[Effects of climate warming on oil flax growth and water use efficiency in semi-arid region of Loess Plateau, Northwest China].
By using the site-specific observation data of oil flax growth and related meteorological records in semi-arid region of Loess Plateau, this paper studied the effects of climate change on the oil flax growth, and analyzed the relationships between the oil flax water use efficiency and meteorological condition. In this region, the annual precipitation displayed a decreasing trend, and its climatic trend rate was -15.80 mm (10 a)(-1), with an annual periodic change of 3 a and 6 a, whereas the annual air temperature had an increasing trend, and its climatic trend rate was 0.36 degrees C (10 a)(-1). In crop growth period, the aridity index displayed a marked increasing trend, its climatic trend rate was 0.12 (10 a)(-1), and the aridity tendency was more obvious from the beginning of 1990s to the year 2009. From sowing to maturation, oil flax needed 120-150 d, 1700-2100 degrees C d of > or = 0 degrees C accumulated temperature, 200-250 mm precipitation, and 1000-1300 h sunshine hours. The main meteorological factors affecting the oil flax growth in the region were air temperature and precipitation. The increase of air temperature shortened the prophase vegetative growth stage, whereas the increase of air temperature and the decrease of precipitation extended the reproductive growth stage, causing the extension of the whole growth period of the oil flax. The air temperature in the oil flax whole growth period except at seeding stage and maturing stage had negative effect on the yield formation, being more obvious at squaring stage, whereas the precipitation in the whole growth period except at blooming stage had positive effect on the yield formation, being more obvious at seeding stage. The water use efficiency of the oil flax was significantly positively correlated with the air temperature and sunshine hours at seeding stage as well as the aridity index from squaring stage to maturing stage, and negatively correlated with the precipitation from squaring stage to maturing stage. In the study region, the aridity index from May to July was the key factor affecting the water use efficiency of oil flax.


Endoscopic diverticulotomy for the treatment of Zenker's diverticulum.
First described by Mosher in 1916, endoscopic treatment of Zenker's diverticulum has since been reported infrequently in the surgical literature and continues to engender controversy. Between 1978 and 1989, we treated 11 unselected patients surgically for pharyngoesophageal diverticula. Endoscopic diverticulotomy was used in 11 patients and an external approach was used in the others. The endoscopically treated patients had no serious complications, resumed oral intake early, and were discharged from the hospital earlier. Our review of the surgical literature confirmed our experience with the efficacy and safety of the procedure. We therefore recommend endoscopic diverticulotomy as being equal to external approaches with regard to effectiveness; and it affords the patient a shortened hospital stay and more rapid return to to the premorbid state.


Eye Care Provider Availability for the Medicare Population in U.S. States That Have Expanded Optometrist Scope of Practice.
Estimating a broader set of measures of local eye care provider availability than used in prior research offers information that is useful for policy decisions related to access to eye care. The purpose of this study was to examine whether policy-relevant information was gained when measures of local eye care provider availability in addition to the estimated travel time (ETT) to the closest provider were estimated for the population 65 years or older in Kentucky, New Mexico, and Oklahoma. These states have expanded surgical scope of practice for optometrists. This study used block group-level population data from the 2010 U.S. Decennial Census and eye care provider office address information from the 2016 Medicare Provider Utilization and Payment Data. Geographic information system analysis was used to calculate ETTs between individuals and eye care providers. Expanded measures of availability included the difference in ETT to an individual's second closest and closest ophthalmologist, the difference in ETT to an individual's closest ophthalmologist and closest optometrist, and whether only one ophthalmologist at the closest office accepted Medicare. Descriptive statistics were calculated for each state and by urbanicity. Of the population 65 years or older in each state, between 10.8 (Kentucky) and 16.6% (Oklahoma) had a one-way ETT to the second closest ophthalmologist >15 minutes longer than to the closest ophthalmologist, between 21.1 (Kentucky) and 27.6% (Oklahoma) had a one-way ETT to the closest ophthalmologist >15 minutes longer than to the closest optometrist, and between 56.4 (Kentucky) and 70.0% (Oklahoma) had only one ophthalmologist at the closest office who accepted Medicare. Findings differed substantially by urbanicity. Using a portfolio of travel time-based measures enhances the understanding of local eye care provider availability.


A smartphone-based algorithm comprising cough analysis and patient-reported symptoms identifies acute exacerbations of asthma: a prospective, double blind, diagnostic accuracy study.
Objective: Early and accurate recognition of asthma exacerbations reduces the duration and risk of hospitalization. Current diagnostic methods depend upon patient recognition of symptoms, expert clinical examination, or measures of lung function. Here, we aimed to develop and test the accuracy of a smartphone-based diagnostic algorithm that analyses five cough events and five patient-reported features (age, fever, acute or productive cough and wheeze) to detect asthma exacerbations.Methods: We conducted a double-blind, prospective, diagnostic accuracy study comparing the algorithm with expert clinical opinion and formal lung function testing. Results: One hundred nineteen participants >12 years with a physician-diagnosed history of asthma were recruited from a hospital in Perth, Western Australia: 46 with clinically confirmed asthma exacerbations, 73 with controlled asthma. The groups were similar in median age (54yr versus 60yr, p=0.72) and sex (female 76% versus 70%, p=0.5). The algorithm's positive percent agreement (PPA) with the expert clinical diagnosis of asthma exacerbations was 89% [95% CI: 76%, 96%]. The negative percent agreement (NPA) was 84% [95% CI: 73%, 91%]. The algorithm's performance for asthma exacerbations diagnosis exceeded its performance as a detector of patient-reported wheeze (sensitivity, 63.7%). Patient-reported wheeze in isolation was an insensitive marker of asthma exacerbations (PPA=53.8%, NPA=49%). Conclusions: Our diagnostic algorithm accurately detected the presence of an asthma exacerbation as a point-of-care test without requiring clinical examination or lung function testing. This method could improve the accuracy of telehealth consultations and might be helpful in Asthma Action Plans and patient-initiated therapy.


In Vivo Renin Activity Imaging in the Kidney of Progeroid Ercc1 Mutant Mice.
Changes in the renin-angiotensin system, known for its critical role in the regulation of blood pressure and sodium homeostasis, may contribute to aging and age-related diseases. While the renin-angiotensin system is suppressed during aging, little is known about its regulation and activity within tissues. However, this knowledge is required to successively treat or prevent renal disease in the elderly. Ercc1 is involved in important DNA repair pathways, and when mutated causes accelerated aging phenotypes in humans and mice. In this study, we hypothesized that unrepaired DNA damage contributes to accelerated kidney failure. We tested the use of the renin-activatable near-infrared fluorescent probe ReninSense680™ in progeroid Ercc1d/- mice and compared renin activity levels in vivo to wild-type mice. First, we validated the specificity of the probe by detecting increased intrarenal activity after losartan treatment and the virtual absence of fluorescence in renin knock-out mice. Second, age-related kidney pathology, tubular anisokaryosis, glomerulosclerosis and increased apoptosis were confirmed in the kidneys of 24-week-old Ercc1d/- mice, while initial renal development was normal. Next, we examined the in vivo renin activity in these Ercc1d/- mice. Interestingly, increased intrarenal renin activity was detected by ReninSense in Ercc1d/- compared to WT mice, while their plasma renin concentrations were lower. Hence, this study demonstrates that intrarenal RAS activity does not necessarily run in parallel with circulating renin in the aging mouse. In addition, our study supports the use of this probe for longitudinal imaging of altered RAS signaling in aging.


Modelling the effects of selection temperature and mutation on the prisoner's dilemma game on a complete oriented star.
This paper models the prisoner's dilemma game based on pairwise comparison in finite populations on a complete oriented star (COS). First, we derive a linear system on a COS for calculating the corresponding fixation probabilities that imply dependence of the selection temperature and mutation. Then we observe and analyze the effects of two parameters on fixation probability under different population sizes. In particular, it is found through the experimental results that (1) high mutation is more sensitive to the fixation probability than the low one when population size is increasing, while the opposite is the case when the number of cooperators is increasing, and (2) selection temperature demotes the fixation probability.


Effects of iloprost on visual evoked potentials and brain tissue oxidative stress after bilateral common carotid artery occlusion.
Effects of iloprost on visual evoked potentials and oxidant/antioxidant status were evaluated after bilateral carotid artery occlusion. There were three experimental groups; Sham (S) group (n=10), bilateral common carotid artery occluded (BCCAO) group (n=10) and after bilateral common carotid artery occlusion, iloprost-treated (BCCAOI) group (n=10). Iloprost was administered (0.5ng/kg/day) for 10 days by intraperitoneal injection. N(2) and P(2) latencies (millisecond) and N(2)-P(2) (microV) amplitudes were recorded 10 days after operation for evaluating VEPs. The rats were sacrificed by decapitation immediately after recording of VEPs. Malondialdehyte (MDA), glutathione (GSH), Cu-Zn superoxide dysmutase (SOD) were studied spectrophotometricly. After BCCAO, MDA levels were increased, GSH and Cu-Zn SOD levels were decreased significantly, and abnormal VEPs parameters were observed. Iloprost treatment after BCCAO decreased MDA and increased GSH levels significantly. Low Cu-Zn SOD levels and impaired VEPs remained after iloprost treatment. Iloprost treatment may protect the brain tissue from oxidative damage during cerebral hypoperfusion.


Experience with various 3-dimensional navigation systems in head and neck surgery.
To evaluate the benefits and difficulties encountered when using various 3-dimensional (3-D) navigation systems in head and neck procedures. Five different navigation systems were used for preoperative planning and intraoperative 3-D navigation in procedures at the paranasal sinuses, the frontal and lateral skull bases, and the petrous bone. Intraoperative 3-D localizing systems (position-sensitive mechanical arms, infrared cameras, etc) demand reliable patient fixation on the operating table. We achieved this by developing a noninvasive head holder. Other systems allow patient movements by using magnetic digitizing technology (ARTMA System) and sophisticated programming. Having surpassed an initial learning curve, we now achieve an accuracy of 1 to 2 mm regularly. Especially in paranasal and frontal basal surgery, all navigation systems used provide valuable positioning information during surgery. In particular for revision or tumor surgery, decisive benefits resulted from use of these systems: shorter overall operation time; safer manipulation near delicate structures; and reliable identification of the skull base even in patients with bleeding, scarring, or missing anatomical landmarks. We performed approximately 250 operations with different systems and introduced navigation at the lateral skull base and the petrous bone with mechanical, optic, and magnetic digitizers. In these anatomical areas, navigation was used successfully; the technical challenge is greatest at the lateral skull base, however.


Effect of Sleeve Gastrectomy on Glycometabolism via Forkhead Box O1 (FoxO1)/Lipocalin-2 (LCN2) Pathway.
BACKGROUND The mechanism by which sleeve gastrectomy (SG) improves glycometabolism has remained unclear so far. Increasing evidence has demonstrated that bone is a regulator of glucose metabolism, and osteoblast-derived forkhead box O1 (FoxO1) and lipocalin-2 (LCN2) are regulators of energy metabolism. The aim of this study was to investigate whether the FOXO1/LCN2 signaling pathway is involved in the anti-diabetic effect of SG. MATERIAL AND METHODS Insulin resistance was induced in Wistar rats, which were then intraperitoneally injected with streptozotocin to induce a type 2 diabetic state. Levels of fasting blood glucose, serum insulin, HbA1c, and LCN2 were analyzed at corresponding time points after SG and sham surgeries. The expressions of FOXO1, LCN2, and the melanocortin 4 receptor (MC4R) in bone and hypothalamus were detected by immunofluorescence. FOXO1 siRNA was applied to downregulate FOXO1 expression in osteoblasts of rats. The influence of FOXO1 gene on expression of LCN2 was investigated in cultured osteoblasts by western blot and PCR. RESULTS Glucose metabolism in the SG group was significantly improved. The LCN2 expression in bone in the SG group was higher than that in the sham group, whereas FOXO1 expression in the SG group was lower than that in the sham group. The binding rate of LCN2 and MC4R in the hypothalamus was also higher in the SG group compared with that in the sham group. The downregulation of FOXO1 expression in osteoblasts was accompanied by upregulation of LCN2 expression. CONCLUSIONS These results suggest that the FOXO1/LCN2 signaling pathway participates in the anti-diabetic effect of SG.


Evidence for self-cleaning in fluid-based smooth and hairy adhesive systems of insects.
Insects possess adhesive organs that allow attachment to diverse surfaces. Efficient adhesion must be retained throughout their lifetime even when pads are exposed to contamination. Many insects groom their adhesive structures, but it is possible that self-cleaning properties also play an important role. We measured attachment forces of insect pads on glass after contamination with microspheres and found that both smooth pads (stick insects: Carausius morosus) and hairy pads (dock beetles: Gastrophysa viridula) exhibit self-cleaning. Contaminated pads recovered high levels of adhesion after only eight simulated steps; this was accompanied by the deposition of spheres. Self-cleaning was strongly enhanced by shear movements, and only beetle pads showed the ability to self-clean during purely perpendicular pull-offs. Hairy pads also self-cleaned more efficiently than smooth pads for both large (45 microm) and small (1 microm) particle sizes. However, the beetles' self-cleaning was not superior to smooth pads when contaminated with 10-microm beads. This limitation of self-cleaning is explained by the coincidence of bead diameter and inter-seta distance, which caused beads to remain trapped in between setae.


[Something has gone wrong, what now? Procedures, rights and obligations in Dutch health care].
If something has gone wrong during the care process, a physician must consider the following procedures: VIM reporting, calamity investigation, complaint procedure, civil liability procedure and disciplinary procedure. The physician must report an incident internally and the healthcare institution must report a calamity to the Health Care and Youth Inspectorate. The healthcare institution must draw up a complaints procedure and appoint a complaints officer. The healthcare institution must give an opinion about the complaint within six weeks. In addition, the healthcare institution is obliged to be affiliated with a disputes committee. If the healthcare provider is liable for the healthcare-related damage, the healthcare provider has an obligation to provide information regarding the treatment and the incident and is obliged to exchange such information. The healthcare provider must also mitigate the damage, acknowledge mistakes and inform about possible procedures. The Disciplinary Tribunal reviews the physician's conduct against specific professional standards and may impose specific measures.


DE-CNN: An Improved Identity Recognition Algorithm Based on the Emotional Electroencephalography.
In the past few decades, identification recognition based on electroencephalography (EEG) has received extensive attention to resolve the security problems of conventional biometric systems. In the present study, a novel EEG-based identification system with different entropy and a continuous convolution neural network (CNN) classifier is proposed. The performance of the proposed method is experimentally evaluated through the emotional EEG data. The conducted experiment shows that the proposed method approaches the stunning accuracy (ACC) of 99.7% on average and can rapidly train and update the DE-CNN model. Then, the effects of different emotions and the impact of different time intervals on the identification performance are investigated. Obtained results show that different emotions affect the identification accuracy, where the negative and neutral mood EEG has a better robustness than positive emotions. For a video signal as the EEG stimulant, it is found that the proposed method with 0-75 Hz is more robust than a single band, while the 15-32 Hz band presents overfitting and reduces the accuracy of the cross-emotion test. It is concluded that time interval reduces the accuracy and the 15-32 Hz band has the best compatibility in terms of the attenuation.


Addressing intimate partner violence with female patients with chronic physical disabilities: the role of physical therapists.
Women with disabilities are at heightened risk of intimate partner violence, experiencing higher rates of physical and sexual violence than women without disabilities. Women with disabilities are also at risk of sustaining additional chronic injuries and debilitating conditions associated with intimate partner violence. Physical therapists strive to enhance the well-being and quality of life of individuals experiencing impairments, activity limitations, and/or participation restrictions due to physical health concerns. This professional focus places physical therapists in an important position to identify adverse life situations such as intimate partner violence which seriously degrades the well-being, quality of life, and physical health of patients. Physical therapists encounter numerous individuals with disabilities in their practice, and given the high rates of intimate partner violence within this population, it is important that physical therapists are aware of how to identify and respond to this issue. This article provides background on the problem of intimate partner violence among women with chronic physical disabilities, and explores assessment, practice, and education guidelines intended to assist physical therapists address intimate partner violence with their patients.IMPLICATIONS FOR REHABILITATIONWomen with disabilities are at a heightened risk of intimate partner violence compared to women without disabilities, and are also at risk of sustaining associated chronic injuries and debilitating conditions.Given the high rates of intimate partner violence among individuals with chronic physical disabilities, it is important that physical therapists are able to identify and respond to this issue.Physical therapists possess specialized skills to improve the functioning and overall health of patients, and could assist patients with chronic physical disabilities to escape abusive relationships. Knowledge of intimate partner violence-focused screening, assessment, and trauma-informed practice skills would strengthen skills in this area.


Cloning and functional analysis of the rhesus macaque ABCG2 gene. Forced expression confers an SP phenotype among hematopoietic stem cell progeny in vivo.
Hematopoietic cells can be highly enriched for repopulating ability based upon the efflux of the fluorescent Hoechst 33342 dye by sorting for SP (side population) cells, a phenotype attributed to expression of ABCG2, a member of the ABC transporter superfamily. Intriguingly, murine studies suggest that forced ABCG2 expression prevents hematopoietic differentiation. We cloned the full-length rhesus ABCG2 and introduced it into a retroviral vector. ABCG2-transduced human peripheral blood progenitor cells (PBPCs) acquired the SP phenotype but showed significantly reduced growth compared with control. Two rhesus macaques received autologous PBPCs split for transduction with the ABCG2 or control vectors. Marking levels were similar between fractions with no discrepancy between bone marrow and peripheral blood marking. Analysis for the SP phenotype among bone marrow and mature blood populations confirmed ABCG2 expression at levels predicted by vector copy number long term, demonstrating no block to differentiation in the large animal. In vitro studies showed selective protection against mitoxantrone among ABCG2-transduced rhesus PBPCs. Our results confirm the existence of rhesus ABCG2, establish its importance in conferring the SP phenotype, suggest no detrimental effect of its overexpression upon differentiation in vivo, and imply a potential role for its overexpression as an in vivo selection strategy for gene therapy applications.


Retrospective study of tooth loss in 92 treated periodontal patients.
In this retrospective study, the efficacy of periodontal therapy and maintenance in preventing tooth loss was evaluated. The study included 92 patients with 2310 teeth diagnosed with chronic adult periodontitis and observed over a mean period of 6.7 years, with each patient receiving surgical therapy in two or more quadrants. The group was divided into two subgroups: those who complied with the recommended maintenance schedule and those whose compliance was erratic. Individual tooth prognosis was assigned according to radiographic parameters. At the completion of active periodontal therapy, 2184 teeth were present. During the maintenance period, 44 teeth were lost due to periodontal reasons. Tooth mortality revealed a mean annual adjusted tooth loss rate of 0.07/year. Molars were the teeth most frequently lost; canines the least. The number of teeth lost in the three prognostic categories was: one (0.07%) for teeth with good prognoses, 21 (3.63%) for questionable prognoses and 22 (11.34%) for hopeless prognoses. Patients complying erratically with supportive periodontal therapy were at a 5.6 times greater risk for tooth loss following active therapy than regularly compliant patients. The results demonstrated a low tooth mortality rate in periodontal patients following active treatment combined with a strict maintenance program.


Ca(2+)-antagonistic action of bevantolol on hypothalamic neurons in vitro: its comparison with those of other beta-adrenoceptor antagonists, a local anesthetic and a Ca(2+)-antagonist.
The Ca(2+)-antagonistic action of bevantolol, a beta 1-adrenoceptor antagonist, on high- and low-voltage activated Ca2+ currents (HVA- and LVA-ICa) was examined on neurons dissociated from rat brain. Bevantolol (10(-6) to 10(-4) M) inhibited concentration-dependently both ICa. The IC50 value of bevantolol for LVA-ICa was 4 x 10(-5) M, while bevantolol at 10(-4) M inhibited HVA-ICa by 28.5 +/- 7.7%. The potency of bevantolol in inhibiting both ICa was greater than those of propranolol, labetalol and lidocaine, while the inhibitory action of bevantolol on voltage-activated Na+ current was weakest among them. Bevantolol may possess Ca(2+)-antagonistic action that is independent from local anesthetic action.


Regulation of human megakaryocytopoiesis: analysis of proliferation, ploidy and maturation in liquid cultures.
A liquid culture technique associated with either double staining and flow cytometry or electron microscopy was used to study human megakaryocytopoiesis. During development from the embryo to the adult, a progressive increase in ploidy classes associated with an enhancement of megakaryocyte (meg) size was observed. Granulocyte-macrophage colony-stimulating factor had no effects on adult marrow cultures. In contrast, interleukin (IL) 3 induced a marked proliferation, but was unable to promote polyploidization. Furthermore, it abrogated the effects on endomitosis of aplastic plasma (AP). This negative effect on polyploidization of IL-3 could be partially dissociated from its effects on proliferation by a delayed addition in culture. AP acted on both proliferation and endoreplication, which was not due to the main hematopoietic growth factors, including IL-6. A synthesis of IL-6 was detected by in situ hybridization in cultured cells including megs which also express receptors for IL-6. These results suggest that terminal meg differentiation may be regulated by an autocrine IL-6 loop, and that megakaryocytopoiesis may be independently regulated at early and late stages of differentiation.


A Microporous Metal-Organic Framework Incorporating Both Primary and Secondary Building Units for Splitting Alkane Isomers.
We demonstrate the assembly of a mononuclear metal center, a hexanuclear cluster, and a V-shaped, trapezoidal tetracarboxylate linker into a microporous metal-organic framework featuring an unprecedented 3-nodal (4,4,8)-c lyu topology. The compound, HIAM-302, represents the first example that incorporates both a primary building unit and a hexanuclear secondary building unit in one structure, which should be attributed to the desymmetrized geometry of the organic linker. HIAM-302 possesses optimal pore dimensions and can separate monobranched and dibranched alkanes through selective molecular sieving, which is of significant value in the petrochemical industry.


Variations in the papillary muscles of the normal mitral valve and their surgical relevance.
A mid-mitral plane passing through the middle of the aortic and mural leaflets divides the chordopapillary support of the mitral valve into anterolateral and posteromedial halves. The papillary muscles of the mitral valve were studied in 100 human autopsy hearts collected at random. The anterolateral papillary support had 1 belly in 67 hearts, 2 in 27, 3 in 4, 4 in 1, and 5 in 1 heart. Likewise, the posteromedial papillary support had 1 muscle belly in 50 hearts, 2 in 36, 3 in 11, and 4 in 3. The single papillary muscles were conical, mammillated, flat topped, grooved, stepped, wavy, arched, sloped or saucerized. When there were two bellies they presented a two tiered, interlinked, parallel, arched, V, Y, or H configuration. Three papillary muscles formed a parallel, interlinked or arched arrangement; or two bellies were interlinked or formed a two tiered arrangement with the third belly separate. When four or five bellies existed, they were parallel or interlinked. In the anterolateral and posteromedial group, the papillary muscle bellies were mostly intraluminal in 14% and 11%, mostly intraluminal with the tip anchored in 19% and 28%, equally sessile and intraluminal in 54.5% and 41.5%, mostly sessile in 12.5% and 19.5%, respectively. In the anterolateral group 19% of papillary muscle bellies arose from the upper third of the ventricle, 79.5% from middle third, and 1.5% from lower third. The corresponding figures for posteromedial group are 6%, 92.5%, and 1.5%, respectively. Four to 22 chordae originated from the anterolateral papillary group, ending in 14 to 72 chordal insertions into the corresponding half of the valve. Likewise, 2 to 18 chordae arose from the posteromedial papillary group ended in 12 to 80 leaflet insertions. The chordae in each group are best considered in toto as a fan. The configuration of the fan is unique in each heart. Imaging techniques need to be refined to outline these variations more precisely. The relevance of chordopapillary variations in rheumatic heart disease, reparative procedures, papillary muscle dysfunction, mitral valve prolapse, mitral valve replacement, and use of mitral valve homograft for mitral/tricuspid replacement is discussed.


Kinesin associates with anterogradely transported membranous organelles in vivo.
Biochemical, pharmacological and immunocytochemical studies have implicated the microtubule-activated ATPase, kinesin, in the movement of membrane bounded organelles in fast axonal transport. In vitro studies suggested that kinesin moves organelles preferentially in the anterograde direction, but data about the function and precise localization of kinesin in the living axon were lacking. The current study was undertaken to establish whether kinesin associates with anterograde or retrograde moving organelles in vivo. Peripheral nerves were ligated to produce accumulations of organelles moving in defined directions. Regions proximal (anterograde) and distal (retrograde) to the ligation were analyzed for kinesin localization by immunofluorescence, and by immunogold electron microscopy using ultracryomicrotomy. Substantial amounts of kinesin were associated with anterograde moving organelles on the proximal side, while significantly less kinesin was detected distally. Statistical analyses indicated that kinesin was mostly associated with membrane-bounded organelles. These observations indicate that axonal kinesin is primarily associated with anterograde moving organelles in vivo.


Health-related quality of life in morbid obesity.
In order to evaluate the impact of severe obesity and its treatment on quality of life (QoL), it would be important to first identify the areas of QoL most likely to be affected by the disease. We first constructed a list of 187 items potentially related to QoL of patients with morbid obesity. From this list, consecutive candidates for bariatric surgery were asked to identify what they felt were the most significant items and to grade their importance. The item impact was determined from the proportion of patients who identified it as important, and the mean importance score attributed to this item (impact score = frequency X importance). 100 patients (68 female; mean body mass index 51.5 kg/m(2); mean age 42) were interviewed. Overall, the impact of morbid obesity was more important in women than in men. The areas of impairment were very similar in both groups, with the important difference that women ranked their dissatisfaction with physical appearance higher than men. The items having the most important impact on QoL clustered into 7 domains: 1) activity/mobility; 2) symptoms; 3) personal hygiene/clothing; 4) emotions; 5) social interactions; 6) sexual life; and 7) eating behavior. The impact of morbid obesity on QoL is not limited to the activity/mobility domain. Morbid obesity contributes to the impairment of all domains of what is usually referred to as "health-related quality of life".


Treatment strategies in controlling strongyloidiasis.
Strongyloidiasis is an intestinal parasite infection caused by Strongyloides stercoralis. Spontaneous cure cannot be expected due to the unique life cycle of the parasite, termed autoinfection. The disease occurs worldwide, but especially in tropical and subtropical regions. Serious clinical problems with complications and refractory strongyloidiasis are observed, especially in immunocompromised patients, such as those infected with human T cell leukaemia virus Type 1 (HTLV-1) or HIV, or corticosteroid-treated patients. Thiabendazole is effective against S. stercoralis infection; however, serious side effects have been reported. Recently, ivermectin, which has been introduced for the treatment of human onchocerciasis, has been reported to be effective against strongyloidiasis, without serious side effects. The interval of administration is important for treatment, because if autoinfective migrating larvae are not eradicated, S. stercoralis will resume its life cycle and multiply again. To evaluate the results of treatment of S. stercoralis, stool examinations and S. stercoralis-specific antibody titres should be examined for at least 1 or 2 years if possible. This article provides a review of treatments and methods of evaluation of patients infected with S. stercoralis.


Androstenediol analogs as ER-beta-selective SERMs.
A series of 19-substituted androstenediol derivatives was prepared. Some of the novel analogs were surprisingly potent and selective ligands for ER-beta.


[Changes of the metabolism of anti-oxidation competence of endothelial cells induced from mesenchymal stem cells after fluid shear stress loading].
This study examined the effects of flow shear stress on the bio-capacity of the endothelial cells' induced from mesenchymal stem cells (MSCs). After cultivating the SD rat mesenchymal stem cells in vitro, we exposed them under different intensity of flow shear stress and induced these cells to endothelial cells. The variations of total anti-oxidation competence (T-AOC) and quantity of nitrogen monoxide (NO) were tested. The results showed that shear stress has an enhanced effect on the T-AOC and NO of endothelial cells induced from MSCs in an intensity-dependent manner. Flow shear stress could provide a protective action on the in vitro induction of endothelial cells, thus formulating a theoretical foundation for the therapeutics of ischemic heart diseases and vascular tissue engineering.


Immunotherapy for Epstein-Barr virus-associated tumors.
Epstein-Barr Virus (EBV) is associated with a number of tumors, including lymphomas in solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, patients with the acquired immunodeficiency syndrome (AIDS), Burkitt's lymphoma, as well as a subset of patients with nasopharyngeal carcinoma (NPC) and Hodgkin's disease (HD). The types of latent EBV infections vary in these tumors, which influences the EBV antigens expressed and ultimately the immunogenicity of tumor cells. Not all EBV associated malignancies are directly related to altered cellular immunity, as is the case with EBV induced lymphoproliferations in immunocompromised patients. Treatment strategies have ranged from restoration of normal cellular immunity, which is generally successful in SOT and HSCT patients, anti-B cell monoclonal antibodies, and conventional chemotherapy and radiation. The fact that these tumors express EBV antigens for which many individuals have high circulating levels of protective cytotoxic T lymphocytes (CTL) has lead to investigation into the applicability of adoptive transfer of EBV specific T cells. Initial success with adoptive immunotherapy for HSCT and SOT patients has lead to current studies examining the feasibility and efficacy of this strategy for other EBV associated tumors, such as NPC and HD. We will review the pathogenesis of these disorders, current therapies, and future investigations aimed at targeting EBV antigen expression on these tumors.


Knowledge, Attitudes, and Risk for Sudden Unexpected Infant Death in Children of Adolescent Mothers: A Qualitative Study.
To investigate practices, knowledge, attitudes, and beliefs regarding infant sleep among adolescent mothers, a demographic at high risk for sudden unexpected infant death, and to identify novel public health interventions targeting the particular reasons of this population. Seven targeted focus groups including 43 adolescent mothers were conducted at high school daycare centers throughout Colorado. Focus groups were recorded, transcribed, validated, and then analyzed in NVivo 10. Validation included coding consistency statistics and expert review. Most mothers knew many of the American Academy of Pediatrics recommendations for infant sleep. However, almost all teens reported bedsharing regularly and used loose blankets or soft bedding despite being informed of risks. Reasons for nonadherence to recommendations included beliefs that babies are safest and sleep more/better in bed with them, that bedsharing is a bonding opportunity, and that bedsharing is easier than using a separate sleep space. The most common justifications for blankets were infant comfort and concern that babies were cold. Participants' decision making was often influenced by their own mothers, with whom they often resided. Participants felt that their instincts trumped professional advice, even when in direct contradiction to safe sleep recommendations. Among focus group participants, adherence with safe sleep practices was poor despite awareness of the American Academy of Pediatrics recommendations. Many mothers expressed beliefs and instincts that infants were safe in various unsafe sleep environments. Future study should investigate the efficacy of alternative educational strategies, including education of grandmothers, who have significant influence over adolescent mothers.


Kidney transplant anastomosis: internal or external iliac artery?
We compared the best technique for arterial anastomosis in kidney transplantation, end-to-side anastomosis to the external iliac artery or end-to-end anastomosis to the internal iliac artery. A total of 38 patients with end-stage renal disease who received a kidney transplant from a deceased donor were randomized into two groups in order to undergo either end-to-end anastomosis to the internal iliac artery or end-to-side anastomosis to the external iliac artery. Length of arterial anastomosis, cold ischemia time, hospital stay, serum creatinine level, recovery of urinary output, and surgical and clinical complications during hospitalization were evaluated. After 3 years, in the patients with a functioning allograft, creatinine clearance measure, Doppler ultrasonographic study, survival, graft loss, and erectile function were compared between the two groups. Postoperative analyses showed similar recovery of urinary output (P = .39) and creatinine (P = .95) between the two groups. No differences in clinical (P = .55) and surgical (P = .80) complications or in hospital stay (P = .90) were noted. The 3-year follow-up demonstrated no differences in Doppler ultrasonography results, creatinine clearance (P = .80), patient survival (P = .22), and graft loss (P = .72). Erectile dysfunction was similar, being related only to pre-operative medical history and age. Both techniques showed similar results in short- and long-term follow-ups. Larger prospective studies are warranted to clarify the risk of renal artery stenosis and development of erectile dysfunction.


Effect of sub-lethal doses of vancomycin and oxacillin on biofilm formation by vancomycin intermediate resistant Staphylococcus aureus.
Biofilms are means of protection to bacteria against antibiotics and antibodies. Catheters and others tube devices used by patients are prone to accumulation of thick layers of biofilms as hiding place for etiologic agents, resulting in substantial morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections. Vancomycin remains the only treatment of choice for MRSA infections. In the present study a vancomycin resistant S. aureus (VRSA) (Labeled as CP2) was isolated from the blood of a post-operative cardiac patient. It harbors a plasmid which carry vanA gene and exhibited low-level vancomycin resistance (MIC 16 μg/ml), high level of oxacillin/methicillin resistance (MIC 500 μg/ml) and was sensitive to teicoplanin. CP2 also found to carry icaA gene on its chromosome. This strain exhibited resistance to triton-X100 induced autolysis under sub-inhibitory concentration of vancomycin and produced some extracellular matrix material that surrounding the cells. These characteristic features have warranted us to study the biofilm formation by CP2 on biomedical indwellings in presence of vancomycin and oxacillin. Our findings suggest that sub-lethal dose of vancomycin induced the biofilm formation by CP2 on nylon and silicon indwellings whereas oxacillin facilitated the biofilm formation on glass surfaces exclusively. This implicates that not only the antibiotics but also the indwelling material influences biofilm formation. Therefore, these implants serve as potential surfaces for bacterial adhesion that lead to biofilm formation, thus provide hiding places for pathogens from the actions of antimicrobials.


Bonding and bending in zirconium(IV) and hafnium(IV) hydrazides.
Reaction of the dichloro complexes [M(N(2) (TBS)N(py))Cl(2)] (M=Zr: 1, Hf: 2; TBS: tBuMe(2)Si; py: pyridine) with one molar equivalent of LiNHNPh(2) gave mixtures of the two diastereomeric chlorohydrazido(1-) complexes [M(N(2) (TBS)N(py))(NHNPh(2))Cl] (M=Zr: 3 a,b, Hf: 4 a,b) in which the diphenylhydrazido(1-) ligand adopts a bent kappa(1) coordination. This mixture of isomers could be cleanly converted into the deep green diphenylhydrazido(2-) complexes [Zr(N(2) (TBS)N(py))(NNPh(2))(py)] (5) and [Hf(N(2) (TBS)N(py))(NNPh(2))(py)] (6), respectively, by dehydrohalogenation with lithium hexamethyldisilazide (LiHMDS) in the presence of one molar equivalent of pyridine. Both complexes contain a linearly coordinated hydrazinediide for which a DFT-based frontier orbital analysis established bonding through one sigma and two pi orbitals. A high polarity of the M=N bond was found, in accordance with the description of hydrazinediide(2-) acting as a six-electron donor ligand. The pyridine ligand in [M(N(2) (TBS)N(py))(NNPh(2))(py)] (M=Zr: 5, Hf: 6) is substitutionally labile as established by line-shape analysis of the dynamic spectra (DeltaG(not equal)=19 kcal mol(-1)). A change in denticity of the hydrazido unit from kappa(1) to kappa(2) was studied by DFT methods. Both forms are calculated to be very close in energy and are only separated by shallow activation barriers, which supports the notion of a rapid kappa(1) to kappa(2) interconversion. This process is believed to happen early on in the N-N scission in the presence of coupling reagents. Frontier orbital and natural population analyses suggest that a primarily charge-controlled nucleophilic attack at N(alpha) is unlikely whereas interaction with an electrophile could play an important role. This hypothesis was tested by the reaction of 5 and 6 with one molar equivalent of B(C(6)F(5))(3) to give [Zr(N(2) (TBS)N(py))(NNPh(2)){B(C(6)F(5))(3)}] (7) and [Hf(N(2) (TBS)N(py))(NNPh(2)){B(C(6)F(5))(3)}] (8). In these products, B(C(6)F(5))(3) becomes attached to the N(alpha) atom of the side-on bound hydrazinediide and there is an additional interaction of an ortho-F atom of a C(6)F(5) ring with the metal centre.


Discovery of highly reactive self-splicing group II introns within the mitochondrial genomes of human pathogenic fungi.
Fungal pathogens represent an expanding global health threat for which treatment options are limited. Self-splicing group II introns have emerged as promising drug targets, but their development has been limited by a lack of information on their distribution and architecture in pathogenic fungi. To meet this challenge, we developed a bioinformatic workflow for scanning sequence data to identify unique RNA structural signatures within group II introns. Using this approach, we discovered a set of ubiquitous introns within thermally dimorphic fungi (genera of Blastomyces, Coccidioides and Histoplasma). These introns are the most biochemically reactive group II introns ever reported, and they self-splice rapidly under near-physiological conditions without protein cofactors. Moreover, we demonstrated the small molecule targetability of these introns by showing that they can be inhibited by the FDA-approved drug mitoxantrone in vitro. Taken together, our results highlight the utility of structure-based informatic searches for identifying riboregulatory elements in pathogens, revealing a striking diversity of reactive self-splicing introns with great promise as antifungal drug targets.


Modern genomic techniques in the identification of genetic causes of cardiomyopathy.
Over the past three decades numerous disease-causing genes have been linked to the pathogenesis of heritable cardiomyopathies, but many causal genes are yet to be identified. Next-generation sequencing (NGS) platforms have revolutionised clinical testing capacity in familial cardiomyopathy. In this review, we summarise how NGS technologies have advanced our understanding of genetic non-syndromic cardiomyopathy over the last decade. First, 26 putative new disease-causing genes have been identified to date, mostly from whole-exome sequencing, and some of which (FLNC, MTO1, HCN4) have had a considerable clinical impact and are now included in routine diagnostic gene panels. Second, we consider challenges in variant interpretation and the importance of large-scale NGS population control cohorts for this purpose. Third, an emerging role of common variation in some forms of genetic cardiomyopathy is being elucidated through recent studies which have illustrated an additive effect of numerous polymorphic loci on cardiac parameters; this may explain phenotypic variability and low rates of genetic diagnosis from sequencing studies. Finally, we discuss the clinical utility of genetic testing in cardiomyopathy in Western settings, where NGS panel testing of core disease genes is currently recommended with possible implications for patient management. Given the findings of recent studies, whole-exome or whole-genome sequencing should be considered in patients of non-European ancestry with clearly familial disease, or severe paediatric disease, when no result is obtained on panel sequencing. The clinical utility of polygenic risk assessment needs to be investigated further in patients with unexplained dilated cardiomyopathy and hypertrophic cardiomyopathy in whom a pathogenic variant is not identified.


Prevalence of plasmid-mediated quinolone resistance in Escherichia coli isolates in Wenzhou, Southern China, 2002-2008.
A total of 514 consecutive clinical Escherichia coli isolates, irrespective of resistance background, were collected in the period 2002-2008 in Wenzhou, southern China, to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR). The dominant PMQR gene was aac(6')-Ib-cr, followed by qnr, whereas qepA was absent. A total of 253 (49.2%) of these isolates were aac(6')-Ib-positive. Subsequently, 134 of these isolates were sequenced and 42 (31.3%) found to harbor aac(6')-Ib-cr, 18 to harbor new aac(6')-Ib mutants, and 74 to harbor wild-type aac(6')-Ib. The genes qnrA, qnrB, and qnrS were found in 2 (0.4%), 6 (1.2%), and 14 (2.7%) of 514 isolates, respectively, with 2 isolates co-harboring qnrB and qnrS genes. Sequencing allowed us to identify qnrA1, qnrB4, qnrB6, and qnrS1 in 20 qnr-positive isolates, with qnrS1 being the most prevalent allele. The genes qnrC and qnrD were not found in any isolates. Interestingly, 35% of qnr-positive isolates and 16.7% of aac(6')-Ib-cr-positive isolates were susceptible to ciprofloxacin. PMQR genes are therefore present in both quinolone-resistant and -susceptible isolates and can also be transferred by conjugation experiments, thus suggesting a likely future increase in quinolone resistance.


Impact, Growth, Capacity-building of Mixed Methods Research in the Health Sciences.
The use of mixed methods research (MMR) by health scientists has expanded in recent years. The growth of MMR reflects the complexity of health-related research questions including the need to understand stakeholder perspectives. MMR is further incentivized by the release of the National Institutes of Health's (NIH) first version of "Best Practices for Mixed Methods Research in the Health Sciences" in 2011 and their revised version which was released in early 2018, and the increase in federal funding awarded to MMR projects. Realizing the need to train health scientists, several training initiatives are underway. In this commentary, we discuss: characteristics of MMR; the rise of MMR in the health sciences; the growing need and efforts to train health scientists in MMR approaches; and the graduate-level course in MMR that was launched at the University of Maryland School of Pharmacy.


Structural basis of Ty3 retrotransposon integration at RNA Polymerase III-transcribed genes.
Retrotransposons are endogenous elements that have the ability to mobilise their DNA between different locations in the host genome. The Ty3 retrotransposon integrates with an exquisite specificity in a narrow window upstream of RNA Polymerase (Pol) III-transcribed genes, representing a paradigm for harmless targeted integration. Here we present the cryo-EM reconstruction at 4.0 Å of an active Ty3 strand transfer complex bound to TFIIIB transcription factor and a tRNA gene. The structure unravels the molecular mechanisms underlying Ty3 targeting specificity at Pol III-transcribed genes and sheds light into the architecture of retrotransposon machinery during integration. Ty3 intasome contacts a region of TBP, a subunit of TFIIIB, which is blocked by NC2 transcription regulator in RNA Pol II-transcribed genes. A newly-identified chromodomain on Ty3 integrase interacts with TFIIIB and the tRNA gene, defining with extreme precision the integration site position.


Global gene expression profiling of chemically induced rat mammary gland carcinomas and adenomas.
Chemical carcinogens induce both benign and malignant mammary gland tumors in female Sprague-Dawley rats. To identify gene expression profiles associated with malignancy, cDNA microarray analysis was used to compare gene expression profiles in rat mammary gland carcinomas, adenomas, and normal mammary gland. Tumors were induced with various chemical carcinogens including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 7-12-dimethylbenz[a]anthracene (DMBA), N-nitrosomethylurea (NMU), and 4-aminobiphenyl. The global gene expression profiles in carcinomas and adenomas were distinguishable by hierarchical clustering and multi-dimensional scaling analyses. Permutation analysis revealed 110 clones statistically differentially expressed between benign and malignant tumors (p < 0.0005). Carcinomas showed relatively high expression of several genes associated with mammary epithelial cell growth and proliferation (e.g., cyclin D1, PDGFalpha) and relatively low expression of differentiation marker genes (e.g., beta -casein, whey acidic protein, transferrin). Other categories of genes showing differential expression between carcinomas and adenomas were associated with protein homeostasis, cytoskeleton, extracellular matrix, and cell metabolism (fatty acid metabolism, oxidative phosphorylation, and glycolysis). Major gene families implicated in malignancy by over-expression in carcinomas included the annexins (annexin A1 and A4) and Stat family of transcription factors (Stat3 and Stat5a). The elevated expression of the prolactin receptor in carcinomas concomitant with several components of the mitogenic prolactin signaling pathway implicated prolactin/prolactin receptor/Stat5a/cyclin D1 in rat mammary gland malignancy.


Tumor-specific novel taxoid-monoclonal antibody conjugates.
Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.


Benzyladenine-induced increase in DNA content per chloroplast in intact bean leaves.
Benzyladenine (BA) treatment was found to induce chloroplast DNA (ctDNA) synthesis after it had stopped in primary leaves of light-grown intact bean plants (Phaseolus vulgaris L.). The leaves were treated with BA from 7 days after sowing. Chloroplasts were isolated and the ctDNA content per chloroplast was determined. Chloroplast division occurred until 13 days after sowing in untreated leaves. BA stimulated the division keeping the level of ctDNA content per chloroplast the same as that in the untreated controls. After the division period, the ctDNA content per chloroplast increased in BA-treated leaves, but not in controls. Consequently, ctDNA per leaf (or per cell) increased immediately after the beginning of BA treatment, but remained constant in the control leaves.


Vets' and Pet Owners' Views About Antibiotics for Companion Animals and the Use of Phages as an Alternative.
Antimicrobial resistance (AMR) is a global health burden. Although a complex and multi-faceted problem, inappropriate antibiotic use has repeatedly been identified as one of the main drivers of the acceleration and spread of AMR. Behaviors associated with antibiotic prescription and use have been extensively investigated in human medicine and in the livestock sector of veterinary medicine. There is now a growing interest in the factors that drive inappropriate antibiotic use in companion animal medicine, as the significance of antimicrobial use in this sector is being recognized. Additionally, the possibility of an alternative antimicrobial, phage therapy, being implemented into companion animal medicine is explored in this study. Interviews revealed complexities in the vet-owner relationship including conflicting perceptions of responsibility regarding antibiotic prescription and use, distrust of vets' intentions, and misconception of clients' needs. A need for alternative antimicrobials was evident, as all vets were able to report difficulties finding antibiotics to treat infections as a common occurrence. Questionnaire results indicated that vets and pet owners are open to the use of phage therapy in companion animals. This study shows that an alternative antimicrobial such as phage therapy could be accepted into companion animal medicine in the UK; however, effective communication between vets and pet owners is vital if antibiotic use is to be reduced and new antimicrobials are successfully implemented.


Is it necessary to biopsy the obvious?
The radiologist and oncologist are often confident that biopsy will confirm their suspicion of recurrent disease, but a biopsy is performed to confirm the histologic diagnosis before beginning or altering therapy. We have examined data to determine how often the biopsied lesion represents recurrent disease from the primary tumor or is an instance of new cancer, and whether recurrent disease can be predicted. We reviewed the medical and imaging records of 253 patients who underwent CT-guided biopsy of an abdominal or pelvic lesion between 1993 and 1996. Sixty-nine of the 253 patients had a previously diagnosed primary tumor and were being examined for possible tumor recurrence or metastasis. The images of these 69 patients were analyzed to determine if the pattern of disease was typical of recurrence or metastasis. In 55 of the 69 patients, the pattern was judged to be typical of metastatic or recurrent disease. Biopsy confirmed this suspicion in all 55 patients. In 14 of the 69 patients, the pattern of spread was judged not to be typical of recurrence or metastasis. These 14 patients were found to have a new primary tumor (n = 4), benign processes (n = 2), and recurrences (n = 8). Of the patients for whom radiographic findings suggested recurrence, we found no patients in whom a new primary tumor would have been missed if biopsy had been avoided. Data should now be acquired prospectively to determine whether it may be prudent to make treatment decisions on the basis of imaging findings alone, without histologic confirmation.


An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population.
Are the maternal gene variants MTHFR: c.665C>T, MTHFR: c.1286A>C, MTR: c.2756A>G, MTRR: c.66A>G, RFC1: c.80C>T and TCN2: c.776G>C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free β-subunit of human chorionic gonadotropin β (free-β-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and β-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C>T MTHFR and c.776G>C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G>C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and β-hCG MoM values remain independent risk factors for fetal-T21.


The N-terminal disulfide linkages of human insulin-like growth factor-binding protein-6 (hIGFBP-6) and hIGFBP-1 are different as determined by mass spectrometry.
The actions of insulin-like growth factors (IGFs) are modulated by a family of six high affinity binding proteins (IGFBPs 1-6). IGFBP-6 differs from other IGFBPs in having the highest affinity for IGF-II and in binding IGF-I with 20-100-fold lower affinity. IGFBPs 1-5 contain 18 conserved cysteines, but human IGFBP-6 lacks 2 of the 12 N-terminal cysteines. The complete disulfide linkages of IGFBP-6 were determined using electrospray ionization mass spectrometry of purified tryptic peptide complexes digested with combinations of chymotrypsin, thermolysin, and endoproteinase Glu-C. Numbering IGFBP-6 cysteines sequentially from the N terminus, the first three disulfide linkages are Cys1-Cys2, Cys3-Cys4, and Cys5-Cys6. The next two linkages are Cys7-Cys9 and Cys8-Cys10, which are analogous to those previously determined for IGFBP-3 and IGFBP-5. The C-terminal linkages are Cys11-Cys12, Cys13-Cys14, and Cys15-Cys16, analogous to those previously determined for IGFBP-2. Disulfide linkages of IGFBP-1 were partially determined and show that Cys1 is not linked to Cys2 and Cys3 is not linked to Cys4. Analogous with IGFBP-3, IGFBP-5, and IGFBP-6, Cys9-Cys11 and Cys10-Cys12 of IGFBP-1 are also disulfide-linked. The N-terminal linkages of IGFBP-6 differ significantly from those of IGFBP-1 (and, by implication, the other IGFBPs), which could contribute to the distinctive IGF binding properties of IGFBP-6.


Extraction of Microcrystalline Cellulose and Silica from Agriculture Waste and Its Application in Synthesis of Wheat Gluten and Fish Scales Derived Bioplastic.
Plastics play a significant part in human life and the world we live in. The use of plastics results in detrimental effects on the natural world, which compels us to look for viable replacements. As a result of their enhanced capacity to biodegrade, bioplastics are becoming increasingly important materials. In recent years, there has been a rapid ascent in the utilization of biopolymers in various applications. The objective of this research is to investigate the impact that silica obtained from rice hull ash (RHA) and microcrystalline cellulose (MCC) obtained from groundnut husk have on the properties of bioplastic obtained from wheat gluten and fish scales. The usage of fish scales has been shown to have a positive effect on weight reduction and debasement rates. Microcrystalline cellulose (MCC) is utilized in a wide range of concentrations, and the influence of MCC on bioplastic is researched. The biodegradability tests of bioplastic revealed that the plastic lost 35% of its weight in just 14 days. The experiments that were done to evaluate the chemical stability and tensile strength of the bioplastic indicated that the MCC content has a significant effect in improving the characteristics of the material.


MiR-99a suppresses cell migration and invasion by regulating IGF1R in gastric cancer.
Gastric cancer is a common kind of gastrointestinal malignancies. Increasing evidence indicates dysregulation of microRNA-99a (miR-99a) in gastric cancer, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. The purpose of this study is to explore how miR-99a worked in gastric cancer on migration and invasion. The mRNA and protein levels of miR-99a and insulin-like growth factor 1 receptor (IGF1R) in gastric cancer were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot. Transwell assay was employed to analyze the migratory and invasive capacities. The Dual-Luciferase reporter assay was performed to confirm miR-99a mediated the expression of IGF1R by directly targeting its mRNA 3'-untranslated regions (3'-UTR) in gastric cancer cells. MiR-99a was discovered to be significantly downregulated while IGF1R was upregulated in gastric cancer tissues and cell lines. The expression of miR-99a had a negative correlation with the IGF1R expression in gastric cancer tissues. Moreover, miR-99a was low expressed in gastric cancer cells HGC-27 and MGC-803 compared to the normal cell line. MiR-99a suppressed the migration and invasion through directly binding to the 3'-UTR of IGF1R mRNA in HGC-27 cells. In addition, IGF1R could reverse partial roles of miR-99a on migration and invasion in gastric cancer. MiR-99a inhibited the migratory and invasive abilities by regulating the expression of IGF1R. MiR-99a was downregulated while IGF1R was upregulated in gastric cancer cell lines. The newly identified miR-99a/IGF1R axis provides novel insight into the pathogenesis of gastric cancer.


Intergenerational effects on size at birth in South India.
Several studies have shown that a baby's birthweight correlates with the birthweight and adult size of both its parents, but more strongly with those of its mother, suggesting that both the 'maternal environment' and inherited genes influence size at birth. There are no previous such intergenerational data from India. Holdsworth Memorial Hospital (HMH), Mysore, South India, has preserved birth records containing the birthweight, length and head circumference of all newborns since 1934. We identified 468 mother-offspring and 341 father-offspring pairs born in the hospital. Daughters and sons (born 1990-95) were heavier at birth than their mothers and fathers, respectively, with a mean (SD) increase in birthweight of 121 g (24 g) between the two generations. The birthweight of both parents predicted offspring birthweight equally (mother: regression slope beta = 255 g/kg; father beta = 251 g/kg; P < 0.001 for both). Paternal birth length had a stronger effect than maternal birth length on offspring birth length. The mother's adult body mass index (BMI) had a greater effect than paternal BMI on offspring birthweight (mother: 18 g/kg/m(2); P < 0.001; father: 15 g/kg/m(2); P = 0.04). In a regression model including data for both parents (available for 57 children) this difference was greater (mother: 46 g/kg/m(2); P < 0.001; father: -10 g/kg/m(2); ns). In contrast, paternal height had stronger effects than maternal height on offspring birth length (mother: 0.8 mm/cm; ns; father: 1.5 mm/cm; P < 0.001). In conclusion, size at birth is influenced by a combination of environmental and genetic factors. Both maternal and paternal birthweight correlate with offspring size at birth. Maternal nutritional status (BMI) influences birthweight. Paternal factors appear to contribute to neonatal skeletal size.


How Does Ossification of Posterior Longitudinal Ligament Progress in Conservatively Managed Patients?
Retrospective cohort study. The aim of this study was to elucidate the progression of ossification of the posterior longitudinal ligament (OPLL) in conservatively managed patients and determine its risk factors SUMMARY OF BACKGROUND DATA.: Although several studies have demonstrated how OPLL progresses after laminoplasty or fusion, its progression in conservatively managed patients remains unclear. The vertical length of the ossified mass and its thickness at each segment were evaluated on sagittal computed tomography images. Patients with vertical growth >2 mm were included in the vertical progression group. Segments with a thickness progression >1 mm were classified as thickness progressed segments, and patients who had at least one progressed segment were included in the thickness progression group. Based on the characteristics at each disc level, the ossified mass at each segment was classified into four types: type 1, no disc space involvement; type 2, involving the disc space, but not crossing; type 3, crossing the disc space, but not fused; and type 4, completely fused. The progression of ossified mass was observed in younger patients (P < 0.01) and in C2-C3 involvement (P < 0.01) cases. Moreover, progression in both directions was observed more frequently in the mixed-type OPLL (P < 0.01). Progression occurred most often in type 3 segments (72.0%, P < 0.01). In type 3 segments, thickness progression was found more frequently in segments with segmental range of motion (ROM) ≥5° (55.6% vs. 27.8%, P = 0.04). The proportion of segments whose initial thickness was >5 mm was significantly higher among progressed segments (60.0% vs. 35.2%, P = 0.03). Young age, C2-C3 involvement, and mixed-type OPLL are risk factors for OPLL progression. Segments with morphology of crossing the segment, but without fusion (type 3), segmental ROM ≥5°, and initial thickness >5 mm need special attention. 3.


Influence of nootropic drugs on the memory-impairing effect of diethyldithiocarbamate and clonidine in "step down" passive avoidance in albino rats.
Experiments on albino rats were carried out to study the effects of the nootropic drugs piracetam, aniracetam, meclofenoxate and fipexide on the DA-beta-hydroxylase inhibitor diethyldithiocarbamate- and the alpha 2-adrenoceptor agonist clonidine-impaired cognitive functions. The changes in memory were studied by the step down passive avoidance with punishment reinforcement. Diethyldithiocarbamate, injected intraperitoneally at a dose of 300 mg/kg and clonidine at a dose of 0.1 mg/kg i. p. considerably impaired retention for passive avoidance. The administration of piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg) orally for 5 days prior to training completely abolished the memory-impairing effect of diethyldithiocarbamate and clonidine. The role of NAergic neurotransmitter system for the memory disturbances caused by diethyldithiocarbamate and clonidine as well as for the protective effects of the nootropic agents tested is discussed.


Drug Target Interference in Immunogenicity Assays: Recommendations and Mitigation Strategies.
Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided.


MRI edge enhancement as a diffusive discord of spin phase structure.
The enhancement of magnetic resonance image intensity near impermeable boundaries can be nicely described by a new approach where the diffusional spin echo attenuation is linked to the correlation function of molecular motion. In this method the spin phase structure created by the applied gradient is considered to be a composition of plane waves with the wave vectors representing feasible momentum states of a particle in confinement. The enhancement of edges on the magnetic resonance images (MRI) comes out as a discord of plane waves due to particle motion. It results from the average of the wave phase by using the cumulant expansion in the Gaussian approximation. The acquired analytical expression describes the MRI signal space distribution where the enhancement of edges depends on the intensity and the duration of gradient sequence as well as on the length of the mean squared particle displacement in restricted geometry. This new method works well with gradients of general waveform and is, therefore, suitable for imaging sequences where finite or even modulated gradients are usually used.


Myasthenic crisis: report of 24 cases.
Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG) with a high mortality rate. The aim of our study was to review the different therapeutics approaches in the treatment of MC and their impact in the final outcome. We reviewed the medical files of patients diagnosed with MG admitted between February 1993 and October 1997, who developed MC. Sex, mean age, disease's duration, functional scale, symptoms preceding the crisis, crisis therapy in each set and mortality were then analysed. There were 24 patients who developed MC, 21 females and 3 males, with 1 neonatal, 1 congenital sporadic, 17 juvenile/adult, 3 over 50 years and 2 with thymoma. Dysphagia, dysphonia and dysartria were the most common symptoms preceding the crisis. A precipitating factor was elicited in 8 cases and the most common was infection (upper airway infection, urinary tract infection and pneumonia). 16 patients needed a nasogastric tube and 9 had a tracheostomy performed. 24 patients used anticholinesterase drugs, 21 prednisone, 7 immunosuppressive agents, 5 plasmapheresis, 3 human hyperimune gamma immunoglobulin and 12 had thymectomy. A good response was obtained in 13, satisfactory in 7 and there were 4 deaths. We concluded that in spite of all the therapeutics options, there were non statistically significant differences in the outcome of patients that underwent thymectomy and those who did not.


On the Interpretation of Response Time vs Onset Asynchrony Functions: Application to Dual-Task and Precue-Utilization Paradigms.
The central bottleneck model of dual-task performance (H. Pashler and J. C. Johnston, 1998, Quarterly Journal of Experimental Psychology, 46A, 51-82) and the serial processing model of precue utilization (R. Gottsdanker, 1992, Acta Psychologica, 79, 21-43) are based on a common formal structure: They both represent response time as RT(tau)=max(X-tau, Y)+Z, where X, Y, Z denote the duration of certain processing stages specified by the models and tau denotes the onset asynchrony (SOA) between two stimuli. We consider this model within a stochastic framework in which the stage durations are random variables following an arbitrary joint distribution and derive properties of the function relating E[RT(tau)] to SOA. We present a distribution-free result which relates the slope of this function to the distribution of the random durations of the assumed processing stages. Our results allow for a direct, model-based interpretation of data from related experiments; specifically, they show how the slope of the SOA-function depends on experimental factors which selectively influence individual processing stages. We explain the implications of our results for models of dual-task performance and precue utilization and illustrate their application to data obtained by M. C. Smith (1969, Acta Psychologica, 30, 220-231) and R. Gottsdanker (1992, loc. cit.) Copyright 2001 Academic Press.


A Microfluidic Chip Embracing a Nanofiber Scaffold for 3D Cell Culture and Real-Time Monitoring.
Recently, three-dimensional (3D) cell culture and tissue-on-a-chip application have attracted attention because of increasing demand from the industries and their potential to replace conventional two-dimensional culture and animal tests. As a result, numerous studies on 3D in-vitro cell culture and microfluidic chip have been conducted. In this study, a microfluidic chip embracing a nanofiber scaffold is presented. A electrospun nanofiber scaffold can provide 3D cell culture conditions to a microfluidic chip environment, and its perfusion method in the chip can allow real-time monitoring of cell status based on the conditioned culture medium. To justify the applicability of the developed chip to 3D cell culture and real-time monitoring, HepG2 cells were cultured in the chip for 14 days. Results demonstrated that the cells were successfully cultured with 3D culture-specific-morphology in the chip, and their albumin and alpha-fetoprotein production was monitored in real-time for 14 days.


Synthesis Strategies for Ultrastable Zeolite GIS Polymorphs as Sorbents for Selective Separations.
Designing zeolites with tunable physicochemical properties can substantially impact their performance in commercial applications, such as adsorption, separations, catalysis, and drug delivery. Zeolite synthesis typically requires an organic structure-directing agent to produce crystals with specific pore topology. Attempts to remove organics from syntheses to achieve commercially viable methods of preparing zeolites often lead to the formation of impurities. Herein, we present organic-free syntheses of two polymorphs of the small-pore zeolite P (GIS), P1 and P2. Using a combination of adsorption measurements and density functional theory calculations, we show that GIS polymorphs are selective adsorbents for H2 O relative to other light gases (e.g., H2 , N2 , CO2 ). Our findings refute prior theoretical studies postulating that GIS-type zeolites are excellent materials for CO2 separation/sequestration. We also show that P2 is significantly more thermally stable than P1, which broadens the operating conditions for GIS-type zeolites in commercial applications and opens new avenues for exploring their potential use in processes such as catalysis.


Aqueous Ln(III) luminescence agents derived from a tasty precursor.
The synthesis, characterization, and photophysical properties are reported for several Ln(III) complexes of a tetradentate chelate, 5LIO-MAM, derived from the common flavor enhancer "maltol". Eu(III), Yb(III), and Nd(III) form stable ML2 complexes in aqueous solution that emit in the red or near-infrared (NIR) upon excitation at ca. 330 nm. The synthesis, aqueous stability, and photophysical properties are reported for a novel tetradentate ligand derived from maltol, a commonly used flavor enhancer. In aqueous solution, this chelate forms stable complexes with Ln(III) cations, and sensitized emission was observed from Eu(III), Yb(III), and Nd(III). A comparison with recently reported and structurally analogous ligands reveals a slightly higher basicity but lower complex stability with Eu(III) [pEu = 14.7(1)]. A very poor metal-centered quantum yield with Eu(III) was observed (Phi(tot) = 0.04%), which can be rationalized by the similar energy of the ligand triplet state and the Eu(III) (5)D0 emissive level. Instead, sensitized emission from the Yb(III) and Nd(III) cations was observed, which emit in the NIR.


On Network Structural and Temporal Encodings: A Space and Time Odyssey.
The dynamic network visualization design space consists of two major dimensions: network structural and temporal representation. As more techniques are developed and published, a clear need for evaluation and experimental comparisons between them emerges. Most studies explore the temporal dimension and diverse interaction techniques supporting the participants, focusing on a single structural representation. Empirical evidence about performance and preference for different visualization approaches is scattered over different studies, experimental settings, and tasks. This paper aims to comprehensively investigate the dynamic network visualization design space in two evaluations. First, a controlled study assessing participants' response times, accuracy, and preferences for different combinations of network structural and temporal representations on typical dynamic network exploration tasks, with and without the support of standard interaction methods. Second, the best-performing combinations from the first study are enhanced based on participants' feedback and evaluated in a heuristic-based qualitative study with visualization experts on a real-world network. Our results highlight node-link with animation and playback controls as the best-performing combination and the most preferred based on ratings. Matrices achieve similar performance to node-link in the first study but have considerably lower scores in our second evaluation. Similarly, juxtaposition exhibits evident scalability issues in more realistic analysis contexts.


[The genetic evidence for sympatric speciation pattern of Cyprinus from Erhai Lake].
In the present paper, mtDNA RFLP and mtDNA D-loop sequencing were investigated in three species of Cyprinus from Erhai Lake. The results indicated that two mtDNA haplotypes were identified in three species of Cyprinus from Erhai Lake by using 16 restriction endonucleases. All individuals share the dominant type I except one individual of C. longipectoralis shows type II just with only one cleavage site polymorphism when tested by Dra I. Compared to the reported interspecific and intraspecific sequence divergence in fishes, the present divergence values of 0% - 0.0075% from the Cyprinus species native to Erhai Lake were too much lower. Furthermore, 449 bp of mtDNA D-loop region sequencing was investigated in these three Cyprinus species. There were six mtDNA haplotypes indicated by seven variation sites. The interspecific sequence divergence were 0.082% - 0.171%. It is also at least one degree lower than some allopatric Cyprinus species we studied. A remarkably low level of genetic divergence detected among the three species of Cyprinus species in Erhai Lake both by mtDNA RFLP and D-loop region sequencing provides direct genetic evidence for its sympatric speciation pattern, which could occurred without progressive adaptive genetic variation.


The KNS1 gene of Saccharomyces cerevisiae encodes a nonessential protein kinase homologue that is distantly related to members of the CDC28/cdc2 gene family.
A novel protein kinase homologue (KNS1) has been identified in Saccharomyces cerevisiae. KNS1 contains an open reading frame of 720 codons. The carboxy-terminal portion of the predicted protein sequence is similar to that of many other protein kinases, exhibiting 36% identity to the cdc2 gene product of Schizosaccharomyces pombe and 34% identity to the CDC28 gene product of S. cerevisiae. Deletion mutations were constructed in the KNS1 gene. kns1 mutants grow at the same rate as wild-type cells using several different carbon sources. They mate at normal efficiencies, and they sporulate successfully. No defects were found in entry into or exit from stationary phase. Thus, the KNS1 gene is not essential for cell growth and a variety of other cellular processes in yeast.


The Integration of Metabolomic and Proteomic Analyses Revealed Alterations in Inflammatory-Related Protein Metabolites in Endothelial Progenitor Cells Subjected to Oscillatory Shear Stress.
Endothelial progenitor cells (EPCs) play essential roles in vascular repair. Our previous study suggests OSS would lead EPCs transdifferention into the mesenchymal cell that aggravates pathological vascular remodeling. The primary purpose of this study was to apply OSS in vitro in EPCs and then explore proteins, metabolites, and the protein-metabolite network of EPCs. Endothelial progenitor cells were kept in static or treated with OSS. For OSS treatment, the Flexcell STR-4000 parallel plate flow system was used to simulate OSS for 12 h. Subsequently, an untargeted metabolomic LC/MS analysis and a TMT-labeled quantitative proteomic analysis were performed. A total of 4,699 differentially expressed proteins (DEPs) were identified, among which 73 differentially expressed proteins were potentially meaningful (P < 0.05), with 66 upregulated and 7 downregulated expressions. There were 5,664 differential metabolites (DEMs), of which 401 DEMs with biologically potential marker significance (VIP > 1, P < 0.05), of which 137 were upregulated and 264 were downregulated. The Prison correlation analysis of DEPs and DEMs was performed, and the combined DEPs-DEMs pathway analyses of the KGLM database show 39 pathways. Among the DEPs, including the Phosphoserine phosphatase (PSPH), Prostaglandin E synthase 3 (PTGES3), Glutamate-cysteine ligase regulatory subunit (GCLM), Transaldolase (TALDO1), Isocitrate dehydrogenase 1 (IDH1) and Glutathione S-transferase omega-1 (GSTO1), which are significantly enriched in the citric acid cycle (TCA cycle) and fatty acid metabolic pathways, promoting glycolysis and upregulation of fatty acid synthesis. Moreover, we screened the 6 DEPs with the highest correlation with DEMs for predicting the onset of early AS and performed qPCR to validate them. The comprehensive analysis reveals the following main changes in EPCs after the OSS treatment: dysregulation of glutamate and glycine metabolism and their transport/catabolic related proteins. Disorders of fatty acid and glycerophospholipid metabolism accompanied by alterations in the corresponding metabolic enzymes. Elevated expression of glucose metabolism.


Executive function and latent classes of childhood obesity risk.
Executive function (EF) is the set of neuro-cognitive processes associated with self-regulation, decision-making, and goal-directed behavior. The goal of this study is to examine cross-sectional relationships between EF and latent classes of youth characterized by patterns of obesity-related health behaviors (i.e., high fat/high sugar intake, fruit and vegetable intake, physical activity, sedentary behavior, and dieting). Participants were 997 4th grade youth in a school-based obesity prevention program. Cross-sectional relationships at study baseline between established latent classes of obesity risk and EF problems were assessed. General linear models demonstrated that EF problems were associated with classification into two unhealthy latent obesity risk classes. One potential implication of study findings is that obesity intervention efforts include EF promotion content tailored for latent classes of youth at different levels of obesity risk.


Technological and Sensory Aspects of Macaroni with Free or Encapsulated Azolla Fern Powder.
Azolla might be considered an alternative and promising dietary ingredient for antioxidants. There have not been any reports on the incorporation of free Azolla fern powder (FAP) or its microcapsules in foods, especially fresh pasta, yet. Microencapsulation was used to mask the undesirable taste and odour of Azolla, as well as to preserve its antioxidant potential. The current study concentrated on two major goals. The first goal was to use alginate as a wall material for FAP encapsulation, as well as to characterise the FAP microcapsule for its encapsulation efficiency, solubility, and thermal stability. The second goal was to assess the impact of integrating FAP or its microcapsules into fresh macaroni on its colour parameters, cooking quality, texture properties, and sensory characteristics. The microspheres had a high encapsulation efficiency (88.19%) and a low water solubility (85.23 g/kg), making them suitable for use in foods that require cooking in water. When compared to free Azolla powder, encapsulation reduced the antioxidant activity loss rate by 67.73%. All the cooking and textural properties of fresh macaroni were not significantly affected, except for water absorption and weight gain, but the overall acceptability index (85.13%) was not affected by microcapsule incorporation.


[Duloxetine. A new preparation for patients with urinary incontinence].
Stress Urinary Incontinence is a common symptom among women. The urethral closure is insufficient. Pelvic floor exercise can minish the symptoms, but many women need an operation. Duloxetine, a new drug, is believed to strengthen the contraction of the external urethral sphincter through central neuromodulation, resulting in enhanced urethral closure during the urine storage phase. In controlled studies a significant effect are found in women suffer from Stress Urinary Incontinence. Discontinuate rates for adverse events were high especially nausea and fatigue. The adverse event deminish after 4 weeks.


Pharmacokinetics of clomipramine in dogs following single-dose and repeated-dose oral administration.
To determine pharmacokinetics of clomipramine and its principle metabolite (desmethylclomipramine) in the plasma of dogs following single-dose and repeated-dose oral administration at various dosages. 9 male and 9 female Beagles. Clomipramine was administered orally at a dose of 1, 2, or 4 mg/kg to 3 male and 3 female dogs, first as a single dose and then, after an interval of 14 days, twice daily for 10 days. Plasma clomipramine and desmethylclomipramine concentrations were measured by use of a gas chromatography with mass-selection method. Dose-related accumulation was detected following repeated-dose administration. Accumulation ratios after administration of clomipramine at dosages of 1, 2, and 4 mg/kg twice daily were 1.4, 1.6, and 3.8, respectively, for clomipramine and 2.1, 3.7, and 7.6, respectively, for desmethylclomipramine. Terminal half-life increased slightly (1.6-fold for clomipramine and 1.2-fold for desmethylclomipramine) with repeated-dose administration but remained short in all groups (< or = 4 hours). Steady state was reached within 4 days in all animals. Ratios of the areas under the concentration versus time curves from time 0 to 12 hours for clomipramine and desmethylclomipramine were 3.9, 3.1, and 1.5 after repeated administration at dosages of 1, 2, and 4 mg/kg every 12 hours, respectively. Areas under the concentration versus time curve, mean residence times, and terminal half-lives were not significantly different between male and female dogs. Repeated administration of clomipramine results in higher concentrations of clomipramine than desmethylclomipramine in dogs.


Comparative characteristics of mesenchymal stem cells derived from reamer-irrigator-aspirator, iliac crest bone marrow, and adipose tissue.
Mesenchymal stem cells (MSCs) have been considered promising tools for new clinical concepts in supporting cellular therapy and regenerative medicine. More recently, Ream/Irrigator/Aspirator (RIA) was introduced as a source of MSCs. In this study we compared MSCs derived from three different sources (iliac crest bone marrow (ICBM), adipose tissue (AT), and (RIA)) regarding the morphology, the success rate of isolating MSCs, colony frequency, expansion potential, osteogenic and chondrogenic differentiation capacity. MSCs were isolated from three different sources and flow cytometric analyses were performed for cell characterization. Colony-forming unit-fibroblast (CFU-F) assay and population doubling time (PDT) were evaluated for MSCs derived from three different sources and differentiation potential of RIA, ICBM-, and AT-MSCs were determined by staining. Additionally, gene expression profiles for tissue specific markers corresponding to osteogenesis and chondrogenesis were analyzed using real time polymerase chain reaction (RT-PCR). Cultured with the appropriate condition, osteogenic and chondrogenic differentiation could be confirmed in all MSC preparations. Flow cytometry analysis indicated that RIA- and AT-derived MSCs have more homogenous populations than ICBM-MSCs. A comparison of the colonogenic ability in different tissues by CFU-F assay after 10 days showed that more colonies are formed from RIA-MSCs than from ICBM-MSCs, and AT-MSCs. AT-MSCs, were dispersed with no obvious colonies. The RIA-MSCs underwent osteogenesis and chondrogenesis at a faster rate than ICBM and AT-MSCs. Direct comparisons of RIA- to ICBM- and AT-MSCs have shown the RIA-MSCs have higher differentiation toward osteoblast and chondrocytes compared to other sources of MSCs. Hence, RIA-MSCs may be recommended as a more suitable source for treating orthopedic disorders.


Di-K19Hc, an antimicrobial peptide as new ototopical agent for treatment of otitis media.
Di-K19Hc is a promising new ototopical antibiotic for treatment of middle ear infections associated with antibiotic-resistant bacteria. Di-K19Hc was previously shown to exert profound antimicrobial activity against a variety of antibiotic-resistant bacteria and fungi. In this study, we evaluated the potential use of di-K19Hc as a topical agent for the treatment of otitis media (OM) caused by a variety of microbial pathogens including bacteria resistant to conventional antibiotics. Antimicrobial activity of di-K19Hc was measured by colony count assay. Hearing threshold was determined by measurement of auditory brainstem response in mice treated with di-K19Hc. Mice treated with gentamicin were used as a control. Di-K19Hc showed much stronger antimicrobial activity against methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa associated with human OM than did ofloxacin. Also, it was shown that the peptide exhibited substantial dose-dependent antimicrobial activity against microbes from middle ear fluid of patients with OM. Topically applied di-K19Hc caused neither a decrease of hearing level nor loss of hair cells.


What the clock tells the eye: lessons from an ancient arthropod.
Circadian changes in visual sensitivity have been observed in a wide range of species, vertebrates, and invertebrates, but the processes impacted and the underlying mechanisms largely are unexplored. Among arthropods, effects of circadian signals on vision have been examined in most detail in the lateral compound eye (LE) of the American horseshoe crab, Limulus polyphemus, a chelicerate arthropod. As a consequence of processes influenced by a central circadian clock, Limulus can see at night nearly as well as they do during the day. The effects of the clock on horseshoe crab LE retinas are diverse and include changes in structure, gene expression, and rhabdom biochemistry. An examination of the known effects of circadian rhythms on LEs shows that the effects have three important outcomes: an increase in visual sensitivity at night, a rapid decrease in visual sensitivity at dawn, and maintenance of eyes in a relatively low state of sensitivity during the day, even in the dark. All three outcomes may be critically important for species' survival. Specific effects of circadian rhythms on vision will certainly vary with species and according to life styles. Studies of the circadian regulation of Limulus vision have revealed that these effects can be extremely diverse and profound and suggest that circadian clocks can play a critical role in the ability of animals to adapt to the dramatic daily changes in ambient illumination.


The Relationship Between Supportive Friendships, Conflictual Friendships, and Deviance During Emerging Adulthood.
As deviant behavior is increasing during emerging adulthood and friends are a driving force behind deviance, the goal of this study is to explore the relationships between friend support, conflict, and crime. Using a large sample of friendship pairs and developmental interpretations of social control and differential association theories, a series of mixed models are estimated, which investigate the roles of support, conflict, and peer deviance on an individual's self-reported property crime. Results demonstrate that high levels of support and conflict relate to less offending in both independent and interdependent ways. However, neither social control nor differential association can provide a clear explanation to these findings, even though support and conflict clearly seem important for offending during emerging adulthood.


Effect of hypoxia on gene expression by human hepatocytes (HepG2).
The full extent to which hypoxia produces gene expression changes in human cells is unknown. We used late-generation oligonucleotide arrays to catalog hypoxia-induced changes in gene expression in HepG2 cells. Five paired sets of cultures were subjected to either control (room air-5% CO(2)) or hypoxic (1% O(2)-5% CO(2)) conditions for 24 h, and RNA was analyzed on an Affymetrix cDNA array containing approximately 12,600 sequences. A statistically significant change in expression was shown by 2,908 sequences (1,255 increased and 1,653 decreased). The observed changes were highly concordant with published literature on hypoxic stress but showed relatively little overlap (12-22%) with changes in gene expression that have been reported to occur after heat stress in other systems. Of note, of these 2,908 sequences, only 387 (213 increased and 174 decreased) both exhibited changes in expression of twofold or greater and were highly expressed in at least three of the five experiments. We conclude that the effect of hypoxia on gene expression by HepG2 cells is broad, has a significant component of downregulation, and includes a relatively small number of genes whose response is truly independent of cell and stress type.


Visceral fat accumulation and postdexamethasone serum cortisol levels in patients with adrenal incidentaloma.
Visceral fat is a significant cardiovascular risk factor. Because visceral fat has not been measured systematically in patients with adrenal incidentalomas, we have tested the hypothesis that visceral fat volume may be associated with cutoffs for serum cortisol levels post dexamethasone. This was a retrospective, cross-sectional study. The study was conducted at the Endocrine Investigation Unit, University Teaching Hospital. Seventy-three women and 52 men diagnosed with adrenal incidentalomas and 9 patients with overt Cushing's syndrome participated in this study. The following was measured for serum cortisol level after dexamethasone suppression and visceral fat ratios: visceral-subcutaneous (V:S) and visceral-total volume (V:TV) measured by computed tomography. Sixty-eight patients with a postdexamethasone serum cortisol greater than 1.8 μg/dL (50 nmol/L) showed a significantly higher mean V:S and V:TV fat ratio compared with those whose serum cortisol was less than 1.8 μg/dL: women, lnV:S, -0.45 vs -0.69 [mean difference 0.24 (95% confidence interval [CI] 0.08-0.41); P = .004] and V:TV, 0.39 vs 0.34 [mean difference 0.05 (95% CI 0.02-0.09); P = .004]; men, lnV:S, 0.64 vs 0.29 [mean difference 0.35 95% CI 0.08-0.63); P = .01] and V:TV, 0.65 vs 0.57 [mean difference 0.08 (95% CI 0.02-0.14); P = .02]. By ANOVA and post hoc analysis (Fisher's least significant differences), there was no difference in fat ratios between the postdexamethasone serum cortisol groups [1.8-2.9 μg/dL (50-82 nmol/L), 3.0-5.0 μg/dL (83-137 nmol/L), > 5.0 μg/dL (>138 nmol/L) and Cushing's syndrome (mean V:TV: 0.38, 0.40, 0.40, 0.41, respectively)], but they all differed significantly from the less than the 1.8-μg/dL group (V:TV: 0.34, P = .03). Visceral fat is increased in patients with adrenal incidentalomas and a postdexamethasone serum cortisol of greater than 1.8 μg/dL and is similar to that found in patients with overt Cushing's syndrome.


[Problems and recommendations for use of G-CSF in lung cancer patients with neutropenia after chemotherapy].
Reports are reviewed on G-CSF studies in neutropenia after lung cancer chemotherapy, especially randomized trials including our data. With preventive administration of G-CSF after dose-intensive chemotherapy in small-cell lung cancer, three studies showed that G-CSF shortened the duration of neutropenia, and reduced the incidence of neutropenic fever, the use of antibiotics and hospitalization with statistical significance, but showed no advantage in response rate or the incidence of infection-related death. And the effect on survival has not been proved clearly. When G-CSF was administered to afebrile neutropenic patients, it accelerated recovery from neutropenia significantly, but did not clearly reduce the incidence of neutropenic fever or infection. When G-CSF was administered to febrile neutropenic patients combined with antibiotics concurrently, it also could accelerate recovery of neutropenia significantly, but could not reduce neutropenic fever or infection compared with no CSF. For optimal use, it has not been proved when G-CSF should be started. Marginal therapy is considered to be administration in neutropenia with fever or infection and in severe neutropenia. Investigational therapy is considered for administration in neutropenia without fever or infection and use in clinical trials. Because no standard therapy with G-CSF has been established, additional clinical trials are necessary.