Inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase thapsigargin stimulates production of nitric oxide and secretion of interferon-gamma.
Thapsigargin is a sesquiterpene lactone of guaianolide type isolated from the Mediterranean plant Thapsia garganica L. It is widely used experimentally as a potent and selective inhibitor of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) leading to rapid elevation of intracellular calcium [Ca2+]i. Several previous reports have shown that thapsigargin interferes with production of nitric oxide (NO) by mouse peritoneal macrophages and mouse macrophage cell lines. The present data confirm that thapsigargin is a modest inducer of NO in mouse macrophages, production of NO being slightly enhanced by lipopolysaccharide. However, thapsigargin on its own very potently induces NO in macrophages of rats under conditions in vitro. The highest effect was observed after the concentration of 0.25 microM thapsigargin, producing approximately 30 microM accumulation of nitrites in supernatants of cells cultured for 24 h. The aim of our experiments was to investigate immune mechanisms implicated in activation of high-output NO biosynthesis. It has been found that thapsigargin dose-dependently induces secretion of interferon-gamma (IFN-gamma) in macrophages of both rats and mice, and also in human peripheral blood mononuclear cells. The IFN-gamma production was rather low in macrophages of mice while relatively very high levels of IFN-gamma were found in cultures of rat macrophages and human peripheral blood mononuclear cells. The concentration of IFN-gamma produced by 5 microM thapsigargin within the interval of 24 h exceeded 3 ng/ml in rat macrophages and approached 2 ng/ml in cultures of human peripheral blood mononuclear cells. The effects are mediated by mitogen-activated protein kinases (MAPKs) such as p38 mitogen-activated protein kinase (p38) and extracellular signal-regulated kinases 1/2 (ERK1/2), and by nuclear transcriptional factor NF-kappaB. In summary, the original findings demonstrate immunostimulatory potential of thapsigargin and warrant more detailed preclinical studies.


The selection and maintenance of the V region determinant repertoire is germ-line encoded and T cell-independent.
The number of lipopolysaccharide-sensitive precursor cells synthesizing immunoglobulin (Ig) which reacts with the monoclonal anti-M460 antibody F6(51) has been determined in the spleen and in the bone marrow of different strains of mice. These precursor frequencies fall into two quantitatively different groups. The first group includes mice with the same Igh haplotype as BALB/c animals (Igha). In this group, spleen cells contained between 1:10(4) to 1:5 X 10(4) B cell precursors secreting Ig which bound F6(51). The second level of precursor was obtained with animals with allotypic haplotypes other than Igha. These values were too low to allow accurate frequency determinations. The frequency of these cells in mice of the latter group, however, increased dramatically when these animals were hyperimmunized with the monoclonal anti-M460 antibody. Similar results were obtained when the frequencies were determined using the Ig- fraction of bone marrow cells. Surprisingly, the numbers of lipopolysaccharide-sensitive B cell precursors secreting F6(51)-binding Ig in spleen cells of nude mice was found to be similar to the one in splenocytes of normal mice, and even in this case, the frequencies reflected the genetic background of the animals tested. Taken together these data support the notion that the establishment and the maintenance of the M460 idiotypic repertoire is germ-line encoded and independent of regulatory T cells.


[Spanish version of the Satisfaction With Decision scale: cross-cultural adaptation, validity and reliability].
The aim of this study is to develop a Spanish version of the Satisfaction With Decision scale (SWDs) and analyse the psychometric properties of validity and reliability. An observational, descriptive study and validation of a tool to measure satisfaction with the decision. Urology, Radiation oncology, and Medical oncology Departments of the Hospital Universitari Germans Trias i Pujol, Institut Català d'Oncologia and the Institut Oncològic del Vallès - Hospital General de Catalunya. A total of 170 participants diagnosed with prostate cancer, and who could read and write in Spanish and gave their informed consent. A translation, back-translation and cross-cultural adaptation to Spanish was performed on the SWDs. The content validity, criterion validity, construct validity and reliability (internal consistency and stability) of the Spanish version were evaluated. The SWDs contains 6 items with 5-item Likert scales. A Spanish version (ESD) was obtained that was linguistically and conceptually equivalent to the original version. Criterion validity, the ESD correlated with "satisfaction with the decision" using a linear analogue scale, was significant (r=0.63, P<.01) for all items. The factorial analysis showed a unique dimension to explain 82.08% of the variance. The ESD showed excellent results in terms of internal consistency (Cronbach alpha=0.95) and good test-retest reliability with intraclass correlation coefficient of 0.711. The ESD is a validated Spanish scale to measure the satisfaction with the decisions taken in health, and demonstrates a correct validity and reliability.


High efficacy of gemcitabine and cisplatin in patients with predominantly anthracycline- and taxane-pretreated metastatic breast cancer.
Effective and tolerable regimens are sought specifically in patients who have been pretreated with anthracyclines and taxanes. Gemcitabine and cisplatin demonstrated synergistic activity in vitro and provides a new mechanism of drug interaction. Previously treated patients with metastatic breast cancer (MBC) were enrolled in a multicentre phase II study. Treatment consisted of gemcitabine (750 mg/m(2)) and cisplatin (30 mg/m(2)) given on day 1 and 8 every 3 weeks. Thirty-eight patients were recruited, all of whom had previously received chemotherapy (35 pretreated with taxanes, 33 pretreated with anthracyclines). A median of 5 cycles of the study treatment was delivered. There were 2 complete and 13 partial responses, for an overall response rate of 40% (95% confidence interval: 23-56%). Thirteen patients (35%) had stable disease. Tumour response appeared independent of previously applied chemotherapy. Median time-to-progression was 6 months and median overall survival was 13.5 months. Main toxicities were leucopenia and thrombocytopenia (grade 3/4 in 26 and 16% of cycles, respectively). Non-haematological toxicity was rarely severe. Combination chemotherapy with gemcitabine and cisplatin given on 2 out of 3 weeks is well tolerated and active in heavily pretreated patients with MBC, even after prior exposure to anthracyclines and taxanes.


Obesity-Related Glomerulopathy: Clinical Management.
Obesity-related glomerulopathy (ORG) and other obesity-associated kidney diseases pose a major challenge to the treating nephrologist. We review the benefits of weight loss and optimal management of ORG and kidney disease in the setting of obesity. Therapeutic strategies in ORG were limited mainly in the past to weight loss through lifestyle interventions and bariatric surgery, antihypertensive treatment, and renin-angiotensin-aldosterone system blockade. Current approaches to obtain the desired weight loss include novel pharmacologic therapies that have been approved for the treatment of diabetes while offering kidney protection, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1-receptor agonists. This review focuses on the nephroprotective role of the renin-angiotensin-aldosterone system blockade and of these new pharmacologic agents, and on the renal effects of bariatric surgery in chronic kidney disease.


Effect of castration on eicosanoid and catecholamine-induced luteinizing hormone-releasing hormone release in vitro.
The castration of adult rats four weeks before experimentation did not alter either the basal production of prostaglandin (PG) E2 (intact rats 1157 +/- 160 pg/mg protein, castrated rats 1093 +/- 90 pg/mg protein) or the A 23187-induced production of PGE2 (1591 +/- 209 or 1701 +/- 286 pg/mg protein respectively) or that of leucotriene (LT) C4 (474 +/- 33, 389 +/- 39 pg/mg protein). Castration significantly reduced the absolute amounts of luteinizing hormone-releasing hormone (LHRH) released under basal conditions (594 +/- 56 pg/mg protein to 34% of intact controls) and after A 23187 stimulation (to 28% of controls). The LHRH released by the median eminence (ME) of castrated rats in the presence of PGE2 (10(-6) M), LTC4 (10(-8) M), norepinephrine (NE) (10(-5) M) or dopamine (DA) (10(-5) M and 10(-4) M) was significantly lower than the LHRH released by intact animals in the presence of these factors. However the relative values for LHRH release (e.g. as % of controls) indicated that the degree of stimulation was identical in intact and castrated rats (2-3 times). These data suggest that the absence of gonadal steroids resulting from long-term castration does not block the stimulatory action of eicosanoids or catecholamines on the release of LHRH by the ME of adult male rats in vitro. Furthermore, castration does not interfere with the biosynthesis of PGE2 and LTC4.


Modeling group heteroscedasticity in single-cell RNA-seq pseudo-bulk data.
Group heteroscedasticity is commonly observed in pseudo-bulk single-cell RNA-seq datasets and its presence can hamper the detection of differentially expressed genes. Since most bulk RNA-seq methods assume equal group variances, we introduce two new approaches that account for heteroscedastic groups, namely voomByGroup and voomWithQualityWeights using a blocked design (voomQWB). Compared to current gold-standard methods that do not account for group heteroscedasticity, we show results from simulations and various experiments that demonstrate the superior performance of voomByGroup and voomQWB in terms of error control and power when group variances in pseudo-bulk single-cell RNA-seq data are unequal.


Growth hormone isoforms and segments/fragments: molecular structure and laboratory measurement.
Endocrine diagnostic tests are dependent on the molecular characteristics of protein hormones, a property that is also intimately tied to function. The structure-function relationship is of particular importance for multifunctional protein hormones such as growth hormone (GH). For clinical diagnosis, it is imperative to understand the relationship between GH structure (and its molecular fragments) and function and their potential interaction with single or multiple receptors. The existence of a single or aggregated intact GH 22 kDa form such as the 20 kDa GH isoform has been described, but GH fragments cannot be excluded a priori. Recent advances and probable similarity of GH with other protein hormones such as natriuretic peptides (ANP, BNP and their proANP and proBNP fragments) and POMC (ACTH, beta-endorphin, etc.) lend support to the hypothesis that GH fragments should also be present. This brief review focuses on GH heterogeneity and feasible post-synthesis events. The aim of the review is to describe which GH forms/fragments have already been recognized and/or are potentially present in the circulation. The impacts of GH isoforms (namely the intact 20 and 22 kDa isoforms) and fragments thereof on quantitative measurement are discussed with reference to traditional immunoassay technology and innovative immunofunctional laboratory assays.


Problems and pitfalls of 3-D TOF magnetic resonance angiography of the intracranial circulation.
3-D Time of flight (TOF) Magnetic resonance angiography (MRA) is being increasingly adopted as a technique for assessment of the intracranial circulation in neuroradiological practice. We describe our recent experience of 3-D time of flight Magnetic resonance angiography. We describe some of the problems and potential pitfalls that we have experienced employing 3-D TOF MRA in these circumstances, and the diagnostic dilemmas that have arisen. A range of problems have been encountered. When performing 3-D TOF MRA, other phenomena such as sub-acute thrombus and high signal structures may be incorporated into the Maximal Intensity Projection (MIP) reconstruction and masquerade as vascular abnormalities. Interpretation of MIP reconstructions can also be difficult or impossible in the presence of sizeable haematoma. Conversely, vascular structures may not be appreciated because of loss of signal from saturation effects or dephasing due to slow or complex flow. Local susceptibility artefacts, from aneurysm clips or coils, may reduce the signal from vascular structures. Interpretation of 3-D TOF MRA must take account of potential pitfalls which can be minimized by adoption of appropriate imaging and review strategies. This requires careful consideration of MRA source data, the spin-echo axial images as well as the MIP reconstructions.


The metabolic syndrome is associated with the risk of urothelial carcinoma from a health examination database.
The metabolic syndrome was associated with bladder cancer in the previous studies. However, there have no large-scale cohort studies to elucidate the relationship between metabolic syndromes and urothelial carcinoma including urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC). We analyze a population-based cohort study by using physical examination data and diagnosis of UC from the Taiwan Cancer Registry Database. Differences in demographic and clinical characteristics among UTUC and non-UTUC groups, UBUC and non-UBUC groups were compared. Odds ratios (ORs) for determining risk factors were estimated through the multiple logistic regression model. A total of 557,063 records for 211,319 participants which consisted of 31 UTUC and 309 UBUC met the eligibility criteria in this study. Our results showed that female are more likely to develop UTUC than male. As opposed to UTUC, male are more likely to develop UBUC than female. It also showed that participants smoked or chewed betel quid daily are more likely to develop UBUC. Age and estimated glomerular filtration rate (eGFR) are significantly increased the risk of developing UTUC. The association between the eGFR and risk of UTUC is stronger (P < 0.001) for eGFR < 45 (vs. eGFR ≥ 75, OR = 6.795; 95% CI 2.901-15.917). Metabolic syndrome is related to higher risk of UBUC incidence [OR was 1.373 (95% CI 1.104-1.707)]. There was a significant relationship between the incidence of UBUC and metabolic syndrome. Renal function impairment presents higher risk in both UBUC and UTUC development.


Transient blood flow reduction induced by intra-arterial injection of degradable starch microspheres. Experiments on rats.
Starch microspheres, degradable by endogenous blood amylase were selectively injected into the femoral and superior mesenteric arteries, respectively, to obtain temporary local ischemia in foot and gut of the rat. The experimental models are described. Studies with tracer microspheres demonstrated, that the blood flow in the foot and the small intestine immediately declined to near zero, but latter resumed control levels.


Ketoprofen-loaded pomegranate seed oil nanoemulsion stabilized by pullulan: Selective antiglioma formulation for intravenous administration.
This study aimed to prepare pomegranate seed oil nanoemulsions containing ketoprofen using pullulan as a polymeric stabilizer, and to evaluate antitumor activity against in vitro glioma cells. Formulations were prepared by the spontaneous emulsification method and different concentrations of pullulan were tested. Nanoemulsions presented adequate droplet size, polydispersity index, zeta potential, pH, ketoprofen content and encapsulation efficiency. Nanoemulsions were able to delay the photodegradation profile of ketoprofen under UVC radiation, regardless of the concentration of pullulan. In vitro release study indicates that nanoemulsions were able to release approximately 95.0% of ketoprofen in 5h. Free ketoprofen and formulations were considered hemocompatible at 1 μg/mL, in a hemolysis study, for intravenous administration. In addition, a formulation containing the highest concentration of pullulan was tested against C6 cell line and demonstrated significant activity, and did not reduce fibroblasts viability. Thus, pullulan can be considered an interesting excipient to prepare nanostructured systems and nanoemulsion formulations can be considered promising alternatives for the treatment of glioma.


[Effect of obsidan on some mechanisms of the heart productivity regulation].
In acute experiments on anesthetized cats obsidan caused a decrease in the venous blood inflow to the heart and increased the volume of the vascular bed. It is suggested that the blockade of the myocardial beta-adrenoreceptors is not the only cause of such an effect.


Effect of Erythropoietin on Morphofunctional Properties of Mesenchymal Stem Cells.
We studied the effect of erythropoietin on the morphofunctional status of bone marrow mesenchymal stem cells in patients with coronary heart disease. It was shown that the duration of cell exposure with erythropoietin had different effects on the expression levels of adhesion molecules, erythropoietin receptors, and co-expression of the erythropoietin receptor and common β-chain of cytokines, apoptosis/necrosis, and the cell cycle. In most cases, erythropoietin increased proliferation, migration, and NO production by "aged" mesenchymal stem cells (passage 8) and passage 4 mesenchymal stem cells grown during the previous 3 passages in the presence of 33.4 U/ml erythropoietin. Erythropoietin increased the expression of the autophagy marker LC3B in mesenchymal stem cells grown in the presence of erythropoietin in the culture medium. Thus, long-term culturing of mesenchymal stem cells in the presence of erythropoietin in the culture medium increased their resistance to adverse microenvironment factors - oxidative stress and hyperglycemia.


Knowledge, Attitude, and Perception of Barriers for Eye Care among Diabetic Persons Registered at Employee Health Department of a Tertiary Eye Hospital of Central Saudi Arabia.
To evaluate the level of knowledge, attitudes, and barriers to diabetic retinopathy (DR) screening among diabetic healthcare staff at a tertiary eye hospital in central Saudi Arabia. This was a descriptive survey using a closed-ended questionnaire. A. 5-grade. Likert scale was used for responses to each question. Data were collected on patient demographics and the status of diabetes. Survey responses related to knowledge, attitude, and barriers were grouped. The study sample was comprised of 45 diabetics employed at the hospital. The mean age was 49 ± 11 years and 33 diabetics were males. One-third of the study population was referred to the eye clinic for DR screening. DR screening was performed in 25% of diabetics over the previous year. Twenty-nine (64%; 95% confidence intervals: 50-78) participants had excellent knowledge of eyecare for diabetic complications. Thirteen percent of participants had a positive attitude toward periodic eye checkups. Travel distance to an eyecare unit, no referral from family physicians for annual eye checkups and the lack of availability of gender-specific eyecare professionals were the main perceived barriers. Annual DR screening needs to be promoted to primary healthcare providers and diabetic patients. Barriers should be addressed to improve the uptake of DR screening.


Mechanisms underlying the serotonergic modulation of the spinal circuitry for locomotion in lamprey.
The central nervous system of the lamprey contains serotonergic (5-hydroxytryptamine, 5-HT) neurones both in the spinal cord and in the brainstem. Endogenously released 5-HT from these systems modulates the pattern of fictive locomotion induced in the in vitro preparation; the burst rate is lowered and burst discharges become longer and of higher intensity. Local application of 5-HT, mimicking activation of the 5-HT systems, has a specific effect on the late phase of the afterhyperpolarization (AHP) in motoneurones and interneurones. 5-HT markedly reduces the amplitude of the late AHP without affecting passive membrane properties or the shape or threshold of the action potential. This 5-HT effect appears to result from a direct action on the calcium-dependent potassium channels underlying the late phase of the AHP. A reduction of the amplitude of the AHP will result in altered spike discharge characteristics, with potentiation of the response (discharge rate) to a given excitatory input in all neurones influenced by 5-HT. It is suggested that the modulatory effect of 5-HT on fictive locomotion can be attributed to its action on the late AHP and thereby to the potentiation of excitability in excitatory and inhibitory interneurones in the generator circuitry. This has been further corroborated in computer simulation studies of a network model, where the action of 5-HT was simulated by decreasing AHP amplitude, resulting in a slowing of the rhythm analogous to the effect demonstrated experimentally.


Charles Henry Turner and the cognitive behavior of bees.
Social movements in several countries are stimulating a reconsideration of academic structures and historic figures and promoting reparation and recognition of marginalized and forgotten black scientists. A paradigmatic case in that sense is Charles Henry Turner (1867-1923) who was the first African American to receive a graduate degree at the University of Cincinnati and one of the first in earning a PhD degree of the University of Chicago. He performed numerous experiments on sensory perception, orientation, and mating of solitary and social bees, most of which have been unjustly forgotten despite the fact that they anticipated fundamental concepts of animal cognition. We review these studies and highlight the importance of his ideas for modern views of animal cognition and the study of bee behavior. We conclude that besides his scientific contributions, Turner is an inspiration for scientists fighting against social adversity and prejudices.


Biochemical properties of a penicillin beta-lactamase mediated by R factor from Bordetella bronchiseptica.
The beta-lactamase specified by an R(te16) plasmid in Bordetella bronchiseptica was purified 200-fold by carboxymethyl-Sephadex column chromatography and electrofocusing. The enzyme has a molecular weight of 46,000 +/- 3,000 and an isoelectric point of 8.3 and was highly active against phenethicillin, oxacillin, and propicillin. The enzyme activity was inhibited by sodium chloride but not by ferrous ion. The maximal enzyme activity to benzylpenicillin was observed at pH 7.0 to 7.5 and at 40 C. It is concluded that this enzyme is different from the R-mediated beta-lactamases, i.e., the type I and type II beta-lactamases which have been classified in previous papers.


Risk factors of frailty and death or only frailty after intensive care in non-frail elderly patients: a prospective non-interventional study.
Frailty status is recognized as an important parameter in critically ill elderly patients, but nothing is known about outcomes in non-frail patients regarding the development of frailty or frailty and death after intensive care. The aim of this study was to determine risk factors for frailty and death or only frailty 6 months after intensive care unit (ICU) admission in non-frail patients ≥ 65 years. A prospective non-interventional study performed in an academic ICU from February 2015 to February 2016 included non-frail ≥ 65-year-old patients hospitalized for > 24 h in the ICU. Frailty was assessed by calculating the frailty index (FI) at admission and 6 months later. Patients who remained non-frail (FI < 0.2) were compared to patients who presented frailty (FI ≥ 0.2) and those who presented frailty and death at 6 months. Among 974 admissions, 136 patients were eligible for the study and 88 patients were analysed at 6 months (non-frail n = 34, frail n = 29, death n = 25). Multivariable analysis showed that mechanical ventilation duration was an independent risk factor for frailty/death at 6 months (per day of mechanical ventilation, odds ratio [OR] = 1.11; 95% confidence interval [CI] 1.04-1.19, p = 0.002). When excluding patients who died, mechanical ventilation duration remained the sole risk factor for frailty at 6 months (OR = 1.19; 95% CI 1.07-1.33, p = 0.001). Mechanical ventilation duration was the sole predictive factor of frailty and death or only frailty 6 months after ICU hospitalization in initially non-frail patients.


Effects of Zostera marina on the patterns of spatial distribution of sediments and macrozoobenthos in the boreal lagoon of Furen (Hokkaido, Japan).
Understanding patterns of spatial variations in benthic seagrass assemblages is a central issue in seagrass ecology. However, how patterns of spatial variations in macrozoobenthos and associated sediments differ between vegetated and unvegetated areas remain largely unexplored. In the present study, two different habitats represented by dense Zostera marina beds (Zostera) and unvegetated sediments (Bare) were compared at three locations, 100's meters apart, located at progressive distance from the Furen river in the boreal lagoon of Furen (Hokkaido, Japan). We tested the hypothesis that Z. marina influences the patterns of spatial distribution of abiotic and biotic components along an environmental (estuarine) gradient. The results showed considerable differences between Zostera and Bare, as well as between and within locations, in the distribution of both sediment variables (mud, total organic carbon [TOC] and total nitrogen, acid volatile sulfide, chlorophyll-a and pheopigments) and macrozoobenthic assemblage metrics (total number of species [S], Shannon-Weiner diversity index [H'], total abundance and abundance of dominant species). TOC content, associated to a high mud content, was highest in Bare irrespective of differences between locations (all being above a critical TOC threshold of 3.6%), while S and H' were higher in Zostera than in Bare at all locations. Significant location x habitat effects were found in the abundance of dominant species, represented mainly by mollusks and crustaceans. Furthermore, the proportions of spatial variance were greater at the scale of replicates (meters apart) than at the scale of stations (10's meters apart) for both sediment variables and the dominant species. Importantly, for the dominant species the spatial variance at the smaller scale was much higher in Zostera than in Bare, indicating that at the scale of meters Zostera beds increase the patchiness in the spatial distribution of individuals compared to bare sediments. Overall, our results demonstrate that Z. marina has a strong effect on the spatial heterogeneity in the intensity of the ecological processes influencing patterns of sediment and macrozoobenthos distribution along an environmental gradient. The present study provides a general framework to evaluate patterns of spatial distribution across various scales within several hundreds of meters in seagrass-dominated, eutrophic coastal lagoons.


Chronic ethanol exposure in rats affects rabs-dependent hepatic trafficking of apolipoprotein E and transferrin.
Because of the important roles of rabs in protein trafficking, we tested whether chronic ethanol exposure affected the trafficking of newly synthesized apolipoprotein E (apoE) or transferrin (O-glycosylated and N-glycosylated proteins, respectively) attached to acylated or prenylated rabs. The in vivo 30-min incorporation ratios of [3H]palmitate:[35S]methionine or [3H]mevalonate:[35S]methionine (relative ratios of rabs acylation or prenylation to total protein or to immunoisolated apoE or transferrin) were measured in various hepatic subcellular organelles of 8 week-ethanol-fed (E) and pair-fed control (C) Wistar-Furth rats. With respect to total protein trafficking, ethanol increased rabs acylation ratio by 136% (P <.01), 69% (P <.05), and 64% (P <.01) in the endoplasmic reticulum (ER), Golgi light fraction (GLF), and Golgi heavy fraction (GHF), respectively, and decreased this ratio by 76% (P <.01) in carrier vesicle fraction 2 (CV2). With respect to apoE trafficking, ethanol increased rabs acylation ratio by 121% in GHF and decreased this ratio by 27% in CV2. Rabs prenylation ratio increased by 21% and 53% in GHF and CV2, respectively, and decreased by 42% in GLF. With respect to transferrin trafficking, ethanol increased rabs acylation ratio by 53% (P <.01) in GHF, with no significant effect in ER, whereas rabs prenylation ratio increased by 26% (P <.05) in ER, with no significant effect in GHF. Therefore, we conclude that ethanol-induced impaired trafficking of newly synthesized O- and N-glycosylated proteins occurs primarily in ER and Golgi and is due to altered lipidation of rabs, possibly rabs 1, 2, or 6 or combinations of these three rabs.


Measuring walking-related performance fatigability in clinical practice: a systematic review.
Fatigability, a change in performance according to tasks and circumstances, can contribute to walking limitations in daily life. Walking-related fatigability (WF) has been assessed subjectively, but current knowledge on best objective measurement methods is limited. The aim of this study was to provide an overview of objective clinical measurement methods assessing WF in different populations. Articles were searched in Pubmed and Web Of Science by two independent raters. Studies were included when meeting inclusion criteria of measuring WF objectively in a clinical setting, with no exclusion towards any population. Case studies and reviews were not included in the review (systematic review registration number: PROSPERO - CRD42017074121). In total, 28 articles were included. The study populations were older adults (N.=7), multiple sclerosis (N.=14), spinal muscle atrophy (N.=3), osteoarthritis (N.=3), interstitial lung diseases (N.=1), and myasthenia gravis (N.=1). Data about patient characteristics, walking task, WF formula and interpretation (cut-off values and/or psychometric properties) got extracted from included literature. Every included article got checked for quality and risk of bias. WF was mostly measured during longer walking test such as six-minute walking test (6MWT) and 500 or 400-m walking test, by comparing the first and last minute or lap for spatiotemporal or kinematic changes in well-defined formulas. No gold standard is however available yet given different tasks or outcome measures across study populations. Longer walking test were most often used, with a preference towards the 6MWT, thereby comparing the changes over the last and first part of the test. Psychometric properties need more documentation before inclusion as experimental outcome.


Antispasmodic activity on the gallbladder of the mouse of CR 1409 (lorglumide) a potent antagonist of peripheral CCK.
Cholecystokinin (CCK) is a hormonal regulator of the motility of the gallbladder. CCK-8, i.e. the biologically active C-terminal octapeptide of the hormone, elicits contraction and emptying of the gallbladder. Endogenous CCK released by egg yolk or fatty acids in the duodenum gives the same results. CR 1409 (lorglumide), a glutaramic acid derivative with peripheric competitive CCK-antagonistic activity, was evaluated in comparison with proglumide (the model CCK-receptor antagonist) and other conventional antispasmodic drugs, for their ability to inhibit the emptying of the gallbladder induced in mice by CCK-8 or by lyophylized egg yolk. CR 1409 (1-10 mg/kg) prevented dose-dependently the emptying of the gallbladder in both experimental models; proglumide exhibited a comparable activity at much higher doses (200-800 mg/kg). On the contrary the anticholinergic drug atropine, the calcium-antagonist nifedipine, and the phosphodiesterase inhibitor papaverine were almost ineffective. The present data support the hypothesis that the effects of CCK on gallbladder motility are mediated by a CCK-dependent specific mechanism.


The variability of muscle nerve sympathetic activity in resting recumbent man.
1. Pulse synchronous bursts of multi-unit sympathetic activity was recorded from median or peroneal muscle nerve fascicles in fourteen subjects resting in the recumbent position. The neural activity was quantitated in terms of burst incidence, i.e. the number of bursts in the mean voltage neurogram/100 heart beats, during successive rest periods of 2-4 min.2. For each individual the burst incidence was fairly constant between different rest periods but the mean burst incidence varied widely between individuals, the range being from less than 10 to more than 90 bursts/100 heart beats.3. Simultaneous double nerve recordings were made on one subject from median and peroneal nerves and on eight subjects from the two peroneal nerves. There was always close similarity between the two records in such experiments regardless of which muscles the nerve fascicles innervated. When analysed separately the difference in burst incidence between the two sides ranged from 0.7 to 5.1 bursts/100 heart beats. The findings suggest that sympathetic neurones destined to skeletal muscles are subjected to a homogenous central drive and that contributions to the activity from ganglionic or segmental sources are of lesser importance.4. On seven subjects repeated recordings at rest were made with intervals of 3 weeks-21 months between recordings. In each subject mean burst incidences were similar in all recordings (range of differences 0.5-11.2 bursts/100 heart beats) suggesting an individually constant level of sympathetic activity in muscle nerves.5. For each individual the variability of burst amplitudes in the mean voltage neurogram was described by burst amplitude spectra. Most subjects had a relatively larger proportion of small than high amplitude bursts, but there was a tendency for more even amplitude distributions in subjects with high burst incidence. The finding may be an indication of interindividual differences in the average number of impulses/burst.6. It is concluded that the multi-unit recording technique can be used for comparisons of the level of muscle nerve ;sympathetic tone' between different subjects.


Perception of social support among family caregivers of vegetative patients: A qualitative study.
A vegetative state (VS) is the probable result after brain damage. After VS patients are discharged from the hospital, the responsibility of caring of them is transferred to their families, which impacts a caregiver's physical and psychological health. Social support as a valuable resource reduces the negative effects of stressful events. This study aimed to explore the perception of social support among family caregivers of VS patients. This study is a part of a larger qualitative study which used the descriptive and qualitative method. Purposeful and theoretical sampling was done, and data was gathered through face-to-face, in-depth interviews. The four categories of "Family, a supporter in all aspects," "Beautiful emanation of the nurse's role," "Revitalization via empathy and companionship," and "Defects in support," were extracted. The primary concern of participants was receiving social support which can facilitate caregiving and coping with difficulties, but there are many shortcomings in supporting these caregivers.


A bibliometrix-based visualization analysis of international studies on conversations of people with aphasia: Present and prospects.
In recent years, there has been a rapid increase in the number of people with aphasia due to brain lesions worldwide, which has prompted researchers to carry out in-depth studies on the pathogenesis, inducement and prognosis of aphasia from neurology, clinical medicine, psychology and other disciplines. With the deepening of research and understanding of aphasia, it is generally believed that a single discipline can no longer meet the needs of the academic community. Therefore, multidisciplinary integration has emerged and achieved fruitful results. This paper, based on the biblioshiny package run by R, conducts bibliometric analysis on the international interdisciplinary research status of conversation and aphasia, predicts its future development direction, and provides reference for relevant domestic research from international source journals. The results indicate that led by Australia, the United Kingdom, the United States and other countries, the international conversational aphasia research has formed a complete system, and formed a "descriptive study of patients with language disorders" and "applied study of rehabilitation treatment". In the future, while continuing to focus on these two categories of research, the empathy ability of conversational partners and medical staff may be taken into account, in order to better contribute to improving patients' quality of life.


The dawn of interoperating spatial models in cell biology.
Spatial simulations are becoming an increasingly ubiquitous component in the cycle of discovery, experimentation, and communication across the sciences. In cell biology, many researchers share a vision of developing multiscale models that recapitulate observable behaviors spanning from atoms to cells to tissues. For this dream to become a reality, however, simulation technologies must provide a means for integration and interoperability as they advance. Already, the field has developed numerous methods that span scales of length, time, and complexity to create an extensive body of effective simulation approaches, and although these approaches rarely interoperate, they collectively cover a large spectrum of knowledge that future models may handle in a more unified manner. Here, we discuss the importance of making the data, workflows, and outputs of spatial simulations shareable and interoperable; and how democratization could encourage diverse biologists to participate more easily in developing models to advance our understanding of biological systems.


Vidian artery as a collateral channel between the external and occluded internal carotid arteries--case report--.
A 68-year-old man presented with occlusion of the internal carotid artery (ICA) manifesting as a 6-month history of progressive sensory and motor disturbance of the left lower limb. Angiography clearly demonstrated a collateral arterial network between the ICA and external carotid artery (ECA) through the vidian artery, a small branch of both the ICA and ECA. The vidian artery may form an unusual but important ECA-ICA collateral pathway in patients with occlusive lesion of the ICA.


High prevalence of multiresistance in levofloxacin-nonsusceptible Streptococcus pneumoniae isolates in Korea.
Korea exhibits the highest rates of multidrug resistance among Streptococcus pneumoniae. The increasing use of levofloxacin has raised concern about the dissemination of levofloxacin resistance in dominant multidrug-resistant (MDR) clones of our pneumococcal population. A total of 50 levofloxacin-nonsusceptible S. pneumoniae (MIC, ≥4 μg/mL) collected from a multihospital network from 1996 to 2006 were analyzed for serotype, antibiotic resistance profile, quinolone resistance-determining region mutation, and multilocus sequence type. Most levofloxacin-nonsusceptible S. pneumoniae (94.0%) exhibited an MDR phenotype. This phenotype was closely associated with a limited number of epidemic MDR clones that are well-known key agents of the global spread of antimicrobial resistance in S. pneumoniae. However, the clonal dissemination of levofloxacin-nonsusceptible S. pneumoniae was rare. Levofloxacin-nonsusceptible clones with nonvaccine serotypes increased during the post-vaccine era in this study. This result suggests that Korean clinicians must be aware of the levofloxacin resistance trend and need to be more prudent for the first choice of fluoroquinolone for empiric treatment of respiratory tract infections in clinical setting. Moreover, the emergence of new clones and their variations may be more frequently associated with resistance under this selective pressure, such as the introduction of a 7-valent pneumococcal conjugate vaccine into our community.


Adjacent segment degeneration and disease after lumbar fusion compared with motion-preserving procedures: a meta-analysis.
The purpose of our study was to compare lumbar fusion and motion-preserving procedures to determine whether lumbar fusion may be associated with a higher prevalence of adjacent segment degeneration (ASDeg) or adjacent segment disease (ASDis). We performed a systematic review and meta-analysis for articles published up to July 2013. We included randomized controlled trials and cohort studies that reported ASDeg or ASDis after lumbar fusion compared with motion-preserving devices. Two authors independently extracted the articles and the predefined data. A total of 13 studies with 1,270 patients met our inclusion criteria and were included in the final analysis. Our analysis showed that the prevalence of ASDeg and ASDis, and adjacent segment reoperation rate in the fusion group were higher than those in the motion-preserving devices group (P < 0.0001, P = 0.0008, and P < 0.0001, respectively). The prevalence of ASDeg and reoperation rate in the motion-preserving devices group were significantly lower than that in the fusion group for both short- and long-term follow-up (P = 0.0008 and P = 0.001 at <5 years of follow-up; P = 0.003 and P = 0.001 at >5 years of follow-up). The current evidence suggests that lumbar fusion may result in a higher prevalence of adjacent segment degeneration or disease than motion-preserving procedures.


High levels of IL-10 and determination of other cytokines and chemokines in HIV-associated haemophagocytic syndrome.
Haemophagocytic syndrome (HPS) and HIV infection are both associated with cytokine network dysregulation. We therefore analysed plasma levels and mRNA synthesis in peripheral blood mononuclear cells (PBMC) of cytokines, chemokines and chemokine receptors in one HIV-infected patient with HPS. We compared the results with those for eight HIV-infected patients with similar CD4+ T cell counts (207/mm3 versus controls: median 214/mm3) and plasma virus load (4.1 log copies/ml, versus controls: median 4.2 log copies/ml). The HPS patient had a lower viral DNA load in PBMC and higher plasma levels of interferon-gamma, IL-10, and macrophage inflammatory protein (MIP)-1beta. No difference in plasma tumour necrosis factor-alpha (TNF-alpha), IL-6 and MIP-1alpha concentration was observed between the HPS patient and control patients. No difference was observed in TNF-alpha, IL-1beta, IL-10, IL-4, MIP-1alpha, MIP-1beta, RANTES, CXCR-4, and CCR-5 mRNA levels in PBMC, but IL-6 levels were higher in the HPS patient. Our results emphasize the role of IL-10 in the control of immune hyperactivation that is observed in HPS.


Chronotherapeutic efficacy of suvorexant on sleep quality and metabolic parameters in patients with type 2 diabetes and insomnia.
This study aimed to assess the chronotherapeutic efficacy of suvorexant on subjective sleep parameters and metabolic parameters in patients with type 2 diabetes and insomnia. Thirteen patients with type 2 diabetes who met the Pittsburg Sleep Quality index criteria for primary insomnia took suvorexant 20 mg/day (15 mg/day for ≥65 years) for 14 ± 2 weeks. The following parameters were assessed before and after the treatment: sleep diary for sleep duration and quality (i.e., sleep onset latency, waking after sleep onset, and sleep efficiency [sSE]), Insomnia Severity Index, clinical and biochemical data, continuous glucose monitoring (CGM), and validated self-administered questionnaire on food intake. Suvorexant significantly improved sSE, abdominal circumference, and sucrose intake (all p < 0.05), but did not change HbA1c, CGM parameters, or body weight. Correlation analysis revealed that changes in sSE were associated with those in HbA1c and body weight (r = -0.61 and r = -0.66, respectively; both p < 0.05). Suvorexant significantly improved sleep quality and obesity-associated parameters in patients with type 2 diabetes in 14 weeks. Improvements in sleep quality were associated with improvements in glycemic control. Sleep disorder treatment using suvorexant may provide metabolic benefits for patients with type 2 diabetes.


Web-based tool for dynamic functional outcome after acute ischemic stroke and comparison with existing models.
Acute ischemic stroke (AIS) is one of the leading causes of death and adult disability worldwide. In the present study, we aimed to develop a web-based risk model for predicting dynamic functional status at discharge, 3-month, 6-month, and 1-year after acute ischemic stroke (Dynamic Functional Status after Acute Ischemic Stroke, DFS-AIS). The DFS-AIS was developed based on the China National Stroke Registry (CNSR), in which eligible patients were randomly divided into derivation (60%) and validation (40%) cohorts. Good functional outcome was defined as modified Rankin Scale (mRS) score ≤ 2 at discharge, 3-month, 6-month, and 1-year after AIS, respectively. Independent predictors of each outcome measure were obtained using multivariable logistic regression. The area under the receiver operating characteristic curve (AUROC) and plot of observed and predicted risk were used to assess model discrimination and calibration. A total of 12,026 patients were included and the median age was 67 (interquartile range: 57-75). The proportion of patients with good functional outcome at discharge, 3-month, 6-month, and 1-year after AIS was 67.9%, 66.5%, 66.9% and 66.9%, respectively. Age, gender, medical history of diabetes mellitus, stroke or transient ischemic attack, current smoking and atrial fibrillation, pre-stroke dependence, pre-stroke statins using, admission National Institutes of Health Stroke Scale score, admission blood glucose were identified as independent predictors of functional outcome at different time points after AIS. The DFS-AIS was developed from sets of predictors of mRS ≤ 2 at different time points following AIS. The DFS-AIS demonstrated good discrimination in the derivation and validation cohorts (AUROC range: 0.837-0.845). Plots of observed versus predicted likelihood showed excellent calibration in the derivation and validation cohorts (all r = 0.99, P < 0.001). When compared to 8 existing models, the DFS-AIS showed significantly better discrimination for good functional outcome and mortality at discharge, 3-month, 6-month, and 1-year after AIS (all P < 0.0001). The DFS-AIS is a valid risk model to predict functional outcome at discharge, 3-month, 6-month, and 1-year after AIS.


Permethrin-treated bed nets do not have a 'mass-killing effect' on village populations of Anopheles gambiae s.l. in The Gambia.
In The Gambia, the use of permethrin-treated bed nets has led to a reduction in morbidity and mortality from malaria in children. However, no clear evidence has been found for a 'mass-killing effect' on the mosquito vectors as a result of this intervention. Two further entomological studies to investigate this phenomenon have been carried out. In one study, 20 villages were paired so that bed nets in one member of each pair were treated with permethrin. In the other, a cross-over design was used in which treated and untreated bed nets were exchanged between 2 villages. Longevity, biting rate and resting density of the malaria vector population and sporozoite rates were assessed in both studies. Malaria vectors were equally abundant and long-lived, and as likely to be infective, in villages with treated bed nets as in those with untreated nets. However, a clear reduction in the density of the indoor-resting population of mosquitoes in rooms with treated bed nets was found, probably reflecting the excito-repellency of the insecticide. This study confirmed that, in The Gambia, the protection against death and morbidity from malaria seen in children using treated bed nets must be due primarily to personal protection rather than to a 'mass-killing effect' on the mosquito vector population at a village level.


Effects and Mechanisms of Anlotinib and Dihydroartemisinin Combination Therapy in Ameliorating Malignant Biological Behavior of Gastric Cancer Cells.
Gastric Cancer (GC) is currently one of the major malignancies that threaten human lives and health. Anlotinib is a novel small-molecule that inhibits angiogenesis to exert antitumor effects. However, its function in gastric cancer is incompletely understood. The aim of the present study was to investigate the anti-tumor effects and molecular mechanisms of anlotinib combined with Dihydroartemisinin (DHA) in SGC7901 gastric cancer cells. Different concentrations of anlotinib and DHA were used to treat SGC7901 gastric cancer cells, after which cell proliferation was measured. Drug interactions of anlotinib and DHA were analyzed by the Chou-Talalay method with CompuSyn software. Proliferation, apoptosis, invasion, migration, and angiogenesis were measured using the Cell Counting Kit-8 (CCK8) assay, flow cytometry, Transwell invasion assays, scratch assays, and chicken Chorioallantoic Membrane (CAM) assays. Proliferation- associated protein (Ki67), apoptosis-related protein (Bcl-2), and Vascular Endothelial Growth Factor A (VEGF-A) were quantified by Western blotting. The combination of 2.5 μmol/L of anlotinib and 5 of μmol/L DHA was highly synergistic in inhibiting cell growth, significantly increased the apoptosis rate and suppressed obviously the invasion and migration capability and angiogenesis of gastric cancer cells. In addition, the expression levels of Ki67, Bcl-2, and VEGF-A, as well as angiogenesis, were significantly decreased in the Combination of drugs compared with control and either drug alone. The combination of anlotinib and DHA showed synergistic antitumor activity, suggesting their potential in treating patients with gastric cancer.


Na+ transport in human proximal colonic apical membrane vesicles.
The mechanisms of Na+ movement across colonocyte plasma membranes in the human colon are not well understood. Current studies were undertaken to investigate Na+ transport pathways in apical membranes of proximal organ donor colons. Purified apical membrane vesicles and rapid filtration 22Na-uptake techniques were used. An outwardly directed H(+)-gradient (pH 5.5 in/7.5 out) increased 22Na uptake into these vesicles. H+ gradient-driven 22Na uptake was significantly reduced by voltage clamping with K+/valinomycin, but was significantly stimulated by creation of an inside-negative potential. Potential sensitive 22Na uptake was inhibited by Na+ channel inhibitors phenamil and benzamil. Electroneutral 22Na uptake was insensitive to phenamil and benzamil, but was inhibited by amiloride, 5-(N,N-dimethyl)amiloride, 5-(N,N-hexamethylene)amiloride, and 5-(N-ethyl-N-isopropyl)amiloride. Electroneutral 22Na uptake showed saturation kinetics with an apparent Michaelis constant for Na+ of 11.8 +/- 2.4 mmol/L and a maximal velocity of 2.5 +/- 0.6 nmol.mg protein-1 x 5 s-1. The mechanism of amiloride inhibition was noncompetitive with an inhibitor constant for amiloride of 325 mumol/L. Acetazolamide, furosemide, bumetanide, 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stibene, and 4,4'-di-isothiocyanatostilbene-2,2'-disulfonic acid (1 mmol/L each) failed to inhibit 22Na uptake. Li+ and NH4+ (but not Cs+, K+, or choline+) inhibited H(+)-gradient driven 22Na uptake. Na+ transport in human proximal colonic apical membrane vesicles involves both conductive Na+ transport and an electroneutral Na(+)-H+ exchange.


Selective phosphodiesterase 3 inhibitor olprinone attenuates meconium-induced oxidative lung injury.
Since inflammation and oxidation play a key role in the pathophysiology of neonatal meconium aspiration syndrome, various anti-inflammatory drugs have been tested in the treatment. This study evaluated whether the phosphodiesterase (PDE) 3 inhibitor olprinone can alleviate meconium-induced inflammation and oxidative lung injury. Oxygen-ventilated rabbits intratracheally received 4 ml/kg of meconium (25 mg/ml) or saline. Thirty minutes after meconium/saline instillation, meconium-instilled animals were treated by intravenous olprinone (0.2 mg/kg) or were left without treatment. All animals were oxygen-ventilated for an additional 5 h. A bronchoalveolar lavage (BAL) of the left lungs was performed and differential leukocyte count in the sediment was estimated. The right lungs were used to determine lung edema by wet/dry weight ratio, as well as to detect oxidative damage to the lungs. In the lung tissue homogenate, total antioxidant status (TAS) was determined. In isolated lung mitochondria, the thiol group content, conjugated dienes, thiobarbituric acid-reactive substances (TBARS), dityrosine, lysine-lipid peroxidation products, and activity of cytochrome c oxidase (COX) were estimated. To evaluate the effects of meconium instillation and olprinone treatment on the systemic level, TBARS and TAS were determined in the blood plasma, as well. Meconium instillation increased the relative numbers of neutrophils and eosinophils in the BAL fluid, increased edema formation and concentrations of oxidation markers, and decreased TAS. Treatment with olprinone reduced the numbers of polymorphonuclears in the BAL fluid, decreased the formation of most oxidation markers in the lungs, reduced lung edema and prevented a decrease in TAS in the lung homogenate compared to non-treated animals. In the blood plasma, olprinone decreased TBARS and increased TAS compared to the non-treated group. Conclusion, the selective PDE3 inhibitor olprinone has shown potent antioxidative and anti-inflammatory effects in the meconium-induced oxidative lung injury.


Genotype modulates the aggression-promoting quality of progesterone in pregnant mice.
During late pregnancy, female mice of the DBA/2J inbred strain are more likely to exhibit aggressive behavior toward a standard stimulus intruder male than C57BL/6J females. This strain difference can not be accounted for by differences in circulating levels of progesterone (P) since pregnant DBA/2J and C57BL/6J females exhibit similar patterns of the steroid throughout pregnancy. Upon receiving subcutaneously implanted Silastic capsules containing P, virgin DBA/2J mice are more likely than virgin C57BL/6J to respond to the steroid by exhibiting aggression. Strain differences in the aggressive behavior exhibited by pregnant mice may be related to genotype-based variation in central neural tissue sensitivity to P.


Bioactive glass composite for orthodontic adhesives - Formation and characterisation of apatites using MAS-NMR and SEM.
To study the dissolution and fluoroapatite (FAP) formation of a new bioactive glass (BAG)-resin adhesive in an acidic solution in reference to neutral solutions, using the magic angle spinning-nuclear magnetic resonance (MAS-NMR) and the scanning electron microscopy (SEM). BAG composite disks (n = 90) were prepared from, novel fluoride-containing BAG-resin. Three sample groups (n = 30) of the disks were immersed in Tris buffer pH = 7.3 (TB), neutral artificial saliva pH = 7 (AS7) and acidic artificial saliva pH = 4 (AS4) at ten time points (from 6 h to 6 months). Half of the immersed disks at each time point were crushed into a powder and investigated by the solid state MAS-NMR. SEM studies were undertaken by embedding the other half of the immersed disk in a self-cure acrylic where the fracture surface was imaged. MAS-NMR results show that the BAG composite degraded significantly faster in AS4 compared to TB and AS7. At the end of the immersion period (6 months), around 80% of the glass particles in AS4 had reacted to form an apatite, evidenced by the sharp peak at 2.82 ppm in 31P signals compared to a broader peak in TB and AS7. It also shows evidence of fluorapatite (FAP) formation, indicated by 19F signal at -103 ppm, while signal around -108 ppm indicated the formation of calcium fluoride, from the excess Ca2+ and F- especially on longer immersion. SEM images confirm higher degradation rate of the BAG composite in AS4 and reveal the impact of time on the dissolution of more glass particles. The images also indicate apatite formation around the glass particles in TB and AS4, while it forms predominantly over the disk surface in AS7. BAG composite demonstrate smart reactivity in response to pH change which has a potential clinical benefit against demineralization and promoting remineralisation to form more stable fluorapatites.


Comparison of different culture media and growth conditions for recognition of Arcanobacterium haemolyticum.
Detection of Arcanobacterium haemolyticum is based upon typical beta-hemolysis and colony morphology, but it may go undetected if only conventional sheep blood agar media for detection of beta-hemolytic streptococci are used. The influence of different culture media, atmospheres, and times of incubation for the recognition of colonies of 47 isolates of A. haemolyticum was studied. After 48 h of incubation, trypticase soy agar with 5% horse blood in 5% CO(2) was the best medium.


Reversibility with sodium bicarbonate of styrene maleic anhydride, an intravasal injectable contraceptive, in male rats.
A copolymer of styrene and maleic anhydride (SMA) was dissolved in dimethyl sulphoxide (DMSO) and injected into the lumen of the vas deferens of rats. The polymer was retained in the lumen for a period of more than 90 days. Sodium bicarbonate (10%), pH 8.9, was used to flush the polymeric material from the vas deferens lumen. The reversibility and patency of the vas deferens was thus obtained. Sodium bicarbonate proved to be an effective alternative to dimethyl sulphoxide for reversal.


Prognostic value of prognostic nutritional index in nasopharyngeal carcinoma: A meta-analysis containing 4511 patients.
The prognostic nutritional index (PNI) is an index reflecting the nutritional and inflammatory status of patients and is explored for prognosis in nasopharyngeal carcinoma (NPC). However, the data are conflicting. In the current study, a meta-analysis was performed to comprehensively clarify the association between PNI and prognosis of NPC. PubMed, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), and Wanfang database were searched up to July 25, 2020. Hazard ratio (HR) and with 95% confidence interval (CI) were calculated to assess the impact of PNI on the survival outcomes of patients with NPC. A total of 10 studies containing with 4511 patients were identified. The pooled results showed that NPC patients with a low PNI would have a worse overall survival (OS) (HR = 1.89, 95%CI = 1.59-2.25, p < 0.001), distant metastasis-free survival (DMFS) (HR = 2.01. 95%CI = 1.66-2.43, p < 0.001), progression-free survival (PFS) (HR = 1.59, 95%CI = 1.32-1.91, p < 0.001), and locoregional recurrence-free survival (LRRFS) (HR = 1.51, 95%CI = 1.04-2.21, p = 0.032). Subgroup analysis showed that the low PNI was still a significant prognostic factor for OS and DMFS. Our meta-analysis demonstrated that a low PNI was significantly correlated to poor OS, DMFS, PFS, and LRRFS in NPC. Therefore, we suggest PNI applied as an indicator for prediction of the short- and long- term survival outcomes in patients with NPC.


Selective chemical modifications of polymyxin B.
Polymyxin B (1) monohydrochloride was converted to the tetra-BOC derivatives 1b and 1c by reaction with di-tert-butyl dicarbonate. The structures of these protected intermediates were established utilizing a degradative sequence that afforded 3 and 5. A method for the deprotection 2,4-dinitrophenylamines to the free amine, utilizing a strongly basic ion-exchange resin, was developed for use in the degradative sequence. The tetra-BOC derivatives 1b and 1c were used to prepare several Polymyxin B derivatives 6-27 at the DAB1 and DAB9-gamma-amine. The antibacterial activity of these selectively functionalized derivatives is reported here.


[A case of late pneumatocephalon and late meningitis after a conservatively treated fronto-basal fracture (author's transl)].
An unusal case of fronto-basal fractures in reported and the question of the management of such fractures is discussed.


Preventing retinal apoptosis--is there a common therapeutic theme?
There is an urgent need for therapies for retinal diseases; retinitis pigmentosa sufferers have no treatment options available and those targeted at other retinopathies have shown limited effectiveness. The process of programmed cell death or apoptosis although complex, remains a possible target for the treatment of retinal diseases. Having identified apoptosis in the vertebrate retina in populations of immature neurons as an essential part of development it was proposed that re-activation of these developmental cell death pathways might provide insight into the death mechanisms operating in retinal diseases. However, the discovery that numerous factors initiate and mediate the apoptotic cascade in mature photoreceptors has resulted in a relatively untargeted approach to examining and arresting apoptosis in the retina. In the last 5 years, mouse models have been treated with a diverse range of drugs or factors including anti-oxidants, growth factors, steroid hormones, calcium/calpain inhibitors and tetracycline antibiotics. Therefore to draw a unifying theme from these broad research areas is challenging. However, this review focusses on two targets which are currently under investigation, reactive oxygen species and mammalian target of rapamycin, drawing together the common themes of these research areas.


A qualitative exploration of the experiences of post-mortem forensic imaging in Malta: A psychological perspective.
This study aimed to qualitatively explore the experiences of post-mortem forensic imaging on theatre and trauma radiographers from a psychological perspective at a general hospital in Malta. The study utilised purposive sampling to recruit five radiographers undertaking forensic post-mortem imaging in a general hospital in Malta. Individual face-to-face semi-structured interviews were held. Interpretative phenomenological principles and reflexivity were applied throughout the transcription and analysis phases. Four themes were developed from the interpretive phenomenological analysis of semi-structured interviews: 'The impact of the imaging process,' 'Psychological distancing,' 'Finding meaning in work,' and 'Resource needs,' the latter comprising three subordinate themes: 'Protocols,' 'Physical resources,' and 'Psychological training.' Forensic radiography is a rewarding area of practice yet one that can be complex and have a lasting psychological impact. Many factors including working close to the cadaver, a lack of appropriate training and staffing levels and a lack of evidence-based protocols were identified by participants as contributing to potential psychological stress and emotional distress. Exploration and evaluation of the psychological experiences of radiographers undertaking post-mortem imaging will inform the development of appropriate psychological services and reinforce the need for the appropriate application of best practice guidelines and protocols to support radiographers working on traumatic cases within forensic and general radiographic practice.


Ozonation kinetics of cork-processing water in a bubble column reactor.
The oxidative degradation of organic pollutants present in cork-processing water at natural pH (6.45) was studied in a bubble column ozonation reactor. A steady reduction in both chemical oxygen demand (COD) and total organic carbon (TOC) was observed under the action of ozone alone and the feasibility of deep mineralisation (organic matter removal more than 90% in 120 min under the following experimental conditions: liquid volume 9L; superficial gas velocity 6.8x10(-3) m s(-1); ozone partial pressure 1.31 kPa; initial COD 328 mg L(-1); initial TOC 127 mg L(-1)) was demonstrated. The monitoring of pH, redox potential (ORP) and the mean oxidation number of carbon (MOC) was correlated with the oxidation and mineralisation of the organic species in the water. The ozonation of cork-processing water in the bubble column was analysed in terms of a mole balance coupled with ozonation kinetics modelled by the two-film theory of mass transfer and chemical reaction. Under the experimental conditions used, and in contrast with the literature, it was determined that the reaction follows a fast kinetic regime at the beginning of the oxidation process, shifting to the moderate and the slow kinetic regimes at later stages of the oxidation reaction. The dynamic change of the rate coefficient estimated by the model was correlated to changes in the water composition.


Assessment of IgE Reactivity of β-Casein by Western Blotting After Digestion with Simulated Gastric Fluid.
Cow's milk allergy is defined as an immunologically mediated adverse reaction to cow's milk proteins and it is usually, along with hen's egg allergy, the first food allergy identified in childhood.One of the main aspects to consider when evaluating the allergenic potential of food proteins is the effect of gastric digestion. It is known that allergens are usually able to survive the harsh acidic environment of the stomach, tolerate the presence of surfactants, and resist digestion by pepsin. They might also be digested into high molecular weight peptide fragments, which retain the same, or sometimes increased, IgE-binding. In this respect, western blotting is a highly sensitive and efficient technique that we have used to detect IgE-binding to the digests of milk and egg proteins. Given the importance of the resistance of food proteins to gastric digestion in their capacity to modulate the immune response, we describe in this chapter the assessment of IgE reactivity of a relevant cow's milk allergen, β-casein, by western blotting after simulated digestion under relevant physiological conditions.


Transcriptional induction of TGF-β1 and endothelial-to-mesenchymal transition cell markers in human umbilical vein endothelial cells by Ebola virus infection.
Ebola virus (EBOV) causes a serious hemorrhagic disease in humans, with a mortality rate of up to 80%. Despite significant achievements in the past decades elucidating the pathogenesis of EBOV, there is still much to be elucidated about the cell type-specific host response and their functional roles during infection. This study aimed to gain insight into cell type-specific host responses to EBOV infection. Real-time RT-qPCR analysis was used to identify host transcriptional changes in epithelial Caco-2 cells and endothelial HUVECs by EBOV infection. EBOV efficiently infected to both Caco-2 cells and HUVECs, depending on the time of infection. However, changes in the transcriptional levels of several host cellular genes following viral infection showed significant differences between Caco-2 cells and HUVECs. EBOV infection increases the transcription of TGF-β1, a key factor in epithelium-to-mesenchyme transition (EMT), only in HUVECs, but not in Caco-2 cells. This upregulation in turn induces the transcription of other EMT signaling molecules such as snail, slug and MMP9, ultimately leading to endothelial-to-mesenchymal transition (EndMT). Furthermore, this EndMT process appears to be associated with increased transcription of stem-cell markers such as Klf4, Sox2 and Oct4. However, most of these transcriptional changes due to EBOV infection did not occur in Caco-2 cells, suggesting that EMT or EndMT by EBOV infection is cell type-specific. We propose that EBOV infection induces the expression of TGF-β1-mediated signals in endothelial HUVECs, resulting in EndMT. This could provide broader information to elucidate the pathogenesis of Ebola virus disease.


The effect of prostaglandins on the electromyogram and motility of the monkey uterus and oviduct in late pregnancy and postpartum.
The electromyogram of the monkey (Macaca fuscata fuscata and Macaca mulatta) uterus in labor presents spike bursts which accompany the rising intrauterine pressure. Asynchronous localized electrical activity develops into synchronous activity during the course of labor. The early postpartum uterus shows an irregular pattern or continuous small bursts of spikes. During labor it responds markedly to prostaglandins (PGs); this declines in postpartum. Direct intrauterine injection of PGF2a is effective in the early postpartum. Intravaginal application of PGE2 (5 mg/kg) in late pregnancy induces regular, frequent bursts of spikes and successful delivery. Electrical activity of the oviduct was not affected by PGs except in early postpartum.


The Health Service Use of Frequent Users of Telephone Helplines in a Cohort of General Practice Attendees with Depressive Symptoms.
We examined the relationship between frequent use of telephone helplines and health service use over time in a cohort of 789 general practice attendees with depressive symptoms. Telephone helpline use (no use, non-frequent use, frequent use) was measured at 3, 6, 9 and 12 months and analysed using ordered logistic regression. Sixteen participants (2 %) reported frequent use of telephone helplines. Reporting frequent use was associated with visiting multiple general practitioners, using emergency services and visiting mental health specialists in the previous 3 months. Despite this pattern of service use, there was evidence that these services were not meeting the needs of frequent users of telephone helplines, as they were also more likely to report dissatisfaction with their access to health services compared to non-frequent and non-users of telephone helplines. Our findings suggest that a model of care which addresses the complex needs of frequent users of telephone helplines is needed.


Intermediate-Volatility Organic Compound Emissions from Nonroad Construction Machinery under Different Operation Modes.
Intermediate-volatility organic compounds (IVOCs) have been found as important sources for secondary organic aerosol (SOA) formation. IVOC emissions from nonroad construction machineries (NRCMs), including two road rollers and three motor graders, were characterized under three operation modes using an improved portable emission measurement system. The fuel-based IVOC emission factors (EFs) of NRCMs varied from 245.85 to 1802.19 mg/kg·fuel, which were comparable at magnitudes to the reported results of an ocean-going ship and on-road diesel vehicles without filters. The discrepancy of IVOC EFs is significant within different operation modes. IVOC EFs under the idling mode were 1.24-3.28 times higher than those under moving/working modes. Unspeciated b-alkanes and cyclic compounds, which were the unresolved components in IVOCs at the molecular level, accounted for approximately 91% of total IVOCs from NRCMs. The SOA production potential analysis shows that IVOCs dominated SOA formation of NRCMs. Our results demonstrate that IVOC emissions from NRCMs are non-negligible. Thus, an accurate estimation of their IVOC emissions would benefit the understanding of SOA formation in the urban atmosphere.


Systematic analysis, by the yeast two-hybrid, of protein interaction between components of the type II secretory machinery of Erwinia chrysanthemi.
Type II systems allow for the secretion of numerous enzymes and toxins in several Gram-negative pathogens. In Erwinia chrysanthemi, 14 Out proteins are necessary for building the type II apparatus. We performed a systematic two-hybrid analysis to test interactions between the periplasmic regions of the Out proteins. Results obtained using this approach suggested that OutJ (a pseudopilin) was able to interact with (i) OutD, the outer membrane secretin, (ii) OutI, mainly located in the periplasm, and (iii) OutL, an inner membrane protein. Taken together, these results suggest that OutJ is involved in multiple partnerships. Implications of these partnerships in the overall architecture of the type II secretion machinery are discussed.


Insulin resistance in type 1 diabetes mellitus.
For long the presence of insulin resistance in type 1 diabetes has been questioned. Detailed metabolic analyses revealed 12%-61% and up to 20% lower whole-body (skeletal muscle) and hepatic insulin sensitivity in type 1 diabetes, depending on the population studied. Type 1 diabetes patients feature impaired muscle adenosine triphosphate (ATP) synthesis and enhanced oxidative stress, predominantly relating to hyperglycemia. They may also exhibit abnormal fasting and postprandial glycogen metabolism in liver, while the role of hepatic energy metabolism for insulin resistance remains uncertain. Recent rodent studies point to tissue-specific differences in the mechanisms underlying insulin resistance. In non-obese diabetic mice, increased lipid availability contributes to muscle insulin resistance via diacylglycerol/protein kinase C isoforms. Furthermore, humans with type 1 diabetes respond to lifestyle modifications or metformin by 20%-60% increased whole-body insulin sensitivity, likely through improvement in both glycemic control and oxidative phosphorylation. Intensive insulin treatment and islet transplantation also increase but fail to completely restore whole-body and hepatic insulin sensitivity. In conclusion, insulin resistance is a feature of type 1 diabetes, but more controlled trials are needed to address its contribution to disease progression, which might help to optimize treatment and reduce comorbidities.


Genetic variation screening and association studies of the adenylate cyclase activating polypeptide 1 (ADCYAP1) gene in patients with type 2 diabetes.
Adenylate cyclase activating polypeptide 1 (ADCYAP1) is a pancreatic neuropeptide and modulates glucose-stimulated insulin secretion. The ADCYAP1 gene is located on chromosome 18p11 linked to type 2 diabetes. To test whether it is a candidate gene for type 2 diabetes, screening of the gene in Finnish and Swedish type 2 diabetic patients was done. Two novel SNPs, g.9863G>A (G54D) in exon 3 and g.12712C>G in the 3'-UTR of exon 5 of the ADCYAP1 gene (accession number X60435), were found. PCR-RFLP genotyping was then performed in a total of 253 type 2 diabetic patients and 253 non-diabetic control subjects. Transmission disequilibrium test (TDT) was performed in 132 parent-offspring trios. The G allele frequencies of g.9863G>A (G54D) and g.12712C>G of the ADCYAP1 gene were higher in type 2 diabetic patients than in non-diabetic control subjects (21.0% vs 15.8%, P=0.04; 5.3% vs 3.0%, P=0.045). However, no significant differences in clinical variables was seen between the different genotype carriers, and also no transmission distortion of the G allele of SNP g.9863G>A (G54D) was observed in 132 parent-offspring trios. The present study thus suggest that the variants in the ADCYAP1 gene may not be major influence of the susceptibility to type 2 diabetes in Finnish and Swedish Caucasians.


Physical measurements of the lumbar spine.
This article describes measurement of lumbar function. The simplest range of motion devices are compared with the progressive, more complex computerized devices for range and strength testing. The author presents his own opinion as to the place of these devices in both research and clinical practices. The economics of accurate physical testing is compared to the clinical realities of current payment systems.


Altered metabolism of LDL in the arterial wall precedes atherosclerosis regression.
Plasma cholesterol lowering is beneficial in patients with atherosclerosis. However, it is unknown how it affects entry and degradation of low-density lipoprotein (LDL) particles in the lesioned arterial wall. We studied the effect of lipid-lowering therapy on LDL permeability and degradation of LDL particles in atherosclerotic aortas of mice by measuring the accumulation of iodinated LDL particles in the arterial wall. Cholesterol-fed, LDL receptor-deficient mice were treated with either an anti-Apob antisense oligonucleotide or a mismatch control antisense oligonucleotide once a week for 1 or 4 weeks before injection with preparations of iodinated LDL particles. The anti-Apob antisense oligonucleotide reduced plasma cholesterol by ≈90%. The aortic LDL permeability and degradation rates of newly entered LDL particles were reduced by ≈50% and ≈85% already after 1 week of treatment despite an unchanged pool size of aortic iodinated LDL particles. In contrast, the size, foam cell content, and aortic pool size of iodinated LDL particles of aortic atherosclerotic plaques were not reduced until after 4 weeks of treatment with the anti-Apob antisense oligonucleotide. Improved endothelial barrier function toward the entry of plasma LDL particles and diminished aortic degradation of the newly entered LDL particles precede plaque regression.


Radius fracture after total wrist arthroplasty.
Four cases of radius fracture are presented; each was caused by a fall and happened at least 18 months after total wrist arthroplasty. One patient had bilateral fractures occurring 12 months apart. All injuries were initially treated nonoperatively. Nonunion or healing with deformity occurred in three fractures. Revision arthroplasty was done in two cases with satisfactory results, and is being considered for a third.


Late phase II study of novel oral fluoropyrimidine anticancer drug S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium) in advanced gastric cancer patients.
S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). CDHP inhibits dihydropyrimidine dehydrogenase (DPD), an enzyme which degrades 5-FU, and maintains prolonged 5-FU concentrations in the blood and tumours. Oxo is distributed in the gastrointestinal tract at a high concentration after oral administration and alleviates gastrointestinal toxicity due to 5-FU. S-1 improves the tumour-selective toxicity of 5-FU by the actions of two modulators, CDHP and Oxo. We conducted a late phase II clinical trial of S-1 as an open trial in patients with advanced gastric cancer, to confirm its antitumour effect and adverse reactions. 51 patients with advanced gastric cancer were enrolled in the trial. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2/day. One course consisted of consecutive administration for 28 days and 14 days' rest. Administration was repeated over four courses. A complete response was obtained in 1 patient and partial responses in 24 patients, producing a response rate of 49% (25/51) (95% confidence interval (CI) 35.9-62.3%). The incidence of adverse reactions was 78% (40/51) and that of adverse reactions of grades 3 and 4 was 20%. Adverse reactions of grades 3 and 4 included a decrease in the haematocrit, leucopenia, granulocytopenia, diarrhoea, malaise and proteinuria. No serious unexpected adverse reactions were observed. In conclusion, S-1 was effective and well tolerated in patients with advanced gastric cancer.


Assessment of the Chemosensitivity of Uveal Melanoma Cells Ex Vivo.
The study was designed to create a primary cell culture of uveal melanoma and to evaluate its resistance to chemotherapy. Of the obtained 20 samples of uveal melanoma, the primary cultures with proliferation sufficient for MTT test were derived in only 7 cases. However, even these cultures were unable to survive more than 4 passages; the cells accumulated melanin and underwent apoptosis. Retinol palmitate and nepafenac produced no cytotoxic effect on uveal melanoma cells. Of 5 cultures treated with sodium valproate (Convulex), no pronounced cytotoxic effect was observed in one culture (UM4); in 2 cultures, 50% cells died in the presence of the lowest drug concentration of 1.88 mg/ml; and in 2 cultures, the same effect was achieved at drug concentrations 7-10 mg/ml. The cytotoxic effect of treosulfan was evaluated in only 4 cultures of uveal melanoma: the drug exhibited pronounced antitumor activity on all cultures, in 2 cases, it was effective at a concentration of 0.16 mg/ml. Gemcitabine in a concentration of 2.5 mg/ml produced a pronounced cytotoxic effect in 4 out of 7 cultures (death of 70-80% cells) and induced death of ~45% cells in the remaining 3 cultures. Mitoxantrone had ambiguous effect: in 2 of 5 cultures, the drug in high concentrations stimulated the growth of tumor cells, but in 3 cultures, the drug even in minimum concentrations induced death of 70-80% cells.


Multiple metastases from basal cell naevus syndrome.
A patient with basal cell naevus syndrome (Gorlin-Goltz Syndrome) is presented. Of note in the case was the extensive symmetrical tumour invasion of both external auditory canals requiring bilateral radical resection. The patient expired 14 months later, at which time the autopsy revealed widespread metastases to the pleura, diaphragm, pericardium, epicardium and myocardium. Although lung metastases have been reported in this syndrome, no cases have been reported of metastases to these sites.


The patients with clinically isolated syndrome and relapsing remitting multiple sclerosis show different levels of advanced protein oxidation products and total thiol content in plasma and CSF.
Advanced oxidation protein products (AOPP) and total thiol (SH) groups levels in plasma and CSF were studied in a cohort of 50 clinically isolated syndrome (CIS) and 57 relapsing remittent multiple sclerosis (RRMS) patients related to 20 control group (CG) patients' values. The obtained results were compared regarding patients demographic, biochemical, clinical (EDSS) and MRI features (total T2 weighted lesions number and Gd enhancement lesion volume). Plasma and CSF AOPP levels in CIS and RRMS patients were higher than those in CG, while SH groups showed lower values compared to CG (p<0.05). Both parameters were higher in CIS than in RRMS patients (p<0.05). Related to EDSS median range, all patients were divided into those with slight or mild and those with severe clinical presentation. AOPP and SH group changes were more pronounced in both, CIS and RRMS patients with higher, compared to those with lower EDSS (p<0.05). AOPP, SH group levels and EDSS positive correlations were observed in both study groups (p<0.01). Both parameters showed the same approach regarding the median range of total T2 weighted lesions and Gd enhancement lesion volume mean values (p<0.05), but no correlation was found between AOPP and SH levels and these patients radiological characteristics (p>0.01). The data support the fact that oxidative stress is always involved in CIS and RRMS pathophysiology, but not always as a disease determinant dependent on its intensity, which might be important for new therapeutic strategies based on antioxidant approach in those patients.


Effects of carbon tetrachloride on calcium homeostasis. A critical reconsideration.
The incubation of isolated rat hepatocytes with 0.172 mM carbon tetrachloride caused a rapid decrease in the calcium content of both mitochondrial and extramitochondrial compartments. However, the release of Ca2+ from the intracellular stores was not associated with an increase in the cytosolic Ca2+ levels as measured by activation of phosphorylase alpha or by Quin-2 fluorescence. A rapid rise in hepatocyte free calcium was only observed with concentrations of CCl4 higher than 0.172 mM. The lack of activation of phosphorylase alpha was not due to the inhibition of the enzyme by CCl4, since in CCl4-treated hepatocytes the phosphorylase activity could be stimulated by glucagon, butyryl--cAMP or by the increase of cell calcium induced by the addition of A23187. Ca2+-dependent ATPase of plasma membranes was only slightly affected in the early phases of poisoning with CCl4 when both mitochondrial and extramitochondrial calcium pools were already lowered. This led to the conclusion that calcium released from intracellular organelles could be extruded from the cells in sufficient amounts to prevent the increase of the cytosolic levels. A rise in hepatocyte free calcium was observed during the second hour of incubation with CCl4, concomitantly with the appearance of both LDH leakage and plasma membrane blebbing. The addition of EGTA to the medium prevented both the increase in cytosolic Ca2+ and the blebbing suggesting that they were a consequence of an influx of calcium into the cells. However, neither EGTA nor the addition of inhibitors of calcium-dependent phospholipase A2 or non-lysosomal proteases were able to protect against cell death. These latter results suggested that the alterations of calcium distribution induced by CCl4 in isolated hepatocytes were not a primary cause of the toxic effects, although they did not exclude that a sustained rise in cytosolic Ca2+ could contribute in the progression of cell injury.


Regional left ventricular asynchrony and impaired global left ventricular filling in hypertrophic cardiomyopathy: effect of verapamil.
Left ventricular relaxation and filling are impaired in many patients with hypertrophic cardiomyopathy. To investigate the influence of regional heterogeneity on these global abnormalities, 48 patients with hypertrophic cardiomyopathy and sinus rhythm were studied by radionuclide angiography before and after 1 to 2 weeks of verapamil therapy (320 to 640 mg/day, median 480). Left ventricular regional function was assessed by subdividing the ventricular region of interest into 20 sectors and into four quadrants from which regional time-activity curves were derived. Diastolic asynchrony was measured as the regional variation in timing between minimal volume and peak filling rate, and heterogeneity in the magnitude of rapid diastolic filling was measured as the regional variation in percent contribution of atrial systole to end-diastolic volume. Compared with 28 normal subjects, the patients with hypertrophic cardiomyopathy had greater regional variation in both timing (35 +/- 24 versus 12 +/- 6 ms, p less than 0.001) and magnitude (10 +/- 6 versus 7 +/- 4%, p less than 0.02) of rapid filling. Verapamil reduced the regional variation in timing (to 21 +/- 16 ms, p less than 0.001) and magnitude (to 7 +/- 3%, p less than 0.001) of rapid filling. These regional changes, indicating more uniform regional diastolic performance after verapamil, were associated with improved global diastolic filling: global rapid filling increased in both rate and magnitude and time to peak filling rate decreased. These findings indicate that the beneficial effect of verapamil on left ventricular diastolic function in hypertrophic cardiomyopathy may be mediated by reduction in regional asynchrony.


The Ethno-linguistic Community and Premature Death: a Register-Based Study of Working-Aged Men in Finland.
One of the most striking features of premature death in Finland is the ethno-linguistic mortality gradient in working-aged men. Finnish speakers have a notably higher mortality risk than Swedish speakers. The underlying reasons are not fully clear, but one suggested explanation has been that the level of social integration is lower in the Finnish-speaking community than that in the Swedish-speaking one, as people in the former are geographically less rooted at the local level. In this paper, we derive a proxy for the influence of the ethno-linguistic community as a contextual factor on the Finnish-Swedish mortality gradient. The strategy is based on a unique setup that makes it possible to identify people not only by their ethno-linguistic background and ethno-linguistic affiliation, but we indirectly know also in which community a person has been raised. Results of multivariate regressions provide poor support for this contextual hypothesis, however, and rather suggest that some latent individual characteristics might be important, hence illuminating the complexity behind the excess mortality of Finnish speakers.


Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor alpha/retinoid X receptor.
In response to cellular hypoxia, cardiomyocytes adapt to consume less oxygen by shifting ATP production from mitochondrial fatty acid beta-oxidation to glycolysis. The transcriptional activation of glucose transporters and glycolytic enzymes by hypoxia is mediated by hypoxia-inducible factor 1 (HIF-1). In this study, we examined whether HIF-1 was involved in the suppression of mitochondrial fatty acid beta-oxidation in hypoxic cardiomyocytes. We showed that either hypoxia or adenovirus-mediated expression of a constitutively stable hybrid form (HIF-1alpha/VP16) suppressed mitochondrial fatty acid metabolism, as indicated by an accumulation of intracellular neutral lipid. Both treatments also reduced the mRNA levels of muscle carnitine palmitoyltransferase I which catalyzes the rate-limiting step in the mitochondrial import of fatty acids for beta-oxidation. Furthermore, adenovirus-mediated expression of HIF-1alpha/VP16 in cardiomyocytes under normoxic conditions also mimicked the reduction in the DNA binding activity of peroxisome proliferator-activated receptor alpha (PPARalpha)/retinoid X receptor (RXR), in the presence or absence of a PPARalpha ligand. These results suggest that HIF-1 may be involved in hypoxia-induced suppression of fatty acid metabolism in cardiomyocytes by reducing the DNA binding activity of PPARalpha/RXR.


Probiotic potential of enterococci isolated from canine feed.
Enterococci isolated from 28 different commercially available feeds (10-1000 CFU/mL) were identified and their probiotic potential was determined. Species identification of 22 selected strains was performed by intergenic length-polymorphism analysis (tRNA-PCR); PCR products were analyzed using capillary electrophoresis. Six strains were allotted to the species Enterococcus faecium, four to E. faecalis, one to E. hirae; the remaining strains were not classed. The strains were sensitive to vancomycin, ampicillin, tetracycline and rifampicin. They were able to adhere to human as well as canine intestinal mucus. They produced lactic acid (0.99-1.04 mmol/L) and most of them were urease-positive with sufficient survival in 5 % Oxgall-bile. They did not show any inhibitory activity due to antimicrobial substances. Plasmid DNA was detected in 8 strains, the bands responding to small molecular size (10 kbp). Considering all probiotically important properties, E. faecium strain EE3 was suggested as potential feed additive.


Enhancement of cytotoxicity of modeccin by nigericin in modeccin-resistant mutant cell lines.
We have isolated a Chinese hamster ovary cell mutant (DMPR-2) simultaneously resistant to diphtheria toxin and modeccin. In addition to the increased resistance to these two toxins used in the selection, this mutant is more resistant to Pseudomonas toxin and hypersensitive to ricin than the parental cell line. In contrast to the wild-type cells in which nigericin protects cells from modeccin, the cytotoxicity of modeccin in the DMPR-2 mutant is enhanced by nigericin. We have also studied the effects of nigericin and NH4Cl on the cytotoxicity of modeccin in a modeccin-resistant mutant of HeLa cells (ModRI). The cytotoxicity of modeccin is enhanced by nigericin in ModRI mutant cells, in contrast to the protection of modeccin cytotoxicity by nigericin in the parental HeLa cells. Our results suggest that modeccin can reach the cytosol of mammalian cells by two distinct routes; the major route requires endosomal acidification and the minor route is activated by nigericin.


Low versus high pulse oxygen saturation directed oxygen therapy in critically ill patients: a randomized controlled pilot study.
Data on the safety and feasibility of pulse oxygen saturation (SpO2) directed oxygen therapy in mainland China are scarce. The aim of this pilot study was to test the feasibility of SpO2 directed oxygen therapy and to calculate sample size base on differences in 28-day mortality rates for a large sample-sized randomized trial. This prospective pilot study enrolled 214 adult patients with an expected intensive care unit (ICU) stay of more than 72 hours. Patients were randomized into a low SpO2 group (SpO2 90-95%) or high SpO2 group (SpO2 96-100%). The primary outcome was 28-day mortality. One hundred patients were included in the low SpO2 group, and 114 patients were included in the high SpO2 group. The demographic and baseline characteristics were not different. The time-weighted SpO2 average was significantly lower in the low SpO2 group than in the high SpO2 group [mean ± standard deviation (SD), 95.7%±2.3% vs. 98.2%±1.8%, P<0.001]. Twenty-six patients (26%) in the low SpO2 group died within 28 days after inclusion, while 37 patients (32.5%) in the high SpO2 group died (P=0.301). The time to death within 28 days between the two groups was not different (P=0.284). SpO2 directed oxygen therapy in critically ill patients was feasible. Our pilot trial necessitates and rationalizes our large-sample multicenter trial.


What came first, the chicken or the egg?
Current empirical evidence does not seem to confirm that an improvement in living conditions is the cause of the shift in the human mindset toward innovation and long-term risky investment. However, it may well be one of the conditions for greater tolerance of income inequality in exchange for a steady increase in average income.


Application of an MEG eigenspace beamformer to reconstructing spatio-temporal activities of neural sources.
We have applied the eigenspace-based beamformer to reconstruct spatio-temporal activities of neural sources from MEG data. The weight vector of the eigenspace-based beamformer is obtained by projecting the weight vector of the minimum-variance beamformer onto the signal subspace of a measurement covariance matrix. This projection removes the residual noise-subspace component that considerably degrades the signal-to-noise ratio (SNR) of the beamformer output when errors in estimating the sensor lead field exist. Therefore, the eigenspace-based beamformer produces a SNR considerably higher than that of the minimum-variance beamformer in practical situations. The effectiveness of the eigenspace-based beamformer was validated in our numerical experiments and experiments using auditory responses. We further extended the eigenspace-based beamformer so that it incorporates the information regarding the noise covariance matrix. Such a prewhitened eigenspace beamformer was experimentally demonstrated to be useful when large background activity exists.


[Suppression of Kiss-1 gene inhibits HCT116 human colorectal carcinoma cell migration in vitro via nuclear factor-κB signaling pathway].
To investigate the effect of Kiss-1 gene suppression on the metastatic capacity of HCT116 human colorectal carcinoma cells in vitro and the involvement of nuclear factor-κB (NF-κB) signaling pathway. A recombinant lentiviral vector of Kiss-1 gene pGC-LV-Kiss-1-EGFP or the empty vector was transfected in HCT116 cells. Cell Counting Kit-8 (CCK8) and Transwell chamber assay were used to detect the changes in cell proliferation, invasion and migration ability after the transfection. Western blotting was used to detect the expression of I-κB, the inhibitive protein of NF-κB signal pathway, and the expression of the downstream effector MMP-9 before and after transfection. In cells over-expressing Kiss-1, I-κB expression increased and MMP-9 expression decreased significantly compared to those in the blank control and vector-transfected cells (P<0.05). Kiss-1 gene over-expression resulted in significant inhibition of HCT116 cell proliferation, invasion, and migration as compared to the control cells (P<0.05). Lentivirus-mediated Kiss-1 gene over-expression can inhibit the proliferation, invasion, and migration of HCT116 cells via the NF-B signaling pathway.


Quantitative ultrasound in the assessment of skeletal status in children and adolescents.
The aim of this study was to provide normative data for quantitative ultrasound (US) through the phalanges and to evaluate the influence of age and body size on Ad-SoS (amplitude-dependent speed-of-sound). Measurements were performed in 1020 healthy Polish children ages 7 to 19 years, using a DBM Sonic 1200 (IGEA, Carpi, Italy). The Ad-SoS increased with age in all studied subjects; in girls from 1926 to 2124 m/s and in boys from 1916 to 2114 m/s. The statistically significant increases in Ad-SoS values were noted between the ages of 10 and 16 years in girls and 13 and 18 years in boys. Correlations and regressions between Ad-SoS and age and body were dependent on the phases of growth. In stepwise multiple linear regression of Ad-SoS on age and body size, the following equations were obtained: in girls, Ad-SoS (m/s)=1843 + 18 x age (years) + 2.3 x weight (kg) - 9.4 x body mass index (BMI) (kg/m2), r=0.85, standard error of estimate (SEE)=42; and, in boys, Ad-SoS (m/s)=2443 + 14 x age (years) - 3.7 x height (cm) + 8.4 x weight (kg) - 24.8 x BMI (kg/m2), r=0.83, SEE=45. In conclusion, the study showed the ability of US measurements at hand phalanges to monitor the skeletal maturation during childhood and adolescence.


Total arterial anastomosis heterotopic heart transplantation model.
Mouse transplant models offer a valuable platform for studying the biology of a spectrum of diseases, particularly those of the immune system. We have developed a modified abdominal heterotopic heart transplantation (AHHT) model with a total arterial anastomosis and compared the results with the cervical heterotopic heart transplantation (CHHT) and the non-modified AHHT models. Mice were randomly assigned to four groups: sham, AHHT, CHHT, and modified AHHT groups. Each group (except for the sham) included donor and recipient animals. Postoperative outcome, operative mortality, operative time, and tissue damage were assessed by measuring plasma levels of tumor necrosis factor α. The modified AHHT group had significantly lower values. However, hind limb paralysis was observed equally and only in AHHT and modified AHHT models. The modified AHHT group had the highest success rate of functioning hearts.