'Don't forget the children': a qualitative study when a parent is at end of life from cancer.
Preparation for end of life is one of the greatest challenges faced by parents with cancer who have dependent children (< 18 years old), with requirement for support from professionals. The aim of this study is to explore how parents can be best supported in relation to their children, when a parent is at end of life from cancer. This is an interpretive qualitative study, using 79 semi-structured interviews with parents at end of life (n3), bereaved parents (n21), health and social care professionals (HSCPs) (n32) and funeral directors (n23). Data were analysed thematically and triangulated. Parents are central to preparing their children for the death of a parent. Striving for everyday ordinariness, maximising social networks, maintaining hope and making preparations for the future are helpful for families when a parent is at end of life. Most HSCPs were unaware of the challenges faced by parents at end of life, and psychosocial support was often left outside the caring realm. As a result, funeral directors noted complexities faced by the families after the death. Results are discussed under four themes: (1) communication with the children as a process, (2) coping throughout the unfolding end of life experience, (3) tension and complexities at end of life and (4) preparing for the future. Parents should be reassured that by involving the children early in the end of life experience when the ill-parent is 'well enough' to parent enables them to be actively involved in supporting their child through one of the greatest life changing event. A number of recommendations are discussed for professionals.


On the substrate specificity of human CYP27A1: implications for bile acid and cholestanol formation.
The mitochondrial sterol 27-hydroxylase (CYP27A1) is required for degradation of the C27-sterol side chain in bile acid biosynthesis. CYP27A1 seems, however, to have roles beyond this, as illustrated by patients with a deficient sterol 27-hydroxylase due to mutations of the CYP27A1 gene [cerebrotendinous xanthomatosis (CTX)]. These subjects have symptoms ranging from accumulation of bile alcohols and cholestanol to accelerated atherosclerosis and progressive neurologic impairment. The present work describes a detailed investigation on the substrate specificity of recombinant human CYP27A1. In accordance with some previous work with rat liver mitochondria, the activity in general increased with the polarity of the substrate. An obvious example was the finding that cholesterol was 27-hydroxylated more efficiently than cholesterol oleate but less efficiently than cholesterol sulfate. The oxysterols 24S-hydroxycholesterol and 25-hydroxycholesterol were 27-hydroxylated less efficiently than cholesterol, possibly due to steric hindrance. Surprisingly, sterols with a 3-oxo-Delta4 structure were found to be hydroxylated at a much higher rate than the corresponding sterols with a 3beta-hydroxy-Delta5 structure. The rates of hydroxylation of the sterols were: 7alpha-hydroxy-4-cholesten-3-one>4-cholesten-3-one>7alpha-hydroxycholesterol>24-hydroxy-4-cholesten-3-one> cholesterol>25-hydroxy-4-cholesten-3-one>24-hydroxycholesterol>or=25-hydroxycholesterol. The possibility is discussed that the findings may have implications for oxysterol-mediated regulation of gene expression. The very high activity of CYP27A1 towards the cholestanol precursor 4-cholesten-3-one may be of importance in connection with the accumulation of cholestanol in patients with CTX.


Transport of gold nanoparticles through plasmodesmata and precipitation of gold ions in woody poplar.
Poplar plants (Populus deltoides × nigra, DN-34) were used as a model to explore vegetative uptake of commercially available gold nanoparticles (AuNPs) and their subsequent translocation and transport into plant cells. AuNPs were directly taken up and translocated from hydroponic solution to poplar roots, stems and leaves. Total gold concentrations in leaves of plants treated with 15, 25 and 50 nm AuNPs at exposure concentrations of 498±50.5, 247±94.5 and 263±157 ng/mL in solutions were: 0.023±0.006, 0.0218±0.004 and 0.005±0.0003 µg/g dry weight, respectively, which accounted for 0.05, 0.10 and 0.03%, respectively, of the total gold mass added. The presence of total gold in plant tissues was measured by inductively coupled plasma mass spectrometry, while AuNPs were observed by transmission electron microscopy in plant tissues. In solution, AuNPs were distinguished from Au(III) ions by membrane separation and centrifugation. AuNPs behaved conservatively inside the plants and were not dissolved into gold ions. On the other hand, Au(III) ions were taken up and reduced into AuNPs inside whole plants. AuNPs were observed in the cytoplasm and various organelles of root and leaf cells. A distinct change in color from yellow to pink was observed as Au(III) ions were reduced and precipitated in hydroponic solution. The accumulation of AuNPs in the plasmodesma of the phloem complex in root cells clearly suggests ease of transport between cells and translocation throughout the whole plant, inferring the potential for entry and transfer in food webs.


The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored.
An essential prerequisite for any systems-level understanding of cellular functions is to correctly uncover and annotate all functional interactions among proteins in the cell. Toward this goal, remarkable progress has been made in recent years, both in terms of experimental measurements and computational prediction techniques. However, public efforts to collect and present protein interaction information have struggled to keep up with the pace of interaction discovery, partly because protein-protein interaction information can be error-prone and require considerable effort to annotate. Here, we present an update on the online database resource Search Tool for the Retrieval of Interacting Genes (STRING); it provides uniquely comprehensive coverage and ease of access to both experimental as well as predicted interaction information. Interactions in STRING are provided with a confidence score, and accessory information such as protein domains and 3D structures is made available, all within a stable and consistent identifier space. New features in STRING include an interactive network viewer that can cluster networks on demand, updated on-screen previews of structural information including homology models, extensive data updates and strongly improved connectivity and integration with third-party resources. Version 9.0 of STRING covers more than 1100 completely sequenced organisms; the resource can be reached at http://string-db.org.


Animal care practices in experiments on biological rhythms and sleep: report of the Joint Task Force of the Society for Research on Biological Rhythms and the Sleep Research Society.
Many physiological and molecular processes are strongly rhythmic and profoundly influenced by sleep. The continuing effort of biological, medical, and veterinary science to understand the temporal organization of cellular, physiological, behavioral and cognitive function holds great promise for the improvement of the welfare of animals and human beings. As a result, attending veterinarians and IACUC are often charged with the responsibility of evaluating experiments on such rhythms or the effects of sleep (or its deprivation) in vertebrate animals. To produce interpretable data, animals used in such research must often be maintained in carefully controlled (often constant) conditions with minimal disruption. The lighting environment must be strictly controlled, frequent changes of cages and bedding are undesirable, and daily visual checks are often not possible. Thus deviations from the standard housing procedures specified in the Guide for the Care and Use of Laboratory Animals are often necessary. This report reviews requirements for experiments on biological rhythms and sleep and discusses how scientific considerations can be reconciled with the recommendations of the Guide.


Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear Polarization-Enhanced NMR Spectroscopy.
Here, we show how dynamic nuclear polarization (DNP) NMR spectroscopy experiments permit the atomic level structural characterization of loaded and empty lipid nanoparticles (LNPs). The LNPs used here were synthesized by the microfluidic mixing technique and are composed of ionizable cationic lipid (DLin-MC3-DMA), a phospholipid (distearoylphosphatidylcholine, DSPC), cholesterol, and poly(ethylene glycol) (PEG) (dimyristoyl phosphatidyl ethanolamine (DMPE)-PEG 2000), as well as encapsulated cargoes that are either phosphorothioated siRNA (50 or 100%) or mRNA. We show that LNPs form physically stable complexes with bioactive drug siRNA for a period of 94 days. Relayed DNP experiments are performed to study 1H-1H spin diffusion and to determine the spatial location of the various components of the LNP by studying the average enhancement factors as a function of polarization time. We observe a striking feature of LNPs in the presence and in the absence of encapsulating siRNA or mRNA by comparing our experimental results to numerical spin-diffusion modeling. We observe that LNPs form a layered structure, and we detect that DSPC and DMPE-PEG 2000 lipids form a surface rich layer in the presence (or absence) of the cargoes and that the cholesterol and ionizable cationic lipid are embedded in the core. Furthermore, relayed DNP 31P solid-state NMR experiments allow the location of the cargo encapsulated in the LNPs to be determined. On the basis of the results, we propose a new structural model for the LNPs that features a homogeneous core with a tendency for layering of DSPC and DMPE-PEG at the surface.


Abrogation of TGF-beta signaling enhances chemokine production and correlates with prognosis in human breast cancer.
In human breast cancer, loss of carcinoma cell-specific response to TGF-beta signaling has been linked to poor patient prognosis. However, the mechanisms through which TGF-beta regulates these processes remain largely unknown. In an effort to address this issue, we have now identified gene expression signatures associated with the TGF-beta signaling pathway in human mammary carcinoma cells. The results strongly suggest that TGF-beta signaling mediates intrinsic, stromal-epithelial, and host-tumor interactions during breast cancer progression, at least in part, by regulating basal and oncostatin M-induced CXCL1, CXCL5, and CCL20 chemokine expression. To determine the clinical relevance of our results, we queried our TGF-beta-associated gene expression signatures in 4 human breast cancer data sets containing a total of 1,319 gene expression profiles and associated clinical outcome data. The signature representing complete abrogation of TGF-beta signaling correlated with reduced relapse-free survival in all patients; however, the strongest association was observed in patients with estrogen receptor-positive (ER-positive) tumors, specifically within the luminal A subtype. Together, the results suggest that assessment of TGF-beta signaling pathway status may further stratify the prognosis of ER-positive patients and provide novel therapeutic approaches in the management of breast cancer.


Clinical Application of Folate Receptor-Mediated Staining Solution Detection in Cervical Cancer Screening.
Cervical cancer is the fourth most deadly women's cancer worldwide, and regular screening is essential to lower mortality rates. The folate receptor-mediated staining solution detection (FRD) has been suggested to be a rapid and cost-effective screening method. We aim to evaluate the validity of FRD testing in cervical cancer screening. A total of 207 participants were enrolled in the study. The validity of screening by FRD, cytology screening, and a HPV test were compared using histopathology as the gold standard. Sensitivity, specificity, positive predictive value, negative predictive value, Kappa value, positive likelihood ratio, negative likelihood ratio, percent agreement, and positive detection rates were compared among the three screening methods. 83(40.1%) participants were diagnosed as NILM, 50(24.15%) were diagnosed as CIN1, and 74(35.74%) were diagnosed as CIN2+. For CIN2+, the detection rates for the FRD, cytology screening, and HPV were 75.68%, 82.09% and 93.22%, respectively. For CIN2+, the sensitivity of HPV testing (93.22%) was significantly higher than that of cytology screening (82.09%) and FRD (75.68%), while the specificity of FRD (63.91%) was higher than that of cytology screening (35.34%) and HPV test (7.56%). The percent agreement and Kappa value of FRD were significantly higher than those of the cytology screening and HPV test. In HPV-HC2+ and ASCUS patients, FRD was associated with a lower false positive rate compared to other screening methods. Our study indicates that FRD has a good sensitivity and high specificity in cervical cancer screening, and could be a rapid, valid and cost-effective screening test.


Added noise affects the neural correlates of upright and inverted faces differently.
In five experiments, we examine the neural correlates of the interaction between upright faces, inverted faces, and visual noise. In Experiment 1, we examine a component termed the N170 for upright and inverted faces presented with and without noise. Results show a smaller amplitude for inverted faces than upright faces when presented in noise, whereas the reverse is true without noise. In Experiment 2, we show that the amplitude reversal is robust for full faces but not eyes alone across all noise levels. In Experiment 3, we vary contrast to see if this reversal is a result of degrading a face. We observe no reversal effects. Thus, across conditions, adding noise to full faces is a sufficient condition for the N170 reversal. In Experiment 4, we delay the onsets of the faces presented in noise. We replicate the smaller N170 for inverted faces at no delay but observe partial recovery of the N170 for inverted faces at longer delays in static noise. Experiment 5 demonstrates the interaction in low contrast at a behavioral level. We propose a model in which noise interacts with the processing properties of inverted faces more so than upright faces.


Limited use of surgeon's advice on exercise for knee osteoarthritis.
The Good Life with osteoArthritis in Denmark (GLA:D) programme consists of patient education and supervised exercise therapy and adheres to clinical guidelines for knee osteoarthritis (OA). The purpose of this study was to present the treatment choice and clinical results of patients who were advised to participate in GLA:D before deciding on undergoing knee replacement. Patient records from all patients with knee OA consulting one orthopaedic surgeon in 2015 were reviewed to identify those who were advised to seek GLA:D. Radiologic OA was classified with Kellgren-Lawrence (KL) grade 0-4: none-severe. Results after three months were extracted from the GLA:D database, including a visual analogue scale (VAS) for knee pain 0-100: best-poorest. Out of 142 patients with primary referrals due to knee OA, 83 (58.5%) were advised to participate in GLA:D. They had a mean age of 65.0 years (standard deviation (SD): ± 10.7), 59 (71.1%) were female, 34 (44.8%) had a KL grade 3-4 and were either not eligible for surgery or awaiting surgical decision. Only 18 (22%) participated in GLA:D, out of whom 14 (16.9%) had available three-month data. They improved (mean (SD)) from 61.4 (± 18.6) to 42.7 (± 25.1) (p < 0.001) with respect to VAS pain after three months. Few patients followed the surgeon's advice on GLA:D participation, indicating that treatment with GLA:D is underutilised. The pain reduction found in GLA:D participants confirms that patient education and supervised exercise therapy are beneficial prior to deciding on knee replacement, or if surgery is not indicated. none. not relevant.


High physician concern about malpractice risk predicts more aggressive diagnostic testing in office-based practice.
Despite widespread agreement that physicians who practice defensive medicine drive up health care costs, the extent to which defensive medicine increases costs is unclear. The differences in findings to date stem in part from the use of two distinct approaches for assessing physicians' perceived malpractice risk. In this study we used an alternative strategy: We linked physicians' responses regarding their levels of malpractice concern as reported in the 2008 Health Tracking Physician Survey to Medicare Parts A and B claims for the patients they treated during the study period, 2007-09. We found that physicians who reported a high level of malpractice concern were most likely to engage in practices that would be considered defensive when diagnosing patients who visited their offices with new complaints of chest pain, headache, or lower back pain. No consistent relationship was seen, however, when state-level indicators of malpractice risk replaced self-rated concern. Reducing defensive medicine may require approaches focused on physicians' perceptions of legal risk and the underlying factors driving those perceptions.


The Utility of FDG-PET/CT in Clinically Suspected Paraneoplastic Neurological Syndrome: A Literature Review and Retrospective Case Series.
Paraneoplastic neurological syndrome (PNS) describes a spectrum of rare, heterogeneous neurological conditions associated with an underlying malignancy. Diagnosis of PNS is inherently difficult, with frequent misdiagnosis and delay. The literature suggests an underlying immune-mediated pathophysiology, and patients are usually tested for the presence of onconeural antibodies. With direct tumor therapy being the most effective method of stabilizing patients, there is a strong emphasis on detecting underlying tumors. The sensitivity of conventional CT imaging is often inadequate in such patients. While FDG-PET imaging has already been shown to be effective at detecting these tumors, FDG-PET/CT, combining both structural and functional imaging in a single study, is a more recent technique. To study the utility of FDG-PET/CT, we conducted a systematic literature review and a retrospective study. We identified 41 patients who underwent imaging for clinically suspected PNS at the regional PET-CT and neurosciences center based at the Royal Preston Hospital between 2007 and 2014 and compared the results to conventional investigations. Five patients had FDG-PET/CT tracer avidity suspicious of malignant disease, and four of these were subsequently diagnosed with cancer. Sensitivity and specificity were calculated to be 100 and 97.3%, respectively, with positive predictive value 80% and negative predictive value 100%. This compares to a sensitivity and specificity of 50 and 100%, respectively, for CT and 50 and 89%, respectively, for onconeural antibodies. These findings are in line with previous studies and support the diagnostic accuracy of FDG-PET/CT for the detection of underlying malignancy.


Barriers to nutritional care for the undernourished hospitalised elderly: perspectives of nurses.
To identify what nurses experience as barriers to ensuring adequate nutritional care for the undernourished hospitalized elderly. Undernutrition occurs frequently among the hospitalised elderly and can result in a variety of negative consequences if not treated. Nevertheless, undernutrition is often unrecognised and undertreated. Nurses have a great responsibility for nutritional care, as this is part of the patient's basic needs. Exploring nurses' experiences of preventing and treating undernourishment among older patients in hospitals is therefore highly relevant. A focus group study was employed based on a hermeneutic phenomenological methodological approach. Four focus group interviews with totally 16 nurses working in one large university hospital in Norway were conducted in spring 2012. The nurses were recruited from seven somatic wards, all with a high proportion of older (≥70 years) inpatients. The data were analysed in the three interpretative contexts: self-understanding, a critical common-sense understanding and a theoretical understanding. We identified five themes that reflect barriers the nurses experience in relation to ensuring adequate nutritional care for the undernourished elderly: loneliness in nutritional care, a need for competence in nutritional care, low flexibility in food service practices, system failure in nutritional care and nutritional care is being ignored. The results imply that nutritional care at the university hospital has its limits within the hospital structure and organisation, but also regarding the nurses' competence. Moreover, the barriers revealed that the undernourished elderly are not identified and treated properly as stipulated in the recommendations in the national guidelines on the prevention and treatment of undernutrition. The barriers revealed in this study are valuable when considering improvements to nutritional care practices on hospital wards to enable undernourished older inpatients to be identified and treated properly.


Histologic characteristics of pancreatic intraepithelial neoplasia associated with different pancreatic lesions.
Pancreatic intraepithelial neoplasia (PanIN) has been found in association with pancreatic ductal adenocarcinoma, intraductal papillary-mucinous neoplasm (IPMN), mucinous cystic neoplasm, and other pancreatic lesions, but the characteristics of PanINs associated with these lesions are not well characterized. In this study, 185 partial or total pancreatectomy specimens were collected, and 173 had complete slides for reviewed, which included 74 pancreatic ductal adenocarcinomas, 28 IPMNs, 7 mucinous cystic neoplasms, 44 other nonductal tumors, and 20 nontumorous lesions. Differences in grade, extent, and duct involvement among PanINs associated with different lesions were analyzed. Patients with PanINs were older than those without, regardless of associated tumor or lesions. No sex predilection was noted. PanINs were found in 89%, 96%, 86%, 64%, and 55% pancreata with ductal adenocarcinomas, IPMNs, mucinous cystic neoplasm, other nonductal tumors, and nontumorous lesions, respectively. PanIN 1 and 2 were commonly associated with all types of lesions, but high-grade PanIN 3 was more frequently associated with ductal adenocarcinomas. Ductal involvement of PanINs was more extensive in association with ductal adenocarcinomas than in any other types of pancreatic tumors or lesions. PanINs associated with pancreatic ductal adenocarcinomas affected both the main and branched ducts, whereas PanINs associated with other types of pancreatic tumors or lesions were mainly present in the branch ducts. No statistical differences were observed in distribution, extent, and grade of PanINs among IPMNs, mucinous cystic neoplasms, other nonductal tumors, and nontumorous lesions. Our study demonstrated a high concurrence between PanINs and other precancerous lesions and histologic features of PanINs associated with different pancreatic diseases.


Instruction Matters: Spelling of Vowels by Children in England and the US.
Letter names are stressed in informal and formal literacy instruction with young children in the US, whereas letters sounds are stressed in England. We examined the impact of these differences on English children of about 5 and 6 years of age (in reception year and Year 1, respectively) and US 6 year olds (in kindergarten). Children in both countries spelled short vowels, as in bag, more accurately than long vowels, as in gate. The superiority for short vowels was larger for children from England, consistent with the instructional emphasis on letter sounds. Errors such as gat for words with long vowels such as gate were more common among US children, reflecting these children's use of vowels' names as a guide to spelling. The English children's performance on a letter knowledge task was influenced by the fact that they are often taught letter sounds with reference to lowercase letters and letter names with reference to uppercase letters, and their spellings showed some effects of this practice. Although emphasis on letter sounds as opposed to letter names influences children's patterns of performance and types of errors, it does not make the difficult English writing system markedly easier to master.


Bartonella (Rochalimaea) quintana infections.
Bartonella (formerly Rochalimaea) quintana is the etiological agent of trench fever, a disease extensively reported during the World Wars. Recent molecular biology approaches have allowed dramatic extension of the spectrum of Bartonella infections. B. quintana is now also recognized as an etiological agent of fever and bacteremia, endocarditis, bacillary angiomatosis, and chronic lymphadenopathy. Human immunodeficiency virus-infected patients and/or homeless people are the most vulnerable to infection. Poverty and louse infestation were the main epidemiological factors associated with B. quintana infections during wartime. Although poverty and chronic alcoholism have been associated with modern cases of trench fever and bacteremia due to B. quintana in Europe and the United States, vectors for B. quintana have not been clearly identified and B. quintana has not been isolated from modern-day lice. Microscopic bacillary angiomatosis lesions are characterized by tumor-like capillary lobules, with proliferating endothelial cells. In vitro experiments have shown that B. quintana survives within endothelial cells and stimulates cell proliferation. These observations, together with the finding that lesions may regress when antibiotic therapy is administered, strongly suggest that B. quintana itself stimulates angiogenesis. Bartonella infections are characterized by a high frequency of relapses after brief courses of antibiotic therapy. It is to be noted that in vitro, although Bartonella species are highly susceptible to antibiotics, only the aminoglycosides have proved to be bactericidal. However, the most effective antibiotic regimen for Bartonella infections remains to be established.


Impacts of multiple stressors on ecosystem function: Leaf decomposition in constructed urban wetlands.
The impact of stormwater on stream biota is well documented, but less is known about the impacts on ecosystem processes, such as the breakdown of organic matter. This study sought to establish whether the degree of urbanisation affected rates of leaf-litter breakdown within constructed wetlands. A litter bag method was used to ascertain rate of decomposition along a gradient of urbanisation (total imperviousness, TI), in constructed wetlands in western and south-eastern Melbourne. A significant positive relationship between TI and breakdown rate was found in the south-eastern wetlands. The significant reduction in rate of invertebrate-mediated breakdown with increasing concentration of certain metals was consistent with other studies. However, overall there was an increase in rate of breakdown. Studies have shown that the effects of heavy metals can be negated if nutrient levels are high. Our results suggest that other parameters besides exposure to contaminants are likely to affect leaf litter breakdown.


Chronic non-communicable diseases in Cameroon - burden, determinants and current policies.
Cameroon is experiencing an increase in the burden of chronic non-communicable diseases (NCDs), which accounted for 43% of all deaths in 2002. This article reviews the published literature to critically evaluate the evidence on the frequency, determinants and consequences of NCDs in Cameroon, and to identify research, intervention and policy gaps. The rising trends in NCDs have been documented for hypertension and diabetes, with a 2-5 and a 10-fold increase in their respective prevalence between 1994 and 2003. Magnitudes are much higher in urban settings, where increasing prevalence of overweight/obesity (by 54-82%) was observed over the same period. These changes largely result from the adoption of unfavorable eating habits, physical inactivity, and a probable increasing tobacco use. These behavioral changes are driven by the economic development and social mobility, which are part of the epidemiologic transition. There is still a dearth of information on chronic respiratory diseases and cancers, as well as on all NDCs and related risk factors in children and adolescents. More nationally representative data is needed to tract risk factors and consequences of NCDs. These conditions are increasingly been recognized as a priority, mainly through locally generated evidence. Thus, national-level prevention and control programs for chronic diseases (mainly diabetes and hypertension) have been established. However, the monitoring and evaluation of these programs is necessary. Budgetary allocations data by the ministry of health would be helpful, to evaluate the investment in NCDs prevention and control. Establishing more effective national-level tobacco control measures and food policies, as well as campaigns to promote healthy diets, physical activity and tobacco cessation would probably contribute to reducing the burden of NCDs.


Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.
To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD.


Analysis of 953 human proteins from a mitochondrial HEK293 fraction by complexome profiling.
Complexome profiling is a novel technique which uses shotgun proteomics to establish protein migration profiles from fractionated blue native electrophoresis gels. Here we present a dataset of blue native electrophoresis migration profiles for 953 proteins by complexome profiling. By analysis of mitochondrial ribosomal complexes we demonstrate its potential to verify putative protein-protein interactions identified by affinity purification-mass spectrometry studies. Protein complexes were extracted in their native state from a HEK293 mitochondrial fraction and separated by blue native gel electrophoresis. Gel lanes were cut into gel slices of even size and analyzed by shotgun proteomics. Subsequently, the acquired protein migration profiles were analyzed for co-migration via hierarchical cluster analysis. This dataset holds great promise as a comprehensive resource for de novo identification of protein-protein interactions or to underpin and prioritize candidate protein interactions from other studies. To demonstrate the potential use of our dataset we focussed on the mitochondrial translation machinery. Our results show that mitoribosomal complexes can be analyzed by blue native gel electrophoresis, as at least four distinct complexes. Analysis of these complexes confirmed that 24 proteins that had previously been reported to co-purify with mitoribosomes indeed co-migrated with subunits of the mitochondrial ribosome. Co-migration of several proteins involved in biogenesis of inner mitochondrial membrane complexes together with mitoribosomal complexes suggested the possibility of co-translational assembly in human cells. Our data also highlighted a putative ribonucleotide complex that potentially contains MRPL10, MRPL12 and MRPL53 together with LRPPRC and SLIRP.


Levetiracetam Prophylaxis for Post-traumatic Brain Injury Seizures is Ineffective: A Propensity Score Analysis.
Early seizures after severe traumatic brain injury (TBI) have a reported incidence of up to 15 %. Prophylaxis for early seizures using 1 week of phenytoin is considered standard of care for seizure prevention. However, many centers have substituted the anticonvulsant levetiracetam without good data on the efficacy of this approach. Our hypothesis was that the treatment with levetiracetam is not effective in preventing early post-traumatic seizures. All trauma patients sustaining a TBI from January 2007 to December 2009 at an urban level-one trauma center were retrospectively analyzed. Seizures were identified from a prospectively gathered morbidity database and anticonvulsant use from the pharmacy database. Statistical comparisons were made by Chi square, t tests, and logistic regression modeling. Patients who received levetiracetam prophylaxis were matched 1:1 using propensity score matching with those who did not receive the drug. 5551 trauma patients suffered a TBI during the study period, with an overall seizure rate of 0.7 % (39/5551). Of the total population, 1795 were diagnosed with severe TBI (Head AIS score 3-5). Seizures were 25 times more likely in the severe TBI group than in the non-severe group [2.0 % (36/1795) vs. 0.08 % (3/3756); OR 25.6; 95 % CI 7.8-83.2; p < 0.0001]. Of the patients who had seizures after severe TBI, 25 % (9/36) received pharmacologic prophylaxis with levetiracetam, phenytoin, or fosphenytoin. In a matched cohort by propensity scores, no difference was seen in seizure rates between the levetiracetam group and no-prophylaxis group (1.9 vs. 3.4 %, p = 0.50). In this propensity score-matched cohort analysis, levetiracetam prophylaxis was ineffective in preventing seizures as the rate of seizures was similar whether patients did or did not receive the drug. The incidence of post-traumatic seizures in severe TBI patients was only 2.0 % in this study; therefore we question the benefit of routine prophylactic anticonvulsant therapy in patients with TBI.


Characterization of transient noise in Advanced LIGO relevant to gravitational wave signal GW150914.
On September 14, 2015, a gravitational wave signal from a coalescing black hole binary system was observed by the Advanced LIGO detectors. This paper describes the transient noise backgrounds used to determine the significance of the event (designated GW150914) and presents the results of investigations into potential correlated or uncorrelated sources of transient noise in the detectors around the time of the event. The detectors were operating nominally at the time of GW150914. We have ruled out environmental influences and non-Gaussian instrument noise at either LIGO detector as the cause of the observed gravitational wave signal.


Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.
Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. Eleven UK specialist vascular centres. Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. Current Controlled Trials ISRCTN51995477. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 27. See the NIHR Journals Library website for further project information.


Extracellular enzyme activities potentially involved in the pathogenicity of Mycobacterium tuberculosis.
To evaluate the potential contribution of extracellular enzymes to the pathogenicity of mycobacteria, the presence of selected enzyme activities was investigated in the culture filtrates of the obligate human pathogen Mycobacterium tuberculosis, M. bovis BCG, the opportunistic pathogens M. kansasii and M. fortuitum, and the non-pathogenic species M. phlei and M. smegmatis. For M. tuberculosis and M. bovis, 22 enzyme activities were detected in the culture filtrates and/or cell surfaces, of which eight were absent from the culture fluids of non-pathogens: alanine dehydrogenase, glutamine synthetase, nicotinamidase, isonicotinamidase, superoxide dismutase, catalase, peroxidase and alcohol dehydrogenase. These activities, which correspond to secreted enzymes, formed a significant part (up to 92%) of the total enzyme activities of the bacteria and were absent from the culture fluids and the cell surfaces of the non-pathogenic species M. smegmatis and M. phlei. The extracellular location of superoxide dismutase and glutamine synthetase seemed to be restricted to the obligate pathogens examined. The difference in the enzyme profiles was not attributable to the growth rates of the two groups of bacteria. The presence of the eight enzyme activities in the outermost compartments of obligate pathogens and their absence in those of non-pathogens provides further evidence that these enzymes may be involved in the pathogenicity of mycobacteria. In addition, the eight enzyme activities were demonstrated in the cell extract of M. smegmatis. Stepwise erosion of the cell surface of M. smegmatis to expose internal capsular constituents showed that the various enzyme activities, with the possible exception of superoxide dismutase, were located more deeply in the cell envelope of this bacterium. This suggests that the molecular architecture of the mycobacterial envelopes may play an important role in the pathogenicity of these organisms.


Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission.
The role of the gut in diabetes remission after Roux-en-Y gastric bypass (RYGB) is incompletely understood. We assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Longitudinal, prospective measures of β-cell function were assessed after oral glucose intake and graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n = 29), 12 (n = 24), and 24 (n = 20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. The decreases in body weight, fat mass, waist circumference, and insulin resistance after surgery (all P < 0.001 at 12 and 24 months) did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose intake differed by remission status (P = 0.04): greater (6.5-fold; P < 0.01) and sustained in those in full remission, moderate and not sustained past 12 months in those with partial remission (3.3-fold; P < 0.001), and minimal in those not experiencing remission (2.7-fold; P = not significant). The improvement in β-cell function after IV glucose administration was not apparent until 12 months, significant only in those in full remission, and only ∼33% of that observed after oral glucose intake. Preintervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.


Role of haematopoietic cells and endothelial progenitors in tumour angiogenesis.
Bone marrow-derived cells include haematopoietic cell lineages and the recently described endothelial progenitor cells (EPCs). It has been recently emphasised that these marrow-derived cells contribute to tumour angiogenesis, and different mechanisms have been proposed that account for this activity. Whereas haematopoietic cells may promote tumour angiogenesis through the release of proangiogenic factors or by creating permissive conditions in the tumour microenvironment that favour the growth of locally derived blood vessels ("paracrine" role), endothelial progenitors are thought to directly incorporate into nascent blood vessels as bona fide endothelial cells ("building block" role). The relative contribution of these distinct pathways to tumour angiogenesis is the subject of intense investigation and debate.


Nutrient foraging strategies are associated with productivity and population growth in forest shrubs.
Temperate deciduous forest understoreys are experiencing widespread changes in community composition, concurrent with increases in rates of nitrogen supply. These shifts in plant abundance may be driven by interspecific differences in nutrient foraging (i.e. conservative vs. acquisitive strategies) and, thus, adaptation to contemporary nutrient loading conditions. This study sought to determine if interspecific differences in nutrient foraging could help explain patterns of shrub success and decline in eastern North American forests. Using plants grown in a common garden, fine root traits associated with nutrient foraging were measured for six shrub species. Traits included the mean and skewness of the root diameter distribution, specific root length (SRL), C:N ratio, root tissue density, arbuscular mycorrhizal colonization and foraging precision. Above- and below-ground productivity were also determined for the same plants, and population growth rates were estimated using data from a long-term study of community dynamics. Root traits were compared among species and associations among root traits, measures of productivity and rates of population growth were evaluated. Species fell into groups having thick or thin root forms, which correspond to conservative vs. acquisitive nutrient foraging strategies. Interspecific variation in root morphology and tissue construction correlated with measures of productivity and rates of cover expansion. Of the four species with acquisitive traits, three were introduced species that have become invasive in recent decades, and the fourth was a weedy native. In contrast, the two species with conservative traits were historically dominant shrubs that have declined in abundance in eastern North American forests. In forest understoreys of eastern North America, elevated nutrient availability may impose a filter on species success in addition to above-ground processes such as herbivory and overstorey canopy conditions. Shrubs that have root traits associated with rapid uptake of soil nutrients may be more likely to increase in abundance, while species without such traits may be less likely to keep pace with more productive species.


ALS-associated TDP-43 induces endoplasmic reticulum stress, which drives cytoplasmic TDP-43 accumulation and stress granule formation.
In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons and glia, where it associates with stress granules (SGs) and forms large inclusions. SGs form in response to cellular stress, including endoplasmic reticulum (ER) stress, which is induced in both familial and sporadic forms of ALS. Here we demonstrate that pharmacological induction of ER stress causes TDP-43 to accumulate in the cytoplasm, where TDP-43 also associates with SGs. Furthermore, treatment with salubrinal, an inhibitor of dephosphorylation of eukaryotic initiation factor 2-α, a key modulator of ER stress, potentiates ER stress-mediated SG formation. Inclusions of C-terminal fragment TDP-43, reminiscent of disease-pathology, form in close association with ER and Golgi compartments, further indicating the involvement of ER dysfunction in TDP-43-associated disease. Consistent with this notion, over-expression of ALS-linked mutant TDP-43, and to a lesser extent wildtype TDP-43, triggers several ER stress pathways in neuroblastoma cells. Similarly, we found an interaction between the ER chaperone protein disulphide isomerase and TDP-43 in transfected cell lysates and in the spinal cords of mutant A315T TDP-43 transgenic mice. This study provides evidence for ER stress as a pathogenic pathway in TDP-43-mediated disease.


The effectiveness of physiotherapy for cervical dystonia: a systematic literature review.
Cervical dystonia is a form of adult-onset, focal dystonia characterized by involuntary contractions of the neck muscles, leading to a disabling, abnormal head posture. CD has a great impact on the activities of daily living (ADL) and quality of life. Currently, the most widely used and recommended first line treatment is botulinum toxin type A (BoNT/A) injections. Physiotherapy is a potentially useful adjuvant, but little is known about its effectiveness. Consequently, our objective was to investigate the effectiveness of physiotherapy alone or as an adjuvant treatment to BoNT/A injections in cervical dystonia (CD) by means of a systematic literature review. Two online databases, PubMed and Web of Science, were searched for articles describing the effectiveness of physiotherapy treatment for CD. After screening, based on predefined in- and exclusion criteria, 16 studies were retained. Their methodological quality was assessed according to Cochrane guidelines. The methodological quality of most studies was low. Examples of shortcomings are small sample sizes, lack of randomization or blinding, and diversity in therapeutic techniques and outcome measures. Only seven studies were clinical trials; the remaining were either case reports or case series. The reported physiotherapy treatments included EMG biofeedback training, muscular elongation, postural exercises and electrotherapy. Improvements in head position, pain, cervical range of motion, quality of life and ADL have been reported, which is promising. Cautious interpretation on the effectiveness of physiotherapy as an adjuvant therapy is required. Before firm conclusions can be drawn, additional high quality trials are needed.


Pseudo actinometry for the measurement of reactive species density.
To compensate for the effect of plasma parameters in the signal of optical emission spectroscopy, we should normalize the emission intensity from the species against that of an inert gas (i.e., the actinometer). In many plasma processes in the semiconductor industry, plasma etching without using a neutral gas for the actinometer has become popular to achieve better critical dimension uniformity. We propose "pseudo actinometry" for normalization in the absence of an inert gas in the process plasma. Based on the theory of optical actinometry, we define a correction factor as the ratio of the emission intensity to the number density of the inert gas. As we reduced the density of the inert gas, we experimentally determined the correction factor by taking its convergence when the concentration of the inert gas was zero. As proof of concept, we applied pseudo actinometry to measure the density distribution of atomic chlorine in a photomask etching process without an inert gas. By comparing the distributions of chlorine radicals and the etch rate as measured by an ellipsometer, we calculated the correlation coefficient between the distributions. The correlation coefficient rapidly decreased to 0.60 when we used the correction factor determined at a flow rate for the inert gas of 20 standard cubic centimeters per minute at STP. By using pseudo actinometry, we successfully determined the distribution of chlorine radicals with a correlation coefficient of 0.98 in a plasma etching process without an inert gas.


NFIB Mediates BRN2 Driven Melanoma Cell Migration and Invasion Through Regulation of EZH2 and MITF.
While invasion and metastasis of tumour cells are the principle factor responsible for cancer related deaths, the mechanisms governing the process remain poorly defined. Moreover, phenotypic divergence of sub-populations of tumour cells is known to underpin alternative behaviors linked to tumour progression such as proliferation, survival and invasion. In the context of melanoma, heterogeneity between two transcription factors, BRN2 and MITF, has been associated with phenotypic switching between predominantly invasive and proliferative behaviors respectively. Epigenetic changes, in response to external cues, have been proposed to underpin this process, however the mechanism by which the phenotypic switch occurs is unclear. Here we report the identification of the NFIB transcription factor as a novel downstream effector of BRN2 function in melanoma cells linked to the migratory and invasive characteristics of these cells. Furthermore, the function of NFIB appears to drive an invasive phenotype through an epigenetic mechanism achieved via the upregulation of the polycomb group protein EZH2. A notable target of NFIB mediated up-regulation of EZH2 is decreased MITF expression, which further promotes a less proliferative, more invasive phenotype. Together our data reveal that NFIB has the ability to promote dynamic changes in the chromatin state of melanoma cells to facilitate migration, invasion and metastasis.


Effectiveness of Yoga on Quality of Life of Breast Cancer Patients Undergoing Chemotherapy: A Randomized Clinical Controlled Study.
Cancer of breast is most common cancer among women in India and vast majority of countries worldwide. While undergoing chemotherapy for carcinoma management, women encounter side effects, which affects their quality of life (QOL). A randomized controlled study with quantitative research approach and time series design was conducted, to study the effectiveness of yoga on QOL of breast cancer patients undergoing chemotherapy. One hundred breast cancer patients scheduled for 3-weekly, day-care adjuvant chemotherapy (CEF regimen) were enrolled with consecutive sampling technique, into control (n = 52) and experiment (n = 48) groups, by concealed randomization following written informed consent. Baseline data on QOL were collected before first-cycle chemotherapy using the European Organization for Research and Treatment of Cancer QLQ C30. Patients in the experimental group were taught diaphragmatic breathing techniques, systematic relaxation, and alternate nostril breathing, and Joints and Glands neck and shoulder exercises were instructed to practice twice daily at home. They were supervised in practicing these techniques while they received second, third, fourth, fifth, and sixth cycles of chemotherapy in the day-care facility. Participants in the control group received only routine care. All participants received standard post chemotherapy prescription. Data on QOL were collected from all patients during the second, third, fourth, fifth, and sixth cycles of chemotherapy. The analysis revealed that at the baseline (first chemotherapy cycle), breast cancer patients in control and experimental groups were homogeneous in terms of their sociodemographic and clinical variables and QOL score. Yoga practices were effective in improving the QOL of breast cancer patients in the experimental group in the areas of global health status, physical function, role function, and emotional function and decreasing the symptoms of fatigue, insomnia, loss of appetite, and constipation, during the period of chemotherapy. Yoga practices comprising of relaxation techniques reduce many side effects and improve the QOL of women undergoing chemotherapy for breast cancer.


Alterations of red cell membrane properties in neuroacanthocytosis.
Neuroacanthocytosis (NA) refers to a group of heterogenous, rare genetic disorders, namely chorea acanthocytosis (ChAc), McLeod syndrome (MLS), Huntington's disease-like 2 (HDL2) and pantothenate kinase associated neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated with similar neurological symptoms. PKAN is also assigned to a group of rare neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron accumulation), associated with iron accumulation in the basal ganglia and progressive movement disorder. Acanthocytosis, the occurrence of misshaped erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS patients but less prevalent in PKAN (about 10%) and HDL2 patients. The pathological factors that lead to the formation of the acanthocytic red blood cell shape are currently unknown. The aim of this study was to determine whether NA/NBIA acanthocytes differ in their functionality from normal erythrocytes. Several flow-cytometry-based assays were applied to test the physiological responses of the plasma membrane, namely drug-induced endocytosis, phosphatidylserine exposure and calcium uptake upon treatment with lysophosphatidic acid. ChAc red cell samples clearly showed a reduced response in drug-induced endovesiculation, lysophosphatidic acid-induced phosphatidylserine exposure, and calcium uptake. Impaired responses were also observed in acanthocyte-positive NBIA (PKAN) red cells but not in patient cells without shape abnormalities. These data suggest an "acanthocytic state" of the red cell where alterations in functional and interdependent membrane properties arise together with an acanthocytic cell shape. Further elucidation of the aberrant molecular mechanisms that cause this acanthocytic state may possibly help to evaluate the pathological pathways leading to neurodegeneration.


Tinnitus improvement with ultra-high-frequency vibration therapy.
This study reports on the long-term benefit of ultra-high-frequency masking with the UltraQuiet device. A commercial product, UltraQuiet provides a new form of high-frequency bone conduction therapy. To assess its effectiveness in tinnitus treatment, we selected 15 patients with problematic tinnitus and randomly assigned them to three variations of the medical-audiological tinnitus patient protocol modified for the UltraQuiet study. We assessed tinnitus relief by questionnaires directed at weighing patient response to overall effectiveness, tinnitus loudness, tinnitus severity, and tinnitus annoyance. Additionally, we performed audiological measures (including pure-tone and speech audiometry, minimal masking levels, pitch and loudness matching, and residual inhibition). All patients showed some long-term gains, and most exhibited relief in at least one measurement parameter, providing support for the use of high-frequency vibration in the treatment of tinnitus.


Real time single cell analysis of Bid cleavage and Bid translocation during caspase-dependent and neuronal caspase-independent apoptosis.
Bcl-2 homology domain (BH) 3-only proteins couple stress signals to evolutionarily conserved mitochondrial apoptotic pathways. Caspase 8-mediated cleavage of the BH3-only protein Bid into a truncated protein (tBid) and subsequent translocation of tBid to mitochondria has been implicated in death receptor signaling. We utilized a recombinant fluorescence resonance energy transfer (FRET) Bid probe to determine the kinetics of Bid cleavage and tBid translocation during death receptor-induced apoptosis in caspase 3-deficient MCF-7 cells. Cells treated with tumor necrosis factor-alpha (200 ng/ml) showed a rapid cleavage of the Bid-FRET probe occurring 75.4 +/- 12.6 min after onset of the tumor necrosis factor-alpha exposure. Cleavage of the Bid-FRET probe coincided with a translocation of tBid to the mitochondria and a collapse of the mitochondrial membrane potential (DeltaPsim). We next investigated the role of Bid cleavage in a model of caspase-independent, glutamate-induced excitotoxic apoptosis. Rat cerebellar granule neurons were transfected with the Bid-FRET probe and exposed to glutamate for 5 min. In contrast to death receptor-induced apoptosis, neurons showed a translocation of full-length Bid to the mitochondria. This translocation occurred 5.6 +/- 1.7 h after the termination of the glutamate exposure and was also paralleled with a collapse of the DeltaPsim. Proteolytic cleavage of the FRET probe also occurred, however, only 25.2 +/- 3.5 min after its translocation to the mitochondria. Subfractionation experiments confirmed a translocation of full-length Bid from the cytosolic to the mitochondrial fraction during excitotoxic apoptosis. Our data demonstrate that both tBid and full-length Bid have the capacity to translocate to mitochondria during apoptosis.


Screening for Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: US Preventive Services Task Force Final Recommendation Statement.
Intimate partner violence (IPV) and abuse of older or vulnerable adults are common in the United States but often remain undetected. In addition to the immediate effects of IPV, such as injury and death, there are other health consequences, many with long-term effects, including development of mental health conditions such as depression, posttraumatic stress disorder, anxiety disorders, substance abuse, and suicidal behavior; sexually transmitted infections; unintended pregnancy; and chronic pain and other disabilities. Long-term negative health effects from elder abuse include death, higher risk of nursing home placement, and adverse psychological consequences. To update the US Preventive Services Task Force (USPSTF) 2013 recommendation on screening for IPV, elder abuse, and abuse of vulnerable adults. The USPSTF commissioned a review of the evidence on screening for IPV in adolescents, women, and men; for elder abuse; and for abuse of vulnerable adults. The USPSTF concludes with moderate certainty that screening for IPV in women of reproductive age and providing or referring women who screen positive to ongoing support services has a moderate net benefit. There is adequate evidence that available screening instruments can identify IPV in women. The evidence does not support the effectiveness of brief interventions or the provision of information about referral options in the absence of ongoing supportive intervention components. The evidence demonstrating benefit of ongoing support services is predominantly found in studies of pregnant or postpartum women. The benefits and harms of screening for elder abuse and abuse of vulnerable adults are uncertain, and the balance of benefits and harms cannot be determined. The USPSTF recommends that clinicians screen for IPV in women of reproductive age and provide or refer women who screen positive to ongoing support services. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for abuse and neglect in all older or vulnerable adults. (I statement).


Extraction Method of Crack Signal for Inspection of Complicated Steel Structures Using A Dual-Channel Magnetic Sensor.
Conventional eddy current testing (ECT) using a pickup coil probe is widely employed for the detection of structural cracks. However, the inspection of conventional ECT for steel structures is difficult because of the magnetic noise caused by the nonuniform permeability of steel. To combat this challenge, we have developed a small magnetic sensor probe with a dual-channel tunneling magnetoresistance sensor that is capable of reducing magnetic noise. Applying this probe to a complicated component of steel structures-such as the welds joining a U-shaped rib and deck plate together-requires the reduction of signal fluctuation caused by the distance (liftoff) variations between the sensor probe and the subject. In this study, the fundamental crack signal and the liftoff signal were investigated with the dual-channel sensor. The results showed that the liftoff signals could be reduced and differentiated from the crack signals by the differential parameters of the dual-channel sensor. In addition, we proposed an extraction technique for the crack signal using the Lissajous curve of the differential parameters. The extraction technique could be applied to the inspections not only for flat plates but also for welded angles to detect cracks without the influence of the liftoff signal.


ACL and meniscal injuries increase the risk of primary total knee replacement for osteoarthritis: a matched case-control study using the Clinical Practice Research Datalink (CPRD).
The aim of this study was to investigate whether ACL injury (ACLi) or meniscal injury increases the risk of end-stage osteoarthritis (OA) resulting in total knee replacement (TKR). A matched case-control study of all TKRs performed in the UK between January 1990 and July 2011 and recorded in the Clinical Practice Research Datalink (CPRD) was undertaken. The CPRD contains longitudinal data on approximately 3.6 million patients. Two controls were selected for each case of TKR, matched on age, sex and general practitioner location as a proxy for socioeconomic status. Individuals with inflammatory arthritis were excluded. The odds of having TKR for individuals with a CPRD-recorded ACLi were compared with those without ACLi using conditional logistic regression, after adjustment for body mass index, previous knee fracture and meniscal injury. The adjusted odds of TKR in individuals with a recorded meniscal injury compared with those without were calculated. After exclusion of individuals with inflammatory arthritis, there were 49 723 in the case group and 104 353 controls. 153 (0.31%) cases had a history of ACLi compared with 41 (0.04%) controls. The adjusted OR of TKR after ACLi was 6.96 (95% CI 4.73 to 10.31). 4217 (8.48%) individuals in the TKR group had a recorded meniscal injury compared with 669 (0.64%) controls. The adjusted OR of TKR after meniscal injury was 15.24 (95% CI 13.88 to 16.69). This study demonstrates that ACLi is associated with a sevenfold increased odds of TKR resulting from OA. Meniscal injury is associated with a 15-fold increase odds of TKR for OA.


The impact of state tobacco control program funding cuts on teens' exposure to tobacco control interventions: evidence from Florida.
Explore the impact of dramatic budget cuts to the Florida Tobacco Control Program (FTCP) on Florida teens' exposure to tobacco control interventions. Survey data on teens in Florida and a comparison sample of the remainder of the United States. Data were collected in six waves between 2002 and 2006, with three waves collected before and three waves collected after the FTCP budget cut in fiscal year (FY) 2004. Florida. Twelve- to 17-year-old teens in Florida and the remainder of the United States. Between spring 2002 and summer 2006, 7841 interviews of Florida teens and 10,875 interviews of teens in the remainder of the United States were conducted. Exposure to FTCP interventions, including tobacco countermarketing, school and community organizations, and in-school tobacco prevention curricula. Multivariable logistic regression models were used to test whether declines in Florida youth's exposure to FTCP interventions were associated with the FTCP budget cut. Following the FY2004 FTCP budget cut, there were greater declines in teens' exposure to tobacco countermarketing campaigns in Florida compared with the remainder of the United States (odds ratio [OR] = .42; p < .001). The FY2004 budget cut also may have had an impact on exposure to in-school tobacco prevention curricula and school youth organizations (OR = .67; p < .001). Program budget cuts in Florida resulted in significant declines in exposure to some FTCP interventions (particularly tobacco countermarketing). Research on the correlates of smoking suggests that these budget cuts could have a significant impact on tobacco-related outcomes among teens.


Backbone-Degradable Polymers Prepared by Chemical Vapor Deposition.
Polymers prepared by chemical vapor deposition (CVD) polymerization have found broad acceptance in research and industrial applications. However, their intrinsic lack of degradability has limited wider applicability in many areas, such as biomedical devices or regenerative medicine. Herein, we demonstrate, for the first time, a backbone-degradable polymer directly synthesized via CVD. The CVD co-polymerization of [2.2]para-cyclophanes with cyclic ketene acetals, specifically 5,6-benzo-2-methylene-1,3-dioxepane (BMDO), results in well-defined, hydrolytically degradable polymers, as confirmed by FTIR spectroscopy and ellipsometry. The degradation kinetics are dependent on the ratio of ketene acetals to [2.2]para-cyclophanes as well as the hydrophobicity of the films. These coatings address an unmet need in the biomedical polymer field, as they provide access to a wide range of reactive polymer coatings that combine interfacial multifunctionality with degradability.


Temporal pattern of ICAM-I mediated regulatory T cell recruitment to sites of inflammation in adoptive transfer model of multiple sclerosis.
Migration of immune cells to the target organ plays a key role in autoimmune disorders like multiple sclerosis (MS). However, the exact underlying mechanisms of this active process during autoimmune lesion pathogenesis remain elusive. To test if pro-inflammatory and regulatory T cells migrate via a similar molecular mechanism, we analyzed the expression of different adhesion molecules, as well as the composition of infiltrating T cells in an in vivo model of MS, adoptive transfer experimental autoimmune encephalomyelitis in rats. We found that the upregulation of ICAM-I and VCAM-I parallels the development of clinical disease onset, but persists on elevated levels also in the phase of clinical remission. However, the composition of infiltrating T cells found in the developing versus resolving lesion phase changed over time, containing increased numbers of regulatory T cells (FoxP3) only in the phase of clinical remission. In order to test the relevance of the expression of cell adhesion molecules, animals were treated with purified antibodies to ICAM-I and VCAM-I either in the phase of active disease or in early remission. Treatment with a blocking ICAM-I antibody in the phase of disease progression led to a milder disease course. However, administration during early clinical remission aggravates clinical symptoms. Treatment with anti-VCAM-I at different timepoints had no significant effect on the disease course. In summary, our results indicate that adhesion molecules are not only important for capture and migration of pro-inflammatory T cells into the central nervous system, but also permit access of anti-inflammatory cells, such as regulatory T cells. Therefore it is likely to assume that intervention at the blood brain barrier is time dependent and could result in different therapeutic outcomes depending on the phase of CNS lesion development.


Childhood obesity and interpersonal dynamics during family meals.
Family meals have been found to be associated with a number of health benefits for children; however, associations with obesity have been less consistent, which raises questions about the specific characteristics of family meals that may be protective against childhood obesity. The current study examined associations between interpersonal and food-related family dynamics at family meals and childhood obesity status. The current mixed-methods, cross-sectional study included 120 children (47% girls; mean age: 9 years) and parents (92% women; mean age: 35 years) from low-income and minority communities. Families participated in an 8-day direct observational study in which family meals were video-recorded in their homes. Family meal characteristics (eg, length of the meal, types of foods served) were described and associations between dyadic (eg, parent-child, child-sibling) and family-level interpersonal and food-related dynamics (eg, communication, affect management, parental food control) during family meals and child weight status were examined. Significant associations were found between positive family- and parent-level interpersonal dynamics (ie, warmth, group enjoyment, parental positive reinforcement) at family meals and reduced risk of childhood overweight. In addition, significant associations were found between positive family- and parent-level food-related dynamics (ie, food warmth, food communication, parental food positive reinforcement) and reduced risk of childhood obesity. Results extend previous findings on family meals by providing a better understanding of interpersonal and food-related family dynamics at family meals by childhood weight status. Findings suggest the importance of working with families to improve the dyadic and family-level interpersonal and food-related dynamics at family meals.


Effects of artificial light at night on human health: A literature review of observational and experimental studies applied to exposure assessment.
It has frequently been reported that exposure to artificial light at night (ALAN) may cause negative health effects, such as breast cancer, circadian phase disruption and sleep disorders. Here, we reviewed the literature assessing the effects of human exposure to ALAN in order to list the health effects of various aspects of ALAN. Several electronic databases were searched for articles, published through August 2014, related to assessing the effects of exposure to ALAN on human health; these also included the details of experiments on such exposure. A total of 85 articles were included in the review. Several observational studies showed that outdoor ALAN levels are a risk factor for breast cancer and reported that indoor light intensity and individual lighting habits were relevant to this risk. Exposure to artificial bright light during the nighttime suppresses melatonin secretion, increases sleep onset latency (SOL) and increases alertness. Circadian misalignment caused by chronic ALAN exposure may have negative effects on the psychological, cardiovascular and/or metabolic functions. ALAN also causes circadian phase disruption, which increases with longer duration of exposure and with exposure later in the evening. It has also been reported that shorter wavelengths of light preferentially disturb melatonin secretion and cause circadian phase shifts, even if the light is not bright. This literature review may be helpful to understand the health effects of ALAN exposure and suggests that it is necessary to consider various characteristics of artificial light, beyond mere intensity.


Residents' perceptions of work environment during their postgraduate medical training in Pakistan.
In Pakistan, there is a lack of information about the work environment of residency programs. This lack is a major impediment in their improvement. One of the approaches for improvement in these programs can be directed through the residents' own perception of their working conditions. Therefore, we collected data which would reflect working conditions of residents. To assess the perceived status of "work environment" in different specialities. A cross-sectional survey was conducted in four teaching hospitals of Karachi from July 1999 to January 2000. Residents from selected programs were grouped into four broad groups: specialist, medical, surgical and multidisciplinary. Responses of residents were obtained on a Likert scale of 0 to 4. Indices were formed for two components of work environment: academic and mistreatment. Differences between residents' groups were assessed through analysis of variance (ANOVA) at 5% significance. A total of 341 registered residents responded (response rate: 75%). Surgical residents were working more than 80 h/week and this was more than the other three groups. Medical residents were spending the highest actual time on research and teaching activities (10% and 14%, respectively). Academic index score was highest for surgical group (15.81, SD = 4.69) and lowest for multidisciplinary group (11.82, SD = 4.80). Medical group had the highest perceived mistreatment index score (5.56, SD = 4.57). In a study of work environment of residency programs, differential impact was found for the four groups on work environment perceptions. Most of the residents recognized undergraduate teaching, grand rounds, patient rounds and seminars or workshops as contributing to their academic learning. Reporting of sexual harassment was low, indicating either underreporting or cultural dynamics of our setting.


Contralateral mastectomy improves survival in women with BRCA1/2-associated breast cancer.
BRCA1/2 mutation carriers with breast cancer are at high risk of contralateral disease. Such women often elect to have contralateral risk-reducing mastectomy (CRRM) to reduce the likelihood of recurrence. This study considers whether CRRM improves overall survival. 105 female BRCA1/2 mutation carriers with unilateral breast cancer who underwent CRRM were compared to controls (593 mutation carriers and 105 specifically matched) not undergoing CRRM and diagnosed between 1985 and 2010. Survival was assessed by proportional hazards models, and extended to a matched analysis using stratification by risk-reducing bilateral salpingo-oophorectomy (RRBSO), gene, grade and stage. Median time to CRRM was 1.1 years after the primary diagnosis (range 0.0-13.3). Median follow-up was 9.7 years in the CRRM group and 8.6 in the non-CRRM group. The 10-year overall survival was 89 % in women electing for CRRM (n = 105) compared to 71 % in the non-CRRM group (n = 593); p < 0.001. The survival advantage remained after matching for oophorectomy, gene, grade and stage: HR 0.37 (0.17-0.80, p = 0.008)-CRRM appeared to act independently of RRBSO. CRRM appears to confer a survival advantage. If this finding is confirmed in a larger series it should form part of the counselling procedure at diagnosis of the primary tumour. The indication for CRRM in women who have had RRBSO also requires further research.


Calcifying/ossifying synovial sarcoma: a clinicopathologic and molecular study of 5 cases.
Synovial sarcoma (SS) is a soft tissue sarcoma with a generally aggressive behavior. Calcifying/ossifying SS is a rare variant associated with a favorable prognosis. The aim was to report clinicopathological features and molecular analysis of 5 cases of calcifying/ossifying SS. Record of 370 cases of SS reported in the section of Histopathology, of a tertiary care Hospital, between 2002 and 2011 were retrieved. Five cases exhibiting extensive calcification and ossification were identified. Immunohistochemistry was performed using Flex technique. Molecular analysis of these 5 cases was performed later at the collaborative Hospital abroad, by reverse transcription polymerase chain reaction. The ages of the patients ranged from 13 to 44 years (mean age 27 years; female to male ratio 1.6:1). The duration of symptoms ranged from 5 months to 5 years. Histologically, 4 were monophasic, and 1 was biphasic. Three cases exhibited extensive calcification and two extensive ossification. Immunohistochemical stain (epithelial membrane antigen was positive in all 5 cases, CKAE1/AE3 (3/4), Bcl2 (4/4), S100 (4/4), CK7 (2/2), CD99 (1/3) and vimentin (2/2). Intact RNA was obtained from 3 cases, all of which were positive for the SYT/SSX fusion transcript. Follow-up was available in 4 cases and ranged from 19 months to 85 months (mean 50 months). Local recurrence was seen in 2 cases. In conclusions, we report clinicopathologic features of 5 cases of calcifying/ossifying SS. The duration of symptoms and mean age of patients is similar to the literature. A slight female predominance was seen in contrast to a male predominance described in the literature. The clinical course of our cases validates the favorable prognosis of this rare type of SS.


Expression in systemic lupus erythematosus of an idiotype common to DNA-binding and nonbinding monoclonal antibodies produced by normal human lymphoid cells.
Rabbit antiserum raised against a normal-derived monoclonal anti-DNA antibody KIM 4.6.3 (IgM lambda) was used for idiotype analyses. This anti-serum (anti-4.6.3 ID) was rendered specific for KIM 4.6.3 idiotype (4.6.3 ID) by absorption with normal human IgM and IgG. The specificity of anti-4.6.3 was shown by its ability to bind to KIM 4.6.3 antibody but not to normal human IgM and IgG, by inhibition of anti-4.6.3 ID reactivity with KIM 4.6.3 antibody by the homologous monoclonal antibody and by the ability of anti-4.6.3 ID to inhibit the binding of single stranded DNA with KIM 4.6.3 antibody. The 4.6.3 ID was found to be commonly expressed since it was detected among 33% (10/30) DNA and 32% (23/72) non-DNA-reactive monoclonal antibodies that were obtained from five different unrelated normal individuals. The binding to ssDNA of the majority of idiotype positive anti-DNA antibodies however was not blocked by anti-4.6.3 ID suggesting that among these other monoclonal antibodies its expression is outside of the antigen binding site. The 4.6.3 ID, which was present among some normal-derived monoclonal IgM molecules was also found at a high frequency (90%) in the sera of patients with systemic lupus erythematosus (SLE) but only at a low frequency (24%) and concentration in normal sera. The level of 4.6.3 ID in SLE did not correlate with serum IgM and IgG nor with anti-DNA antibody concentrations. Idiotypic relatedness between SLE serum antibodies and monoclonal anti-DNA antibodies of normals implies the existence of a cross-reactive idiotype family and implies that a conserved common gene or closely related genes exist in the germ line encoding these 4.6.3 ID positive antibodies some of which are not exclusively associated with nucleic acid reactivity. The expression of these germ line genes in vivo thus distinguishes SLE from normals.


Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs.
A comparison study of several vasoconstrictor and vasodilator agents was conducted measuring changes in intestinal blood flow and oxygen consumption during 10-min periods of intra-arterial infusion. Blood flow was measured in a branch of the superior mesenteric artery of anesthetized dogs with an electromagnetic blood flow meter, and the arteriovenous oxygen content difference across the gut segment was determined photometrically. Vasopressin (4 x 10(-3) and 7x 10(-4) U/kg-min) diminished blood flow 60 and 28% and reduced oxygen consumption 54 and 22%, respectively (all P less than 0.001). In a dose which did not lower blood flow, vasopressin still caused a decline in oxygen consumption (P less than 0.01). Epinephrine (5 x 10(-2) mug/kg-min) decreased blood flow 19% (P less than 0.001) but did not reduce oxygen consumption. After beta-adrenergic blockade, however, the same dose of epinephrine decreased blood flow 41% and oxygen consumption 33% (both P less than 0.001). Responses to angiotension II, calcium chloride, and prostaglandin F2alpha resembled effects of vasopressin rather than those of epinephrine, namely decreased blood flow and decreased oxygen consumption. The vasodilator agents, prostaglandin E1, is isoproterenol, and histamine, increased (P less than 0.001) both blood flow (130, 80, and 98%, respectively) and oxygen consumption (98, 64, and 70%, respectively). Vasopressin, angiotensin II, calcium chloride, and prostaglandin F2alpha appear to contract arteriolar and precapillary sphincteric smooth muscle indiscriminately to evoke both intestinal ischemia and hypoxia. Epinephrine is the exceptional constrictor in this case, producing diminished blood flow without a reduction in oxygen uptake.


Increased risk for second primary malignancies in women with breast cancer diagnosed at young age: a population-based study in Taiwan.
Studies conducted in Western countries have reported excess risks for second primary malignancies after breast cancer. However, there is little documentation of ethnic differences in these excess risks. Asian women are characterized by younger age at diagnosis of breast cancer, but very few reports are available on the incidences and risks for second primary cancers in this region. Using population-based data from the Taiwan National Cancer Registry (TNCR) for the period 1979 to 2003, we quantified standardized incidence ratios and cumulative incidence of second cancers among 53,783 women with initial diagnoses of breast cancer. Age-specific incidences showed peaks among women in their 40s, and 1,085 cases (2.02%) developed nonbreast second primary cancers. The risk for second cancers differs significantly according to age at diagnosis of breast cancer. In comparison with women diagnosed when >or=50 years (standardized incidence ratio, 0.96; 95% confidence interval; 0.89-1.04), there were significantly greater risks for bone, corpus uterine, ovarian, thyroid, esophageal, kidney and lung cancers, nonmelanoma skin cancer, and leukemia or lymphoma in women diagnosed when <50 years (standardized incidence ratio, 1.43; 95% confidence interval, 1.29-1.58). The survival probabilities differed between breast cancer patients with and without second cancers (P<0.001). After diagnosis of the second cancer, the median survival time was only 2.87 years. In conclusion, we confirmed that young age at diagnosis of breast cancer predicted a subsequently increased risk for second malignancies, and the second cancers indeed worsen survivorship in patients who survived breast cancer.


Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses.
To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment. Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design. Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005. 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment. There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.


Experimental studies of hypothallus growth in the lichen Rhizocarpon geographicum.
Removal of the areolae of the crustose lichen Rhizocarpon geographicum (L.) DC. resulted in either low or no measurable radial growth of the marginal hypothallus. Radial growth of the hypothallus was also significantly reduced compared with intact thalli when (I) aerolae were removed to within 1 and 2 mm of the hypothallus and (2) a 5 mm wide 'moat' was created between the areolae and the hypothallus. Adding ribitol (0.01 M) to isolated hypothalli at 3-month intervals over 15 months resulted in total radial growth c. 60% that of intact thalli. Adding an arabitol/mannitol mixture (0.05 M arabitol, 0.03 M mannitol) increased radial growth compared with deionized water and ribitol treatments. Adding ribitol (0.7M), arabitol (0.2 M) and mannitol (0.08 M) to the areolae of intact thalli had no significant effects on radial growth of the hypothallus. On a south-facing rock surface, isolated hypothalli grew at a similar rate to intact thalli for 2 months. Growth then declined and the hypothalli disappeared from the rock surface within 6 months. The effects of addition of carbohydrate suggests that the marginal hypothallus has the capacity to utilize exogenous materials. However, in intact thalli in the field, the radial growth of the hypothallus is likely to be a result of transfer of materials from the areolae through hyphal connections.


Kinetics of the hydrolysis of atmospherically relevant isoprene-derived hydroxy epoxides.
Isoprene (the most abundant nonmethane hydrocarbon emitted into the atmosphere) is known to undergo oxidation to 2-methyl-1,2,3,4-butanetetraol, a hydrophilic compound present in secondary organic aerosol (SOA) in the atmosphere. Recent laboratory work has shown that gas phase hydroxy epoxides are produced in the low NOx photooxidation of isoprene and that these epoxides are likely to undergo efficient acid-catalyzed hydrolysis on SOA to 2-methyl-1,2,3,4-butanetetraol at typical SOA acidities. In order to confirm this hypothesis, the specific hydroxy epoxides observed in the isoprene photooxidation experiment (as well as several other related species) were synthesized, and the hydrolysis kinetics of all species were studied via nuclear magnetic resonance (NMR) techniques. It was determined that the isoprene-derived hydroxy epoxides should undergo efficient hydrolysis under atmospheric conditions, particular on lower pH SOA. An empirical structure-reactivity model was constructed that parametrized the hydrolysis rate constants according to the carbon substitution pattern on the epoxide ring and number of neighboring hydroxy functional groups. Compared to the previously studied similar nonfunctionalized epoxides, the presence of a hydroxy group at the alpha position to the epoxy group was found to reduce the hydrolysis rate constant by a factor of 20, and the presence of a hydroxy group at the beta position to the epoxy group was found to reduce the hydrolysis rate constant by a factor of 6.


A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity.
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLCγ2 pathway as drug-target.


ZEB1 promotes epithelial-mesenchymal transition in cervical cancer metastasis.
To investigate role of Zinc finger E-box binding homeobox 1 (ZEB1) in cervical cancer tissue (squamous cell carcinoma, SCC). Exploratory study. University hospital. Sixty patients with SCC, including stage CINIII (n = 10), IB1 (n = 10), IB2 (n = 10), IIA1 (n = 10), IIA2 (n = 10), and IIB (n = 10) were studied. Caski cells were transfected with recombinant shZEB1 lentivirus or shCtrl lentivirus to generate stable ZEB1-knockdown Caski cells. ZEB1 expression was analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry in cervical cancer tissues. ZEB1 expression in Caski cells was down-regulated by short-hairpin RNA (shRNA) interference, and changes in ZEB1 expression corresponded with changes in the proliferation and migratory ability of Caski cells. Quantitative real-time polymerase chain reaction and immunohistochemistry results revealed that ZEB1 expression and the ratio of Vimentin to E-cadherin were high in 27 of 50 SCC patients and correlated with advanced International Federation of Gynecology and Obstetrics stage, tumor size >4 cm, and parametrial invasion. However, the expression of ZEB1 in cervical cancer tissue was independent of age and SCC antigen level. Transfection of ZEB1 shRNA in Caski cells significantly decreased the messenger RNA and protein expression of ZEB1, parallel with increased expression of the epithelial marker E-cadherin and decreased expression of the mesenchymal marker Vimentin. Furthermore, the proliferation and migratory ability of Caski cells were significantly lower in the transfected group than in the nontransfected control group. Down-regulation of ZEB1 expression may protect the invasive front of the tumors from converting to a mesenchymal phenotype by reducing the proliferation and motility of cervical cancer cells, suggesting that ZEB1 might be a potential therapeutic target for SCC.


Mutations in DMI3 and SUNN modify the appressorium-responsive root proteome in arbuscular mycorrhiza.
Modification of the Medicago truncatula root proteome during the early stage of arbuscular mycorrhizal symbiosis was investigated by comparing, using two-dimensional electrophoresis, the protein patterns obtained from non-inoculated roots and roots synchronized for Glomus intraradices appressorium formation. This approach was conducted in wild-type (J5), mycorrhiza-defective (TRV25, dmi3), and autoregulation-defective (TR122, sunn) M. truncatula genotypes. The groups of proteins that responded to appressorium formation were further compared between wild-type and mutant genotypes; few overlaps and major differences were recorded, demonstrating that mutations in DMI3 and SUNN modified the appressorium-responsive root proteome. Except for a chalcone reductase, none of the differentially displayed proteins that could be identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry previously was known as appressorium responsive. A DMI3-dependent increased accumulation of signal transduction-related proteins (dehydroascorbate reductase, cyclophilin, and actin depolymerization factor) was found to precede mycorrhiza establishment. Differences in the accumulation of proteins related to plant defense reactions, cytoskeleton rearrangements, and auxin signaling upon symbiont contact were recorded between wild-type and hypermycorrhizal genotypes, pointing to some putative pathways by which SUNN may regulate very early arbuscule formation.


Resilience offers escape from trapped thinking on poverty alleviation.
The poverty trap concept strongly influences current research and policy on poverty alleviation. Financial or technological inputs intended to "push" the rural poor out of a poverty trap have had many successes but have also failed unexpectedly with serious ecological and social consequences that can reinforce poverty. Resilience thinking can help to (i) understand how these failures emerge from the complex relationships between humans and the ecosystems on which they depend and (ii) navigate diverse poverty alleviation strategies, such as transformative change, that may instead be required. First, we review commonly observed or assumed social-ecological relationships in rural development contexts, focusing on economic, biophysical, and cultural aspects of poverty. Second, we develop a classification of poverty alleviation strategies using insights from resilience research on social-ecological change. Last, we use these advances to develop stylized, multidimensional poverty trap models. The models show that (i) interventions that ignore nature and culture can reinforce poverty (particularly in agrobiodiverse landscapes), (ii) transformative change can instead open new pathways for poverty alleviation, and (iii) asset inputs may be effective in other contexts (for example, where resource degradation and poverty are tightly interlinked). Our model-based approach and insights offer a systematic way to review the consequences of the causal mechanisms that characterize poverty traps in different agricultural contexts and identify appropriate strategies for rural development challenges.


IgG4-related disease involving vital organs diagnosed with lip biopsy: A case report and literature review.
Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized new disease entity characterized by elevated serum IgG4 and infiltration of IgG4 plasma cells in affected tissues. Histological examination is essential for definitive diagnosis, as other pathological conditions can also present with serum IgG4 elevation. However, IgG4-RD frequently involves vital or internal organs that are difficult to perform biopsies. We herein report a unique case of IgG4-RD involving vital organs that could be successfully diagnosed by alternative lip biopsy, an accessible, little invasive procedure, despite no apparent manifestation demonstrating the involvement in labial salivary gland.A 60-year-old man with swelling of both submandibular glands and elevated serum creatinine level visited our hospital. His labial salivary glands appeared normal. His blood test showed high serum IgG4, and positron-emission computed tomography revealed abnormal uptake in submandibular glands, periaorta, and left kidney with hydronephrosis. We suspected him of IgG4-RD; however, the involved organs were difficult to approach for histological examination. Alternatively, we performed lip biopsy and proved massive infiltration of IgG4 plasma cells leading to the diagnosis with IgG4-RD. Treatment with prednisolone resulted in the remarkable improvement of organ involvements and the normalization of serum IgG4 level after 3 months. Prednisolone was gradually tapered without the relapse of disease.The early recognition and diagnosis of IgG4-RD is clinically important because delay in the treatment initiation leads to fibrosis with irreversible organ damage. Our case highlights the possibility that lip biopsy is a promising option for histological examination in patients with IgG4-RD in whom affected organs are difficult to access, leading to early diagnosis with appropriate treatment.