Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.
Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.


Trends in self-rated health in European and North-American adolescents from 2002 to 2010 in 32 countries.
Self-rated health (SRH) in adolescence is known to be associated with health outcomes in later life. We carried out a trend analysis on data coming from three waves of data collected in 32 countries (mostly European) from 2002 to 2010 coming from the Health Behaviour in School-Aged Children surveys. SRH in adolescents was assessed using a Likert scale (excellent, good, fair and poor). Responses were dichotomized into 'excellent' vs. 'rest'. Country, age and gender groups were compared based on the odds ratio of declaring excellent SRH in 2010 with respect to 2002 and 2006. The trend for European adolescents indicates an improvement over the last decade, although, in the majority of countries, a higher proportion of adolescents rate their health as excellent during the period 2002-06 with respect to the second half of the decade (2006-10).Girls were found to constantly rate their health as poorer, compared to their male peers, in all countries. Age has also a very stable trend towards a decreasing rating of health with increasing age. Decreased rating of health in the period 2006-10 may be a signal of the socio-economic difficulties of Europe in the last part of this decade.


Nanomedicine and nanotoxicology: the pros and cons for neurodegeneration and brain cancer.
Current strategies for brain diseases are mostly symptomatic and noncurative. Nanotechnology has the potential to facilitate the transport of drugs across the blood-brain barrier and to enhance their pharmacokinetic profile. However, to reach clinical application, an understanding of nanoneurotoxicity in terms of oxidative stress and inflammation is required. Emerging evidence has also shown that nanoparticles have the ability to alter autophagy, which can induce inflammation and oxidative stress, or vice versa. These effects may increase neurodegenerative processes damage, but on the other hand, they may have benefits for brain cancer therapies. In this review, we emphasize how nanomaterials may induce neurotoxic effects focusing on neurodegeneration, and how these effects could be exploited toward brain cancer treatment.


Bond strength of orthodontic light-cured resin-modified glass ionomer cement.
The purpose of this study was to compare the bond strengths and debonded interfaces achieved with light-cured resin-modified glass ionomer cement (RMGIC) and conventional light-cured composite resin. In addition, the effects of acid etching and water contamination were examined. One hundred human premolars were randomly divided into five equal groups. The mini Dyna-lock upper premolar bracket was selected for testing. The first four groups were treated with light-cured RMGIC with or without 15 per cent phosphoric acid-etching treatment and with or without water contamination preceding bracket bonding. The control samples were treated with the conventional light-cured Transbond composite resin under acid etching and without water contamination. Subsequently, the brackets were debonded by tensile force using an Instron machine. The modified adhesive remnant index (ARI) scores were assigned to the bracket base of the debonded interfaces using a scanning electron microscope. The bond strength and modified ARI scores were determined and analysed statistically by one-way analysis of variance and chi-square test. Under all four conditions, the bond strength of the light-cure RMGIC was equal to or higher than that of the conventional composite resin. The highest bond strength was achieved when using RMGIC with acid etching but without water contamination. The modified ARI scores were 2 for Fuji Ortho LC and 3 for Transbond. No enamel detachment was found in any group. Fifteen per cent phosphoric acid etching without moistening the enamel of Fuji Ortho LC provided the more favourable bond strength. Enamel surfaces, with or without water contamination and with or without acid etching, had the same or a greater bond strength than Transbond.


The role of memory in processing relative clauses in children with specific language impairment.
This study investigated the relationship between 2 components of memory--phonological short-term memory (pSTM) and working memory (WM)--and the control of relative clause constructions in children with specific language impairment (SLI). Children with SLI and 2 control groups--an age-matched and a younger group of children with typical development--repeated sentences, including relative clauses, representing 5 syntactic roles and 2 levels of matrix clause complexity. The Working Memory Test Battery for Children was administered. All 3 groups showed significant associations between pSTM and both types of matrix clause construction. For children with SLI, significant associations emerged between (a) WM and more complex matrix clause constructions, (b) WM and relative clauses including a range of syntactic roles, and (c) pSTM and the least difficult syntactic role. In contrast, the age-matched control group could repeat almost all syntactic roles without invoking the use of either memory component. The role of pSTM and WM in the production of relative clauses by children with SLI is influenced by the degree of difficulty of the structure to be recalled. In therapy, the effect of WM limitations can be minimized by approaching each structure within the context of a simple matrix clause.


High-resolution 3-T MR neurography of the lumbosacral plexus.
The lumbosacral plexus comprises a network of nerves that provide motor and sensory innervation to most structures of the pelvis and lower extremities. It is susceptible to various traumatic, inflammatory, metabolic, and neoplastic processes that may lead to lumbrosacral plexopathy, a serious and often disabling condition whose course and prognosis largely depend on the identification and cure of the causative condition. Whereas diagnosis of lumbrosacral plexopathy has traditionally relied on patients' medical history, clinical examination, and electrodiagnostic tests, magnetic resonance (MR) neurography plays an increasingly prominent role in noninvasive characterization of the type, location, and extent of lumbrosacral plexus involvement and is developing into a useful diagnostic tool that substantially affects disease management. With use of 3-T MR imagers, improved coils, and advanced imaging sequences, which provide exquisite spatial resolution and soft-tissue contrast, MR neurography provides excellent depiction of the lumbrosacral plexus and its peripheral branches and may be used to confirm a diagnosis of lumbrosacral plexopathy with high accuracy or provide superior anatomic information should surgical intervention be necessary.


Evidence of selection for clones having genetic inactivation of the activin A type II receptor (ACVR2) gene in gastrointestinal cancers.
The activin signaling pathway parallels the transforming growth factor (TGF)-beta pathway. Both use extracellular ligands and cell surface receptors that are structurally and functionally related, as well as the same intracellular mediators (SMADs 2-4) to transmit these signals. Members of both pathways have been characterized previously as tumor suppressor genes on the demonstration of inactivating mutations in human neoplasms, e.g., genetic inactivation of the activin type I receptor was reported recently in pancreatic cancer. Here, we present evidence of selection for mutations of the activin A type II receptor (ACVR2) gene during human gastrointestinal carcinogenesis. Two 8-bp polyadenine tracts of the ACVR2 gene are targets for inactivating frameshift mutations in gastrointestinal neoplasms having microsatellite instability (MSI). These mutations are similar to those of the 10-bp polyadenine tract within the TGF-beta type II receptor (TGFBR2), a well-characterized target of frameshift mutations in the same neoplasms. We identified biallelic mutations of ACVR2 in 25 of 28 MSI colorectal and pancreatic cancers. In addition, a mutation in the ACVR2 gene combined with loss of the wild-type allele was found in a non-MSI pancreatic cancer. This evidence is compatible with a high degree of selection for inactivation of the ACVR2 gene in tumorigenesis, supporting ACVR2 as a candidate tumor suppressor gene in gastrointestinal cancers.


'Doubly deprived': a post-death qualitative study of primary carers of people who died in Western Australia.
This paper explores the daily experiences and occupational needs of family carers of people who were dying, with particular reference to their daily routines and ability to undertake other varied activities during the period of care. The impact of the caring experience on these occupations was then examined to determine how, and if, these occupational needs were addressed in the community using potential and available services. An exploratory approach using grounded theory was employed to examine these experiences. Participants were recruited from metropolitan (n = 10) and rural (n = 4) locations across Western Australia between February and June 2009, using a purposive sampling method. A semi-structured interview guide was developed following consultation with the literature, expert opinion and piloting. Interviews were conducted in participants' homes and questions were asked about their experiences as a carer including routines, engagement in usual activities and the impact of the caring role on their daily life during and after the period of care. Each interview was transcribed verbatim and analysed to determine potential themes. Two important themes were identified: (1) Carers experienced disengagement and deprivation from their usual occupations during and after the period of care; and (2) Participants described significant disempowerment in their role as carer. Carers are 'doubly disadvantaged' as a result of their caring role; they are unable to participate in their usual occupations and they are not recognised for their contributions as carers. Carers experienced disengagement and deprivation from their usual occupations, contributing to physical, psychological and emotional difficulties and this may result in long term consequences for health and well-being. In addition, the current services and support available for carers in the community are deemed inadequate; placing further stress on a health care system which needs to cope with increasing demands as a result of the ageing population in Australia.


Endocrine changes associated with relapse in advanced breast cancer patients on aminoglutethimide therapy.
About one third of unselected postmenopausal women with advanced breast cancer respond to treatment with aminoglutethimide and hydrocortisone, but they all eventually relapse, and further progression of disease occurs. In this study, 36 patients who initially responded to this treatment were evaluated to determine whether clinical relapse was associated with escape from endocrine suppression. Plasma estrone levels rose significantly (mean increase, 6.8 pg/ml) during the final 15% of time on treatment before relapse. Mean plasma estradiol, dehydroepiandrosterone sulfate, and androstenedione levels also rose with the approach of the relapse, but the increases were not statistically significant. The increase in estrone may contribute to the progression of disease.


The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model.
To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths. Decision modelling using Markov chains compared costs and effects over 5 years. The analysis was from the perspective of the National Health Service (NHS) in England and Wales. The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment. We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources. We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided. Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20,000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100,000 patients compared to psychosocial support alone over the course of 5 years. Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits. This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).


Molecular dynamics study of nanoparticle stability at liquid interfaces: effect of nanoparticle-solvent interaction and capillary waves.
While the interaction of colloidal particles (sizes in excess of 100 nm) with liquid interfaces may be understood in terms of continuum models, which are grounded in macroscopic properties such as surface and line tensions, the behaviour of nanoparticles at liquid interfaces may be more complex. Recent simulations [D. L. Cheung and S. A. F. Bon, Phys. Rev. Lett. 102, 066103 (2009)] of nanoparticles at an idealised liquid-liquid interface showed that the nanoparticle-interface interaction range was larger than expected due, in part, to the action of thermal capillary waves. In this paper, molecular dynamics simulations of a Lennard-Jones nanoparticle in a binary Lennard-Jones mixture are used to confirm that these previous results hold for more realistic models. Furthermore by including attractive interactions between the nanoparticle and the solvent, it is found that the detachment energy decreases as the nanoparticle-solvent attraction increases. Comparison between the simulation results and recent theoretical predictions [H. Lehle and M. Oettel, J. Phys. Condens. Matter 20, 404224 (2008)] shows that for small particles the incorporation of capillary waves into the predicted effective nanoparticle-interface interaction improves agreement between simulation and theory.


Factors affecting degeneration in human temporomandibular joints as assessed histologically.
The influence of sex, age, tooth loss, and articular disc position on temporomandibular joint (TMJ) degeneration was evaluated in specimens collected at autopsy from 15 women and 38 men ranging in age from 15 to 92 yr. The position of the articular discs was classified as normal or abnormal, tooth loss was both counted and categorized. Degenerative changes of the articular tissues were assessed histologically and quantified, taking into account both the severity of structural alterations and their extension along the articular surface. This was recorded separately in the condyle, disc, and temporal component, three latero-medial joint regions, and putative load-bearing and non-load-bearing surfaces. Analysis of covariance with repeated measures served for testing contributing factors. It showed that the effects of sex and the number of missing teeth were insignificant, whereas age up to about 55-60 yr and reduction of dental arch length proved to be the most important factors. Load-bearing seemed to play a significant role mainly at younger ages, and the effect of disc position was significant, when internal derangement was combined with reduction of dental arch length. Thus, rising severity of TMJ degenerative changes appears to be associated primarily with increasing age. In addition, it may also depend on mechanical factors, in particular loss of molar support and, to a minor degree, abnormal disc position.


Vibration training intervention to maintain cartilage thickness and serum concentrations of cartilage oligometric matrix protein (COMP) during immobilization.
To test the hypotheses that 1) 14-days of immobilization of young healthy subjects using a 6 degrees -"head-down-tilt-bed-rest"-model (6 degrees -HDT) would reduce cartilage thickness in the knee and serum Cartilage oligometric matrix protein (COMP) concentration and 2) isolated whole body vibration training would counteract the bed rest effects. The study was performed and designed in compliance with the Declaration of Helsinki and is registered as trial DRKS00000140 in the German Clinical Trial Register (register.germanctr.de). Eight male healthy subjects (78.0+/-9.5kg; 179+/-0.96cm, 26+/-5 years) performed 14 days of 6 degrees -HDT. The study was designed as a cross-over-design with two study phases: a training and a control intervention. During the training intervention, subjects underwent 2x5-min whole body vibration training/day (Frequency: 20Hz; amplitude: 2-4mm). Magnetic resonance (MR) images (slice thickness: 2mm; in-plane resolution: 0.35x0.35mm; pixels: 448x512) were taken before and after the 6 degrees -HDT periods. Average cartilage thicknesses were calculated for the load bearing regions on the medial and lateral articulating surfaces in the femur and tibia. While the control intervention resulted in an overall loss in average cartilage thickness of -8% (pre: 3.08mm+/-0.6mm post: 2.82mm+/-0.6mm) in the weight-bearing regions of the tibia, average cartilage thickness increased by 21.9% (pre: 2.66mm+/-0.45mm post: 3.24mm+/-0.63mm) with the vibration intervention. No significant differences were found in the weight-bearing regions of the femur. During both interventions, reduced serum COMP concentrations were observed (control intervention: -13.6+/-8.4%; vibration intervention: -9.9+/-3.3%). The results of this study suggest that articular cartilage thickness is sensitive to unloading and that vibration training may be a potent countermeasure against these effects. The sensitivity of cartilage to physical training is of high relevance for training methods in space flight, elite and sport and rehabilitation after illness or injury.


Intake of fruit, vegetables, and fruit juices and risk of diabetes in women.
The purpose of this study was to examine the association between fruit, vegetable, and fruit juice intake and development of type 2 diabetes. A total of 71,346 female nurses aged 38-63 years who were free of cardiovascular disease, cancer, and diabetes in 1984 were followed for 18 years, and dietary information was collected using a semiquantitative food frequency questionnaire every 4 years. Diagnosis of diabetes was self-reported. During follow-up, 4,529 cases of diabetes were documented, and the cumulative incidence of diabetes was 7.4%. An increase of three servings/day in total fruit and vegetable consumption was not associated with development of diabetes (multivariate-adjusted hazard ratio 0.99 [95% CI 0.94-1.05]), whereas the same increase in whole fruit consumption was associated with a lower hazard of diabetes (0.82 [0.72-0.94]). An increase of 1 serving/day in green leafy vegetable consumption was associated with a modestly lower hazard of diabetes (0.91 [0.84-0.98]), whereas the same change in fruit juice intake was associated with an increased hazard of diabetes (1.18 [1.10-1.26]). Consumption of green leafy vegetables and fruit was associated with a lower hazard of diabetes, whereas consumption of fruit juices may be associated with an increased hazard among women.


Osteoradionecrosis of the jaw bones at the University of Kentucky Medical Center.
There is disagreement over the management of teeth in irradiated head and neck cancer patients. Some oral surgeons support preirradiation extraction; others favor maintaining teeth. Before 1974, The University of Kentucky Department of Radiation Medicine found osteoradionecrosis (ORN) of the jaw in 10.9% of 220 irradiated cancer patients. After a program of oral care was instituted, the incidence declined to 2.7%. Of 109 patients who received radiotherapy between 1976 and 1985, only three (2.7%) developed ORN of the mandible. There was also a reduction in patients treated with interstitial therapy during this time. A review of the most recent experiences shows that, with present management methods at the University of Kentucky, ORN is not a significant problem. Of 30 patients treated in 1986, only one had ORN, and this was of the maxilla. Post-irradiation extractions were not identified as a significant risk for necrosis. Hyperbaric oxygen is used as a treatment for persistent ORN.


Theoretical elastic deformations of a thick horizontal circular mirror on a double-ring support.
This paper gives exact, closed-form expressions for the deflection, under its own weight, moments, and shears, in a thick, horizontally oriented, circular mirror on a double-ring support. A theory developed by Reissner for thick plates that includes shear deformations is used, and the results are reduced to those of classical plate theory. It is found that for mirrors having thickness-to-diameter ratios greater than approximately one-tenth, shearing deformations can contribute significantly to the total deflection, and hence should not be neglected. Numerical results are presented and interpreted in detail.


A systems biology approach identifies inflammatory abnormalities between mouse strains prior to development of metabolic disease.
Type 2 diabetes and obesity are increasingly affecting human populations around the world. Our goal was to identify early molecular signatures predicting genetic risk to these metabolic diseases using two strains of mice that differ greatly in disease susceptibility. We integrated metabolic characterization, gene expression, protein-protein interaction networks, RT-PCR, and flow cytometry analyses of adipose, skeletal muscle, and liver tissue of diabetes-prone C57BL/6NTac (B6) mice and diabetes-resistant 129S6/SvEvTac (129) mice at 6 weeks and 6 months of age. At 6 weeks of age, B6 mice were metabolically indistinguishable from 129 mice, however, adipose tissue showed a consistent gene expression signature that differentiated between the strains. In particular, immune system gene networks and inflammatory biomarkers were upregulated in adipose tissue of B6 mice, despite a low normal fat mass. This was accompanied by increased T-cell and macrophage infiltration. The expression of the same networks and biomarkers, particularly those related to T-cells, further increased in adipose tissue of B6 mice, but only minimally in 129 mice, in response to weight gain promoted by age or high-fat diet, further exacerbating the differences between strains. Insulin resistance in mice with differential susceptibility to diabetes and metabolic syndrome is preceded by differences in the inflammatory response of adipose tissue. This phenomenon may serve as an early indicator of disease and contribute to disease susceptibility and progression.


Religious circumcision, invasive rites, neutrality and equality: bearing the burdens and consequences of belief.
The decision of the German regional court in Cologne on 26 June 2012 to prohibit the circumcision of minors is important insofar as it recognises the qualitative similarities between the practice and other prohibited invasive rites, such as female genital cutting. However, recognition of similarity poses serious questions with regard to liberal public policy, specifically with regard to the exceptionalist treatment demanded by certain circumcising groups. In this paper, I seek to advance egalitarian means of dealing with invasive rites which take seriously cultural diversity, minimise harm and place responsibility for the burdens and consequences of beliefs upon those who promote practices.


Distinct phenotypes distinguish the molecular classes of Angelman syndrome.
Angelman syndrome (AS) is a severe neurobehavioural disorder caused by defects in the maternally derived imprinted domain located on 15q11-q13. Most patients acquire AS by one of five mechanisms: (1) a large interstitial deletion of 15q11-q13; (2) paternal uniparental disomy (UPD) of chromosome 15; (3) an imprinting defect (ID); (4) a mutation in the E3 ubiquitin protein ligase gene (UBE3A); or (5) unidentified mechanism(s). All classical patients from these classes exhibit four cardinal features, including severe developmental delay and/or mental retardation, profound speech impairment, a movement and balance disorder, and AS specific behaviour typified by an easily excitable personality with an inappropriately happy affect. In addition, patients can display other characteristics, including microcephaly, hypopigmentation, and seizures. We restricted the present study to 104 patients (93 families) with a classical AS phenotype. All of our patients were evaluated for 22 clinical variables including growth parameters, acquisition of motor skills, and history of seizures. In addition, molecular and cytogenetic analyses were used to assign a molecular class (I-V) to each patient for genotype-phenotype correlations. In our patient repository, 22% of our families had normal DNA methylation analyses along 15q11-q13. Of these, 44% of sporadic patients had mutations within UBE3A, the largest percentage found to date. Our data indicate that the five molecular classes can be divided into four phenotypic groups: deletions, UPD and ID patients, UBE3A mutation patients, and subjects with unknown aetiology. Deletion patients are the most severely affected, while UPD and ID patients are the least. Differences in body mass index, head circumference, and seizure activity are the most pronounced among the classes. Clinically, we were unable to distinguish between UPD and ID patients, suggesting that 15q11-q13 contains the only significant maternally expressed imprinted genes on chromosome 15.


The COPE index--a first stage assessment of negative impact, positive value and quality of support of caregiving in informal carers of older people.
Data was collected in five countries from informal carers of older people (n = 577) via a common protocol. Carers completed: (1) a 17-item version of the Carers of Older People in Europe (COPE) Index, an assessment of carers' perceptions of their role : (2) a questionnaire on demographic and caregiving circumstances : and (3) three instruments included for the criterion validation of the COPE Index (the General Health Questionnaire, the Hospital Anxiety and Depression Scale, and the World Health Organization Quality of Life-BREF). Principal Component Analysis of the COPE Index was followed by internal consistency analysis of emergent components. Scales derived by summing items loading on the components were analyzed for their association with the criterion measures. Two components, negative impact and positive value, emerged consistently across countries. A third component, quality of support was less consistent across countries. Scales derived from the negative impact and positive value components were internally consistent and significantly associated with the criterion validity measures. These two scales and four items drawn from the quality of support component were retained in the final COPE Index. While further testing is required, the COPE Index has current utility in increasing understanding of the role perceptions of carers of older people.


New pharmacotherapy for stroke prevention in atrial fibrillation: update 2010.
Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice and is associated with substantial morbidity and mortality. Its prevalence increases with age, affecting about 1% of patients aged <60 years and almost 10% of patients >80 years. AF is associated with a fivefold increasing risk of embolism or stroke with absolute risk ranging from less than 1% to 20% per year, depending on patient age and the presence of clinical risk factors including congestive heart failure, systemic hypertension, diabetes mellitus and prior history of cardioembolic events. Vitamin K antagonists (VKAs) and acetyl salicylic acid are currently the only licensed antithrombotic therapies for stroke prevention in patients with AF. Anticoagulants are very effective for stroke prevention in patients with AF, overall a 64% relative risk reduction. Nonetheless, approximately 50% of patients with AF who have an indication for VKA receive anticoagulant therapy, of which only 50% maintain adequate therapeutic ranges. Furthermore, 50% will discontinue VKAs within 3 to 5 years regardless of appropriate international normalized ratio control. Underutilization of VKAs is related, in part, to their numerous limitations and difficulty in maintaining adequate therapeutic control, prompting the development of new antithrombotic strategies that are equally effective and safer, and easier to manage than VKAs. This review focuses on new antithrombotic therapies for stroke prevention in patients with AF.


Steroidogenic and pressor activity of angiotensin analogues in the rat.
1. A classical 6 point assay in vitro for measuring aldosterone stimulating activity has been developed. 2. The steroidogenic potency of Ile5-angiotensin II was 62% of that given by Val5-angiotensin II. Ile5-angiotensin III (Des-Asp1-Ile5-angiotensin II) was likewise 50% as active as Val5-angiotensin III (Des-Asp1-Val5-angiotensin II). Similar results were obtained in the pressor and myotropic assays. 3. Ile5-angiotensin III and Val5-angiotensin III had only 7% and 16% respectively of the steroidogenic activity of Val5-angiotensin II. 4. Sar1-Ile5-angiotensin II was 2.3 times as potent as Val5-angiotensin II in aldosterone-stimulating activity. The corresponding activities of Me2-Gly1-angiotensin II, Pro1-angiotensin II and Pro31-angiotensin II were 71%, 15% and 3% of Val5-angiotensin II respectively.


Employer health insurance offerings and employee enrollment decisions.
To determine how the characteristics of the health benefits offered by employers affect worker insurance coverage decisions. The 1996-1997 and the 1998-1999 rounds of the nationally representative Community Tracking Study Household Survey. We use multinomial logistic regression to analyze the choice between own-employer coverage, alternative source coverage, and no coverage among employees offered health insurance by their employer. The key explanatory variables are the types of health plans offered and the net premium offered. The models include controls for personal, health plan, and job characteristics. When an employer offers only a health maintenance organization married employees are more likely to decline coverage from their employer and take-up another offer (odds ratio (OR)=1.27, p<.001), while singles are more likely to accept the coverage offered by their employer and less likely to be uninsured (OR=0.650, p<.001). Higher net premiums increase the odds of declining the coverage offered by an employer and remaining uninsured for both married (OR=1.023, p<.01) and single (OR=1.035, p<.001) workers. The type of health plan coverage an employer offers affects whether its employees take-up insurance, but has a smaller effect on overall coverage rates for workers and their families because of the availability of alternative sources of coverage. Relative to offering only a non-HMO plan, employers offering only an HMO may reduce take-up among those with alternative sources of coverage, but increase take-up among those who would otherwise go uninsured. By modeling the possibility of take-up through the health insurance offers from the employer of the spouse, the decline in coverage rates from higher net premiums is less than previous estimates.


Recurrence of mesothelioma after a macroscopic complete resection procedure: is a second radical surgery justified?
A best evidence topic was written according to a structured protocol. The question addressed was: In patients with mesothelioma who develop a local recurrence after macroscopic complete resection (MCR) surgery, does performing a second radical surgery lead to improvement in survival? A total of 2076 papers were identified using the reported search, of which 3 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. The 2 largest studies included 16 patients each who underwent a second surgery for radical resection of recurrence after MCR for mesothelioma. One study (with 16 chest wall resections) had no in-hospital mortality, whereas the other study showed 2/16 (12.5%) patients dying in the hospital, both of whom had a contralateral pleurectomy. One study correlated the median survival after the second surgery with the time to recurrence and epithelioid pathology. The other study showed better post-recurrence survival after a second surgery, with patients having a significantly longer median post-recurrence survival (16 months) compared with those who received other types of second-line therapy (9 months) and those who received no therapy at all (2 months) (P < 0.0005), although selection bias is a possibility. The last study included 8 patients who underwent a second surgery for radical intent after MCR for mesothelioma. The median time to recurrence was 29 months and the survival after second surgery was 14.5 months with no correlation to disease-free interval (expected due to the small number of patients). In patients presenting with recurrence of mesothelioma after an MCR procedure, radical surgery to resect the recurrent tumour could have a role in improvement of survival in selected patients. Positive prognostic factors include epithelioid pathology and a longer disease-free interval after the first procedure.


Family members' experiences of personal assistance given to a relative with disabilities.
Personal assistance is a type of home care common to many countries even though entitlement and legislative framework may vary from country to country. At present, there exists no knowledge about the family members' experiences of such assistance; therefore, the aim of this study was to investigate family members' experiences of personal assistance given to a relative of working age with a functional disability. Twenty-five family members who had a relative with a severe neurological disease in Sweden were interviewed about the significance of personal assistance, and the qualitative interviews were subjected to qualitative latent content analysis. The overall findings verify the close connection between the family members' experiences and their perception of the quality of the caring relationship between the personal assistant and the person with disability. The main finding was an appreciation of the personal assistance on the part of the family members. However, in situations where the encounter between the assistant and the relative with disability was perceived negatively, the family members experienced great anxiety. The shortcomings were the inability to maintain a private life with assistance and the limitation of choice because of the shortage of personal assistants. Beyond these general findings, this study found that personal assistance was experienced by the family members in terms of dignity and empowering care. This theme was generated from seven subthemes: Insight into private life, Security through the close relation, Social life through freedom of movement, Influence over the organisation of assistance, Self-determination and understanding, Friendship and mutual respect and Adaption to the dependency on assistance. The findings indicate that responsible officials, work leaders and assistants need constantly to improve the implementation of the law. In such efforts, the experiences of family members described in this study are a source of knowledge.


Cascade Radical Cyclization of N-Propargylindoles: Substituents Dictate Stereoselective Formation of N-Fused Indolines versus Indoles.
An efficient protocol for the synthesis of pyrrolo[1,2-a]indole derivatives having sulfide functionality using cascade radical cyclization on propargylindole is described. The nature of the substituents at the propargylic carbon bearing nitrogen of the indole has a profound effect on the rate, yield, and nature of the product obtained by the cascade radical cyclization. An expeditious one-pot route for cascade radical cyclization-desulfurization is also presented. Products obtained were elaborated to the core of the putative structure of the yuremamine and indoline derivative with five contiguous stereocenters.


Diet quality and genetic association with body mass index: results from 3 observational studies.
It is unknown whether dietary quality modifies genetic association with body mass index (BMI). This study examined whether dietary quality modifies genetic association with BMI. We calculated 3 diet quality scores including the Alternative Healthy Eating Index 2010 (AHEI-2010), the Alternative Mediterranean Diet score (AMED), and the Dietary Approach to Stop Hypertension (DASH) diet score. We examined the interactions of a genetic risk score (GRS) based on 97 BMI-associated variants with the 3 diet quality scores on BMI in 30,904 participants from 3 large cohorts. We found significant interactions between total GRS and all 3 diet scores on BMI assessed after 2-3 y, with an attenuated genetic effect observed in individuals with healthier diets (AHEI: P-interaction = 0.003; AMED: P = 0.001; DASH: P = 0.004). For example, the difference in BMI (kg/m2) per 10-unit increment of the GRS was smaller among participants in the highest tertile of AHEI score compared with those in the lowest tertile (0.84; 95% CI: 0.72, 0.96 compared with 1.14; 95% CI: 0.99, 1.29). Results were consistent across the 3 cohorts with no significant heterogeneity. The interactions with diet scores on BMI appeared more significant for central nervous system GRSs (P < 0.01 for 3 diet scores) than for non-central nervous system GRSs (P > 0.05 for 3 diet scores). A higher diet quality attenuated genetic predisposition to obesity. These findings underscore the importance of maintaining a healthful diet for the prevention of obesity, particularly for those individuals with a strong genetic predisposition to obesity. This trial was registered with the Clinical Trial Registry as NCT03577639.


Primary osteosarcoma of the breast: case report.
Mammary sarcomas are very uncommon and make up less than 1% of all primary breast malignancies.Primary osteosarcoma of the breast is extremely rare and represents 12.5% of mammary sarcomas. A secondary lesion from a primary osteosarcoma of the bone should be considered in the differential diagnosis. In addition, the absence of a direct connection between the tumour and the underlying skeleton is mandatory for the diagnosis.We report a case of primary osteosarcoma of the breast occurring in young patient with fatal evolution.


Contribution of platelet-derived CD40 ligand to inflammation, thrombosis and neoangiogenesis.
CD40-CD40L interactions have been involved in inflammation and thrombosis. Several diseases are characterized by inflammation, hypercoagulability and increased prevalence of thromboembolic events. In the past decade, a series of preclinical and clinical studies has provided more insight into the pathogenetic mechanisms linking inflammatory mediators to the activation and regulation of the haemostatic system. In particular, the study of CD40-CD40L interactions has greatly contributed to understanding the role of platelets in a variety of pathophysiological conditions, including atherothrombosis, immuno-inflammatory diseases and, possibly, cancer. A wide variety of preclinical and clinical studies have generated clinical interest in the use of CD40L as a prognostic marker of thrombotic risk. However, the use of sCD40L in clinical studies requires reliable methods. For the correct interpretation of results, clinical and research laboratories and physicians must be aware of the limitations of immunoassays for this cytokine, which underlines the need for standardization of preanalytic conditions. This review will focus on biochemical evidence of CD40L involvement in platelet activation, contribution of platelet-derived CD40L to inflammation, thrombosis and neoangiogenesis, and possible methodological pitfalls regarding the appropriate specimen and preparation for laboratory evaluation of blood soluble CD40L as a biomarker in various human diseases characterized by underlying inflammation, such as atherothrombosis, cancer and immuno-inflammatory diseases.


Morphological Observation on Critical-Sized Cranial Defect Repaired by Icariin and Autologous Concentrate Growth Factors in Rabbits.
BACKGROUND Morphological changes repaired by icariin and autologous concentrate growth factors (ACGF) in critical-sized cranial defect were observed and their promoting effects were investigated. MATERIAL AND METHODS Seventy-two New Zealand white rabbits weighing 1.8~2.0kg were used to build a critical-sized cranial defect model and were randomly divided into 3 groups. X-ray, HE staining, general and histological observation, and immunohistochemistry were used to describe the changes caused by normal saline, icariin, and ACGF. RESULTS Cranial defects were covered with newly formed bone tissue at the 12th week in icariin and ACGF groups, with red color, hard surface, and no obvious boundary. Densities were the same in 2 groups at 4 timepoints. HE staining showed defects filled with a large amount of fibrous connective tissue, thick collagen fibers, and abundant osteoclasts. No new bone matrix appeared in any of the 3 groups. Trabecular area, trabeculae width, and osteoblast number in 2 groups were more than that of the control group, and osteoclast number was lower. However, osteoclast number among the 3 groups at the 12th week had no significant difference, which was the same with 4 indicators between the icariin and ACGF groups. From the 4th to 12th week, regenerated cartilage was formed and showed positive reaction with BMP-2 and TGFβ1 from primary bone, which also was demonstrated by granulation tissue and uniform dyeing. CONCLUSIONS ACGF and icariin both can increase new bone quantity and improve bone quality, which can also promote healing. The effects and mechanisms of icariin and ACGF on the expression of gene are not exactly the same.


Structural insight into Ca2+ specificity in tetrameric cation channels.
Apparent blockage of monovalent cation currents by the permeating blocker Ca(2+) is a physiologically essential phenomenon relevant to cyclic nucleotide-gated (CNG) channels. The recently determined crystal structure of a bacterial homolog of CNG channel pores, the NaK channel, revealed a Ca(2+) binding site at the extracellular entrance to the selectivity filter. This site is not formed by the side-chain carboxylate groups from the conserved acidic residue, Asp-66 in NaK, conventionally thought to directly chelate Ca(2+) in CNG channels, but rather by the backbone carbonyl groups of residue Gly-67. Here we present a detailed structural analysis of the NaK channel with a focus on Ca(2+) permeability and blockage. Our results confirm that the Asp-66 residue, although not involved in direct chelation of Ca(2+), plays an essential role in external Ca(2+) binding. Furthermore, we give evidence for the presence of a second Ca(2+) binding site within the NaK selectivity filter where monovalent cations also bind, providing a structural basis for Ca(2+) permeation through the NaK pore. Compared with other Ca(2+)-binding proteins, both sites in NaK present a novel mode of Ca(2+) chelation, using only backbone carbonyl oxygen atoms from residues in the selectivity filter. The external site is under indirect control by an acidic residue (Asp-66), making it Ca(2+)-specific. These findings give us a glimpse of the possible underlying mechanisms allowing Ca(2+) to act both as a permeating ion and blocker of CNG channels and raise the possibility of a similar chemistry governing Ca(2+) chelation in Ca(2+) channels.


Reliability of a Malay-translated questionnaire for use in a hand-arm vibration syndrome study in Malaysia.
Validity and reliability of the information relating to hand-transmitted vibration exposure and vibration-related health outcome are very important for case finding in hand-arm vibration syndrome (HAVS) studies. In a local HAVS study among a group of construction workers in Kuala Lumpur, Malaysia, a questionnaire translated into Malay was created based on the Hand-transmitted Vibration Health Surveillance--Initial Questionnaire and Clinical Assessment, from Vibration Injury Network. This study was conducted to determine the reliability of standardised questions in the questionnaire used in the study. 15 subjects were selected randomly from the sampling frame of the HAVS study. Test-retest reliability was conducted on all items contained in parts 1-6 of the questionnaire and clinical assessment form, with an interval of 13-14 days between the first and second administration. Kappa coefficient and percentage agreement were calculated for all standardised questions. The kappa coefficient and percentage agreement for all standardised questions varied from -0.174 to 1.000 and 66.7 to 100.0 percent, respectively. The kappa coefficient for important questions related to current vibratory tool usage, tingling, numbness and hand grip weakness were 0.714, 0.432, -0.077 and -0.120, respectively, while the percentage agreement for current vibratory tool usage, finger colour change, tingling, numbness and hand grip weakness were 85.7 percent, 92.8 percent, 79.5 percent, 85.7 percent and 71.4 percent, respectively. Intra-rater reliability on the extent of vibration exposure was good, with the intra-class correlation coefficient (95 percent confidence interval) ranging from 0.786 (0.334-0.931) to 0.975 (0.923-0.992). Critical questions on vascular, neurological and musculoskeletal symptoms of HAVS were found to be reliable. The history on the extent of vibration exposure revealed good reliability when explored by the investigator alone. This questionnaire is considered reliable to be used in the study of HAVS among construction workers working in a construction site.


Music-based cognitive remediation therapy for patients with traumatic brain injury.
Traumatic brain injury (TBI) is one of the common causes of disability in physical, psychological, and social domains of functioning leading to poor quality of life. TBI leads to impairment in sensory, motor, language, and emotional processing, and also in cognitive functions such as attention, information processing, executive functions, and memory. Cognitive impairment plays a central role in functional recovery in TBI. Innovative methods such as music therapy to alleviate cognitive impairments have been investigated recently. The role of music in cognitive rehabilitation is evolving, based on newer findings emerging from the fields of neuromusicology and music cognition. Research findings from these fields have contributed significantly to our understanding of music perception and cognition, and its neural underpinnings. From a neuroscientific perspective, indulging in music is considered as one of the best cognitive exercises. With "plasticity" as its veritable nature, brain engages in producing music indulging an array of cognitive functions and the product, the music, in turn permits restoration and alters brain functions. With scientific findings as its basis, "neurologic music therapy" (NMT) has been developed as a systematic treatment method to improve sensorimotor, language, and cognitive domains of functioning via music. A preliminary study examining the effect of NMT in cognitive rehabilitation has reported promising results in improving executive functions along with improvement in emotional adjustment and decreasing depression and anxiety following TBI. The potential usage of music-based cognitive rehabilitation therapy in various clinical conditions including TBI is yet to be fully explored. There is a need for systematic research studies to bridge the gap between increasing theoretical understanding of usage of music in cognitive rehabilitation and application of the same in a heterogeneous condition such as TBI.


A Liberal Account of Addiction.
Philosophers and psychologists have been attracted to two differing accounts of addictive motivation. In this paper, we investigate these two accounts and challenge their mutual claim that addictions compromise a person's self-control. First, we identify some incompatibilities between this claim of reduced self-control and the available evidence from various disciplines. A critical assessment of the evidence weakens the empirical argument for reduced autonomy. Second, we identify sources of unwarranted normative bias in the popular theories of addiction that introduce systematic errors in interpreting the evidence. By eliminating these errors, we are able to generate a minimal, but correct account, of addiction that presumes addicts to be autonomous in their addictive behavior, absent further evidence to the contrary. Finally, we explore some of the implications of this minimal, correct view.


Personal health technology: A new era in cardiovascular disease prevention.
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide yet the majority of related risk factors are largely preventable (primary prevention [PP]) and effectively treatable (secondary prevention [SP]) with healthy lifestyle behaviors. The use of information and communication technology (ICT) offers a unique approach to personal health and CVD prevention, as these mediums are relatively affordable, approachable, and accessible. The purpose of this review is to provide an overview of ICT-driven personal health technologies and their potential role in promoting and supporting self-care behaviors for PP and SP of CVD. In this review, we focus on technological interventions that have been successful at supporting positive behavior change in order to determine which tools, resources, and methods are most appropriate for delivering interventions geared towards CVD prevention. We conducted a literature search from a range of sources including scholarly, peer-reviewed journal articles indexed in PubMed and CINAHL, gray literature, and reputable websites and other Internet-based media. A synthesis of existing literature indicates that the overall efficacy of ICT-driven personal health technologies is largely determined by: 1) the educational resources provided and the extent to which the relayed information is customized or individually tailored; and 2) the degree of self-monitoring and levels of personalized feedback or other interactions (e.g. interpersonal communications). We conclude that virtually all the technological tools and resources identified (e.g. Internet-based communications including websites, weblogs and wikis, mobile devices and applications, social media, and wearable monitors) can be strategically leveraged to enhance self-care behaviors for CVD risk reduction and SP but further research is needed to evaluate their efficacy, cost-effectiveness, and long-term maintainability.


Dynamics and stability of running on rough terrains.
Stability of running on rough terrain depends on the propagation of perturbations due to the ground. We consider stability within the sagittal plane and model the dynamics of running as a two-dimensional body with alternating aerial and stance phases. Stance is modelled as a passive, impulsive collision followed by an active, impulsive push-off that compensates for collisional losses. Such a runner has infinitely many strategies to maintain periodic gaits on flat ground. However, these strategies differ in how perturbations due to terrain unevenness are propagated. Instabilities manifest as tumbling (orientational instability) or failing to maintain a steady speed (translational instability). We find that open-loop strategies that avoid sensory feedback are sufficient to maintain stability on step-like terrains with piecewise flat surfaces that randomly vary in height. However, these open-loop runners lose orientational stability on rough terrains whose slope also varies randomly. The orientational instability is significantly mitigated by minimizing the tangential collision, which typically requires sensory information and anticipatory strategies such as leg retraction. By analysing the propagation of perturbations, we derive a single dimensionless parameter that governs stability. This parameter provides guidelines for the design and control of both biological and robotic runners.


Aortic Valve Replacement with a Conventional Stented Bioprosthesis versus Sutureless Bioprosthesis: a Study of 763 Patients.
The aim of this retrospective study was to compare early postoperative outcomes after aortic valve replacement (AVR) with sutureless bioprostheses and conventional stented bioprostheses implanted through median sternotomy. From January 2011 to December 2016, 763 patients underwent aortic valve replacement with bioprostheses; of these, 139 received a Perceval S sutureless valve (Group A) and 624 received a Perimount Magna Ease valve (Group B). These groups were further divided into A1 (isolated Perceval AVR), A2 (Perceval AVR with coronary artery bypass grafting [CABG]), B1 (isolated conventional stented bioprosthesis), and B2 (conventional stented bioprosthesis + CABG). Patients in Group A were older (mean 74 years vs. 71 years; P<0.0001), predominantly women (53% vs. 32%; P<0.0001), had a higher logistic EuroSCORE (3.26 vs. 2.43; P<0.001), more preoperative atrial fibrillation (20% vs. 13%; P=0.03), and had a lower reopening rate for bleeding (2.1% vs. 6.7%; P=0.04). Compared to Group B1, Group A1 had shorter cross-clamp (mean 40 min vs. 57 min; P≤0.0001) and bypass times (mean 63 min vs. mean 80 min; P=0.02), and they bled less postoperatively (mean 295 ml vs. mean 393 ml; P=0.002). The mean gradient across Perceval valve was 12.5 mmHg while its effective orifice area was 1.5 cm2. In our retrospective study of 763 patients, sutureless valve group patients are older, mostly women, more symptomatic preoperatively, and have higher logistic EuroSCORE. They have shorter cross-clamp and bypass times, less postoperative bleeding, and reduced incidence of reopening. Further studies are needed to evaluate the clinical benefits in short, mid, and long-terms.


SAS-6 assembly templated by the lumen of cartwheel-less centrioles precedes centriole duplication.
Centrioles are 9-fold symmetric structures duplicating once per cell cycle. Duplication involves self-oligomerization of the centriolar protein SAS-6, but how the 9-fold symmetry is invariantly established remains unclear. Here, we found that SAS-6 assembly can be shaped by preexisting (or mother) centrioles. During S phase, SAS-6 molecules are first recruited to the proximal lumen of the mother centriole, adopting a cartwheel-like organization through interactions with the luminal wall, rather than via their self-oligomerization activity. The removal or release of luminal SAS-6 requires Plk4 and the cartwheel protein STIL. Abolishing either the recruitment or the removal of luminal SAS-6 hinders SAS-6 (or centriole) assembly at the outside wall of mother centrioles. After duplication, the lumen of engaged mother centrioles becomes inaccessible to SAS-6, correlating with a block for reduplication. These results lead to a proposed model that centrioles may duplicate via a template-based process to preserve their geometry and copy number.


Photodermatitis and photokeratoconjunctivitis in a ball python (Python regius) and a blue-tongue skink (Tiliqua spp.).
A male ball python (Python regius) and a female blue tongue skink (Tiliqua spp.) of unknown age were evaluated for anorexia, lethargy, excessive shedding, corneal opacity (python), and weight loss (skink) of approximately three weeks' duration. These animals represented the worst affected animals from a private herpetarium where many animals exhibited similar signs. At necropsy, the python had bilateral corneal opacity and scattered moderate dysecdysis. The skink had mild dysecdysis, poor body condition, moderate intestinal nematodiasis, and mild liver atrophy. Microscopic evaluation revealed epidermal erosion and ulceration, with severe epidermal basal cell degeneration and necrosis, and superficial dermatitis (python and skink). Severe bilateral ulcerative keratoconjunctivitis with bacterial colonization was noted in the ball python. Microscopic findings within the skin and eyes were suggestive of ultraviolet (UV) radiation damage or of photodermatitis and photokeratoconjunctivitis. Removal of the recently installed new lamps from the terrariums of the surviving reptiles resulted in resolution of clinical signs. Evaluation of a sample lamp of the type associated with these cases revealed an extremely high UV output, including very-short-wavelength UVB, neither found in natural sunlight nor emitted by several other UVB lamps unassociated with photokeratoconjunctivitis. Exposure to high-intensity and/or inappropriate wavelengths of UV radiation may be associated with significant morbidity, and even mortality, in reptiles. Veterinarians who are presented with reptiles with ocular and/or cutaneous disease of unapparent cause should fully evaluate the specifics of the vivarium light sources. Further research is needed to determine the characteristics of appropriate and of toxic UV light for reptiles kept in captivity.


A novel approach to the detection of synchronisation in EEG based on empirical mode decomposition.
Transient neural assemblies mediated by synchrony in particular frequency ranges are thought to underlie cognition. We propose a new approach to their detection, using empirical mode decomposition (EMD), a data-driven approach removing the need for arbitrary bandpass filter cut-offs. Phase locking is sought between modes. We explore the features of EMD, including making a quantitative assessment of its ability to preserve phase content of signals, and proceed to develop a statistical framework with which to assess synchrony episodes. Furthermore, we propose a new approach to ensure signal decomposition using EMD. We adapt the Hilbert spectrum to a time-frequency representation of phase locking and are able to locate synchrony successfully in time and frequency between synthetic signals reminiscent of EEG. We compare our approach, which we call EMD phase locking analysis (EMDPL) with existing methods and show it to offer improved time-frequency localisation of synchrony.


Paracetamol (acetaminophen) for acute treatment of episodic tension-type headache in adults.
Tension-type headache (TTH) affects about 1 person in 5 worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (two to 14 headaches per month), and chronic TTH (15 headache days a month or more). Paracetamol (acetaminophen) is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of paracetamol for the acute treatment of frequent episodic TTH in adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (CRSO), MEDLINE, EMBASE, and the Oxford Pain Relief Database to October 2015, and also reference lists of relevant published studies and reviews. We sought unpublished studies by asking personal contacts and searching online clinical trial registers and manufacturers' websites. We included randomised, double-blind, placebo-controlled studies (parallel-group or cross-over) using oral paracetamol for symptomatic relief of an acute episode of TTH. Studies had to be prospective, with participants aged 18 years or over, and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion and extracted data. We used the numbers of participants achieving each outcome to calculate the risk ratio (RR) and number needed to treat for one additional beneficial outcome (NNT) or one additional harmful outcome (NNH) for oral paracetamol compared to placebo or an active intervention for a range of outcomes, predominantly those recommended by the International Headache Society (IHS).We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created 'Summary of findings' tables. We included 23 studies, all of which enrolled adults with frequent episodic TTH. Twelve studies used the IHS diagnostic criteria or similar, six used the older classification of the Ad Hoc Committee, and five did not describe specific diagnostic criteria but generally excluded participants with migraines. Participants had moderate or severe pain at the start of treatment. While 8079 people with TTH participated in these studies, the numbers available for any analysis were lower than this because outcomes were inconsistently reported and because many participants received active comparators.None of the included studies were at low risk of bias across all domains considered, although for most studies and domains this was likely to be due to inadequate reporting rather than poor methods. We judged five studies to be at high risk of bias for incomplete outcome reporting, and seven due to small size.For the IHS preferred outcome of being pain free at two hours the NNT for paracetamol 1000 mg compared with placebo was 22 (95% confidence interval (CI) 15 to 40) in eight studies (5890 participants; high quality evidence), with no significant difference from placebo at one hour. The NNT was 10 (7.9 to 14) for pain-free or mild pain at two hours in five studies (5238 participants; high quality evidence). The use of rescue medication was lower with paracetamol 1000 mg than with placebo, with an NNTp to prevent an event of 7.8 (6.0 to 11) in six studies (1856 participants; moderate quality evidence). On limited data, the efficacy of paracetamol 500 mg to 650 mg was not superior to placebo, and paracetamol 1000 mg was not different from either ketoprofen 25 mg or ibuprofen 400 mg (low quality evidence).Adverse events were not different between paracetamol 1000 mg and placebo (RR 1.1 (0.94 to 1.3); 5605 participants; 11 studies; high quality evidence). Studies reported no serious adverse events.The quality of the evidence using GRADE comparing paracetamol 1000 mg with placebo was moderate to high. Where evidence was downgraded it was because a minority of studies reported the outcome. For comparisons of paracetamol 500 mg to 650 mg with placebo, and of paracetamol 1000 mg with active comparators, we downgraded the evidence to low quality or very low quality because of the small number of studies and events. Paracetamol 1000 mg provided a small benefit in terms of being pain free at two hours for people with frequent episodic TTH who have an acute headache of moderate or severe intensity.


Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam, Cefepime, or Meropenem.
Critically ill patients are frequently treated with empirical antibiotic therapy, including vancomycin and β-lactams. Recent evidence suggests an increased risk of acute kidney injury (AKI) in patients who received a combination of vancomycin and piperacillin-tazobactam (VPT) compared with patients who received vancomycin alone or vancomycin in combination with cefepime (VC) or meropenem (VM), but most studies were conducted predominately in the non-critically ill population. A retrospective cohort study that included 2,492 patients was conducted in the intensive care units of a large university hospital with the primary outcome being the development of any AKI. The rates of any AKI, as defined by the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, were 39.3% for VPT patients, 24.2% for VC patients, and 23.5% for VM patients (P < 0.0001 for both comparisons). Similarly, the incidences of stage 2 and stage 3 AKI were also significantly higher for VPT patients than for the patients in the other groups. The rates of stage 2 and stage 3 AKI, respectively, were 15% and 6.6% for VPT patients, 5.8% and 1.8% for VC patients, and 6.6% and 1.3% for VM patients (P < 0.0001 for both comparisons). In multivariate analysis, the use of vancomycin in combination with piperacillin-tazobactam was found to be an independent predictor of AKI (odds ratio [OR], 2.161; 95% confidence interval [CI], 1.620 to 2.883). In conclusion, critically ill patients receiving the combination of VPT had the highest incidence of AKI compared to critically ill patients receiving either VC or VM.


Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.
The viruses HIV-1, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and hepatitis C virus (HCV) are characterized by the establishment of lifelong infection in the human host, where their replication is thought to be tightly controlled by virus-specific CD8+ T cells. Here we present detailed studies of the differentiation phenotype of these cells, which can be separated into three distinct subsets based on expression of the costimulatory receptors CD28 and CD27. Whereas CD8+ T cells specific for HIV, EBV and HCV exhibit similar characteristics during primary infection, there are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections. These findings challenge the current definitions of memory and effector subsets in humans, and suggest that ascribing effector and memory functions to subsets with different differentiation phenotypes is no longer appropriate.


Comparative genomics of 274 Vibrio cholerae genomes reveals mobile functions structuring three niche dimensions.
Vibrio cholerae is a globally dispersed pathogen that has evolved with humans for centuries, but also includes non-pathogenic environmental strains. Here, we identify the genomic variability underlying this remarkable persistence across the three major niche dimensions space, time, and habitat. Taking an innovative approach of genome-wide association applicable to microbial genomes (GWAS-M), we classify 274 complete V. cholerae genomes by niche, including 39 newly sequenced for this study with the Ion Torrent DNA-sequencing platform. Niche metadata were collected for each strain and analyzed together with comprehensive annotations of genetic and genomic attributes, including point mutations (single-nucleotide polymorphisms, SNPs), protein families, functions and prophages. Our analysis revealed that genomic variations, in particular mobile functions including phages, prophages, transposable elements, and plasmids underlie the metadata structuring in each of the three niche dimensions. This underscores the role of phages and mobile elements as the most rapidly evolving elements in bacterial genomes, creating local endemicity (space), leading to temporal divergence (time), and allowing the invasion of new habitats. Together, we take a data-driven approach for comparative functional genomics that exploits high-volume genome sequencing and annotation, in conjunction with novel statistical and machine learning analyses to identify connections between genotype and phenotype on a genome-wide scale.


Interleukin 1 alpha mediated inhibition of myogenic terminal differentiation: increased sensitivity of Ha-ras transformed cultures.
The commitment of myogenically determined cells to terminal differentiation can be modulated by a variety of agents, including growth factors and activated oncogenes. We have examined the effect of interleukin 1 alpha (IL-1 alpha) on the terminal differentiation of a normal myogenically determined cell line and two myogenically determined, differentiation competent cell lines which contain either one or six copies of the activated c-Ha-ras oncogene. Treatment of all cell lines with IL-1 alpha decreased but did not totally inhibit terminal myogenic differentiation. Over the range of IL-1 alpha concentrations assayed (1-40 ng/ml), the c-Ha-ras transformed cell lines demonstrated a significantly greater sensitivity to the inhibitory effects of IL-1 alpha. The inhibition of differentiation was not the result of enhanced proliferation. Interestingly, transformation with activated c-Ha-ras resulted in a decrease in IL-1 alpha receptor number and affinity. The enhanced IL-1 alpha responsiveness of the ras transformants was not the result of increased proliferation or changes in either ras gene expression or protein kinase C activity. IL-1 alpha treatment decreased the steady-state levels of both MyoD1 and myogenin transcripts in the c-Ha-ras transformed but not the normal myogenic cell line. Further studies are required to determine the mechanism(s) responsible for the increased sensitivity of the c-Ha-ras transformed cultures to the inhibitory effects of IL-1 alpha.


Waste Mismanagement in Developing Countries: A Review of Global Issues.
Environmental contamination due to solid waste mismanagement is a global issue. Open dumping and open burning are the main implemented waste treatment and final disposal systems, mainly visible in low-income countries. This paper reviews the main impacts due to waste mismanagement in developing countries, focusing on environmental contamination and social issues. The activity of the informal sector in developing cities was also reviewed, focusing on the main health risks due to waste scavenging. Results reported that the environmental impacts are pervasive worldwide: marine litter, air, soil and water contamination, and the direct interaction of waste pickers with hazardous waste are the most important issues. Many reviews were published in the scientific literature about specific waste streams, in order to quantify its effect on the environment. This narrative literature review assessed global issues due to different waste fractions showing how several sources of pollution are affecting the environment, population health, and sustainable development. The results and case studies presented can be of reference for scholars and stakeholders for quantifying the comprehensive impacts and for planning integrated solid waste collection and treatment systems, for improving sustainability at a global level.


Chronic intermittent hypoxia predisposes to liver injury.
Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). OSA is associated with nonalcoholic steatohepatitis (NASH) in obese subjects. The aim of this study was to investigate the effects of CIH on the liver in the absence of obesity. Lean C57BL/6J mice (n = 15) on a regular chow diet were exposed to CIH for 12 weeks and compared with pair-fed mice exposed to intermittent air (IA, n = 15). CIH caused liver injury with an increase in serum ALT (224 +/- 39 U/l versus 118 +/- 22 U/l in the IA group, P < 0.05), whereas AST and alkaline phosphatase were unchanged. CIH also induced hyperglycemia, a decrease in fasting serum insulin levels, and mild elevation of fasting serum total cholesterol and triglycerides (TG). Liver TG content was unchanged, whereas cholesterol content was decreased. Histology showed swelling of hepatocytes, no evidence of hepatic steatosis, and marked accumulation of glycogen in hepatocytes. CIH led to lipid peroxidation of liver tissue with a malondialdehyde (MDA)/free fatty acids (FFA) ratio of 0.54 +/- 0.07 mmol/mol versus 0.30 +/- 0.01 mmol/mol in control animals (P < 0.01), and increased levels of active nuclear factor kappaB (NF-kappaB) in the nuclear fraction of hepatocytes, suggesting that CIH induced oxidative stress in the liver. Finally, CIH greatly exacerbated acetaminophen-induced liver toxicity, causing fulminant hepatocellular injury. In the absence of obesity, CIH leads to mild liver injury via oxidative stress and excessive glycogen accumulation in hepatocytes and sensitizes the liver to a second insult, whereas NASH does not develop.


Implementation and evaluation of the VA DPP clinical demonstration: protocol for a multi-site non-randomized hybrid effectiveness-implementation type III trial.
The Diabetes Prevention Program (DPP) study showed that lifestyle intervention resulted in a 58% reduction in incidence of type 2 diabetes among individuals with prediabetes. Additional large randomized controlled trials have confirmed these results, and long-term follow-up has shown sustained benefit 10-20 years after the interventions ended. Diabetes is a common and costly disease, especially among Veterans, and despite strong evidence supporting the feasibility of type 2 diabetes prevention, the DPP has not been widely implemented. The first aim of this study will evaluate implementation of the Veterans Affairs (VA) DPP in three VA medical centers. The second aim will assess weight and hemoglobin A1c (A1c) outcomes, and the third aim will determine the cost-effectiveness and budget impact of implementation of the VA DPP from a health system perspective. This partnered multi-site non-randomized systematic assignment study will use a highly pragmatic hybrid effectiveness-implementation type III mixed methods study design. The implementation and administration of the VA DPP will be funded by clinical operations while the evaluation of the VA DPP will be funded by research grants. Seven hundred twenty eligible Veterans will be systematically assigned to the VA DPP clinical demonstration or the usual care VA MOVE!® weight management program. A multi-phase formative evaluation of the VA DPP implementation will be conducted. A theoretical program change model will be used to guide the implementation process and assess applicability and feasibility of the DPP for VA. The Consolidated Framework for Implementation Research (CFIR) will be used to guide qualitative data collection, analysis, and interpretation of barriers and facilitators to implementation. The RE-AIM framework will be used to assess Reach, Effectiveness, Adoption, Implementation, and Maintenance of the VA DPP. Twelve-month weight and A1c change will be evaluated for the VA DPP compared to the VA MOVE! Mediation analyses will be conducted to identify whether program design differences impact outcomes. Findings from this pragmatic evaluation will be highly applicable to practitioners who are tasked with implementing the DPP in clinical settings. In addition, findings will determine the effectiveness and cost-effectiveness of the VA DPP in the Veteran population.


Isolated sleep paralysis.
Sleep paralysis (SP) is a cardinal symptom of narcolepsy. However, little is available in the literature about isolated sleep paralysis. This report discusses the case of a patient with isolated sleep paralysis who progressed from mild to severe SP over 8 years. He also restarted drinking alcohol to be able to fall asleep and allay his anxiety symptoms. The patient was taught relaxation techniques and he showed complete remission of the symptoms of SP on follow up after 8 months.


Suppression of androgen receptor-mediated transactivation and cell growth by the glycogen synthase kinase 3 beta in prostate cells.
Androgens play important roles in the growth of normal prostate and prostate cancer via binding to the androgen receptor (AR). In addition to androgens, AR activity can also be modulated by selective growth factors and/or kinases. Here we report a new kinase signaling pathway by showing that AR transactivation was repressed by wild type glycogen synthase kinase 3beta (GSK3 beta) or constitutively active S9A-GSK3 beta in a dose-dependent manner. In contrast, the catalytically inactive kinase mutant GSK3 beta showed little effect on the AR transactivation. The suppression of AR transactivation by GSK3 beta was abolished by the GSK3 beta inhibitor lithium chloride. The in vitro kinase assay showed that GSK3 beta prefers to phosphorylate the amino terminus of AR that may lead to the suppression of activation function 1 activity located in the NH(2)-terminal region of AR. GSK3 beta interrupted the interaction between the NH(2) and COOH termini of AR, and overexpression of the constitutively active form of GSK3 beta, S9A-GSK3 beta, reduced the androgen-induced prostate cancer cell growth in stably transfected CWR22R cells. Together, our data demonstrated that GSK3 beta may function as a repressor to suppress AR-mediated transactivation and cell growth, which may provide a new strategy to modulate the AR-mediated prostate cancer growth.


2D FSI determination of mechanical stresses on aneurismal walls.
In this study, a fluid-structure interaction analysis based on the application of patient-specific mechanical parameters of the aneurismal walls was carried out to predict the rupture side during an abdominal aortic aneurysm (AAA). Realistic geometry of the aneurysm was reconstructed from CT data acquired from the patient, and patient-specific flow conditions were applied as boundary conditions. A newly developed non-invasive methodology for determining the mechanical parameters of the patient-specific aortic wall was employed to simulate realistic aortic wall behaviors. Analysis of the results included time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and von Mises stress (VMS). Results of the TAWSS, OSI, and VMS were compared to identify the most probable region of the AAA's rupture. High OSI, which identified the region of wall degradation, coincided with the location of maximum VMS, meaning that the anterior part of the aneurismal wall was a potential region of rupture.


A case of allergic bronchopulmonary aspergillosis successfully treated with mepolizumab.
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and pulmonary infiltrates. Oral corticosteroids and anti-fungal agents are standard therapy for ABPA, but long-term use of systemic corticosteroids often causes serious side effects. A 64-year-old woman was diagnosed with ABPA based on a history of bronchial asthma (from 40 years of age), elevated total IgE, the presence of serum precipitating antibodies and elevated specific IgE antibody to A. fumigatus, and pulmonary infiltration. Bronchoscopy showed eosinophilic mucoid impaction. Systemic corticosteroid therapy was initiated, and her symptoms disappeared. Peripheral eosinophilia and pulmonary infiltration recurred five months after cessation of corticosteroid treatment. Systemic corticosteroids were re-initiated and itraconazole was added as an anti-fungal agent. The patient was free of corticosteroids, aside from treatment with a short course of systemic corticosteroids for asthma exacerbation, and clinically stable with itraconazole and asthma treatments for 3 years. In 2017, she experienced significant deterioration. Laboratory examination revealed marked eosinophilia (3017/μL) and a chest computed tomography (CT) scan demonstrated pulmonary infiltration in the left upper lobe and mucoid impaction in both lower lobes. The patient was treated with high-dose inhaled corticosteroid/long-acting beta-agonist, a long-acting muscarinic antagonist, a leukotriene receptor antagonist, and theophylline; spirometry revealed a forced expiratory volume in 1 s (FEV1) of 1.01 L. An uncontrolled asthma state was indicated by an Asthma Control Test (ACT) score of 18. Mepolizumab, 100 mg every 4 weeks, was initiated for the treatment of severe bronchial asthma with ABPA exacerbation. Bronchial asthma symptoms dramatically improved, and ACT score increased to 24, by 4 weeks after mepolizumab treatment. Peripheral eosinophil count decreased to 174/μL. Spirometry revealed improvement of lung function (FEV1: 1.28 L). A chest CT scan demonstrated the disappearance of pulmonary infiltration and mucoid impaction. To our knowledge, this is the first case of ABPA to be treated with mepolizumab. Dramatic improvements were observed in symptoms, lung function, peripheral eosinophil counts, and chest images. Mepolizumab could serve as an alternative treatment with the potential to provide a systemic corticosteroid-sparing effect.


Alpha-lipoic acid inhibits lung cancer growth via mTOR-mediated autophagy inhibition.
Lung cancer is the leading cause of cancer-related death, and there remains a need for novel therapies for this malignancy. Here, we examined the effects of alpha-lipoic acid (LA), a drug used for treating human diabetic complications, on lung cancer growth. We report that LA limited lung cancer growth in xenograft mice and reduced lung cancer A549 cell viability. We observed autophagy activation in human lung cancers, and report that LA inactivated autophagy in A549 cells. In addition, LA activated mammalian target of rapamycin (mTOR)/p70S6K signaling. Inhibition of mTOR with rapamycin reversed LA-induced inactivation of autophagy and abolished LA-induced suppression of A549 cell viability. Altogether, the data suggest that LA exerts an anti-lung cancer effect through mTOR-mediated inhibition of autophagy, and thus LA may have therapeutic potential for lung cancer management.


Survey of the rural allied health workforce in New South Wales to inform recruitment and retention.
To investigate the demographics, employment, education and factors affecting recruitment and retention of New South Wales (NSW) rural allied health professionals. Descriptive study, cross-sectional survey. Regional, rural and remote areas of NSW, Australia. The sample includes 1879 respondents from more than 21 different allied health occupations. Variables included gender, age, marital status, employment sector, hours worked, community size, highest qualification, rural origin and continuing education, as well as others. Certain variables were compared for profession and gender. Women made up 70% of respondents, with a mean age of 42 years. Men were older, with more experience. Sixty per cent were of rural origin and 74% partnered, most with their partner also working. Eighty-four per cent worked in centres of 10,000 or more people. The public sector accounted for 46% of positions and the private sector 40%. Eleven per cent worked across multiple sectors and 18% were self-employed. Two-thirds worked 35 hours or more per week, although only 49% were employed full-time. Job satisfaction was high but 56% intended leaving within 10 years, 28% to retire. Over 90% of respondents qualified in Australia and more than 80% held a degree or higher qualification. Almost half were dissatisfied with access to continuing education. The NSW rural allied health workforce is strongly feminised, mature and experienced. Recruitment should target rural high school students and promote positive aspects of rural practice, such as diversity and autonomy. Retention strategies should include flexible employment options and career development opportunities.


The TOPGAME-study: effectiveness of extracorporeal shockwave therapy in jumping athletes with patellar tendinopathy. Design of a randomised controlled trial.
Patellar tendinopathy is a major problem for many athletes, especially those involved in jumping activities. Despite its frequency and negative impact on athletic careers, no evidence-based guidelines for management of this overuse injury exist. Since functional outcomes of conservative and surgical treatments remain suboptimal, new diagnostic and therapeutic strategies have to be developed and evaluated. Extracorporeal shockwave therapy (ESWT) appears to be a promising treatment in patients with chronic patellar tendinopathy. ESWT is most often applied after the known conservative treatments have failed. However, its effectiveness as primary therapy has not been studied in athletes who keep playing sports despite having patellar tendon pain. The aim of this study is to determine the effectiveness of ESWT in athletes with patellar tendinopathy who are still in training and competition. The TOPGAME-study (Tendinopathy of Patella Groningen Amsterdam Maastricht ESWT) is a multicentre two-armed randomised controlled trial with blinded participants and outcome assessors, in which the effectiveness of patient-guided focussed ESWT treatment (compared to placebo ESWT) on pain reduction and recovery of function in athletes with patellar tendinopathy will be investigated. Participants are volleyball, handball and basketball players with symptoms of patellar tendinopathy for a minimum of 3 to a maximum duration of 12 months who are still able to train and compete. The intervention group receives three patient-guided focussed medium-energy density ESWT treatments without local anaesthesia at a weekly interval in the first half of the competition. The control group receives placebo treatment. The follow-up measurements take place 1, 12 and 22 weeks after the final ESWT or placebo treatment, when athletes are still in competition. Primary outcome measure is the VISA-P (Victorian Institute of Sport Assessment - patella) score. Data with regard to pain during function tests (jump tests and single-leg decline squat) and ultrasound characteristics are also collected. During the follow-up period participants also register pain, symptoms, sports participation, side effects of treatment and additional medical consumption in an internet-based diary. The TOPGAME-study is the first RCT to study the effectiveness of patient-guided ESWT in athletes with patellar tendinopathy who are still in training and competition. Trial registration number NTR1408.


Risk Behaviors in Teens with Chronic Kidney Disease: A Study from the Midwest Pediatric Nephrology Consortium.
There is a paucity of information about risk behaviors in adolescents with chronic kidney disease (CKD). We designed this study to assess the prevalence of risk behaviors among teens with CKD in the United States and to investigate any associations between risk behavior and patient or disease characteristics. After informed consent, adolescents with CKD completed an anonymous, confidential, electronic web-based questionnaire to measure risk behaviors within five domains: sex, teen driving, alcohol and tobacco consumption, illicit drug use, and depression-related risk behavior. The reference group was composed of age-, gender-, and race-matched US high school students. When compared with controls, teens with CKD showed significantly lower prevalence of risk behaviors, except for similar use of alcohol or illicit substances during sex (22.5% vs. 20.8%, p=0.71), feeling depressed for ≥2 weeks (24.3% vs. 29.1%, p=0.07), and suicide attempt resulting in injury needing medical attention (36.4% vs. 32.5%, p=0.78). Furthermore, the CKD group had low risk perception of cigarettes (28%), alcohol (34%), marijuana (50%), and illicit prescription drug (28%). Use of two or more substances was significantly associated with depression and suicidal attempts (p < 0.05) among teens with CKD. Teens with CKD showed significantly lower prevalence of risk behaviors than controls. Certain patient characteristics were associated with increased risk behaviors among the CKD group. These data are somewhat reassuring, but children with CKD still need routine assessment of and counselling about risk behaviors.


Biosynthesis of the ergot alkaloids.
The ergots are a structurally diverse group of alkaloids derived from tryptophan and dimethylallyl pyrophosphate (DMAPP) . The potent bioactivity of ergot alkaloids have resulted in their use in many applications throughout human history. In this highlight, we recap some of the history of the ergot alkaloids, along with a brief description of the classifications of the different ergot structures and producing organisms. Finally we describe what the advancements that have been made in understanding the biosynthetic pathways, both at the genomic and the biochemical levels. We note that several excellent review on the ergot alkaloids, including one by Wallwey and Li in Nat. Prod. Rep., have been published recently. We provide a brief overview of the ergot alkaloids, and highlight the advances in biosynthetic pathway elucidation that have been made since 2011 in Section 4.


[Effects of combined influence of ionizing radiation and light on the retina].
The continuous irradiation of rats with a light (3500 1x) for 48 hours led to destruction of 7.5 +/- 0.43% of neurosensoric cells (the control value was 0.2 +/- (0.02%). Longer photodamage caused progressing decrease in a population of the cells, narrowing followed by disappearance of corresponding layers of retina by the 30th day of the experiment. Preliminary exposure to X-rays with a dose of 5 Gy modified light damages of retina. The combination of two factors caused death of more than 30% of neurosensoric cells and redused the number of rows of nucleis of the external nuclear layer twice for the first 48 hours of illumination. After a longer influence of light a preliminary ionizing irradiation increased the number of destructively changed neurosensoric cells, reaching minimun of 41.7% by 30th day of the experiment. At the same time after a long combined irradiation less changes in row number quantity, numerical density of nucleus of the external nuclear layer and a population of neurosesoric cells in general was observed than after only one light exposure. Changes of choriocapillaries (thrombosis, obliteration, narrowing of a gap) which were more expressed at a combination of factors, led to infringement of blood circulation and played the important role in mechanisms of retina degeneration. Radial glia and neurons of internal layers of retina showed relative resistance to the investigated influences.


Long-term amelioration of acidity accelerates decomposition in headwater streams.
The secondary production of culturally acidified streams is low, with a few species of generalist detritivores dominating invertebrate assemblages, while decomposition processes are impaired. In a series of lowland headwater streams in southern England, we measured the rate of cellulolytic decomposition and compared it with values measured three decades ago, when anthropogenic acidification was at its peak. We hypothesized that, if acidity has indeed ameliorated, the rate of decomposition will have accelerated, thus potentially supporting greater secondary production and the longer food chains that have been observed in some well-studied recovering freshwater systems. We used cellulose Shirley test cloth as a standardized bioassay to measure the rate of cellulolytic decomposition, via loss in tensile strength, for 31 streams in the Ashdown Forest over 7 days in summer 2011 and 49 days in winter 2012. We compared this with data from an otherwise identical study conducted in 1978 and 1979. In a secondary study, we determined whether decomposition followed a linear or logarithmic decay and, as Shirley cloth is no longer available, we tested an alternative in the form of readily available calico. Overall mean pH had increased markedly over the 32 years between the studies (from 6.0 to 6.7). In both the previous and contemporary studies, the relationship between decomposition and pH was strongest in winter, when pH reaches a seasonal minimum. As in the late 1970s, there was no relationship in 2011/2012 between pH and decay rate in summer. As postulated, decomposition in winter was significantly faster in 2011/2012 than in 1978/1979, with an average increase in decay rate of 18.1%. Recovery from acidification, due to decreased acidifying emissions and deposition, has led to an increase in the rate of cellulolytic decomposition. This response in a critical ecosystem process offers a potential explanation of one aspect of the limited biological recovery that has been observed so far, an increase in larger bodied predators including fish, which in turn leads to an increase in the length of food chains.


Lipase and protease extraction from activated sludge.
In the process of wastewater treatment hydrolysis of polymeric substances is the first and rate-limiting step. A closer study of the enzymes catalysing these reactions is essential for a better understanding of the microbial activity in the wastewater treatment process. Therefore, development of gentle and efficient enzyme extraction methods from environmental samples is very important. In this study we present a method for the extraction of lipases and proteases from activated sludge using the non-ionic detergent Triton X-100, EDTA, and cation exchange resin (CER), alone or in combination for the extraction of lipases and proteases from activated sludge. The sludge was continuously stirred in the presence of either buffer alone or in the presence of detergent and/or chelating agents. In all cases, a marked reduction in floc size was observed upon continuous stirring. However, no lipase activity and negligible protease activity was extracted in the presence of buffer alone, indicating that enzyme extraction was not due to shear force alone. The highest lipase activity was extracted using 0.1% Triton X-100 above which the activity was gradually decreasing. For proteases, the highest activity was obtained in the presence of 0.5% Triton X-100 and no decrease in activity was observed. Differences observed in the extraction efficiency of the two enzymes indicate the need for optimisation of the extraction process for the different enzymes or the extracellular polymeric substances from activated sludge.


One step fabrication of novel Ag-CdS@EP floating photocatalyst for efficient degradation of organic pollutants under visible light illumination.
In this paper, we present the fabrication of an expanded-perlite (EP)-based floating photocatalyst comprising CdS and Ag nanoparticles. In the Ag-CdS/EP nanocomposite, Ag-CdS was introduced as the photocatalytically active components and EP was employed as a low cost and sustainable support to reduce the problem of easy aggregation and improve the floating behavior of the designed catalyst. The Ag-CdS/EP photocatalyst was characterized via transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-vis diffuse spectroscopy (UV-vis DRS), energy dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and photoluminescence (PL) and photoelectrochemical measurements. The XRD and HR-TEM results confirmed the formation of cubic crystalline silver nanoparticles anchored on the surface of EP-immobilized hexagonal cubic CdS. The significantly enhanced photocatalytic activities of the Ag-CdS/EP nanocomposite with varying Ag contents were investigated for the degradation of rhodamine B (RhB) and phenol under visible light irradiation, and it was found that the photocatalytic reaction proceeds via first order kinetics. Furthermore, the desirable cycling ability (5 runs) of the Ag-CdS/EP photocatalyst indicates its promising stability and reusability. The designed novel photocatalyst also conforms to the development of green chemistry since no organic solvents were required.