Comparison of the pharmacokinetics of paracetamol from two generic products in patients after total gastric resection.
Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect drug absorption and pharmacokinetic parameters (PK). The need to apply orally administered analgesics in this group of patients is often related with alternative application of currently available generic products. Thus, from the clinical point of view it is necessary to evaluate the PK of these drugs to confirm their equivalence. The aim of the study was therefore an analysis of the pharmacokinetics of paracetamol from two generic products in patients after total gastric resection. The research was carried out on two groups of patients after gastrectomy with Roux-en-Y reconstruction (n = 30; mean [SD] age, 63.0 [11.5] years; weight, 67.6 [13.7] kg; and height, 166.4 [9.1] cm). The patients received paracetamol in a single orally administered dose of 1,000 mg. Blood samples were collected within 6 h of drug administration. The concentration of paracetamol and paracetamol glucuronide in the blood plasma was marked by means of a validated high-pressure liquid chromatography with ultraviolet detection (HPLC-UV). The main PK for paracetamol in group 1 (n = 17) and 2 (n = 13) were as follows: C(max), 9.46 (3.66) and 12.79 (5.32) μg/ml, respectively (p = 0.0517); AUMC(0-t), 77.64 (30.37) and 51.01 (15.76) μg h(2)/ml (p = 0.0046); AUC(0-inf), 41.61 (23.52) and 30.28 (9.74) μg h/ml (p = 0.0862); t(max), 1.68 (0.63) and 0.50 (0.25) h (p < 0001). The obtained C(max) and AUC values in patients after gastrectomy were reduced in comparison with healthy subjects. Total gastrectomy therefore affected the pharmacokinetics of paracetamol administered in tablets. In our patients, we also observed significant differences between the PK of paracetamol and two generic preparations. These two drugs can thus be used interchangeably, but with caution.


Hirayama disease: Is surgery an option?
Hirayama disease is a rare cervical myelopathy, predominantly affecting young males, which presents with distal atrophy of the upper limbs as its first and main symptom. It must be differentiated from motor neuron diseases because its natural history is different and because HD tends to stabilise in less than 5 years. Diagnosis is based on clinical findings and dynamic flexion MRI showing segmental spinal muscular atrophy, detachment of the posterior dura mater and venous congestion in the epidural space. The tendency is to indicate conservative treatment and no indications for surgery have been established. We present 4 cases meeting both clinical criteria and dynamic MRI imaging criteria for a diagnosis of Hirayama disease. Two have stabilised spontaneously over the course of many years, and MRI scans show that typical changes have disappeared. Another case also remains stable following a shorter observation time. The fourth case is a young man who developed severe myelopathy in just over a year, and therefore underwent surgery. While his follow-up time is still short, his condition remains stable. Our 4 cases suggest that the condition of most patients with Hirayama stabilises naturally; patients should be evaluated for surgery on an individual basis, and surgery should probably be limited to the most severe cases that have progressed quickly.


Bounded Confidence and Cohesion-Moderated Pressure: A General Model for the Large-Scale Dynamics of Ordered Opinion.
Due to the development of social media, the mechanisms underlying consensus and chaos in opinion dynamics have become open questions and have been extensively researched in disciplines such as sociology, statistical physics, and nonlinear mathematics. In this regard, our paper establishes a general model of opinion evolution based on micro-mechanisms such as bounded confidence, out-group pressure, and in-group cohesion. Several core conclusions are derived through theorems and simulation results in the model: (1) assimilation and high reachability in social networks lead to global consensus; (2) assimilation and low reachability result in local consensus; (3) exclusion and high reachability cause chaos; and (4) a strong "cocoon room effect" can sustain the existence of local consensus. These conclusions collectively form the "ideal synchronization theory", which also includes findings related to convergence rates, consensus bifurcation, and other exploratory conclusions. Additionally, to address questions about consensus and chaos, we develop a series of mathematical and statistical methods, including the "energy decrease method", the "cross-d search method", and the statistical test method for the dynamical models, contributing to a broader understanding of stochastic dynamics.


Synthesis and turnover of 3H-5-hydroxytryptamine in the later cerebroventricle.
The lateral cerebroventricle was perfused using two different labelling procedures in three separate experiments on 5-hydroxytryptamine metabolism. The sensitivity of 5-hydroxytryptamine metabolism to various drugs was subsequently determined. The results demonstrate that two serotonin reuptake blockers, imipramine and fluoxetine, increase the efflux of 3h-5-hydroxytryptamine into the ventricle without affecting the efflux of 3H-5-hydroxyindoleacetic acid. BL-3912 A, a drug with weak serotonin agonist activity, also increased the efflux of 3H-5-hydroxytryptamine into the ventricle.


Radiofrequency ablation versus magnetic resonance guided focused ultrasound surgery for minimally invasive treatment of osteoid osteoma: a propensity score matching study.
To compare outcomes in pain relief and motor functional recovery in patients with an osteoid osteoma treated by magnetic resonance guided focused ultrasound surgery (MRgFUS) or radiofrequency ablation (RFA) using a propensity score matching study design. Thirty patients with osteoid osteomas were included in this institutional review board (IRB)-approved study. MRgFUS was performed in 15 subjects. These subjects were matched by propensity analysis with a group of 15 subjects treated by RFA. Pain relief in terms of complete response (CR) and motor functional recovery were measured. A similar proportion of subjects treated by MRgFUS (94 %) or RFA (100 %) experienced CR 12 weeks after treatment, with no significant difference. The improvement in pain control following MRgFUS or RFA paralleled with improved motor functional recovery. The treatment failure rate was 6.6 % in the MRgFUS group and 0 % in the RFA group. No major complications were observed following either ablative treatment. Although this study involved a limited number of patients, MRgFUS favourably improves perceived pain and motor functional recovery, with no major complications. No difference was found in the achievement of primary and secondary outcome measures with respect to RFA. • To demonstrate the effectiveness of a recent technique for treating osteoid osteoma • MRgFUS results compared with results of the gold standard treatment (RFA) • MRgFUS is effective both from a clinical and functional point of view • No significant side effects compared with RFA.


Regulation of kynurenic acid levels in the developing rat brain.
Several brain-specific mechanisms control the formation of the endogenous excitatory amino acid receptor antagonist kynurenic acid (KYNA) in the adult rat brain. Two of these, dopaminergic neurotransmission and cellular energy metabolism, were examined in the brain of immature (postnatal day 7) rats. The results indicate that during the early postnatal period cerebral KYNA synthesis is exceptionally amenable to modulation by dopaminergic mechanisms but rather insensitive to fluctuations in cellular energy status. These findings may be of relevance for the role of KYNA in the function and dysfunction of the developing brain.


Clinical and histological findings in nephrogenic systemic fibrosis.
Nephrogenic systemic fibrosis (NSF) is a relative newcomer to the world of medicine. NSF was introduced just over 10 years ago as nephrogenic fibrosing dermopathy, but with further investigation, its systemic nature was determined. The strict adherence to a definition requiring both clinical and pathological concordance has allowed for careful separation of this entity from other fibrosing disorders, leading eventually to the realization that gadolinium-based contrast agents were closely associated with its onset. As planned prospective studies get underway, it is of paramount importance that researchers and clinicians realize that NSF remains a very challenging diagnosis, and that both clinical and histopathological criteria must be employed to reach the most accurate diagnosis possible.


[Skiing and snowboarding trauma in children: epidemiology, physiopathology, prevention and main injuries].
Skiing and snowboarding are leading to a risk of injuries in children. Beginners and experienced have higher risk of injuries, however, the first have less severe injuries than the latest. Risk factors of injury are: ability and experience, binding adjustment, slope characteristics, speed, collisions with objects or jumping and risky behavior of the young skiers and snowboarders. Lower limb injuries are most common in skier, especially knee sprains, conversely snowboarders present more upper limb injuries, especially wrist fractures. The frequency of head injuries does not decrease while helmet use increases but severity decreases. Despite prevention and wearing protections, the frequency of trauma does not decrease significantly, which could be in relation with higher speed and increased risky behavior. Main prevention factors are safety knowledge and safety behavior, correct binding adjustment, and use of protections.


Paediatric bilateral adrenal phaeochromocytomas in association with a novel mutation in the von Hippel Lindau gene.
Functional phaeochromocytoma and paraganglioma are rare in children and adolescents. We report a 12-year-old male with bilateral phaeochromocytoma in whom germ line testing identified a novel mutation in the von Hippel Lindau gene. Early age of onset, bilateral phaeochromocytoma and other clinical features should prompt germ line DNA testing for mutations in genes associated with familial phaeochromocytoma and paraganglioma syndromes.


[Formation and release of antibodies in lymphocytes].
An immunohistochemical study proved that lymphocytes were the dominant cell type responsible for the production of antibodies during the local humoral immune response to human serum albumin in the mouse omentum. Ultrastructurally, specific antibodies were detected on ribosomes and polysomes linked to the perinuclear cisterna and placed in it, as well as on the free intracytoplasmic ribosomes and polysomes. In no case antibodies were found in other cell organelles involved in protein synthesis. Most probably the mechanismus of antibody release from lymphocytes are different from similar processes taking place in plasma cells.


Management of Stromal Lesions.
Breast stromal lesions include fibroadenomas, phyllodes tumors, pseudoangiomatous stromal hyperplasia, periductal stromal tumors, and lipomas. Most of these lesions are benign and can be managed with observation or surgical excision. Phyllodes tumors, however, are subcategorized into benign, borderline, and malignant. Benign phyllodes tumors may be removed without a margin of breast tissue while borderline and malignant phyllodes tumors need a wide excision with a greater than 1 cm margin. Because malignant phyllodes tumors have a poor prognosis, efforts should be made to discuss their treatment in a multidisciplinary setting and enrollment in a clinical trial should be considered.


The Impact of Uncertain Contact Location on Situation Awareness and Performance in Simulated Submarine Track Management.
The aim of these studies was to examine the extent to which uncertainty in contact location in submarine track management affected operator situation awareness (SA), workload, and performance and whether operator SA predicted unique variance in performance. We extend prior research by manipulating uncertainty in contact location and by including a sample of expert track managers in a submarine combat system. In Experiment 1, university students completed a track management task. In Experiment 2, expert submariners were embedded in a real submarine combat system. Uncertainty was manipulated and SA was measured using the situation present assessment method. Increased uncertainty led to higher student workload and moderately impaired SA and performance, and SA predicted incremental variance in performance. Uncertainty had no effect on expert SA or the accuracy of the tactical picture compiled. On average, experts took 20 s to accept SA queries (compared with 2.18 s for students). The time taken for experts to accept SA queries, but not their subsequent response to SA queries, was positively associated with their tactical picture accuracy. Uncertainty can negatively impact SA, workload, and performance. Some key findings from the laboratory were replicated using experts, but the fact that experts took on average 20 s to accept SA queries presents a challenge for using SPAM in submarine control rooms. Contact location is uncertain due to the use of passive sonar and hostile deception. It is essential to measure track manager SA in order to inform work design and training.


Combined DSA- and US-guided management of acute bleeding: effectiveness of percutaneous glue embolization in six cases.
This study aims to report on safety and effectiveness of glue embolization of acute hemorrhages performed by US-guided percutaneous direct puncture, in patients where the standard endovascular approach is technically unfavourable. In this single center retrospective analysis, patients affected by traumatic or non traumatic acute hemorrhages were treated with glue embolization technically performed by US-guided direct puncture. Patients suffered from active bleeding detected at contrast-enhanced Computer Tomography and confirmed at Digital Subtracted Arteriography, with concomitant hemoglobin drop and blood pressure reduction. Six patients were reviewed; hemorrhages occurred in liver parenchima (1), gallbladder (1) and lower limbs (4). Bleedings etiologies were post-traumatic (5) and inflammatory (1); four had extraluminal blushes while 2 were pseudoaneurysms. In five cases (4 limbs and 1 hepatic bleedings) the direct-puncture approach was adopted because of technically unfavourable vascular anatomy for superselective embolization; in one case (cystic artery pseudoaneurysm), an endovascular embolization would entail a high risk of gallbladder ischemia because of its terminal arterial supply. Technical success was defined disappearance of bleeding signs at last arteriography; clinical success was considered stabilization and/or improvement of hemoglobin values and arterial pressure without additional interventions. Both technical and clinical successes were obtained in 100% of the cases without major complications. No needle occlusion occurred during glue injection. In this study percutaneous US-guided embolization by direct puncture was a safe and effective approach to manage acute bleedings; it could be considered as an alternative in patients with unfavourable vascular anatomy for the standard catheter-directed endovascular embolization.


A gene-based approach for testing association of rare alleles.
Rare genetic variants have been shown to be important to the susceptibility of common human diseases. Methods for detecting association of rare genetic variants are drawing much attention. In this report, we applied a gene-based approach to the 200 simulated data sets of unrelated individuals. The test can detect the association of some genes with multiple rare variants.


Synthesis, structure and urease inhibition studies of Schiff base copper(II) complexes with planar four-coordinate copper(II) centers.
Seven new Schiff base copper(II) complexes with planar four-coordinate copper(II) centers have been synthesized and structurally characterized. The solid state structures of complexes 1, 3, 4, 5, 6 and 7 present a square-planar coordination geometry at the metal centers while complex 2 shows a slightly distorted square-planar geometry. Density functional theory calculations have been performed to evaluate the electronic structure of copper(II) complex 7. Inhibition of jack bean urease by copper(II) complexes 1-7 have also been investigated, and potent inhibitory activities with IC50 range of 2.60-17.00μM have been observed for these mononuclear copper(II) complexes. A docking analysis using a DOCK program was conducted to explain the urease inhibitory activity of the copper(II) complexes and the structure-activity relationships were further discussed.


'You can't turn back the clock': conceptualizing time after institutionalization.
ABSTRACTTime is a phenomenon that is often taken for granted. In gerontology, time is often equated with chronological or linear time, which thereby causes time to be defined as chronological age. With this paper, my purpose is to illuminate further understandings of time and how the passage of time is experienced in old age, particularly in the context of a move to a long-term care institution. Towards that end, I describe a case study of a gentleman coming to live in a long-term care facility. In this case study, time was perceived as an element outside day-to-day experience that structured daily life. Specific dimensions of temporality are evident, including biographical time, embodied time, and embedded time (including institutional time). These dimensions of time provide further understanding of the experiences of age and institutionalization.


Evidence of GnRH receptors in cultured pituitary cells of the winter flounder (Pseudopleuronectes americanus W.).
For continued studies of GnRH receptor regulation in the winter flounder, we have developed an in vitro system consisting of cultured pituitary cells dissociated by collagenase. Using immunocytochemical staining methods for gonadotropin, growth hormone, and prolactin, these cell types were represented at the levels of 25, 20, and 19.5% of total pituitary cell population, respectively. Receptors for GnRH were characterized in intact monolayered attached pituitary cells, maintained in RPMI culture medium. The cell GnRH receptor characteristics were compared with those previously described using pituitary homogenates. The cells were capable of binding GnRH in a similar manner on Day 2 or Day 3 of culture, indicating the integrity of GnRH receptors. The specificity of binding was demonstrated since only high doses of cold GnRHa competed with 125I-GnRHa uptake, different peptides being without effect. The specific binding is saturable and the data suggest the presence of a single class of high-affinity (apparent Ka = 1.50 x 10(9) M-1), high-capacity sites (binding capacity = 25.03 fmol/2.5 x 10(5) cells or 242.23 x 10(3) sites/gonadotroph) which is in accordance with the characteristics of GnRH receptors present in homogenates of pooled male and female pituitary glands. All these observations suggest that such an in vitro pituitary cell system would be appropriate for studying GnRH receptor characteristics under different physiological conditions.


Electrocardiographic findings and myocardial damage in acute myocarditis detected by cardiac magnetic resonance.
Delayed-contrast-enhancement (DCE) magnetic resonance imaging (MRI) can identify areas of myocardial damage in patients with acute myocarditis (AM). The aim of this study was to assess the electrocardiographic findings in AM diagnosed by DCE-MRI. Eighty-one patients (72 men, 35 ± 13 years) with AM were prospectively enrolled. All of them underwent MRI and 12-lead-ECG recordings. In the admission electrocardiogram (ECG 1), as well as in that obtained 48 h later (ECG 2), the following parameters were analyzed: rhythm, PR, QRS, and QTc-intervals, intraventricular conduction, abnormal Q waves, ST segment elevation, and T wave inversion. On admission, 77 patients (95%) were in sinus rhythm, while four patients (6%) manifested severe arrhythmias. No difference between ECG 1 and ECG 2 was observed regarding abnormal Q waves, PR, QRS, and QTc-intervals. Electrocardiogram 1 was normal in 26 patients (32%, normal ECG group), and abnormal in 55 patients (68%, abnormal ECG group). ST elevation was found in 46 patients (57%), inverted T wave in seven patients (9%) and left bundle branch block (LBBB) in two patients (3%). Areas of DCE suggesting AM were found in each patient. No relationship concerning the location of the involved region (s) was found between ECG (leads with ST/T abnormalities) and MRI (areas showing DCE). The ECG in AM can either be normal or reflect abnormalities including arrhythmias, LBBB, ST segment elevation, and T wave inversion. The location of myocardial involvement deduced on the basis of ECG leads showing ST/T changes is not in close relationship with the areas of ventricular damage detected by MRI.


Pneumocystis pneumonia in hospitalized patients: a detailed examination of symptoms, management, and outcomes in human immunodeficiency virus (HIV)-infected and HIV-uninfected persons.
Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection for immunocompromised individuals. Robust data and clear guidelines are available for prophylaxis and treatment of human immunodeficiency virus (HIV)-related PCP (HIV-PCP), yet few data and no guidelines are available for non-HIV-related PCP (NH-PCP). We postulated that prevention and inpatient management of HIV-PCP differed from NH-PCP. We performed a retrospective case review of all pathologically confirmed cases of PCP seen at the University of Alabama Medical Center from 1996 to 2008. Data on clinical presentation, hospital course, and outcome were collected using a standardized data collection instrument. Bivariate analysis compared prophylaxis, adjunctive corticosteroids, and clinical outcomes between patients with HIV-PCP and NH-PCP. Our analysis of the cohort included 97 cases of PCP; 65 HIV and 32 non-HIV cases. Non-HIV cases rarely received primary prophylaxis (4% vs. 38%, P = 0.01) and received appropriate antibiotics later in the course of hospitalization (5.2 days vs. 1.1 days, P < 0.005). Among transplant patients, NH-PCP was diagnosed a mean of 1066 days after transplantation and most patients were on low-dose corticosteroids (87%) at the time of disease onset. No significant differences in adjunctive corticosteroid use (69% vs. 77%, P = 0.39) and 90-day mortality (41% vs. 28%, P = 0.20) were detected. Patients who have undergone organ or stem cell transplant remain at risk for PCP for many years after transplantation. In our cohort, patients who developed NH-PCP were rarely given prophylaxis, and initiation of appropriate antibiotics was significantly delayed compared to cases of HIV-PCP. Medical providers should be aware of the ongoing risk for NH-PCP, even late after transplantation, and consider more aggressive approaches to both prophylaxis and earlier empirical therapy for PCP.


Anti-inflammatory effect of flavonoids from chestnut flowers in lipopolysaccharide-stimulated RAW 264.7 macrophages and acute lung injury in mice.
Chestnut flowers were one of the by-products during chestnut industrial processing. Chestnut (Castanea mollissima Blume) flower is rich in flavonoids and has been used as a traditional medicine to treat a variety of diseases including respiratory disorders for a long history. The present study aims to investigate the potential anti-inflammatory effect of flavonoids from chestnut flower (FCF) in lipopolysaccharide (LPS)-treated RAW 264.7 cells and stimulated acute lung injury (ALI) in mice. HPLC-ESI-MS/MS was applied to identify flavonoids from Chestnut flower. The ROS content in cells and lung tissue was measured by flow cytometry. The malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and glutathione (GSH) content in cells and bronchoalveolar lavage fluid (BALF) was analyzed by photometry. Furthermore, the level of pro-inflammatory factors was analyzed by ELISA, and the expression of inflammatory gene mRNA by fluorescence quantitative PCR. H&E staining was used to evaluate the degree of lung tissue injury in mice. MPO activity was used to measure the degree of neutrophil infiltration. Total protein content was detected by BCA method. A total of forty-nine flavonoids compounds were tentatively identified in FCF by mass spectrometry analysis. The results of cell experiment suggested that FCF could alleviate oxidative injury via increasing SOD activity and GSH content, as well as inhibiting the production of intracellular ROS and MDA. FCF exerted its protective effect by suppressing the expression of both inducible nitric oxide synthase (iNOS) and cycooxygenase 2 (COX-2) to inhibit the synthesis of pro-inflammatory factors and cytokines, including NO, PGE2, TNF-α, IL-6 and IL-1β. Besides, FCF treatment could alleviate the thickening of alveolar wall and pulmonary congestion in LPS-treated ALI mice, and significantly inhibit the activity of myeloperoxidas (MPO) and the expression of cytokines in BALF. FCF could ameliorate inflammation and oxidative stress in LPS-treated inflammation, resulting in an overall improvement in both macroscopic and histological parameters.


Improvement of survival in Polish stroke patients is related to reduced stroke severity and better control of risk factors: the Krakow Stroke Database.
In the last decade, the stroke mortality rate in Poland significantly decreased. We hypothesised that stroke severity, the major determinant of outcome, is lowered in Polish stroke patients. We compared the stroke severity in two cohorts of first-ever ischaemic stroke patients admitted within 24 h after stroke onset to the Department of Neurology, Jagiellonian University, Krakow in the years 1994-2000 and 2008-2012. To assess stroke severity we used the National Institute of Health Stroke Scale (NIHSS). We defined mild stroke as an NIHSS score ≤ 4. We included 816 patients hospitalised in the years 1994-2000 and 569 patients hospitalised in the years 2008-2012. NIHSS score on admission was higher in the former (mean: 12.0 ±7.0 vs. 8.0 ±6.0, p < 0.01), and the frequency of mild stroke was higher in the latter (12.7% vs. 41.8%, p < 0.01). Although the frequency of hypertension (67.3% vs. 81.2%, p < 0.01), diabetes mellitus (20.8% vs. 26.4%, p = 0.02) and atrial fibrillation (20.7% vs. 26.2%, p = 0.02) was higher in patients hospitalised in the years 2008-2012, the systolic and diastolic blood pressure values and the frequency of fasting hyperglycaemia were lower in this cohort. This cohort also less frequently suffered from hypercholesterolaemia (25.4% vs. 16.3%, p < 0.01). Reduced stroke severity is associated with better recognition and control of risk factors and explains the improvement of survival in Polish stroke patients.


Spatial influences on colour opponent contributions to pattern detection.
The contribution of colour opponent mechanisms to detection thresholds is investigated at different spatial frequencies by presenting monochromatic, sinusoidal gratings on a uniform white background. Colour opponent mechanisms, characterised by a triple peaked spectral sensitivity function, determine threshold at low spatial frequencies (below 1 c/deg) and their contribution flattens the Weber function. They display low pass spatial frequency characteristics, becoming relatively more sensitive than non-opponent mechanisms as spatial frequency decreases. Colour opponent contributions are not revealed when the test grating and background are presented dichoptically.


Incidental and deliberate memory for words and faces after focal cerebral lesions.
It was predicted that right-hemisphere lesions cause a more marked deficit of shallow incidental memory than deep incidental or deliberate memory, the degree of the deficits being reversed after left-hemisphere lesions. This hypothesis was studied by measuring memory for words and faces in brain-damaged patients and nine controls after: shallow incidental learning, i.e. detecting words containing the letter 'A' and counting male and female faces; deep incidental learning, i.e. detecting words that mean man-made things and searching for well-known faces; and deliberate learning of words and faces. The results failed to support the hypothesis, but were consistent with the well-established finding that left- and right-hemisphere lesions disturb memory for words and faces, respectively.


Erratum to: Effects-based spatial assessment of contaminated estuarine sediments from Bear Creek, Baltimore Harbor, MD, USA.
The original publication of this paper contains an error. The correct image of figure 5 is shown in this paper.


Effect of recombinant human erythropoietin therapy on ambulatory blood pressure in normotensive and in untreated borderline hypertensive hemodialysis patients.
The effect of recombinant human erythropoietin (r-HuEPO) on ambulatory blood pressure (ABP) was studied in 13 anemic hemodialysis patients. Eight patients were normotensive and five patients had untreated borderline systolic hypertension. Mean hemoglobin increased from 82 +/- 3 g/L to 114 +/- 3 g/L (P < .01) after 3 to 4 months of r-HuEPO therapy (30 to 40 U/kg) administered subcutaneously three times weekly. Mean 24-h systolic and diastolic ABP measurements were significantly increased by 16 +/- 4 mm Hg and 10 +/- 2 mm Hg, respectively (P < .01 for both). Blood pressure was increased in all but one patient. In six patients, the mean 24-h systolic and diastolic ABP measurements were more than 160 mm Hg or 90 mm Hg at the end of the study. The increase in ABP was slightly but not significantly greater during the waking period as compared with the sleeping period and the circadian blood pressure pattern was not modified by r-HuEPO treatment. The blood pressure load (percentage of ABP reading exceeding 140/90 mm Hg during the waking period and 120/90 mm Hg during the sleeping period) was significantly increased (P < .05) after r-HuEPO therapy. Nine of the 13 patients failed to show the expected reduction in blood pressure during the sleeping period and were defined as "nondippers"; the others were defined as "dippers." During r-HuEPO therapy, the increase in ABP was similar in both dippers and nondippers. This suggests that the nondipper condition is not a risk factor for the development of hypertension during r-HuEPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of pramlintide on hormonal, metabolic or symptomatic responses to insulin-induced hypoglycaemia in patients with type 1 diabetes.
Pramlintide, a human amylin analogue, is a potential new adjunctive therapy to insulin for patients with type 1 diabetes and insulin-using patients with type 2 diabetes. Early clinical trials have shown a transient increased risk of hypoglycaemia in some patients at the time of initiating pramlintide therapy. This may be the result of combining the postprandial glucose, lowering effect of pramlintide with the existing hypoglycaemic potential of insulin without appropriate adjustment of insulin doses. However, the possibility that pramlintide may exert an independent detrimental effect on the physiological responses to insulin-induced hypoglycaemia needs to be excluded. We conducted three separate randomized, placebo-controlled studies in patients with type 1 diabetes treated with adjunctive pramlintide. These studies utilized pramlintide at high doses (either 0.1-1 mg pramlintide daily or 0.1-0.8 mg pramlintide four times a day for 5 or 6 days) as well as doses closer to those anticipated for therapeutic usage (30, 100 or 300 microg three times daily for 14 days), and examined the hormonal, metabolic and symptomatic responses to an insulin-infusion hypoglycaemic challenge conducted at baseline and after days of therapy. Pramlintide had no effect on the counter-regulatory hormonal, metabolic and symptomatic responses to hypoglycaemia. These findings demonstrated that pramlintide, when used as adjunctive therapy to insulin in patients with type 1 diabetes, has no independent effect on the response to hypoglycaemia.


Reliability of the beighton score and impact of generalized joint mobility and resting scapular position on Median Neurodynamic Test 1.
There is a lack of understanding of the impact of generalized joint mobility, joint hypermobility, and resting scapular position on neurodynamic testing of the median nerve. The objectives of the study were to determine: 1) the reliability of the Beighton score (BS) with and without the cutoff score for general joint hypermobility (GJH); 2) if there are differences in the Median Neurodynamic Test 1 (MNT 1) based on the Beighton cutoff score for GJH; 3) if there are differences in the MNT 1 based on an assessment of resting scapular position; 4) if there are relationships between the BS with and without the cutoff score for GJH, resting scapular position, and MNT 1. Testing was performed by two testers at two-time intervals at least 1 week apart. The population of interest was healthy asymptomatic adults. The outcome measures included the BS, resting scapular position, and MNT 1. Intraclass correlation coefficients (ICC2,1) were 0.52 for intertester reliability at visit 1 and 0.86 at visit 2, with intratester reliability of 0.88 for Tester 1 and 0.71 for Tester 2 for the BS. Intertester prevalence-adjusted bias-adjusted kappa (PABAK) values for the Beighton GJH cutoff scores were 0.80-0.84 and 0.80 to 0.92 for intratester reliability. There were no statistically significant differences or relationships for any of the other variables of interest. Joint mobility and resting scapular position are not confounding variables when performing MNT 1 in an asymptomatic population.


Differential effects of mild repeated restraint stress on behaviors and GABA(A) receptors in male and female rats.
We previously reported that the very mild stress of individual housing influenced seizure risk and gamma-amino butyric acid (GABA(A)) receptor activity differentially between male and female rats. The aim of the present set of studies was to assess sex differences in behavioral responses to a more pronounced type of stressor, repeated restraint stress. We also wanted to determine the role of GABA(A) receptors in effects of this stressor. Our data suggest that repeated restraint stress afforded short-term protection against seizure induction in both male and female rats. Moreover, this protection was more persistent in female than male rats. This stress paradigm also elicited a reduction in general activity in male rats, whereas female rats displayed prolonged increased activity following the repeated restraint stress exposure. However, there were limited effects on anxiety-like behaviors, as determined by time spent in the open arms on the elevated plus maze. Sex differences in stress-induced increases in plasma corticosterone levels were observed, which generally correlated with sex differences in behavioral measures. There were no significant effects of the repeated restraint stress exposure on benzodiazepine/GABA(A) receptor density or affinity nor on receptor function. Taken together, these findings provide additional evidence to support the important influences of sex in responding to stress and highlight the need to consider this context when addressing the role of stress in health issues for women and men.


Clinical evaluation of medetomidine, a novel sedative and analgesic drug for dogs and cats.
Medetomidine, a potent alpha 2-adrenoceptor agonist, was investigated in open, multicenter clinical trials with patients of various canine and feline breeds (1736 dogs and 678 cats). The purpose of the study was to find an optimal dose of medetomidine for sedation and analgesia in clinical practice and to study how well the intended procedure could be performed under the influence of the drug. The mean dose (i.m.) of medetomidine used for examinations, clinical procedures and minor surgical interventions was 40 micrograms/kg, and for radiography 30 micrograms/kg. In cats the dose was 80-110 micrograms/kg. On the doses chosen, almost all animals were recumbent and 72% of the dogs and 85% of the cats were in a slight anaesthetic stage, unable to rise. The evaluation of the overall suitability of medetomidine (% of cases) in different indications was "very satisfactory" or "satisfactory" in 95% of dogs and 81-96% of cats. Side effects reported were limited almost exclusively to vomiting and muscle jerking in dogs (12% and 0.5% of the cases) and to vomiting in cats (65%). Medetomidine seems to suffice for pharmacological restraint of dogs and cats. The concomitant use of medetomidine (80-100 micrograms/kg) and ketamine (7 mg/kg) in cats (n = 295) provided a good anaesthesia (20-40 min). The recovery was smooth. The present study shows that medetomidine provides an effective level of sedation and analgesia for clinical use.


Accurate Quantitative Sensing of Intracellular pH based on Self-ratiometric Upconversion Luminescent Nanoprobe.
Accurate quantitation of intracellular pH (pHi) is of great importance in revealing the cellular activities and early warning of diseases. A series of fluorescence-based nano-bioprobes composed of different nanoparticles or/and dye pairs have already been developed for pHi sensing. Till now, biological auto-fluorescence background upon UV-Vis excitation and severe photo-bleaching of dyes are the two main factors impeding the accurate quantitative detection of pHi. Herein, we have developed a self-ratiometric luminescence nanoprobe based on förster resonant energy transfer (FRET) for probing pHi, in which pH-sensitive fluorescein isothiocyanate (FITC) and upconversion nanoparticles (UCNPs) were served as energy acceptor and donor, respectively. Under 980 nm excitation, upconversion emission bands at 475 nm and 645 nm of NaYF4:Yb3+, Tm3+ UCNPs were used as pHi response and self-ratiometric reference signal, respectively. This direct quantitative sensing approach has circumvented the traditional software-based subsequent processing of images which may lead to relatively large uncertainty of the results. Due to efficient FRET and fluorescence background free, a highly-sensitive and accurate sensing has been achieved, featured by 3.56 per unit change in pHi value 3.0-7.0 with deviation less than 0.43. This approach shall facilitate the researches in pHi related areas and development of the intracellular drug delivery systems.


Pharmacological insight into the activation of the human neuropeptide FF2 receptor.
The neuropeptide FF2 (NPFF2) receptor, predominantly expressed in the central nervous system, plays an important role in the modulation of sensory input and opioid analgesia, as well as in locomotion, feeding, intestinal motility, reward, and the control of obesity. The NPFF2 receptor belongs to the RFamide peptide receptor family and to the G protein coupled receptor (GPCR) super family, but contrary to many other class A GPCRs, no 3D structure has been solved. Thus, it is essential to perform mutagenesis to gain information on the fine functioning of the NPFF2 receptor. In this study, we examined the role of aspartic acid (D) from the "D/ERY/F" motif found in the second intracellular loop (ICL2) and the role of the C-terminal end of the receptor in ligand binding and signal transduction. We found that mutation D3.49A does not impair binding capacities but inhibits G protein activation as well as adenylyl cyclase regulation. Truncation of the C terminal part of the receptor has different effects depending on the position of truncation. When truncation was realized downstream of the putative acylation site, ligand binding and signal transduction capabilities were not lost, contrary to total deletion of the C terminus, which totally impairs the activity of the receptor.


Changes in the EEG as the subject learns to recall.
The EEG was monitored from posterior leads located above the left and right hemispheres, while the subject learned to recall visually presented 9-digit strings. Processing of material to be recalled led to systematic and progressive activation of the left hemisphere together with an increasing ratio in the EEG activity of the two hemispheres. As performance improved with practice, the initial activation (during the first six digits) was followed by deactivation just prior to recall. This is interpreted as reflecting a shift from active processing (rehearsal) to passive processing (echoic buffer storage). Subjects who recalled well more activated in the left hemisphere than in the right and the level of EEG activity in the left hemisphere during early trials predicted overall recall performance throughout the task. Activity in the right hemisphere was unresponsive to the presentation of material and unrelated to performance. This study shows therefore that: (i) rehearsal for short term recall is a function of left hemisphere activity, (ii) individual differences in left hemisphere activity predict performance, and finally (iii) dynamic changes in brain organisation accompany an overall improvement in performance.


Zwitterionic Ammonium Sulfonate Polymers: Synthesis and Properties in Fluids.
Polymer zwitterions continue to emerge as useful materials for numerous applications, ranging from hydrophilic and antifouling coatings to electronic materials interfaces. While several polymer zwitterion compositions are now well established, interest in this field of soft materials science has grown rapidly in recent years due to the introduction of new structures that diversify their chemistry and architecture. Nonetheless, at present, the variation of the chemical composition of the anionic and cationic components of zwitterionic structures remains relatively limited to a few primary examples. In this article, the versatility of 4-vinylbenzyl sultone as a precursor to ammonium sulfonate zwitterionic monomers, which are then used in controlled free radical polymerization chemistry to afford "inverted sulfobetaine" polymer zwitterions, is highlighted. An evaluation of the solubility, interfacial activity, and solution configuration of the resultant polymers reveals the dependence of properties on the selection of tertiary amines used for nucleophilic ring-opening of the sultone precursor, as well as useful properties comparisons across different zwitterionic compositions.


Inflammatory bowel disease in individuals seropositive for the human immunodeficiency virus.
CD4 lymphocytes mediate disease expression in both human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD). Analysis of the clinical course of IBD in HIV-seropositive individuals may elucidate aspects of the role of CD4 lymphocytes in the pathogenesis of these conditions. A retrospective case series study. Diagnostic coding for IBD and pharmacy records for 5-aminosalicylic acid compounds and rectal steroid preparations were examined for all HIV-seropositive subjects attending the Chelsea and Westminster Hospitals between January 1988 and December 1993. Eight HIV-seropositive individuals with a confirmed diagnosis of IBD were identified. HIV/Genitourinary medicine (GUM) units. Change in CD4 count. Four subjects with an intact colon had a decline in CD4 count of 85 cells/mm3/year, four patients undergoing colectomy had a subsequent rise of four cells/mm3/year and eight case matched controls had a decline of 47 cells/mm3/year. Acute exacerbations of IBD did not cause a significant change in CD4 count. There were no exacerbations of IBD in patients with a CD4 count below 200 cells/mm3. HIV infection may influence the pathogenesis of IBD. A chronically inflamed colon may accelerate CD4 cell depletion which is reversed by colectomy.


Human T cell expansion and experimental autoimmune encephalomyelitis inhibited by Lenaldekar, a small molecule discovered in a zebrafish screen.
Immune-mediated diseases [multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE)] are driven by proliferating, highly activated autoreactive T-cells that are unresponsive to in vivo immunoregulatory mechanisms. The compound Lenaldekar (LDK) was identified in a zebrafish screen by inhibiting T-cell expansion. By monitoring mitogen- and antigen-driven proliferation, we found that LDK inhibited human and murine T-cell expansion in a non-cytolytic manner. This suppressive activity directly correlated with the degree of activation/proliferation of the T-cells. In testing LDK in an EAE model of MS, exacerbations were suppressed in treated animals. Therefore, LDK represents a novel therapeutic approach to T-cell-mediated autoimmune diseases.


Abnormalities in the sequence of filling and emptying of mesenteric arteries and veins: a guide to ischemic disease of the bowel.
Functional abnormalities in the sequence of filling and emptying of mesenteric arteries and veins may indicate significant disease of the bowel which is not associated with identifiable structural alterations in the blood vessels. In three patients, focal ischemic damage to the bowel was associated with significantly delayed arterial emptying, delayed or absent filling and emptying of mesenteric veins or a combination of both. Evaluation for sequential filling and emptying of vessels proved most helpful since an abnormal pattern may represent the only angiographic abnormality indicative of intestinal infarction.


Glia cell stimulating factor (GSF): a new lymphokine. Part 1. Cellular sources and partial purification of murine GSF, role of cytoskeleton and protein synthesis in its production.
The effect of activated-lymphocyte supernatant on glia cells was investigated. When treated in vitro with Concanavalin A (ConA), murine spleen cells released a soluble product, termed glia cell stimulating factor (GSF), which stimulated RNA and DNA synthesis in cultured murine glia cells. Furthermore, GSF appeared to promote the maturation of undifferentiated glia cells to astrocytes having a high content of glial fibrillary acidic protein. GSF secretion occurred after a lag period of 16 hours and proceeded at a constant rate for more than 48 hours. This GSF produced by ConA-stimulated murine lymphocytes has an apparent molecular weight between 60,000 and 80,000. Antigenic stimulation of primed lymph node cells with BGG resulted in a similar GSF production. Cellular sources of mitogen-induced GSF were investigated by using isolated lymphoid populations. GSF release by ConA-activated pure T-lymphocytes reconstituted with peritoneal macrophages was equivalent to that of unseparated spleen cells, whereas GSF production by T-lymphocytes alone was low. Macrophages alone did not elaborate detectable levels of GSF. GSF was also secreted by enriched -B-lymphocytes populations stimulated by Protein A. Formation of GSF was suppressed when cytochalasin B or cyclo-heximide was added to the cultures, while colchicine failed to have any effect. DNA synthesis is not required for GSF production as determined by resistence to treatment with mitomycin C. The data indicate that the GSF production and secretion mechanism is much like that described for other lymphokines.


Predictive factors of sleep quality and burnout in nurses working in transplant units during the COVID-19 lockdown - A cross-sectional study.
Background: There is minimal information regarding sleep disturbance and burnout during COVID-19 in nurses working within haematology-oncology and hematopoietic stem cell transplantation (HSCT) settings.Aim: To identify socio-demographic and professional factors that predicted burnout and sleep disturbance during COVID-19 in nurses working in HSCT settings.Design/Methods: Data were collected using the Maslach Burnout Inventory and the Pittsburgh Sleep Quality Index. Descriptive statistics and linear regression examined relationships.Results: 308 responses were received. Nurses working in outpatient settings had greater emotional exhaustion (Rpartial = -0.12, n = 308, p = 0.03). Negative predictors for quality of sleep were transplant programme setting (Rpartial = -0.19, n = 308, p < 0.01) and years working in HSCT (Rpartial = -0.17, n = 308, p < 0.01). Other relationships were found on univariate analysis.Conclusion: Institutions must offer programmes for nurses to develop sleep strategies, self-care, and work-related stress management.


Gender and the language of pain in chronic and terminal illness: A corpus-based discourse analysis of patients' narratives.
Drawing on the notion of gender as a socially constructed category performed inter alia through language, this study examines the ways in which women and man use language to do person-in-pain in real-life interactions about chronic and terminal illness. It is based on a secondary analysis of a large corpus of health and illness narratives collected by the Health Experiences Research Group at the University of Oxford and published by the DIPEx charity. Sixteen chronic and terminal conditions were identified in which men and women talked about physical pain and their narratives examined using the linguistic approach of a corpus-assisted discourse analysis. Our study shows that there are significant quantitative and qualitative differences in the ways in which women and men report pain pointing to the existence of distinctive feminine and masculine lexical repertoires of pain talk. While these repertoires conform to some of the dominant societal stereotypes surrounding masculinity and femininity, they also transgress those. Women refer to pain more frequently and have a wider lexical repertoire for pain reporting. They use more specific and factual references as well as cognitive and psychological words in their pain talk. In contrast, men tend to use fewer descriptors in general, most of which are highly emotive suggesting that they report pain when it becomes unbearable enduring it until this point. There is also a conspicuous absence of references to psychological processes in the male narratives and the focus is on pain killers. Understanding this nuanced role of gender in communicating pain can help health professionals respond effectively to people's talk about pain and develop more holistic practices in pain consultation, assessment and treatment leading potentially to the reduction of gender biases and inequalities in healthcare.


Lutetium(III) acetate phthalocyanines for photodynamic therapy applications: Synthesis and photophysicochemical properties.
The development of new water-soluble photosensitizers for photodynamic therapy (PDT) applications is a very active research topic. Efforts have been made to obtain the far-red absorbing phthalocyanine complexes with molecular design that facilitates the uptake and selectivity for a high PDT efficiency. The monomolecular lutetium(III) acetate phthalocyanines (LuPcs) substituted with methylpyridyloxy groups at non-peripheral (5) and peripheral (6) positions were synthesized by following the modification of the well-known synthetical routes. The photo-physicochemical properties of the both quaternized LuPcs were evaluated by the steady-state and time-resolved spectroscopy. The photochemical technique was applied to study the generation of the singlet oxygen. Two water-soluble and cationic LuPcs were synthesized and chemically characterized. The photo-physicochemical properties of absorption (675 and 685nm) and the red shifted fluorescence (704 and 721nm) as well as the fluorescence lifetimes (2.24 and 3.27ns) were studied. The promising values of singlet oxygen quantum yields (0.32 for 5 and 0.35 for 6) were determined. Lutetium(III) acetate phthalocyanine complexes were synthesized and evaluated with physicochemical properties suitable for future photodynamic therapy applications.


[The structure of the morbidity among people working at computers with video display terminals].
The authors analyzed data of ane examination of 407 user of video display terminals of large computer centers in Kiev and revealed high morbidity of the circulatory digestive and locomotor organs. An analysis of 878 analogous cases in the GDR revealed lower involvement of the mentioned organs. Causes are analyzed. Ways of prophylaxis are outlined.


Ambient air pollution exposed during preantral-antral follicle transition stage was sensitive to associate with clinical pregnancy for women receiving IVF.
Maternal exposure to air pollution is associated with poor reproductive outcomes in in vitro fertilization (IVF). However, the susceptible time windows are still not been known clearly. In the present study, we linked the air pollution data with the information of 9001 women receiving 10,467 transfer cycles from August 2014 to August 2019 in The Second Hospital of Hebei Medical University, Shijiazhuang City, China. Maternal exposure was presented as individual average daily concentrations of PM2.5, PM10, NO2, SO2, CO, and O3, which were predicted by spatiotemporal kriging model based on residential addresses. Exposure windows were divided to five periods according to the process of follicular and embryonic development in IVF. Generalized estimating equation model was used to evaluate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association between clinical pregnancy and interquartile range increased average daily concentrations of pollutants during each exposure period. The increased PM2.5 (adjusted OR = 0.95, 95% CI: 0.90, 0.99), PM10 (adjusted OR = 0.93, 95% CI: 0.89, 0.98), NO2 (adjusted OR = 0.89, 95% CI: 0.85, 0.94), SO2 (OR = 0.94, 95% CI: 0.90, 0.98), CO (adjusted OR = 0.93, 95% CI: 0.89, 0.97) whereas decreased O3 (OR = 1.08, 95% CI: 1.02, 1.14) during the duration from preantral follicles to antral follicles were the strongest association with decreased probability of clinical pregnancy among the five periods. Especially, women aged 20-29 years old were more susceptible in preantral-antral follicle transition stage. Women aged 36-47 years old were more vulnerable during post-oocyte retrieve period. Our results suggested air pollution exposure during preantral-antral follicle transition stage was a note-worthy challenge to conceive among females receiving IVF.


Diagnostic Accuracy of Computed Tomography for the Prediction of the Need for Laparotomy for Traumatic Hollow Viscus Injury: Systematic Review and Meta-Analysis.
Traumatic hollow viscus injury (THVI) is one of the most difficult challenges in the trauma setting. Computed tomography (CT) is the most common modality used to diagnose THVI; however, various performance outcomes of CT have been reported. We conducted a systematic review and meta-analysis to analyze how precise and reliable CT is as a tool for the assessment of THVI. A systematic review and meta-analysis were conducted on studies on the use of CT to diagnose THVI. Publications were retrieved by performing structured searches in databases, review articles and major textbooks. For the statistical analysis, summary receiver operating characteristic (SROC) curves were constructed using hierarchical models. Sixteen studies enrolling 12,514 patients were eligible for the final analysis. The summary sensitivity and specificity of CT for the diagnosis of THVI were 0.678 (95% CI: 0.501-0.809) and 0.969 (95% CI: 0.920-0.989), respectively. The summary false positive rate was 0.031 (95% CI 0.011-0.071). In this meta-analysis, we found that CT had indeterminate sensitivity and excellent specificity for the diagnosis of THVI.


Impact of changes in community psychiatric service provision on mental health presentations to the emergency department.
The reconfiguration of many Irish stand-alone psychiatric units has led to many patients in acute mental health need now being assessed in emergency departments (EDs). This has implications for ED resources and raises questions about appropriate assessment location for this group. This report aims to examine the impact of removal of a direct community access point for patients in acute mental health need on ED presentations in a Dublin hospital. We examined data on ED referrals to psychiatry over 5 years: 12 months before the service change, and four subsequent 12-month periods. We compared numbers referred, mode of referral, average ED length of stay, proportion with no physical issue requiring psychiatric assessment only, and numbers who did not wait for psychiatry assessment. In the year directly after the service change, referrals to psychiatry from ED increased by 200%, remaining at this level for the subsequent 3 years. Of these, 32.5% were referred by a GP-more than a threefold increase in numbers from the previous year, with both numbers remaining similarly elevated over subsequent years. In the year after the service change, 52.1% of total ED to psychiatry presented solely for mental health reasons-nearly a fourfold increase in cases from the previous year, and remained high. Removing a direct community access point for this group resulted in a substantial increase in ED presentations, many of which did not have physical needs. This study has implications for future policy to address the needs of this group, especially in light of the pandemic.


Emerging and zoonotic infections in women.
Emerging infections, many zoonotic, are caused by a variety of pathogens with global distribution. Previously rare pathogens have emerged; global travel facilitates their rapid spread. Human encroachment on remote areas has brought contact with zoonotic diseases never before characterized. Although systematic study of rare outbreaks can be challenging, knowledge of emerging pathogens and their effects on women is accumulating. This article discusses effects of lymphocytic choriomeningitis virus, West Nile virus, severe acute respiratory syndrome coronavirus, avian influenza A virus, viral hemorrhagic fevers, spirochetal illnesses, and Chagas' disease. The potential impact of candidate bioterror agents and issues of prophylaxis and therapy are discussed.


[Analysis of causative factors for lower limb deep vein thrombosis complicated with artery pulmonary embolism in orthopedics patients].
To explore the causative factors of lower limb deep vein thrombosis complicated with pulmonary artery embolism in orthopedics patients. The clinical manifestations and causes of thrombosis defluxion of pulmonary artery embolism patients whose diagnosis were confirmed by computed tomography pulmonary angiography (CTPA) during May 2009-May 2012 were retrospectively analyzed. Among 45 cases of CTPA-confirmed pulmonary artery embolism patients, 5 patients had no obvious clinical manifestation. The initial symptoms included chest stuffiness and dyspnea (n = 9) and cough (n = 8). And the major causes of thrombosis defluxion were early postoperative mobilization (n = 11), postoperative functional exercise (n = 9), rollover or defecation in bed (n = 7), sneezing (n = 2) and unknown causes (n = 14). The patients with lower limb deep vein thrombosis have a high risk of thrombosis defluxion during unstable period. Despite adequate anticoagulation, early mobilization and functional exercise are likely to cause thrombosis defluxion and lead to pulmonary artery embolism.


Evaluation of Urinary Big Endothelin-1 in Feline Spontaneous CKD.
The endothelin-1 (ET-1) system has been implicated in the development and progression of chronic kidney disease (CKD). No information on big ET-1 in feline urine is available. The purpose of this study was to evaluate if urinary big endothelin-1 (bigET-1) is associated with feline CKD. Sixty urine samples were prospectively collected from 13 healthy cats at risk of developing CKD and 22 cats with CKD of different International Renal Interest Society (IRIS) stages (1-4). Urinary bigET-1 was measured using a commercially available ELISA. BigET-1 normalized to urine creatinine (bigET-1:UC) was compared amongst stages and substages, as proposed by IRIS, and correlated with serum creatinine concentration, proteinuria and blood pressure. BigET-1:UC at the time of inclusion was compared between cats that remained stable and cats that progressed after 12 months. BigET-1:UC was significantly higher (p = 0.002) in cats at IRIS stages 3-4 (median: 21.9; range: 1.88-55.6), compared to all other stages, and in proteinuric (n = 8, median: 11.0; range: 0.00-46.4) compared with nonproteinuric cats (n = 38 median: 0.33; range: 0.00-55.6) (p = 0.029). BigET-1:UC was not associated with CKD progression. Urinary bigET-1 increased in advanced stages of CKD and in proteinuric patients, suggesting that ET-1 may be indicative of the severity of feline CKD.


Temperature-sensitive aspects of evoked and spontaneous transmitter release at the frog neuromuscular junction.
1. The temperature dependence of presynaptic processes involved in neuromuscular transmission was studied by rapidly increasing the temperature of cooled frog neuromuscular junctions by 4--10 degrees C using pulses from a neodymium laser. The temperature elevation was complete within 0.5 msec, and decayed back to control levels with a time constant of about 7--8 sec. 2. Temperature jumps completed before nerve stimulation increased the quantal content and decreased the latency of the end-plate potential (e.p.p.). The Q10 for e.p.p. quantal content in low [Ca2+] Ringer averaged about 3.9 over the range 1--18 degrees C. 3. Temperature jumps occurring during the synaptic delay (the interval between the presynaptic action potential and the onset of the e.p.p.) also increased the quantal content and decreased the latency of the e.p.p. These effects diminished as the onset of the temperature jump was moved closer to the expected onset of the e.p.p. Temperature jumps applied after the onset of the e.p.p. immediately accelerated the time course of the e.p.p. but did not significantly alter quantal content. These results demonstrate that the magnitude and timing of evoked release are influenced by temperature-sensitive processes that operate both during and shortly after the presynaptic nerve action potential, but are largely complete before the onset of release. 4. Temperature jumps were applied at various times during the interval between two nerve stimuli. The amplitude of the second e.p.p. decreased as the temperature jump was moved earlier in the interstimulus interval, suggesting that the rise in temperature following the first nerve stimulus accelerates the decay of facilitation. When the temperature jump was moved from 10 msec after to 10 msec before the onset of the first e.p.p., the amplitude of the second e.p.p. either decreased or showed no change. The fact that the second e.p.p. did not increase suggests that the temperature-sensitive processes that increase the quantal content of the conditioning e.p.p. do not greatly increase the facilitation following that e.p.p. 5. Temperature jumps immediately accelerated the time course of spontaneous miniature end-plate potentials (m.e.p.p.s) and increased their frequency. Experiments using slow temperature changes revealed that the Q10 for m.e.p.p. frequency in normal Ringer is about 10 over the range 10--20 degrees C. M.e.p.p. frequency was much less sensitive to temperature changes below about 10 degrees C. When the nerve terminal was depolarized by 20 mM-K+ in the presence of Ca2+, the Q10 for the rate of spontaneous release over the range 10--20 degrees C decreased to about 4, similar to the Q10 for e.p.p. quantal content. In the absence of extracellular Ca2+ the Q10 for m.e.p.p. frequency in 20 mM-K+ remained near 10. 6. The marked difference in Q10S for spontaneous transmitter release under different experimental conditions suggests that not all transmitter release uses identical mechanisms...


Toxicity and exposure of an adenovirus containing human interferon alpha-2b following intracystic administration in cynomolgus monkeys.
The safety and toxicokinetics of SCH 721015, an adenovirus encoding the human interferon alpha-2b gene, and Syn3 (SCH 209702), a novel excipient, were assessed in cynomolgus monkeys administered intravesical doses of 2.5 × 10E11 or 1.25 × 10E13 particles SCH 721015 in 25 mg Syn3 or 25 mg Syn3 alone on study days 1 and 91. There was no systemic toxicity. Monkeys dosed with SCH 721015 in Syn3 were positive for SCH 721015-specific DNA in the urine for 2 to 3 days following each dose and had interferon alpha-2b protein in the urine for 1-3 days after a single dose and in fewer animals after a second dose. Intracystic administration was associated with inflammation and focal/multifocal ulceration in the urinary bladder and irritation in the ureters and urethra at necropsy. The physical trauma from catheterization and filling/emptying of the bladder was likely a contributing factor and Syn3 exacerbated the trauma. There was nearly complete resolution of these findings 2 months after the last dose. The trauma to the bladder likely contributed to low, transient systemic exposure to Syn3, SCH 721015 and human interferon protein. The results of this study support the clinical investigation of SCH 721015 in Syn3.


Endoscopic ultrasonography as additional preoperative workup is valuable in half of the patients with a pancreatic body or tail lesion.
The management of pancreatic body and tail lesions is underexposed. It remains unclear whether endoscopic ultrasonography (EUS) increases the accuracy of the preoperative workup. This study assessed the diagnostic value and safety of EUS in addition to cross-sectional imaging in a surgical cohort of patients with pancreatic body or tail lesions. A multicenter retrospective cohort study was performed of patients who underwent distal pancreatectomy from 2010 to 2017. The composite primary outcome was the additional value of EUS, defined as: (a) EUS confirmed an uncertain diagnosis on cross-sectional imaging, (b) EUS was correct in case of discrepancy with cross-sectional imaging, or (c) EUS provided tissue diagnosis for neoadjuvant treatment. Furthermore, serious adverse events and needle tract seeding were assessed. In total, 181 patients were included, of whom 123 (68%) underwent EUS besides cross-sectional imaging. Postoperative pathology was heterogeneous: 91 was malignant, 49 premalignant, 41 benign. Most lesions were solid (n = 117). EUS had additional value in 59/123 (48%) patients; 27/50 (54%) of cystic and 32/73 (44%) of solid lesions. No serious adverse event or needle tract seeding following EUS occurred. EUS had additional value besides cross-sectional imaging in half of the patients and showed low associated risks.


Modulation of the pattern of axonal projections of a leech motor neuron by ablation or transplantation of its target.
The sixth segmental ganglion in the ventral nerve cord of the leech H. medicinalis contains a bilateral pair of rostral penile evertor motor neurons (RPEs) that in the adult innervate the male genitalia. During embryogenesis, the RPEs extend numerous extraganglionic projections. Only two of these innervate the target and are normally retained in the adult, while the others retract. Early, but not late, removal of the male genitalia results in the indefinite retention and continued growth of projections that would normally retract. Any of these projections can innervate targets transplanted to ectopic locations. We conclude that an RPE motor neuron requires a signal, provided by its interaction with the target organ during a critical period, in order to stop extending axons, stabilize those axons that contact the target, and retract those that do not.


New insulin analogues and insulin delivery devices for the perioperative management of diabetic patients.
With the rising incidence of diabetes mellitus in the United States today, more and more patients with this comorbidity will present for surgical or interventional procedures. Treatments are becoming more varied and complex so anesthesiologists must be familiar with new drugs and delivery modalities used in the treatment of this patient population. New types of insulin have revolutionized diabetic care. The introduction of rapid acting and long acting insulin has enabled more precise glucose control to be achieved. New delivery modes of insulin both by the inhaled/buccal route and premeasured pen have been introduced. The newer oral hypoglycemic agents are also in use and have mechanisms of action that differ from the older treatments. Anesthesiologists must keep themselves updated with the rapidly changing treatment options for diabetic patients with both type 1 and type 2 diseases. The mechanism of action and duration of newer drugs are important for clinicians to know when managing intraoperative serum glucose control.


Timing Differences in Stride Cycle Phases in Retired Racehorses Ridden in Rising and Two-Point Seat Positions at Trot on Turf, Artificial and Tarmac Surfaces.
Injuries to racehorses and their jockeys are not limited to the racetrack and high-speed work. To optimise racehorse-jockey dyads' health, well-being, and safety, it is important to understand their kinematics under the various exercise conditions they are exposed to. This includes trot work on roads, turf and artificial surfaces when accessing gallop tracks and warming up. This study quantified the forelimb hoof kinematics of racehorses trotting over tarmac, turf and artificial surfaces as their jockey adopted rising and two-point seat positions. A convenience sample of six horses was recruited from the British Racing School, Newmarket, and the horses were all ridden by the same jockey. Inertial measurement units (HoofBeat) were secured to the forelimb hooves of the horses and enabled landing, mid-stance, breakover, swing and stride durations, plus stride length, to be quantified via an in-built algorithm. Data were collected at a frequency of 1140 Hz. Linear Mixed Models were used to test for significant differences in the timing of these stride phases and stride length amongst the different surface and jockey positions. Speed was included as a covariate. Significance was set at p < 0.05. Hoof landing and mid-stance durations were negatively correlated, with approximately a 0.5 ms decrease in mid-stance duration for every 1 ms increase in landing duration (r2 = 0.5, p < 0.001). Hoof landing duration was significantly affected by surface (p < 0.001) and an interaction between jockey position and surface (p = 0.035). Landing duration was approximately 4.4 times shorter on tarmac compared to grass and artificial surfaces. Mid-stance duration was significantly affected by jockey position (p < 0.001) and surface (p = 0.001), speed (p < 0.001) and jockey position*speed (p < 0.001). Mean values for mid-stance increased by 13 ms with the jockey in the two-point seat position, and mid-stance was 19 ms longer on the tarmac than on the artificial surface. There was no significant difference in the breakover duration amongst surfaces or jockey positions (p ≥ 0.076) for the ridden dataset. However, the mean breakover duration on tarmac in the presence of a rider decreased by 21 ms compared to the in-hand dataset. Swing was significantly affected by surface (p = 0.039) and speed (p = 0.001), with a mean swing phase 20 ms longer on turf than on the artificial surface. Total stride duration was affected by surface only (p = 0.011). Tarmac was associated with a mean stride time that was significantly reduced, by 49 ms, compared to the turf, and this effect may be related to the shorter landing times on turf. Mean stride length was 14 cm shorter on tarmac than on grass, and stride length showed a strong positive correlation with speed, with a 71 cm increase in stride length for every 1 m s-1 increase in speed (r2 = 0.8, p < 0.001). In summary, this study demonstrated that the durations of the different stride cycle phases and stride length can be sensitive to surface type and jockey riding position. Further work is required to establish links between altered stride time variables and the risk of musculoskeletal injury.


Interferons: several questions and few answers.
Interferons, which have been studied for many years as antiviral agents, are now receiving considerable attention as antitumor and immunomodulatory agents. The data to date are sufficiently interesting to warrant further studies on several fronts. Clearly, the results that have been obtained so far tend to pose more questions than they answer.


Intermolecular interactions between natural polysaccharides and silk fibroin protein.
Fabricating novel functional and structural materials from natural renewable and degradable materials has attracted much attention. Natural polysaccharides and proteins are the right natural candidates due to their unique structures and properties. The polysaccharide-protein composites or blends were widely investigated, however, there are few systematical studies on the interactions between natural polysaccharides and silk fibroin protein at the molecular level. Among various interactions, hydrogen bonding, electrostatic interactions and covalent bonding play important roles in the structure and properties of the corresponding materials. Therefore, the focus is placed on the three interactions types in this review. A future challenge is to create polysaccharide and protein composites or blends with tailored structure and properties for the wide applications.


First-principles Dzyaloshinskii-Moriya interaction in a non-collinear framework.
We have derived an expression of the Dzyaloshinskii-Moriya interaction (DMI), where all the three components of the DMI vector can be calculated independently, for a general, non-collinear magnetic configuration. The formalism is implemented in a real space-linear muffin-tin orbital-atomic sphere approximation (RS-LMTO-ASA) method. We have chosen the Cr triangular trimer on Au(111) and Mn triangular trimers on Ag(111) and Au(111) surfaces as numerical examples. The results show that the DMI (module and direction) is drastically different between collinear and non-collinear states. Based on the relation between the spin and charge currents flowing in the system and their coupling to the non-collinear magnetic configuration of the triangular trimer, we demonstrate that the DMI interaction can be significant, even in the absence of spin-orbit coupling. This is shown to emanate from the non-collinear magnetic structure, that can induce significant spin and charge currents even with spin-orbit coupling is ignored.


[Deep interscapular temperature and thermogenesis of brown fat during sleep].
Deep interscapular temperature measured just below the brown fat lobes was studied in rats during sleep at two ambient temperatures (24 degrees C and 4 degrees C) before and after adaptation (9 days) to cold (4 degrees C). The results show that in the cold ambient deep interscapular temperature decreases during desynchronized sleep independently of adaptation. Such change in temperature is probably the result of the depression in sympathetic vasoconstrictor influences on heat exchangers producing blood and brown fat cooling in sequence during this stage of sleep.


Lumbar Extensor Muscle Size and Isometric Muscle Strength in Women with Symptomatic Lumbar Degenerative Diseases.
A cross-sectional design. To determine the characteristics of lumbar extensor muscle (LEM) size and isometric muscle strength and examine their correlations in women with lumbar degenerative diseases (LDDs). Many studies have evaluated the relationship between muscle size and strength, but the results have been controversial. Seventy-four female patients (mean age, 66 years) who consecutively underwent posterior lumbar interbody fusion (L1-S1) were recruited. The cross-sectional area (CSA) of the back extensor muscles was measured between L1-2 to L5-S1, and the total sum of the CSAs at each disc level was calculated. Back extensor muscle strength was evaluated using a MedX lumbar extension machine. The Oswestry Disability Index (ODI, 0-100) and Visual Analog Scale (VAS, 0-10) of lower back pain were determined. The mean CSAs of the LEM at each level (L1/2-L5/S1) and the total sum were 34.3, 36.3, 35.1, 31.4, 21.9, and 156.2 cm2, respectively. The mean isometric strength at each angle (range, 0°-72°) was 32.5, 50.1, 72.0, 88.7, 100.7, 112.2, and 126.2 ft-lb, respectively. The mean ODI and VAS scores were 54.6 and 6.6, and the mean body weight and body mass index (BMI) were 59.9 kg and 24.9 kg/m2, respectively. The CSAs of the upper lumbar level (L1-4) and the total sum of the CSAs were associated with isometric strength, which was negatively correlated with patients' age and ODI and positively associated with body weight and BMI, mainly at higher lumbar flexion angles (48°-72°). In women with LDD, LEM sizes of the upper lumbar levels (L1-4) were larger than those of the lower levels (L4-S1) and were positively associated with muscle strength. The upper lumbar levels in patients with LDDs appear to play a compensatory role when degenerative lesions are present in the lower lumbar levels.


A novel method for measuring medial compartment pressures within the knee joint in-vivo.
A novel method for the measurement of knee joint forces in-vivo is described. A thin (0.2mm) flexible electronic pressure sensor was inserted through a narrow arthroscopic portal into the osteoarthritic medial compartment of the knee joint. The sensor partially covered the load bearing area. The surgery was performed under local anaesthetic during normal arthroscopic examination following patient consent. Results are presented for 11 patients. The method was used in a pilot study to assess the effects of four valgus knee braces on medial compartment forces. An analysis of variance could not detect un-loading by any brace although there were large variations in force output. These variations may be attributable to shifts in the sensor position. In-vivo measurement of joint force is technically feasible.


Sub-Golgi distribution in rat liver of CMP-NeuAc GM3- and CMP-NeuAc:GT1b alpha 2----8sialyltransferases and comparison with the distribution of the other glycosyltransferase activities involved in ganglioside biosynthesis.
Using a sucrose density gradient fractionation of a highly purified Golgi apparatus from rat liver, we determined the sub-Golgi distribution of CMP-NeuAc:GM3 ganglioside alpha 2----8sialyltransferase (GM3-SAT) and CMP-NeuAc:GT1b ganglioside alpha 2----8sialyltransferase (GT1b-SAT), in comparison with that of the other glycosyltransferase activities involved in ganglioside biosynthesis. While GM3-SAT was recovered in several density fractions, GT1b-SAT was mainly found on less dense sub-Golgi membranes; this indicates that these two activities are physically separate. Moreover, with regard to the monosialo pathway, CMP-NeuAc:lactosylceramide alpha 2----3sialyltransferase, UDP-GalNAc:GM3 ganglioside beta 1----4N-acetylgalactosaminyltransferase, UDP-Gal:GM2 ganglioside beta 1----3galactosyltransferase, and CMP-NeuAc:GM1 ganglioside alpha 2----3sialyltransferase were resolved from more dense to less dense fractions, respectively. In the disialo pathway, UDP-GalNAc:GD3 ganglioside beta 1----4N-acetylgalactosaminyltransferase, UDP-Gal:GD2 ganglioside beta 1----3galactosyltransferase and CMP-NeuAc:GD1b ganglioside alpha 2----3sialyltransferase co-distributed with the corresponding activities of the monosialo pathway. These last results indicate that many Golgi glycosyltransferases involved in ganglioside biosynthesis are localized in the order in which they act.


Computer assisted diagnostic system in tumor radiography.
An improved and efficient method is presented in this paper to achieve a better trade-off between noise removal and edge preservation, thereby detecting the tumor region of MRI brain images automatically. Compass operator has been used in the fourth order Partial Differential Equation (PDE) based denoising technique to preserve the anatomically significant information at the edges. A new morphological technique is also introduced for stripping skull region from the brain images, which consequently leading to the process of detecting tumor accurately. Finally, automatic seeded region growing segmentation based on an improved single seed point selection algorithm is applied to detect the tumor. The method is tested on publicly available MRI brain images and it gives an average PSNR (Peak Signal to Noise Ratio) of 36.49. The obtained results also show detection accuracy of 99.46%, which is a significant improvement than that of the existing results.


Mode of action of coumarin in immune cells.
In order to characterize further the mode of action of coumarin, binding studies were undertaken using human monocytes and radioactively labelled drug. Since coumarin is only a small compound and we wanted to exclude possible artefacts due to variations in size or conformation, the drug was produced by synthesis in the presence of radioactive 14C. Adding increasing amounts of a mixture of labelled and unlabelled drug to monocytes resulted in saturating conditions only at rather high concentrations. Performing Scatchard analysis demonstrated that binding sites for coumarin appeared to be present in relatively high numbers (7.5 x 10(8)/cell) but their affinity was rather low (K alpha approximately 2 x 10(2) M-1). Inhibition studies with 7-hydroxycoumarin revealed that an approximately four times higher molar concentration of the derivative was necessary to cause 50% displacement of coumarin from its binding site. These results indicate that binding of the drug to cells is characterized by high-capacity but low-affinity conditions. This would be compatible with the hypothesis that coumarin interacts with ubiquitous intracellular receptor proteins able to interact with aromatic hydrocarbons, which might form the basis for enzyme induction, and leads to the effects observed in vitro and in vivo.


Impact of deductibles on initiation and continuation of psychotherapy for treatment of depression.
To estimate the impact of deductibles on the initiation and continuation of psychotherapy for depression. Data from health care encounters and claims from Group Health Cooperative, a large integrated health care system in Washington State, was merged with information from a centralized behavioral health triage call center to conduct study analyses. A retrospective observational design using a hierarchical logistic regression model was used to estimate initiation and continuation probabilities for use of psychotherapy, adjusting for key sociodemographic/economic factors and prior use of behavioral health services relevant to individual decisions to seek mental health care. Analyses were based on merged datasets on patient enrollment, insurance benefits, use of mental health and general medical services and information collected by a triage specialist at a centralized behavioral health call center. Among individuals with unmet deductibles between $100 and $500, we found a statistically significant lower likelihood of making an initial visit, but there was no statistically significant effect on making an initial or subsequent visit among individuals that had met their deductible. Unmet deductibles appear to influence the likelihood of initiating psychotherapy for treating depression.


Surveyed from Afar: Household water security, emotional well-being, and the reliability of water supply in the Ethiopian lowlands.
Almost half of the world's population is expected to experience water stress in their daily lives by 2050. The impacts of water scarcity on physical and psychosocial health are especially felt in arid regions of Ethiopia where semi-nomadic pastoralist populations are heavily reliant on groundwater for domestic and livestock needs. However, functional water supply infrastructure and reliable service delivery remain a challenge. A cross-sectional water security household survey of 469 heads of households and borehole runtime sensor data in Afar Region, Ethiopia, has three main findings. First, higher levels of household water insecurity experiences (HWISE) and water-related emotional distress (WRED) are positively correlated (0.57, p<0.01) and are significantly associated with "limited" water service levels, the non-use of boreholes, and more vulnerable household demographics (female-headed households and lower household incomes). Lower HWISE scores are associated with increased borehole pump usage and reliability, with a cut-off point of 6 h of pump usage per day measured with electronic sensors. Adding additional water points to the dry lowlands of Afar have led to overcrowding and rangeland degradation in the past, highlighting a need to balance increased production for human consumption with livestock use. When it comes to climate resilience and adaptation, ensuring the reliability of what has already been constructed is a top priority for the regional government. Our findings suggest that increasing the reliability and daily usage of existing water supply systems over the short-sighted expansion of sources is worth the investment in services it will take to reach even the most far-flung communities.


Association of dyslipidaemia and oral statin use, and dry eye disease symptoms in the Blue Mountains Eye Study.
There is limited literature on oral statin use and its association with dry eye. To analyse the association between dyslipidaemia, use of oral statin drugs, and symptoms of dry eye disease (DED) among older adults. Population-based study. Participants of the Blue Mountains Eye Study III (BMESIII), a large cohort study in suburban Sydney, aged 60 years or older (mean age = 74, range = 60-97, n = 1680) were analysed. Information on DED symptoms and statin use were obtained from an interviewer-administered questionnaire. Serum lipid profiles were determined from fasting blood tests. The association of various DED symptoms, as well as their number and their severity, with dyslipidaemia and oral statin intake was evaluated. At least one DED symptom was reported in 52% (n = 1029) of the population. Patients with hypercholesterolaemia (>5.5 mmol/L) did not report more DED symptoms than those without hypercholesterolaemia. Neither serum high-density lipoprotein nor low-density lipoprotein levels were associated with any DED symptoms. Patients taking oral statins were more likely to report one or more moderate to severe symptoms of DED (odds ratio: 2.054, 95% confidence interval: 1.281-3.295). The association between oral statin use and presence of moderate to severe DED symptomatology is a novel finding that deserves further mechanistic and clinical correlation in order to determine its potential, or lack thereof, for the management of dry eye.


Mapping the double-strand breaks at the mating-type locus in fission yeast by genomic sequencing.
In fission yeast mating-type switching is initiated by the formation of a double-strand DNA break at the mating-type locus. A prerequisite for generation of the break is some 'imprinting' of the DNA in the previous cell cycle. We have used the technique of genomic sequencing to map the position of the break directly on chromosomal DNA cleaved in vivo. On one strand the break is situated very close to the right-hand border of the expressed mat1 cassette. Cells of opposite mating type, P and M, have their breaks at slightly different positions on this strand. On the other DNA strand of both alleles the ends are probably masked by tightly bound proteins and therefore the precise nature of the break could not be determined. Since the break is stable throughout the cell cycle, these proteins may function in vivo to confer structural stability on the chromosomes having the break. The implications of these findings for models of mating-type switching are discussed.


Is There a Consensus when Physicians Evaluate the Relevance of Retrieved Systematic Reviews?
A significant challenge associated with practicing evidence-based medicine is to provide physicians with relevant clinical information when it is needed. At the same time it appears that the notion of relevance is subjective and its perception is affected by a number of contextual factors. To assess to what extent physicians agree on the relevance of evidence in the form of systematic reviews for a common set of patient cases, and to identify possible contextual factors that influence their perception of relevance. A web-based survey was used where pediatric emergency physicians from multiple academic centers across Canada were asked to evaluate the relevance of systematic reviews retrieved automatically for 14 written case vignettes (paper patients). The vignettes were derived from prospective data describing pediatric patients with asthma exacerbations presenting at the emergency department. To limit the cognitive burden on respondents, the number of reviews associated with each vignette was limited to three. Twenty-two academic emergency physicians with varying years of clinical practice completed the survey. There was no consensus in their evaluation of relevance of the retrieved reviews and physicians' assessments ranged from very relevant to irrelevant evidence, with the majority of evaluations being somewhere in the middle. This indicates that the study participants did not share a notion of relevance uniformly. Further analysis of commentaries provided by the physicians allowed identifying three possible contextual factors: expected specificity of evidence (acute vs chronic condition), the terminology used in the systematic reviews, and the micro environment of clinical setting. There is no consensus among physicians with regards to what constitutes relevant clinical evidence for a given patient case. Subsequently, this finding suggests that evidence retrieval systems should allow for deep customization with regards to physician's preferences and contextual factors, including differences in the micro environment of each clinical setting.


The effects of replacing a portion of endurance training by explosive strength training on performance in trained cyclists.
To investigate the effects of replacing a portion of endurance training by strength training on exercise performance, 14 competitive cyclists were divided into an experimental (E; n = 6) and a control (C; n = 8) group. Both groups received a training program of 9 weeks. The total training volume for both groups was the same [E: 8.8 (1.1) h/week; C: 8.9 (1.7) h/week], but 37% of training for E consisted of explosive-type strength training, whilst C received endurance training only. Simulated time trial performance (TT), short-term performance (STP), maximal workload (Wmax) and gross (GE) and delta efficiency (DE) were measured before, after 4 weeks and at the end of the training program (9 weeks). No significant group-by-training effects for the markers of endurance performance (TT and Wmax) were found after 9 weeks, although after 4 weeks, these markers had only increased (P < 0.05) in E. STP decreased (P < 0.05) in C, whereas no changes were observed in E. For DE, a significant group-by-training interaction (P < 0.05) was found, and for GE the group-by-training interaction was not significant. It is concluded that replacing a portion of endurance training by explosive strength training prevents a decrease in STP without compromising gains in endurance performance of trained cyclists.


Association between ABO blood group and risk of Crohn's disease: A case-control study in the Chinese Han population.
Blood group O has been reported to be a potentially protective factor for Crohn's disease (CD) susceptibility in Caucasian and Korean populations, but a similar conclusion was not found in a Chinese study. The present study investigated the potential association in the Chinese Han population. We included 275 CD patients, 132 ulcerative colitis (UC) patients and 1201 healthy individuals in this case-control study. The demographic characteristics and ABO blood group were compared among the three groups. The clinical characteristics and treatment of CD were further investigated according to the blood group distribution. The blood group distribution in CD patients was significantly different from healthy controls, and the frequency of O blood in CD patients was significantly lower compared to healthy controls. After adjusting for age and gender, the non-O blood groups remained significantly associated with CD susceptibility in propensity score-adjusted and propensity score-matched analyses. Compared to CD patients with non-O blood groups, patients with O blood were at a lower risk of developing penetrating disease, more likely to receive immunosuppressant treatment and less likely to receive biological treatment. Our results confirmed that non-O blood groups were significantly associated with an increased risk of CD in the Chinese Han population.


Rat genetics: attaching physiology and pharmacology to the genome.
During the past five years, the Rat Genome Project has been rapidly gaining momentum, especially since the announcement in August 2000 of plans to sequence the rat genome. Combined with the wealth of physiological and pharmacological data for the rat, the genome sequence should facilitate the discovery of mammalian genes that underlie the physiological pathways that are involved in disease. Most importantly, this combined physiological and genomic information should also lead to the development of better pre-clinical models of human disease, which will aid in the development of new therapeutics.


Anti-inflammatory quinoline-4(1H)-one derivatives from the aerial parts of Waltheria indica linn.
Eight previously undescribed quinoline-4(1H)-one derivatives (1-8) and five known analogues (9-13) were isolated from the 95% aqueous extract of the aerial parts of Waltheria indica Linn. Their chemical structures were determined by analyzing 1D NMR, 2D NMR and HRESIMS data comprehensively. Compounds 1-8 possess diverse side chains at C-5 of quinoline-4(1H)-one or tetrahydroquinolin-4(1H)-one skeleton. The absolute configurations were assigned via comparison of the experimental and calculated ECD spectra, and analysis of the ECD data of the in situ formed [Rh2(OCOCF3)4] complex. Additionally, all 13 isolated compounds were evaluated for their anti-inflammatory activities by measuring the inhibitory effects of nitric oxide (NO) production in lipopolysaccharide-induced BV-2 cells. Compounds 2, 5 and 11 showed moderate inhibition toward NO production with IC50 values of 40.41 ± 1.01, 60.09 ± 1.23 and 55.38 ± 0.52 μM, respectively.


Prevalence of nonsuppressed viral load and associated factors among HIV-positive adults receiving antiretroviral therapy in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017): results from population-based nationally representative surveys.
The global target for 2020 is that ≥90% of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) will achieve viral load suppression (VLS). We examined VLS and its determinants among adults receiving ART for at least four months. We analysed data from the population-based HIV impact assessment (PHIA) surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe (2015 to 2017). PHIA surveys are nationally representative, cross-sectional household surveys. Data collection included structured interviews, home-based HIV testing and laboratory testing. Blood samples from PLHIV were analysed for HIV RNA, CD4 counts and recent exposure to antiretroviral drugs (ARVs). We calculated representative estimates for the prevalence of VLS (viral load <1000 copies/mL), nonsuppressed viral load (NVL; viral load ≥1000 copies/mL), virologic failure (VF; ARVs present and viral load ≥1000 copies/mL), interrupted ART (ARVs absent and viral load ≥1000 copies/mL) and rates of switching to second-line ART (protease inhibitors present) among PLHIV aged 15 to 59 years who participated in the PHIA surveys in Eswatini, Lesotho, Malawi, Zambia and Zimbabwe, initiated ART at least four months before the survey and were receiving ART at the time of the survey (according to self-report or ARV testing). We calculated odds ratios and incidence rate ratios for factors associated with NVL, VF, interrupted ART, and switching to second-line ART. We included 9200 adults receiving ART of whom 88.8% had VLS and 11.2% had NVL including 8.2% who experienced VF and 3.0% who interrupted ART. Younger age, male sex, less education, suboptimal adherence, receiving nevirapine, HIV non-disclosure, never having married and residing in Zimbabwe, Lesotho or Zambia were associated with higher odds of NVL. Among people with NVL, marriage, female sex, shorter ART duration, higher CD4 count and alcohol use were associated with lower odds for VF and higher odds for interrupted ART. Many people with VF (44.8%) had CD4 counts <200 cells/µL, but few (0.31% per year) switched to second-line ART. Countries are approaching global VLS targets for adults. Treatment support, in particular for younger adults, and people with higher CD4 counts, and switching of people to protease inhibitor- or integrase inhibitor-based regimens may further reduce NVL prevalence.


Non-surgical treatment of mild to moderate peri-implantitis with an oscillating chitosan brush or a titanium curette-12-month follow-up of a multicenter randomized clinical trial.
To study clinical and radiographic outcomes after non-surgical treatment of peri-implantitis using either an oscillating chitosan brush (OCB) or titanium curette (TC) and to observe changes in clinical signs of inflammation after repeated treatment. Thirty-nine patients with dental implants (n = 39) presented with radiographic bone level (RBL) of 2-4 mm, bleeding index (BI) ≥ 2, and probing pocket depth (PPD) ≥ 4 mm were randomly assigned to mechanical debridement with OCB (test) or TC (control). Treatment was performed at baseline and repeated at 3, 6, and 9 months in cases with > 1 implant site with BI ≥ 1 and PPD≥4 mm. Blinded examiners recorded PPD, BI, pus, and plaque. The radiographic bone level change between baseline and 12 months was calculated. A multistate model was used to calculate transitions of BI. Thirty-one patients completed the study. Both groups exhibited a significant reduction in PPD, BI, and pus at 12 months compared to baseline. Radiographic analysis showed stable mean RBL in both groups at 12 months. There was no statistically significant difference in any of the parameters between the groups. Within the limitations of this 12-month multicenter randomized clinical trial, non-surgical treatment of peri-implantitis with OCB or TC showed no statistically significant differences between the groups. Clinical improvements and, in some cases, disease resolution, was observed in both groups. However, persistent inflammation was a common finding which further puts emphasis on the need for further treatment.