Role of fetal DNA in preeclampsia (review).
Preeclampsia is an autoimmune disorder characterized by hypertension. It begins with abnormal cytotrophoblast apoptosis, which leads to inflammation and an increase in the levels of anti-angiogenic factors followed by the disruption of the angiogenic status. Increased levels of fetal DNA and RNA coming from the placenta, one of the most commonly affected organs in pregnancies complicated by preeclampsia, have been found in pregnant women with the condition. However, it remains unknown as to whether this is a cause or a consequence of preeclampsia. Few studies have been carried out on preeclampsia in which an animal model of preeclampsia was induced by an injection of different types of DNA that are mimic fetal DNA and provoke inflammation through Toll-like receptor 9 (TLR9) or cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). The specific mechanisms involved in the development of preeclampsia are not yet fully understood. It is hypothesized that the presence of different fragments of fetal DNA in maternal plasma may cause for the development of preeclampsia. The function of DNase during preeclampsia also remains unresolved. Studies have suggested that its activity is decreased or the DNA is protected against its effects. Further research is required to uncover the pathogenesis of preeclampsia and focus more on the condition of patients with the condition.


AR-Supported Supervision of Conditional Autonomous Robots: Considerations for Pedicle Screw Placement in the Future.
Robotic assistance is applied in orthopedic interventions for pedicle screw placement (PSP). While current robots do not act autonomously, they are expected to have higher autonomy under surgeon supervision in the mid-term. Augmented reality (AR) is promising to support this supervision and to enable human-robot interaction (HRI). To outline a futuristic scenario for robotic PSP, the current workflow was analyzed through literature review and expert discussion. Based on this, a hypothetical workflow of the intervention was developed, which additionally contains the analysis of the necessary information exchange between human and robot. A video see-through AR prototype was designed and implemented. A robotic arm with an orthopedic drill mock-up simulated the robotic assistance. The AR prototype included a user interface to enable HRI. The interface provides data to facilitate understanding of the robot's "intentions", e.g., patient-specific CT images, the current workflow phase, or the next planned robot motion. Two-dimensional and three-dimensional visualization illustrated patient-specific medical data and the drilling process. The findings of this work contribute a valuable approach in terms of addressing future clinical needs and highlighting the importance of AR support for HRI.


Vibrational behavior of adsorbed CO2 on single-walled carbon nanotubes.
We present theoretical and experimental evidence for CO(2) adsorption on different sites of single walled carbon nanotube (SWNT) bundles. We use local density approximation density functional theory (LDA-DFT) calculations to compute the adsorption energies and vibrational frequencies for CO(2) adsorbed on SWNT bundles. The LDA-DFT calculations give a range of shifts for the asymmetric stretching mode from about -6 to -20 cm(-1) for internally bound CO(2), and a range from -4 to -16 cm(-1) for externally bound CO(2) at low densities. The magnitude of the shift is larger for CO(2) adsorbed parallel to the SWNT surface; various perpendicular configurations yield much smaller theoretical shifts. The asymmetric stretching mode for CO(2) adsorbed in groove sites and interstitial sites exhibits calculated shifts of -22.2 and -23.8 cm(-1), respectively. The calculations show that vibrational mode softening is due to three effects: (1) dynamic image charges in the nanotube; (2) the confining effect of the adsorption potential; (3) dynamic dipole coupling with other adsorbate molecules. Infrared measurements indicate that two families of CO(2) adsorption sites are present. One family, exhibiting a shift of about -20 cm(-1) is assigned to internally bound CO(2) molecules in a parallel configuration. This type of CO(2) is readily displaced by Xe, a test for densely populated adsorbed species, which are expected to be present on the highest adsorption energy sites in the interior of the nanotubes. The second family exhibits a shift of about -7 cm(-1) and the site location and configuration for these species is ambiguous, based on comparison with the theoretical shifts. The population of the internally bound CO(2) may be enhanced by established etching procedures that open the entry ports for adsorption, namely, ozone oxidation followed by annealing in vacuum at 873 K. Xenon displacement experiments indicate that internally bound CO(2) is preferentially displaced relative to the -7 cm(-1) shifted species. The -7 cm(-1) shifted species is assigned to CO(2) adsorbed on the external surface based on results from etching and Xe displacement experiments.


Extra-Mediterranean glacial refuges in barred and common grass snakes (Natrix helvetica, N. natrix).
Extra-Mediterranean glacial refugia of thermophilic biota, in particular in northern latitudes, are controversial. In the present study we provide genetic evidence for extra-Mediterranean refugia in two species of grass snake. The refuge of a widely distributed western European lineage of the barred grass snake (Natrix helvetica) was most likely located in southern France, outside the classical refuges in the southern European peninsulas. One genetic lineage of the common grass snake (N. natrix), distributed in Scandinavia, Central Europe and the Balkan Peninsula, had two distinct glacial refuges. We show that one was located in the southern Balkan Peninsula. However, Central Europe and Scandinavia were not colonized from there, but from a second refuge in Central Europe. This refuge was located in between the northern ice sheet and the Alpine glaciers of the last glaciation and most likely in a permafrost region. Another co-distributed genetic lineage of N. natrix, now massively hybridizing with the aforementioned lineage, survived the last glaciation in a structured refuge in the southern Balkan Peninsula, according to the idea of 'refugia-within-refugia'. It reached Central Europe only very recently. This study reports for the first time the glacial survival of a thermophilic egg-laying reptile species in Central Europe.


Endoscopic ultrasound-guided sampling of solid pancreatic masses: 22-gauge aspiration versus 25-gauge biopsy needles.
Biopsy needles have recently been developed to obtain both cytological and histological specimens during endoscopic ultrasound (EUS). We conducted this study to compare 22-gauge (G) fine needle aspiration (FNA) needles, which have been the most frequently used, and new 25G fine needle biopsy (FNB) needles for EUS-guided sampling of solid pancreatic masses. We conducted a retrospective cohort study of all EUS-guided sampling performed between June 2010 and October 2013. During the study period, 76 patients with pancreatic masses underwent EUS-guided sampling with a 22G FNA needle (n = 38) or a 25G FNB needle (n = 38) for diagnosis. An on-site cytopathologist was not present during the procedure. Technical success, the number of needle passes, cytological diagnostic accuracy, cytological sample quality (conventional smear and liquid-based preparation), histological diagnostic accuracy, and complications were reviewed and compared. There were no significant differences in technical success (100% for both), the mean number of needle passes (5.05 vs. 5.55, P = 0.132), or complications (0% for both) between the 22G FNA group and the 25G FNB group. The 22G FNA and 25G FNB groups exhibited comparable outcomes with respect to cytological diagnostic accuracy (97.4% vs. 89.5%, P = 0.358) and histological diagnostic accuracy (34.2% vs. 52.6%, P = 0.105). In the cytological sample quality analysis, the 25G FNB group exhibited higher scores for the amount of diagnostic cellular material present (22G FNA: 0.92 vs. 25G FNB: 1.32, P = 0.030) and the retention of appropriate architecture (22G FNA: 0.97 vs. 25G FNB: 1.42, P = 0.010) in the liquid-based preparation. The 25G FNB group showed a better histological diagnostic yield for specific tumor discrimination compared with the 22G FNA group (60 % vs. 32.4%, P = 0.018). Use of the 25G FNB needle was technically feasible, safe, efficient, and comparable to use of the standard 22G FNA needle in patients with solid pancreatic masses in the absence of an on-site cytopathologist. The cytological sample quality in the liquid-based preparation and the histological diagnostic yield for specific tumor discrimination of EUS-guided sampling using a 25G FNB needle were significantly higher than those using a 22G FNA needle.


Multidisciplinary assessment at triage: a new way forward.
To evaluate a dual doctor and nurse triage system at a tertiary referral hospital. Data were compared between periods of multidisciplinary triage and periods of standard triage. Data comparison was also made between rostered multidisciplinary triage shifts and non-multidisciplinary triage shifts. Staff satisfaction with the process was assessed. The percentage of patients seen within Australasian Triage Scale performance indicator thresholds increased from 75% to 81% in Category 2 patients (P = 0.12) and 56% to 78% in Category 3 patients (P < 0.0001). There was a reduction of 50% in the number of patients who left prior to being seen by a doctor (P = 0.024). Surveys showed high staff satisfaction with the process. We feel that multidisciplinary triage performs a useful function in our department enabling us to reduce waiting times. The process is widely accepted amongst the staff and it ensures a senior doctor assesses most patients. It reduces the number of patients leaving prior to being seen by a doctor and it provides one way of getting around access block and a physically small department.


Role of the lecturer practitioner: 1.
The lecturer practitioner role is a practice-led educational development which has been sparsely studied. This two-part article aims to show that the role is central to dynamic development within the nursing profession and that, despite many potential problems, it can be both rewarding and valuable. Part 1 describes the development of the lecturer practitioner role and examines various aspects of the role, including clinical learning and assessment.


The development of an improved preclinical mouse model of intracerebral hemorrhage using double infusion of autologous whole blood.
The present study was conducted in mice to validate a double blood infusion model of intracerebral hemorrhage (ICH) that does not use anticoagulant. We investigated the effect of intrastriatal infusion of blood on hematoma volume, neurologic function, brain edema and swelling, and markers of neuroinflammation and oxidative DNA damage. Anesthetized C57BL/6 adult male mice were infused in the left striatum with 4 microl of blood over 20 min at 0.2 microl /min; the needle was left in place for 7 min, and the remaining 6 microl of blood was then infused over 30 min. The injection needle was slowly withdrawn 20 min after the second injection. Sham-operated control mice received only needle insertion. The hematoma produced in this model was primarily restricted to the striatum, and the mice demonstrated severe neurologic deficits that appeared within 60 min and remained evident at 72 h. Brain water content and swelling were significantly increased and were associated with a marked increase in ICH-induced neutrophil infiltration, microglial/macrophage and astrocyte activation, cytochrome c release, and oxidative DNA damage. Other groups have mixed the anticoagulant heparin with the infused blood, an agent that could affect in vivo clot formation. We believe that this double blood infusion model that does not use anticoagulant improves upon the procedure and provides an easy and reproducible alternative for inducing ICH in mice; it should be useful for studying the pathophysiology of ICH and for testing potential pharmaceutical and surgical interventions.


Medication therapy management in pharmacy practice: core elements of an MTM service model (version 2.0).
To further develop the service model for medication therapy management (MTM) delivery by pharmacists in settings where patients or their caregivers can be actively involved in managing their medications. Peer-reviewed literature, structured discussions with pharmacy leaders from diverse patient care settings, input from pharmacists and pharmacy associations, recommendations on patient-centered documents (personal medication record and medication-related action plan) from experts in the field of health literacy, and incorporation of extensive feedback received during an extended public comment period open to all MTM stakeholders and interested parties. Built on an MTM consensus definition adopted by 11 national pharmacy organizations in July 2004, Medication Therapy Management in Community Pharmacy Practice: Core Elements of an MTM Service (Version 1.0) described core elements of an MTM service model that can be provided by pharmacists across the spectrum of community pharmacy. Version 2.0 of that model, presented in this article, maintains the original five core elements of an MTM service: medication therapy review (MTR), a personal medication record (PMR), a medication-related action plan (MAP), intervention and referral, and documentation and follow-up. The MTR can be comprehensive or targeted, depending on the needs of the patient. In Version 2.0, the PMR and MAP have been redesigned with the assistance of a health literacy expert to be more "patient friendly," effective, and efficient for patients to use in medication self-management. The developing service model presented in this article for use by pharmacists involved in providing MTM services in diverse patient care settings consists of five core elements. The service model provides a consistent and recognizable framework for MTM service delivery by pharmacists that enhances efficient delivery of the service and improves patient outcomes.


Ultrafast laser inscription of volume phase gratings with low refractive index modulation and self-images of high visibility.
Ultrafast laser inscription of volume phase gratings with low index contrast and self-images with visibility of 0.96 is demonstrated. It is also demonstrated that phase differences of π/2 for visible light are achievable with only one layer of structures induced in bulk borosilicate glass by direct laser writing. The fabrication method avoids the stitching of several layers of structures and significantly reduces the time of process. The increment of visibility with the induced phase difference is proved and results are compared with the expected for planar phase gratings.


Ligand-based Pharmacophore Modeling; Atom-based 3D-QSAR Analysis and Molecular Docking Studies of Phosphoinositide-Dependent Kinase-1 Inhibitors.
Phosphoinositide-dependent kinase-1 plays a vital role in the PI3-kinase signaling pathway that regulates gene expression, cell cycle growth and proliferation. The common human cancers include lung, breast, blood and prostate possess over stimulation of the phosphoinositide-dependent kinase-1 signaling and making phosphoinositide-dependent kinase-1 an interesting therapeutic target in oncology. A ligand-based pharmacophore and atom-based 3D-QSAR studies were carried out on a set of 82 inhibitors of PDK1. A six point pharmacophore with two hydrogen bond acceptors (A), three hydrogen bond donors (D) and one hydrophobic group (H) was obtained. The pharmacophore hypothesis yielded a 3D-QSAR model with good partial least square statistics results. The training set correlation is characterized by partial least square factors (R(2) = 0.9557, SD = 0.2334, F = 215.5, P = 1.407e-32). The test set correlation is characterized by partial least square factors (Q(2) ext = 0.7510, RMSE = 0.5225, Pearson-R =0.8676). The external validation indicated that our QSAR model possess high predictive power with good value of 0.99 and value of 0.88. The docking results show the binding orientations of these inhibitors at active site amino acid residues (Ala162, Thr222, Glu209 and Glu166) of phosphoinositide-dependent kinase-1 protein. The binding free energy interactions of protein-ligand complex have been calculated, which plays an important role in molecular recognition and drug design approach.


Transcatheter Therapy for Mitral Regurgitation Clinical Challenges and Potential Solutions.
Severe mitral regurgitation is a common and complex disease that is associated with an adverse prognosis. For decades, surgical treatment has been the standard of care. Recently, multiple technologies for transcatheter mitral therapy have emerged, with the potential for both repair and replacement in patients with native mitral regurgitation. Transcatheter mitral technologies have potential as solutions for unmet clinical needs. Further rigorous clinical studies are needed to determine their efficacy and safety, as well as the appropriate patient candidates. These evaluations will help to define the role of transcatheter mitral therapy as a potentially exciting new strategy to improve the lives of patients with mitral regurgitation.


Variance-Constrained State Estimation for Complex Networks With Randomly Varying Topologies.
This paper investigates the variance-constrained state estimation problem for a class of nonlinear time-varying complex networks with randomly varying topologies, stochastic inner coupling, and measurement quantization. A Kronecker delta function and Markovian jumping parameters are utilized to describe the random changes of network topologies. A Gaussian random variable is introduced to model the stochastic disturbances in the inner coupling of complex networks. As a kind of incomplete measurements, measurement quantization is taken into consideration so as to account for the signal distortion phenomenon in the transmission process. Stochastic nonlinearities with known statistical characteristics are utilized to describe the stochastic evolution of the complex networks. We aim to design a finite-horizon estimator, such that in the simultaneous presence of quantized measurements and stochastic inner coupling, the prescribed variance constraints on the estimation error and the desired performance requirements are guaranteed over a finite horizon. Sufficient conditions are established by means of a series of recursive linear matrix inequalities, and subsequently, the estimator gain parameters are derived. A simulation example is presented to illustrate the effectiveness and applicability of the proposed estimator design algorithm.


Lessons from the NSW laboratory response to pandemic (H1N1) 2009 influenza.
Procedures undertaken by NSW Health in the laboratory response to pandemic (H1N1) 2009 influenza were reviewed to assist planning for a future infectious disease emergency. Laboratory plans developed prior to the pandemic sought rapid detection of pandemic virus in the early phases of the pandemic response until demonstration of widespread community transmission, followed then by limited testing when indicated clinically. As planned, the laboratory response was based on the Pandemic Influenza Management System with a web-based outbreak management tool, NetEpi, as the single public health database used for cases and test results. This was found to be effective for tracking specimens and results, and enhanced the public health response. The sustained large volume of community testing during this mild pandemic had an adverse effect on the timely delivery of priority results.


Flexible Aggregation-Induced Emission-Active Hydrogel for On-Site Monitoring of Pesticide Degradation.
Benefiting from the stimuli-responsive property and powerful loading capacity, functionalized hydrogels are favorable for the fabrication of sensing devices. Herein, we design aggregation-induced emission (AIE)-active hydrogel discs by embedding gold nanoclusters@zeolite-like imidazole framework (AuNCs@ZIF) composites in double-network hydrogels to build a sensitive pesticide biosensor. The hydrogel discs integrate an AIE effect of AuNCs, a stimuli-responsive property of ZIF, and a porous network structure of the hydrogel, which enhances the sensing sensitivity via boosting the stable fluorescent signal and antifouling performance. In conjunction with a homemade device, the fluorescence images of hydrogel discs could be transduced into data information for accurate quantification of chlorpyrifos pesticide with a detection limit of 0.2 ng/mL. The dynamic degradation of chlorpyrifos in Chinese cabbage is demonstrated to confirm the practical application of hydrogel discs. Such AIE-active hydrogel discs could be a plant health sensor for the on-site quantification of pesticide residues on crops, holding great promise for precision agriculture.


Key interventions and outcomes in joint arthroplasty clinical pathways: a systematic review.
SUMMARY RATIONALE, AIMS AND OBJECTIVES: Clinical pathways are globally used to improve quality and efficiency of care. Total joint arthroplasty patients are one of the primary target groups for clinical pathway development. Despite the worldwide use of clinical pathways, it is unclear which key interventions multidisciplinary teams select as pathway components, which outcomes they measures and what the effect of this complex intervention is. This literature study is aimed at three research questions: (1) What are the key interventions used in joint arthroplasty clinical pathways? (2) Which outcome measures are used? (3) What are the effects of a joint arthroplasty clinical pathway? Systematic literature review using a multiple reviewer approach. Five electronic databases were searched comprehensively. Reference lists were screened. Experts were consulted. After application of inclusion and exclusion criteria and critical appraisal, 34 of the 4055 publications were included. Joint arthroplasty clinical pathways address pre-admission education, pre-admission exercises, pre-admission assessment and testing, admission and surgical procedure, postoperative rehabilitation, minimal manipulation, symptoms management, thrombosis prophylaxis, discharge management, primary caregiver involvement, home-based physiotherapy and continuous follow-up. An overview of target dimensions and corresponding indicators is provided. Clinical pathways for joint arthroplasty could improve process and financial outcomes. The effects on clinical outcome are mixed. Evidence on team and service outcome is lacking. A set of key interventions and outcome measures is available to support joint arthroplasty clinical pathways. Team and service outcomes should be further addressed in practice and research. Meta-analysis on the outcome indicators should be performed. Future studies should more rigorously comply with existing reporting standards.


Cardiotoxicity in a citalopram and olanzapine overdose.
This is a case of a citalopram and olanzapine overdose causing seizures and severe cardiotoxicity. A 21-year-old man presented unresponsive, with seizures, to an Emergency Department. The patient's initial electrocardiogram demonstrated a widened QRS of 160 ms and a normal QT/QTc interval of 400/487 ms consistent with cardiac sodium channel blockade. Within 30 min of arrival, peak citalopram and olanzapine levels were measured to be 522 ng/mL and 505 ng/mL, respectively. Measured levels remained supratherapeutic until 13.6 h and 42.6 h after arrival for citalopram and olanzapine, respectively. The patient developed bradycardia and hypotension that required multimodal therapies including sodium bicarbonate boluses, vasopressors, and transvenous pacing. Seizures and cardiotoxicity continued while citalopram, but not olanzapine, was supratherapeutic. This case describes cardiotoxicity directly correlated with supratherapeutic citalopram levels in overdose.


Epidemiology of children's fractures.
Fractures constitute 10% to 25% of all pediatric injuries and are more common in boys than in girls, and after age 13 or 14 years are twice as common. The results from an epidemiologic study in Malmö indicate that a child's risk of sustaining a fracture is 42% in boys and 27% in girls from birth to age 16 years. Fractures of the distal end of the radius are the most common injury, followed by fractures of the phalanges of the hand. From 1950 to 1979 there was a twofold increase in the risk of fracture, due to an increase in light-energy trauma, mainly sporting activities. Since the end of the 1970s there has been no further increase in the fracture risk. The data also indicate that preventive measures have been effective in decreasing severe accidents.


Age-Related Variations in Corneal Asphericity and Long-Term Changes.
Corneal front-surface asphericity is directly related with the optical quality of the eye and with contact lenses fitting. The purpose of this study was to evaluate the corneal asphericity as a function of age, sex, and refractive error measured with autokeratometry and corneal topography and its long-term changes (5- to 10-year period). The asphericity and corneal curvature were obtained with the autorefractometer/autokeratometer NIDEK ARK-700A and with the videokeratoscope MODI 2.0 and compared. Corneal asphericity was retrospectively analyzed with NIDEK ARK-700A. The longitudinal study of asphericity was conducted with the same device between 2 appointments within an interval of 5 to 10 years. NIDEK ARK-700A showed agreement of asphericity values with those of MODI 2.0 (P=0.172) for a 7-mm diameter chord. The mean Q value of 1,484 right eyes (58.6% female), with a mean age of 40.2±18.4 years, was -0.24±0.12. No differences were found for Q value between sexes (P=0.424), age groups (P=0.268), and refractive error groups (P=0.107). The longitudinal analysis of corneal asphericity in 190 eyes (62.1% female) over a mean period of 5.9±1.4 years showed no significant differences in the Q value (0.00±0.08, P=0.813) over time. However, 14% showed asphericity changes of ±0.10 or higher while 86% of the subjects showed a change below ±0.10. The mean Q value observed in this study agrees with the average values of a white population and contributes to slightly reduce the positive spherical aberration of the eye. For the large majority of this population, the asphericity did not show significant changes within a period of 5 to 10 years, but significant changes can be observed in some patients.


[The function of the pancreatic islet cells during prolonged hypokinesia].
The content of insulin, C-peptide, glucagon, somatostatin, and glucose was studied in the blood of animals experiencing 3, 10, 30, 70, and 140-day hypokinesia (HK) and the cAMP content--in their liver and renal cortex. It was found that in 3-day HK insulin production and catabolism are sharply stimulated, the glucagon and glucose content is increased, the somatostatin level is reduced, and cAMP content in the liver and kidneys is reduced. Ten-day HK is characterized by hyperglycemia, an almost normal hormone content, and increased cAMP level in the renal cortex. In 30-day HK the blood insulin and glucagon content, the content of cAMP in the liver and renal cortex are sharply increased, and the level of somatostatin and glucose is reduced. In 70-day HK the content of glucose and hormones in the blood is reduced, the cAMP level in both organs does not differ from that in the controls. In 140-day HK the concentration of insulin and glucagon in the blood of the animals increases significantly and the level of glycemia normalizes, evidently through increase of cAMP in the liver and kidneys.


Reprogrammed lipid metabolism protects inner nuclear membrane against unsaturated fat.
The cell nucleus is surrounded by a double membrane. The lipid packing and viscosity of membranes is critical for their function and is tightly controlled by lipid saturation. Circuits regulating the lipid saturation of the outer nuclear membrane (ONM) and contiguous endoplasmic reticulum (ER) are known. However, how lipid saturation is controlled in the inner nuclear membrane (INM) has remained enigmatic. Using INM biosensors and targeted genetic manipulations, we show that increased lipid unsaturation causes a reprogramming of lipid storage metabolism across the nuclear envelope (NE). Cells induce lipid droplet (LD) formation specifically from the distant ONM/ER, whereas LD formation at the INM is suppressed. In doing so, unsaturated fatty acids are shifted away from the INM. We identify the transcription circuits that topologically reprogram LD synthesis and identify seipin and phosphatidic acid as critical effectors. Our study suggests a detoxification mechanism protecting the INM from excess lipid unsaturation.


The four community dimensions of primary care practice.
Despite the growing belief that "the community" should play a larger role in the work of physicians, there is no clear understanding of exactly how physicians should participate in their communities. The primary goals of this study were to propose and test an organizing framework that identified four distinct categories of activities whereby physicians can interact with their communities: (1) identifying and intervening in the community's health problems; (2) responding to the particular health issues of local cultural groups when caring for patients; (3) coordinating local community health resources in the care of patients; and (4) assimilating into the community and its organizations. Other goals were to characterize physicians' level of involvement in each of these four types of community activities, and to identify the correlates of greater and lesser involvement. A questionnaire was mailed to a random sample of 500 young primary care physicians in the United States. The response rate was 66.6%. Physicians reported how confident they were in performing each of 15 specific community-relevant activities. Confidence ratings were factor-analyzed to test the hypothesis that physician involvement in community activities can be organized into the four proposed categories. Physicians also self-rated their involvement in various community activities within each of these four categories, and predictors of involvement were identified through ordinary least-squares regression models. Using factor analysis, the community activities sorted cleanly into the four postulated community dimensions of medical practice, providing a measure of validation for the distinctiveness of the four dimensions. Physicians reported active involvement in some activities (eg, speaking to community groups and gaining acceptance in their communities) and little involvement in other activities (eg, working with community groups to address local health problems, familiarity with local women's shelters). Contrary to expectations, physicians who worked with minority and poorer patient populations and counties generally reported less community involvement. Physicians caring for more patients covered by HMO or capitated health insurance plans also reported lower participation in their communities. This study provides support for the hypothesis that the community plays a role in the work of physicians that can be categorized into four types of activities. This framework may help physicians and practices recognize the breadth of ways they can meet the growing demand that they approach their work with a community perspective.


Dualistic nature of adhesive protein function: fibronectin and its biologically active peptide fragments can autoinhibit fibronectin function.
Fibronectin and certain polypeptide regions of this adhesive glycoprotein mediate cell attachment and spreading on various substrates. We explored the theoretical prediction that this adhesive protein could become a competitive inhibitor of fibronectin-mediated processes if present in solution at appropriately high concentrations. Fibronectin function was inhibited by purified plasma fibronectin at 5-10 mg/ml, by a 75,000-dalton cell-interaction fragment of the protein at 0.5-1 mg/ml, and even by two synthetic peptides containing a conserved, hydrophilic amino acid sequence at 0.1-0.5 mg/ml. Inhibition of fibronectin-dependent cell spreading was dose dependent, noncytotoxic, and reversible. It was competitive in nature, since increased quantities of substrate-adsorbed fibronectin or longer incubation periods decreased the inhibition. A peptide inhibitory for fibronectin-mediated cell spreading also inhibited fibronectin-mediated attachment of cells to type I collagen, but it did not affect concanavalin A-mediated spreading. These results demonstrate the potential of a cell adhesion molecule and its biologically active peptide fragments to act as competitive inhibitors, and they suggest that fibronectin may act by binding to a saturable cell surface receptor.


Use of a new generation ophthalmoscope.
A new optical configuration for an ophthalmoscope is a hybrid of the present direct and indirect instruments, combining the strengths of both to increase overall efficiency. Cross polarization is used as a means of reducing glare and increasing clarity of detail. A fiberoptic light source increases light intensity, but reduces heat, weight, and inconvenience. These characteristics result in a self-contained, handheld indirect instrument. This ophthalmoscope is mechanically aligned and therefore easy to use. Both ophthalmologist and nonophthalmologist may find this instrument of benefit in ocular examinations.


Clinico-bacteriological study of chronic dacryocystitis cases in northern karnataka, India.
The aim of this study was to identify the organisms responsible and to determine the antibiotic susceptibility pattern of the bacterial isolates from conjunctiva and nasal mucosa in cases of chronic dacryocystitis and comparing with lacrimal sac specimen. Prospective longitudinal study. A prospective analysis of 44 lacrimal sac contents of patients with chronic dacryocystitis conducted during the period from April 2012 to March 2013. Material was obtained directly from the lacrimal sac while making sac flap during external dacryocystorhinostomy for chronic dacryocystitis. Samples were also collected from ipsilateral conjunctiva and inferior meatus of nose. The specimens were cultured and results analyzed. The results were analyzed by using Chi-square (χ(2)) test. All the patients were in age group of 30 and above. Gram positive bacteria i.e., Coagulase negative staphylococci and Staphylococcus aureus were the most common isolates (71% and 14% respectively). Vancomycin, amikacin, 3(rd) generation cephalosporins and amoxyclav were most sensitive antibiotics (100%, 89%, 83%, and 78% respectively). Comparison between lacrimal and nasal/conjunctival isolates showed high degree of identicalness between the isolates of two sites (p< 0.05). Majority of the chronic dacryocystitis cases are caused by Coagulase negative Staphylococci and Staphylococcus aureus. Amoxyclav and 3(rd) generation cephalosporins can be used to treat chronic dacryocystitis. Commensal flora of nose and conjunctiva have a direct role in pathogenesis of chronic dacryocystitis.


Nephron progenitor commitment is a stochastic process influenced by cell migration.
Progenitor self-renewal and differentiation is often regulated by spatially restricted cues within a tissue microenvironment. Here, we examine how progenitor cell migration impacts regionally induced commitment within the nephrogenic niche in mice. We identify a subset of cells that express Wnt4, an early marker of nephron commitment, but migrate back into the progenitor population where they accumulate over time. Single cell RNA-seq and computational modelling of returning cells reveals that nephron progenitors can traverse the transcriptional hierarchy between self-renewal and commitment in either direction. This plasticity may enable robust regulation of nephrogenesis as niches remodel and grow during organogenesis.


Tropisms of AAV for subretinal delivery to the neonatal mouse retina and its application for in vivo rescue of developmental photoreceptor disorders.
Adeno-associated virus (AAV) is well established as a vehicle for in vivo gene transfer into the mammalian retina. This virus is promising not only for gene therapy of retinal diseases, but also for in vivo functional analysis of retinal genes. Previous reports have shown that AAV can infect various cell types in the developing mouse retina. However, AAV tropism in the developing retina has not yet been examined in detail. We subretinally delivered seven AAV serotypes (AAV2/1, 2/2, 2/5, 2/8, 2/9, 2/10, and 2/11) of AAV-CAG-mCherry into P0 mouse retinas, and quantitatively evaluated the tropisms of each serotype by its infecting degree in retinal cells. After subretinal injection of AAV into postnatal day 0 (P0) mouse retinas, various retinal cell types were efficiently transduced with different AAVs. Photoreceptor cells were efficiently transduced with AAV2/5. Retinal cells, except for bipolar and Müller glial cells, were efficiently transduced with AAV2/9. Horizontal and/or ganglion cells were efficiently transduced with AAV2/1, AAV2/2, AAV2/8, AAV2/9 and AAV2/10. To confirm the usefulness of AAV-mediated gene transfer into the P0 mouse retina, we performed AAV-mediated rescue of the Cone-rod homeobox gene knockout (Crx KO) mouse, which exhibits an outer segment formation defect, flat electroretinogram (ERG) responses, and photoreceptor degeneration. We injected an AAV expressing Crx under the control of the Crx 2kb promoter into the neonatal Crx KO retina. We showed that AAV mediated-Crx expression significantly decreased the abnormalities of the Crx KO retina. In the current study, we report suitable AAV tropisms for delivery into the developing mouse retina. Using AAV2/5 in photoreceptor cells, we demonstrated the possibility of gene replacement for the developmental disorder and subsequent degeneration of retinal photoreceptors caused by the absence of Crx.


[Prevention of impulsive suicide with antidepressants in outpatients].
Self-poisoning is a common method of suicide, for which various medications are used, including antidepressants. A non-systematic review of Russian-language and English-language publications, by keywords, in the databases: ELibrary.ru, PubMed, Cochrane Database of Systematic Reviews. The purpose of the review was to analyze the literature on new risk factors and methods of their reduction in suicides with self-poisoning with antidepressants. Every fifth (20%) self-poisoning performed with antidepressants. In self-poisoning attempts, one drug used in 55% of cases, and more than one drug was used in 45% of cases. Impulsive suicides account for up to half of all suicide cases. Risk factors for impulsive suicides include the presence of impulsive character traits, female gender, young age, and the use of psychostimulants. The WHO Regional Office for Europe's mhGAP-IG guidelines recommend limiting access to a patient at risk of suicide to a weekly dose of an antidepressant. Preferably, the use of antidepressants from the group of SSRIs in small forms of release.


[tRNA- and aminoacyl-tRNA in the rabbit liver in ontogenesis (author's transl)].
The acceptor capacity of tRNAs and tRNA-synthetases activities of liver extracts was compared for rabbits of different age groups. The level of maximum tRNA aminoacylation in vitro of newborn rabbit (3-5 days) liver for glycine, glutamic acid, leucine, tryptophan, and phenylalanine and tRNA of old rabbits (5 years) liver for glutamic acid, leucine, phenylalanine, and glycine was 1,5-3 times lesser in comparison to that of 1 and 2 years rabbits. The pool of endogenous aminoacyl-tRNAs in 3-5 days rabbits liver was also considerably lower for above mentioned amino acids. The results of short-term heating of tRNA preparations in the presence of Mg2- given the possibility to assume that the decreases tRNA preparations in the presence of Mg2+ give the possibility to assume that the decreases tRNA acceptor activity of the newborn animals depends upon the presence of tRNA inactive conformers. Another reason is the greater loss of the CCA-end in mentioned tRNA. None of these factors in the reason of low acceptor activity of old rabbit liver tRNA which seems to be caused by more considerable disturbances in he molecular structure. Aminoacyl-tRNA-synthetases activities of liver extracts of the same age groups increases during development of animals and decrease subsequently in the liver of old (5 years) rabbits. However, dynamics and quantitative characteristics of these changes are not similar for enzymes of different amino acid specificities.


[Effect of segmental Le Fort I osteotomy and bilateral sagittal split ramus osteotomy on the condyle position in skeletal class III malocclusion patients].
To investigate the effect of segmental Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) on the condyle position in skeletal class III malocclusion patients. In this retrospective study, 19 patients with skeletal class III malocclusion who met the inclusion criteria were enrolled. All the patients underwent the segmental Le Fort I osteotomy and BSSRO. Cone beam computed tomography (CBCT) scans were performed in the following phases: T1: within one week before the surgeries; T2: within one week post-surgery;T3:three months post-surgery; T4: 6 to 14 months post-surgery. The posterior spaces, anterior spaces and the superior spaces of the bilateral temporomandibular joints were measured according to the Kamelchuk method respectively. The fossa ratios of the condyle and the distribution of the condyle positions related to the glenoid fossa (anterior, concentric and posterior position)were calculated. The results were analyzed statistically. The posterior space, the anterior space and the superior space of bilateral temporomandibular joints in T2 phase[right: (2.78±1.23) mm, (2.47±0.89) mm, (3.07±0.85) mm; left: (2.93±0.83) mm, (2.69±1.14) mm, (3.44±1.16) mm] showed significantly larger spaces than those in T1 phase [right: (1.81±0.95) mm, (1.65±0.55) mm, (2.13±0.52) mm; left: (2.12± 1.05) mm, (1.79±0.59) mm, (2.15±0.93) mm],in T3 phase [right: (2.08±1.25) mm, (1.79±0.68) mm, (1.80±0.76) mm; left: (2.05±0.75) mm, (1.99±0.94) mm, (2.14±0.71) mm] and in T4 phase [right: (1.94±0.77) mm, (1.81±0.69) mm, (2.05±0.69) mm; left: (1.89±0.69) mm, (1.80±0.61) mm, (2.19±0.75) mm], P<0.05. No significant differences were observed among T1,T3 and T4 phases in the terms of the joint spaces of both sides(P>0.05).The fossa ratio and the condyle position related to the glenoid fossa had no significant difference in all the four phases (P>0.05).The results suggested that the condyle moved downward in T2 phase and changed to the original pre-surgery position in T3 phase, then keot stable in T4 phase. Segmental Le Fort I osteotomy and BSSRO caused significant and transient changes of the condyle position in skeletal class III malocclusion patients. However, the condyle tended to move back to the original pre-surgery position and might keep stable.


Comparison of ZOOMit-DWI sequence and conventional DWI sequence in endometrial cancer.
Magnetic resonance diffusion-weighted imaging (DWI) has important clinical value in diagnosis and curative effect evaluation on endometrial carcinoma. How to improve the detection rate of endometrial small lesions by DWI is the research focus of MRI technology. This study aims to analyze the image quality of small field MRI ZOOMit-DWI sequence and conventional single-shot echo-planar imaging (SS-EPI) DWI sequence in the scanning of endometrial carcinoma, and to explore the clinical value of ZOOMit-DWI sequence. A total of 37 patients with endometrial carcinoma diagnosed by operation and pathology in the Second Xiangya Hospital of Central South University from July 2019 to May 2021 were collected. All patients were scanned with MRI ZOOMit-DWI sequence and SS-EPI DWI sequence before operation. Two radiologists subjectively evaluated the anatomical details, artifacts, geometric deformation and focus definition of the 2 groups of DWI images. At the same time, the signal intensity were measured and the signal-to-noise ratio (SNR), contrast to noise ratio (CNR), and apparent diffusion coefficient (ADC) of the 2 DWI sequences were calculated for objective evaluation. The differences of subjective score, objective score and ADC value of the 2 DWI sequences were analyzed. The SNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (301.96±141.85 vs 94.66±41.26), and the CNR of the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (185.05±105.45 vs 57.91±31.54, P<0.05). There was no significant difference in noise standard deviation between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). The subjective score of anatomical detail and focus definition in the ZOOMit-DWI group was significantly higher than that of the SS-EPI DWI group (both P<0.05). The subjective score of artifacts and geometric deformation of ZOOMit-DWI group was significantly lower than that of the SS-EPI DWI group (both P<0.05). ADC had no significant difference between the ZOOMit-DWI group and the SS-EPI DWI group (P>0.05). The image quality of ZOOMit-DWI is significantly higher than that of conventional SS-EPI DWI. In the MRI DWI examination of endometrial carcinoma, ZOOMit-DWI can effectively reduce the geometric deformation and artifacts of the image, which is more conducive to clinical diagnosis and treatment.


Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection and Select for Attenuated Virulence in an Enteric Pathogen.
Pathogen virulence exists on a continuum. The strategies that drive symptomatic or asymptomatic infections remain largely unknown. We took advantage of the concept of lethal dose 50 (LD50) to ask which component of individual non-genetic variation between hosts defines whether they survive or succumb to infection. Using the enteric pathogen Citrobacter, we found no difference in pathogen burdens between healthy and symptomatic populations. Iron metabolism-related genes were induced in asymptomatic hosts compared to symptomatic or naive mice. Dietary iron conferred complete protection without influencing pathogen burdens, even at 1000× the lethal dose of Citrobacter. Dietary iron induced insulin resistance, increasing glucose levels in the intestine that were necessary and sufficient to suppress pathogen virulence. A short course of dietary iron drove the selection of attenuated Citrobacter strains that can transmit and asymptomatically colonize naive hosts, demonstrating that environmental factors and cooperative metabolic strategies can drive conversion of pathogens toward commensalism.


Mainstream smoke chemistry analysis of samples from the 2009 US cigarette market.
A survey of selected mainstream smoke constituents from commercially marketed US cigarettes was conducted in 2009. The US cigarette market was segmented into thirteen (13) strata based on Cambridge Filter Method (CFM) "tar" category and cigarette design parameters. Menthol and non-menthol cigarettes were included. Sixty-one (61) cigarette brand styles were chosen to represent the market. Another thirty-four (34) brand styles of interest were included in the survey along with a Kentucky 3R4F reference cigarette. Twenty mainstream smoke constituents were evaluated using the Health Canada smoking regimen. By weighting the results of the 61 brand styles using the number of brand styles represented by each stratum, the mainstream smoke constituent means and medians of the US cigarette market were estimated. For nicotine, catechol, hydroquinone, benzo(a)pyrene and formaldehyde the mean yields increased with increasing "tar" yields. Constituent yields for the ultra-low "tar" and low "tar" cigarettes were not significantly different for most other analytes as ventilation blocking defeated any filter air dilution design features. In contrast, normalization per mg nicotine provided an inverse ranking of cigarette yields per CFM "tar" categories. Menthol cigarette mean constituent yields were observed to be within the range of the non-menthol cigarettes of similar "tar" categories.


Geometric measurements of the lumbar spine in Chinese men during trunk flexion.
An analysis of the geometric data of the lumbar spine in Chinese men. Lateral radiographs were obtained of 16 men in the upright position to a trunk flexion of 90 degrees in 30 degrees increments. To establish reference data concerning the geometry of the lumbar spine for various degrees of trunk flexion. In previous studies, the morphometry and alignment of the lumbar spine have been investigated. Reports of systematic analyses of the lumbar spine in trunk flexion have lacked adequate radiographic data. Moreover, few studies have focused on measuring lumbar spine geometric data in Chinese individuals. A total of 67 landmarks on each radiograph were identified. They were marked by investigators and digitized using a HyperSpace digitizing system (V.17: Mira Imaging Inc., Salt Lake City, UT). The geometric configuration of the vertebrae and discs then was derived from the digitized points. The dimensions of the vertebrae and disc on the lumbar spine obtained in this study were similar to those of previous studies. The motion of the lumbosacral spine had the greatest contribution in trunk flexion, approximately 90% (i.e., rotating at the rate of 9 degrees for each 10 degrees of trunk flexion) when the trunk was flexed from 30 degrees to 60 degrees. After that, the hips were dominant in accomplishing the trunk flexion from 60 degrees to horizontal. This motion patterns may be useful for making clinical diagnoses of lumbar function in Chinese men. No obvious interracial differences were found in the geometric data found in this study, which suggests that morphometric data obtained from Caucasian individuals may be applied to Chinese patients for clinical purposes.


iPSC modeling of severe aplastic anemia reveals impaired differentiation and telomere shortening in blood progenitors.
Aplastic Anemia (AA) is a bone marrow failure (BMF) disorder, resulting in bone marrow hypocellularity and peripheral pancytopenia. Severe aplastic anemia (SAA) is a subset of AA defined by a more severe phenotype. Although the immunological nature of SAA pathogenesis is widely accepted, there is an increasing recognition of the role of dysfunctional hematopoietic stem cells in the disease phenotype. While pediatric SAA can be attributable to genetic causes, evidence is evolving on previously unrecognized genetic etiologies in a proportion of adults with SAA. Thus, there is an urgent need to better understand the pathophysiology of SAA, which will help to inform the course of disease progression and treatment options. We have derived induced pluripotent stem cell (iPSC) from three unaffected controls and three SAA patients and have shown that this in vitro model mimics two key features of the disease: (1) the failure to maintain telomere length during the reprogramming process and hematopoietic differentiation resulting in SAA-iPSC and iPSC-derived-hematopoietic progenitors with shorter telomeres than controls; (2) the impaired ability of SAA-iPSC-derived hematopoietic progenitors to give rise to erythroid and myeloid cells. While apoptosis and DNA damage response to replicative stress is similar between the control and SAA-iPSC-derived-hematopoietic progenitors, the latter show impaired proliferation which was not restored by eltrombopag, a drug which has been shown to restore hematopoiesis in SAA patients. Together, our data highlight the utility of patient specific iPSC in providing a disease model for SAA and predicting patient responses to various treatment modalities.


Reduced Syntactic Processing Efficiency in Older Adults During Sentence Comprehension.
Researchers have frequently reported an age-related decline in semantic processing during sentence comprehension. However, it remains unclear whether syntactic processing also declines or whether it remains constant as people age. In the present study, 26 younger adults and 20 older adults were recruited and matched in terms of working memory, general intelligence, verbal intelligence and fluency. They were then asked to make semantic acceptability judgments while completing a Chinese sentence reading task. The behavioral results revealed that the older adults had significantly lower accuracy on measures of semantic and syntactic processing compared to younger adults. Event-related potential (ERP) results showed that during semantic processing, older adults had a significantly reduced amplitude and delayed peak latency of the N400 compared to the younger adults. During syntactic processing, older adults also showed delayed peak latency of the P600 relative to younger adults. Moreover, while P600 amplitude was comparable between the two age groups, larger P600 amplitude was associated with worse performance only in the older adults. Together, the behavioral and ERP data suggest that there is an age-related decline in both semantic and syntactic processing, with a trend toward lower efficiency in syntactic ability.


The subjectively perceived injectability as an early indicator for adverse events?
With an increasing demand of aesthetic soft-tissue filler treatments, the occurrence of adverse events rises likewise. An optimized injection algorithm adapted to product characteristics (eg, rheology) of the soft-tissue filler is crucial in order to ensure satisfying clinical outcomes and high patient safety. To identify a subjective feedback mechanism for the avoidance of adverse events after soft-tissue filler injection procedures. A retrospective data analysis of n = 387 aesthetic treatments performed on n = 291 patients (4 males, 287 females) with different soft-tissue fillers with regard to loss of volume (filling effect), injected layer, injectability ("ease of injection"), injected volume, and injection technique was conducted. The subjectively perceived injectability during the injection process was statistically significantly related to G-Prime value with rs = 0.101 with p = 0.048, indicating an increased difficulty while injecting products with higher G-Prime. The occurrence of adverse events was also statistically significantly related to the injectability: injections with increased subjectively perceived difficulty showed increasing odds of developing adverse events by OR 0.157 with p = 0.002. Injections that were subjectively more difficult to perform are more likely to develop adverse events. Respecting the layered arrangement of the face, the recommended and approved depth and facial region for each specific treatment enable practitioners to achieve satisfying outcomes while keeping the rate of adverse events low.


Molecular structure and mechanical properties of keratins.
Keratinized epidermal appendages have mechanical properties which are typical of those expected for composite materials with a filament-matrix texture. At 100% relative humidity the matrix is highly hydrated, mechanically weak and exhibits viscoelastic behaviour. As the water content is reduced the matrix becomes progressively stiffer until at 0% relative humidity its properties approach those of the filaments. In the normally encountered range of relative humidities the advantages of such a texture are that stress is evenly distributed over the filaments, which constitute the load-bearing elements, thus preventing the propagation of cracks from local imperfections. Based on studies of synthetic filament-matrix composites potentialities for the adaptation of the mechanical properties to specific functions are to be found in variation of the properties of the filaments and the matrix and also of the cross-linking. Since keratin is a filament-matrix composite at the molecular level the great diversity of molecular species presumably has its origin in such adaptation. Superimposed on filament and matrix composition and properties are the variables of filament orientation and proportion and there is abundant evidence that many of the subtler properties of keratinized appendages stem from variations in these factors.


Detection of fluid motion direction based on the rotational Doppler effect of grafted perfect vortex beam.
Vortex beams have attracted much attention due to their unique rotational Doppler effect. With the in-depth study of vortex beams, many new vortex beams have been proposed gradually, while the detection of fluid motion is of great significance for the study of ocean turbulence. Based on the rotational Doppler effect of the grafted perfect vortex beam, we propose a non-embedded optical method for real-time detection of the magnitude and direction of fluid velocity and establish a two-dimensional fluid model for simulation verification. It is proved that the grafted perfect vortex beam can detect the magnitude and direction of the fluid velocity at the same time, which may provide a new way and theoretical support for the detection of fluid motion direction.


Bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophila oogenesis.
Organized boundaries between different cell fates are critical in patterning and organogenesis. In some tissues, long-range signals position a boundary, and local Notch signaling maintains it. How Notch activity is restricted to boundary regions is not well understood. During Drosophila oogenesis, the long-range signals EGF and Dpp regulate expression of bunched (bun), which encodes a homolog of mammalian transcription factors TSC-22 and GILZ. Here, we show that bun establishes a boundary for Notch signaling in the follicle cell epithelium. Notch signaling is active in anterior follicle cells and is required for concurrent follicle cell reorganizations including centripetal migration and operculum formation. bun is required in posterior columnar follicle cells to repress the centripetal migration fate, including gene expression, cell shape changes and accumulation of cytoskeletal components. bun mutant clones adjacent to the centripetally migrating follicle cells showed ectopic Notch responses. bun is necessary, but not sufficient, to down-regulate Serrate protein levels throughout the follicular epithelium. These data indicate that Notch signaling is necessary, but not sufficient, for centripetal migration and that bun regulates the level of Notch stimulation to position the boundary between centripetally migrating and stationary columnar follicle cells.


Characterization of a novel cysteine-rich antifungal protein from Fusarium graminearum with activity against maize fungal pathogens.
Filamentous fungi are an invaluable source for biocontrol strategies and for production and development of different antifungal polypeptides. Within this context, cysteine-rich antifungal AFP-like peptides stand out among many different antimicrobial compounds given their production easiness, stability, versatility, and efficacy. AFP from Aspergillus giganteus represents the hallmark of this still increasing family of antifungal polypeptides. Close in silico analyses of the Fusarium graminearum genome revealed the presence of an AFP-like peptide, here designated as FgAFP. This new peptide was cloned, produced in the yeast Pichia pastoris, and characterized. The results obtained showed its strong and specific antifungal activity against several well-recognized maize pathogens, but inefficacy against F. oxysporum, which has not been described as a natural biological competitor of other fungal pathogens assayed. All results together suggest that this small peptide is an important factor for the fungal interplays involved in maize infection and reveals unforeseen potential biotechnological applications for FgAFP in maize production and storage.


Short term hypothermic perfusion for intestinal preservation with dimethyl sulfoxide.
Morphologic changes, resulting from intracellular or extracellular perfusates with dimethyl sulfoxide as a cryophylactic agent, are similar and probably due to the anoxic period, after short term perfusion. These changes are temporary and are followed by complete recovery. No statistically significant changes in disaccharidase activity between intracellular and extracellular perfusates are found in the jejunal mucosa. No differences are found between normal disaccharidase activity and values obtained experimentally. Results of this study support the suggestion that vascular endothelial damage, as observed in evaluations utilizing the electron microscope, is certainly an important factor in the limitation of perfusion techniques of the intestine.


Dementia Care Content in Prelicensure Nursing Curricula: A Pilot Mixed-Methods Study.
Having a nursing workforce equipped to provide quality care for patients living with dementia is essential. The purpose of this study was to investigate how undergraduate nursing programs integration of dementia care content into their curricula. Using sequential explanatory mixed methods, a stratified sample of 137 representatives of programs in 11 states with dense elderly populations completed a quantitative survey. A subsample (n = 8) completed qualitative e-mail interviews. Most respondents indicated dementia care content was integrated into their curricula (n = 103, 92.8%). Clinical partnership with dementia care centers was associated with a greater proportion of students interacting with individuals having dementia (p = .02). Curriculum overload was the most significant challenge to integrating dementia content (n = 61, 43.9%). Qualitative themes supported the quantitative results. Future research is needed to identify best practices to ensure that nursing curricula provide essential content to meet the care needs of the growing population of individuals with dementia. [J Nurs Educ. 2018;57(2):88-95.].


Short communication: Prioritizing communities for HIV prevention in sub-Saharan Africa.
HIV prevalence is the most commonly used measure to prioritize communities for HIV prevention. We show that data on two HIV infection stages (early vs. nonearly and late vs. nonlate) allow estimation of two better measures of prevention need: HIV incidence (for prevention of HIV acquisition) and expected probability of HIV transmission in unprotected sex acts between HIV-infected community members and susceptible individuals (for prevention of HIV transmission). The three ranking schemes--by prevalence, incidence, and transmission probability--lead to significantly different community rank orders. Disease stage information should be collected in HIV surveys.


Epidemiological features of moyamoya disease in Japan.
To clarify the clinical features of moyamoya disease in Japan, 941 patients with definite moyamoya disease were analyzed from the databases constructed by the Research Committee on Moyamoya Disease, established by the Ministry of Health, Labour and Welfare. Moyamoya disease occurs much more frequently among women than men, with a female-to-male ratio of 1.98. A family history of the disease was observed in 14.9%. The age at onset was characterized by two peaks: one at 5-9 years and another lower peak at around 40 years. Initial clinical features were transient ischemic attack in 46%, infarction in 20%, hemorrhage in 21%, headache in 6%, and epilepsy in 4%. The distribution of the age at onset showed one peak at around 40 years in patients with hemorrhage but two peaks in patients with ischemia.


Influence of hydroxyapatite granule size, porosity, and crystallinity on tissue reaction in vivo. Part B: a comparative study with biphasic synthetic biomaterials.
The aim of this study was to compare the influence of the physical-chemical properties of synthetic hydroxyapatite (HA) and biphasic commercial materials on the biological behavior of study materials through material characterization and SEM analysis before and after application in rabbit tibias. Two defects were performed in each tibiae for a total of 180 defects: Group I HA granules (2000-4000 μm), Group II HA granules (1000-2000 μm), Group III HA granules (600-1000 μm), Group IV Ossceram® nano (Bredent medical GmbH & Co. KG, Senden, Germany), Group V 4Bone® granules (MIS Implants Technologies Ltd, Shlomi, Israel), and Group VI: empty defect acted as control. Comparison was performed by mean of material characterization, SEM, and EDX. 4Bone: Pores between 300 μm and 100 μm with intra- and interparticle spaces. Ossceram show also interparticle and intraparticle pores, between 100 μm and 26 μm, but the proportion of interparticles in the 4Bone is clearly minor than in the Ossceram. Related with pure HA, Group III has the greatest porosity (69.3%). For Group I, the intraparticle pores (0.71 μm) are about 8 times larger than those of the other two samples. The analysis of the images of in vivo SEM shown as biphasic groups has presented a more gradual resorption of the material. HA-based biomaterials, both pure and biphasic, are an effective means for bone regeneration processes; of these, materials with higher initial and secondary porosimetry allow greater cell colonization and therefore more effective substitution by new bone. The two-phase materials have a higher ion release to the environment in the early stages and thus allow greater colonization by collagen fibers that can be matured into new bone.


Comparison of MR pulse sequences in the detection of multiple sclerosis lesions.
To compare the sensitivity of conventional spin-echo, fast spin-echo, fast fluid-attenuated inversion recovery (FLAIR), and turbo gradient spin-echo MR sequences in the detection of multiple sclerosis lesions. Conventional spin-echo, fast spin-echo, fast FLAIR, and turbo gradient spin-echo sequences were performed on a 1.0-T MR imager in seven patients with clinically definite multiple sclerosis. The images in each sequence were evaluated by two raters and consensus was reached by agreement. In comparing conventional spin-echo with fast spin-echo sequences, five lesions were seen only by conventional spin-echo and 63 were seen only by fast spin-echo; in comparing conventional spin-echo with fast FLAIR sequences, 18 lesions were seen only by conventional spin-echo and 109 only by fast FLAIR; in comparing conventional spin-echo with turbo gradient spin-echo sequences, 51 lesions were seen only by conventional spin-echo and seven only by turbo gradient spin-echo; in comparing fast spin-echo with fast FLAIR sequences, 45 lesions were seen only by fast spin-echo and 52 only by fast FLAIR. Fast spin-echo and fast FLAIR sequences improve the sensitivity of MR imaging in the detection of multiple sclerosis lesions with reduced acquisition time as compared with conventional spin-echo sequences. These sequences should therefore be considered for serial studies in patients with multiple sclerosis. The sensitivity of turbo gradient spin-echo was inferior to the other sequences, but its reduced acquisition time could make this technique the ideal choice for patients who cannot tolerate longer examination times.


Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in acute myeloid leukemia evolving from myelodysplastic syndromes: a pilot study.
Acute myeloid leukemia preceded by a myelodysplastic syndrome (MDS-AML) is generally regarded as a high-risk type of AML, where remissions are rare and of short duration. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is suggested to increase the sensitivity of leukemic cells to cycle-specific drugs. In this study 14 MDS-AML patients were given rhGM-CSF together with standard induction chemotherapy (TAD). rhGM-CSF was started 48 h prior to chemotherapy and given for up to 3 weeks. The results showed eight (58%) complete and two (14%) partial remissions, while another two (14%) patients had minor responses. One patient relapsed after 1 year, and then responded a second time. rhGM-CSF had to be stopped owing to local allergic reactions in two patients, both non-responders, but was otherwise well tolerated. Compared with our historical group of controls we found significantly higher remission rates, fewer early deaths, fewer fever days, and fewer days with both neutropenia and thrombocytopenia among the patients treated with rhGM-CSF and TAD. The estimated median over-all survival was 332 days. The severity of initial myelodysplastic changes did not correlate to the outcome of therapy but the degree of peripheral blood dysplasia decreased among responding patients. MDS-AML patients in this pilot study did respond better, and with minimal toxicity, when standard induction chemotherapy was given in combination with rhGM-CSF.


Acute BDNF treatment upregulates GluR1-SAP97 and GluR2-GRIP1 interactions: implications for sustained AMPA receptor expression.
Brain-derived neurotrophic factor (BDNF) plays several prominent roles in synaptic plasticity and in learning and memory formation. Reduced BDNF levels and altered BDNF signaling have been reported in several brain diseases and behavioral disorders, which also exhibit reduced levels of AMPAr subunits. BDNF treatment acutely regulates AMPA receptor expression and function, including synaptic AMPAr subunit trafficking, and implicates several well defined signaling molecules that are required to elicit long term potentiation and depression (LTP and LTD, respectively). Long term encoding of synaptic events, as in long term memory formation, requires AMPAr stabilization and maintenance. However, factors regulating AMPAr stabilization in neuronal cell membranes and synaptic sites are not well characterized. In this study, we examine the effects of acute BDNF treatment on levels of AMPAr-associated scaffolding proteins and on AMPAr subunit-scaffolding protein interactions. We also examine the effects of BDNF-dependent enhanced interactions between AMPAr subunits with their specific scaffolding proteins on the accumulation of both types of proteins. Our results show that acute BDNF treatment upregulates the interactions between AMPAr subunits (GluR1 and GluR2) with their scaffold proteins SAP97 and GRIP1, respectively, leading to prolonged increased accumulation of both categories of proteins, albeit with distinct mechanisms for GluR1 and GluR2. Our findings reveal a new role for BDNF in the long term maintenance of AMPA receptor subunits and associated scaffolding proteins at synapses and further support the role of BDNF as a key regulator of synaptic consolidation. These results have potential implications for recent findings implicating BDNF and AMPAr subunits in various brain diseases and behavioral disorders.


Effect of Simulated Bone Resorption on the Biomechanical Performance of Intramedullary Devices for Foot and Ankle Arthrodesis.
Midfoot and subtalar arthrodesis surgeries are performed to correct foot deformities and relieve arthritic pain. These procedures often employ intramedullary (IM) devices. The aim of the present study was to evaluate the biomechanical performance of a sustained dynamic compression (SDC) IM device compared to mechanically static devices in withstanding the effects of simulated bone resorption. Mechanically static and SDC IM devices were implanted in simulated bone blocks (n = 5/device). Compressive loads were measured with a custom-made mechanism to simulate bone resorption. The construct bending stiffness was determined from a 4-point bend test. Resorption was simulated by cutting a 1 mm or 2 mm gap in the midpoint of each construct and repeating the loading (n = 6/device). Initial compressive loads after device insertion were greater in the SDC IM devices when compared to the static devices (p < .01). The SDC device was able to sustain compression from 2 mm to 5.5 mm of simulated resorption depending upon device length, while the static devices lost compression within 1 mm of simulated resorption regardless of implant length (p < .001). In the 4-point bend test, the SDC device maintained its bending stiffness during simulated resorption whereas the static device displayed a significant loss in bending stiffness after 1 mm of simulated resorption (p < .001). The SDC device exhibited a significantly higher bending stiffness than the static device (p < .001). The SDC IM device demonstrated superior biomechanical performance during simulated resorption compared to static devices (p < .001). In conclusion, the ability of SDC IM devices to maintain construct stability and sustain compression across the fusion site while adapting to bone resorption may lead to greater fusion rates and overall quicker times to fusion than static IM devices. Surgeons who perform midfoot and subtalar arthrodesis procedures should be aware of a device's ability to sustain compression, especially in cases where bone resorption and joint settling are prevalent postoperatively.


Thin wafer-level camera lenses inspired by insect compound eyes.
We propose a microoptical approach to ultra-compact optics for real-time vision systems that are inspired by the compound eyes of insects. The demonstrated module achieves approx. VGA resolution with a total track length of 1.4 mm which is about two times shorter than comparable single-aperture optics on images sensors of the same pixel pitch. The partial images that are separately recorded in different optical channels are stitched together to form a final image of the whole field of view by means of image processing. A software correction is applied to each partial image so that the final image is made free of distortion. The microlens arrays are realized by state of the art microoptical fabrication techniques on wafer-level which are suitable for a potential application in high volume e.g. for consumer electronic products.


Adaptive ammoniagenesis in chronic renal failure.
The role of gamma-glutamyltransferase (gamma-GT) in renal ammoniagenesis, glutamine (Gln), and glutathione (GSH) utilization was evaluated in the intact functioning rat kidney of subtotal nephrectomy (SNX) model of chronic renal failure (CRF). NH4+ derived from extracellular gamma-GT hydrolysis of Gln and GSH was differentiated from the intramitochondrial phosphate-dependent glutaminase by using acivicin, a gamma-GT-specific inhibitor. In the control (C) group Gln extraction accounted for 61% of total NH4+ production (sum of renal venous and urinary NH4+), but only 41% in SNX group. In the SNX group GSH extraction accounted for 10% of total NH4+ production, but only 1% in the C group. Acivicin inhibited 44% and 33% of total NH4+ production in SNX and C group respectively, as compared to baseline before acivicin. In CRF, gamma-GT a key enzyme of the gamma-glutamyl cycle plays a significant role in adaptive ammoniagenesis.


Vesicular stomatitis virus polymerase's strong affinity to its template suggests exotic transcription models.
Vesicular stomatitis virus (VSV) is the prototype for negative sense non segmented (NNS) RNA viruses which include potent human and animal pathogens such as Rabies, Ebola and measles. The polymerases of NNS RNA viruses only initiate transcription at or near the 3' end of their genome template. We measured the dissociation constant of VSV polymerases from their whole genome template to be 20 pM. Given this low dissociation constant, initiation and sustainability of transcription becomes nontrivial. To explore possible mechanisms, we simulated the first hour of transcription using Monte Carlo methods and show that a one-time initial dissociation of all polymerases during entry is not sufficient to sustain transcription. We further show that efficient transcription requires a sliding mechanism for non-transcribing polymerases and can be realized with different polymerase-polymerase interactions and distinct template topologies. In conclusion, we highlight a model in which collisions between transcribing and sliding non-transcribing polymerases result in release of the non-transcribing polymerases allowing for redistribution of polymerases between separate templates during transcription and suggest specific experiments to further test these mechanisms.


Excentric cleavage products of beta-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1-mediated transcriptional activation.
Both retinoids and carotenoids are potentially useful chemopreventive agents. In this study we tested the effect of synthetic excentric cleavage products of beta-carotene on the growth of the MCF-7, Hs578T and MDA-MB-231 human breast cancer cells. The apo-beta-carotenoic acids (beta-apo-CA) beta-apo-14'-, beta-apo-12'-, beta-apo-10'- and beta-apo-8'-CA are structurally similar to all-trans-retinoic acid (atRA) but have different side chain lengths. Nine days of treatment with atRA inhibited MCF-7 and Hs578T cell proliferation in a dose-dependent manner. beta-apo-14'-CA and beta-apo-12'-CA significantly inhibited MCF-7 growth, whereas only beta-apo-14'-CA inhibited Hs578T growth. None of these treatments inhibited the growth of MDA-MB-231 cells. Potential mechanisms of growth inhibition, i.e., regulation of the cell cycle control proteins E2F1 and retinoblastoma protein (RB), and effect on activator protein-1 (AP-1)-mediated gene regulation were examined. beta-apo-14'-CA and atRA inhibited the expression of E2F1 protein in MCF-7 and Hs578T cells. beta-apo-14'-CA, beta-apo-12'-CA and atRA down-regulated RB protein expression in MCF-7 but not in Hs578T cells. The effect of phorbol ester-induced transcriptional activation of a collagenase promoter-reporter gene construct was strongly inhibited by 1 micromol/L beta-apo-14'-CA, atRA (MCF-7, Hs578T) or beta-apo-12'-CA (MCF-7). These effects were due neither to cellular conversion of beta-apo-CA to atRA nor to high affinity binding to the retinoid acid receptors. Thus, beta-apo-CAs were effective inhibitors of breast tumor cell proliferation, possibly mediated through down-regulation of cell cycle regulatory proteins and/or inhibition of AP-1 transcriptional activity. The ability of beta-apo-CA to regulate breast tumor cell growth independently of conversion to atRA suggests that these compounds may have fewer side effects than retinoids and, therefore, have a potential chemotherapeutic value that deserves further examination.


Semen Parameters Among Transgender Women With a History of Hormonal Treatment.
To report on the semen quality parameters in transgender women who pursued semen cryopreservation either in the presence or absence of gender-affirming hormonal medication. This retrospective cohort study was conducted as a chart review of consecutive transgender women presenting for semen cryopreservation between January 1, 2012 and March 31, 2018. Demographic data and semen parameters were assessed. Primary outcomes were the semen parameters in subjects with either no exposure, previous exposure or current exposure to gender-affirming hormonal medication. Twenty-eight patients presented for semen cryopreservation and produced 69 specimens. Using a Kruskal-Wallis test, semen analyses were compared between patients who had never used gender-affirming hormonal medication, those who had previously used hormonal medication but discontinued prior to specimen collection, and those who used medication at the time of specimen collection. Median semen parameters for each group were as follows: volume-2.7 mL, 2.1 mL, 0.9 mL, respectively (P = .12); concentration-63.6 M/mL, 39.0 M/mL, 2.4 M/mL, respectively (P < .01); percent motility-51.5%, 34.3%, 15.6%, respectively (P < .01); and the total motile count was 63.2 M,39.1 M, 0.2 M, respectively (P < .01). Fifteen specimens were collected after discontinuing hormonal medication with a mean discontinuation period of 4.4 months. Specimens collected in the presence of hormonal medication were associated with abnormal semen parameters. Specimens collected after discontinuation of gender-affirming treatments were comparable to transgender women who had never used hormonal medication. Transgender women should be counseled about the potential impact of gender-affirming hormones and to consider fertility preservation prior to gender-affirming treatments.


Non-specific aorto-arteritis (Takayasu's disease) in children.
Digital subtraction panaorto-arteriography was performed in 32 consecutive children (21 females, mean age 10.8 years) with non-specific aorto-arteritis to assess digital subtraction angiography (DSA) in imaging these children and to study the patterns of involvement in the Indian sub-continent. Diagnostic quality DSA images were obtained in 21 out of 27 intravenous and nine out of 11 intra-arterial studies. Obstructive lesions were present in all the patients and commonly involved the abdominal aorta (24 patients) and renal arteries (20 patients). Aneurysms were seen in five patients and predominantly involved the descending thoracic aorta. Pulmonary artery involvement was uncommon (five out of 20 patients) and clinically silent. Based on clinical and angiographic features, percutaneous transluminal angioplasty was performed for the management of uncontrolled hypertension in eight patients (10 lesions). Initial success was obtained in eight procedures (80%). Re-stenosis occurred after 5.5 months in one patient, but was successfully re-dilated. The follow-up period ranged between 5 and 16 months (mean 9 months). Long-term efficacy of transluminal angioplasty in the management of these children is awaited.


[Microorganisms isolated from urinary tract infection and their beta-lactamase production and evaluation of clinical efficacy of sulperazone].
Clinical survey of microorganisms isolated from urinary tract infection (UTI) was carried out at the four major hospitals in Mie Prefecture from May to July, 1987, and production of beta-lactamase of the microorganisms was determined by the acidimetric method, "beta-checker". Among the total of 460 strains isolated from urine samples, 135 of gram positive cocci and 325 of gram negative rods were contained. Sixty percent of the gram negative rods and 14% of gram positive cocci produced beta-lactamase. Pseudomonas aeruginosa, E. coli and Serratia marcescens were representative organisms which produced beta-lactamase. Acinetobacter, Klebsiella, Enterobacter and Citrobacter species produced beta-lactamase at a higher rate but those were not so frequently isolated. In the sensitivity test to Sulperazone, the representative organisms isolated from urine, as a whole, had a sensitivity of 74% and E. coli, Klebsiella, S. epidermidis and Pseudomonas aeruginosa were highly sensitive, while Enterobacter cloacae and Serratia marcescens showed low sensitivity. The clinical efficacy of Sulperazone was evaluated in 26 patients with complicated UTI. Overall effectiveness rate and eradication rate of beta-lactamase production organisms were 73.1 and 63%, respectively. Sulperazone is concluded to be a useful antibiotic for treating complicated UTI induced by beta-lactamase production organisms from the point of microbiology and safety.


Trauma induced heterotopic ossification patient serum alters mitogen activated protein kinase signaling in adipose stem cells.
Post-traumatic heterotopic ossification (HO) is the formation of ectopic bone in non-osseous structures following injury. The precise mechanism for bone development following trauma is unknown; however, early onset of HO may involve the production of pro-osteogenic serum factors. Here we evaluated serum from a cohort of civilian and military patients post trauma to determine early induction gene signatures in orthopaedic trauma induced HO. To test this, human adipose derived stromal/stem cells (hASCs) were stimulated with human serum from patients who developed HO following trauma and evaluated for a gene panel with qPCR. Pathway gene analysis ontology revealed that hASCs stimulated with serum from patients who developed HO had altered gene expression in the activator protein 1 (AP1) and AP1 transcriptional targets pathways. Notably, there was a significant repression in FOS gene expression in hASCs treated with serum from individuals with HO. Furthermore, the mitogen-activated protein kinase (MAPK) signaling pathway was activated in hASCs following serum exposure from individuals with HO. Serum from both military and civilian patients with trauma induced HO had elevated downstream genes associated with the MAPK pathways. Stimulation of hASCs with known regulators of osteogenesis (BMP2, IL6, Forskolin, and WNT3A) failed to recapitulate the gene signature observed in hASCs following serum stimulation, suggesting non-canonical mechanisms for gene regulation in trauma induced HO. These findings provide new insight for the development of HO and support ongoing work linking the systemic response to injury with wound specific outcomes.


Effect of dietary fat level on growth and lipogenesis in the colostrum deprived neonatal pig.
Thirty male neonatal pigs were obtained by cesarean section and randomly allotted from littermate groups to three diets containing 2%, 17%, and 32% fat on a dry matter basis. Butterfat was used to replace glucose in the isoenergetic liquid, semipurified diets. Each pig was placed in a sterile isolator and fed ad libitum five times daily. After 14 days, pigs were weighed, killed, and samples of liver and backfat were obtained. The carcass of each pig was ground and samples obtained for determination of total body fat and protein. An increase in the level of dietary fat resulted in a significant increase in 14 day weight gain and a tendency for improved feed efficiency. These results demonstrate not only that the neonatal pig can utilize semipurified liquid diets high in butterfat content, but also that energy from butterfat appears to be used as efficiently as energy from glucose from growth purposes. Increasing dietary fat level decreased the activity of fatty acid synthetase and citrate cleavage enzyme in adipose tissue and liver, and decreased the activity of malic enzyme in adipose tissue. The specific activities of these three enzymes were higher in adipose tissue than in liver.


[Spas in Gallo-roman Aquitaine].
We have various witnesses about spas during the gallo-roman period; it is in Luchon, Dax, Bagnères-de-Bigorre and Amélie les Bains, that we have the most important number of documents, coins, various chinas, and votive stones. It is interesting to note that after two thousand years the therapeutic qualities of mineral hot waters springs are still recognized; and in addition to the four mentioned spas, we can add: Barbotan, Prechacq, Saint-Christau, Capvern, Encausse, Salies-du-Salat, Ax-les-Thermes, Aulus, Alet, Rennes-les-Bains. It is interesting also to note that goddesses exhibited near the springs, were later replaced by Saints, which were the only explanation about the activity of the springs during several centuries.


Comparative evaluation of five protocols for protein extraction from stony corals (Scleractinia) for proteomics.
Corals especially the reef-building species are very important to marine ecosystems. Proteomics has been used for researches on coral diseases, bleaching and responses to the environment change. A robust and versatile protein extraction protocol is required for coral proteomics. However, a comparative evaluation of different protein extraction protocols is still not available for proteomic analysis of stony corals. In the present study, five protocols were compared for protein extraction from stony corals. The five protocols were TRIzol, phenol-based extraction (PBE), trichloroacetic acid (TCA)-acetone, glass bead-assisted extraction (GBAE) and a commercially available kit. PBE, TRIzol and the commercial kit were more robust for extracting proteins from stony corals. The protein extraction efficiency and repeatability, two dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI TOF MS) were employed to evaluate the protocols. The results indicated that PBE protocol had the better protein extraction efficiency than the others. Protein extraction coverage varied among the procedures. Each protocol favored for certain proteins. Therefore, it is very important for coral proteomic analysis to select a suitable protein protocol upon the experimental design. In general, PBE protocol can be the first choice for extracting proteins from stony corals.


Influence of oral cimetidine and ranitidine on gastric emptying in active duodenal ulcer.
The effect on gastric emptying of 400 mg cimetidine and two doses of ranitidine (150 and 300 mg) given orally was evaluated in 45 patients with endoscopically proved duodenal ulcer and in 28 healthy controls. Gastric emptying of a radiolabeled solid phase meal was assessed. Cimetidine was confirmed not to have any significant influence on gastric emptying in duodenal ulcer patients or in healthy subjects. The significant delay in gastric emptying observed with ranitidine was dose dependent, and at the same time more pronounced in patients with duodenal ulcer than in healthy subjects. Early ulcer healing was unrelated to the changes in gastric emptying elicited by the tested drugs.


Protective effects of non-mitogenic human acidic fibroblast growth factor on hydrogen peroxide-induced damage to cardiomyocytes in vitro.
To study the protective effect of non-mitogenic human acidic fibroblast growth factor (FGF) on cardiac oxidative injury in vivo. Ventricular cardiomyocytes were isolated from 1- to 3-d-old neonatal SD mice and cultured in Dulbecco's minimum essential medium supplemented with 15% fetal bovine serum under an atmosphere of 50 mL/L CO2-95% air at 37 degrees, as well as assessed by immunocytochemical assay. We constructed the cardiomyocyte injury model by exposure to a certain concentration of H2O2. Cellular viability, superoxide dismutase (SOD) activity, leakage of maleic dialdehyde and anti-apoptosis effect were included to evaluate the cardiac protective effect of non-mitogenic human acidic FGF. Over 50% of the cardiomyocytes beat spontaneously on the 2nd d of culture and synchronously beat after being cultured for 3 d. Forty-eight hours after plating was completed, the purity of such cultures was 95% myocytes, assessed by an immunocytochemical assay. Cellular viability dramatically decreased with the increasing of the concentration of H2O2. Non-mitogenic human acidic FGF showed significant resistance to the toxic effect of H2O2, significantly increased the cellular viability as well as the activity of SOD, and dramatically decreased the leakage of maleic dialdehyde as well as the cellular apoptosis rate. Hydrogen peroxide shows strong cytotoxicity to the cultured cardiac myocytes, and non-mitogenic human acidic FGF shows strong cardio-protective effect when exposed to a certain concentration of H2O2.


[Cardiopulmonary stress test in variable frequency stimulation: a comparison of Activitrax and Nova-MR pacemakers in VVI/AAI stimulation].
In seven patients with implanted intermedics NOVA MR pacemakers, we examined the cardiopulmonary effects of maximum bicycle ergometer exercise for three types of pacing in a randomized sequence: VVI or AAI at 70/min (SSI 70), rate adaptive temperature controlled with the implanted NOVA MR, and rate adaptive activity controlled by means of a Medtronic Activitrax pacemaker taped to the chest wall, which triggered the implanted Nova MR in the VVT or AAT mode via skin electrodes. The maximum exercise tolerance was 67 W with SSI 70, 71 W with Activitrax and 91 W with Nova MR. The maximum oxygen uptake was accordingly 17.6 ml/min/kg with SSI 70, 19.5 ml/min/kg with Activitrax, and 21.5 ml/min/kg with Nova MR. The highest heart rate reached was 81 beats/min with SSI 70,98 beats/min with Activitrax and 118 beats/min with Nova MR. The rate increase from rest to maximum exercise was 11 beats/min with SSI 70,29 beats/min with Activitrax and 47 beats/min with Nova MR. An increase in exercise tolerance and maximum heart rate could be achieved with both rate adaptive types of pacing, but significantly more clearly with the temperature controlled Nova MR than with the activity controlled Activitrax. However, using a different form of exercise, e.g. treadmill ergometry, the rate response of the Activitrax would presumably have been somewhat clearer.


Size- and support-dependent electronic and catalytic properties of Au0/Au3+ nanoparticles synthesized from block copolymer micelles.
Supported Au nanoclusters synthesized from diblock copolymer micelles can be reliably prepared with well-controlled sizes and dispersions. For particles with diameters between approximately 1 and 6 nm, the particle size and the support were found to strongly influence the oxygen reactivity, the formation and stabilization of a metal-oxide, and the catalytic activity for electrooxidation of carbon monoxide. The smallest particles studied (1.5 nm) were the most active for electrooxidation of CO and had the largest fraction of oxygen associated with gold at the surface as measured by the Au(3+)/Au(0) X-ray photoemission intensities. Conducting and semiconducting substrates, ITO-coated glass and TiO(2), respectively, were associated with greater stabilization of Au(3+) oxide as compared to insulating, SiO(2), substrates.


All-digital pulse-expansion-based CMOS digital-to-time converter.
This paper presents a new all-digital CMOS digital-to-time converter (DTC) based on pulse expansion. Pulse expansion is achieved using an all-digital pulse-mixing scheme that can effectively improve the timing resolution and enable the DTC to be concise. Without requiring the Vernier principle or a costly digital-to-analog converter, the DTC comprises a pulse generator for generating a pulse, a pulse-expanding circuit (PEC) for programming timing generation, and a time subtractor for removing the time width of the pulse. The PEC comprises only a delay chain composed of proposed pulse-expanding units and a multiplexer. For accuracy enhancement, a pulse neutralization technique is presented to eliminate undesirable pulse variation. A 4-bit converter was fabricated in a 0.35-μm Taiwan Semiconductor Manufacturing Company CMOS process and had a small area of nearly 0.045 mm2. Six chips were tested, all of which exhibited an improved resolution (approximately 16 ps) and low integral nonlinearity (less than ±0.4 least significant bit). The power consumption was 0.2 mW when the sample rate was 1M samples/s and the voltage supply was 3.3 V. The proposed DTC not only has favorable cost and power but also achieves an acceptable resolution without requiring an advanced CMOS process. This study is the first to use pulse expansion in digital-to-time conversion.


In vitro amplification of scrapie and chronic wasting disease PrP(res) using baculovirus-expressed recombinant PrP as substrate.
Protein misfolding cyclic amplification (PMCA) is an in vitro simulation of prion replication, which relies on the use of normal brain homogenate derived from host species as substrate for the specific amplification of abnormal prion protein, PrP(Sc). Studies showed that recombinant cellular PrP, PrP(C), expressed in Escherichia coli lacks N-glycosylation and an glycophosphatidyl inositol anchor (GPI) and therefore may not be the most suitable substrate in seeded PMCA reactions to recapitulate prion conversion in vitro. In this study, we expressed 2 PRNP genotypes of sheep, V136L141R154Q171 and A136F141R154Q171, and one genotype of white-tailed deer (Q95G96, X132,Y216) using the baculovirus expression system and evaluated their suitability as substrates in seeded-PMCA. It has been reported that host-encoded mammalian RNA molecules and divalent cations play a role in the pathogenesis of prion diseases, and RNA molecules have also been shown to improve the sensitivity of PMCA assays. Therefore, we also assessed the effect of co-factors, such as prion-specific mRNA molecules and a divalent cation, manganese, on protein conversion. Here, we report that baculovirus-expressed recombinant PrP(C) shows a glycoform and GPI-anchor profile similar to mammalian brain-derived PrP(C) and supports amplification of PrP(Sc) and PrP(CWD) derived from prion-affected animals in a single round of seeded PMCA in the absence of exogenous co-factors. Addition of species-specific in vitro transcribed PrP mRNA molecules stimulated the conversion efficiency resulting in increased PrP(Sc) or PrP(CWD) production. Addition of 2 to 20 μM of manganese chloride (MnCl2) to unseeded PMCA resulted in conversion of recombinant PrP(C) to protease-resistant PrP. Collectively, we demonstrate, for the first time, that baculovirus expressed sheep and deer PrP can serve as a substrate in protein misfolding cyclic amplification for sheep and deer prions in the absence of additional exogenous co-factors.


[Tests of hand functionality in upper limb amputation with prosthesis].
The need for standardized instruments for clinical measurements has become pressing in the fields of occupational rehabilitation and ergonomics. This is particularly the case for instruments that allow a quantitative evaluation of upper limb function, and especially hand function in patients who have undergone an amputation and then application of an upper limb prosthesis. This study presents a review of the main tests used to evaluate hand function, with a critical analysis of their use in subjects with an upper limb prosthesis. The tests are divided into: tests to evaluate strength, tests to evaluate co-ordination and dexterity, tests of global or overall function, and tests proposed specifically for subjects with an upper limb prosthesis. Of the various tests presented, the authors give their preference to the Bimanual Functional Assessment, Abilhand and/or the ADL Questionnaire, because of the practical usefulness, clinimetric features, simplicity and ease of administration of these tests.