Chylomicron apoprotein alteration after plasma exposure.
Purified rat lymph chylomicrons were incubated with chylomicron-free rat plasma and examined for changes in lipid and apoprotein constituents. Upon incubation there was a five-fold increase in the arginine rich apoprotein and a concomitant reduction in chylomicron Apo A-I to less than one-sixth its preincubation mass. These apoprotein changes were most faithfully reproduced when chylomicrons were incubated with the rat HDL fraction, although incubations of chylomicrons with rat lipoprotein-free plasma showed that arginine-rich apoprotein could readily associate with chylomicrons without concomitant changes in chylomicron lipid constituents. The gain in chylomicron apoprotein paralleled an increased affinity of the incubated chylomicron for heparin, when examined by heparin affinity chromatography. The apoprotein alterations were consistent in incubations in which the triglyceride concentrations varied from 330 mg/dl to 4200 mg/dl, and were not affected by inhibition of the Lecithin:Cholesterol Acyl Transferase (LCAT) reaction in the incubation mixture. The demonstration that in vivo alimentary lipemia chylomicrons have an apoprotein pattern identical to that of chylomicrons following in vitro plasma incubation suggests that these apoprotein alterations occur physiologically in alimentary lipemia.


Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources.
Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti- Candida host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility. A comprehensive analysis of multiple independent sources reporting Candida adverse events during biologics inhibiting the Th17 pathway was performed. Association between Th17 inhibitors and candidiasis was assessed using safety reports of (1) WHO and (2) EMA, (3) a population-based prescriptions registry, and (4) a psoriasis cohort. In a cohort of psoriasis patients experiencing candidiasis during Th17 inhibitors, Candida killing by immune cells and serum inflammatory proteome were analyzed. A strong association between IL-17 inhibitors and candidiasis (ROR 10·20) was found in the WHO database, particularly for cutaneous (ROR 12·28), oropharyngeal (ROR 19·18), and esophageal candidiasis (ROR 21·20). Risk was higher relative to TNF-α inhibitors (4-10-fold, depending on candidiasis type), confirmed by EMA reports (16-33-fold), prescriptions registry (2-42-fold), and a psoriasis cohort (3-25-fold). After start of IL-17 inhibitors, patients' risk of candidiasis requiring antifungals increased 2-16 fold. In the psoriasis cohort, 58% of IL-17 treatment episodes were associated with candidiasis. In Th17 inhibitor recipients, proteins involved in anti- Candida immunity and Candida killing by mononuclear leukocytes were impaired. IL-17 inhibitors are associated with an increased risk of oropharyngeal, esophageal, and cutaneous candidiasis, posing a significant disease burden for IL-17 inhibitor recipients. RadboudUMC.


An angiotensin-converting enzyme gene variant is associated with acute myocardial infarction in women but not in men.
We believe our data may speak to the issue of sexual dimorphism with respect to MI. Most studies have concentrated on men with this disease. In a recent study, Lindpaintner et al10 could find no relationship between the D/D genotype and AMI in subjects of the Physicians Health Study. However, this study consisted entirely of men. The D allele may provide an avenue to discern differences in the pathogenesis of MI in men and women.


Association between adipokines and thyroid carcinoma: a meta-analysis of case-control studies.
The incidence of thyroid carcinoma is increasing all over the world. Some studies have suggested that the change of adipokines expression can induce thyroid carcinoma. However, other studies have come to the opposite conclusion. Therefore, we studied the relationship between adipokines and thyroid carcinoma. Databases-PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries were searched. A meta-analysis was then performed through a fixed or random-effects model to calculate I values for heterogeneity analysis. Twenty-nine articles were finally included for analysis. The level of serum tumor necrosis factor-alpha (TNF-α) [standardized mean difference (SMD) =1.31, 95% confidence interval (95% CI): 0.35 to 2.28, I2 = 98%, P = 0.008] and the ratio of TNF-α immunoreactivity in tissues [odds ratios (OR) =6.36, 95% CI: 1.92 to 21.05, I2 = 66%, P = 0.002] in thyroid carcinoma are significantly higher than those in control. The serum interleukin-6 (IL-6) in patients with thyroid carcinoma is higher than that in control (SMD = 1.04, 95% CI: 0.40 to 1.67, I2 = 96%, P = 0.001). There is no significant difference of the ratio of IL-6 immunoreactivity in tissues between carcinoma and control (OR = 1.23, 95% CI: 0.62 to 2.43, I2 = 86%, P = 0.55). The ratio of leptin immunoreactivity in tissues is significantly associated with the risk of thyroid carcinoma (OR = 12.21, 95% CI: 3.36 to 44.40, I2 = 85%, P < 0.00001). However, after analyzing the expression level of serum adiponectin in three studies, no significant difference is found between thyroid carcinoma and the control (P = 0.81). Adipokines (TNF-α, IL-6 and leptin) show a strong relationship between elevated concentrations (in serum and/or tissue) and thyroid carcinoma. However, the association between adiponectin and thyroid carcinoma needs further research.


Stimulation of mutagenesis by proportional deoxyribonucleoside triphosphate accumulation in Escherichia coli.
Intracellular pool sizes of deoxyribonucleoside triphosphates (dNTPs) are highly regulated. Unbalanced dNTP pools, created by abnormal accumulation or deficiency of one nucleotide, are known to be mutagenic and to have other genotoxic consequences. Recent studies in our laboratory on DNA replication in vitro suggested that balanced accumulation of dNTPs, in which all four pools increase proportionately, also stimulates mutagenesis. In this paper, we ask whether proportional dNTP pool increases are mutagenic also in living cells. Escherichia coli was transformed with recombinant plasmids that overexpress E. coli genes nrdA and nrdB, which encode the two protein subunits of aerobic ribonucleotide reductase. Roughly proportional dNTP pool expansion, by factors of 2- to 6-fold in different experiments, was accompanied by increases in spontaneous mutation frequency of up to 40-fold. Expression of a catalytically inactive ribonucleotide reductase had no effect on either dNTP pools or mutagenesis, suggesting that accumulation of dNTPs is responsible for the increased mutagenesis. Preliminary experiments with strains defective in SOS regulon induction suggest a requirement for one or more SOS functions in the dNTP-enhanced mutagenesis. Because a replisome extending from correctly matched 3'-terminal nucleotides is almost certainly saturated with dNTP substrates in vivo, whereas chain extension from mismatched nucleotides almost certainly proceeds at sub-saturating rates, we propose that the mutagenic effect of proportional dNTP pool expansion is preferential stimulation of chain extension from mismatches as a result of increases in intracellular dNTP concentrations.


Deep semi-supervised multiple instance learning with self-correction for DME classification from OCT images.
Supervised deep learning has achieved prominent success in various diabetic macular edema (DME) recognition tasks from optical coherence tomography (OCT) volumetric images. A common problematic issue that frequently occurs in this field is the shortage of labeled data due to the expensive fine-grained annotations, which increases substantial difficulty in accurate analysis by supervised learning. The morphological changes in the retina caused by DME might be distributed sparsely in B-scan images of the OCT volume, and OCT data is often coarsely labeled at the volume level. Hence, the DME identification task can be formulated as a multiple instance classification problem that could be addressed by multiple instance learning (MIL) techniques. Nevertheless, none of previous studies utilize unlabeled data simultaneously to promote the classification accuracy, which is particularly significant for a high quality of analysis at the minimum annotation cost. To this end, we present a novel deep semi-supervised multiple instance learning framework to explore the feasibility of leveraging a small amount of coarsely labeled data and a large amount of unlabeled data to tackle this problem. Specifically, we come up with several modules to further improve the performance according to the availability and granularity of their labels. To warm up the training, we propagate the bag labels to the corresponding instances as the supervision of training, and propose a self-correction strategy to handle the label noise in the positive bags. This strategy is based on confidence-based pseudo-labeling with consistency regularization. The model uses its prediction to generate the pseudo-label for each weakly augmented input only if it is highly confident about the prediction, which is subsequently used to supervise the same input in a strongly augmented version. This learning scheme is also applicable to unlabeled data. To enhance the discrimination capability of the model, we introduce the Student-Teacher architecture and impose consistency constraints between two models. For demonstration, the proposed approach was evaluated on two large-scale DME OCT image datasets. Extensive results indicate that the proposed method improves DME classification with the incorporation of unlabeled data and outperforms competing MIL methods significantly, which confirm the feasibility of deep semi-supervised multiple instance learning at a low annotation cost.


The "metabolovirus" model of hepatitis B virus suggests nutritional therapy as an effective anti-viral weapon.
Hepatitis B virus (HBV) is a small DNA virus that targets the liver almost exclusively. Chronic infection with HBV might lead to severe liver-related pathologies including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Based on its enhancer composition, which links nutritional signals that control hepatic glucose and fat metabolism in the liver to HBV gene expression and replication, it appears that the virus has adopted a regulatory system that is unique to the major hepatic metabolic genes. This unique virus-host interaction, mediated by metabolic events in the liver, is designated by us the "metabolovirus model". We hypothesize that by mimicking the expression of key genes implicated in glucose homeostasis, HBV sophisticatedly exploits the host resources to ensure its persistence. Specifically, by recruiting transcription factors and coactivators common to essential hepatic metabolic genes the virus avoids a possible resistance by its host, on the one hand, and ensures a timely and proper response to changes in its environment in terms of metabolic milieu, on the other hand. Furthermore, by coupling its gene expression to the expression of hepatic metabolic genes that fluctuate during the day, we predict a fluctuating nature of HBV gene expression. This can serve the virus in its attempts to escape the host immune system in addition to other immune evading strategies adopted by the virus, such as the secretion of the e antigen. Based on our "metabolovirus model", we suggest new mechanisms to previously unexplained clinical phenomena, such as the observed diversity in disease severity between different geographical areas that differ in nutritional habits. Furthermore, given the up-regulatory effect of food deprivation on HBV gene expression and replication, we suggest that conditions of short-term starvation should be completely avoided by HBV-infected individuals, and dietary recommendations such as the ingestion of complex carbohydrates before sleep should be adopted. Thus, our hypothesis sets the stage for viral manipulation by controlling food intake, and opens additional avenues towards food or nutritional therapy as an effective anti-HBV weapon.


Stress-induced immune-related diseases and health outcomes of pharmacy students: A pilot study.
Stress in health sciences students has been studied extensively. Nevertheless, only few studies have been conducted on pharmacy students and nothing was done to compare stress effects on the immune responses of Pharmacy and Doctor of Pharmacy (PharmD) students. The aim of this pilot study was (1) to measure the self-reported perceived stresses, immune-related diseases and health outcomes of pharmacy and PharmD students, (2) to investigate the relationship between perceived stresses, health outcomes and immune-related diseases and (3) to compare stress induced changes in the health and immune system of pharmacy and PharmD students. The study represents a cross sectional survey using an interviewer administered questionnaire about stress and students' health states during the fall semester of 2009/2010. At commence of this study, 222 of pharmacy and PharmD participant students (113 and 109 respectively) from the third and uppermost levels of study were picked up randomly. They were found to perceive stress related to program intensity, lack of exercise and social activities, bad nutritional routines and accommodation. Effects of increased study loads on students' health and immune-related diseases were more pronounced on PharmD students, while showing significant changes on Pharmacy students. In general, more than 50% of students of each program got ill several times, mainly during the midterm period, had cold/flu, were under medical care and had problems in skin and/or hair. Also, PharmD students reported relatively higher levels of perceived stress and lower emotional and satisfaction quality of life compared to Pharmacy students. Results may help to increase the awareness of students to get prepared to what they might face, and may enable them to reduce the program's negative effects.


Effect of Surgical Atrial Fibrillation Ablation at the Time of Cardiac Surgery on Risk of Postoperative Pacemaker Implantation.
The aim of this study was to retrospectively investigate whether performing surgical atrial fibrillation (AF) ablation in conjunction with cardiac surgery (CS) increases the risk for postoperative permanent pacemaker (PPM) requirement. The 30-day risk for PPM requirement was analyzed in consecutive patients who underwent CS from January 2007 to August 27, 2013. Patients were divided into 3 groups: (1) those who underwent AF ablation concomitant with CS (AF ABL), (2) patients with any history of AF who underwent surgery who did not undergo ablation (AF NO ABL), and (3) those with no histories of AF who underwent surgery (NO AF). Logistic regression analysis was performed adjusting for age, gender, and surgery type. Of 13,453 CS patients, 353 (3%) were in the AF ABL group, 1,701 (12%) in the AF NO ABL group, and 11,399 (85%) in the NO AF group. A total of 7,651 patients (57%) underwent coronary artery bypass grafting, 4,384 (33%) underwent valve surgery, and 1,418 (10%) underwent coronary artery bypass grafting and valve surgery. The overall PPM risk was 1.6% (212 of 13,453); risk was 5.7% (20 of 353) in the AF ABL group, 3.1% (53 of 1,701) in the AF NO ABL group, and 1.2% (139 of 11,399) in the NO AF group. The unadjusted and adjusted odds of PPM were higher in the AF ABL and AF NO ABL groups than in the NO AF group (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.7 to 4.4, and adjusted OR 1.7, 95% CI 1.2 to 2.4, respectively). The unadjusted OR comparing the AF ABL group and the AF NO ABL group was significant (unadjusted OR 1.9, 95% CI 1.9 to 3.2); however, the OR adjusted for surgery type, age, and gender showed a trend toward significance (adjusted OR 1.6, 95% CI 0.9 to 2.7). In conclusion, in this large cohort of patients who underwent CS, surgical AF ablation appeared to carry an increased risk for postoperative PPM implantation.


Basic walker-assisted gait characteristics derived from forces and moments exerted on the walker's handles: results on normal subjects.
This paper describes a method that passively assesses basic walker-assisted gait characteristics using only force-moment measurements from the walker's handles. The passively derived gait characteristics of 22 subjects were validated against motion capture gait analysis. The force-moment based heel initial contact detection algorithm have produced a high level of concordance with heel initial contacts detected by a human inspecting the heel marker data sets of the Vicon video capture system. The algorithm has demonstrated 97% sensitivity and 98% specificity with a narrow 95% confidence interval of +/-1% during all experiments, which included five navigational scenarios. Temporal error in detecting the instances of heel initial contacts were within 5.27+/-3.66% of the overall stride time obtained from Vicon when the subjects walked in a straight line, whereas the toe-off instance estimates were within 5.18+/-2.75% of the gait cycle. The errors in determining the duration of stride time, single support, and double support were within 5.86+/-2.49%, 5.24+/-2.29%, and 4.34+/-2.13% of the gait cycle respectively. The stride time estimated, using the method presented here, correlated well with stride time computations based on visual inspection of Vicon's data, Pearson correlation coefficient r=0.86 for straight line segments. However, absolute errors were too high to estimate the single and double support phases with acceptable accuracy. The potential application of the instrumented walker and the method presented here is longitudinal basic gait assessment that can be performed outside of the conventional gait labs.


Life stage- dependent bioconcentration of a nonylphenol isomer in Daphnia magna.
Bioaccumulation is an important aspect for the fate and effects of xenobiotics in the environment. In this study we used a radiolabeled nonylphenol isomer to investigate the bioconcentration in Daphnia magna at different ages. Apart from the total radioactivity we measured the metabolism of p353-NP in D. magna, to calculate the amount of p353-NP compared to total radioactivity found within the daphnids. Bioconcentration factors, based on wet weight, calculated from the rate constants for total radioactivity in neonates and adults were 4271 kg/l and 760 kg/l respectively, leading to a 5.6 deviance in bioconcentration. This deviance was even more pronounced, nearly one order of magnitude, for the p353-NP concentration with bioconcentration factors of 302 kg/l for neonates and 31 kg/l for adults. We were able to describe the bioconcentration for all daphnids by a weight-dependent one- compartment model. These results pointed out that it is not possible to compare bioconcentration experiments conducted with different substances and different sized daphnids. Additionally it was shown that it is not possible to describe the bioconcentration by measuring the total radioactivity. Metabolism of nonylphenol occurs at a very fast rate and bioconcentration is not triggered by the partition between two phases, but by metabolism. Discrimination between the two mechanisms was achieved using radiolabeled substances and a pseudo two-compartment model to describe metabolism and elimination by two rate constants which afterwards can be compared between different substances.


The effects of ginsenosides on platelet aggregation and vascular intima in the treatment of cardiovascular diseases: From molecular mechanisms to clinical applications.
Thrombosis initiated by abnormal platelet aggregation is a pivotal pathological event that precedes most cases of cardiovascular diseases (CVD). Recently, growing evidence indicates that platelet could be a potential target for CVD prevention. However, as the conventional antithrombotic management strategy, applications of current antiplatelet agents are somewhat limited by their various side effects, such as bleeding risk and drug resistance. Hence, efforts have been made to search for agents as complementary therapies. Ginsenoside, the principal active component extracted from Panax ginseng, has gained much attention for its regulations on multiple crucial events of platelet aggregation. From structural characteristics to clinical applications, this review anatomized the intrinsic structure-function relationship of antiplatelet potency of ginsenosides, and the involved signal pathways were specifically summarized. Additionally, the emphasis was placed on clinical studies that investigate the antithrombotic efficacy of ginsenosides in the treatment of CVD. Further, a broad overview of approaches for improving the bioavailability of ginsenosides was concluded. Limitations and prospects of current studies were also discussed. This study may provide some new insights into the systematic understanding of ginsenosides in CVD treatment and lay a foundation for future research.


Urinary excretion of pyridinium crosslinks: a new marker of bone resorption in metabolic bone disease.
The pyridinium derivatives hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular crosslinking compounds of collagen which are only present in its mature form. Contrasting to the wide distribution of type I and II collagens, HP and LP are absent from skin, ligament and fascia, and their major sources are bone and cartilage. Using a specific HPLC assay, we have determined the 24-h excretion of HP and LP crosslinks in normal adults of both sexes, in patients with primary hyperparathyroidism and in patients with Paget's disease of bone before and after intravenous treatment with amino-propylidene bisphosphonate (APB). Mean adult normal values were 33 +/- 13 pmol/mumol creatinine for HP and 6.3 +/- 3.4 pmol/mumol creatinine for LP. In women, menopause induced a 2-3-fold increase of HP and LP reflecting the well documented postmenopausal increase of bone turnover. In the urine of patients with primary hyperparathyroidism and of patients with active Paget's disease of bone, urinary crosslinks were significantly higher than in age-matched controls, with a mean 3- and 12-fold increase, respectively. Urinary excretion of hydroxyproline is a well recognized but poorly sensitive marker of bone turnover, reflecting resorption. In the same patients, the effect of menopause and disease state on hydroxyproline excretion was much less dramatic than on HP and LP. During intravenous APB treatment of pagetic patients, there was an early decrease of HP and LP, which was significant after 24 h and reached 62% at 4 days, contrasting with a late and milder decrease of urinary hydroxyproline. Because APB is a potent inhibitor of resorption which does not have a direct short-term effect on bone formation, these data also indicate that urinary excretion of HP and LP reflect only collagen degradation occurring during osteoclastic resorption and not the degradation of newly synthesized collagen. We conclude that urinary HP and LP excretion represents the first sensitive and specific marker of bone resorption. Its use should be valuable in the clinical investigation of metabolic bone diseases, especially osteoporosis.


[Clinical and immunological indicators in patient with viral hepatitis A combined with ascariasis].
The data obtained point to the aggravation of virus hepatitis A time-course in case of a mixed pathology. This may be due to the state of a certain immune deficiency characteristic of parasitic diseases, including helminthiasis. It is also possible that immune deficiency is an inevitable condition for helminths' existance in the host. This suggestion is supported by the fact of helminthic invasion of virus hepatitis patients.


Enhancing meaningful learning and self-efficacy through collaboration between dental hygienist and physiotherapist students - a scholarship project.
Within the field of Dental Hygiene (DH) and Physiotherapy (PT), students are taught to use an evidence-based approach. Educators need to consider the nature of evidence-based practice from the perspective of content knowledge and learning strategies. Such effort to seek best available evidence and to apply a systematic and scholarly approach to teaching and learning is called scholarship of teaching and learning. To evaluate the application of the scholarship model including an evidence-based approach to enhance meaningful learning and self-efficacy among DH and PT students. Based on the research on student learning, three central theories were identified (constructivism, meaningful learning and self-efficacy). These were applied in our context to support learner engagement and the application of prior knowledge in a new situation. The DH students performed an oral health examination on the PT students, and the PT students performed an individual health test on the DH students; both groups used motivational interviewing. Documentation of student's learning experience was carried out through seminars and questionnaires. The students were overall satisfied with the learning experience. Most appreciated are that it reflected a 'real' professional situation and that it also reinforced important learning from their seminars. The scholarship model made the teachers aware of the importance of evidence-based teaching. Furthermore, the indicators for meaningful learning and increased self-efficacy were high, and the students became more engaged by practising in a real situation, more aware of other health professions and reflected about tacit knowledge.


Soilless revegetation: An efficient means of improving physicochemical properties and reshaping microbial communities of high-salty gold mine tailings.
Soilless revegetation is a cost-effective and eco-friendly method for the ecological restoration of gold mine tailings. However, due to gold mine tailings are high-salty, alkaline and low-nutrient, little research has been done on soilless revegetation of gold mine tailings. The aim of study was to apply soilless revegetation to gold mine tailings, and investigate the changes of physicochemical properties and microbial communities of tailings after soilless revegetation. Six selected herbaceous plants (Melilotus officinalis, Xanthium sibiricum, Festuca elata, Zoysia japonica, Amaranthus tricolor L., Artemisia desertorum) grew well on the bare tailings, and their heights reached as high as 16.28 cm after 90 days. After soilless revegetation, tailings salinity dramatically dropped from 547.15 to 129.24 μS cm-1, and pH went down from 8.68 to 7.59 at most. The content of available phosphorus (AP), available nitrogen (AN) and organic matter (OM) in tailings gradually improved, especially the content of AP and OM increased 53.36% and 52.58%, respectively. Furthermore, microbial metabolic activity and diversity in tailings obviously increased 70.33-264.70% and 1.64-13.97% respectively. The relative abundance of potential plant growth-promoting bacteria increased 1.40-3.05%, while the relative abundance of opportunistic pathogens and halophilic bacteria decreased 10.58-17.03% and 2.98-6.52% respectively. Such variations of microbial communities were beneficial for tailings restoration. This study provided insight into soilless revegetation and its impact on tailings microorganisms, which could be a new strategy for ecological restoration of gold mine tailings.


Suppressive effects of a pyrazole derivative of curcumin on airway inflammation and remodeling.
To advance the control of airway epithelial cell function and asthma, we investigated the effects of a new curcumin derivative, CNB001, which possesses improved pharmacological properties. Normal human bronchial epithelial (NHBE) cells were stimulated with synthetic double-stranded RNA, Poly(I:C). CNB001 significantly suppressed IL-6, TNF-α, and GM-CSF production by NHBE cells, and did so more effectively than did curcumin or dexamethasone (DEX). CNB001 significantly inhibited the decrease of E-cadherin mRNA expression and increase of vimentin mRNA expression observed in NHBE cells induced by a combination of TGF-β1 and TNF-α, which are markers of airway remodeling. In NHBE cells stimulated by TGF-β1, CNB001 significantly downregulated the level of active serine peptidase inhibitor clade E member (SERPINE) 1, which is also reported to be related to airway remodeling. Whereas DEX alone significantly increased the active SERPINE1 level, the combination of DEX and CNB001 significantly suppressed active SERPINE1. In addition, CNB001 significantly suppressed neutrophil infiltration, IL-6, TNF-α, IL-13 and active SERPINE1 production in bronchoalveolar lavage fluid of the murine asthma model, which was not observed in the case of DEX. In conclusion, the curcumin derivative, CNB001, is a promising candidate to treat asthma associated with neutrophilic airway inflammation and remodeling.


Acetabular reinforcement rings associated with allograft for severe acetabular defects.
Acetabular revisions with severe bone defects can be challenging procedures. Several grading systems have been set into place to help the surgeon adequately gauge the degree of bone loss within the acetabulum. Internationally innovative research in orthopedics and bio-engineering has helped with progression of successful techniques and rings to re-establish the normal anatomy of the hip. The purpose of this review is to evaluate the outcomes of the different acetabular reinforcement rings in the setting of severe acetabular defects. A successive report of relevant data from the literature of multiple techniques will be provided. The procedures include the cup-cage, the Müller ring, the Ganz Ring, the Kerboull acetabular reinforcement device (KARD), the graft augmentation prosthesis (GAP) ring, and the Burch-Schneider ring. The main focus of this overview is rings only; other devices such as trabecular augments, custom-made cages, or oblong cups are not discussed. Furthermore, a special emphasis on the surgical technique of the KARD is also given. Procedures using these rings are usually associated with bone grafts either bulk or morselized. When considering the available data on these various rings used for reconstruction of the severely damaged acetabulum, the cup-cage, the KARD, and the Burch-Schneider ring appear to be reliable options for more successful long-term outcomes.


Technique for PBSC harvesting in children of weight under 10 kg.
Peripheral blood stem cell (PBSC) harvesting in the smallest children (weight <10 kg) using separators is complicated by specific problems. The volume of the separation set exceeds 25% of the total blood volume and the vascular access is generally not sufficient. Therefore, a simple manual technique for PBSC harvesting was developed. Three children (6-9 kg), with newly diagnosed tumours were scheduled to be treated with three to six sequential courses of high-dose chemotherapy, each followed by PBSC support. PBSC harvests were started after mobilization using cyclophosphamide and G-CSF when the peripheral blood CD34+ cell count exceeded 50/microl. About 50 ml of blood was drawn from a venous catheter, injected into a transfer bag containing ACD-A, and centrifuged. The buffy coat obtained was pooled in a collection bag, remaining plasma and erythrocytes were immediately reinfused and a subsequent cycle started. From three to 13 cycles were performed in 1-3 days and 18.0-32.2 x 10(6) CD34+cells/kg were collected. We did not detect any bacterial contamination or any notable complications. Fifteen PBSC reinfusions have been performed to date, each with rapid engraftment taking between 7 and 13 days. Patients are in very good PR (18 months from diagnosis) or in CR (6 and 8 months). We can conclude that this procedure is feasible and safe.


Prescribing incentive schemes : a useful approach?
From 2000 to 2004, primary care organisations (PCOs) in England were legally required to operate a prescribing incentive scheme for their general practices. A statutory framework specified the types of target, maximum rewards and use of 'good cause for failure' provisions that schemes should include. Our objective was to explore whether schemes might be a useful approach to encourage 'good quality' prescribing. We requested copies of the original schemes from all PCOs in England in 2001 and 2002. Data were extracted on the rewards offered, types of budgetary targets set and additional conditions specified. Many schemes had not been finalised, some PCOs had no scheme, and one scheme operated without rewards. Although schemes covered similar therapeutic areas, they varied considerably in their length, complexity, reward levels and reward structure. Over half the schemes contained no 'good cause for failure' provision. PCOs are offering diverse incentives to general practices and some have interpreted the statutory framework imaginatively. Better use of the 'good cause for failure' provision may help to overcome inflationary pressures on prescribing, but further research is needed to clarify the role of financial incentives in influencing prescribing.


A hereditary genetic marker closely associated with microsatellite instability in lung cancer.
Alterations in 5 microsatellite loci were analyzed in tumors from 137 patients with primary non-small cell lung carcinomas that were also genotyped for the Hras1 variable number of tandem repeats (VNTR) locus. Twenty-nine patients (21%) had changes in at least one microsatellite locus. A majority of these cases (24 of 29, 83%) had VNTR alleles classified as rare in the population. The frequency of these rare alleles were significantly higher among lung cancer patients than in healthy controls (P = 0.016 or 1.80; 95% confidence interval = 1.13-2.85). Microsatellite alterations were significantly more frequent among patients with at least one rare Hras1 VNTR allele (24 of 40, 60%) compared to patients with two common alleles (5 of 97, 5%; P < 0.001 or 27.6; 95% confidence interval = 8.18-82.9). Microsatellite alterations were also more frequent among patients below 50 years of age (8 of 21, 38%) than for older patients (21 of 112, 19%).


Differences in chemical composition of plants grown at constant relative growth rates with stable mineral nutrition.
Leaf chemistry of a willow clone (Salix aquatica Smith) differed significantly when grown at constant relative growth rates depending upon the relative availability of nutrients and light. Concentration of amino acids and nitrate were high in plants grown with a relative surplus of nutrients. Concentrations of starch, tannin, and lignin, on the other hand, were high in plants grown with a relative surplus of carbon. Photosynthetic rates, expressed per unit leaf area, were similar when plants were grown under high light conditions, regardless of nutrient availability. Dark respiration was much higher in plants supplied with abundant nutrients than in those with a more limited supply, reflecting differences in nitrogen concentration of the tissue. The experimental approach allows plants to be grown to a standard size with differing, but highly uniform chemistry. Plants grown in such a manner may provide good experimental material to evaluate interactions between herbivores or pathogens and their hosts.


GABA and histamine interaction in the basolateral amygdala of rats in the plus-maze test of anxiety-like behaviors.
In the present study, we have investigated the effects and the interaction of the GABAergic and histaminergic systems in the basolateral amygdala (BLA) of rats using the plus-maze test of anxiety-like behaviors. Unilateral injection of different doses of muscimol (GABA(A) receptor selective agonist; 0.01, 0.05 and 0.1 microg/rat) into the BLA (intra-BLA) increased the percentage of open arm time (%OAT) and open arm entries (%OAE) at the doses of 0.05 and 0.1 microg/rat that are representative of an anxiolytic response. Intra-BLA injection of bicuculline (GABA(A) receptor selective antagonist; 0.05, 0.1 and 0.5 microg/rat) decreased %OAT and %OAE at the doses of 0.1 and 0.5 microg/rat showing an anxiogenic-like effect. Intra-BLA administration of histamine (0.05, 0.1 and 0.5 microg/rat) also showed anxiogenic-like effects at the doses of 0.1 and 0.5 microg/rat while intra-BLA administration of pyrilamine (an H1 receptor selective antagonist; 5, 10 and 20 microg/rat) induced anxiolytic effects at the dose of 20 microg/rat. Coadministration of histamine (0.1 microg/rat) with muscimol reversed the anxiolytic effect of muscimol at the dose of 0.1 microg/rat while coadministration of histamine (0.1 microg/rat) with bicuculline increased the anxiogenic effect of bicuculline at the dose of 0.05 microg/rat. On the other hand, coadministration of pyrilamine (10 microg/rat) with bicuculline decreased anxiety-like behaviors of bicuculline at the dose of 0.5 microg/rat while pyrilamine could not affect the anxiolytic effect of muscimol. In conclusion, it seems that both GABAergic and histaminergic systems not only play a part in the modulation of anxiety-like behaviors in the BLA of rats but may also have opposite effects in this brain region.


Therapeutic effects of synbiotic on neonates with gestational age over 34 weeks admitted for jaundice.
Hyperbilirubinemia is a common problem in neonates. The aim of this study was to evaluate the effect of synbiotic in addition to routine phototherapy on the treatment of neonatal jaundice. This double-blind clinical trial, was performed on 194, 3-14 days old neonates. Neonates were divided into intervention and placebo groups. The intervention group received 5 drops of oral synbiotic daily along with phototherapy and the placebo group underwent phototherapy plus a placebo. Gestational age, age, weight, sex, initial and daily bilirubin level, frequency of defecation, mode of delivery, and length of hospitalization were assessed. The rate of bilirubin reduction on the first day of admission was significantly higher in the intervention group (2.9±1.81 vs. 2.06±1.93, p = 0.002). The mean level of bilirubin on the second (9.8±1.92 vs. 10.88±2.26) and third days (8.06±1.54 vs. 9.86±1.7) was lower in the intervention group (p = 0.001). The proportion of discharged patients in the third and fourth days was higher in the intervention group compared to the control (65% vs. 41%, 99% vs. 86.5%, respectively, p = 0.001). However, the duration of hospitalization was shorter in the intervention group compared to the control (2.36±0.5 vs. 2.74±0.74, p = 0.001). Based on our results, daily treatment with 5 drops of synbiotic along with phototherapy can be a safe and effective modality in faster bilirubin reduction, decreasing the hospitalization period and phototherapy. Therefore, it seems that it can be used as an adjunct therapy for neonates with jaundice.


Targeting acid ceramidase inhibits YAP/TAZ signaling to reduce fibrosis in mice.
Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein β-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis.


Distrust as a form of inequality.
Navigating social hierarchies is a ubiquitous aspect of human life. Social status shapes our thoughts, feelings, and actions toward others in various ways. However, it remains unclear how trust is conferred within hierarchies and how status-related cues are used when resources are on the line. This research fills this knowledge gap by examining how ascribed, consensus-based status appearance, and perceived status appearance impact investment decisions for high- and low-status partners during a Trust Game. In a series of pre-registered experiments, we examined the degree to which participants trusted unfamiliar others with financial investments when the only available information about that person was their socioeconomic status (SES). In Study 1, SES was ascribed. Studies 2 and 3 conveyed SES with visual antecedents (clothing). Across all three experiments, participants trusted high SES partners more than low SES partners. In addition, subjective perceptions of status based on visual cues were a stronger predictor of trust than consensus-based status judgments. This work highlights a high status-trust bias for decisions where an individual's money is on the line. In addition, high-status trust bias may occur simply because of an individual's subjective assumptions about another's rank.


The endocrinology of feeding in the newborn.
During the last 20 years there has been an explosion of interest in and knowledge of hormones and regulatory peptides manufactured by specialized cells in the gut. Evidence has been presented in this chapter to suggest that these substances have essential roles to play in the effective utilization of food in the human adult, and that they also have an essential role to play in the differentiation and functional development of the fetal gut. It is, perhaps, during the days immediately following birth that they have their greatest and most important influence, in determining the successful adaptation to postnatal enteral feeding. There is good evidence to show that the initiation of enteral feeding is an important environmental trigger which provokes massive surges in the concentrations of these peptides in the first postnatal days in both premature and full term infants. The mode of administration and the composition of feeds have further influences, whilst deprivation of enteral feeding prevents the appearance of postnatal hormonal surges. In view of the fact that sub-nutritional volumes of milk are capable of inducing these surges, the concept of minimal enteral feeding in seriously ill premature and full term infants and even the therapeutic use of regulatory peptides warrants further investigation. Finally, it is evident that much more study is required to define the ontogeny, regulation of secretion, interaction and mechanism of effect of these fascinating substances.


Orchestration of pathogen recognition by inflammasome diversity: Variations on a common theme.
Innate immunity is a crucial part of the immune system, capable of mounting specific host responses against distinct pathogens. An integral component of the innate immune system is a network of pathogen recognition receptors, which are present at the surface of the cell or in the cytoplasm. Nucleotide oligomerization domain (Nod)-like receptors form the largest known family of intracellular innate immune sensors of microbes and danger signals that initiate early host responses. Some Nod-like receptors, such as NALP, NAIP and IPAF, form molecular machines termed inflammasomes, which are involved in the activation of inflammatory cytokines such as IL-1beta and IL-18. The diversity and the role of the different types of inflammasomes remain poorly defined. In this issue of the European Journal of Immunology, it is reported that the Gram-negative human pathogen Pseudonomas aeruginosa specifically activates an IPAF inflammasome. This finding, in combination with other recently published reports, reveals how different pathogens engage distinct types of inflammasomes, further highlighting the diversity and plasticity of inflammasomes activation.


Determinants of farmers' adoption of improved soil conservation technology in a middle mountain watershed of Central Nepal.
This study explores different socio-economic and institutional factors influencing the adoption of improved soil conservation technology (ISCT) on Bari land (Rainfed outward sloping terraces) in the Middle Mountain region of Central Nepal. Structured questionnaire survey and focus group discussion methods were applied to collect the necessary information from farm households. The logistic regression model predicted seven factors influencing the adoption of improved soil conservation technology in the study area including years of schooling of the household head, caste of the respondent, land holding size of the Bari land, cash crop vegetable farming, family member occupation in off farm sector, membership of the Conservation and Development Groups, and use of credit. The study showed that technology dissemination through multi-sectoral type community based local groups is a good option to enhance the adoption of improved soil conservation technology in the Middle Mountain farming systems in Nepal. Planners and policy makers should formulate appropriate policies and programs considering the farmers' interest, capacity, and limitation in promoting improved soil conservation technology for greater acceptance and adoption by the farmers.


Eye lens dose of medical personnel involved in fluoroscopy and interventional procedures at a Malaysian Hospital.
This study measured the radiation exposure of the eye lens of medical personnel performing fluoroscopy and interventional procedures at the Sarawak General Hospital in Kuching, Sarawak, Malaysia. This study was the first in Malaysia to utilise in vivo radiation measurement relatively near the eye lens. 41 medical personnel performing 79 procedures were monitored for their eye lens exposure using the NanoDot™ optically-stimulated luminescence dosimeters (OSLD) taped to the outer canthus of their eyes. The air-kerma area product (KAP), fluoroscopy time (FT) and number of procedure runs were also recorded. KAP, FT and number of runs were strongly correlated. However, only weak to moderate correlations were observed between these parameters with the measured eye lens doses. The average median equivalent eye lens dose was 0.052 mSv (ranging from 0.0155 to 0.672 mSv). The eye lens doses of primary operators were found to be significantly higher than their assistants due to the closer proximity to the patient and X-ray tube. The left eye lens of the operators received the highest amount of radiation due to their habitual positioning towards the radiation source. KAP and FT were not useful in predicting the equivalent eye lens dose exposure in interventional radiological procedures. Direct in vivo measurements were needed to provide a better estimate of the eye lens doses received by medical personnel during these procedures. This study highlights the importance of using direct measurement, such as OSLDs, instead of just indirect factors to monitor dose in the eye lens in radiological procedures.


[Specific features of pollination in the Manchurian birthwort Aristolochia manshuriensis].
An analysis of pollination system in Aristolochia manshuriensis has shown that flower structure in this species is strictly adapted to cross-pollination, but the possibility of an autogamous or geitonogamous type of self-pollination with the involvement of insects is not excluded. The flowers of A. manshuriensis are most frequently visited by flies of the family Anthomyiidae, which markedly contribute to their pollination. Males account for 65% of pollinator insects collected from the flowers.


Air pollution and elite adolescent soccer players' performance and well-being; an observational study.
Exercising outdoors may inadvertently lead to individuals inhaling levels of air pollution that may be detrimental to their health and activity-related performance. Endurance athletes are a particularly susceptible subgroup due to their high ventilation rates sustained over prolonged periods of time coupled with high training loads that often occur outdoors. In this study, we estimate the effects of air pollution on a series of athletic performance parameters in an elite adolescent soccer team. External, internal, and subjective loads and wellness questionnaires were recorded for the 26 matches and 197 training sessions carried out during the 2018-19 season for a U19 team competing in Germany. Each session was combined with hourly information on the concentration of PM10, O3 and NO2 in spatial proximity to each playing field for the duration of training or playing. Increases in PM10 and O3 had significant (p <.001) associations with decreasing total distance (m) ran per session. Furthermore, increases in O3 and NO2 concentrations were related to an increase in average heart rate (p <.05). Moreover, increases in PM10 concentration was associated with increased rating of perceived exertion (p <.001). Last, the total inhaled dose of O3 and NO2 over one session was linked to significant (p <.05) decreases in athletes' wellness scores on the following morning. We find supporting evidence of the negative effects of air pollution in elite adolescent soccer players in both matches and training. The negative impacts observed on several aspects of performance are present within an elite team that regularly trained in pollution levels well within the normal ranges of what the World Health Organisation (WHO) reports to be suitable air quality. Therefore, mitigation strategies such as monitoring the air quality at the training pitch are recommended to reduce athlete exposure to air pollution even when exercising in moderate air quality.


Characterization of the avian progesterone receptor through the use of inhibitors.
Several chemical agents have been identified which block interaction of the avian progesterone receptor with isolated nuclei, ATP-Sepharose, DNA-cellulose or phosphocellulose. Four of these inhibitors, rifamycin AF/103, o-phenanthroline, aurintricarboxylic acid and pyridoxal 5-phosphate appear to block directly binding of the activated receptor complex to the above "acceptors." Another inhibitor, sodium molybdate, only blocks receptor interactions when added before receptor activation and therefore appears to interfere with the activation process. When nuclear receptor complexes were formed in vivo and labeled by nuclear exchange with [3H]progesterone in vitro, these complexes could not be disrupted by incubation of the nuclei with inhibitors. Therefore, the receptor complex bound in nuclei appears to be modified or masked in a way which resists the action of these chemical agents. These results indicate the value of inhibitors as chemical probes for the analysis of steroid receptors.


Anti-coccidial, anthelmintic and antioxidant activities of pomegranate (Punica granatum) peel extract.
Coccidiosis and helminthosis in poultry are responsible for worldwide economic losses. The methanolic extract of Punica granatum (pomegranate) peel was used in vivo for its pharmacological, antioxidant and anti-coccidial properties and in vitro for its anthelmintic activity. For the in vivo study, four groups of mice were investigated. The first group was inoculated only with sterile saline and served as the control group. The second group was treated by oral gavage with pomegranate extract (300 mg/kg) daily for 5 days. The third and fourth groups were infected with 10(3) sporulated oocysts of Eimeria papillata. The fourth group was also treated once daily with pomegranate peel extract for 5 days. For the in vitro study, the anthelmintic effect of pomegranate peel extract was observed on live adult Allolobophora caliginosa. Paraffin sections from jejunum as well as jejunal homogenate were prepared for the histopathological and biochemical investigations, respectively. The data showed that mice infected with E. papillata revealed an output of approximately 2.9 × 10(5) oocysts per gram faeces on day 5 p.i. This output is significantly decreased to 50 % in pomegranate-treated mice. Infection with E. papillata induced marked histopathological alterations in jejunum in the form of inflammation, vacuolation of the epithelium and destruction of some villi. In addition, pomegranate extract caused a great diminish in body weight loss of infected mice. Moreover, the number of goblet cells stained with Alcian blue within the infected villi was significantly increased by about 26 % after pomegranate treatment. In addition, Pomegranate significantly lowered the increased number of apoptotic cells due to E. papillata infection by about 36 %. The results showed that E. papillata enhanced hydrogen peroxide, lipid peroxidation and nitric oxide production with concomitant reduction in glutathione. Pomegranate induced marked improvements in all of the studied parameters as well as the histopathological features of jejunum. In addition, pomegranate was able to exert a significant anthelmintic effect on live adult A. caliginosa worms in terms of the paralysis and death of the worms at different concentrations (100, 200 and 300 mg/ml). The study revealed that pomegranate as a natural product has protective effects against E. papillata-induced coccidiosis as well as it possesses an anthelmintic activity.


Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism.
One of the major environmental factors that induce PD is Manganese (Mn). Cellular and molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that Mn exposure caused abnormal projection of dopaminergic neurons and decreased mRNA expression and protein levels of FTO. This is due to Mn-induced the upregulation of Foxo3a. Using the cell model of overexpression of FTO, we found that FTO could antagonize Mn-induced the down-regulation of axon guidance molecule ephrin-B2 through RNA-seq, MeRIP-qPCR, and RT-qPCR experiments. Through RIP-seq and actinomycin D experiments, it was found that FTO can up-regulate the mRNA m6A level of ephrin-B2, which can be recognized by YTHDF2 and degraded. Finally, it is proved that Mn induces dopaminergic neurons projection injury and motor dysfunction through Foxo3a/FTO/m6A/ephrin-B2/YTHDF2 signal pathway.


Mothers and their children look at baby pictures: the NICU experience in retrospect.
Photographs of Neonatal Intensive Care Unit (NICU) patients are frequently given to parents to promote bonding, but little attention has been paid to how families respond years later to viewing these special baby pictures. This study examines how 71 mothers of 3 to 7-year-old developmentally normal (DQ greater than or equal to 80) children who weighed less than 1,500 g at birth describe this experience. Compared to a group of mothers whose children were full term at birth, the NICU mothers described personally feeling and perceiving their children as more fearful (p less than .05), inquisitive (p less than .0001), worried (p less than .01), thoughtful (p less than .0001), and tearful (p less than .05). The responses of NICU mothers were significantly more highly correlated with their perceptions of their children's responses than were the mother-child correlations observed in a comparison group. The NICU children were reported by their mothers to ask about the NICU equipment, pain, being alone, their physical scars, and if their being "bad" caused their need for intensive neonatal care. Recommendations are provided on how pediatric care providers can assist NICU parents anticipate questions and respond to their children's concerns as they view these potentially distressing photographs.


Oxygen-organophosphate linkage in hemoglobin A. The double hump effect.
At low concentrations of chloride ions, and in the presence of nonsaturating concentrations of organophosphates, the oxygen equilibrium curves (OEC) for solutions of human adult hemoglobin exhibit a biphasic shape conveniently revealed by graphical analysis of the first derivative of the Hill equation with a characteristic form that we call "the double hump effect." This shape, observed for sub-saturating concentrations of organophosphates, stands in marked contrast to the simple lateral shifts of the OEC represented largely by scaling factors when pH or chloride are varied. In the case of protons or chloride, there is a self-buffering effect due to the presence of a large reservoir of proton or chloride binding sites not necessarily linked to oxygen, whereas such sites do not exist in the case of organophosphates. In addition, in the former case, we are dealing with curves measured at constant activity of the effector, while in the latter, at constant concentration. In the presence of saturating concentrations of inositol hexaphosphate (IHP), at low chloride concentration, the entire OEC is shifted to the right, including both its upper and lower asymptotes, indicating a decrease in the intrinsic oxygen affinities of both the T and R states. Theoretical considerations leading to a successful modeling of OEC obtained under nonsaturating and saturating concentrations of IHP required an expanded two-state allosteric model in which IHP-dependent variations in oxygen association constants for both the T and R conformations are taken into account.


[Biologically Active Peptides of King Crab Hepatopancreas].
Substances of a peptide nature isolated from the hepatopancreas of the king crab Paralithodes camtschaticus exhibited physicochemical properties and membranotropic and specific activities similar to those of membranotropic homeostatic tissue-specific bioregulators previously found in different mammalian and plant tissues. Their biological effect on vertebrate tissues was demonstrated on a model of roller organotypic cultivation of Pleurodeles waltl newt liver tissue.


Women in urology: Gender differences in urologists' authorship in high impact journals.
The number of women among medical doctors and surgeons continues to rise. However, urology remains one of the least preferred specialties by female physicians, resulting in the inadequate academic representation of female urologists. In this study we examined changes in the representation of female urologists in the journals European Urology (EU) and Journal of Urology (JOU) and investigated in which urology subspecialties female urologists focus their academic studies. Original articles, reviews and case reports published in EU and JOU were included in the study. The analysis was limited to 4 years, starting with 2004 and continuing at 5-year intervals until 2019.The publications were also classified according to urology subspecialty and geographic location. In total, 2708 articles were analysed. Overall, women accounted for 9.9% of first authors (267/2708) and 5.9% of senior authors (161/2708).The proportion of female first authors was 8.2% in 2004 and increased to 10.7% in 2009, 10.6% in 2014, and 11.6% in 2019 (P = 0.062). The proportion of female last authors was 7% in 2004 and 5.3%, 6.1%, and 2.5% in 2009, 2014, and 2019, respectively (P = 0.011). Women accounted for a significantly higher proportion of first authors than men in publications related to female and paediatric urology (P = 0.001 and P = 0.002, respectively). The increasing number of women urologists worldwide is not reflected in the scientific authorship of female urologists. Multicenter studies focusing on the elimination of gender disparity in academic representation are needed in surgical branches such as urology.


Assessment of the functionality and stability of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology.
In our previous study we examined the functionality and stability of nicotinic acetylcholine receptor (nAChR)-detergent complexes (nAChR-DCs) from affinity-purified Torpedo californica (Tc) using fluorescence recovery after photobleaching (FRAP) in Lipidic Cubic Phase (LCP) and planar lipid bilayer (PLB) recordings for phospholipid and cholesterol like detergents. In the present study we enhanced the functional characterization of nAChR-DCs by recording macroscopic ion channel currents in Xenopus oocytes using the two electrode voltage clamp (TEVC). The use of TEVC allows for the recording of macroscopic currents elicited by agonist activation of nAChR-DCs that assemble in the oocyte plasma membrane. Furthermore, we examined the stability of nAChR-DCs, which is obligatory for the nAChR crystallization, using a 30 day FRAP assay in LCP for each detergent. The present results indicate a marked difference in the fractional fluorescence recovery (ΔFFR) within the same detergent family during the 30 day period assayed. Within the cholesterol analog family, sodium cholate and CHAPSO displayed a minimum ΔFFR and a mobile fraction (MF) over 80%. In contrast, CHAPS and BigCHAP showed a marked decay in both the mobile fraction and diffusion coefficient. nAChR-DCs containing phospholipid analog detergents with an alkylphosphocholine (FC) and lysofoscholine (LFC) of 16 carbon chains (FC-16, LFC-16) were more effective in maintaining a mobile fraction of over 80% compared to their counterparts with shorter acyl chain (C12, C14). The significant differences in macroscopic current amplitudes, activation and desensitization rates among the different nAChR-DCs evaluated in the present study allow to dissect which detergent preserves both, agonist activation and ion channel function. Functionality assays using TEVC demonstrated that LFC16, LFC14, and cholate were the most effective detergents in preserving macroscopic ion channel function, however, the nAChR-cholate complex display a significant delay in the ACh-induce channel activation. In summary, these results suggest that the physical properties of the lipid analog detergents (headgroup and acyl chain length) are the most effective in maintaining both the stability and functionality of the nAChR in the detergent solubilized complex.


Composition and mutagenicity of PAHs associated with urban airborne particles in Córdoba, Argentina.
The comet assay and micronucleous test were used to assess the genotoxicity of organic compounds associated with particulate material collected in the city of Córdoba, Argentina. Samples were collected on fiber glass filters and their organic extracts were analyzed by GC-MS. These extracts were used for the comet assay on human lymphocytes and for the MCN test with Tradescantia pallida. The concentrations of polycyclic aromatic hydrocarbons as well as some of their nitro derivates were higher during winter. Their composition suggested that their main emission sources were gasoline and diesel vehicles. We observed genotoxic effects of these organic extracts due to the presence of both direct and indirect acting mutagens. We found a good agreement between the two test systems employed, which encourages the further use of plant bioassays for air pollution monitoring, especially in developing countries, due to their flexibility, low cost and efficiency.


Career destinations of University of Ghana Medical School graduates of various year groups.
To report on the current career destination of the University of Ghana Medical School (UGMS) qualified doctors in the year groups, 1998, 2000, 2003, 2005 and 2008. Interview of doctors from each year group currently working at the Korle-Bu Teaching Hospital corroborated by phone calls to the doctors. All Ghanaian doctors from each graduating year group. 1. Current location of employment in Ghana or abroad, 2. Gender ratios of the doctors retained in Ghana. Three hundred and seventy-two (372) UGMS doctors consisting of 353 Ghanaians and 19 foreign students graduated over the five year groups. Of the 353 Ghanaians, 113 emigrated, while all but one of the 240 living in Ghana, practice medicine. The retention rate improved from 54.2% in 1998 to 86.3% in 2008. The overall retention rate however is 68.0% while the retention rates for the male and female doctors were 69.3% and 64.6% respectively. Of the 177 doctors practicing in Ghana from the first 4 year-groups (i.e. 1998, 2000, 2003 and 2005,) 139 (i.e. 31, 31, 34 and 43 from the respective year groups) have either completed postgraduate training or are in the residency training programme. Thus 78.5% of these doctors working in Ghana have opted for postgraduate training. The establishment of the GCPS and to a lesser extent the introduction of the ADHA before it appear to have slowed down the medical brain drain as more and more doctors avail themselves of the local opportunities. The GCPS therefore needs supporting effectively in order to continue to be a strong incentive for the retention of doctors in Ghana, apart from helping to staff district general hospitals with specialists.


Melatonin for sleep disturbance in children with neurodevelopmental disorders: prospective observational naturalistic study.
Although melatonin is increasingly used for sleep disturbances in children with neurodevelopmental disorders, evidence on effective dose and impact on specific types of sleep disturbance is limited. We assessed 45 children (35 males, mean age: 6.3 ± 1.7 years) with neurodevelopmental disorders (n = 29: intellectual disability; n = 9: autism spectrum disorder; n = 7: attention-deficit/hyperactivity disorder) and sleep disturbances, treated with melatonin (mean duration: 326 days) with doses increased according to response. Thirty-eight percent of children responded to low (2.5-3 mg), 31% to medium (5-6 mg) and 9% to high doses (9-10 mg) of melatonin, with a significant increase in total hours of sleep/night, decreased sleep onset delay and decreased number of awakenings/night (all: p = 0.001), as measured with sleep diaries. No serious adverse events were reported. Melatonin is generally effective and safe in children with neurodevelopmental conditions. Increasing above 6 mg/night adds further benefit only in a small percentage of children.


Incidence of mitral valve prolapse in one hundred clinically stable newborn baby girls: an echocardiographic study.
Clinical and echocardiographic examinations were performed on 100 clinically stable, newborn baby girls. Mitral valve prolapse was noted on the echocardiograms of seven babies. Three subjects had systolic clicks, two of whom had systolic murmurs following the click. The four other babies who had echocardiographic evidence of mitral valve prolapse had no abnormal auscultatory signs. Of the 93 babies without evidence of mitral prolapse, 91 had normal echocardiograms and auscultatory features; one was noted to have a murmur consistent with a ventricular septal defect, and another had an eccentric aortic valve on the echocardiogram which was suggestive of a bicuspid aortic valve. Serial studies on our group of subjects will yield useful information regarding the natural history of mitral valve prolapse.


Evaluation of strategies to improve nutrition in people with dementia in an assessment unit.
To evaluate strategies designed to improve nutrition in elderly hospitalised patients with dementia. Observation phase followed by sequential interventions. A Short stay assessment unit. Hospital Inpatients with a variety of conditions causing dementia. Phase 1: Observation. Phase 2: Encouraging dietary, 'Grazing'. Phase 3: Using volunteers to feed patients. Phase 4: Improving dining room ambience by playing soothing music. Body Mass Index (BMI), mid arm circumference, mini nutrition index and caloric intake by plate waste measurement. BMI fell in the Observation phase 0.6 +/- 0.68 kg/m2 (p < 0.001), but increased in each of the Intervention phases. Phase2 0.3 +/- 0.86 kg/m2 (p < 0.04), Phase 3 0.37 +/- 0.4 kg/m2 (p < 0.04), Phase 4 0.39 +/- 0.7 kg/m2 (p < 0.007). Caloric intake increased in the intervention phases. Simple, inexpensive and easy to implement strategies can improve nutrition in hospital inpatients with dementia.


Nocardia asteroides aortitis with perforation of the aorta.
A 53-year-old man died of nocardial aortitis eight months after undergoing aortic valve replacement. Autopsy revealed vegetation in the area of a previous aortotomy incision and a small perforation of the aorta enclosed by pericardium immediately above the prosthetic valve ring. Prosthetic valve endocarditis was not present. Multiple splenic infarcts, microabscesses of both kidneys, and myocarditis were identified. Antemortem blood cultures and postmortem cultures of the aortic vegetation grew Nocardia asteroides.


Missense Variants in PAX4 Are Associated with Early-Onset Diabetes in Chinese.
East Asians are more susceptible to early-onset diabetes than Europeans and exhibit reduced insulin secretion at earlier stages. PAX4 plays a critical role in the development of β-cells. The dysfunction-missense variants PAX4 R192H and PAX4 R192S are common in East Asians but rare in Europeans. Therefore, we aim to investigate the diabetes-associated genes, including PAX4 R192H/S, in East Asians with early-onset diabetes. Exome variants of 80 Chinese early-onset diabetes patients (onset age < 35 years) after the exclusion of type 1 diabetes (T1D) were detected by a customized gene panel covering 32 known diabetes-associated genes. Then, 229 subjects with early-onset diabetes (T1D excluded) and 1679 controls from the Chinese population were genotyped to validate the association of PAX4 R192H/S with early-onset diabetes and related phenotypes. The gene panel detected 11 monogenic diabetes patients with five novel mutations among the 80 early-onset diabetes patients. Asian-specifically enriched PAX4 R192H and R192S were associated with early-onset diabetes (R192H: OR 1.88, 95% CI 1.37-2.60, P = 8.41 × 10-5; R192S: OR 1.71, 95% CI 1.17-2.51, P = 0.005). In early-onset diabetes patients, PAX4 R192H carriers had higher haemoglobin A1c (HbA1c) levels (P = 0.030) and lower 2 h C-peptide levels in the oral glucose tolerance test (OGTT) (P = 0.040); R192S carriers had lower fasting C-peptide (FCP) (P = 0.011) and 2 h C-peptide levels (P = 0.033) in OGTT than non-variant carriers. The ethnic-specific enrichment of PAX4 R192H/S predisposing East Asians to early-onset diabetes with decreased C-peptide levels may be one explanation of the discrepancy of diabetes between East Asians and Europeans. ClinicalTrials.gov (NCT01938365).


Time-action analysis of instrument positioners in laparoscopic cholecystectomy.
Instrument positioners can position and lock a laparoscopic instrument. This study uses time-action analysis to evaluate objectively whether IPs can substitute for a surgical assistant efficiently and safely. In four hospitals, 78 laparoscopic cholecystectomies were randomly assisted by a surgical assistant or an instrument positioner (AESOP and PASSIST) The efficiency and safety of laparoscopic cholecystectomies were analyzed with respect to time, number and type of actions, positioning accuracy, and peroperative complications. A questionnaire evaluated the difficulties for each operation and the comfort of instrument positioner use. The PASSIST and AESOP were able to replace the surgical assistant during laparoscopic cholecystectomies without significantly changing either the efficiency or the safety of the operation. The questionnaire showed that the surgeons preferred to operate with an instrument positioner. This study assessed objectively that instrument positioners can substitute for a surgical assistant efficiently and safely in elective laparoscopic cholecystectomies.


Costs associated with office visits for diarrhea in infants and toddlers.
We determined costs associated with diarrhea in a < 36-month-old ambulatory population. Children with acute diarrhea were enrolled during the rotavirus season at three centers. Questionnaires to assess costs of both medical and nonmedical factors were administered at the enrollment visit and 1 week later. Office computer records were reviewed to identify all visits by children with diarrhea during 1 year. Fifty-one patients were enrolled. The average cost per episode of diarrhea was $289, which included: $144, missed work; $57, office visits; $23, laboratory tests; $21, medications; $18, changed diet/oral rehydration solutions; $15, travel; $7, extra diapers; and $6, extra child care. During 1 year diarrhea accounted for 4% of all visits and 10% of visits among those < 36 months old. The annual cost at the three centers was $346,000, which extrapolates to $0.6 to $1.0 billion for the United States. Twenty-one percent of this cost was attributable to rotavirus diarrhea. We conclude that outpatient care for pediatric diarrhea is a major health care cost in the United States.


Comprehensive studies on the nature of interaction between carboxylated multi-walled carbon nanotubes and bovine serum albumin.
Herein, the interaction between carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) and bovine serum albumin has been investigated by using circular dichroism, UV-vis, and fluorescence spectroscopic methods and molecular modeling in order to better understand the basic behavior of carbon nanotubes in biological systems. The spectral results showed that MWCNTs-COOH bound to BSA and induced the relatively large changes in secondary structure of protein by mainly hydrophobic forces and π-π stacking interactions. Thermal denaturation of BSA in the presence of MWCNTs-COOH indicated that carbon nanotubes acted as a structure destabilizer for BSA. In addition, the putative binding site of MWCNTs-COOH on BSA was near to domain II. With regard to human health, the present study could provide a better understanding of the biological properties, cytotocicity of surface modified carbon nanotubes.


Psychological characteristics of early remitters in patients with panic disorder.
We aimed to examine whether anxiety sensitivity and agoraphobic fear could affect the time taken to remission after 24 weeks of open-label escitalopram treatment of patients with panic disorder (PD). We recruited 158 patients, and 101 patients completed the study. Clinical severity and psychological characteristics were assessed at baseline and 4, 12, and 24 weeks after the treatment, using the Clinical Global Impression-Severity (CGI-S), the Hamilton Rating Scales for Anxiety and Depression, the Anxiety Sensitivity Index-Revised (ASI-R), the Albany Panic and Phobia Questionnaire (APPQ), and the Panic Disorder Severity Scale (PDSS). Remission was defined as the absence of full panic attacks and PDSS scores of 7 or less. Completing patients were stratified according to the time taken to remit: early (n=20) and late (n=58) remission and non-remission groups (n=23). There were no significant differences among the three groups at baseline on the CGI-S and the PDSS mean scores. However, early remitters had significantly lower scores than late remitters and non-remitters on the ASI-R and APPQ. In conclusion, anxiety sensitivity and agoraphobic fear can affect the time to remission after pharmacotherapy, and clinicians should consider the psychological characteristics of PD patients in order to achieve an optimal response to pharmacotherapy.


Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge.
Color patterns of bird plumage affect animal behavior and speciation. Diverse patterns are present in different species and within the individual. Here, we study the cellular and molecular basis of feather pigment pattern formation. Melanocyte progenitors are distributed as a horizontal ring in the proximal follicle, sending melanocytes vertically up into the epithelial cylinder, which gradually emerges as feathers grow. Different pigment patterns form by modulating the presence, arrangement, or differentiation of melanocytes. A layer of peripheral pulp further regulates pigmentation via patterned agouti expression. Lifetime feather cyclic regeneration resets pigment patterns for physiological needs. Thus, the evolution of stem cell niche topology allows complex pigment patterning through combinatorial co-option of simple regulatory mechanisms.


Arterial Stiffness and Cerebral Small Vessel Disease.
Background and Objective: Studies on relations between arterial stiffness and full spectrum of radiological features of cerebral small vessel disease (CSVD) are scarce. We aim to investigate the association of arterial stiffness with lacunes, white matter hyperintensities (WMH), microbleeds (CMBs), dilated perivascular spaces (PVS), and brain atrophy in a community-based sample. Methods: A total of 953 participants (55.7 ± 9.4 years) who underwent brachial-ankle pulse wave velocity (baPWV) and brain magnetic resonance imaging were included. Lacunes, CMBs, and PVS were visually rated. Brain structure and WMH were automatically segmented. Brain parenchyma fraction (BPF), a surrogate index of brain atrophy, was calculated as a ratio of brain parenchyma volume to total intracranial volume. Multivariable logistic and linear regressions were used to investigate the associations between baPWV and CSVD. Subsequently, we explored these associations in strata of age. Results: Increased baPWV was associated with severe PVS in white matter (OR, 1.09; 95%CI, 1.01-1.17; p = 0.022), larger WMH volume (β, 0.08; 95%CI, 0.04-0.12; p < 0.001), lower BPF (β, -0.09; 95%CI, -0.15- -0.03; p = 0.007), and marginally associated with strictly lobar CMBs (OR, 1.11; 95%CI, 1.00-1.23; p = 0.055), but not with lacunes. WMH volume mediated the relation between baPWV and BPF. In age subgroup analysis, the association of baPWV with PVS in white matter was stronger among those aged <55 years, whereas the association with brain atrophy was more prominent among those aged ≥55 years. Increased baPWV was associated with larger WMH volume in both younger and older individuals. Conclusions: Increased arterial stiffness was associated with most of imaging markers of CSVD, including PVS in white matter, larger WMH volume, strictly lobar CMBs, and brain atrophy, but not lacunes. The mechanisms underlying these associations and their potential clinical significances warrant further investigations.


Diagnosis and immunotherapy of mould allergy. VII. IgG subclass response and relation to the clinical efficacy of immunotherapy with Cladosporium.
The IgG subclass response was evaluated by a sensitive allergen- and subclass-specific solid phase immunoradiometric assay during a 1-year placebo-controlled, double-blind study of immunotherapy with Cladosporium herbarum in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG2 and IgG3 responders. An intense and early IgG1 response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom-medication score was significantly correlated to the preseasonal IgG1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG1 and IgG4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome. Little or no increase of IgG1 and IgG4 was associated with improvement, i.e. decrease in symptom-medication score. The magnitude of the IgG1 response during the dose-increase phase was directly correlated to the number of systemic side effects. No relation of IgG1, IgG4 or IgG4/IgG1 ratio to changes in the IgE-mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects.


Prognostic value of POD18 combined with improved IELSG in primary central nervous system lymphoma.
The International Extranodal Lymphoma Study Group (IELSG) score is widely used in clinical practice to stratify the risk of primary central nervous system lymphoma (PCNSL) patients. Our study aims to confirm and improve the IELSG score in PCNSL patients based on Chinese populations. A total of 79 PCNSL patients were retrospectively analyzed. All patients treated with high-dose methotrexate (HD-MTX)-based therapy collected clinical data. The receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values for the factors in IELSG score. Progression of disease (POD) at the most landmark time point was determine by Epanechnikov kernel and the area under the ROC curve (AUROC). Kaplan-Meier and multivariable regression methods were used to analyze survival data. Nomogram was generated for calculating the weight of each selected factor. The traditional IELSG score had no significant difference on OS and PFS except ECOG ≥ 2 and could not stratify the risk groups in PCNSL. The improved IELSG scoring system was established, which incorporated age ≥ 54 years, ECOG ≥ 2, deep brain structure, elevated CSF protein, and LDH/ULN > 0.75. On the other hand, POD18 was identified as a new powerful prognostic factor for PCNSL. In multivariate analysis, POD18 and the improved IELSG scoring system were independent prognostic factors for OS. Nomogram including the two significant variables showed the best performance (C-index = 0.828). In this study, the IELSG score was improved and a new prognostic indicator POD18 was incorporated to construct a nomogram prognostic model, thereby further improving the predictive ability of the model.


Gynura procumbens ethanol extract and its fractions inhibit macrophage derived foam cell formation.
Gynura procumbens (Lour.) Merr. displayed cardio-protective effect that may prevent atherogenesis. The primary underlying pathological process of cardiovascular disease is atherosclerosis. Atherosclerotic lesion composed of macrophages, T cells and other immune cells which incorporated with cholesterol that infiltrates from the blood. The present study was performed to determine underlying mechanism of G. procumbens ethanol extract and its fractions such as aqueous, chloroform, ethyl acetate and hexane affect macrophage derived foam cell formation. Lipid droplets accumulation in treated macrophages were visualized by Oil Red O staining while the total cholesterol present in the treated macrophages were measured using Cholestryl Ester quantification assay kit. Enzyme-Linked Immunosorbent Assay (ELISA) were used to detect TNF-α and IL-1β secretion in the supernatant of treated macrophages. Gene expression of Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and ATP-binding cassette transporter A-1 (ABCA-1) in treated macrophages were analyzed using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). G. procumbens ethanol extract and its fractions reduced lipid droplet accumulation and total cholesterol in oxLDL-treated macrophages together with significantly reduction of TNF-α and IL-1β secretions in supernatant oxLDL-treated macrophages. LOX-1 gene expression was significantly reduced when G. procumbens ethanol extract and its fractions were added in oxDL-treated macrophages. In contrast, G. procumbens ethanol extract and its fractions significantly increased the expression of ABCA-1 gene in oxLDL-treated macrophages. In conclusion, G. procumbens ethanol extract and its fractions inhibit the formation of macrophage derived foam cell by reducing TNF-α and IL-1β expression, which usually highly expressed in atherosclerotic plaques, suppressing scavenger receptor LOX-1 gene that binds oxLDL but induced ABCA-1 gene that mediate lipid efflux from macrophages.


Stem Cells in Dermatology and Anti-aging Care of the Skin.
Multipotent stem cells have paved the way for new applications and deeper understanding in regenerative medicine and the pathophysiology of aging. During skin aging, cumulative photodamage, exhaustion of endogenous stem cell populations, mechanical stress, and increased fibrosis lead to skin with decreased epidermal thickness and compromised dermal integrity. Specific stem cells in the hair follicle create new keratinocytes after activation by defensin peptides, released by neutrophils during wounding. Studies pertaining to defensin peptides' efficacy on skin aging have been published, highlighting their potential as a new therapy for skin rejuvenation.


Trends in mortality by labour market position around retirement ages in three European countries with different welfare regimes.
In the face of economic downturn and increasing life expectancy, many industrial nations are adopting a policy of postponing the retirement age. However, questions still remain around the consequence of working longer into old age. We examine mortality by work status around retirement ages in countries with different welfare regimes; Finland (social democratic), Turin (Italy; conservative), and England and Wales (liberal). Death rates and rate ratios (RRs) (reference rates = 'in-work'), 1970 s-2000 s, were estimated for those aged 45-64 years using the England and Wales longitudinal study, Turin longitudinal study, and the Finnish linked register study. Mortality of the not-in-work was consistently higher than the in-work. Death rates for the not-in-work were lowest in Turin and highest in Finland. Rate ratios were smallest in Turin (RR men 1972-76 1.73; 2002-06 1.63; women 1.22; 1.68) and largest in Finland (RR men 1991-95 3.03; 2001-05 3.80; women 3.62; 4.11). Unlike RRs for men, RRs for women increased in every country (greatest in Finland). These findings signal that overall, employment in later life is associated with lower mortality, regardless of welfare regime.


Abjection in nursing: silently reading the body.
Throughout their careers, nurses must deal with patients that may invoke feelings of dejection, repulsion, or distress. This abjection of the patient is a real issue already established within the literature. This article seeks to enlighten what continues to be silenced in nursing practice. This article will present a paradigm of the nurse, patient's body, and professional caring through the lens of abjection as theoretically defined by Julia Kristeva, using body hair in women as a forum for discussion. Abjection is linked, by its very nature, to the definitions of professional caring. The ability to read a body through the abjection of one's own self is a rite of passage for most nurses.


Methanol fixed feeder layers altered the pluripotency and metabolism of bovine pluripotent stem cells.
The pluripotency maintenance of pluripotent stem cells (PSCs) requires the suitable microenvironment, which commonly provided by feeder layers. However, the preparation of feeder layers is time consuming and labor exhaustive, and the feeder cells treated with mitomycin C or γ-ray irradiation bring heterologous contamination. In this study, mouse embryonic fibroblasts (MEFs) were treated by methanol to generate chemical fixed feeder cells, and bovine embryonic stem cells F7 (bESC-F7) cultured on this feeder layer. Then the pluripotency and metabolism of bESC-F7 cultured on methanol-fixed MEFs (MT-MEFs) named MT-F7 was compared with mitomycin C treated MEFs (MC-MEFs). The results showed that bESC-F7 formed alkaline phosphatase positive colonies on MT-MEFs, the relative expression of pluripotent markers of these cells was different from the bESCs cultured on the MC-MEFs (MC-F7). The long-term cultured MT-F7 formed embryoid bodies, showed the ability to differentiate into three germ layers similar to MC-F7. The analyses of RNA-seq data showed that MT-MEFs lead bESCs to novel steady expression patterns of genes regulating pluripotency and metabolism. Furthermore, the bovine expanded pluripotent stem cells (bEPSCs) cultured on MT-MEFs formed classical colonies, maintained pluripotency, and elevated metabolism. In conclusion, MT-MEFs were efficient feeder layer that maintain the distinctive pluripotency and metabolism of PSCs.


A Systematic Review and Meta-Synthesis of Patients' Experiences and Perceptions of Seeking and Using Benzodiazepines and Z-Drugs: Towards Safer Prescribing.
Benzodiazepines and Z-drugs are used to treat complaints like insomnia, anxiety and pain. These drugs are recommended for short-term use only, but many studies report long-term use, particularly in older people. The aim of this study was to identify and synthesise qualitative studies exploring patients' experiences and perceptions of receiving benzodiazepines and Z-drugs, and through this identify factors which perpetuate use of these drugs, and strategies for achieving safer prescribing. A systematic search of six databases for qualitative studies exploring patients' experiences and perceptions of primary care benzodiazepine and z-drug prescribing published between January 2000 and April 2014 in a European language, and conducted in Europe, the United States, Australia or New Zealand. Reference lists of included papers were also searched. Study quality was assessed using the Critical Appraisal Skills Programme qualitative checklist. Findings were synthesised using thematic synthesis. Nine papers were included and seven analytical themes were identified relating to patients' experiences and perceptions and, within that, strategies for safer prescribing of benzodiazepines and Z-drugs: (1) patients' negative perceptions of insomnia and its impact, (2) failed self-care strategies, (3) triggers to medical help-seeking, (4) attitudes towards treatment options and service provision, (5) varying patterns of use, (6) withdrawal, (7) reasons for initial or ongoing use. Inappropriate use and prescribing of benzodiazepines and Z-drugs is perpetuated by psychological dependence, absence of support and patients' denial/lack of knowledge of side effects. Education strategies, increased availability of alternatives, and targeted extended dialogue with patients could support safer prescribing.


Anterior vs Posterior Periarticular Multimodal Drug Injections: A Randomized, Controlled Trial in Simultaneous Bilateral Total Knee Arthroplasty.
Currently, various techniques are used to overcome postoperative pain after total knee arthroplasty. A local analgesic infiltration with periarticular multimodal drug injection (PMDI) is favorable because of its simplicity, safety, and efficacy. The present study compared the efficacy of a PMDI at the anterior vs posterior compartments. Forty-six patients were randomized to receive the PMDI at either the anterior or posterior compartment, with the contralateral knee receiving the PMDI at the opposite compartment. The PMDI injected to the posterior capsule, medial and lateral meniscal remnant, was defined as the posterior compartment injection, whereas the injection to the medial retinaculum, quadriceps muscle, pes anserinus, and retropatellar fat pad was defined as the anterior compartment injection. Pain scores at rest, knee flexion angle, quadriceps function, and drainage blood loss were evaluated in both groups. The anterior PMDI group had significantly lower pain scores at rest during 96 hours postoperatively. On the day of discharge, 19 patients (41.3%) favored the knee with the anterior PMDI, which was superior to 9 patients (19.6%) who favored the knee with the posterior PMDI. The anterior PMDI demonstrated a superior recovery of quadriceps function during the same period, but there was no significant difference in terms of other parameters. The PMDI at the anterior compartment can reduce pain after total knee arthroplasty with potentially better quadriceps function compared with that in the PMDI at the posterior compartment. We recommend infiltrating the anterior compartment with a greater amount of PMDI than the posterior compartment.


Effects of almitrine bismesylate on arterial blood gases in patients with chronic obstructive pulmonary disease and moderate hypoxaemia: a multicentre, randomised, double-blind, placebo-controlled study.
Advanced chronic obstructive pulmonary disease (COPD) generates high costs, especially when patients require domiciliary long-term oxygen therapy (LTOT). Almitrine bismesylate has been shown to improve gas exchange in the lungs. Our hypothesis was that long-term treatment with almitrine might postpone the prescription of LTOT. To evaluate the effects of almitrine sequential treatment on arterial blood gases in COPD patients with moderate hypoxaemia. COPD patients with moderate hypoxaemia [partial oxygen tension in arterialised blood (PaO(2)) between 7.33 and 8.66 kPa (56-65 mm Hg)] were investigated. After a 1-month run-in period, patients were given either almitrine 100 mg per day or placebo for sequential treatment for a total of 12 months. 115 patients in a steady state (57 in the almitrine and 58 in the placebo group) were included. Mean age was 60 years, mean forced expiratory volume in 1 s was 34 +/- 13% of predicted and mean PaO(2) was 8.04 +/- 0.5 kPa (60.5 +/- 3.8 mm Hg). 38 patients were lost to follow-up, 23 in the almitrine and 15 in the placebo group. The majority of drop-outs were due to adverse events (AE; 16 in the almitrine and 9 in the placebo group). Almitrine treatment resulted in PaO(2) improvement of 0.43 +/- 0.88 kPa (3.2 +/- 6.6 mm Hg) (p = 0.003). The treatment effect between almitrine and placebo was 0.45 kPa (3.4 mm Hg) (p = 0.003). In the almitrine group, two distinct subgroups were observed: responders (n = 19) and non-responders (n = 38). Almitrine treatment in responders resulted in a clinically significant improvement in PaO(2) of 1.36 +/- 0.7 kPa (10.2 +/- 5.3 mm Hg) (p < 0.0001) and a reduction of partial carbon dioxide tension in arterialised blood. 31 patients experienced serious AE: 17 in the almitrine and 14 in the placebo group. Five patients died during the study (3 in the almitrine and 2 in the placebo group). Most AE occurring during the study were related to underlying disease. Clinical diagnosis of polyneuropathy resulted in the withdrawal of 5 patients in the almitrine group and 3 patients in the placebo group. Four patients in the almitrine group experienced weight loss. Almitrine treatment of patients with severe COPD and moderate hypoxaemia resulted in a small but significant improvement in PaO(2) over 12 months. A clinically important improvement in gas exchange was observed in 33% of treated patients. These patients may be candidates for long-term treatment.


Laser-assisted microinjection into targeted animal cells.
A pulsed (17 nanoseconds) Nd:YAG laser (1064 nm) was used to inject impermeable dyes (propidium iodide andiodide and merocyanine 540) and a plasmid (pEGFP-N1) encoding green fluorescent protein (GFP) into human breast adenocarcinoma cells (MCF-7). The cell membrane integrity and viability were fully preserved in this laser-assisted transfer.


Protective Role of Catechin on d-Galactosamine Induced Hepatotoxicity Through a p53 Dependent Pathway.
Objective of this study was to obtain a better understanding of the mechanism responsible for the d-galactosamine (d-GalN) induced hepatotoxicity and to study the effect of catechin against d-GalN induced hepatotoxicity. Catechin 50 and 100 mg/kg b.wt was administered for 1 week by oral route. Liver damage was induced by intra-peritoneal administration of 400 mg/kg b.wt d-galactosamine on the last day of catechin treatment. At the end of treatment all animals were killed and liver enzyme levels were estimated. Dissected hepatic samples were used for histopathology, RNA isolation, expression studies of Bax, Bcl-2 and p53 mRNA levels and mitochondrial membrane potential studies. We found that increases in the liver enzyme activity and decrease in antioxidant enzyme activity by d-GalN were significantly restricted by oral pretreatment with catechin. Disruption of mitochondrial membrane potential, up regulation of p53, Bax and down regulation of Bcl-2 mRNA levels in the liver of d-GalN intoxicated rats were effectively prevented by pretreatment with catechin.


Characteristics of multiple sclerosis in aboriginals living in British Columbia, Canada.
The objectives of this study were to identify and describe the demographic and clinical characteristics of multiple sclerosis (MS) in aboriginals in British Columbia (BC), Canada and compare these findings with non-aboriginal MS patients. This retrospective chart and database review accessed patient information from the linked BC-wide MS clinical and genetics databases. Data gathered included: demographics (age, sex and ethnicity); clinical characteristics (MS onset date, disease course and disability scores (Expanded Disability Status Scale [EDSS]). Aboriginals were identified via the database linkage augmented by physician and nurse recall. Two non-aboriginal comparator groups with definite MS were selected. Group one included all definite MS patients in the BC MS database, and group two comprised MS patients matched by sex, age at onset and initial disease course. Patient characteristics were compared using the Student's t-test, chi-squared test, and Kaplan-Meier survival analysis was used to examine disease progression (time to sustained and confirmed EDSS 6) We identified 26 aboriginals with MS, of which 19/26 (73%) were female, 23/26 (89%) had relapsing-onset MS and a mean onset age of 31.1 years. There were no significant differences between the MS aboriginals and the non-matched (n = 5708) comparator group with respect to age, sex or disease course (p > 0.1), However, aboriginals progressed more rapidly to EDSS 6 from disease onset (p < 0.001) when compared with the matched and unmatched comparator groups. We identified a small, but important cohort of aboriginals with MS; being the largest identified to date. There was evidence of more rapid MS progression in aboriginals compared with non-aboriginals.