic surgery or distraction osteogenesis, meticulous monitoring of mandibular growth until growth completion is important.


Non-neutral plasma column in an asymmetric trapping field.
A non-neutral plasma column in an asymmetric trapping field is considered in this paper. It is shown that nonlinearly interacting bulk plasma oscillations and quadrupole surface waves allow an exact analytical description. The absence of symmetry leads to nonintegrability and other nonlinear phenomena, such as passage through different resonances and phase locking. These phenomena should be observable in experiments involving elliptical traps and rotating walls and can affect the latters' applications.


Interaction between misfolded PrP and the ubiquitin-proteasome system in prion-mediated neurodegeneration.
Prion diseases are associated with the conformational conversion of cellular prion protein (PrP(C)) to pathological β-sheet isoforms (PrP(Sc)), which is the infectious agent beyond comprehension. Increasing evidence indicated that an unknown toxic gain of function of PrP(sc) underlies neuronal death. Conversely, strong evidence indicated that cellular prion protein might be directly cytotoxic by mediating neurotoxic signaling of β-sheet-rich conformers independent of prion replication. Furthermore, the common properties of β-sheet-rich isoform such as PrP(Sc) and β amyloid protein become the lynchpin that interprets the general pathological mechanism of protein misfolding diseases. Dysfunction of the ubiquitin-proteasome system (UPS) has been implicated in various protein misfolding diseases. However, the mechanisms of this impairment remain unknown in many cases. In prion disease, prion-infected mouse brains have increased levels of ubiquitin conjugates, which correlate with decreased proteasome function. Both PrP(C) and PrP(Sc) accumulate in cells after proteasome inhibition, which leads to increased cell death. A direct interaction between 20S core particle and PrP isoforms was demonstrated. Here we review the ability of misfolded PrP and UPS to affect each other, which might contribute to the pathological features of prion-mediated neurodegeneration.


Routine postoperative duplex ultrasonography screening and monitoring for the detection of deep vein thrombosis. A survey of 110 total hip arthroplasties.
The use of duplex ultrasonography for routine noninvasive screening, monitoring, and management of deep venous thrombosis after total hip arthroplasty was evaluated. The reliability of duplex ultrasonography for detection of deep vein thrombosis was confirmed in an initial cohort of 51 total hip arthroplasty patients (102 lower extremities), demonstrating 91% sensitivity, 98% specificity, and 97% accuracy when compared with venography. A second cohort of 110 total hip arthroplasty patients using pneumatic compression stockings and aspirin as deep vein thrombosis prophylaxis underwent screening duplex ultrasonography of both lower extremities on postoperative Day 4. Duplex ultrasonography screening showed 10 (9.1%) patients with proximal deep vein thrombosis and 10 (9.1%) with distal deep vein thrombosis, all of whom were asymptomatic. The 10 patients with proximal deep vein thrombosis on duplex ultrasonography were prescribed therapeutic anticoagulation. Duplex ultrasonography subsequently confirmed resolution of proximal deep vein thrombosis in these patients before discontinuation of anticoagulation; none developed symptomatic pulmonary embolism through 12-month clinical followup. The 10 patients with distal deep vein thrombosis diagnosed by duplex ultrasonography were not treated with anticoagulation, but were monitored by serial duplex ultrasonography through postoperative Day 14 for propagation of distal to proximal deep vein thrombosis; none manifested symptomatic deep vein thrombosis or pulmonary embolism through 12-month clinical followup. The 90 patients with negative duplex ultrasonography results were followed clinically; 3 developed late symptomatic proximal deep vein thrombosis (1 of these later manifested pulmonary embolism). Therefore, duplex ultrasonography was used after total hip arthroplasty for the following: (1) to screen routinely in the hospital for asymptomatic proximal and distal deep vein thrombosis; (2) to monitor for potential propagation of distal to proximal deep vein thrombosis; (3) to minimize exposure to therapeutic anticoagulation by confirming the absence of proximal deep vein thrombosis in 97 of 110 patients; and (4) to demonstrate the effectiveness of mechanical and systemic deep vein thrombosis management by confirming the absence or resolution of deep vein thrombosis in all 110 patients.


Trisomy for the distal half of the short arm of chromosome 9. A variant of the trisomy 9p syndrome.
Three patients with partial trisomy for the distal one half of the short arm of chromosome 9 were studied. These patients represent a mild clinical variant of the trisomy 9p syndrome.


Sensitive Detection of Deliquescent Bacterial Capsules through Nanomechanical Analysis.
Encapsulated bacteria usually exhibit strong resistance to a wide range of sterilization methods, and are often virulent. Early detection of encapsulation can be crucial in microbial pathology. This work demonstrates a fast and sensitive method for the detection of encapsulated bacterial cells. Nanoindentation force measurements were used to confirm the presence of deliquescent bacterial capsules surrounding bacterial cells. Force/distance approach curves contained characteristic linear-nonlinear-linear domains, indicating cocompression of the capsular layer and cell, indentation of the capsule, and compression of the cell alone. This is a sensitive method for the detection and verification of the encapsulation status of bacterial cells. Given that this method was successful in detecting the nanomechanical properties of two different layers of cell material, i.e. distinguishing between the capsule and the remainder of the cell, further development may potentially lead to the ability to analyze even thinner cellular layers, e.g. lipid bilayers.


VNUT and VMAT2 segregate within sympathetic varicosities and localize near preferred Cav2 isoforms in the rat tail artery.
ATP and norepinephrine (NE) are coreleased from peripheral sympathetic nerve terminals. Whether they are stored in the same vesicles has been debated for decades. Preferential dependence of NE or ATP release on Ca2+ influx through specific voltage-gated Ca2+ channel (Cav2) isoforms suggests that NE and ATP are stored in separate vesicle pools, but simultaneous imaging of NE and ATP containing vesicles within single varicosities has not been reported. We conducted an immunohistochemical study of vesicular monoamine transporter 2 (VMAT2/SLC18A2) and vesicular nucleotide translocase (VNUT/SLC17A9) as markers of vesicles containing NE and ATP in sympathetic nerves of the rat tail artery. A large fraction of varicosities exhibited neighboring, rather than overlapping, VNUT and VMAT2 fluorescent puncta. VMAT2, but not VNUT, colocalized with synaptotagmin 1. Cav2.1, Cav2.2, and Cav2.3 are expressed in nerves in the tunica adventitia. VMAT2 preferentially localized adjacent to Cav2.2 and Cav2.3 rather than Cav2.1. VNUT preferentially localized adjacent to Cav2.3 > Cav2.2 >> Cav2.1. With the use of wire myography, inhibition of field-stimulated vasoconstriction with the Cav2.3 blocker SNX-482 (0.25 µM) mimicked the effects of the P2X inhibitor suramin (100 µM) rather than the α-adrenergic inhibitor phentolamine (10 µM). Variable sensitivity to SNX-482 and suramin between animals closely correlated with Cav2.3 staining. We concluded that a majority of ATP and NE stores localize to separate vesicle pools that use different synaptotagmin isoforms and that localize near different Cav2 isoforms to mediate vesicle release. Cav2.3 appears to play a previously unrecognized role in mediating ATP release in the rat tail artery. NEW & NOTEWORTHY Immunofluorescence imaging of vesicular nucleotide translocase and vesicular monoamine transporter 2 in rat tail arteries revealed that ATP and norepinephrine, classical cotransmitters, localize to well-segregated vesicle pools. Furthermore, vesicular nucleotide translocase and vesicular monoamine transporter 2 exhibit preferential localization with specific Cav2 isoforms. These novel observations address long-standing debates regarding the mechanism(s) of sympathetic neurotransmitter corelease.


Phylogenetic, functional and taxonomic responses of wild bee communities along urbanisation gradients.
Increasing urbanisation is one of the primary drivers of land-use change that threaten biodiversity. Wild bee communities have been reported with contrasting responses to urbanisation, with varying effects on abundance and taxonomical diversity. The suite of functional traits exhibited by wild bee species might determine their persistence in urban areas. Urbanisation thus can impose an environmental filter with potential consequences on the functional and phylogenetical diversity of wild bee communities. Here, we sampled 2944 wild bee specimens from 156 species in 29 sites located along an urbanisation gradient using a replicated design in three mid-sized cities in the Loire valley (France). We show that urban landscape cover has a negative effect on overall species richness and taxonomical diversity indices, while total abundance remains constant. Species loss was taxon dependent, mainly driven by Andrenidae and Halictidae. Only a few species, especially of the genus Lasioglossum, were positively affected by the urban landscape cover. Urban and peri-urban areas differed in their composition of bee assemblages. Species turnover was the main component of beta diversity, driving community dissimilarities through the urban gradient. Urbanisation favours bees with small body sizes, social structure and extended flight periods but did not affect the phylogenetic or the functional diversity of communities. Our findings have implications for understanding the factors involved in the environmental filter exerted through the urban gradient on bee communities helping to implement conservation measures and managing urban spaces for bees.


The insulin pump: why not use it for every type I diabetic patient?
Critical care nurses are likely to care for patients with insulin pumps, and it is essential that they understand the rationale for using them selectively for individuals with diabetes mellitus. The assets and limitations of the technology associated with insulin pump use must be appreciated in regard to glycemic control during hospitalization. Although most patients and family members are well indoctrinated on insulin protocols, pump use, and self-monitoring, it is vital that nurses are aware of the unique issues that surface during critical illness.


Effects of cyproheptadine on insulin secretion by isolated perifused rat islets.
The effects of cyproheptadine on basal and glucose-induced insulin release by isolated rat islets was studied by use of a perifusion system. A forty-five minute preincubation of islets with a medium containing both 34.3 mug./ml. (10(-4) M) cyproheptadine and 1.0 mg./ml. glucose completely abolished the biphasic pattern of increased insulin secretion normally obtained after islets are stimulated with a medium containing 3.0 mg./ml. glucose. In another series of experiments, similar results were obtained when the cyproheptadine and 3.0 mg./ml. glucose were presented together. Here, however, the inhibition of the first phase of insulin secretion did not achieve statistical significance and some recovery of the islets' secretory capacity was observed late during the second phase. In studies designed to investigate the influence of cyproheptadine on basal insulin secretion, no obvious effect was observed. These results are discussed in relation to the species-specific alterations in pancreatic beta-cell morphology that have been reported in rats after the oral administration of cyproheptadine.


Automated chemical crystallography.
The first fully automated small-molecule robotic X-ray diffractometer is described. After demonstrating the utility of the instrument using multiple samples of ammonium bitartrate, we investigated the conformational chirality of diphenyl dichalcogenide (E(2)Ph(2), where E = S, Se, or Te). Structural and computational studies suggest that the two enantiomers are energetically indistinguishable. Therefore, it was unsurprising that we found (in 35 suitable data collections) the proportion 0.51:0.49 of M-S(2)Ph(2) to P-S(2)Ph(2) in the bulk sample. Interestingly, after 65 data collections of Te(2)Ph(2), (46 provided suitable data sets), we found the proportion 0.72 +/- 0.13 of M-Te(2)Ph(2), suggesting there could be a statistically significant preference for the M-enantiomer in the sample examined here. We found that Se(2)Ph(2) underwent homochiral crystallization, with all 24 crystals being M. Our experiments may represent a salutary lesson in statistical analysis.


Surface treatment of flow channels in microfluidic devices fabricated by stereolithography.
A microfluidic device with three-dimensional flow channels was fabricated by stereolithography, and hydrophilic surface treatment of the flow channel was performed by coating the wall of the channel with a silica layer. After the treatment, the device produced monodisperse oil-in-water (O/W) emulsions. The silica layer on the channel surface was then coated with a fluorinated silane coupling agent to make it hydrophobic, thus enabling the treated device to produce monodisperse inverted water-in-oil (W/O) emulsions.


In vitro and in vivo assessment of the abuse potential of PF614, a novel BIO-MD™ prodrug of oxycodone.
The need for pain medication which will not lead to abuse is well recognized. Ensysce has designed prodrug analogs of the commonly used pain medications including hydromorphone, oxycodone (OC), hydrocodone, and morphine that limit their use to oral delivery, two of which are in clinical development. This study was undertaken to demonstrate that PF614, an extended-release prodrug of OC, allows the release of OC as designed when delivered orally, yet it resists ex vivo extraction with household chemicals and is pharmacologically inactive when administered by nonoral routes (nasal and parenteral), thereby substantially reducing its intravenous (IV) and intranasal abuse potential. In vitro and in vivo methods were used to determine release of OC from PF614 and to show potential µ-opioid receptor activity. Plasma and cerebral spinal fluid levels of OC were evaluated following in vivo IV administration of PF614 in rats. In vitro extraction of OC from PF614 was explored using enzymes, common solvents, and household chemicals at room temperature and elevated temperature over time to determine release of OC from the prodrug. PF614 was stable with in vitro exposure to human plasma, saliva, and liver microsomes or culinary enzyme preparations. PF614 was stable (≥90 percent remaining as intact prodrug) under all room temperature conditions evaluated for 24 hours. At 80°C for 1 hour, no OC was released. Incubation at 80°C for 24 hours in vinegar or vodka produced a conversion to OC of 6 percent. Incubation with trypsin at 37°C converted PF614 approximately stoichiometric to OC with half-life of 4 hours. PF614's penetration of the central nervous system was 83-fold lower than OC and it had a 6.5-fold reduced potency as a µ-opioid agonist. Finally, oral PF614 delivers OC into plasma with an extended-release profile in dogs (reduced Cmax; delayed Tmax). The Bio-Activated Molecular Delivery prodrug design limits the use of PF614 to the intended oral route of delivery with reduced potential for IV or nasal abuse, as it cannot be activated intravenously or nasally to provide an active opioid. Unlike existing opioid formulations, the extended-release profile of PF614 cannot be accelerated by chewing or ex vivo extraction to pharmacologically active substances.


Maternal nutrition--effect on fetal growth and outcome of pregnancy.
During the first half of the 20th century, chronic energy undernutrition due to low dietary intake, repeated infections, and rapid succession of pregnancy were the factors most responsible for maternal undernutrition and consequent adverse outcomes of pregnancy. Efforts to improve dietary intake, treatment of infections, and provision of contraceptive care were the major focuses of intervention from 1950 to 1990. These interventions resulted in reduction in severe grades of undernutrition. However, there was no reduction in mild and moderate degrees of undernutrition and anemia during pregnancy and there was no significant improvement in the course and outcome of pregnancy, or in birth weight. During the 1990s, among the middle- and upper-income groups, there has been a progressive rise in obesity and consequent adverse effects. The advent of HIV infection in India in the 1980s will inevitably lead to increases in severe undernutrition associated with HIV infection in pregnancy and an adverse impact of maternal HIV infection on the fetus. Practicing physicians and nutritionists in the new millennium will therefore have to assess each person individually and provide appropriate advice regarding diet, exercise, fertility, and infection prevention and control in order to achieve optimum health and nutrition status during pregnancy and to prevent adverse pregnancy outcomes.


Coping with the isotretinoin registry.
The isotretinoin registry has arrived. It has a lofty goal of preventing all isotretinoin pregnancies. How we got to this point and what the registry means to prescribers and patients have many dermatologists confused and concerned. Will it be burdensome, will it preclude the use in most offices of this most important drug? Will it breed a new group of "isotretinologists" who are willing to take on the challenge? This article endeavors to answer these questions and to put most concerns at rest. The new system seems ultimately to have few changes compared to the risk management program we are already (technically) following. The difference is that compliance with all the rules will be monitored and mandatory. The system seems user friendly, is accessible to the computer-savvy as well as those of us still addicted to telephone, and may well turn out to be much fuss made over minimal hassle. What is clear is that this is likely our last chance to save this wonderful drug from oblivion. It is time for dermatologists to step to the plate and do what is in the best interest of their patients.


Timolol induces HSV-1 ocular shedding in the latently infected rabbit.
Timolol iontophoresis into the eye can induce herpes simplex virus type 1 (HSV-1) shedding in rabbits latently infected with HSV-1 strain McKrae. Anodal iontophoresis of 0.01% timolol was done at 0.8 mAmp for 8 min once a day for 3 consecutive days. Viral shedding was determined by the presence of HSV-1 in the preocular tear film obtained by eye swabs. In two experiments, iontophoresis of 0.01% timolol resulted in all eyes (18/18) shedding HSV-1 for an average duration of 4.3 days. When 5.0% timolol was applied topically to rabbit eyes supersensitized by iontophoresis of 6-hydroxydopamine (6-HD), all eyes (10/10) shed virus for an average duration of 2.9 days. All eyes (12/12) receiving iontophoresis of 6-HD, pre- and posttreatment with topical application of 5.0% timolol, and posttreatment with topical application of 1.0% epinephrine shed virus for an average duration of 3.6 days. Eyes treated with topical application of 5.0% timolol alone showed no difference in HSV-1 ocular shedding, compared with untreated eyes. We concluded that both iontophoresis of 0.01% timolol and topical application of 5.0% timolol to adrenergically supersensitized eyes induced HSV-1 shedding reliably and with a high frequency, and that topically applied timolol does not block the HSV-1 ocular shedding induced by epinephrine in adrenergically supersensitized eyes.


Killing, letting die, and withdrawing aid.
One of the aims of this article is to contribute to the identification of the empirical criteria governing the use of the concepts of killing and letting die. I will not attempt a comprehensive analysis of the concepts but will limit the inquiry to certain problematic cases -- namely, cases involving the removal or withdrawal of life-supporting aid or protection. The analysis of these cases will, however, shed light on the criteria for distinguishing killing and letting die in other cases as well. My overall aims in the article are partly constructive and partly skeptical. I hope to advance our understanding of the nature of the distinction between killing and letting die. This, I believe, will enable us to defend the moral relevance of the distinction against certain objections -- in particular, objections that claim that the distinction fails to coincide with commonsense moral intuitions. Yet I will suggest that, as we get clearer about the nature of the distinction and the sources of its intuitive appeal, it may seem that the intuitions it supports are not so well grounded as one could wish.


Concurrent and predictive validity of the Mann Assessment of Swallowing Ability in Belgian acute stroke patients based on a one-year follow-up study.
The Mann Assessment of Swallowing Ability (MASA) is a standardized clinical swallowing examination, specifically developed as a diagnostic test for the presence of oropharyngeal dysphagia and aspiration in the early period after stroke onset. In the original validation study, cut-off scores of <178 and <170 points, respectively, for the identification of dysphagia and aspiration risk are reported. However, a literature search revealed that alternative cut-off scores for dysphagia and/or aspiration provide better diagnostic accuracy. The aim of this secondary data analysis study was to evaluate the concurrent and predictive validity of the MASA. Data were derived from a Belgian cohort study of an acute stroke population (n = 151). The MASA total score (MASA-TS), which is the sum of weighted scores on the 24 items, was evaluated against the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) to assess concurrent validity. To assess predictive validity of the MASA-TS, pneumonia during hospitalization and over one year, and mortality acted as a future criterion. Analyses included receiver operating characteristic curves (ROC), and area under the curve (AUC). Diagnostic accuracy of the MASA-TS was good for dysphagia (AUC = 0.85) and for the presence of relevant aspiration risk (AUC = 0.84). Using the original cut-off scores, the MASA-TS showed perfect sensitivity (Se = 1.00) for the identification of dysphagia and aspiration, but inadequate specificity (Sp) for dysphagia (Sp = 0.16) and aspiration (Sp = 0.43). After determining new MASA cut-off scores, the optimal MASA cut-off scores were ≤146 for both dysphagia and aspiration with adequate thresholds (Se = 0.71 and Sp = 0.81 for dysphagia; Se = 0.73 and Sp = 0.80 for aspiration). The MASA-TS was a significant predictor of pneumonia during hospitalization (AUC = 0.85) and one-year follow-up (AUC = 0.86), and of mortality (AUC = 0.79). The MASA-TS showed good concurrent validity with the FEDSS. Furthermore, using new cut-off scores (≤146 for the identification of dysphagia and aspiration) lead in general to more accurate diagnostic indexes. The MASA-TS is a good predictor of aspiration pneumonia during hospitalization and one-year follow-up, and of mortality.


[On the phenomena of extravasation of contrast media in cerebral angiogram of the case of hypertensive intracerebral hematoma and their clinical significance-analysis of 14 cases (author's transl)]?
Since Westerburg (1966) reported a case of hypertensive intracerebral hemorrhage who showed extravasation of contrast media on the cerebral angiogram, only 21 cases demonstrated extravasation of contrast media were reported by several authors. The author experienced 14 cases of hypertensive intracerebral hemorrhage whose cerebral angiogram showed extravasation of contrast media. These 14 cases occupied 21.1% of 58 cases whom cerebral angiographies were performed within 24 hours after the stroke. 6 out of 14 cases were cured by evacuation of the hematoma surgically. These 14 cases were dividied into three types by the shape of extravasation of contrast media as followed: Type I showed widespread leakage of contrast media. Type II showed sash-like leakage of contrast media surrounded by diffuse thin shadow and Type III showed small spotlike leakage of contrast media. These three types indicated the arterial bleeding stage, the stage of accerelated arterial wall permeability and the subsquent venous bleeding respectively. The author concluded that these extravasation of contrast media not only demonstrated the bleeding artery but also indicated the process of the hematoma formation in each case.


Tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury in an 8-year-old girl: a case report.
Tracheobronchial injury in children is rare but can be highly fatal in severe cases. Therefore, prompt diagnosis and treatment are required. The appropriate treatment method depends on the extent and severity of the injury. An 8-year-old girl fell from the fifth floor and was transported to a local hospital. She had a tracheobronchial injury, went into cardiopulmonary arrest during transportation to our hospital. She was revived with cardiopulmonary resuscitation, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was commenced. Subsequently, we performed tracheobronchial reconstruction by inverted Barclay's method for tracheobronchial injury. She was switched from VA-ECMO to venovenous (VV)-ECMO 4 days postoperatively, and VV-ECMO was eventually discontinued 27 days after the surgery. The patient was awake and weaned off the ventilator on postoperative day 58. She was discharged 97 days after the surgery. Tracheobronchial reconstruction by inverted Barclay's method is the preferred surgical technique when other reconstruction techniques are expected to cause excessive tension on the anastomosis of the right main bronchus.


Programming of Vascular Dysfunction by Maternal Stress: Immune System Implications.
A growing body of evidence highlights that several insults during pregnancy impact the vascular function and immune response of the male and female offspring. Overactivation of the immune system negatively influences cardiovascular function and contributes to cardiovascular disease. In this review, we propose that modulation of the immune system is a potential link between prenatal stress and offspring vascular dysfunction. Glucocorticoids are key mediators of stress and modulate the inflammatory response. The potential mechanisms whereby prenatal stress negatively impacts vascular function in the offspring, including poor hypothalamic-pituitary-adrenal axis regulation of inflammatory response, activation of Th17 cells, renin-angiotensin-aldosterone system hyperactivation, reactive oxygen species imbalance, generation of neoantigens and TLR4 activation, are discussed. Alterations in the immune system by maternal stress during pregnancy have broad relevance for vascular dysfunction and immune-mediated diseases, such as cardiovascular disease.


The SWI/SNF chromatin remodeling complex selectively affects multiple aspects of serotonergic neuron differentiation.
Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development.


Familial SYN1 variants related neurodevelopmental disorders in Asian pediatric patients.
SYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years. In the study, we reported two male patients with familial SYN1 variants related neurodevelopmental disorders from Asian population. Previously published cases with significant SYN1 variants from the literature were also included to analyze the phenotype and genotype of the disorder. Two maternally inherited SYN1 variants, including c.C1076A, p.T359K in proband A and c.C1444T, p. Q482X in proband B (NM_133499) were found, which have never been described in detail. Combining with our research, all reported probands were male in the condition, whose significant SYN1 variants were inherited from their asymptomatic or mild affected mother. Although the disorder encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, patients' clinical manifestations vary in genders and individuals, even in the same pedigree. We firstly reported two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Gender and phenotype differences should be highly valued in the disorder.


Effect of TiO2 nanoparticles on the hydrogen sorption characteristics of magnesium hydride.
The present paper explores the enhancement in hydrogen sorption behavior of MgH2 with TiO2 nanoparticles. The catalytic effect of TiO2 nanoparticles with different sizes (7, 25, 50, 100 and 250 nm) were used for improving the sorption characteristics of MgH2. The MgH2 catalyzed with 50 nm of TiO2 exhibited the optimum catalytic effect for hydrogen sorption behavior. The desorption temperature of MgH2 catalyzed through 50 nm TiO2 was found to be 310 degrees C. This is 80 degrees C lower as compared to MgH2 having a desorption temperature of 390 degrees C. It was noticed that the dehydrogenated MgH2 catalyzed with 50 nm TiO2 reabsorbed 5.1 wt% of H2 within 6 minutes at temperature and pressure of 250 degrees C and 50 atm, respectively. The 50 nm TiO2 catalyst lowered the absorption activation energy of MgH2 from - 92 to - 52.7 kJ mol(-1).


Suitability of Creeping Bentgrass and Bermudagrass Cultivars for Black Cutworms and Fall Armyworms (Lepidoptera: Noctuidae).
The black cutworm, Agrotis ipsilon Hufnagel, and fall armyworm, Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), are common turfgrass pests of golf courses in the southeastern United States. Heat-tolerant bentgrass (Agrostis stolonifera L.) cultivars are expanding the range of bentgrass further south, but these cultivars have not been studied for their potential host plant resistance to black cutworm or fall armyworm. The goals of the study were to investigate feeding response of black cutworm and fall armyworm to these newer heat-tolerant creeping bentgrass cultivars, as well as commonly used cultivars of bermudagrass [Cynodon dactylon (Loppers.)]. Choice and no-choice feeding assays and fecundity tests were conducted in the laboratory and greenhouse to evaluate performance and preference of the two insects. When given a choice, neither black cutworm nor fall armyworm showed a preference for the majority of new cultivars tested. There were no differences in leaf area consumption or insect development for either pest in no-choice feeding assays. Black cutworm females preferred laying eggs in bentgrass compared with bermudagrass, but will oviposit onto bermudagrass, suggesting that both turf species are suitable hosts of this pest. The broad host ranges of generalist caterpillar pests of turfgrass hinder the application of host plant resistance in integrated pest management on golf courses.


Intraocular Pharmacokinetics of Intravitreal Aflibercept (Eylea) in a Rabbit Model.
We determined the intraocular pharmacokinetic properties of intravitreally injected aflibercept (Eylea) in a rabbit model. Aflibercept was injected intravitreally in 21 eyes from New Zealand White rabbits. The eyes were enucleated 1, 24, 48, 120, 216, 360, and 720 hours (1, 2, 5, 9, 15, and 30 days, respectively) after injection and immediately frozen at -80°C. The concentrations of aflibercept in the vitreous, aqueous humor, and retina/choroid were determined by performing an indirect enzyme-linked immunosorbent assay, and analyzed to understand the pharmacokinetic properties of the drug. The maximum concentration of aflibercept was observed 1, 48 (2 days), and 24 (1 day) hours after intravitreal administration in the vitreous, aqueous humor, and retina/choroid, respectively. The one-compartment model was selected as the final model for all three ocular tissues. In the vitreous, aqueous humor, and retina/choroid, the estimated half-lives of aflibercept were 94.1, 48.0, and 58.2 hours, and the estimated mean residence times (MRTs) were 135.8, 69.2, and 84.0 hours, respectively. The area under curve from time 0 to the end point (AUClast) was 135,810.6 hours × μg/mL for the vitreous, 13,889.7 hours × μg/mL for the aqueous humor, and 2453.1 hours × μg/g for the retina/choroid. In rabbits, the vitreous half-life of aflibercept is 94.1 hours (3.92 days). This is shorter than that of bevacizumab (6.99 days), and longer than that of ranibizumab (2.51 days) and VEGF-Trap (3.63 days).


Trait Emotional Intelligence Questionnaire-Short Form: Brazilian Validation and Measurement Invariance between the United Kingdom and Latin-American Datasets.
The present study aimed to evaluate the psychometric properties of the Brazilian adaptation of the Trait Emotional Intelligence Questionnaire-Short Form (TEIQue-SF). In a sample of 512 participants, we tested model fit by bifactor Exploratory Structural Equation Modeling (ESEM), followed by measurement invariance testing against UK and Chilean datasets of the measure. The Big Five Mini-Markers, Satisfaction with Life Scale and Subjective Happiness Scale were also administered as external validation measures. We obtained the following results: (a) final adequate bifactor ESEM model fit; (b) a significantly higher global trait EI mean for men (d = .27); (c) high internal consistency for global trait EI (α = .88), in spite of lower Cronbach's α values at the factor level (.60-.85); (d) high correlation (r = .89) in the test-retest; (e) significant correlation between global trait EI and most of the Big Five dimensions (r = -.66-.46), life satisfaction (.59) and happiness (.68); (f) evidence of incremental validity of trait EI for life satisfaction and happiness over and above the Big Five; (g) equivalent measurement across the Brazilian, UK and Chilean versions of the TEIQue-SF. We conclude that the Brazilian TEIQue-SF is psychometrically sound and can be recommended for research and practical use.


High-throughput DNA sequencing of the moose rumen from different geographical locations reveals a core ruminal methanogenic archaeal diversity and a differential ciliate protozoal diversity.
Moose rumen samples from Vermont, Alaska and Norway were investigated for methanogenic archaeal and protozoal density using real-time PCR, and diversity using high-throughput sequencing of the 16S and 18S rRNA genes. Vermont moose showed the highest protozoal and methanogen densities. Alaskan samples had the highest percentages of Methanobrevibacter smithii, followed by the Norwegian samples. One Norwegian sample contained 43 % Methanobrevibacter thaueri, whilst all other samples contained < 10 %. Vermont samples had large percentages of Methanobrevibacter ruminantium, as did two Norwegian samples. Methanosphaera stadtmanae represented one-third of sequences in three samples. Samples were heterogeneous based on gender, geographical location and weight class using analysis of molecular variance (AMOVA). Two Alaskan moose contained >70 % Polyplastron multivesiculatum and one contained >75 % Entodinium spp. Protozoa from Norwegian moose belonged predominantly (>50 %) to the genus Entodinium, especially Entodinium caudatum. Norwegian moose contained a large proportion of sequences (25-97 %) which could not be classified beyond family. Protozoa from Vermont samples were predominantly Eudiplodinium rostratum (>75 %), with up to 7 % Diploplastron affine. Four of the eight Vermont samples also contained 5-12 % Entodinium spp. Samples were heterogeneous based on AMOVA, principal coordinate analysis and UniFrac. This study gives the first insight into the methanogenic archaeal diversity in the moose rumen. The high percentage of rumen archaeal species associated with high starch diets found in Alaskan moose corresponds well to previous data suggesting that they feed on plants high in starch. Similarly, the higher percentage of species related to forage diets in Vermont moose also relates well to their higher intake of fibre.


Linkage and association study of discoidin domain receptor 1 as a novel susceptibility gene for childhood IgA nephropathy.
In several experimental studies, it has been suggested that discoidin domain receptor 1 (DDR1) plays an important role in the regulation of mesangial proliferation, glomerular basement membrane thickening, renal fibrosis, and in the development of inflammation in several tissue types, including renal tissues. The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the DDR1 gene and childhood IgA nephropathy (IgAN). The genotyping data of 180 childhood IgAN patients and 336 controls showed significant differences in the frequency of rs1264319 (dominant model, P=0.040). Subgroup analysis revealed that development of proteinuria (>4 and <or=4 mg/m(2)/h; n=131 and 49) was significantly associated with rs2267641 (codominant model, P=0.004; dominant, P=0.024; recessive, P=0.010) and rs9468844 (codominant model, P=0.003; dominant, P=0.017; recessive, P=0.012). Furthermore, rs1264319 frequencies were significantly different in those with pathologically mild and advanced disease subgroups (n=162 and 18; codominant and dominant model, P=0.022). Our results suggest that DDR1 gene is associated with increased susceptibility, pathological advancement, and the development of proteinuria in childhood IgAN.


Intercostal muscle flap reduces the pain of thoracotomy: a prospective randomized trial.
Thoracotomy is associated with significant pain and morbidity. We performed a prospective randomized trial over 4 months. Patients were randomized to a standard posterior-lateral thoracotomy or an identical procedure, except an intercostal muscle was harvested from the lower rib (to protect the intercostal nerve) before chest retraction. To ensure an equal distribution among both groups, patients were stratified by race, sex, and type of pulmonary resection. All patients received similar pain management. Pain was assessed by using multiple pain scores during hospitalization and after discharge. Outcomes assessed were pain scores, spirometric values, analgesic use, and activity level. There were 114 patients. The median time for intercostal muscle harvesting was 3.7 minutes. The numeric pain scores were lower for the intercostal muscle group on postoperative days 1 and 2 and at weeks 1, 2, 3, 4, 8, and 12 (P < .05 for all). In addition, patients in the intercostal muscle group had a smaller decrease in spirometric values, were less likely to be using analgesics, and were more likely to have returned to normal activity. The harvesting of an intercostal muscle flap before chest retraction decreases the pain of thoracotomy and leads to a lower decrease in spirometry. In addition, patients have less pain at 1, 2, 3, 4, 8, and 12 weeks postoperatively and are less likely to be using narcotics. Finally, it offers a pedicled muscle flap that takes little time to harvest and is able to buttress all bronchi after lobectomy.


Circulating immune complexes after splenectomy.
Circulating immune complexes were evaluated in 25 patients (age range 10 to 46 years) who had undergone splenectomy for non-malignant conditions by studying a polyethylene glycol insoluble serum fraction. Although the extent of binding to Clq was within normal limits, these patients had increased concentrations of factor B in the immune complex serum fraction. These findings indicate that an unusual type of circulating immune complex may be detected after splenectomy, suggesting a possible role for the spleen in the removal of circulating immune complexes.


Olive Leaf Extract (OLE) as a Novel Antioxidant That Ameliorates the Inflammatory Response in Cystic Fibrosis.
The deletion of phenylalanine at position 508 (F508del) produces a misfolded CFTR protein that is retained in the ER and degraded. The lack of normal CFTR channel activity is associated with chronic infection and inflammation which are the primary causes of declining lung function in Cystic Fibrosis (CF) patients. Moreover, LPS-dependent oxidative stress downregulates CFTR function in airway epithelial cells. Olive leaf extract (OLE) is used in traditional medicine for its effects, including anti-oxidant and anti-inflammatory ones. We found that OLE decreased the intracellular ROS levels in a dose-response manner in CFBE cells. Moreover, OLE attenuates the inflammatory response to LPS or IL-1β/TNFα stimulation, mimicking the infection and inflammatory status of CF patients, in CFBE and primary nasal epithelial (HNE) cells. Furthermore, we demonstrated that OLE restored the LPS-mediated decrease of TrikfaftaTM-dependent F508del-CFTR function in CFBE and HNE cultures. These findings provide strong evidence of OLE to prevent redox imbalance and inflammation that can cause chronic lung damage by enhancing the antioxidant activity and attenuating inflammation in CF airway epithelial cells. Additionally, OLE might be used in combination with CFTR modulators therapy to improve their efficacy in CF patients.


CRISPR- mediated Mutation in Cinnamoyl- CoA Reductase 4 in Allohexaploid Oilseed Crop Camelina sativa, Revealed its Pivotal Role in Resistance Against Sclerotinia sclerotiorum.
Sclerotinia sclerotiorum (Ss) is a broad host range necrotrophic ascomycete fungus affecting over 400 plant species. Ss causes stem rot disease on Camelina sativa (Cs) an allohexaploid crucifer species that is promoted as a low input crop and industrial oil attributes suitable as biofuel and lubricant. Histochemical and molecular studies has linked resistance to Ss in C. sativa with the cell wall lignification (Eynck et al., 2012) and reported constitutive expression of Cinnamoyl-CoA Reductase 4 (CsCCR4) gene, in the Cs resistant line CN114263. Modern breeding efforts, such as gene editing, are needed to improve commercial lines and to limit the risk of crop loss which would be substantial to producers. To investigate the importance of monolignol biosynthesis and the role of CsCCR4 in Camelina resistance to Ss we generated CsCCR4 knockout mutants of CN114263 Camelina line using CRISPR/Cas9-mediated gene editing. Thirty T1 plants were produced via floral dip transformation followed by glyphosate spraying that was used in the first step of screening procedures and were confirmed by PCR method. Transgene's T-DNA copy number variation, T-DNA CNV, in T1 and T2 progenitors were determined using digital droplet PCR (ddPCR) and the occurrence of mutation in the three copies of CsCCR4 homeologues in T1 and T2 generations were scrutinized by drop-off assay technique. To make sure that if the created mutants in T2 plants are real, TOPO TA sequencing flanking the Cas9/gRNA specific hot point of cleavage for three of them was conducted. In the T1 generation, 25 plants were confirmed which had between one to nine T-DNA copies in the corresponding Camelina genome. In T2 generation the population were screened for potential mutation in CsCCR4 gene. Various types of mutations, including insertions and deletions, were demonstrated in three copies of CsCCR4. In fact, CRISPR system could have cut one, two or three copies of the gene in events numbered T2-plant 10, T2-plant 15 and T2-plant 19, respectively. The T3-plant 19 which showed mutation in all versions of CsCCR4 in previous generation had susceptibility to S. sclerotiorum invasion and was kept as real csccr4 mutant material for further investigations of Camelina-Sclerotinia interaction. Mutation in CsCCR4 had occurred through error-prone none- homologous end joining (NHEJ) nucleus DNA repair pathway. Ss challenge on the early flowering T3 generation. The T3 plants with mutation causing premature stop codon at position 217 of CsCCR4 were compromised in their resistance to Ss compared to the wildtype resistant control parent CN114263. Using ddPCR it easily was possible to identify both the T-DNA CNV and occurrence of mutation in CsCCR4 homeologues in T1 and T2 progenitors. We illustrated that CRISPR/Cas9-mediated mutation is a decent technique that can be utilized to expedite the mutant line development which could assist to figure out the activity of a CsCCR4 gene in defense responses to the pathogens in C. sativa as prospective oilseed crop for biodiesel production.


The functional synergy between IL-12 and IL-2 involves p38 mitogen-activated protein kinase and is associated with the augmentation of STAT serine phosphorylation.
IL-12 and IL-2 can stimulate mitogen- or CD3-activated T cells to proliferate, produce IFN-gamma, and kill tumor cells. The magnitude of these functional responses is greatly augmented when T cells are activated by the combination of IL-12 and IL-2. Although peripheral blood T cells are largely unresponsive to these cytokines without prior activation, a small subset of CD8+ T cells (CD8+CD18bright) is strongly activated by the combination of IL-12 and IL-2. In this report we show that the functional synergy between IL-12 and IL-2 in CD8+CD18bright T cells correlates with the activation of the stress kinases, p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase (SAPK)/Jun N-terminal kinase, but not with the activation of the extracellular signal-regulated kinases. The functional synergy between IL-2 and IL-12 is also associated with a prominent increase in STAT1 and STAT3 serine phosphorylation over that observed with IL-12 or IL-2 alone. By contrast, STAT tyrosine phosphorylation is not augmented over that seen with either cytokine alone. A specific inhibitor of p38 MAP kinase completely inhibits the serine phosphorylation of STAT1 and STAT3 induced by IL-12 and IL-2 and abrogates the functional synergy between IL-12 and IL-2 without affecting STAT tyrosine phosphorylation. This suggests that p38 MAP kinase may play an important role in regulating STAT serine phosphorylation in response to the combination of IL-12 and IL-2. Furthermore, these findings indicate that the optimal activation of T cells by IL-12 and IL-2 may depend on an interaction between the p38 MAP kinase and Janus kinase/STAT signaling pathways.


Dissipation of chlorantraniliprole, chlorpyrifos-methyl and indoxacarb-insecticides used to control codling moth (Cydia Pomonella L.) and leafrollers (Tortricidae) in apples for production of baby food.
Dissipations of three insecticides: chlorantraniliprole, chlorpyrifos-methyl and indoxacarb in apples were studied following their foliar application on apples intended for production of baby food. The apples were sprayed with formulations for control of codling moth (Cydia Pomonella L.) and leafrollers (Tortricidae). Six experiments were conducted; each insecticide was applied individually on dessert apples. A validated gas chromatography-based method with simultaneous electron capture and nitrogen-phosphorus detection (GC-ECD/NPD) was used for the residue analysis. The analytical performance of the method was satisfactory, with expanded uncertainties ≤36% (a coverage factor, k = 2, and a confidence level of 95%). The dissipations of insecticides were studied in pseudo-first-order kinetic models (for which the coefficient of determination, R 2 , ranged between 0.9188 and 0.9897). Residues of studied insecticides were below their maximum residue limits of 0.5 mg/kg at an early stage of growth of the fruit. The half-lives of chlorantraniliprole, chlorpyrifos-methyl and indoxacarb were 16-17, 4-6 and 20-24 days, respectively. The initial residue levels declined gradually and reached the level of 0.01 mg/kg in 1 month for chlorpyrifos-methyl, 2 months for chlorantraniliprole and 2.5 months for indoxacarb. To obtain the insecticide residue levels below 0.01 mg/kg, which is the default MRL for food intended for infants and young children, the application of the studied insecticides should be carried out at recommended doses not later then: 1 month before harvest for chlorpyrifos-methyl, 2 months for chlorantraniliprole and 2.5 months for indoxacarb.


The Growth of Children's Semantic and Phonological Networks: Insight From 10 Languages.
Children tend to produce words earlier when they are connected to a variety of other words along the phonological and semantic dimensions. Though these semantic and phonological connectivity effects have been extensively documented, little is known about their underlying developmental mechanism. One possibility is that learning is driven by lexical network growth where highly connected words in the child's early lexicon enable learning of similar words. Another possibility is that learning is driven by highly connected words in the external learning environment, instead of highly connected words in the early internal lexicon. The present study tests both scenarios systematically in both the phonological and semantic domains across 10 languages. We show that phonological and semantic connectivity in the learning environment drives growth in both production- and comprehension-based vocabularies, even controlling for word frequency and length. This pattern of findings suggests a word learning process where children harness their statistical learning abilities to detect and learn highly connected words in the learning environment.


Draft Genome Sequence of the Probiotic Yeast Saccharomyces cerevisiae var. boulardii Strain ATCC MYA-796.
Saccharomyces boulardii is the only yeast approved as a probiotic for human consumption. Here, we report the draft genome sequence of the strain ATCC MYA-796, derived from the French Ultra Levure probiotic drug. The genome has a size of 11.6 Mb with 5,305 putative open reading frames predicted.


The role of laminins in cartilaginous tissues: from development to regeneration.
As a key molecule of the extracellular matrix, laminin provides a delicate microenvironment for cell functions. Recent findings suggest that laminins expressed by cartilage-forming cells (chondrocytes, progenitor cells and stem cells) could promote chondrogenesis. However, few papers outline the effect of laminins on providing a favorable matrix microenvironment for cartilage regeneration. In this review, we delineated the expression of laminins in hyaline cartilage, fibrocartilage and cartilage-like tissue (nucleus pulposus) throughout several developmental stages. We also examined the effect of laminins on the biological activities of chondrocytes, including adhesion, migration and survival. Furthermore, we scrutinized the potential influence of various laminin isoforms on cartilage-forming cells' proliferation and chondrogenic differentiation. With this information, we hope to facilitate the understanding of the spatial and temporal interactions between cartilage-forming cells and laminin microenvironment to eventually advance cell-based cartilage engineering and regeneration.


Gastroenteritis due to Vibrio cholerae El-Tor Ogawa in Dhule.
For V. Cholerae isolation, stool sample is better than rectal swab. Direct oxidase test on stool is easy and reliable. V. cholerae El-Tor Ogawa is predominant type in Dhule area. New phage type T27 was reported. Tetracyclin resistance needs further studies.


The use of morphokinetics as a predictor of implantation: a multicentric study to define and validate an algorithm for embryo selection.
Can we use morphokinetic markers to select the embryos most likely to implant and are the results likely to be consistent across different clinics? Yes, morphokinetic markers can be used to select the embryos most likely to implant and the results were similar in different IVF clinics that share methods and organization to some extent. With the introduction of time-lapse technology several authors have proposed the use of kinetic markers to improve embryo selection. The majority of these markers can be detected as early as Day 2 of development. Morphology remains the gold standard but kinetic markers have been proven as excellent tools to complement our decisions. Nevertheless, the majority of time-lapse studies are based on small data sets deriving from one single clinic. Retrospective multicentric study of 1664 cycles of which 799 were used to develop an algorithm (Phase 1 of the study) and 865 to test its predictive power (Phase 2 of the study). University-affiliated infertility centres patients undergoing first or second ICSI cycle using their own or donated oocytes. Embryo development was analysed with a time-lapse imaging system. Variables studied included the timing to two cells (t2), three cells (t3), four cells (t4) and five cells (t5) as well as the length of the second cell cycle (cc2 = t3 - t2) and the synchrony in the division from two to four cells (s2 = t4 - t3). Implantation (IR) and clinical pregnancy (CPR) rates were also analysed. During Phase 1 of the study we identified three variables most closely related to implantation: t3 (34-40 h), followed by cc2 (9-12 h) and t5 (45-55 h). Based on these results we elaborated an algorithm that classified embryos from A to D according to implantation potential. During Phase 2 of the study the algorithm was validated in a different group of patients that included 865 cycles and 1620 embryos transferred. In this phase of the study, embryos were categorized based on the algorithm and significant differences in IR were observed between the different categories ('A' 32%, 'B' 28%, 'C' 26%, 'D' 20% and 'E' 17%, P < 0.001). In addition we identified three quality criteria: direct cleavage from one to three cells, uneven blastomere size in second cell cycle and multinucleation in third cell cycle. The retrospective nature of the study limits its potential value, although the use of one database to generate the algorithm (embryos from this database were not selected by any morphokinetic criteria) and one database to validate it reinforces our conclusions. The elaboration of an algorithm based on a larger database derived from different (albeit related) clinics raises the possibility that such algorithms could be applied in different clinical settings.


Effects of homologous plasma cross-circulation on liver function in galactosamine-induced hepatic necrosis in rats.
Plasma cross-circulation that resembles clinical plasma exchange was carried out in rats with galactosamine (GalN)-treated hepatic failure to investigate its effect on the damaged liver function. Twenty-four hours after the injection of GalN, plasma cross-circulation was performed at a plasma flow rate of 0.1 ml/min for 6 h. At 48 h after the injection of GalN, survival was obtained in 6 of 8 GalN-injected rats treated with plasma cross-circulation as compared with 4 of 10 GalN-injected rats treated with sham circulation. State 3 oxygen consumption and ATP synthesis (mitochondrial respiratory function) and ATP, ADP, and total adenine nucleotide contents in the liver were significantly higher in the former group than in the latter group at that period, as determined by sacrificing the surviving animals. Although the survival rate was not significantly improved, evidence suggests that plasma cross-circulation enhanced mitochondrial phosphorylative activity and produced an augmented high-energy state of the liver, which had been markedly reduced by GalN administration. An efficient removal of toxic metabolites as well as an influx of a large amount of fresh plasma by plasma cross-circulation would be beneficial for the regenerative process of the necrosing liver tissues.


Repulsive atomic gas in a harmonic trap on the border of itinerant ferromagnetism.
Alongside superfluidity, itinerant (Stoner) ferromagnetism remains one of the most well-characterized phases of correlated Fermi systems. A recent experiment has reported the first evidence for novel phase behavior on the repulsive side of the Feshbach resonance in a two-component ultracold Fermi gas. By adapting recent theoretical studies to the atomic trap geometry, we show that an adiabatic ferromagnetic transition would take place at a weaker interaction strength than is observed in experiment. This discrepancy motivates a simple nonequilibrium theory that takes account of the dynamics of magnetic defects and three-body losses. The formalism developed displays good quantitative agreement with experiment.


Embracing complexity across disciplines: Reflective supervision and postdegree training integrate mental health concepts with speech-language therapy and graduate education.
This article illustrates how relationship-based practice and reflective supervision can augment the practice of professionals in allied health disciplines in the earliest childhood fields. The authors describe how mental health constructs were integrated into the discipline-specific expertise of one speech-language pathologist and how, in turn, that affected her leadership as graduate program director. The article highlights the transformations that took place within one discipline through the assimilation of a transdisciplinary, relationship-based, and reflective model. The ongoing individual and group supervision of a speech-language pathologist through an intensive, reflective, 2-year experience in a postdegree certificate training program is described to explore the change process; a detailed analysis of one case is used to illustrate shifts in clinical practice and the broadening of theoretical paradigms. Further, the authors illustrate how the graduate program director implemented the use of these constructs with clinical supervisors at her university upon completion of the postdegree training program so that the supervisors could, in turn, introduce and use them with their graduate students. Finally, the benefits, concerns, and limitations of engaging in transdisciplinary work are briefly addressed.


Microbiological effects of mouthrinses containing antimicrobials.
A number of mouthrinse formulations containing antimicrobials have been evaluated to determine their effectiveness as antiplaque and/or antigingivitis agents. These have included the bis-biguanides, phenols, quaternary ammonium compounds, oxygenating compounds, plant extracts, fluorides, antibiotics and antimicrobial combinations. These mouthrinses have often been tested as adjuncts to normal oral hygiene procedures as well as in the experimental gingivitis model. 2 agents in particularly, chlorhexidine gluconate and listerine, have been shown to both inhibit or reduce plaque accumulation and the severity of gingivitis. Chlorhexidine has been reported to reduce the accumulation of plaque by approximately 60% and the severity of gingivitis by 50-80% as determined by improvements in clinical indices. A 0.12% chlorhexidine gluconate rinse resulted in significant reductions after both 3 and 6 months use in the numbers of total anaerobes, total aerobes, streptococci, and actinomyces recovered from supragingival plaque. Listerine has been reported to retard the development of plaque by 45 to 56% and to reduce existing plaque by 39 to 48%. Gingivitis scores were reduced as much as 59%. Microbial studies have shown that the effect of listerine is exerted against the total microbial mass and results in an overall decrease in both the biomass and the activity. Long-term use of neither mouthrinse, chlorhexidine or listerine, resulted in the emergence of opportunistic or oral pathogens. Preliminary data obtained following the use of a novel mouthrinse consisting of a combination of povidone-iodine and hydrogen peroxide appears promising. This combination was more effective than was more effective than either single component alone in reducing gingivitis scores.(ABSTRACT TRUNCATED AT 250 WORDS)


Netrins as prophylactic targets in skeletal diseases: A double-edged sword?
The netrin family of proteins are involved in axon guidance during central nervous system development. In vertebrates, two membrane bound forms and five secreted forms of netrin have been reported. In addition to their critical role in neural morphogenesis, a growing number of reports suggest that netrin family proteins also play a role in inflammatory conditions, angiogenesis, and tumorigenesis. In these processes, Unc5 and DCC family proteins serve as receptors of netrin proteins. Recently, it was reported that some netrin family proteins may be involved in the pathogenesis of skeletal diseases including osteoporosis and arthritis. For example, administration of secreted netrin family proteins such as netrin 1 and netrin 4 has prophylactic potential in pathogenic bone degradation in mice. However, netrin 1 blocking antibody also protects mice from inflammatory bone destruction. Therefore, netrin family proteins are involved in the regulation of bone homeostasis, but their bona fide roles in the skeletal system remain controversial. In this review, we discuss the osteo-innate-immune functions of the netrin family of proteins, and summarize their therapeutic potential.


Relationships between unoccupied classroom acoustical conditions and elementary student achievement measured in eastern Nebraska.
Building standards recommend maximum background noise levels (BNL) and reverberation times (RT) for unoccupied classrooms. However, existing research does not show a consistent correlation between these parameters and student achievement. Through in situ testing, this research seeks to determine what acoustical conditions should be attained in elementary schools for students to meet educational goals. Acoustical measurements were conducted in a Nebraska public school system and correlated to achievement scores from students in the surveyed classrooms. Unoccupied BNLs and RTs were gathered in 34 third and 33 fifth-grade classrooms. Additionally, binaural room impulse response measurements were gathered in a subset of the classrooms. The results suggest that student reading and language subject areas may be negatively impacted by higher unoccupied BNLs; to meet the upper half of NE state targets, these levels should be less than 45 dBA. However, the percentage of students receiving free or reduced price lunches is more strongly correlated to achievement than BNLs, and the negative correlations between noise and achievement are not significant when controlling for this demographic variable. One statistically significant relationship that remained when controlling for demographics was that classrooms with lower distortion of frequency-smoothed magnitude values generally had students with higher language scores.


Triterpene glycosides and glucosyl esters, and a triterpene from the leaves of Schefflera actinophylla.
From the EtOAc and 1-BuOH fractions, three new ursane-type and four new lupane-type triterpenes, along with nine known glycosides and glycosyl esters of lupane-type were isolated from the leaves of Schefflera actinophylla. All the isolated compounds were obtained for the first time from this plant. The structures of the new triterpenes were determined through a combination of spectroscopic and chemical analyses.


Artificial Neural Network-Based Density Functional Approach for Adiabatic Energy Differences in Transition Metal Complexes.
During the past decades, approximate Kohn-Sham density functional theory schemes have garnered many successes in computational chemistry and physics, yet the performance in the prediction of spin state energetics is often unsatisfactory. By means of a machine learning approach, an enhanced exchange and correlation functional is developed to describe adiabatic energy differences in transition metal complexes. The functional is based on the computationally efficient revision of the regularized, strongly constrained, and appropriately normed functional and improved by an artificial neural network correction trained over a small data set of electronic densities, atomization energies, and/or spin state energetics. The training process, performed using a bioinspired nongradient-based approach adapted for this work from the particle swarm optimization, is analyzed and discussed extensively. The resulting machine learned meta-generalized gradient approximation functional is shown to outperform most known density functionals in the prediction of adiabatic energy differences for a diverse set of transition metal complexes with varying local coordinations and metal choices.


Epithelial cell motility on laminin-5: regulation by matrix assembly, proteolysis, integrins and erbB receptors.
Cell migration plays a central role in a wide variety of biological events, including embryogenesis, inflammatory immune response, wound healing, or cancer invasion. Tight regulation of cell motility is a prerequisite for normal development and maintenance of an organism, and to avoid metastatic spread of tumor cells. An important determinant of migratory efficiency is the substrate over which a cell migrates. Laminin-5 (Ln-5) is an extracellular matrix component prominent in basement membranes and as such it is a substrate in direct contact with epithelial cells. Interestingly, Ln-5 has been shown to both stimulate and downregulate epithelial cell migration. In this article, we plan to give an overview on the different mechanisms cells employ to regulate their migratory behavior on Ln-5. We will discuss how proteolytic processing of Ln-5 acts as posttranslational modification that plays a major role in the regulation of cell migration. The different proteolytic Ln-5 species may bind to distinct cell surface receptors called integrins, which translate substrate binding into a specific cellular response that triggers cell motility. Furthermore, interaction between Ln-5-binding integrins and other transmembrane and cytoplasmic proteins increases complexity and may allow fine-tuning of cell migration in response to the cellular environment.


The development of word recognition processes.
To observe the course of the development of automatic processes in word recognition, two experiments were performed in which a distracting word interacted with a target stimulus. In Expt 1 the subjects named a simple line drawing, and in Expt 2 they named a word appearing in a rectangle. The distracting word (i) was a semantic associate of the target stimulus, (ii) was graphemically similar to the name of the target, (iii) was phonemically similar to the name of the target, (iv) was unrelated in meaning, orthography and phonology, or (v) was replaced with an unpronounceable letter string. Three groups of subjects were tested. Skilled adult readers were compared with two groups of children. Matched groups of children were used, with similar ages (9-12 years old) and non-verbal spatial abilities, but dissimilar reading ages. All groups of subjects showed semantic interference and graphemic priming from the distractor word in Expt 1, and the children showed phonemic priming. In Expt 2, only the poor readers showed semantic interference, and no groups showed graphemic or phonemic effects. The sensitivity of the poor readers to the distractors indicates that the semantic, graphemic and phonemic codes of words are generated by these subjects, and that the difference in reading age between them and the good readers can be attributed to post-lexical processes such as text integration and articulatory planning and execution.


Static dipole polarizability of ytterbium.
The static dipole polarizability of the ground state ytterbium atom is calculated using full and approximate relativistic ab initio methods. Our recommended polarizability of 143 au is consistent with experimental atomic spectral data. The corresponding van der Waals coefficient C6 of Yb2, derived using Padé approximants, is 2062 (200) au.


Amorphous fluorescent organic emitters for efficient solution-processed pure red electroluminescence: synthesis, purification, morphology, solid-state photoluminescence, and device characterizations.
New soluble and intrinsic amorphous red emitters 1 and 2 were obtained by Suzuki coupling. Due to the close molecular polarities, separation of target products from monocoupling impurities presents a challenge. The results showed highly pure 2 would be a potentially valuable fluorophore for solution-processed pure red electroluminescence in terms of visual sensitivity with respect to 1.


Correction of Sagittal Deformity with Bone Resection and Soft Tissue Releases.
Fixed flexion deformities (FFDs) present several unique challenges in total knee arthroplasty (TKA) and require careful consideration to achieve optimal outcomes. FFD alters normal knee biomechanics and increases energy expenditure (1). They may be attributed to both bony deformities and fibrosed soft tissues, which must be addressed in stepwise fashion at the time of surgery. A literature review was conducted utilizing keywords "fixed flexion deformity TKA." This review article aims to discuss the anatomy and pathology, preoperative evaluation, classification system, surgical techniques for addressing deformity, implant selection considerations, postoperative protocols, clinical outcomes, and potential complications associated with correcting FFD. By comprehensively addressing these aspects, surgeons can optimize surgical planning and improve outcomes in patients with FFD undergoing TKA.


Caste and Choice: The Influence of Developmental Idealism on Marriage Behavior.
Is the marriage behavior of young people determined by their socioeconomic characteristics or their endorsement of developmental idealism? This article addresses this question using a unique longitudinal data set from Nepal and provides the first individual-level test of developmental idealism theory. The authors find that unmarried individuals with greater endorsement of developmental idealism in 2008 were more likely by 2012 to choose their own spouse, including a spouse of a different caste, rather than have an arranged marriage. Those with salaried work experience were also less likely to have arranged marriages, but urban proximity and education were not significant. The authors conclude that both developmental idealism and socioeconomic characteristics influence marriage and that their influences are largely independent.