Synergistic effects of octahedral TiO2-MIL-101(Cr) with two heterojunctions for enhancing visible-light photocatalytic degradation of liquid tetracycline and gaseous toluene.
The photocatalytic performance of TiO2 is severely restricted by its low photocatalytic activity and high charge-carrier recombination rate. In order to overcome these defects, a novel octahedral TiO2-MIL-101(Cr) (T-MCr) photocatalyst with type-II heterojunction and surface heterojunction is prepared by growth of TiO2 particles on MIL-101(Cr) via optimizing the synthesis conditions. The physicochemical, optical and photoelectrochemical properties of the samples are characterized utilizing several techniques, and its photocatalytic activity for liquid tetracycline and gaseous toluene degradation is evaluated under visible light irradiation. Particularly, the T-MCr-60 shows the outstanding photocatalytic activity. The improved photocatalytic performance of T-MCr-60 is ascribed to strong interfacial contact between (0 0 1) facets, (1 0 1) facets, and MIL-101 and the synergistic effects of two heterojunctions promoting efficient charge transfer. The possible photocatalytic mechanisms involving pollutants degradation pathway and charge transfer mechanisms during the process of pollutants degradation is also discussed.


Usefulness of angiogenic factors in prenatal counseling of late-onset fetal growth-restricted and small-for-gestational-age gestations: a prospective observational study.
To create a predictive model including biomarkers and evaluate its ability to predict adverse perinatal outcomes in late-onset small fetuses, ultimately helping to provide individualized counseling at the time of diagnosis. This was a prospective observational study, including singleton pregnancies with an estimated fetal weight (EFW) below the 10th percentile, at a gestational age between 32 + 0 and 36 + 6 weeks of gestation (WG). Variables recorded at diagnosis to predict adverse pregnancy outcomes were: soluble fms-like tyrosine-kinase-1 to placental growth factor ratio (sFlt-1/PlGF), fetal Doppler (umbilical artery and middle cerebral artery), uterine artery pulsatility index (UtAPI), EFW percentile, gestational age, and the presence of maternal risk factors for placental insufficiency. Logistic regression models were developed for the prediction of three co-primary outcomes: composite adverse perinatal outcomes (APO), and the need for elective delivery before 35 or 37 WG. Sixty (52.2%) fetal growth restricted (FGR) and 55 (47.8%) small for gestational age (SGA) were enrolled. Thirteen (11.3%) women needed elective delivery before 35 WG and 27 (23.5%) women before 37 WG. At least one APO occurred in 43 (37.4%) pregnancies. The best marker in univariate analyses was the sFlt-1/PlGF ratio [AUC = 0.932 (95% CI, 0.864-0.999)]. The multivariate model including sFlt-1/PlGF showed a better predictive performance for APO than the multivariate model without sFlt-1/PlGF (P < 0.024). sFlt-1/PlGF is a good predictor of APO at the time of late-onset FGR/SGA diagnosis. Our predictive models may be useful to provide early individualized prenatal counseling in this group of women. Further studies are needed to validate these preliminary findings in a larger cohort.


Diverging racial and ethnic disparities in access to physician care: comparing 2000 and 2007.
To examine recent changes in racial and ethnic disparities in access to physician services in the United States, and investigate the economic factors driving the changes observed. Using nationally representative data on adults aged 25-64 from the 2000 and 2007 Medical Expenditure Panel Survey, we examine changes in two measures of access: whether the individual reported having a usual source of care, and whether he/she had any doctor visits during the past year. In each year, we calculate disparities in access between African Americans and Whites, and between Hispanics and Whites, applying the Institute of Medicine's definition of a disparity. Nonlinear regression decomposition techniques are then used to quantify how changes in personal characteristics, comparing 2000 and 2007, helped shape the changes observed. Large disparities in access to physician care were evident for both minority groups in 2000 and 2007. Disparities in no doctor visits during the past year diminished for African Americans, but disparities in both measures worsened sharply for Hispanics. Disparities in access to physician care are improving for African Americans in one dimension, but eroding for Hispanics in multiple dimensions. The most important contributing factors to the growing disparities between Hispanics and Whites are health insurance, education, and income differences.


Collagen crosslinking and toric iris-claw phakic intraocular lens for myopic astigmatism in progressive mild to moderate keratoconus.
To report the long-term results of combined collagen crosslinking (CXL) and toric phakic intraocular lens (pIOL) implantation to correct myopic astigmatism in patients with progressive mild to moderate keratoconus. Instituto de Microcirugia Ocular, Barcelona, Spain. Case series. From November 2006 to July 2009, CXL was performed in eyes with proven progressive keratoconus. Once refraction and topography stabilized, toric Artiflex/Artisan pIOL implantation was performed to correct residual myopic astigmatism. A complete ophthalmologic examination, including manifest refraction, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, biomicroscopy, tonometry, fundoscopy, keratometry, corneal tomography, and central endothelial cell count (ECC), was performed before each procedure and postoperatively at 3 months and at yearly intervals up to 5 years. Main outcome measures were accuracy and stability of the spherical equivalent (SE) and cylinder, keratometry, UDVA (efficacy), CDVA (safety), central ECC, and complications. The median follow-up in the 9 patients (17 eyes) was 36.9 months ± 15.0 (SD). The median interval between CXL and pIOL implantation was 3.9 ± 0.7 months. Fourteen eyes (82%) were within ± 0.50 diopter (D) of the attempted SE correction and 13 eyes (76%) were within ± 1.00 D of the attempted cylinder correction. The mean difference in simulated keratometry between preoperatively and the last follow-up was 0.17 ± 0.45 D (range -0.55 to 1.45 D). The postoperative UDVA was 20/40 or better in 16 eyes (94%). No eye lost lines of CDVA. No significant decrease in central ECC occurred (P>.05). Combined CXL and toric iris-claw pIOL implantation effectively and safely corrected myopic astigmatism in progressive mild to moderate keratoconus. Dr. Güell is a consultant to Ophtec. No other author has a financial or proprietary interest in any material or methods mentioned.


Left circumflex artery aneurysm with fistula to the coronary sinus.
A giant coronary artery aneurysm with arteriovenous fistula is a unique pathology having few surgical reports. An 82-year-old woman presented with a symptomatic giant left circumflex artery aneurysm with a fistula to the coronary sinus. The left coronary artery was dilated, and an aneurysmal change was visible from the left main trunk to the fistula. Surgery was performed to close the fistula and seclude all parts of the aneurysmal coronary artery. All coronary branches emerging from the aneurysm required bypass grafting. Herein, we present the history of this unusual case and our successful surgical strategy.


Structure of the human cone photoreceptor cyclic nucleotide-gated channel.
Cyclic nucleotide-gated (CNG) channels transduce light-induced chemical signals into electrical signals in retinal cone and rod photoreceptors. Structures of native CNG channels, which are heterotetramers formed by CNGA and CNGB subunits, have not been obtained. In the present study, we report a high-resolution cryo-electron microscopy structure of the human cone CNG channel in the apo closed state. The channel contains three CNGA3 and one CNGB3 subunits. Arg403 in the pore helix of CNGB3 projects into an asymmetric selectivity filter and forms hydrogen bonds with two pore-lining backbone carbonyl oxygens. Arg442 in S6 of CNGB3 protrudes into and occludes the pore below the hydrophobic cavity gate previously observed in homotetrameric CNGA channels. It is interesting that Arg403Gln is a disease mutation, and Arg442 is replaced by glutamine in some animal species with dichromatic or monochromatic vision. These and other unique structural features and the disease link conferred by CNGB3 indicate a critical role of CNGB3 in shaping cone photoresponses.


The effect of atropine and vagal stimulation on the release of neurotensin-like immunoreactivity in man.
This study investigated the food stimulated release of neurotensin-like immunoreactivity (NTLI) in man with and without the administration of atropine, and the influence of vagal stimulation by modified sham feeding and insulin hypoglycaemia. NTLI was measured, after ethanol extraction, by specific C- and N-terminally directed antisera. With both a liquid fat meal and a mixed meal an early peak of NTLI occurred. The mixed meal also produced a second sustained rise in plasma NTLI. An intramuscular injection of 0.6 mg atropine sulphate abolished the early peak, but had no effect on the late peak. Modified sham feeding and insulin hypoglycaemia did not release NTLI. We conclude that it is possible that a cholinergic non-vagal mechanism is responsible for the early phase of food stimulated release of NTLI in man, and that the second sustained rise may be cholinergically independent.


3D-SLIP model based dynamic stability strategy for legged robots with impact disturbance rejection.
Inspired by biomechanical studies, the spring-loaded inverted pendulum model is an effective behavior model to describe the running movement of animals and legged robots in the sagittal plane. However, when confronted with external lateral disturbances, the model has to move out of the 2-D plane and be extended to 3-D locomotion. With the degree of freedom increasing, the computational complexity is higher and the real-time control is more and more difficult, especially when considering the complex legged model. Here, we construct a control strategy based on the classical Raibert controller for legged locomotion under lateral impact disturbances. This strategy, named 3D-HFC, is composed of three core modules: touchdown angle control, body attitude angle control and energy compensation. The energy loss in each step is taken into consideration, and the real-time measured energy loss of the current step is adopted to predict that of the next step. We demonstrate the efficiency of the proposed control strategy on a simulated 3D-SLIP lower order model and a simulated running quadruped, which are perturbed by different impact forces. Furthermore, a quadruped bionic prototype named MBBOT was set up, on which lateral impact experiments were designed and implemented. Both simulation and experimental results show that the proposed approach can realize the impact disturbance rejection.


The Current Role and Implications of Stem Cell Therapy in Erectile Dysfunction: A Transformation from Caterpillar to Butterfly Is Required.
Current noninvasive treatments for erectile dysfunction (ED) include oral medications, intracavernosal injections, and vacuum-assisted devices. Although these therapies work well for many, some patients experience side effects or are unsatisfied with these therapeutic modalities. Restorative therapies are the newest frontier for ED treatments and are focused on regenerating injured tissue and delivering a possible "cure". Stem cell therapy is a regenerative treatment aimed at restoring normal erectile physiology and curing ED. It is promising in cell-based and animal studies and has now been studied in humans. Although the clinical results are not robust, future research may shed more light on the efficacy of this treatment for ED. PATIENT SUMMARY: Stem cell therapy is a promising regenerative treatment for erectile dysfunction, but the clinical results are not robust. It is currently considered an experimental treatment and should not be used outside a clinical trial setting.


The Safety and Strength of a Novel Medial, Partial Nonthreaded Pedicle Screw: A Cadaveric and Biomechanical Investigation.
Cadaveric and biomechanical study. The aim of this study was to assess the safety and pullout strength of medial, partial nonthreaded thoracic pedicle screws compared with conventional screws. The perforation rate of the pedicle screws has been reported as high as 41%. Nerve injury and irritation can result from the compression of malpositioned screw on neural structures. Ten fresh cadavers were studied. Screws, 5.0 and 6.0 mm, were inserted from T1 to T6 and T7 to T12, respectively. Pedicle perforations and fractures were recorded upon screw insertion and final positioning (nonthreaded portion facing medially) after a wide laminectomy. Pullout strength of novel and conventional screws were then tested using an Instron machine in an artificial bone substitute. A total of 240 thoracic pedicle screws were inserted. Of them, 88.8% (213 screws) were fully contained during screw insertion. There were 5.0% (12 screws) grade 1 medial perforations and 6.2% (15 screws) grade 1 lateral perforations during screw insertion. Upon final positioning, 93.8% (225 screws) were fully contained. All grade 1 medial perforations, which occurred during insertion, were converted to grade 0. No dural or nerve root injuries occurred. Pedicle split fractures were noted in 6.7% (16 screws). The use of medial, partial nonthreaded screws reduced the overall perforation rate from 11.2% to 6.2%. The mean pullout load for the 5 mm fully threaded screw versus medial, partial nonthreaded was 1419.3±106.1 N (1275.8-1538.8 N) and 1336.6±44.2 N (1293.0-1405.1 N) respectively, whereas 6 mm pullout load averaged 2126.0±134.8 N (1986.3-2338.3 N) and 2036.5±210.0 N (1818.4-2355.9 N). The difference was not statistically significant. The use of medial, partial nonthreaded pedicle screws reduced the medial perforation rate from 5.0% to 0%; however, the pullout strength was not significantly reduced. The use of this novel screw can potentially reduce the incidence of nerve injury or irritation after medial pedicle perforations.


Two-step mechanism of spiral phyllotaxis.
Fibonacci numbers such as 5, 8, and 13 occur in the spiral arrangement of lateral organs at shoot tips in plants. While the cone scales of conifers are normally arranged in 5 and 8 (or 8 and 13) curved rows in opposite directions, other numbers such as 4 and 7 (or 7 and 11) are found anomalously. The observed numbers still obey the Fibonacci rule, with the next number being the sum of the preceding two. Although these observations have been made for centuries, the underlying mechanisms of the numerical relationship have not been investigated. Here, we show that this phenomenon is caused by a two-step mechanism: (1) maintenance of a constant angle between consecutive lateral organs and (2) strong canalization of this angle to a specific value. The first step of the mechanism precedes the second step of the mechanism because the Fibonacci-rule pattern is due to the first step, while the second step distinguishes normal, anomalous and unobserved types. The current dominance of the normal type is a result of the evolutionary process of the second step.


RU 486 stabilizes a high molecular weight form of the glucocorticoid receptor containing the 90K non-steroid binding protein in intact thymus cells.
The interaction with the glucocorticoid receptor of RU 486, a recently described antiglucocorticoid, was investigated in intact cells. When incubated at 37 degrees C with intact rat thymocytes [3H] RU 486 underwent negligible nuclear transfer. Moreover when assayed in physiological buffers, i.e. physiological ionic strength and absence of molybdate, the cytosolic [3H] RU 486-receptor complexes obtained displayed a 7-8 nm Stokes radius after analysis by high performance size exclusion chromatography (HPSEC). These high size complexes appeared stable in the native cytosol but dissociated during sucrose gradient centrifugation. Western blot analysis of the fractions obtained after HPSEC separation was performed using a monoclonal antibody able to recognize the 90K non steroid binding protein associated with the molybdate stabilized glucocorticoid receptor complexes. This antibody clearly demonstrated the presence of a 90K non-steroid binding protein in the 7-8 nm peak obtained with [3H] RU 486 receptor complexes. On the contrary [3H] triamcinolone acetonide in the same conditions yielded a 5 nm peak of transformed receptor which did not contain the 90K protein. Thus RU 486, in absence of molybdate, stabilized the 90K protein-receptor interaction in intact cells, an event probably related to its antiglucocorticoid activity.


Active bleeding in acute subarachnoid hemorrhage observed by multiphase dynamic-enhanced CT.
Acute SAH is reportedly associated with rebleeding from aneurysms, and recent advances in imaging technology allow us to visualize active bleeding in SAH cases. This study aimed to retrospectively investigate the incidence and characteristics of active bleeding in patients with spontaneous SAH by using multiphase dynamic-enhanced CT. We retrospectively surveyed a series of patients with SAH who underwent CTP with 18-phase dynamic enhancement and confirmed the presence of extravasated contrast medium in the source image. We compared clinical features between 2 groups of patients with and without extravasation. Active bleeding was observed with increasing enhancement in 25.5% (13/51) of patients. All patients with extravasation were in Claassen grade 3 or 4 and WFNS grades 3, 4, or 5. The other group without extravasation included patients in all grades. A significant difference was observed in Claassen grade, WFNS grade, and increase of hematomas in follow-up CT (P < .05, for each) between the 2 groups. All CTP results of patients with extravasation were obtained within 2 hours of the onset of symptoms of SAH (P < .05). There was no significant difference in mortality at 14 days between the 2 groups (P = .128). A high incidence of active bleeding (25.5%) was detected by multiphase dynamic-enhanced CT in patients with acute SAH. These results indicate that an awareness of active bleeding in patients with SAH has the potential to affect the treatment strategy.


How many gamergates is an ant queen worth?
Ant reproductives exhibit different morphological adaptations linked to dispersal and fertility. By reviewing the literature on taxa where workers can reproduce sexually (i.e. become gamergates) we show that (1) species with a single gamergate generally have lost the winged queen caste, whereas only half of the species with several gamergates have, and (2) single-gamergate species have smaller colonies than multiple-gamergate species. Comparison with "classical" ants without gamergates, where having one vs having several winged queens are two distinct syndromes, suggests that having one vs having several gamergates are not. Gamergate number does not affect the success of colony fission, but retention of the queen caste permits the option of independent foundation.


The effects on antioxidant enzymes of PMMA/hydroxyapatite nanocomposites/composites.
In this study, polymer-ceramic nanocomposites and/or composites were prepared by solution removal method using poly(methylmethacrylat) (PMMA) and nano-hydroxyapatite (nHA). They were characterized using X-ray diffraction (XRD), Fourier transform infrared-attenuated total reflection spectroscopy (FTIR-ATR), and differential thermal analysis/thermogravimetry (DTA/TG). Their effects and biocompatibilities on antioxidant enzymes were also investigated in detail. It has been shown that nHA was dramatically dispersed at nanoscale in the polymer matrix. The interaction occurred between OH groups of nHA and carbonyl groups of polymer and introduction of ceramic into the polymer matrix generally resulted in an increase in thermal stability. Nanocomposites and composites had different effects on enzyme activities. Samples synthesized in acetone increased enzyme activities for glutathione reductase (GR) and glucose-6 phosphate dehydrogenase (G6PD) enzymes, while inhibiting glutathione peroxidase (GPx) and catalase (CAT) enzyme activities. On the other hand, samples synthesized in tetrahydrofuran (THF) exhibited inhibitory behavior for G6PD and CAT enzymes. The samples synthesized in different media did not show any regularity on enzyme activities. The nanocomposites and/or composites prepared in acetone media were better hemocompatible than those in THF.


Mapping auditory cortex in the La Plata dolphin (Pontoporia blainvillei).
This study deals with the mapping of the primary and secondary auditory cortex. Due to their important role in echolocation they were the first areas to be examined [P.J. Morgane, M.S. Jacobs, in: R.J. Harrison (Ed.), Functional Anatomy of Marine Mammals, Comparative Anatomy of the Cetacean Nervous System, vol. 1, Academic Press, London, 1972, pp. 117-144]. We analysed the brain of a La Plata dolphin (Pontoporia blainvillei), which had been fixed in formaldehyde, embedded in paraffin, cut in sections of 20mum thickness and stained with cresyl violet. The experimental approach being impossible, we used cytoarchitectonic variations in the neocortex. Former electrophysiological data [T.F. Ladygina, A.Y. Supin, Localization of the projectional sensory areas in the cortex of the porpoise Tursiops truncates, Zh. Evol. Biokhim. Fiziol. 13 (1978) 712-718] [Sokolov, T.F. Ladygina, A.Y. Supin, Location of sensory zones in cerebral cortex of dolphin, Dokl. Biol. Sci., Russian Original 202 (1-6) (1972)] provided the framework for the exact determination of borders between functional cortical areas. We used a stereological observer-independent procedure based on changes in volume density of cell bodies throughout the neocortex [A. Schleicher, et al., Stereological approach to human cortical architecture: Identification and delineation of cortical areas, J. Chem. Neuroanat. 20 (2000) 31-47]. Due to the computer program's high sensitivity to changes in volume density it was possible to analyse the poorly laminated dolphin cortex. The 3D-reconstruction of the auditory cortex was processed using the AMIRA 3.0 Graphics software package comparing the main primary gyri in the histological sections with those in coronal magnetic resonance imaging scans of another intact Pontoporia brain.


Infectiousness for humans of Ixodes ricinus containing Borrelia burgdorferi.
We studied the rate of transmission of Borrelia burgdorferi from ticks (Ixodes ricinus) to man under field conditions in a case control study. At a holiday camp in southern Germany 384 ticks were removed from 272 persons. Information on symptoms possibly related to Borrelia infection were obtained by a questionnaire to be sent back six weeks after the tick bite. Ticks were examined by immunofluorescence microscopy (IFT) for Borrelia and 49 (12.8%) were found positive. Blood was obtained from 41 persons bitten by Borrelia positive and 41 age and sex matched persons bitten by Borrelia negative ticks. Sera from age and sex matched patients of local hospitals and clinics served as additional controls. Antibody titers were obtained by indirect IFT about 13 weeks after tick bite. Titers 1 : greater than 32 suggested recent infection and 1 : 32 immunity. In the exposed group there were about half as many persons with titers 1 : less than 32 (n = 14) than in the control group (n = 27) suggesting that either part of the infected ticks was in a non-infectious state or the hosts were immune. In the exposed group there were 46.4% (n = 19) and in the control group, bitten by Borrelia negative ticks, 14.7% (n = 6) persons with titers 1 : greater than 32, but 5/6 of these persons in the control group recalled additional tick bites in 1984. Only one child (in the exposed group) developed an Erythema chronicum migrans, and no other Borrelia related manifestations were reported. The manifestation rate of the Borrelia-related disease was 4%.


Transcutaneous blood gases and sleep apnea profile in healthy preterm infants during early infancy.
Studying the development of transcutaneous blood gas levels (tcpO2 and tcpCO2) and the sleep apnea profile in relation to sleep states in normal preterm infants between 36 and 52 weeks postconceptual age we found a dynamic increase in tcpO2 during regular breathing (without apnea) and a steady decrease in tcpCO2 during both regular and periodic breathing. The mean tcpO2 of periodic breathing, however, persistently remained well below the corresponding level found during regular breathing. It is suggested that in normal preterm infants there is a continued maturational adjustment of autonomic respiratory control up to 3 months post term and, furthermore, that periodic breathing may persistently be associated with a relative hypoxemia.


The mRNA level of Charcot-Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood in vitro.
CRTH2 is one of the prostaglandin D₂ receptors and plays a proinflammatory role in allergic diseases. Gene expression markers in whole blood induced by CRTH2 activation have not previously been reported. Using microarray analyses of 54 675 genes, we revealed modest gene expression changes in human whole blood stimulated in vitro by a selective CRTH2 agonist, DK-PGD₂. Five genes were found to exhibit 1.5- to 2.6-fold changes in expression. The expression of Charcot-Leyden crystal protein/galectin-10 (CLC/Gal-10) in particular was consistently enhanced in human whole blood stimulated by DK-PGD₂, as confirmed by quantitative real-time polymerase chain reaction analyses. DK-PGD(2)-induced increases in blood CLC/Gal-10 mRNA levels were largely attenuated by the CRTH2 antagonist CAY10471.Thus, the DK-PGD₂-induced CLC/Gal-10 mRNA level can serve as a potential marker for monitoring pharmacodynamic effects of blood exposure to CRTH2 modulating agents.


Role of Hyperketonemia in Inducing Oxidative Stress and Cellular Damage in Cultured Hepatocytes and Type 1 Diabetic Rat Liver.
Type 1 diabetic (T1D) patients have a higher incidence of liver disease. T1D patients frequently experience elevated plasma ketone levels along with hyperglycemia. However, no study has examined whether hyperketonemia per se has any role in excess liver damage in T1D. This study investigates the hypothesis that hyperketonemia can induce oxidative stress and cellular dysfunction. STZ treated diabetic rats, FL83B hepatocytes, and GCLC knocked down (GSH deficient) hepatocytes were used. The blood levels of ALT and AST, biomarkers of liver damage, and ketones were elevated in T1D rats. An increase in NOX4 and ROS along with a reduction in GSH and GCLC levels was observed in T1D rat livers in comparison to those seen in non-diabetic control or type 2 diabetic rats. MCP-1 and ICAM-1 were also elevated in T1D rat livers and ketone treated hepatocytes. Macrophage markers CCR2 and CD11A that interact with MCP-1, and ICAM-1 respectively, were also elevated in the T1D liver, indicating macrophage infiltration. Additionally, activated macrophages increased hepatocyte damage with ketone treatment, which was similar to that seen in GCLC knockdown hepatocytes without ketones. Hyperketonemia per se can induce macrophage mediated damage to hepatocytes and the liver, caused by GSH depletion and oxidative stress up regulation in T1D.


A Scoping Review on Learning Health Networks Available in Pediatric Surgical Specialties.
Learning health networks (LHN) are consortia of institutions that collaborate and embrace the elements of the learning health system (LHS), including quality improvement, education, research, and stakeholder involvement. Their ultimate goal is rapid information dissemination in clinical care. Pediatric surgical specialties perform unique yet high-impact procedures that could benefit from LHN, thereby improving surgical outcomes and care through LHS approaches. Consequently, health system leaders should be aware of LHN and their importance in enhancing surgical care and improving outcomes. This scoping review aims to map and characterize the existing LHN applied in pediatric surgical specialties. A systematic literature search was performed on Medline, EMBASE, and Scopus up to June 2022, with an update search conducted in May 2023. Additionally, Google Scholar, ProQuest and inquiry from topic experts were used for cross-referencing relevant review articles to identify grey literature. This scoping review was conducted and reported according to the PRISMA-scoping review extension. A total of 56 publications for 19 LHN were identified and included in this scoping review. Out of 19 identified LHN in pediatric surgical specialties, 18 were organized in North America. Eight of the networks are related to pediatric general surgery and another eight were related to pediatric transplantation. The 16 out of 19 LHN were initiated after 2001. To date, only eight of the LHNs generated reports of comparative improved outcomes. This scoping review provides an overview of the available LHNs in pediatric surgical specialties. Over the past decade, several pediatric surgical specialties have embraced the principles of learning health systems, forming inter-institutional collaborations that utilize information technology to generate big data on patient-level clinical information, engage in quality improvement cycles, adopt evidence-based practices, and actively involve patients and stakeholders. IV.


7-Chloroquinoline-1,2,3-triazoyl carboxamides induce cell cycle arrest and apoptosis in human bladder carcinoma cells.
In the present study, the antitumoral properties of a series of 7-chloroquinoline-1,2,3-triazoyl-carboxamides (QTCA) were investigated by analyzing their cytotoxic activities against human bladder cells (5637; grade II carcinoma). In addition, their effects on cell viability, cell cycle arrest mechanisms, apoptosis induction, in silico molecular docking, and detection of pro-apoptotic and anti-apoptotic proteins were evaluated. The cytotoxicity assay identified major dose- and time-dependent cytotoxic effects in 5637 cells after they were exposed to treatment with QTCA, only minimal effects were observed on normal cells. A live/dead assay confirmed that significant cell death, arrest in the G0/G1 phase and apoptosis were associated with treatment by 1-(7-Chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) and 1-(7-Chloroquinolin-4-yl)-N-(4-fluorophenyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (QTCA-4). The in silico results indicated that these compounds acted through different mechanisms for the induction of cell cycle arrest and apoptosis. Western blotting confirmed the binding of the QTCAs to pro- and anti-apoptotic proteins. In conclusion, QTCA-1 and QTCA-4 are promising candidates for inducing cytotoxicity, cell cycle arrest, and apoptosis in human bladder cancer cells.


Population pharmacokinetics and model-based dosing optimization of teicoplanin in elderly critically ill patients with pneumonia.
To evaluate the population pharmacokinetics and pharmacodynamics of teicoplanin in elderly critically ill patients with pneumonia for optimal dosages. Fifteen critically ill patients (9 men) ≥ 60 years received teicoplanin 6 mg/kg for three doses followed by standard maintenance doses (6 mg/kg q24h) with renal dosing adjustment. Serial plasma samples from all patients were analyzed simultaneously by population pharmacokinetic modeling using NONMEM. Probability of target attainment (PTA) was calculated through Monte Carlo simulations for various dosing regimens to achieve adequate systemic exposures. The median (interquartile range, IQR) age, body mass index, and creatinine clearance (CrCl) was 75 (64-78) years, 22.5 (20.8-25.4) kg/m2, and 64 (47-106) mL/min, respectively. The median (IQR) peak and trough concentration was 46.5 (42.7-51.0) and 8.7 (7.2-9.5) mg/L. The population pharmacokinetic model showed slower clearance (CL) and larger peripheral volume of distribution (V2) in patients with reduced CrCl: CL (L/h) = 0.629 × (CrCl/64)0.656, V2 (L) = 55.7 × (CrCl/64)-0.665. Model-based simulations showed PTAs ≥85% only for higher-dose regimens (12 mg/kg) up to an MIC of 0.5 mg/L. Standard teicoplanin dosages for pneumonia may provide inadequate systemic exposures in elderly critically ill patients. High-dose regimens should be considered as empiric therapy or for less susceptible pathogens.


Efficient automated semi-quantitative urine culture analysis via BD Urine Culture App.
We aimed to assess the clinical utility of BD KiestraTM Urine Culture App (UCA). High concordance rates were observed between the urine culture colony counts obtained by medical technologists and those produced using UCA. This application may increase the efficiency of obtaining semi-quantitative urine culture results.


Multimodality agents for tumor imaging (PET, fluorescence) and photodynamic therapy. A possible "see and treat" approach.
Methyl 3-(1'-m-iodobenzyloxyethyl)-3-devinylpyropheophorbide-a (2), obtained in a sequence of reactions from pyropheophorbide-a (a chlorophyll-a derivative), was found to be a promising imaging agent and a photosensitizer for photodynamic therapy (PDT). The electrophilic aromatic iodination of the corresponding trimethylstannyl intermediate with Na124I in the presence of an Iodogen bead afforded 124I-labeled photosensitizer 4 with >95% radioactive specificity. In addition to drug-uptake, the light fluence and fluence rate that were used for the light treatment had a significant impact in long-term tumor cure. The iodo photosensitizer 2 (nonlabeled analogue of 4) produced 100% tumor cure (5/5 mice were tumor free on day 60) at a dose of 1.5 micromol/kg and a light dose of 128 J/cm2, 14 mW/cm2 for 2.5 h (lambda(max) 665 nm) at 24 h postinjection. The photosensitizer also showed promising tumor fluorescence and PET imaging ability. Our present work demonstrates the utility of the first 124I-labeled photosensitizer as a "multimodality agent", which could further be improved by using more tumor-avid and/or target-specific photosensitizers.


Testing the validity of a proposed dermal cancer slope factor for Benzo[a]pyrene.
In 2014, the United States Environmental Protection Agency (EPA) proposed a Dermal Slope Factor (DSF) for benzo[a]pyrene (BaP) of 0.006 (μg/day)-1 (USEPA 2014a). It would make cancer risk estimates associated with soil contact 100 times greater than those from soil ingestion and would predict that a large fraction of skin Basal Cell Carcinomas (BCCs) and Squamous Cell Carcinomas (SCCs) worldwide are caused by low level dermal exposures to PAHs, such as BaP. This is not logical given that sunlight (ultraviolet radiation (UV)) exposure is the generally recognized cause of BCCs and SCCs. This paper critically evaluates the proposed DSF. First, a reality check is performed using EPA standard risk assessment methods and comparing the results to actual BCC and SCC rates in the U.S. population. Then, the biological plausibility of the mechanism by which PAHs might cause human skin cancer is evaluated by exploring the generally recognized etiology of human skin cancer and comparing the genetic mutation signatures of rodent skin tumors caused by PAH exposures to those of human skin cancers. It is concluded that scientific flaws resulted in a proposed DSF value that greatly overestimates the skin cancer risk for humans dermally exposed to BaP in soil.


Cancer odor in the blood of ovarian cancer patients: a retrospective study of detection by dogs during treatment, 3 and 6 months afterward.
In recent decades it has been noted that trained dogs can detect specific odor molecules emitted by cancer cells. We have shown that the same odor can also be detected in the patient's blood with high sensitivity and specificity by trained dogs. In the present study, we examined how the ability of dogs to detect this smell was affected by treatment to reduce tumor burden, including surgery and five courses of chemotherapy. In Series I, one drop of plasma from each of 42 ovarian cancer patients (taken between the fifth and sixth courses of chemotherapy) and 210 samples from healthy controls were examined by two trained dogs. All 42 patients in Series I had clinical complete responses, all except two had normal CA-125 values and all were declared healthy after primary treatment. In Series II, the dogs examined blood taken from a new subset of 10 patients at 3 and 6 months after the last (sixth) course of chemotherapy. In Series I, the dogs showed high sensitivity (97%) and specificity (99%), for detecting viable cancer cells or molecular cancer markers in the patients' plasma. Indeed, 29 of 42 patients died within 5 years. In Series II, the dogs indicated positive samples from three of the 10 patients at both the 3- and 6-month follow-up. All three patients had recurrences, and two died 3-4 years after the end of treatment. This was one of the most important findings of this study. Seven patients were still alive in January 2013. Although our study was based on a limited number of selected patients, it clearly suggests that canine detection gave us a very good assessment of the prognosis of the study patients. Being able to detect a marker based on the specific cancer odor in the blood would enhance primary diagnosis and enable earlier relapse diagnosis, consequently increasing survival.


Adjuvant Chemotherapy with S-1 plus Cisplatin for Patients with Stage III Gastric Cancer After Curative Resection.
The aim of this study was to investigate the efficacy and safety of S-1 plus low-dose cisplatin for stage IIIB and stage IIIC gastric cancer patients after D2 gastrectomy. The study group comprised of 52 patients. In the first cycle, S-1 (80 mg/m2) was administered daily for 3 weeks, followed by 2 weeks of rest; low-dose cisplatin (10 mg) was administered on days 1-5 and 8-12. In the second and third cycles, S-1 was administered alone. Overall survival was 47.0 months for stage IIIB patients and 24.0 months for stage IIIC (p=0.038). Disease-free survival was 17.0 and 16.0 months respectively (p=0.739). Grade 3 or 4 adverse events occurred in 20 patients (38.5%). Multivariate analysis identified stage IIIC as independent prognostic factor for survival. Our treatment was manageable and safe for stage IIIB or stage IIIC patients. Stage IIIC gastric cancer portends an especially poor prognosis following D2 gastrectomy.


Use of the iced cystogram to differentiate bladder neck and external sphincter obstruction.
An iced cystogram was done on 31 patients with neurogenic bladder and voiding dysfunction. We observed 5 distinguishable patterns upon which therapeutic measures to improve balance could be based. We found the iced cystogram to be a simple, inexpensive yet reliable technique to assess detrusor sphincter imbalance. With the information obtained from this study the therapeutic options were delineated more clearly and the results of the treatment were made more predictable.


Upper gastrointestinal bleeding in Scotland 2000-2015: trends in demographics, aetiology and outcomes.
Upper gastrointestinal bleeding (UGIB) remains a common cause of presentation and admission to hospital in the UK, with the incidence in Scotland one of the highest in the world. To investigate the difference in demographics, deprivation quintiles, aetiology of bleeding and clinical outcomes in patients presenting with UGIB to hospitals across Scotland over a 16-year period METHODS: Data were collected using the National Data Catalogue and analysed retrospectively using the National Safe Haven. We included 129 404 patients. The annual number of patients presenting with UGIB remained similar over the 16-year period. Mean age at admission increased from 59.2 to 61.4 years. There was a significant drop in variceal bleeding over time from 2.2% to 1.7% (P < 0.001). The incidence of UGIB was highest in the more deprived quintiles. There was a significant decrease in 30-day case-fatality from 10.1% in 2000 to 7.9% in 2015 (P < 0.001), which was observed across all deprivation quintiles. Mean length of stay fell from 3.9 to 2.1 days. There was no difference in 30-day case-fatality or mean length of stay between patients presenting on weekdays or at weekends. In this national study, we demonstrated that case-fatality and mean length of stay after presentation with UGIB in Scotland has fallen over the past 16 years, despite a rise the in mean age of patients. There is a positive correlation between the incidence of UGIB and deprivation. We found no evidence of worse outcomes among patients presenting at weekends.


Risk of interstitial lung disease associated with EGFR-TKIs in advanced non-small-cell lung cancer: a meta-analysis of 24 phase III clinical trials.
To assess the risk of interstitial lung disease (ILD) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) gefitinib, erlotinib, and afatinib. PubMed databases were searched for relevant articles. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR), and 95% confidence intervals (CIs) by using either random-effects or fixed-effect models. The incidence of all-grade and high-grade (≧ grade 3) ILD associated with EGFR-TKIs was 1.6% (95% CI, 1.0-2.4%) and 0.9% (95% CI, 0.6%-1.4%), with a mortality of 13.0% (95% CI, 7.6-21.6%). Patients treated with EGFR-TKIs had a significantly increased risk of developing all-grade (OR, 1.74; 95% CI, 1.25-2.43; P = 0.001) and high-grade (OR, 4.38; 95% CI, 2.18-8.79; P<0.001) ILD. No significant difference in the risk of ILD was found in sub-group analysis according to EGFR-TKIs, percentage of EGFR mutation, study location, EGFR-TKIs-based regimens, and controlled therapy. Treatment with EGFR-TKIs is associated with a significantly increased risk of developing ILD.


[Aflibercept. An approach to pharmacology].
Aflibercept is a fusion protein whose chemical structure combines the constant fraction of any IgG with a variable fraction constructed with fundamental parts of VEGF receptors. Consequently, it is able to bind to various VEGF as well as to placental growth factor (PIGF), which has been related to a possible synergistic effect in efficacy. The affinity of this drug is higher than that of ranibizumab and bevacizumab. Moreover, it has an intraocular antiinflammatory effect. Intravitreal administration leads to the presence of traces of the drug in plasma but the concentrations are so reduced that the presence of systemic adverse effects, including arterial hypertension, is practically nil. Because of its prolonged intraocular elimination half-life and high affinity, the drug can be administered in convenient regimens, since, after an initial monthly injection for the first three doses, the interval between injections is increased to one every two months and, after the first 12 months, the dosing will depend on the visual and anatomical results.


A 3D multi-agent-based model for lumen morphogenesis: the role of the biophysical properties of the extracellular matrix.
The correct function of many organs depends on proper lumen morphogenesis, which requires the orchestration of both biological and mechanical aspects. However, how these factors coordinate is not yet fully understood. Here, we focus on the development of a mechanistic model for computationally simulating lumen morphogenesis. In particular, we consider the hydrostatic pressure generated by the cells' fluid secretion as the driving force and the density of the extracellular matrix as regulators of the process. For this purpose, we develop a 3D agent-based-model for lumen morphogenesis that includes cells' fluid secretion and the density of the extracellular matrix. Moreover, this computer-based model considers the variation in the biological behavior of cells in response to the mechanical forces that they sense. Then, we study the formation of the lumen under different-mechanical scenarios and conclude that an increase in the matrix density reduces the lumen volume and hinders lumen morphogenesis. Finally, we show that the model successfully predicts normal lumen morphogenesis when the matrix density is physiological and aberrant multilumen formation when the matrix density is excessive. The online version contains supplementary material available at 10.1007/s00366-022-01654-1.


Analysis of Genetic Diversity in the Czech Spotted Dog.
Loss off genetic diversity negatively affects most of the modern dog breeds. However, no breed created strictly for laboratory purposes has been analyzed so far. In this paper, we sought to explore by pedigree analysis exactly such a breed-the Czech Spotted Dog (CSD). The pedigree contained a total of 2010 individuals registered since the second half of the 20th century. Parameters such as the mean average relatedness, coefficient of inbreeding, effective population size, effective number of founders, ancestors and founder genomes and loss of genetic diversity-which was calculated based on the reference population and pedigree completeness-were used to assess genetic variability. Compared to the founding population, the reference population lost 38.2% of its genetic diversity, of which 26% is due to random genetic drift and 12.2% is due to the uneven contribution of the founders. The reference population is highly inbred and related. The average inbreeding coefficient is 36.45%, and the mean average relatedness is 74.83%. The effective population size calculated based on the increase of inbreeding coefficient is 10.28. Thus, the Czech Spotted Dog suffered significant losses of genetic diversity that threaten its future existence.


Comparative study of interim materials for direct fixed dental prostheses and their fabrication with CAD/CAM technique.
Prosthodontic treatment sometimes requires a long-term interim fixed dental prosthesis (FDP) until the definitive restoration can be cemented. However, some interim materials are weak and do not have an adequate marginal seal. The purpose of this study was to compare the marginal fit and fracture strengths of interim FDPs fabricated by using a direct technique with different materials (Structur 3, Trim, and DuraLay) with interim prostheses (Telio CAD) made with a computer-aided design and computer-aided manufacturing (CAD/CAM) system. Seventy interim FDPs were fabricated by using different materials (Structur 3, Trim, DuraLay, and Telio CAD) on a metal master model. Resin-impregnated, light-polymerizing glass fiber (GrandTEC) was used to reinforce 10 interim FDPs per material fabricated with the direct technique. Interim FDPs were stored at 37°C for 24 hours before thermocycling. Marginal fit was analyzed at 6 points in each interim FDP before and after thermocycling with either 2500 or 5000 cycles. After fracturing the interim FDPs with a universal testing machine, fracture strength, fragments separation, and fracture point were recorded. Marginal fit data were analyzed with 2-way repeated measure analysis of variance (ANOVA), fracture strength with 1-way ANOVA, and fragments separation and fracture point with the chi-square test at a 99% confidence interval. All interim materials showed marginal discrepancies over time, but no significant differences were found among groups (P>.001), except in the marginal fit of interim FDPs reinforced with glass fiber (S3F), which showed the smallest marginal gap after 5000 cycles (P<.001). Reinforced interim FDPs (S3F, TMF, and DLF) and CAD/CAM FDPs (TCC) presented a fracture strength ranging between 471.3 ±62.4 N and 531.1 ±150.1 N (P>.001). Finally, significant differences were observed in the fracture point and frequency of separation (P<.001). Bis-acryl reinforced with glass fiber showed the least marginal discrepancy. No differences were found between the fracture strengths of interim FDPs fabricated with CAD/CAM system and interim FDPs reinforced with glass fiber. No significant difference in fracture strength was observed between interim FDPs reinforced with glass fiber and prostheses fabricated with CAD/CAM system. However, unreinforced interim FDPs showed the lowest fracture strength.


Cleansing properties of stabilized trypsin and streptokinase-streptodornase in necrotic leg ulcers.
The cleansing effects on pus and debris of streptokinase-streptodornase and of stabilized crystalline trypsin were compared in 40 patients (12 males, 28 females) with necrotic varicose or arteriosclerotic leg ulcers. Both preparations produced significant partial or total cleansing of the ulcers of necrotic material, and both enhanced the granulation and epithelialization of most of the ulcers. Streptokinase-streptodornase was significantly more effective in removing freshly formed damp and smearing pus and debris. Neither preparation prevented the formation of or removed very deep adherent necrotic areas, especially in arteriosclerotic leg ulcers. Trypsin caused significantly more pain than streptokinase-streptodornase during the treatment period and on changing dressings. Both enzymes indirectly reduced the bacterial flora of the ulcers, probably by removal of necrotic wet material.


Vascular changes in cerebellar developmental defects.
A study of arterial vascular changes in different types of cerebellar defects is presented. PICA was found to be hypoplastic or aplastic in a large number of cases. In cases of cerebellar defects involving mostly the vermis, the hypoplastic PICA was frequently associated with a compensatory hyperdevelopment of HCA or MCA. Anomalies at the origin of the vertebral arteries associated with hypoplastic PICA were common.


A systematic review of proteomic biomarkers in oral squamous cell cancer.
Head and neck squamous cell cancer (HNSCC) is the most common cancer associated with chewing tobacco, in the world. As this is divided in to sites and subsites, it does not make it to top 10 cancers. The most common subsite is the oral cancer. At the time of diagnosis, more than 50% of patients with oral squamous cell cancers (OSCC) had advanced disease, indicating the lack of availability of early detection and risk assessment biomarkers. The new protein biomarker development and discovery will aid in early diagnosis and treatment which lead to targeted treatment and ultimately a good prognosis. This systematic review was performed as per PRISMA guidelines. All relevant studies assessing characteristics of oral cancer and proteomics were considered for analysis. Only human studies published in English were included, and abstracts, incomplete articles, and cell line or animal studies were excluded. A total of 308 articles were found, of which 112 were found to be relevant after exclusion. The present review focuses on techniques of cancer proteomics and discovery of biomarkers using these techniques. The signature of protein expression may be used to predict drug response and clinical course of disease and could be used to individualize therapy with such knowledge. Prospective use of these markers in the clinical setting will enable early detection, prediction of response to treatment, improvement in treatment selection, and early detection of tumor recurrence for disease monitoring. However, most of these markers for OSCC are yet to be validated.


Timing of human chorionic gonadotropin (hCG) hormone administration in IVF/ICSI protocols using GnRH agonist or antagonists: a systematic review and meta-analysis.
To evaluate the effect of altering the timing of human chorionic gonadotropin (hCG) administration on the clinical outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) using gonadotropic hormone releasing hormone (GnRH) agonist or antagonist. We systematically searched six databases. Randomized controlled trials (RCTs) of the effects of altering the timing of hCG administration on the clinical outcome of IVF and ICSI using GnRH agonist or antagonist were included. A meta-analysis was conducted following a quality evaluation performed with Cochrane Collaboration's Review Manager (RevMan) 5.0.2. Seven RCTs and a total of 1295 participants were included. Significant difference was observed regarding estradiol and progesterone levels on the day of hCG administration and oocyte retrieval between early hCG and late hCG administration group and in favor of the latter. The fertilization rate was not statistically different between early and 24-h late hCG groups, but it is significantly higher in the 48-h late hCG group. The pooled results showed no significant differences in the ongoing pregnancy rate per oocyte pick-up, the miscarriage rate and the live birth rate. The prolongation of follicular phase by delaying hCG administration could increase estradiol, progesterone levels and oocyte retrieval, which will not influence ongoing pregnancy rate per oocyte pick-up, miscarriage rate and live birth rate. Postponing hCG may enable increased flexibility of cycle scheduling to avoid weekend procedures.


Dendrimer-grafted bioreducible polycation/DNA multilayered films with low cytotoxicity and high transfection ability.
Controlled release of incorporated foreign DNA from multilayered films plays an important role in surface-mediated gene delivery. Herein, multilayered polyelectrolyte complex thin films, composed of dendrimer-grafted bio-reducible cationic poly(disulfide amine) and plasmid DNA, were fabricated via layer-by-layer (LBL) assembly for in vitro localized gene delivery. The UV absorbance and thickness of the LBL films were found to have linear correlation with the numbers of poly(disulfide amine)/DNA bilayers. Although LBL films were stable in PBS buffer, their degradation could be triggered by reducing agents (i.e. glutathione, GSH). The degradation rate of the films is directly proportional to the GSH concentration, which in turn affected the corresponding gene expression. All poly(disulfide amine)/DNA films exhibited lower cytotoxicity and higher transfection activity in comparison with PEI/DNA multilayered films. Moreover, LBL films showed the highest transfection efficiency in the presence of 2.5 mM GSH when cultured with 293T cells, with ~36% GFP-positive 293T cells after 5-days of co-culture. These DNA-containing reducible films could potentially be useful in gene therapy and tissue engineering by controlling the release of incorporated DNA.


Preoperative cytodiagnosis of primitive carcinoid tumor of the Wirsung duct: a case report with immunocytochemical study.
A case of primitive carcinoid tumor of the Wirsung duct detected by fiberoptic guided brushing cytology is reported. The authors describe the main cytomorphologic characteristics and underline the role of immunocytochemistry in helping to reach a reliable preoperative diagnosis.


Who would be a candidate for bridge to recovery during prolonged mechanical left ventricular support in idiopathic dilated cardiomyopathy?
We sought to elucidate the incidence and timing of myocardial recovery in patients with idiopathic dilated cardiomyopathy during prolonged support with a left ventricular assist system and to characterize the factors influencing this phenomenon. Since 2000, 11 patients (mean age, 27.9 years) with end-stage heart failure caused by dilated cardiomyopathy were supported with a left ventricular assist system for more than 6 months. All patients had aggressive pharmacologic treatment, including beta-blockers, together with unloading by means of a left ventricular assist system. During 239 to 663 days (mean, 453 days) of left ventricular assist system support, 5 patients had significant recovery of cardiac function and successfully underwent left ventricular assist system removal. All of these patients have remained in New York Heart Association class 1 during 8 to 29 months of follow-up. The improvement of left ventricular function started at various times. In particular, 2 of 5 recovered patients started to show improvement after 1 year of left ventricular assist system support. The myocardial fibrosis did not resolve but rather worsened in all patients during left ventricular assist system support. However, myocardial fibrosis was less severe in the recovered group (17.7% +/- 8.2% at left ventricular assist system implantation vs 20.1% +/- 5.2% at explantation) in comparison with that in the nonrecovered group (30.5% +/- 13.2% vs 48.4% +/- 5.1%) both before and after use of the left ventricular assist system. Patients with severe congestive heart failure caused by dilated cardiomyopathy have a good chance of myocardial recovery and successful explantation of the left ventricular assist system. A relatively slow response of myocardial recovery during prolonged left ventricular assist system support was demonstrated in some patients. A lesser degree of fibrotic changes in the left ventricle was predictive of recovery.


Cases requiring increased number of repositioning maneuvers in benign paroxysmal positional vertigo.
Benign paroxysmal positional vertigo (BPPV) is a clinical syndrome that is proposed to be caused by dislocated utricular debris into semicircular canals. Although the majority of patients are treated by one or two repositioning maneuvers, some of the patients need repeated maneuvers for relief. The goal of this study was to investigate the factors associated with patients with benign paroxysmal positional vertigo who required multiple repositioning procedures for treatment. Data were obtained from the clinical records of 153 patients diagnosed with benign paroxysmal positional vertigo. Patients were treated by repositioning maneuvers. Demographic data and the factors including age, sex, canal type, duration of symptoms, comorbidities and number of repositioning maneuvers for relief were documented for statistical analysis. Age, sex, canal type and the duration of symptoms had no impact on the number of maneuvers. The most common comorbidity was spine problems. Hypertension was the only comorbidity that significantly associated with increased number of maneuvers. The presence of hypertension is a risk factor for repeated maneuvers in benign paroxysmal positional vertigo treatment. Physicians should be aware of the increased probability of repeated repositioning maneuvers in these group of patients. The role of comorbidities and vascular factors need to be further clarified in the course of benign paroxysmal positional vertigo.


Reconstruction of the water-oxidizing complex in manganese-depleted Photosystem II using synthetic manganese complexes.
The efficiency of a trinuclear and two binuclear manganese complexes in reconstituting electron transport and O(2) evolution activity in Mn-depleted Photosystem II preparations is analyzed. The trinuclear Mn-complex is more efficient than two binuclear Mn-complexes in restoring oxygen evolution, but it is less effective as an electron donor than binuclear Mn-complexes. It is inferred from our results that recovery of electron transport and O(2) evolution with polynuclear Mn-complexes is affected with different factors. Moreover, the trinuclear Mn-complex is extremely sensitive to the addition of CaCl(2). It is suggested that there is an interaction between Ca(2+) and carboxyl within the trinuclear Mn-complex during photoactivation and this interaction benefits the ligation of Mn atom to the apo-WOC and form an active WOC. Binuclear Mn(III)Mn(III) complex shows slightly higher efficiency than binuclear Mn(III)Mn(IV) complex in restoration of O(2) evolution activity. The efficiency of three Mn-complexes in the reconstitution of WOC is in an order: trinuclear Mn(3)(III)>binuclear Mn(III)Mn(III)>binuclear Mn(III)Mn(IV).


Programming effects of maternal and gestational obesity on offspring metabolism and metabolic inflammation.
With the increasing prevalence of obesity in women of reproductive age there is a need to understand the ramifications of this on offspring. The purpose of this study is to investigate the programming effects of maternal obesity during preconception and the preconception/gestational period on adiposity and adipose tissue inflammation in offspring using an animal model. Adult female C57Bl/6J mice were assigned either normal diet, high fat diet (HFD) prior to pregnancy, or HFD prior to and through pregnancy. Some offspring were maintained on normal diet while others started HFD later in life. Offspring were assessed for body composition and metabolic responses. Lipid storing tissues were evaluated for expansion and inflammation. Male offspring from the preconception group had the greatest weight gain, most subcutaneous adipose tissue, and largest liver mass when introduced to postnatal HFD. Male offspring of the preconception/gestation group had worsened glucose tolerance and an increase in resident (CD11c-) adipose tissue macrophages (ATMs) when exposed to postnatal HFD. Female offspring had no significant difference in any parameter between the diet treatment groups. In conclusion, this study demonstrates that prenatal and pregnancy windows have independent programming effects on offspring. Preconception exposure affects body composition and adiposity while gestation exposure affects metabolism and tissue immune cell phenotypes.


Novel approaches for treating diabetic retinopathy based on recent pathogenic evidence.
Diabetic retinopathy remains as a leading cause of blindness in developed countries. Current treatments target late stages of DR when vision has already been significantly affected. A better understanding of the pathogenesis of DR would permit the development of more efficient preventional/interventional strategies against early stages of DR. In this article a critical review of the state of the art of this issue is provided along with a discussion of problems which have yet to be overcome. Neuroprotection as a new approach for the treatment of the early stages of DR has been particularly emphasized. The development and progression of DR is not homogeneous and, apart from blood glucose levels and blood pressure, it depends on genetic factors which remain to be elucidated. In addition, the role of the pathogenic pathways is not the same in all patients. All these factors should be taken into account in the near future when an individualized oriented treatment for DR could become feasible. The new techniques in retinal imaging acquisition, the identification of useful circulating biomarkers and the individualized analysis of biological samples could facilitate the development of early and personalized therapy in the setting of DR. Finally, it should be noted that only a coordinated action among ophthalmologists, diabetologists, basic researchers, experts in pharmaco-economics and health care providers addressed to the design of rational strategies targeting prevention and the early stages of DR will be effective in reducing the burden and improving the clinical outcome of this devastating complication of diabetes.


A nuclear pathway for alpha 1-adrenergic receptor signaling in cardiac cells.
alpha 1-Adrenergic agonists and antagonists constitute an important class of therapeutic agents commonly used for the treatment of various cardiovascular diseases like hypertension, congestive heart failure and supraventricular tachycardia. At the heart level, activation of alpha 1-adrenergic receptors is associated with marked morphological and genetic changes. These include enhancement of contractility, myocardial growth (hypertrophy) and release of the heart major secretory product, atrial natriuretic factor (ANF). However, the signal transduction pathways which link extracellular activation of the receptors to cellular and genetic changes are not well understood. Using primary cardiocyte cultures from neonate rat hearts, an alpha 1-adrenergic regulatory sequence has been identified in the 5' flanking region of the ANF gene. This sequence, which is necessary and sufficient for transcriptional activation in response to the alpha 1-specific agonist phenylephrine, interacts with novel zinc-dependent proteins which are induced by alpha 1-adrenergic stimulation. Consistent with a conserved regulatory mechanism, the alpha 1 response element is highly conserved between rodent, bovine and human ANF genes, and is also present in the promoter region of other alpha 1-responsive cardiac genes. The identification of a nuclear pathway for alpha 1-receptor signaling will be useful for elucidating the intracellular effectors of alpha 1-adrenergic receptors.


Conventional and drug-eluting beads transarterial chemoembolization in patients with unresectable intrahepatic cholangiocarcinoma: a systematic review and pooled analysis.
Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have poor survival. Conventional transarterial chemoembolization (c-TACE) and drug-eluting beads transarterial chemoembolization (DEB-TACE) are two treatment options for ICC, and this systematic review describes the efficacy of each of these modalities for unresectable ICC to guide clinical practice. A literature search was performed in PubMed, Web of Science, and Embase databases regarding transhepatic arterial chemoembolization for intrahepatic cholangiocarcinoma. The Newcastle-Ottawa quality assessment Scale (NOS) was used to assess the risk of bias. Tumor response, disease control, and 1-, 2-, 3-year overall survival rate were pooled for estimation. The number of initial search results was 1035, and 19 articles met the inclusion criteria for this study after the screening. A total of 23 study cohorts and 1091 patients were provided. The pooled objective response rate (ORR) for c-TACE and DEB-TACE treating ICC was 29.4% (95% CI 11.6-50.8%) and 51.2% (95% CI 30.6-71.7%), respectively; disease control rate (DCR) was 72.8% (95% CI 55.6-87.3%) and 88.7% (95% CI 78.8-96.2%), respectively. The pooled survival rate at 1 year, 2 year, and 3 year was 49.7% (95% CI 39.1-60.3%), 24.0% (95% CI 12.6-37.3%), and 23.5% (95% CI 11.1-38.7%) for c-TACE; 58.6% (95% CI 44.2-72.3%), 26.7% (95% CI 18.1-36.3%), and 16.2% (95% CI 6.0-29.4%) for DEB-TACE. The descriptive analysis suggested that DEB-TACE treatment for ICC may have better tumor response and disease control rates than c-TACE treatment, but the impact on overall survival was not demonstrated significantly by DEB-TACE treatment.


The effect of bisamidines of 2,6-diaminoanthraquinone on Entamoeba histolytica infections in rats and hamsters.
Bisamidines of 2,6-diaminoanthraquinone have demonstrated potent activity against cecal and hepatic Entamoeba histolytica infections in rats and hamsters, respectively. A number of these compounds compared favorably, in overall drug efficacy, with metronidazole and other standard agents.


Purinergic agonist and G protein stimulation of phospholipase D in rat liver plasma membranes. Independence from phospholipase C activation.
Hormonal regulation of phospholipase D (PLD) was studied in isolated rat liver plasma membranes. Purinergic agents and a submaximal concentration of guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S), a non-hydrolyzable analog of GTP, synergistically stimulate phosphatidylethanol formation, a measure of PLD activity. The rank order of efficacy for stimulation of PLD activity in the presence of 0.2 microM GTP gamma S was beta, gamma-methylene-ATP > adenosine 5'-0-(3-thiotriphosphate) = ATP = ADP = 2-methylthio-ATP > alpha, beta-methylene-ATP = UTP. This pattern of activation does not conform to the series at known P2 receptors. GTP gamma S stimulated PLD activity in a dose-dependent manner, and the GTP gamma S dose-response curve for phosphatidylethanol formation was shifted to the left by an analog of ATP. Activation of PLD by purinergic agents in the presence of GTP gamma S supports the involvement of a purinergic receptor of the P2 class and a GTP-binding protein. Purinergic agents competitively inhibited [35S]adenosine 5'-0-(3-thiotriphosphate) binding to plasma membranes in the rank order adenosine 5'-0'(3-thiotriphosphate) > ATP > alpha,beta-methylene-ATP = UTP >> beta, gamma-methylene-ATP = ADP. Stimulation of phosphoinositide phospholipase C (PI-PLC) by purinergic agents, as measured by release of radioactivity from endogenously myo[3H]inositol-labeled plasma membranes, occurred in the order alpha, beta-methylene-ATP >> 2-methylthio-ATP. Beta, gamma-methylene-ATP had little effect on PI-PLC activity. Different dose-response relationships for agonist-stimulation of PI-PLC and PLD indicate that activation of PI-PLC is not involved in stimulation of PLD in rat liver plasma membranes, and suggest that purinergic activation of PLD occurs via a pathway involving a G protein and a heretofore uncharacterized P2 receptor.


Purification of a hepatic S6 kinase from cycloheximide-treated Rats.
Cycloheximide injection of rats results in the activation of a protein kinase that phosphorylates 40 S ribosomal protein S6. This Ca2+/cyclic nucleotide-independent kinase exhibits chromatographic properties that are indistinguishable from the S6 kinase in H4 hepatoma cells whose activity is stimulated by insulin and growth factors and the S6 kinase that is activated during liver regeneration. The enzyme has been purified 50,000-fold to near homogeneity: a critical step in purification employs a peptide affinity column using a synthetic peptide corresponding to the carboxyl-terminal 32-amino acid residues of mouse liver S6, which encompasses all S6 phosphorylation sites. The purified enzyme is a 70,000-dalton polypeptide that is reactive with azido-ATP. In addition to 40 S ribosomal S6 and the synthetic peptide, the S6 kinase catalyzes rapid phosphorylation of a number of other protein substrates including histone H2b, glycogen synthase, and ATP citrate lyase; this last protein is phosphorylated by S6 kinase in vitro on the same serine residue that is phosphorylated in response to insulin and epidermal growth factor in intact hepatocytes. Moreover, the S6 kinase catalyzes the phosphorylation of a number of hepatic nonhistone nuclear proteins. This S6 kinase probably underlies the increased hepatic S6 phosphorylation observed after cycloheximide treatment, which in turn corresponds to the mitogen-activated S6 kinase.


Prehabilitation of complex ventral hernia patients with Botulinum: a systematic review of the quantifiable effects of Botulinum.
Complex ventral hernia repair (CVHR) encompasses patient optimization, primary fascial closure (PFC), mesh reinforcement and component separation technique (CST), if needed. High rates of complications after CST are still reported. Prehabilitation by managing pre-operative modifiable risk factors, like abdominal wall compliance, possibly reduces these rates. Compliance can be modified by intramuscular injection of Botulinum in the lateral abdominal wall muscles (LAWM). Paralysis leads to elongation of these muscles, which may facilitate PFC and/or prevent CST. Evidence to use Botulinum in hernia patients is scarce and fragmented. An update of evidence for the effect of Botulinum is presented. A multi-database search was conducted for Botulinum studies in ventral hernia patients. A systematic review was performed to describe its primary effect on compliance (LAWM elongation) and secondary effects like PFC ± CST rate, complications and recurrence. 14 studies were included (377 patients) with a HDW of median 12 (10-15) cm. A typical intervention consisted of 200-300 U Botulinum in 3 points per hemi-abdomen under US guidance, > 2 weeks pre-operatively and evaluated by CT just before the operation. The primary effect was a median LAWM elongation of 4.0 cm per side without complications of the injection (four studies, 107 patients). The median PFC rate was 100%, CST rate 38%, wound-related complications 19%, medical complications 18% and recurrence 0% (14 studies). Botulinum safely elongates the abdominal wall muscles, but the level of evidence available remains low. Any patient in whom PFC is expected to be difficult, could be a candidate for prehabilitation with Botulinum.


i-rDNA: alignment-free algorithm for rapid in silico detection of ribosomal gene fragments from metagenomic sequence data sets.
Obtaining accurate estimates of microbial diversity using rDNA profiling is the first step in most metagenomics projects. Consequently, most metagenomic projects spend considerable amounts of time, money and manpower for experimentally cloning, amplifying and sequencing the rDNA content in a metagenomic sample. In the second step, the entire genomic content of the metagenome is extracted, sequenced and analyzed. Since DNA sequences obtained in this second step also contain rDNA fragments, rapid in silico identification of these rDNA fragments would drastically reduce the cost, time and effort of current metagenomic projects by entirely bypassing the experimental steps of primer based rDNA amplification, cloning and sequencing. In this study, we present an algorithm called i-rDNA that can facilitate the rapid detection of 16S rDNA fragments from amongst millions of sequences in metagenomic data sets with high detection sensitivity. Performance evaluation with data sets/database variants simulating typical metagenomic scenarios indicates the significantly high detection sensitivity of i-rDNA. Moreover, i-rDNA can process a million sequences in less than an hour on a simple desktop with modest hardware specifications. In addition to the speed of execution, high sensitivity and low false positive rate, the utility of the algorithmic approach discussed in this paper is immense given that it would help in bypassing the entire experimental step of primer-based rDNA amplification, cloning and sequencing. Application of this algorithmic approach would thus drastically reduce the cost, time and human efforts invested in all metagenomic projects. A web-server for the i-rDNA algorithm is available at http://metagenomics.atc.tcs.com/i-rDNA/


Response vs excitation in response-dependent and stimulus-dependent lateral inhibitory networks.
Response-dependent and stimulus-dependent lateral inhibitory networks may be distinguished by differences in their net response vs net excitation functions. It is shown that the net response of a stable, response-dependent network is a monotonically increasing function of the net excitation. By contrast, the response of a stimulus-dependent lateral inhibitory network can either increase, decrease or remain constant as the net excitation of the network is increased, depending on the relation of the inhibition to the excitation. These differences make it possible to determine that the inhibition produced by a lateral inhibitory network is stimulus-dependent if the net response of the network declines as the network excitation increases.


Metabolic aspects of pig-to-monkey (Macaca fascicularis) islet transplantation: implications for translation into clinical practice.
Attempts to use an alternative source of islets to restore glucose homeostasis in diabetic patients require preclinical islet xenotransplantation models to be tested. These models raise questions about metabolic compatibility between species and the most appropriate metabolic parameters to be used to monitor graft function. The present study investigated and compared relevant gluco-metabolic parameters in pigs, monkeys and the pig-to-monkey islet transplantation model to gain insight into the potential clinical outcome of pig-to-human islet transplantation. Basal and IVGTT-stimulated blood glucose, C-peptide, insulin and glucagon levels were assessed in non-diabetic pigs and monkeys. The same parameters were used to evaluate the performance of porcine islet xenografts in diabetic monkeys. Non-diabetic cynomolgus monkeys showed lower levels of fasting and stimulated blood glucose but higher levels of C-peptide and insulin than non-diabetic pigs. The reported levels in humans lie between those of monkeys and pigs, and differences in metabolic parameters between pigs and humans appear to be smaller than those between pigs and cynomolgus monkeys. The transplantation data indicated that the degree of graft function (evaluated by the measurement of C-peptide levels) necessary to normalise blood glucose in the recipient was determined by the recipient levels rather than by the donor levels. The differences between donor and recipient species may affect the transplantation outcome and need to be considered when assessing graft function in xenotransplantation models. Given the differences between monkeys and humans as potential recipients of pig islets, it should be easier to reach glucose homeostasis in pig-to-human than in pig-to-non-human primate islet xenotransplantation.


Structure characteristics of self-bonding boards during hot press for leukemia inhibition.
80% leukemia was caused by indoor formaldehyde pollution. And the results have shown that the absorbances of many connection bonds (such as C-O-C, and C-OOC) increased. It could be inferred that a lot of bonds were produced and played the role of molecular crosslinking. After hot press, the content of lignin in Eucalyptus wood fiber was all lower than the ones of self-bonding boards. And the change of content of lignin was closely related to time and temperature of hot press.


Giant Electrocaloric Effect and Ultrahigh Refrigeration Efficiency in Antiferroelectric Ceramics by Morphotropic Phase Boundary Design.
Electrocaloric effect (ECE) in ferroelectric (FE)/antiferroelectric (AFE) materials offers a promising high-efficient and zero-emission solid-state cooling technology, whose materials design is usually focused on the morphotropic phase boundary (MPB) between two FE phases. This work constructs an MPB between an orthorhombic AFE and a rhombohedral FE phase in Pb0.97-xBaxLa0.02Zr0.95Ti0.05O3 (PBLZT100x, x = 0-0.08) ceramics and achieves a superior ECE performance. An unprecedented high electrocaloric strength of 1.52 K·mm/kV and an ultrahigh refrigeration efficiency (coefficient of performance = 16) are obtained in PBLZT4, in the MPB near AFE end. Moreover, a large negative ECE, with the highest strength up to -0.41 K·mm/kV, is also realized due to the electric field-induced AFE-FE transition. The coexistence of giant positive and negative ECEs at adjacent temperatures can further improve the cooling capacity (∼17%) of solid-state refrigeration in a well-designed cooling cycle. This work provides a brand new materials design strategy to achieve giant positive and negative ECEs simultaneously and a novel cooling cycle to efficiently utilize the two effects.


Localized lymphadenitis due to leishmania simulating toxoplasmosis. Value of electron microscopy for differentiation.
Two cases of cervical adenopathy are described. One manifested as lymphoma clinically. Both patients were found to have primary lymph node leishmaniasis without cutaneous, mucosal or visceral involvement. The histologic appearance simulated toxoplasma lymphadenitis. Electron microscopic study differentiated the organism from Toxoplasma, and the condition responded well to antimony therapy.


Relationship between muscle coordination and forehand drive velocity in tennis.
This study aimed at investigating the relationship between trunk and upper limb muscle coordination and stroke velocity during tennis forehand drive. The electromyographic (EMG) activity of ten trunk and dominant upper limb muscles was recorded in 21 male tennis players while performing five series of ten crosscourt forehand drives. The forehand drive velocity ranged from 60% to 100% of individual maximal velocity. The onset, offset and activation level were calculated for each muscle and each player. The analysis of muscle activation order showed no modification in the recruitment pattern regardless of the velocity. However, the increased velocity resulted in earlier activation of the erector spinae, latissimus dorsi and triceps brachii muscles, as well as later deactivation of the erector spinae, biceps brachii and flexor carpi radialis muscles. Finally, a higher level of activation was observed with the velocity increase in the external oblique, latissimus dorsi, middle deltoid, biceps brachii and triceps brachii. These results might bring new knowledge for strength and tennis coaches to improve resistance training protocols in a performance and prophylactic perspective.


Effects of cannabidiol on vacuous chewing movements, plasma glucose and oxidative stress indices in rats administered high dose risperidone.
Atypical antipsychotics, despite their rapid dissociation from dopamine receptors and reduced tendency to induce oxidative stress, have been associated with difficult-to-manage movement disorders, including tardive dyskinesia (TD). The study set out to investigate the effects of cannabidiol (CBD), a potent antioxidant, on risperidone-induced behavioural and motor disturbances; namely vacuous chewing movements (VCM), and oxidative stress markers (e.g. superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), malondialdehyde (MDA), Nitric oxide (NO), and DPPH (2,2-diphenyl-1-picrylhydrazyl)). Oral risperidone (10 mg/kg) or oral CBD (5 mg/kg) were administered to six experimental groups. While risperidone alone was administered for 28 days, CBD concomitantly or in sequential order with risperidone, was administered for 28 days; and CBD alone was administered for 21 days. Behavioural, motor, and specific biochemical parameters, which included VCM, muscle tone, fasting blood sugar (FBS), and oxidative stress markers were assessed at different time points after the last dose of medication. Oral CBD (5 mg/kg) significantly reduced risperidone-induced elevated FBS when given after the administration of risperidone. Oral CBD also had effects on VCM when administered before risperidone and similarly, attenuated risperidone-induced increased muscle tone. It was also established that concomitant or sequential administration of CBD and risperidone did not have any adverse effects on cognition or locomotion. Both CBD and risperidone increased the activity of antioxidant enzymes and decreased the activity of pro-oxidant enzymes. This study suggests CBD could mitigate metabolic dysregulation and extrapyramidal side effects associated with risperidone without producing cognitive impairments.


The effect of topical indomethacin on acute pressure elevation of laser trabeculoplasty in capsular glaucoma.
In this controlled study 24 phakic patients with capsular glaucoma received a 5-drop loading dose of topical 1.0% indomethacin on the eye to be treated and the fellow eye prior to argon laser trabeculoplasty and post-operatively every 3 h to the end of the day. A control group consisted of 25 phakic eyes with capsular glaucoma which were lasered without indomethacin drops. There were no statistically significant differences between the groups in the post-operative mean intraocular pressures (IOP) and mean corrected changes in IOP immediately and one month after laser treatment. However, no eyes in the indomethacin treated group showed a true pressure rise greater than or equal to 10 mmHg whereas 4 eyes in the control group did (P = 0.1).


Protective effect of Sida cordata leaf extract against CCl(4) induced acute liver toxicity in rats.
To investigate the hepatoprotective potential of Sida cordata (Malvaceae) (S. cordata) in experimental rats to validate its traditional claim. Wister albino rats were divided into 6 groups: Group I served as control; Group II served as hepatotoxic (CCl(4) treated) group; Group III, IV and V served as (100, 200 and 400 mg/kg b.w.) S. cordata leaf extract (SCLE) treated groups; Group VI served as positive control (Silymarin) treated group. Liver marker enzymes serum glutamate oxyloacetic transaminase, serum glutamic pyruvic transaminase, pancreatic enzymatic antioxidants superoxide dismutase (SOD), lipid peroxidation, catalase (CAT), reduced glutathione (GSH) were measured and compared along with histopathological studies. Obtained results show that the treatment with SCLE significantly (P<0.05-<0.001) and dose-dependently reduced CCl4 induced elevated serum level of hepatic enzymes. Furthermore, SCLE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels, which was confirmed by the histopathological studies. The results of this study strongly indicate the protective effect of SCLE against CCl(4) induced acute liver toxicity in rats and thereby scientifically support its traditional use.


Exploration of [2 + 2 + 2] cyclotrimerisation methodology to prepare tetrahydroisoquinoline-based compounds with potential aldo-keto reductase 1C3 target affinity.
Tetrahydroisoquinoline (THIQ) is a key structural component in many biologically active molecules including natural products and synthetic pharmaceuticals. Here, we report on the use of transition-metal mediated [2 + 2 + 2] cyclotrimerisation of alkynes to generate tricyclic THIQs with potential to selectively inhibit AKR1C3.


A chip-calorimetric approach to the analysis of Ag nanoparticle caused inhibition and inactivation of beads-grown bacterial biofilms.
With the increasing complexity of model systems for the investigation of antibacterial effects of nanoparticles, the demands on appropriate analysis methods are rising. In case of biofilms grown on small particles, the high inhomogeneity of the samples represents a major challenge for traditional biofilm analysis. For this purpose, we developed a new calorimetric method which allows non-invasive and real-time investigation of the effects of nanoparticles on beads-grown biofilms which meets the requirements for an increased sample throughput. The method employs a newly developed chip calorimeter that is able to detect changes in the metabolic activity of biofilm samples within minutes. Using this novel device, the antibacterial effect of silver nanoparticles on Pseudomonas putida biofilms grown on agarose beads was investigated. The superparamagnetic properties of the embedded particles within the agarose beads allow an automated sample throughput. Growth inhibition and inactivation effects of silver nanoparticles (AgNPs) on biofilm bacteria were quantified by analyzing the metabolic heat production rate. As a result, a concentration dependent manner of growth inhibition and inactivation was found demonstrating the suitability and sensitivity of the methodology.


Glycosylation of polyphenolic compounds: Design of a self-sufficient biocatalyst by co-immobilization of a glycosyltransferase, a sucrose synthase and the cofactor UDP.
Glycosyltransferases catalyze the regioselective glycosylation of polyphenolic compounds, increasing their solubility without altering their antioxidant properties. Leloir-type glycosyltransferases require UDP-glucose as a cofactor to glycosylate a hydroxyl of the polyphenol, which is expensive and unstable. To simplify these processes for industrial implementation, the preparation of self-sufficient heterogeneous biocatalysts is needed. In this study, a glycosyltransferase and a sucrose synthase (as an UDP-regenerating enzyme) were co-immobilized onto porous agarose-based supports coated with polycationic polymers: polyethylenimine and polyallylamine. In addition, the UDP cofactor was strongly ionically adsorbed and co-immobilized with the enzymes, eliminating the need to add it separately. Thus, the optimal self-sufficient heterogeneous biocatalyst was able to catalyze the glycosylation of three polyphenolic compounds (piceid, phloretin and quercetin) with in situ regeneration of the UDP-glucose, allowing multiple consecutive reaction cycles without the addition of exogenous cofactor. A TTN value of 50 (theoretical maximum) was obtained in the reaction of piceid glycosylation, after 5 reaction cycles, using the self-sufficient biocatalyst based on an improved sucrose synthase variant. This result was 5-fold higher than the obtained using soluble cofactor and the co-immobilized enzymes, and much higher than those reported in the literature for similar processes.


Expression of zinc finger 23 gene in human hepatocellular carcinoma.
The aim of this study was to investigate the relationship between human zinc finger 23 (ZNF23) expression and clinico-pathological characteristics in patients suffering from hepatocellular carcinoma (HCC), and to investigate ZNF23 expression in relation to cell apoptosis. Thirty-seven HCC samples were collected and ZFP23 mRNA levels were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Correlation between ZNF23 expression and patients' clinical characteristics was analyzed. For determining the effect of ZNF23 on cell apoptosis, HepG2 cells were exposed to cisplatin at different concentrations and ZNF23 mRNA assayed. Median relative mRNA levels of ZNF23 mRNA in HCC tissues and adjacent tissues were 8.84 (3.59-15.05) and 22.20 (13.85-42.90), respectively (U=259.5, p<0.01). Median mRNA levels of ZNF23 in patients with Edmondson stage I+II disease [12.80 (4.80-19.50)] were much higher than those of patients with stage III+IV disease [5.01 (2.88-11.68), U=99.00, p<0.05]. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that cisplatin significantly inhibited cell proliferation of HepG2 cells in a dose-dependent manner, which was positively correlated to cell apoptosis (F=27.89, p<0.01), and in response to increasing cisplatin concentrations, ZNF23 mRNA levels increased in the cells. Cisplatin-induced apoptotic effect in HepG2 cells may be mediated via the up-regulation of ZNF23, which suggests that the ZNF23 gene could play an important role in the development of hepatocellular carcinoma.


The urge to change appearance in different psychopathological categories.
In professional literature, mainly anecdotic descriptions can be found of striking, sometimes even bizarre manipulations of the appearance by psychiatric patients. In this study, it was examined whether the inclination to (drastically) change the appearance is related to (pre)psychotic symptoms. By means of a questionnaire, the frequency and nature of changing the appearance was studied among a sample of healthy volunteers (n = 38) and psychiatric patients (n = 61). The psychiatric group consisted of 1) patients with schizophrenia (n = 22), 2) patients with a borderline personality disorder (n = 20) and 3) patients with a depressive disorder (n = 19). In accordance with previous findings, self-reports of drastic changes of appearance were associated with scores on various schizotypy scales. Psychiatric patients reported more changes of appearance, compared with healthy volunteers. Patients with schizophrenia reported most changes, followed by the group of patients with borderline personality disordered. Perhaps, drastic changes of the appearance are a visible expression of the loss of ego boundaries and/or of the sense of reality.


Regulation of gap junctional communication in CFTR-expressing pancreatic epithelial cells.
Gap junction channels provide a pathway for coordinating multicellular activity. To evaluate the contribution of cell-to-cell communication in the function of epithelial cells, we studied the strength of gap junctional coupling in pancreatic acinar and duct cells exposed to agents known to elevate the intracellular concentration of Ca(2+) or cAMP. In acinar cells, we observed that maximal concentrations of acetylcholine evoked a biphasic increase in cytosolic Ca(2+) mobilization. The second sustained phase, which depends on Ca(2+) influx into the cell, was associated with the rapid closure of gap junction channels. In duct cells, stimulation of CFTR-dependent Cl(-) currents with cAMP analogs markedly increased gap junctional conductance in pairs of cells. Interestingly, cAMP had no effect on intercellular communication between cells harboring the DeltaF508 mutation of CFTR. An abnormal pattern of gap junctional coupling may contribute to the altered functions of tissues affected in cystic fibrosis.


Transcranial ultrasound-improved thrombolysis: diagnostic vs. therapeutic ultrasound.
Success of stroke treatment with rt-PA depends on rapid vessel recanalization. Enzymatic thrombolysis may be enhanced by additional transcranial application of ultrasound (US). We investigated this novel technique using a 185-kHz probe and compared it to standard diagnostic US. In vitro studies were performed in a continuous pressure tubing system. Clots were placed in a postmortem skull and treated with rt-PA together with or without transtemporal 185-kHz US insonation (2W/cm(2)) and in comparison to 1-MHz diagnostic US (0.5 W/cm(2)). Recanalization time was significantly (p < 0.01) shorter in the 185-kHz (14.1 min) and 1-MHz (17.1 min) US rt-PA treatment group compared to rt-PA treatment alone (29.3 min.). Flow rate was significantly higher (p < 0.025) and increased faster in the combined treatment group with rt-PA + 185-kHz US compared to rt-PA + 1-MHz US. We investigated the blood-brain barrier in rats after 90-min exposure time of the brain with 185-kHz US, but no damage was observed. Results suggest efficacy and safety of the 185-kHz transducer, which is superior to diagnostic US. Such a novel US probe may be able to optimize thrombolytic stroke treatment.


A smartphone integrated ratiometric fluorescent sensor for point-of-care testing of fluoride ions.
In view of the high toxicity and widespread availability, it is of great importance to develop accurate, sensitive, and convenient assays for fluoride ion (F-) detection. Herein, a ratiometric fluorescent system is established for point-of-care testing (POCT) of F- with a smartphone as analyzer. The sensing system of calcein-QDs-Eu3+ contains two fluorescent probes of calcein (green emission) and ZnCdSe/ZnS QDs (red emission). The sensing system only presents red emission in that the calcein emission is quenched due to the combination between calcein and Eu3+. When F- is introduced, the fluorescence of calcein is recovered due to the stronger interaction between F- and Eu3+, which changes the emission from red to green. The ratiometric strategy offers an obvious fluorescence color change of the system, which eliminates interference and improves the detection accuracy. Specifically, the sensing system has excellent selectivity in that Eu3+ is more inclined to bind with F- rather than other anions. The developed assay was further used to prepare a test paper and hydrogel for POCT. To further improve the detection sensitivity and realize quantitative analysis, a smartphone installed with a color scan app is integrated as signal reader and analyzer, which is used for POCT of F- in real samples, showing great application potential in environmental protection and food safety evaluation.


Tooth colour change with Ozicure Oxygen Activator: a comparative in vitro tooth bleaching study.
This in vitro study compared a new tooth bleaching product, Ozicure Oxygen Activator (O3, RSA) with Opalescence Quick (Ultradent, USA) using a randomised block design to assess tooth colour change. Colour change, stability and relapse in canine, incisor and premolar teeth was assessed following three bleach treatments and subsequent tooth colour assessment. Ninety nine teeth (canines, incisors and premolars), which were caries free, had no surface defects and were within the colour range 1M2 and 5M3 were selected. Teeth were randomly divided into the three experimental groups: Opalescence Quick, Ozicure Oxygen Activator and control. The three experimental groups received three treatments of one hour each over three consecutive days. Tooth colour was assessed using the Vitapan 3D Master Tooth Guide (VITA, Germany). A General Linear Models test for analysis of variance for a fractional design with significance set at P < 0.05 was used to test for significance. Both bleaching methods significantly lightened the teeth (P < 0.0001). Tooth colour change was mainly after the first hour of tooth bleaching. The tooth type was significant in tooth colour change (P = 0.0416). Tooth colour relapse and resistance to colour change were observed. Ozicure Oxygen Activator bleached teeth in a manner and to an extent similar to Opalescence Quick.


Mortality and revision risk after femoral neck fracture: comparison of internal fixation for undisplaced fracture with arthroplasty for displaced fracture: a population-based study from Danish National Registries.
Background and purpose - Hemiarthroplasty has lower reoperation frequency and better mobilization compared with internal fixation (IF) in patients with undisplaced femoral neck fractures (FNF), which might translate into lower mortality. In this population-based cohort study we compare the risk of mortality and reoperation in undisplaced FNF treated with IF and displaced FNF treated with arthroplasty in patients older than 70 years old. We assume that, per se, there is no difference in mortality risk between patients with a displaced and an undisplaced FNF.Patients and methods - Hip fracture patients were identified in the Danish Multidisciplinary Hip Fracture Registry during 2005-2015. Data on medication, comorbidities, reoperation, and mortality were retrieved from other Danish medical databases. IF and arthroplasty patients were compared with regards to mortality and reoperation up to 5 years postoperatively. We calculated hazard ratios (HR) with 95% confidence intervals (CI) adjusting for relevant confounders.Results - We included 19,260 FNF treated with arthroplasty and 10,337 FNF with IF. There was an increased risk of mortality for arthroplasty within 30 days, HR 1.3 (95% CI 1.3-1.4), compared with IF but not after 1 and 5 years. Arthroplasty patients had adjusted HRs for reoperation of 0.8 (0.8-0.9) within 1 year, 0.8 (0.7-0.9) within 2 years, and 0.8 (0.8-0.9) within 5 years postoperatively compared with IF.Interpretation - Patients treated for a displaced FNF with arthroplasty had a higher risk of 30-day mortality compared with patients who had an undisplaced FNF treated with IF. It has to be considered that there were baseline differences in the groups but there was no difference in mortality risk up to 5 years post-surgery. Concerning reoperation, patients with a displaced FNF treated with arthroplasty had a lower risk of reoperation compared with IF for undisplaced FNF.


[Immunological treatment of digitalis poisoning with heterologous antibodies].
Our own experience with the production of digoxin-specific antibody preparations from the sheep and the results of the experimental and clinical use are briefly reviewed. Advantages, risks and unsolved problems of therapy with glycoside-specific antibodies are discussed.