Research on the synergetic development of producer services and manufacturing in northwest China's inland central cities-A case study of Lanzhou.
Under the post Ford flexible production organization system, the existence of specialized division of labor has made the forward and backward connections between the producer services as an intermediate input and the manufacturing increasingly close. With the proposal of the "Belt and Road" and the deepening of "The development of the western region in China", the northwest region plays an increasingly important role in China's regional development strategy, and the economic transformation, especially the transformation and upgrading of the manufacturing, and it is crucial to its completion of the strategic mission entrusted by the state. Taking Lanzhou City as a case area, based on the measurement of the cooperative development level of producer services and manufacturing, this paper explores the internal law of the synergetic development of producer services and manufacturing in the northwest inland central city. The study found: The overall synergy development level of producer services and manufacturing in Lanzhou has been significantly improved in the dynamic evolution process, and two industries are in the transition stage from the primary coordinated development to the intermediate coordinated development at present. The spatial layout of producer services and manufacturing in Lanzhou City has certain spatial proximity, and the overall presents a "center-periphery" spatial pattern with the main urban area as the main component. From the perspective of the synergistic development of producer services and manufacturing in Lanzhou, the two industries have initially formed an interactive relationship of two-way promotion at present, but there is a significant asymmetry in the two-way promoting effect of the two industries.


Zinc- and copper-replacement therapy--a must in burns and scalds in children?
The author describes experiences gained in the zinc and copper serum concentration estimations in burned children. Without added substitution therapy the serum zinc concentration rises by 19.9% and the serum copper concentration by 5.8% in the course of time. If only zinc is substituted the values rises by 83.6% for zinc, but the value for copper decreases by 18.8%. If the serum zinc and copper concentration is low on admission and if both added zinc and copper are given, the concentration for zinc rises by 102.5%, but the concentration of copper only rises by 25% and does not reach normal values. Serum zinc and copper concentration drops to its maximal extent 48 hours after the accident. The time of hospitalisation calculated per percentage of burned body surface decreases slightly if substitution therapy is given, although the average serum zinc and copper values do not even reach normal levels. The rate of infection and the type of infection are not markedly different whether no substitution, only zinc and copper serum concentration to the area of the burned body surface, the normal value, the dosages used in substitution therapy and the side effects of the therapy are discussed. Routine therapy is probably not justified because of the normal changes of the serum concentration, because side effects are not completely understood and because of the antagonism between zinc and copper known from veterinary medicine. If more than 20% of the total body surface has been burned zinc and copper deficiency is probable. The dosage referred to in the literature are too high and much lower dosages (10--30 mg of zinc sulphate per day and 0.08 mg/kg of copper sulphate per day) are advised. These amounts should be sufficient if given in addition to a diet, which should be administered as early as possible after the accident.


Nitric oxide binding to the cardiolipin complex of ferric cytochrome C.
Cardiolipin, a phospholipid specific to the mitochondrion, interacts with the small electron transfer heme protein cytochrome c through both electrostatic and hydrophobic interactions. Once in a complex with cardiolipin, cytochrome c has been shown to undergo a conformational change that leads to the rupture of the bond between the heme iron and the intrinsic sulfur ligand of a methionine residue and to enhance the peroxidatic properties of the protein considered important to its apoptotic activity. Here we report that the ferric cytochrome c/cardiolipin complex binds nitric oxide tightly through a multistep process in which the first step is the relatively slow displacement (5 s(-1)) from heme coordination of an intrinsic ligand that replaces methionine in the complex. Nanosecond photolysis of the nitrosyl adduct demonstrated that a fraction of the nitric oxide escapes from the heme pocket and subsequently recombines to the heme in second-order processes (k = 1.8 × 10(6) and 5.5 × 10(5) M(-1) s(-1)) that, under these conditions, were much faster than recombination of the intrinsic ligand with which they compete. Ultrafast (femtosecond) laser photolysis showed that the geminate recombination of nitric oxide to the heme occurred with time constants (τ = 22 and 72 ps) and that ~23% of the photolyzed nitric oxide escaped into the bulk phase. This high value for the escape fraction relative to other heme proteins indicates the open nature of the heme pocket in this complex. These results are summarized in a scheme and are discussed in terms of the possible modulation of the apoptotic activity of cytochrome c by nitric oxide.


A gas-driven capillary based on the synergy of the catalytic and photothermal effect of PB@Au for Salmonella typhimurium detection.
Rapid detection method for Salmonella typhimurium is vital to prevent the spread of food-borne diseases. In this work, a gas-driven capillary detection method was established to achieve sensitive and rapid detection of Salmonella typhimurium using the catalytic and photothermal synergy of Prussian blue-nanogold (PB@Au) nanomaterials. The immuno-PB@Au probe attached to the capillary by specific identification of target bacteria catalyzed the H2O2 under laser irradiation, driving the H2O2 liquid column to move (ΔL) by producing gas, and achieving the quantitative detection of Salmonella typhimurium. After detailed optimization of the critical performance parameters of the gas-driven capillary assay, the limit of detection (LOD) after laser irradiation and being catalyzed by PB@Au was calculated to be 37 CFU mL-1 through the determination of different concentrations of target bacteria. Furthermore, the detection performances of the gas-driven capillary method were evaluated in detail, and the recoveries ranging from 92.9 ± 4.7 % to 107.7 ± 4.1 % were achieved using the spiked actual samples with complex matrices, indicating that the established rapid assay can offer promising strategies for the monitoring and controlling of food-borne pathogenic bacteria.


The curcuminoid, EF-24, reduces cisplatin-mediated reactive oxygen species in zebrafish inner ear auditory and vestibular tissues.
Cisplatin is a widely used chemotherapy drug that can damage auditory and vestibular tissue and cause hearing and balance loss through the intracellular release of reactive oxygen species (ROS). Curcumin has anticancer efficacy and can also counteract cisplatin's damaging effect against sensory tissue by scavenging intracellular ROS, but curcumin's applicability is limited due to its low bioavailability. EF-24 is a synthetic curcumin analog that is more bioavailable than curcumin and can target cancer, but its effects against cisplatin-mediated ROS in auditory and vestibular tissue is currently unknown. In this study, we employed a novel zebrafish inner ear tissue culture system to determine if EF-24 counteracted cisplatin-mediated ROS release in two sensory endorgans, the saccule and the utricle. The zebrafish saccule is associated with auditory function and the utricle with vestibular function. Trimmed endorgans were placed in tissue culture media with a fluorescent reactive oxygen species indicator dye, and intracellular ROS release was measured using a spectrophotometer. We found that cisplatin treatment significantly increased ROS compared to controls, but that EF-24 treatment did not alter or even decreased ROS. Importantly, when equimolar cisplatin and EF-24 treatments are combined, ROS did not increase compared to controls. This suggests that EF-24 may be able to prevent intracellular ROS caused by cisplatin treatment in inner ear tissue.


Crossed aphasia in a patient with complex partial seizures: evidence from intracarotid amobarbital testing, functional cortical mapping, and neuropsychological assessment.
We report a right-handed patient who became transiently aphasic following a right temporal lobectomy for control of intractable complex partial seizures. Preoperative intracarotid amobarbital testing revealed right-hemisphere language dominance, although bilateral language representation was present. Memory testing during unilateral electrical hippocampal simulation with depth electrodes indicated reliance on left-hemisphere mesial temporal lobe structures for verbal memory. Functional mapping for language during surgery established several right perisylvian regions that, when stimulated, produced speech arrest and/or paraphasic substitution. One-year follow-up neuropsychological assessment demonstrated an increase in verbal learning and decrease in visual memory, a pattern associated with patients who have undergone right temporal lobectomy. These data demonstrate that (1) right cerebral language dominance can be observed when ipsilateral seizure onset is present (2) verbal memory and language dominance are not necessarily linked, and (3) some reported cases of crossed aphasia may in fact have bilateral language representation.


Increasing dialysate flow and dialyzer mass transfer area coefficient to increase the clearance of protein-bound solutes.
Clinical hemodialysis systems achieve high single pass extraction of small solutes that are not bound to plasma proteins. But they clear protein-bound solutes much less effectively. This study examines the extent to which clearance of a protein-bound test solute is improved by increasing the dialyzer mass transfer area coefficient (KoA) and the dialysate flow rate (Qd). A reservoir containing test solutes and artificial plasma with albumin concentration approximately 4 g/dl was dialyzed with a standard clinical dialysate delivery system. The clearance of phenol red (ClPR) was compared with the clearances of urea and creatinine at a plasma flow rate (Qp) of 200 ml/min with varying values of KoA and Qd. ClPR increased from 11 +/- 2 ml/min to 23 +/- 2 ml/min when KoA for phenol red, KoAPR, was increased from 238 to 640 ml/min and Qd was increased from 286 +/- 6 ml/min to 734 +/- 9 ml/min. Increasing either KoAPR or Qd alone had lesser effects. Clearance values for phenol red were much lower than clearance values for the unbound solutes urea and creatinine, which ranged from 150 to 200 ml/min and were less affected by varying KoA and Qd. A mathematical model was developed to predict ClPR from values of Qp, Qd, the fraction of phenol red bound to albumin (94% +/- 1%) and KoAPR. The model accurately predicts the pattern of measured results and shows further that ClPR can be made to approach Qp only by very large increases in both KoAPR and Qd.


Nuclear metabolism. II. Further studies on epoxide hydrolase activity.
Apparent Km- and Vmax-values of nuclear styrene 7,8-oxide hydrolase were determined at different protein concentrations. In the protein concentrations range used no significant differences in the apparent Km-values were observed. The influence of the incubation with different modifiers (i.e. SKF-525A, metyrapone, 1,2-epoxy-3,3,3 trichloropropane, cyclohexene oxide) at two different concentrations on this enzyme activity was also determined. Cyclohexene oxide and 1,2-epoxy-3,3,3-trichloropropane, two well known inhibitors of the microsomal epoxide hydrolase(s) caused a marked inhibition, metyrapone had a strong activating effect whereas SKF-525A had no effect. In vivo pretreatment with phenobarbital significantly induced the nuclear epoxide hydrolase whereas beta-naphthoflavone caused a lower degree of induction. This pattern is quantitatively different but qualitatively very similar to the microsomal one. Moreover a toxifying to detoxifying enzymatic activity balance is attempted for the metabolization of the alkenic double bond of styrene, taking into account the ratio between the styrene monooxygenase (toxifying enzyme) and the styrene, 7,8-oxide hydrolase (detoxifying enzyme) after the above mentioned pretreatments, both in the microsomal and nuclear fractions.


An ultrasonic time-of-flight system for hand movement measurement.
We have designed and built an ultrasonic time-of-flight system to measure the three-dimensional coordinates of up to three moving emitters. These emitters are fixed on the hand and arm of a human subject or on a hand-held stylus, to provide information concerning motor control. Three stationary receivers are suspended above the experimental space and provide three diagonal distances which are converted to x, y and z coordinates. The sampling rate for one emitter is 200-400 Hz, depending on the nature of the experiment. Multiple emitters are time-multiplexed. The piezoelectric resonator emitter is pulsed with 200 V for 12 microseconds of each cycle and rings at 40 kHz with a Q factor of four. The piezoelectric resonator receiver drives circuitry with a gain of 500 and a bandwidth of 60 kHz. The system provided highly linear results with a repeatability of +/- 1.64 mm and a resolution of 0.7 mm.


Disseminated toxoplasmosis in cardiac transplantation.
The first case of disseminated toxoplasmosis following cardiac transplantation in the UK is described, with details of Toxoplasma antibody tests made on other cardiac transplant patients. Sixteen of 40 (39%) of recipients had Toxoplasma antibody before operation. Eleven of 30 (37%) of donors had Toxoplasma antibody. The were four occasions when a negative recipient received a heart from a positive donor. Three survived the immediate postoperative period and two became infected with toxoplasmosis. The implications of this are discussed. Disseminated toxoplasmosis appears much more often when heart muscle from a dye test positive donor is given to a dye test negative recipient. Antibiotic therapy is limited by the fact that the antitoxoplasma drugs available are static in their effect, and need to be given for prolonged periods postoperatively.


Reflecting on changes in the drinking and irrigation water quality of rivers Beas, Satluj and confluence waters.
Prevention and control of water pollution for maintaining and restoring the wholesomeness of rivers are unavoidable. The current water quality approach of designated best use has some limitations such as it is non-integrative and inflexible with regard to the consideration of variables and does not provide a separate rating scale for a given designated use. We thus used water quality index approach proposed by the Canadian Council of Ministers of the Environment (CCME WQI) to evaluate and develop a separate rating system for drinking and irrigation purposes of rivers Beas, Satluj and their confluence water of the Indian Punjab using information collected over 4 years (2016 to 2019). River Beas exhibited better water quality compared to river Satluj for irrigation as well as for drinking. The overall drinking water quality index (DWQI) for Beas was marginal (45.5), whereas it was poor for Satluj (37.7) and confluence waters (40.1). The spatial variation in DWQI was greater for Satluj compared to Beas and confluence waters reflecting the effect of dumping of untreated industrial and domestic waste waters. Variables such as Total coliform (T. coli), dissolved oxygen (DO), turbidity and biological oxygen demand (BOD) contributed to the deterioration of DWQI. The irrigation water quality index (IWQI) was good for Beas (86), marginal for Satluj (60.1) and fair for confluence waters (71.2). Faecal coliform (F. coli), Kelly ratio (KR) and %Na contributed to the deterioration of IWQI. Calcium-magnesium-bicarbonate (Ca-Mg-HCO3) was the dominant water type in Beas and confluence waters, whereas for Satluj, in addition to Ca-Mg-HCO3, sodium-potassium-chloride-sulphate and mixed water types were also prevalent. The river waters witnessed salinity hazard but did not pose sodicity hazard except at a few locations of Satluj. The study indicates the need to take location specific measures for improving river water quality for drinking as well as irrigation purposes. The current status of water quality calls for an urgent need to formulate stringent policy regulations to maintain the surface water quality.


Developmental alterations in the transcriptome of three distinct rodent models of schizophrenia.
Schizophrenia is a debilitating disorder affecting just under 1% of the population. While the symptoms of this disorder do not appear until late adolescence, pathological alterations likely occur earlier, during development in utero. While there is an increasing literature examining transcriptome alterations in patients, it is not possible to examine the changes in gene expression that occur during development in humans that will develop schizophrenia. Here we utilize three distinct rodent developmental disruption models of schizophrenia to examine potential overlapping alterations in the transcriptome, with a specific focus on markers of interneuron development. Specifically, we administered either methylazoxymethanol acetate (MAM), Polyinosinic:polycytidylic acid (Poly I:C), or chronic protein malnutrition, on GD 17 and examined mRNA expression in the developing hippocampus of the offspring 18 hours later. Here, we report alterations in gene expression that may contribute to the pathophysiology of schizophrenia, including significant alterations in interneuron development and ribosome function.


Design framework for spherical microphone and loudspeaker arrays in a multiple-input multiple-output system.
Spherical microphone arrays (SMAs) and spherical loudspeaker arrays (SLAs) facilitate the study of room acoustics due to the three-dimensional analysis they provide. More recently, systems that combine both arrays, referred to as multiple-input multiple-output (MIMO) systems, have been proposed due to the added spatial diversity they facilitate. The literature provides frameworks for designing SMAs and SLAs separately, including error analysis from which the operating frequency range (OFR) of an array is defined. However, such a framework does not exist for the joint design of a SMA and a SLA that comprise a MIMO system. This paper develops a design framework for MIMO systems based on a model that addresses errors and highlights the importance of a matched design. Expanding on a free-field assumption, errors are incorporated separately for each array and error bounds are defined, facilitating error analysis for the system. The dependency of the error bounds on the SLA and SMA parameters is studied and it is recommended that parameters should be chosen to assure matched OFRs of the arrays in MIMO system design. A design example is provided, demonstrating the superiority of a matched system over an unmatched system in the synthesis of directional room impulse responses.


Cost-effectiveness of respiratory syncytial virus prophylaxis among preterm infants.
To evaluate the costs and benefits of two new agents, respiratory syncytial virus immune globulin (RSVIG) and palivizumab, to prevent respiratory syncytial virus (RSV) infection among premature infants discharged from the neonatal intensive care unit (NICU) before the start of the RSV season. Method. Decision analysis was used to compare the projected societal cost-effectiveness of three strategies-RSVIG, palivizumab, and no prophylaxis-among a hypothetical cohort of premature infants. Probabilities and costs of hospitalization were derived from a cohort of 1721 premature infants discharged from six Kaiser Permanente-Northern California NICUs. Efficacies of prophylaxis were based on published trials. Costs of prophylaxis were derived from published sources. Mortality among infants hospitalized for RSV was assumed to be 1.2%. Future benefits were discounted at 3%. Palivizumab was both more effective and less costly than RSVIG. Cost-effectiveness varied widely by subgroup. Palivizumab appeared most cost-effective for infants whose gestational age was </=32 weeks, who required >/=28 days of oxygen in the NICU, and who were discharged from the NICU from September through November. In this subgroup, palivizumab was predicted to cost $12,000 per hospitalization averted (after taking into account savings from prevention of RSV admissions) or $33,000 per life-year saved, and the number needed to treat to avoid one hospitalization was estimated at 7.4. However, for all other subgroups, ratios ranged from $39,000 to $420,000 per hospitalization averted or $110,000 to $1,200,000 per life-year saved, and the number needed to treat extended from 15 to 152. The results were sensitive to varying assumptions about the cost and efficacy of prophylaxis, as well as the probability of hospitalization, but were less sensitive to the cost of hospitalization. In our model, the cost of prophylaxis against RSV for most subgroups of preterm infants was high relative to the benefits realized. Lower costs might permit the benefits of prophylaxis to be extended to additional groups of preterm infants.


Proline-rich tyrosine kinase 2 (Pyk2) promotes cell motility of hepatocellular carcinoma through induction of epithelial to mesenchymal transition.
Proline-rich tyrosine kinase 2 (Pyk2), a non-receptor tyrosine kinase of the focal adhesion kinase (FAK) family, is up-regulated in more than 60% of the tumors of hepatocellular carcinoma (HCC) patients. Forced overexpression of Pyk2 can promote the proliferation and invasion of HCC cells. In this study, we aimed to explore the underlying molecular mechanism of Pyk2-mediated cell migration of HCC cells. We demonstrated that Pyk2 transformed the epithelial HCC cell line Hep3B into a mesenchymal phenotype via the induction of epithelial to mesenchymal transition (EMT), signified by the up-regulation of membrane ruffle formation, activation of Rac/Rho GTPases, down-regulation of epithelial genes E-cadherin and cytokeratin as well as promotion of cell motility in presence of lysophosphatidic acid (LPA). Suppression of Pyk2 by overexpression of dominant negative PRNK domain in the metastatic HCC cell line MHCC97L transformed its fibroblastoid phenotype to an epithelial phenotype with up-regulation of epithelial genes, down-regulation of mesenchymal genes N-cadherin and STAT5b, and reduction of LPA-induced membrane ruffle formation and cell motility. Moreover, overexpression of Pyk2 in Hep3B cells promoted the phosphorylation and localization of mesenchymal gene Hic-5 onto cell membrane while suppression of Pyk2 in MHCC97L cells attenuated its phosphorylation and localization. These data provided new evidence of the underlying mechanism of Pyk2 in controlling cell motility of HCC cells through regulation of genes associated with EMT.


Hemocompatible mixed-charge copolymer brushes of pseudozwitterionic surfaces resistant to nonspecific plasma protein fouling.
In this work, the hemocompatibility of a sulfobetaine-like copolymer brush resulting from a mixed-charge copolymerization of the positively charged 11-mercapto-N,N,N-trimethylammonium chloride (TMA) and negatively charged 11-mercaptoundecylsulfonic acid (SA) was studied. Mixed charge distribution in the prepared poly(TMA-co-SA) copolymer brushes was controlled by the regulation of the reaction rate of the surface-initiated atom transfer radical polymerization (ATRP). The adsorption behavior of plasma proteins on a surface grafted with poly(TMA-co-SA) was measured by a surface plasmon resonance (SPR) sensor. The effects of varying temperature, solution pH, and ionic strength on the antifouling characteristics of the mixed-charge copolymer brushes were systematically evaluated, and the protein-fouling resistance was discussed in detail, especially with respect to the effect of ionic strength on the intra- and intermolecular interactions of the poly(TMA-co-SA) with proteins. The adhesion and activation of blood cells on the poly(TMA-co-SA)-grafted surface in contact with human whole blood was also demonstrated. The results suggest that mixed-charge copolymer brushes of poly(TMA-co-SA), which, like zwitterionic homopolymer brushes, have overall charge neutrality, can be used in similar applications for protein-fouling resistance and have excellent hemocompatibility with human whole blood at physiologic temperatures.


Evolution of circuits regulating pleasure and happiness with the habenula in control.
The habenula, which in humans is a small nuclear complex within the epithalamus, plays an essential role in regulating the intensity of reward-seeking and adversity-avoiding behavior in all vertebrate ancestors by regulating the activity of ascending midbrain monoaminergic tracts. In lampreys, considered to possess a brain comparable to humans' earliest evolutionary vertebrate ancestor, the activity of the lateral habenula is controlled by a subset of glutamatergic neurons of the animal's pallidum (habenula-projecting globus pallidus) that inhibit reward-seeking behavior when this conduct is not successful enough. The pathophysiological roles of the habenula and habenula-projecting globus pallidus in humans have hardly been studied, which is probably due to insufficient resolution of common neuroimaging techniques. Their dysregulation may, however, play an essential role in the pathogenesis of mood and stress disorders and addiction.


Dominance of longitudinal muscle in propagation of intestinal slow waves.
The purpose of these experiments was to test the hypothesis that circular muscle plays an active role in the propagation of intestinal slow waves, specifically be providing excitatory current through a process of regenerative amplification. With volume-recording techniques and microelectrode recordings we obtained the following results that are not consistent with such a mechanism: 1) slow waves propagated without delay or decrease in amplitude along segments of cat jejunum devoid of a ring of circular muscle up to 3 mm wide, i.e., across a longitudinal muscle bridge more than 4 space constants long (9 of 11 preparations) but did not propagate across a circumferential cut through the longitudinal muscle layer (14 of 14 preparations); 2) the membrane current associated with the slow wave had a pronounced inward component when recorded from either the serosal or the mucosal side of the longitudinal muscle bridge but was entirely outward when recorded from either the mucosal or the serosal side of exposed circular muscle, including those preparations in which various thicknesses of circular muscle were removed from the mucosal side of the recording area; 3) slow-wave amplitudes recorded intracellularly from intact (n = 9) and isolated (n = 8) longitudinal muscle preparations were not significantly different (27.0 +/- 4.3 vs. 25.4 +/- 5.3 (SD) mV); 4) after 30 min in 4.4 X 10(-6) M verapamil, slow-wave amplitude did not significantly decrease, although contractile activity had long since terminated. These results are more consistent with the hypothesis that longitudinal muscle provides most, if not all, of the current required for slow-wave propagation in the small intestine.


Impact of Socioeconomic Status on Adult Patients with Asthma: A Population-Based Cohort Study from UK Primary Care.
Asthma morbidity and health-care utilization are known to exhibit a steep socioeconomic gradient. Further investigation into the modulators of this effect is required to identify potentially modifiable factors. We identified a cohort of patients with asthma from the Optimum Patient Care Research Database (OPCRD). We compared demographics, clinical variables, and health-care utilization by quintile of the UK 2011 Indices of Multiple Deprivation based on the location of the patients' general practice. Multivariable analyses were conducted using generalized linear models adjusting for year, age, and sex. We conducted subgroup analyses and interaction tests to investigate the impact of deprivation by age, sex, ethnicity, and treatment step. Our analysis included 127,040 patients with asthma. Patients from the most deprived socio-economic status (SES) quintile were more likely to report uncontrolled disease (OR: 1.54, 95% CI: 1.16, 2.05) and to have an exacerbation during follow-up (OR: 1.27, 95% CI: 1.13, 1.42) than the least deprived quintile. They had higher blood eosinophils (ratio: 1.03; 95% CI: 1.00, 1.06) and decreased peak flow (ratio: 0.95, 95% CI: 0.94, 0.97) when compared to those in the least deprived quintile. The effect of deprivation on asthma control was greater among those aged over 75 years (OR = 1.81, 95% CI: 1.20, 2.73) compared to those aged less than 35 years (OR: 1.22, 95% CI: 0.85, 1.74; pinteraction=0.019). Similarly, socioeconomic disparities in exacerbations were larger among those from ethnic minority groups (OR: 1.94, 95% CI: 1.40, 2.68) than white patients (OR: 1.24, 95% CI: 1.10, 1.39; pinteraction=0.012). We found worse disease control and increased exacerbation rates among patients with asthma from more deprived areas. There was evidence that the magnitude of socioeconomic disparities was elevated among older patients and those from ethnic minority groups. The drivers of these differences require further exploration.


Variability and progression in competitive performance of Paralympic swimmers.
Analysis of variability and progression in performance of top athletes between competitions provides information about performance targets that is useful for athletes, practitioners, and researchers. In this study, 724 official finals times were analysed for 120 male and 122 female Paralympic swimmers in the 100-m freestyle event at 15 national and international competitions between 2004 and 2006. Separate analyses were performed for males and females in each of four Paralympic subgroups: S2-S4, S5-S7, S8-S10 (most through least physically impaired), and S11-S13 (most through least visually impaired). Mixed modelling of log-transformed times, with adjustment for mean competition times, was used to estimate variability and progression. Within-swimmer race-to-race variability, expressed as a coefficient of variation, ranged from 1.2% (male S5-S7) to 3.7% (male S2-S4). Swimming performance progressed by approximately 0.5% per year for males and females. Typical variation in mean performance time between competitions was approximately 1% after adjustment for the ability of the athletes in each competition, and the Paralympic Games was the fastest competition. Thus, taking into account variability, progression, and level of competition, Paralympic swimmers who want to increase substantially their medal prospects should aim for an annual improvement of at least 1-2%.


Evaluation of breath alcohol analysers by comparison of breath and blood alcohol concentrations.
The main goal of this study was to determine the reliability of hand-held breath alcohol analysers currently approved for roadside screening of traffic offenders. The first part of the study included a retrospective data analysis of 714 offence records collected in 2011. Blood alcohol concentrations (BAC) obtained from the offenders 0-303 min after the police had screened them for breath alcohol concentration (BrAC) were back-calculated (cBAC) to assess the accuracy of breathalyser screening. All participants were in the alcohol elimination phase, and our analyses did not reveal any significant differences between cBAC and BrAC. To verify our findings, we performed a controlled drinking study that involved 63 healthy volunteers who consumed alcoholic beverages to simulate real drinking conditions. Immediately after alcohol consumption, BrAC was determined with a Dräger breath alcohol analyser model 6810, and 29 participants gave blood and urine sample for concomitant BAC analysis one hour later. BAC and urine alcohol concentrations were determined with headspace gas chromatography. Again, we found no significant differences between BrAC and BAC. These results confirmed the high reliability of breath alcohol analysers for measuring BrAC as long as police officers perform the measurements according to the manufacturer's instructions.


International collaborative study on the occurrence of plasmid-mediated quinolone resistance in Salmonella enterica and Escherichia coli isolated from animals, humans, food and the environment in 13 European countries.
This study was initiated to collect retrospective information on the occurrence of plasmid-mediated quinolone resistance (PMQR) in Salmonella enterica and Escherichia coli isolates in Europe and to identify the responsible genes. Databases of national reference laboratories containing MIC values for Salmonella and E. coli isolated between 1994 and 2009 in animals, humans, food and the environment from 13 European countries were screened for isolates exhibiting a defined quinolone resistance phenotype, i.e. reduced susceptibility to fluoroquinolones and nalidixic acid. PCR and sequence analysis were performed to identify the responsible PMQR genes. Screening of databases of 13 European countries resulted in a selection of 1215 Salmonella and 333 E. coli isolates. PMQR genes were identified in 59% of the Salmonella isolates and 15% of the E. coli isolates selected. In Salmonella, qnrS1 (n = 125) and variants of qnrB (n = 138) were frequently identified, whereas qnrA1 (n = 3) and aac(6')-1b-cr (n = 3) were rarely found. qnrD was detected in 22 Salmonella isolates obtained from humans and animals. In E. coli, qnrS1 was identified in 19 isolates and qnrB19 was found in one isolate. No qnrC or qepA genes were detected in either Salmonella or E. coli. This study shows the occurrence and dissemination of PMQR genes in Salmonella and E. coli in Europe with a defined quinolone resistance phenotype. We also report the first detection of qnrD in Salmonella collected in Europe.


Green tea polyphenol (-)-epigallocatechin gallate prevents oxidative damage on periventricular white matter of infantile rats with hydrocephalus.
Hydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. Emphasizing the periventricular ischemia/hypoxia in hydrocephalus, various authors indicated the secondary biochemical impairment and oxidative damage in experimentally induced and congenital hydrocephalic rat brain. (-)-Epigallocatechin gallate (EGCG), the main constituent of green tea polyphenols, has been shown to be of some protective value in various models of neurological injury as a free oxygen radical scavenger. In the present study the effects of EGCG were examined on the periventricular oxidative damage in experimental childhood-onset hydrocephalus. Hydrocephalus was induced in 3 weeks-old rat pups by kaolin injection into the cisterna magna. A single daily dose of 50 mg/kg of EGCG injected into the peritoneum of the rats for 15 days significantly reduced periventricular white matter malondialdehyde levels when compared to non-treated hydrocephalic animals. Our results indicate that EGCG may have a protective effect against periventricular white matter oxidative damage in hydrocephalus induced infantile rats.


Modeling the Short-Term Dynamics of in Vivo Excitatory Spike Transmission.
Information transmission in neural networks is influenced by both short-term synaptic plasticity (STP) as well as nonsynaptic factors, such as after-hyperpolarization currents and changes in excitability. Although these effects have been widely characterized in vitro using intracellular recordings, how they interact in vivo is unclear. Here, we develop a statistical model of the short-term dynamics of spike transmission that aims to disentangle the contributions of synaptic and nonsynaptic effects based only on observed presynaptic and postsynaptic spiking. The model includes a dynamic functional connection with short-term plasticity as well as effects due to the recent history of postsynaptic spiking and slow changes in postsynaptic excitability. Using paired spike recordings, we find that the model accurately describes the short-term dynamics of in vivo spike transmission at a diverse set of identified and putative excitatory synapses, including a pair of connected neurons within thalamus in mouse, a thalamocortical connection in a female rabbit, and an auditory brainstem synapse in a female gerbil. We illustrate the utility of this modeling approach by showing how the spike transmission patterns captured by the model may be sufficient to account for stimulus-dependent differences in spike transmission in the auditory brainstem (endbulb of Held). Finally, we apply this model to large-scale multielectrode recordings to illustrate how such an approach has the potential to reveal cell type-specific differences in spike transmission in vivo Although STP parameters estimated from ongoing presynaptic and postsynaptic spiking are highly uncertain, our results are partially consistent with previous intracellular observations in these synapses.SIGNIFICANCE STATEMENT Although synaptic dynamics have been extensively studied and modeled using intracellular recordings of postsynaptic currents and potentials, inferring synaptic effects from extracellular spiking is challenging. Whether or not a synaptic current contributes to postsynaptic spiking depends not only on the amplitude of the current, but also on many other factors, including the activity of other, typically unobserved, synapses, the overall excitability of the postsynaptic neuron, and how recently the postsynaptic neuron has spiked. Here, we developed a model that, using only observations of presynaptic and postsynaptic spiking, aims to describe the dynamics of in vivo spike transmission by modeling both short-term synaptic plasticity (STP) and nonsynaptic effects. This approach may provide a novel description of fast, structured changes in spike transmission.


The effect of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) as an adjuvant in patients with resectable pancreatic cancer.
Background - aims: The long-term survival of pancreatic cancer is poor even after potentially curative resection. The incidence of local-regional failures is high. There is evidence that hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) is effective in controlling the local-regional failures. The purpose of the study is to identify the effect of HIPEC after surgical removal of pancreatic carcinoma. Patients - Methods: Prospective study including 33 patients with resectable pancreatic carcinomas. All patients underwent surgical resection (R0) and ΗIPEC as an adjuvant. Morbidity and hospital mortality were recorded. The patients were followed-up for 5 years. Survival was calculated. Recurrences and the sites of failure were recorded. The mean age of the patients was 67.8 ± 11.1 years (38-86). The hospital mortality was 6.1% (2 patients) and the morbidity 24.2% (8 patients). The overall 5-year survival was 24%. The mean and median survival was 33 and 13 months, respectively. The median follow-up time was 11 months. The recurrence rate was 60.6% (20 patients). Three patients were recorded with local-regional failures (9.1%) and the others with liver metastases. It appears that HIPEC as an adjuvant following potentially curative resection (R0) of pancreatic carcinoma may effectively control the local-regional disease. Prospective randomised studies are required.


Dnmt1 deficiency promotes CAG repeat expansion in the mouse germline.
Expanded CAG repeat tracts are the cause of at least a dozen neurodegenerative disorders. In humans, long CAG repeats tend to expand during transmissions from parent to offspring, leading to an earlier age of disease onset and more severe symptoms in subsequent generations. Here, we show that the maintenance DNA methyltransferase Dnmt1, which preserves the patterns of CpG methylation, plays a key role in CAG repeat instability in human cells and in the male and female mouse germlines. SiRNA knockdown of Dnmt1 in human cells destabilized CAG triplet repeats, and Dnmt1 deficiency in mice promoted intergenerational expansion of CAG repeats at the murine spinocerebellar ataxia type 1 (Sca1) locus. Importantly, Dnmt1(+/-) SCA1 mice, unlike their Dnmt1(+/+) SCA1 counterparts, closely reproduced the intergenerational instability patterns observed in human SCA1 patients. In addition, we found aberrant DNA and histone methylation at sites within the CpG island that abuts the expanded repeat tract in Dnmt1-deficient mice. These studies suggest that local chromatin structure may play a role in triplet repeat instability. These results are consistent with normal epigenetic changes during germline development contributing to intergenerational instability of CAG repeats in mice and in humans.


Laparoscopic treatment of hepatic hydatid cysts. Our approach.
In this study, we aimed to evaluate the clinical characteristics and outcome of patients with hydatid cyst (HC) of the liver who were laparoscopically operated at our clinic and to define a new technique and technical details to present our experience in the field of laparoscopic treatment of hepatic hydatid cysts. Between January 2014 and October 2016, 18 patients with hydatid disease of the liver were considered for laparoscopic surgery in Dr. Lutfi Kirdar Education and Research Hospital, Department of General Surgery. All patients were evaluated based on history, physical examination, ultrasound (US), and computed tomography (CT) scan. All ultrasound examinations were classified according to Gharbi. All cases received laparoscopic surgical interventions. Demographic data, clinical presentation, cyst location, operative data, postoperative complications and follow-up results were recorded retrospectively. Eighteen patients underwent laparoscopic surgery for hydatid cysts of the liver. here were 14 female (78%) and 4 male (22%) patients with a mean age of 42.9 years (range, 19-57). The hydatid cysts were solitary in 11 patients, and multiple in 7 patients had 2 or more cysts (4 patients had 2 cysts, 3 patients had 3 cysts). Most of the cysts on USG were Gharbi type III (8 cysts), 4 of Type II, and 3 of Type I. The average operating time was 75 minutes (range 50 - 135 minutes). Conversion to open surgery was necessary in one patients due to cyst in difficult location. Laparoscopic management of hydatid cysts of the liver can be performed safely and successfully. This technique can be used in patients with unique, small sized, superficially located cysts, and also has the advantages of other abdominal laparoscopic operations. Hepatic hydatid cysts, Laparoscopic surgery.


Development of adenosine responsiveness after isolation of Leydig cells.
Effects of adenosine and related compounds on the regulation of steroid production by isolated Leydig cells have been investigated. Steroid production by freshly isolated Leydig cells from testes of immature or mature rats and mice, or from Leydig tumor tissue could not be stimulated with adenosine, nicotinamide-adenine dinucleotide (phosphate) [NADPH, NAD(P)] or N6-(1-2-phenylisopropyl)-adenosine (PIA) (50 microM), whereas luteinizing hormone (LH) stimulated steroid production more than 10-fold. After 24 h incubation all adenosine-related compounds, but not inosine, stimulated steroid production to 20-100% of the maximal LH-stimulated activity. LH- or 22R -hydroxycholesterol-stimulated steroidogenesis in Leydig cells from immature rats did not decrease during the 24-h culture period, whereas ATP levels increased. The first significant effect of adenosine on steroid production in these cells was found after an incubation period of 3 h. In cells incubated for 1 h and 24 h, LH stimulated cyclic adenosine 3':5'-monophosphoric acid (cAMP) production 10-fold. Significant effects of adenosine and PIA on cAMP production or protein phosphorylation could only be shown in cells incubated for 24 h. Effects of adenosine on Leydig cells in intact testis tissue of immature rats could not be determined. The results suggest that after isolation of Leydig cells, specific alterations in the cell membrane occur, causing increased sensitivity to adenosine and related compounds. Adenosine apparently does not play a role in the role of steroid production in Leydig cells in vivo.


Prepregnancy body mass index and gestational age-dependent changes in lipid levels during pregnancy.
To examine the effect of maternal prepregnancy overweight and obesity on gestational age-dependent variation in lipid levels during pregnancy. Women between 6 and 10 weeks of gestation who carry a single, live intrauterine pregnancy were eligible to participate in a prospective pregnancy study (N=142). The exposure, maternal prepregnancy body mass index (BMI), was classified as: normal weight (BMI 18.5-26.0 kg/m) and overweight or obese (BMI over 26.0 kg/m). Our outcomes of interest, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured at 6-10, 10-14, 16-20, 22-26, and 32-36 weeks of gestation. Mixed linear models were used to examine how the trajectory of lipid levels during pregnancy differs between overweight or obese and normal-weight women. Levels of total cholesterol, triglycerides, LDL cholesterol, and HDL choloesterol increased over the prenatal period. The rate of change in LDL cholesterol (P<.001) and total cholesterol (P=.01) levels was lower for overweight or obese women than for normal-weight women in late-second and early-third trimester. As a result, overweight or obese women had significantly lower total cholesterol and LDL cholesterol levels than their normal-weight counterparts between 32-36 weeks of gestation. Overweight and obese women have different lipid profiles during pregnancy than their normal-weight peers. This difference may be the result of metabolic dysregulation associated with maternal overweight and obesity that mediates the increased risk of adverse outcomes found in these women. II.


Dopant Enriched Nitrogen Gas Combined with Sheathless Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry for Improved Sensitivity and Repeatability in Glycopeptide Analysis.
Over the last years, numerous strategies have been proposed to enhance both ionization efficiency and spray stability in electrospray ionization (ESI), in particular for nanospray applications. In nano-liquid chromatography-mass spectrometry (nano-LC-ESI-MS), a better ESI performance has been observed when a coaxial gas flow is added around the ESI emitter. Moreover, enrichment of the gas with an organic dopant has led to an improved desolvation and ionization efficiency with an overall enhanced sensitivity. In this study, the use of a dopant enriched nitrogen (DEN)-gas combined with sheathless capillary electrophoresis (CE)-ESI-MS was evaluated for glycopeptide analysis. Using acetonitrile as a dopant, an increased sensitivity was observed compared to conventional sheathless CE-ESI-MS. Up to 25-fold higher sensitivities for model glycopeptides were obtained, allowing for limits of detection unachieved by state-of-the-art nano-LC-ESI-MS. The effect of DEN-gas on the repeatability and intermediate precision was also investigated. When compared to previously reported nano-LC-ESI-MS measurements, similar values were found for CE-ESI-MS with DEN-gas. The enhanced repeatability fosters the use of DEN-gas sheathless CE-ESI-MS in protein glycosylation analysis, where precision is essential. The use of DEN-gas opens new avenues for highly sensitive sheathless CE-ESI-MS approaches in glycoproteomics research, by significantly improving sensitivity and precision.


Early interaction between mouse hepatitis virus 3 and cells.
The interaction between mouse hepatitis virus 3 (MHV3) and cells was studied in order to investigate whether or not early events occurring after infection could be involved in the difference in virus replication seen between mouse strains with different genetic sensitivities to MHV3 infection. Kinetic data showed that MHV3 uptake by both macrophages and L cells was time- and temperature-dependent. In addition, treatment of cells with cytochalasin B or prostaglandin E1, prior to virus infection, resulted in a strong inhibition of sheep red blood cell phagocytosis without any effect on MHV3 uptake. Similar uptake of radiolabelled MHV3 was shown by whole spleen cells, purified T lymphocytes and thymocytes. Furthermore, no difference in 3H-labelled MHV3 uptake was seen between macrophages originating from resistant A/J mice, semi-susceptible (C57Bl/6 x A/J)F1 and susceptible animals. These results indicate, therefore, that genetically related in vivo sensitivity toward MHV3 infection is not related to differential uptake of virus by cells.


Endoscopic Management of Drain Inclusion in the Gastric Pouch after Gastrojejunal Leakage after Laparoscopic Roux-en-Y Gastric Bypass for the Treatment of Morbid Obesity (LRYGBP).
Background. Drain inclusion inside the gastric pouch is rare and can represent an important source of morbidity and mortality associated with laparocopic Roux-en-Y gastric bypass (LRYGBP). These leaks can become chronic and challenging. Surgical options are often unsuccessful. We present the endoscopic management of four patients with drain inclusion. Patients. All four obese morbidly patients underwent LRYGBP and presented a gastro-jejunal fistula after acute anastomotic leakage. During follow-up endoscopy the drain was found inside the gastric pouch. It was moved into the abdominal cavity. Fistula debit reduced significantly and closed. Results. Gastric leak closure in less than 24 hours was achieved in all, with complete resolution of symptoms. These patients benefited exclusively from endoscopic treatment. Conclusions. Endoscopy is useful and technically feasible in chronic fistulas. This procedure is a less invasive alternative to traditional surgical revision. Other therapeutic strategies can be used such as clips and fibrin glue. Drains should not be placed in contact with the anastomosis or stapled lines. Drain inclusion must be suspected when fistula debit suddenly arises. If so, endoscopy is indicated for diagnostic accuracy. Under endoscopy vision, the drain is gently removed from the gastric reservoir leading to sudden and complete resolution of the fistula.


E-cigarettes in ENT: what do we need to know?
E-cigarette use in the UK is increasing and we are commonly encountering patients in the ENT clinic who are e-cigarette smokers. Currently, there is no regulatory body or licensing for e-cigarettes. This means that the contents, and therefore potential carcinogenic and toxic risks, can vary greatly from product to product. Patients are starting to ask about the risks of e-cigarettes and their use in smoking cessation. This review aimed to examine the regulations, trends, and carcinogenic and health risks of e-cigarettes, and summarise the evidence for their use in smoking cessation. It also aimed to provide a general awareness regarding the advice and information that can be safely given to patients.


Spontaneous regression of melanoma.
Primary cutaneous melanoma has a tendency to disappear spontaneously. Histologically the active phase is characterized by a dense infiltrate of lymphocytes similar to that seen in spontaneously disappearing naevi. The regression process may continue until the tumour has been completely destroyed, or it may cease when only a part of the tumour has been destroyed. The lymphocytes disappear when the process halts leaving vascular scar tissue with a variable number of pigment-containing phagocytes. As a result of this a certain number of distinctive clinical patterns can be recognized: (1) An inflammatory nodule with or without pigmentation; (2) scarring in the tumour; (3) several foci of melanoma simulating multicentricity; (4) pigmented lesion with a depigmented halo; (5) pigmented scar with surviving melanoma cells; (6) pigmented scar without surviving tumour cells; and (7) metastatic melanoma with no demonstrable cutaneous primary. Only melanomas with a component of superficial spreading type have been found undergoing spontaneous regression.


Behavioural Improvements in Children with Autism Spectrum Disorder after Participation in an Adapted Judo Programme Followed by Deleterious Effects during the COVID-19 Lockdown.
The public health lockdown prompted by the novel coronavirus (COVID-19) pandemic, which included school closures that may have potentially serious consequences for people with disabilities or special educational needs, disrupted an ongoing adapted judo training intervention in children with Autism Spectrum Disorder (ASD). The purpose of this study was to compare repetitive behaviours, social interaction, social communication, emotional responses, cognitive style and maladaptive speech scores across four time-points: baseline, after an eight-week control period, after an eight-week judo intervention and after an eight-week lockdown period due to COVID-19. The sample consisted of 11 children diagnosed with ASD according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V), with an intelligence quotient (IQ) range between 60 and 70. Significant improvements were shown following the judo intervention period compared to the baseline and control periods. However, the same values significantly declined during the COVID-19 lockdown period resulting in values lower than those recorded at baseline, and following the control period and the judo intervention. The decline in psychosocial and behavioural scores are likely due to the stress caused by the sudden halt in activity and the increase in sedentary practices associated with the lockdown.


The effect of intraoperative cerebral oxygen desaturations on postoperative cerebral oxygen metabolism in neonates and infants a pilot study.
Cerebral oxygen desaturation during pediatric surgery has been associated with adverse perioperative outcomes. The aim of this pilot study was to analyze the frequency and severity of intraoperative cerebral oxygen desaturations and their impact on postoperative cerebral oxygen metabolism in neonates and infants undergoing pediatric surgery. In a prospective pilot study, intra- and postoperative regional cerebral oxygen saturation and blood flow were measured noninvasively using a device combining laser Doppler flowmetry and white-light-spectrometry. Thirty-seven consecutive neonates and infants undergoing noncardiac surgery under general anesthesia for more than 30 min and necessity for invasive arterial blood pressure monitoring were included. Patients with pre-known congenital structural heart disease or cerebral disease were excluded. Continuously brain monitor recording was started in sedated patients before induction of anesthesia (preoperative baseline) and was completed 1 h postoperatively in the PICU in sedated, intubated, and mechanically ventilated states at the PICU (postoperative state). Baseline and postoperative state for cerebral fractional tissue oxygen extraction and approximated cerebral metabolic rate of oxygen were calculated. Seventeen (46%) of the 37 studied neonates and infants suffered from intraoperative periods of regional cerebral oxygen desaturation below 20% of the baseline (event group). Severity of cerebral desaturations was median 4.0%min/h [range 0.1-58.7; interquartile range [IQR] 0.99-21.29]. In the event group, the duration of surgery was significantly longer (median 135 min [range 11-260; IQR 113.5-167.0] vs median 46.5 min [range 11-180; IQR 30.5-159.3]; difference of -62.94; 95% confidence interval [CI] -105.17 to -20.71; p = .021). In the event group, cerebral fractional tissue oxygen extraction (median 0.41 [range 0.20-0.55; IQR 0.26-0.44] vs. median 0.27 [range 0.11-0.41; IQR 0.20-0.31]; difference of -0.11; 95% CI -0.17 to -0.05; p = .001) and approximated cerebral metabolic rate of oxygen (median 6.15 arbitrary unit [range 2.69-12.07; IQR 5.12-7.21] vs. median 4.14 arbitrary unit [range 1.78-7.86; IQR 3.82-6.31]; difference of -1.76; 95% CI -3.03 to -0.49; p = .009) were significantly higher and the cerebral regional oxygen saturation (median 58.99% [range 44.87-79.1; IQR 54.26-72.61] vs median 70.94% [range 57.9-86.13; IQR 67.07-76.59]; difference of 10.01; 95% CI 4.13-15.90; p = .002) significantly lower after surgery compared to the nonevent group. The increase of approximated cerebral metabolic rate of oxygen could indicate an elevated oxidative energy metabolism in the "stressed" brain, due to repair processes. The increased cerebral fractional tissue oxygen extraction fits with the decreased NIRS cerebral oxygenation. Our data suggest that an increase in cerebral oxygen metabolism was the cause. Cerebral oxygen desaturation during major surgery in neonates and infants is associated with early postoperative increased cerebral oxygen extraction and possibly increased cerebral oxygen metabolism.


Spin-Forbidden Channels in Reactions of Unsaturated Hydrocarbons with O(3P).
The electronic structure of four prototypical Cvetanović diradicals, species derived by addition of O(3P) to unsaturated compounds, is investigated by high-level electronic structure calculations and kinetics modeling. The main focus of this study is on the electronic factors controlling the rate of intersystem crossing (ISC): minimal energy crossing points (MECPs) and spin-orbit couplings (SOCs). The calculations illuminate significant differences in the electronic structure of ethene- and ethyne-derived compounds and explain the effect of methylation. The computed MECP heights and SOCs reveal different mechanisms of ISC in ethene- and ethyne-derived species, thus explaining variations in the observed branching ratios between singlet and triplet products and a puzzling effect of methyl substitution. In the ethene- and propene-derived species, the MECP is very low and the rate is controlled by variations of SOC, whereas in the ethyne- and propyne-derived species the MECP is high and the changes in the ISC rate due to methyl substitutions are driven by the variations of MECP heights.


Palm date fibers: analysis and enzymatic hydrolysis.
Waste palm dates were subjected to analysis for composition and enzymatic hydrolysis of their flesh fibers. The fruit contained 32% glucose and 30% fructose, while the water-insoluble fibers of its flesh consisted of 49.9% lignin and 20.9% polysaccharides. Water-insoluble fibers were settled to 55% of its initial volume in 12 h. The presence of skin and flesh colloidal fibers results in high viscosity and clogging problems during industrial processes. The settling velocity of the fibers was improved by enzymatic hydrolysis. Hydrolysis resulted in 84.3% conversion of the cellulosic part of the fibers as well as reducing the settling time to 10 minutes and the final settled volume to 4% of the initial volume. It implies easier separation of the fibers and facilitates fermentation processes in the corresponding industries. Two kinds of high- and low-lignin fibers were identified from the water-insoluble fibers. The high-lignin fibers (75% lignin) settled easily, while the low-lignin fibers (41.4% lignin) formed a slurry suspension which settled very slowly. The hydrophilicity of these low-lignin fibers is the major challenge of the industrial processes.


Effect of heart rate on the canine end-systolic pressure-volume relationship.
Although the rate dependence of isolated muscle contractility is well known, the ventricular end-systolic pressure-volume relationship (ESPVR) has been reported to be insensitive to heart rate. To resolve this contradiction, we used an isolated, ejecting canine heart preparation perfused at a constant coronary arterial pressure. Heart rate was changed from 60 to 200 beats/min in steps of 20 beats/min. At least 10 pressure-volume loops under different filling pressures were obtained at each heart rate in each of six hearts. Over a heart rate range from 60 to 120 beats/min, the slope of the ESPVR (Ees) increased significantly from 3.5 +/- 0.4 (SE) to 5.3 +/- 0.6 mm Hg/ml. In the range between 120 and 180 beats/min there was little change in Ees (5.3 +/- 0.6 to 5.4 +/- 0.6 mm Hg/ml), but at 200 beats/min Ees increased slightly to 5.7 +/- 0.5 mm Hg/ml. The volume axis intercept (V0) of the ESPVR changed little over the range of heart rate from 60 to 160 beats/min (10.2 +/- 2 ml to 9.4 +/- 1.3 ml) but increased to 15.2 +/- 1.2 ml at a rate of 200 beats/min. The change in ESPVR with increase in heart rate from 60 to 120 beats/min (i.e., increase in Ees without change in V0) is the same as those seen with a positive inotropic intervention with calcium or cathecholamines, whereas the V0 changes over the range from 160 to 200 beats/min is similar to those seen with regional ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Ceramide induces a loss in cytosolic peroxide levels in mononuclear cells.
Ceramide (a sphingolipid) and reactive oxygen species are each partly responsible for intracellular signal transduction in response to a variety of agents. It has been reported that ceramide and reactive oxygen species are intimately linked and show reciprocal regulation [Liu, Andreieu-Abadie, Levade, Zhang, Obeid and Hannun (1998) J. Biol. Chem. 273, 11313-11320]. Utilizing synthetic, short-chain ceramide to mimic the cellular responses to fluctuations in natural endogenous ceramide formation or using stimulation of CD95 to induce ceramide formation, we found that the principal redox-altering property of ceramide is to lower the [peroxide](cyt) (cytosolic peroxide concentration). Apoptosis of Jurkat T-cells, primary resting and phytohaemagglutinin-activated human peripheral blood T-lymphocytes was preceded by a loss in [peroxide](cyt), as measured by the peroxide-sensitive probe 2',7'-dichlorofluorescein diacetate (also reflected in a lower rate of superoxide dismutase-inhibitable cytochrome c reduction), and this was not associated with a loss of membrane integrity. Where growth arrest of U937 monocytes was observed without a loss of membrane integrity, the decrease in [peroxide](cyt) was of a lower magnitude when compared with that preceding the onset of apoptosis in T-cells. Furthermore, decreasing the cytosolic peroxide level in U937 monocytes before the application of synthetic ceramide by pretreatment with either of the antioxidants N -acetyl cysteine or glutathione conferred apoptosis. However, N -acetyl cysteine or glutathione did not affect the kinetics or magnitude of ceramide-induced apoptosis of Jurkat T-cells. Therefore the primary redox effect of cellular ceramide accumulation is to lower the [peroxide](cyt) of both primary and immortalized cells, the magnitude of which dictates the cellular response.


Gastric carcinoma in the Kenyan African population.
Fifty three consecutive patients with histological evidence of gastric carcinoma were studied between June 1987 and June 1989 at Kenyatta National Hospital (KNH). The male to female ration was 3.4:1 and the peak age of occurrence was in the 7th decade with 62.3% of gastric carcinoma being at the gastric antrum. Poorly differentiated adenocarcinoma was found in 68.2% of patients while well differentiated adenocarcinoma in 4.5% of cases. Intestinal metaplasia was a rare finding. If Lauren's classification of gastric carcinoma is considered then diffuse type of gastric cancer is by far the commoner type in our environment.


Efficacy of a needling device for the treatment of acne scars: a randomized clinical trial.
Neocollagenesis can be achieved using a dermal rolling needle device, thereby reducing the appearance of acne scars. To determine the efficacy of a needling device for treatment of acne scars. We performed a single-center, rater-blinded, balanced (1:1), split-face, placebo-controlled, parallel-group randomized clinical trial at an urban academic institution. The study took place from November 30, 2009, through July 27, 2010. Twenty healthy adults (age range, 20-65 years) with acne scars on both sides of the face were enrolled. Fifteen individuals completed the study, and no enrolled participants were withdrawn for adverse effects. For each participant, one side of the face was randomized for needling. Three needling treatments were performed at 2-week intervals. Two blinded dermatologists separately rated participants' acne scars based on standard digital photographs obtained at baseline and at the 3-month and 6-month follow-up visits on the quantitative global scarring grading system. Mean scar scores were significantly lower in the treatment group compared with baseline at 6 months (mean difference, 3.4; 95% CI, 0.2-6.5; P = .03) and nominally but not significantly lower compared with baseline at 3 months (mean difference, 2.4; 95% CI, -0.01 to 4.8; P = .052). In the control group, mean scar scores did not vary significantly from baseline at 3 months (mean difference, 1.0; 95% CI, -1.4 to 3.4; P = .96) and at 6 months (mean difference, 0.4; 95% CI, -2.3 to 3.5; P > .99). The needling procedure was not particularly painful, with a mean pain rating of 1.08 of 10. Participants perceived a 41% mean improvement in overall scar appearance on the treated side. No adverse events were reported. After 3 needling treatments, there was improvement in the appearance of acne scars over time compared with the control group, with minimal pain reported. clinicaltrials.gov Identifier: NCT00974870.


Parasite phylogeographical congruence with salmon host evolutionarily significant units: implications for salmon conservation.
Comparative phylogeographical studies between parasites and their hosts or with biogeographical regions are useful to predict parasite dispersal potential over a broad geographical range. We used both microsatellite markers and mtDNA sequence data from a trematode parasite, Plagioporus shawi, to test for congruence across two evolutionarily significant unit (ESU) boundaries of its salmonid hosts (Oncorhynchus spp.). We find congruent patterns with the nuclear loci of P. shawi and the ESU boundaries of its salmonid hosts. This pattern indicates that broad-scale phylogeographical patterns of a parasite can be predicted by the biogeographical history of their hosts. Furthermore, this pattern provides independent support for these ESU boundaries as biologically relevant barriers. The mtDNA shows some discordance with nuclear loci and a level of genetic differentiation greater than can be explained by genetic drift. Thus, the mtDNA cannot be used in isolation to infer the population history of P. shawi. The genetic differentiation at both the nuclear and mtDNA markers will be useful for salmon fisheries management by providing a tool to assign ocean-migrating salmonids back to their freshwater population of origin.


Orchidopexy san ligation technique of orchidopexy.
Pediatric hernia surgery is the most common operation done by pediatric general surgeons and it is a core competency for general surgeons in the developing world. Herniotomy is performed for the surgical repair of hernia and along with orchiopexy for the closure of associated patent processus vaginalis. Traditionally, ligation of hernial sac during orchiopexy is considered mandatory to prevent postoperative development of hernia. The present report was designed to study the results of non-ligation of the hernial sac during orchiopexy. It was found that non-ligation has no untoward effect on early complications and recurrence rate on long-term follow-up. It is suggested that it is not necessary to ligate the hernial sac during orchiopexy in children.


Respective interest of T2 mapping and diffusion tensor imaging in assessing porcine knee cartilage with MR at 3 Teslas.
Non-invasive quantitative assessment of articular cartilage integrity is essential for early detection and evaluation of osteoarthritis (OA) and for the follow-up of stem-cell-driven cartilage engineering. In this study, we investigated the feasibility of exploiting diffusion tensor imaging (DTI) on porcine knee joints with a clinical magnetic resonance (MR) scanner to extract micro-structural information in order to complement biochemical information quantified by T2 maps. We propose an MR protocol for quantifying T2 and cartilage microstructure with diffusion MR on a clinical scanner. Preliminary results were obtained on four pig knee joints using a 3 T GE clinical MRI scanner and an 8-channel knee coil array. The measured cartilage volume, T2 values, apparent diffusion coefficient and fractional anisotropy (FA) of femoral and tibial cartilage were respectively 9.8/2.3 mm2, 67.0/56.1 ms, 1.3/1.3×10-3 mm2/s and 0.4/0.3. This new protocol has the potential to be combined in vivo with quantitative assessment of both cartilage degradation and restoration in osteoarthritis.


A phase II study of weekly docetaxel in combination with capecitabine in advanced gastric and gastroesophageal adenocarcinomas.
Docetaxel and capecitabine are active agents in advanced gastric and gastroesophageal (GE) carcinomas. This multi-institutional phase II trial evaluates the combination of docetaxel and capecitabine as first- or second-line treatment in patients with advanced gastric and GE adenocarcinomas. Patients who had received 1 or no prior chemotherapy regimens were eligible. The chemotherapy regimen consisted of a 21-day cycle with docetaxel 30 mg/m(2) administered on days 1 and 8 and capecitabine 825 mg/m(2) administered twice daily on days 1-14. The primary end point of the study was overall survival (OS). Forty patients were enrolled in the study; 39 received treatment and were evaluable for response and toxicity. The median patient age was 61 years (range 21-84); 8 patients had received prior chemotherapy in the advanced or metastatic setting. Grade 3/4 adverse events occurred in 15 patients (38%), including diarrhea in 5 patients (13%) and hand-foot syndrome in 5 patients (13%). The overall response rate was 32% [95% confidence interval (CI) 16.7-51.4]. The median time to progression and OS were 3.4 months (95% CI 2.7-5.8) and 10.7 months (95% CI 6.1-12.1), respectively. The regimen of docetaxel and capecitabine is a well-tolerated, easily administered and active outpatient regimen for advanced gastric and GE adenocarcinoma.


On-call hospital pharmacy services in NHS England: service provision and documentation of medicines advice calls.
UK hospital pharmacy services have historically been delivered during typical 'office' hours, which include the provision of medicines advice via the pharmacy's medicines information department. Outside office hours, an on-call service operates whereby pharmacists handle requests for medicine supply and advice. It is not known how this out-of-hours service operates. The aim of this study was to quantify the extent and scope of its provision across England. A piloted self-administered survey was sent to every chief pharmacist in England representing acute hospitals and mental health trusts (n=218). Just over half (n=116/218, 53.2%) of chief pharmacists returned a completed survey. Most hospitals provided an on-call pharmacy service (87.1%, n=101/116). Nearly all on-call pharmacy services (91.1%, n=92/101) provided both supply of medication and medicines advice. Two-thirds (66.2%) of pharmacists who provided on-call services were junior. The majority of trusts (83.1%, n=74/89) receive <20 calls for medicines advice per week. Hospital nurses/midwives were seen as the most common users of the on-call pharmacy service. Medicines advice was documented by on-call pharmacists all (49.5%, n=47/95) or some of the time (49.5%, n=47/95). Just under half of trusts (41.1%, n=39/95) had a standard policy for the documentation of medicines advice. Two-thirds (66.7%, n=62/93) of respondents stated that advice was documented using paper-based forms. Most trusts (81.1%, n=77/95) provided training prior to pharmacists being on-call, with medicines information pharmacists involved in nearly 80% of cases (n=61/77) (respondents could select more than one option). Medicines advice is an integral part of the pharmacy on-call service, which was provided by junior staff. Variability existed in resourcing the service across trusts. In addition to existing standards for documentation of medicines advice, professional standards should be developed for on-call hospital pharmacy service provision and training.


[Cancer chemotherapy in combination with angiotensin-induced hypertension].
It was observed experimentally that rise of the mean arterial blood pressure to about mmHg by angiotensin II resulted in a marked increase in blood flow in tumor tissue without increasing blood flow in normal tissue, such as the liver, brain, bone marrow and subcutis. This result clearly indicated the lack of autoregulation of blood flow in tumor tissue. Considering the physiological characteristics of microcirculation in tumor, it is possible to selectively increase tumor blood flow without affecting blood flow in normal tissues. This finding could be applied to cancer chemotherapy for enhancing drug delivery to tumor tissue selectively. Thus, based on these experimental results, clinical studies have been performed in 86 patients with various advanced cancers. Among 72 evaluable patients, there are 8 complete and 26 partial responders with an overall response rate of 47.2%. Nine of 19 patients with gastric cancer responded to the therapy. The clinical procedure and apparatus using in this treatment were described together with technical precaution.


A new anchialine Stephos Scott from the Yucatan Peninsula with notes on the biogeography and diversity of the genus (Copepoda, Calanoida, Stephidae).
Surveys of the anchialine crustacean fauna of the Yucatan Peninsula (YP), Mexico, have revealed the occurrence of calanoid copepods. The genus Stephos Scott, 1892, belonging to the family Stephidae is among the most frequent and widely distributed groups in anchialine caves but has not been hitherto recorded from the YP. Recent collections from an anchialine cave in an island off the northern coast of the YP yielded many specimens of a new species of Stephos. The new taxon, S. fernandoisp. n., is described here based on male and female specimens. The new species is clearly distinguished from its congeners by the following characters: male left fifth leg with three terminal lamellae plus subdistal process, right leg with distal row of peg-like elements; female fifth leg with single long, acute apical process; genital double-somite with two rows each of 4 long spinules adjacent to operculum; legs 2-4 with articulated setae. The diversity of the genus shows regional differences; the Australia-Western Pacific region is the most diverse (eleven species), followed by the Mediterranean (seven species) and the Northeastern Atlantic (six species); only four species are known from the Northwestern Tropical Atlantic (NWTA). The morphology of the female fifth leg was examined to explore possible biogeographic trends in the genus; patterns suggest multiple colonization events in the highly diverse regions and a relatively recent radiation in the NWTA, characterized by anchialine forms. The introduction of stephid copepods in the region may be a relatively recent event derived from colonization of benthopelagic ancestral forms and subsequent invasion onto cave habitats. The new species appears to be linked to the strictly anchialine Miostephos.


What Can You See? Identifying Cues on Internal States From the Movements of Natural Social Interactions.
In recent years, the field of Human-Robot Interaction (HRI) has seen an increasing demand for technologies that can recognize and adapt to human behaviors and internal states (e.g., emotions and intentions). Psychological research suggests that human movements are important for inferring internal states. There is, however, a need to better understand what kind of information can be extracted from movement data, particularly in unconstrained, natural interactions. The present study examines which internal states and social constructs humans identify from movement in naturalistic social interactions. Participants either viewed clips of the full scene or processed versions of it displaying 2D positional data. Then, they were asked to fill out questionnaires assessing their social perception of the viewed material. We analyzed whether the full scene clips were more informative than the 2D positional data clips. First, we calculated the inter-rater agreement between participants in both conditions. Then, we employed machine learning classifiers to predict the internal states of the individuals in the videos based on the ratings obtained. Although we found a higher inter-rater agreement for full scenes compared to positional data, the level of agreement in the latter case was still above chance, thus demonstrating that the internal states and social constructs under study were identifiable in both conditions. A factor analysis run on participants' responses showed that participants identified the constructs interaction imbalance, interaction valence and engagement regardless of video condition. The machine learning classifiers achieved a similar performance in both conditions, again supporting the idea that movement alone carries relevant information. Overall, our results suggest it is reasonable to expect a machine learning algorithm, and consequently a robot, to successfully decode and classify a range of internal states and social constructs using low-dimensional data (such as the movements and poses of observed individuals) as input.


Viscous, resistive magnetohydrodynamic stability computed by spectral techniques.
Expansions in Chebyshev polynomials are used to study the linear stability of one-dimensional magnetohydrodynamic quasiequilibria, in the presence of finite resistivity and viscosity. The method is modeled on the one used by Orszag in accurate computation of solutions of the Orr-Sommerfeld equation. Two Reynolds-like numbers involving Alfvén speeds, length scales, kinematic viscosity, and magnetic diffusivity govern the stability boundaries, which are determined by the geometric mean of the two Reynolds-like numbers. Marginal stability curves, growth rates versus Reynolds-like numbers, and growth rates versus parallel wave numbers are exhibited. A numerical result that appears general is that instability has been found to be associated with inflection points in the current profile, though no general analytical proof has emerged. It is possible that nonlinear subcritical three-dimensional instabilities may exist, similar to those in Poiseuille and Couette flow.


The roentgenographic staging of sarcoidosis. Historic and contemporary perspectives.
The awareness that sarcoidosis can involve intrathoracic lymph nodes and lung parenchyma in sequential fashion evolved during the first half of this century. This awareness resulted in a roentgenographic staging system that has relevance to the course and prognosis, pulmonary function changes, and the symptom of dyspnea. The following definition or roentgenographic staging is proposed as the simplest, most reproducible system based solely on the roentgenographic appearance, avoiding histopathologic and pathophysiologic inferences. Stage I: bilateral hilar lymphadenopathy; stage II: bilateral hilar lymphadenopathy plus parenchymal infiltration; and stage III: parenchymal infiltration without bilateral hilar lymphadenopathy. The early data concerning bronchoalveolar lavage, determination of serum angiotensin-converting enzyme, and gallium 67 citrate scanning appear to have no clear relationships to staging, suggesting that staging continues to have unique value to the clinician in the classification of sarcoidosis and in the delineation of its clinical course and prognosis.


Auditory to Visual Cross-Modal Adaptation for Emotion: Psychophysical and Neural Correlates.
Adaptation is fundamental in sensory processing and has been studied extensively within the same sensory modality. However, little is known about adaptation across sensory modalities, especially in the context of high-level processing, such as the perception of emotion. Previous studies have shown that prolonged exposure to a face exhibiting one emotion, such as happiness, leads to contrastive biases in the perception of subsequently presented faces toward the opposite emotion, such as sadness. Such work has shown the importance of adaptation in calibrating face perception based on prior visual exposure. In the present study, we showed for the first time that emotion-laden sounds, like laughter, adapt the visual perception of emotional faces, that is, subjects more frequently perceived faces as sad after listening to a happy sound. Furthermore, via electroencephalography recordings and event-related potential analysis, we showed that there was a neural correlate underlying the perceptual bias: There was an attenuated response occurring at ∼ 400 ms to happy test faces and a quickened response to sad test faces, after exposure to a happy sound. Our results provide the first direct evidence for a behavioral cross-modal adaptation effect on the perception of facial emotion, and its neural correlate.


Assessing the ecological impacts of polycyclic aromatic hydrocarbons petroleum pollutants using a network toxicity model.
Polycyclic aromatic hydrocarbons (PAHs) are significant petroleum pollutants that have long-term impacts on human health and ecosystems. However, assessing their toxicity presents challenges due to factors such as cost, time, and the need for comprehensive multi-component analysis methods. In this study, we utilized network toxicity models, enrichment analysis, and molecular docking to analyze the toxicity mechanisms of PAHs at different levels: compounds, target genes, pathways, and species. Additionally, we used the maximum acceptable concentration (MAC) value and risk quotient (RQ) as an indicator for the potential ecological risk assessment of PAHs. The results showed that higher molecular weight PAHs had increased lipophilicity and higher toxicity. Benzo[a]pyrene and Fluoranthene were identified as core compounds, which increased the risk of cancer by affecting core target genes such as CCND1 in the human body, thereby influencing signal transduction and the immune system. In terms of biological species, PAHs had a greater toxic impact on aquatic organisms compared to terrestrial organisms. High molecular weight PAHs had lower effective concentrations on biological species, and the ecological risk was higher in the Yellow River Delta region. This research highlights the potential application of network toxicity models in understanding the toxicity mechanisms and species toxicity of PAHs and provides valuable insights for monitoring, prevention, and ecological risk assessment of these pollutants.


Small molecule signaling, regulation, and potential applications in cellular therapeutics.
Small molecules have many important roles across the tree of life: they regulate processes from metabolism to transcription, they enable signaling within and between species, and they serve as the biochemical building blocks for cells. They also represent valuable phenotypic endpoints that are promising for use as biomarkers of disease states. In the context of engineering cell-based therapeutics, they hold particularly great promise for enabling finer control over the therapeutic cells and allowing them to be responsive to extracellular cues. The natural signaling and regulatory functions of small molecules can be harnessed and rewired to control cell activity and delivery of therapeutic payloads, potentially increasing efficacy while decreasing toxicity. To that end, this review considers small molecule-mediated regulation and signaling in bacteria. We first discuss some of the most prominent applications and aspirations for responsive cell-based therapeutics. We then describe the transport, signaling, and regulation associated with three classes of molecules that may be exploited in the engineering of therapeutic bacteria: amino acids, fatty acids, and quorum-sensing signaling molecules. We also present examples of existing engineering efforts to generate cells that sense and respond to levels of different small molecules. Finally, we discuss future directions for how small molecule-mediated regulation could be harnessed for therapeutic applications, as well as some critical considerations for the ultimate success of such endeavors. WIREs Syst Biol Med 2018, 10:e1405. doi: 10.1002/wsbm.1405 This article is categorized under: Biological Mechanisms > Cell Signaling Biological Mechanisms > Metabolism Translational, Genomic, and Systems Medicine > Therapeutic Methods.


Cardiovascular autonomic dysfunction in multiple sclerosis: correlation with orthostatic intolerance.
Autonomic dysfunction is frequently observed in patients with multiple sclerosis (MS), but clinical studies disagree on the frequency and type of abnormalities in autonomic function tests. Orthostatic dizziness (OD) has been reported in up to 49% of patients, but the pathophysiological mechanisms are poorly understood. This study investigated cardiovascular reflex tests and their association with OD in patients with MS in order to examine the hypothesis that the sympathetic nervous system is specifically involved in these patients. Forty patients with clinically active relapsing-remitting (n = 27) and secondary progressive MS (n = 13), aged 35.0+/-8.5 years, were studied by parasympathetic (heart rate responses to the Valsalva maneuver, deep breathing, and active change in posture) and sympathetic function tests (blood pressure responses to active change in posture and sustained handgrip), and by spectral analysis of heart rate variability during rest and during standing. Results were compared to those obtained in 24 healthy volunteers, aged 29.4+/-7.2 years. A standardized questionnaire was used to evaluate symptoms of orthostatic intolerance. Abnormal responses on at least one cardiovascular reflex test were observed in 40% of MS patients, compared to 17% of the control group, with a statistically significant involvement of the sympathetic vasomotor system. Orthostatic intolerance was reported in 50% of patients (controls: 14%, P<0.006). Subgroup comparison of patients with and without OD suggests that orthostatic intolerance results from impaired sympathetic vasoconstriction. These results provide further evidence that the sympathetic nervous system is involved in patients with MS.


[Influence of a diet enriched with polyunsaturated fatty acids on some indices of the metabolism and course of acute gastro-intestinal diseases in children in the 1st year of life].
The influence of new products "Vitalakt" and "Malysh", enriched with polyunsaturated fatty acids, on the evolution of acute gastro-intestinal diseases and the lipids metabolism characteristics (total lipids, cholesterol and its ethers, phospholipids, nonetherified fatty acids in the blood serum), as well as on blood serum, protein fractions was studied. A total of 137 children were examined and the diet of 87 of them included the new dairy products "Vitalakt" and Malysh". These new dairy mixtures have been found to exert a beneficial effect on the course of the disease, tended to normalize the blood serum lipids characteristics and to reduce dysproteinemia. All this warrants recommending the mixtures "Vitalakt" and "Malysh" to be included in the diet of infants in the first year of life, suffering from acute gastro-intestinal diseases.


High Inequality and Slow Services Improvement in Newborn and Child Health Interventions in Ethiopia.
In the previous years, efforts have been made to reduce the inequality gap in newborn and child health interventions in Ethiopia. However, there is still limited evidence on the extent and trends of inequality on newborn and child health interventions. Thus, we aimed to assess newborn and child health interventions, inequality levels, and trends during four demographic and health survey periods based on inequality dimensions: economic status, education level, residency, and child's sex in Ethiopia. We conducted an inequality analysis on four periods (2000, 2005, 2011, and 2016) of the Ethiopian Demographic and Health Survey (EDHS) data. We estimated inequality related to economic and education status using percentage, relative concentration index, and slope index, while mean percentage difference and ratio were used to assess inequality due to residency and child's sex. The coverage of services was concentrated in the richest quintile, highly educated families, and urban dwellers. Child and newborn health intervention service coverage improvement in the past four survey periods was less than 10.0% for all services, and there is high disparity between sub-national regions. Full immunization-related inequality was highest in Ethiopia compared to four east-central African countries. Increasing service coverage and improving equitable access to routine immunizations could fill the existing inequality gap while focusing on the underserved group. In addition, strengthening regular monitoring processes is also vital to know those left behind.


Learning to be patient-centred healthcare professionals: how does it happen at university and on clinical placements? A multiple focus group study.
This article was migrated. The article was marked as recommended. Background: Developing patient-centred skills in health professional students relies on their learning experiences at the university and on clinical placements. It is not known what students perceive about their teaching on patient-centredness and their views to develop the curriculum in this aspect. Methods: Multiple focus groups were conducted with students who had experienced a minimum of two clinical placements from Medicine, Physiotherapy, Nursing and Speech and language therapy programs. Thematic analysis was conducted independently by two researchers and then themes were compared and integrated. Findings: Five focus groups with 26 participants with a mean age of 23.8 years contributed to 286 minutes of recorded data. The key findings were that their curriculum focussing on patient-centred skills used artificial methods and teaching focussed largely on biomedical aspects, but, shared modules and specialist training enabled learning. Longer and diverse placements with good role models to emulate, enabled learning. As strategies they suggested reflections and role-modelling were vital along with further interprofessional working, goal-setting and understanding of human psychology. Conclusion: Though the study is limited by its generalisability, strategies suggested by students can be further developed by superimposing them on learning theories. These strategies need to be tested in future studies.


Antidepressant effects of different schedules of repetitive transcranial magnetic stimulation vs. clomipramine in patients with major depression: relationship to changes in cortical excitability.
The antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) that have been demonstrated in recent studies could be related to its ability to modulate cortical excitability. Yet, the relationship between stimulus location and frequency and treatment outcome has not been established. The aim of the present study was to compare efficacy of rTMS in various configurations and clomipramine treatment in patients with major depression (MD) and to evaluate the relationship between clinical outcome and changes in cortical excitability. Fifty-nine MD patients were randomized to receive (1) left (n = 12) or right (n = 12) 3 Hz rTMS with placebo medication; (2) left (n = 10) or right (n = 9) 10 Hz rTMS with placebo medication; (3) active medication (clomipramine) with sham rTMS (n = 16). Both 3 Hz and 10 Hz rTMS were administered to the prefrontal cortex by a circular coil at an intensity of 110% and 100% of the resting motor threshold (rMT) respectively. Measurements of cortical excitability were performed prior to and 24 h after completion of 2 wk of daily rTMS or pharmacological treatments. These included the rMT, silent period threshold (SPT), inter-threshold difference (ITD), MEP/M-wave amplitude ratio and silent period duration (SPD). Severity of depression was blindly assessed by the Hamilton Depression Rating Scale (HDRS). The best improvement scores were seen in patients who received left 3 Hz rTMS. The 10 Hz rTMS treatment was less tolerated resulting in a significantly higher dropout rate. A significant increase of the MEP/M wave amplitude ratio accompanied by a shortening of the SPD was evidenced in patients who showed marked clinical improvement (reduction in HDRS by 50% or more) following left rTMS regardless of stimulation frequency. Our results suggest that 3 Hz left rTMS has a higher therapeutic efficacy and tolerability in patients with MD. The enhancement of cortical excitability may be related to the antidepressant action of rTMS.


Biological Properties and Health-Promoting Functions of Laminarin: A Comprehensive Review of Preclinical and Clinical Studies.
Marine algal species comprise of a large portion of polysaccharides which have shown multifunctional properties and health benefits for treating and preventing human diseases. Laminarin, or β-glucan, a storage polysaccharide from brown algae, has been reported to have potential pharmacological properties such as antioxidant, anti-tumor, anti-coagulant, anticancer, immunomodulatory, anti-obesity, anti-diabetic, anti-inflammatory, wound healing, and neuroprotective potential. It has been widely investigated as a functional material in biomedical applications as it is biodegradable, biocompatible, and is low toxic substances. The reported preclinical and clinical studies demonstrate the potential of laminarin as natural alternative agents in biomedical and industrial applications such as nutraceuticals, pharmaceuticals, functional food, drug development/delivery, and cosmeceuticals. This review summarizes the biological activities of laminarin, including mechanisms of action, impacts on human health, and reported health benefits. Additionally, this review also provides an overview of recent advances and identifies gaps and opportunities for further research in this field. It further emphasizes the molecular characteristics and biological activities of laminarin in both preclinical and clinical settings for the prevention of the diseases and as potential therapeutic interventions.


Protective effects of casein-derived peptide VLPVPQK against hydrogen peroxide-induced dysfunction and cellular oxidative damage in rat osteoblastic cells.
Oxidative stress inhibits osteoblast differentiation and function that lead to the development of osteoporosis. Casein-derived peptide VLPVPQK (PEP), a potent antioxidant, was isolated from β-casein of buffalo milk. We used an in vitro oxidative stress model induced by hydrogen peroxide (H2O2) in rat osteoblastic cells to investigate the protective effects of PEP against H2O2-induced dysfunction and oxidative damage. Cells were pretreated with PEP (50-200 ng/mL) for 2, 7 or 21 days followed by 0.3 mM H2O2 treatment for 24 h and then markers of osteogenic development, oxidative damage and apoptosis were examined. PEP significantly increased the viability and differentiation markers of osteoblast cells such as alkaline phosphatase and calcium mineralization. Moreover, PEP suppressed the production of reactive oxygen species (ROS), lipid peroxidation and ameliorated H2O2-induced reduction in glutathione, superoxide dismutase and catalase activities. In addition, PEP partially inhibited caspase-9 and-3 activities and reduced propidium iodide-positive cells. Altogether, our results demonstrated that PEP could protect rat osteoblast against H2O2-induced dysfunction and oxidative damage by reduction of ROS production, lipid peroxidation and increased antioxidant enzyme activities. Thus, our data suggest that PEP might be a valuable protective agent against oxidative stress-related diseases such as osteoporosis.


Rates and Risk Factors for Interval Gastric Cancers at Screening Gastroscopy.
Interval gastric cancers (GCs) can be encountered during screening gastroscopy. This study investigated the rate of interval GCs and their risk factors. We retrospectively investigated subjects who underwent screening gastroscopy from 2005 to 2017 in a university hospital and were diagnosed with GC. Subjects were grouped based on their endoscopic images and descriptive results into interval GC and initially diagnosed GC groups. Interval GCs were defined when endoscopic results within the previous 3 years were negative for GC. The clinico-pathological characteristics of the groups and risk factors for interval GCs were evaluated. Of 54 724 subjects who underwent screening gastroscopy, 234 were diagnosed with GC, of which 43 were interval GCs. The rate of interval GCs was 18.4% (43/234, mean age 61.6 years). Interval GCs were smaller than initially diagnosed GCs (1.6 vs 1.9 cm, P = .011). They were located in the low-to-mid-body in 44.2%, antrum in 48.8%, and high body and cardia in 7%. Their observation time was shorter (248.74 vs 410.64 sec, P = .032). In multivariate analysis, they were associated with short observation time (odds ratio [OR] 0.99, 95% CI 0.994-0.998, P < .001) and location in the low-to-mid-body (OR 2.12, 95% CI 1.071-4.181, P = .031), although differentiation, ulcerated type, metaplasia, Helicobacter pylori infection, and endoscopists' experience were not associated with interval GCs. The rate of interval GCs was significant during screening gastroscopy. They might be reduced by increasing observation time, focusing on smaller lesions, and observing the low-to-mid-body of the stomach more carefully.