Acinetobacter insertion sequence ISAba11 belongs to a novel family that encodes transposases with a signature HHEK motif.
Experimental and in silico PCR analysis targeting ISAba11 and TnAbaR islands in 196 epidemiologically unrelated Acinetobacter strains representative of ≥19 species were performed. The first two Acinetobacter baumannii ISAba11 elements identified had been found to map to the same site on TnAbaR transposons. However, no further evidence of physical linkage between the two elements was demonstrated. Indeed, examination of 25 definite or putative insertion sites suggested limited sequence specificity. Importantly, an aacC1-tagged version of ISAba11 was shown to actively transpose in A. baumannii. Similarity searches identified nine iso-ISAba11 elements in Acinetobacter and one in Enhydrobacter and single representatives of four distant homologs in bacteria belonging to the phyla "Cyanobacteria" and Proteobacteria. Phylogenetic, sequence, and structural analyses of ISAba11 and/or its associated transposase (Tnp(ISAba11)) suggested that these elements be assigned to a new family. All five homologs encode transposases with a shared extended signature comprising 16 invariant residues within the N2, N3, and C1 regions, four of which constituted the cardinal ISAba11 family HHEK motif that is substituted for the YREK DNA binding motif conserved in the IS4 family. Additionally, ISAba11 family members were associated with either no flanking direct repeat (DR) or an ISAba11-typical 5-bp DR and possessed variable-length terminal inverted repeats that exhibited extensive intrafamily sequence identity. Given the limited pairwise identity among Tnp(ISAba11) homologs and the observed restricted distribution of ISAba11, we propose that substantial gaps persist in the evolutionary record of ISAba11 and that this element represents a recent though potentially highly significant entrant into the A. baumannii gene pool.


3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial.
Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13-0·34). Liraglutide induced greater weight loss than placebo at week 160 (-6·1 [SD 7·3] vs -1·9% [6·3]; estimated treatment difference -4·3%, 95% CI -4·9 to -3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Novo Nordisk, Denmark.


A framework for assessment and monitoring of small mammals in a lowland tropical forest.
Development projects in tropical forests can impact biodiversity. Assessment and monitoring programs based on the principles of adaptive management assist managers to identify and reduce such impacts. The small mammal community is one important component of a forest ecosystem that may be impacted by development projects. In 1996, a natural gas exploration project was initiated in a Peruvian rainforest. The Smithsonian Institution's Monitoring and Assessment of Biodiversity program cooperated with Shell Prospecting and Development Peru to establish an adaptive management program to protect the region's biodiversity. In this article, we discuss the role of assessing and monitoring small mammals in relation to the natural gas project. We outline the conceptual issues involved in establishing an assessment and monitoring program, including setting objectives, evaluating the results and making appropriate decisions. We also summarize the steps taken to implement the small mammal assessment, provide results from the assessment and discuss protocols to identify appropriate species for monitoring.


Disorders of consciousness and communication. Ethical motivations and communication-enabling attributes of consciousness.
Envisaged extensions of a functional magnetic resonance imaging (fMRI) technique allowing communication with patients affected by disorders of consciousness are here examined in connection with subjective symptom reporting, informed consent, and continued medical care decision-making. The principles of medical beneficence, personal autonomy protection, and the right to participate in social life are isolated as appropriate sources of ethical motivations for the use of fMRI-enabled communication. Consciousness requirements for each communication context are identified on the basis of qualitative distinctions between the access, phenomenal, and narrative varieties of consciousness. Ethically motivated uses of fMRI-enabled communication are hierarchically organized in terms of progressively more demanding consciousness requirements for successful communication. The outcomes of this analysis can be used to curb unrealistic expectations of these new scientific developments, and to promote mutual trust between medical doctors, patient surrogates and families.


Prevalence of muscular dystrophy in patients with muscular disorders in Tehran, Iran.
Muscular dystrophy is a group of diseases that is characterized by progressive muscle wasting and the weakness of variable distribution and severity. On the basis of the distribution of predominant muscle weakness, there are many different kinds of muscular dystrophy. Some dystrophies are especially frequent in certain populations. There are no studies on the prevalence of muscular dystrophy in Iran. This study was aimed to survey the prevalence of muscular dystrophy among Iranian patients with muscular disorders. This analytical cross-sectional study was conducted on 1000 patients with musculoskeletal disorders who visited the dystrophy association of Bou-Ali Hospital (Tehran) from June 2014 to June 2016. Patients' data were extracted using a checklist that included age, gender, age of onset, family history, findings from clinical diagnostic tests and types of muscular dystrophy. The clinical findings were the results of genetic tests; EMG-NCV; para-clinical findings, including LDH and CPK; and pathological findings. All data were analyzed by SPSS V.22 (IBM Inc., NY) with Chi Square and One way ANOVA tests. All analyses were performed with P = 0.05 considered as the threshold of statistical significant. Out of the 337 patients studied, 262 (77.7%) were male and 75 (22.3%) were female. Subjects had a mean (± SD) age of 26.08 (± 11.86) years with an age range of 3 to 59 years. The most common types of muscular dystrophy were found to be Duchenne dystrophy (131 cases, 38.9%), limb-girdle dystrophy (91 cases, 27%), Becker dystrophy (58 cases, 17.2%), FSHD dystrophy (31 cases, 9.2%), and SMA (26 cases, 7.7%), respectively. The results showed that a statistically significant relationship between dystrophy types and gender, age, family history, age of diagnosis, CPK and LDH levels (P < 0.001). There were no statistical relationship between dystrophy types and pathological findings (P = 0.57), EMG-NCV test results (P = 0.062), and genetic findings (P = 0.06). Since muscular dystrophies often appear during the first decade of life, any information in regard to their prevalence can contribute to better planning and provisioning of required services, as well as better treatment or control of the condition. The results also showed that genetic tests, para-clinical tests, pathology analysis, and EMG-NCV tests can serve as good diagnostic tools for different varieties of dystrophy. Thus, facilitation of these diagnostic tests, particularly the genetic tests, can lead to a faster and more accurate diagnosis of dystrophy, especially in people with a family history of the disease.


Endogenous retroviruses in systemic response to stress signals.
Infection of germline cells with retroviruses initiates permanent proviral colonization of the germline genome. The germline-integrated proviruses, called endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order and belong to the transposable element family. Endogenous retroviruses and other long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse genomes, respectively. It is likely that each individual has a distinct genomic ERV profile. Recent studies have revealed that a substantial fraction of ERVs retains the coding potentials necessary for virion assembly and replication. There are several layers of potential mechanisms controlling ERV expression: intracellular transcription environment (e.g., transcription factor pool, splicing machinery, hormones), epigenetic status of the genome (e.g., proviral methylation, histone acetylation), profile of transcription regulatory elements on each ERV's promoter, and a range of stress signals (e.g., injury, infection, environment). Endogenous retroviruses may exert pathophysiologic effects by infection followed by random reintegration into the genome, by their gene products (e.g., envelope, superantigen), and by altering the expression of neighboring genes. Several studies have provided evidence that ERVs are associated with a range of pathogenic processes involving multiple sclerosis, systemic lupus erythematosus, breast cancer, and the response to burn injury. For instance, the proinflammatory properties of the human ERV-W envelope protein play a central role in demyelination of oligodendrocytes. As reviewed in this article, recent advances in ERV biology and mammalian genomics suggest that ERVs may have a profound influence on various pathogenic processes including the response to injury and infection. Understanding the roles of ERVs in the pathogenesis of injury and infection will broaden insights into the underlying mechanisms of systemic immune disorder and organ failure in these patients.


Homozygosity for moyamoya disease risk allele leads to moyamoya disease with extracranial systemic and pulmonary vasculopathy.
Moyamoya disease is characterized by diffuse distal intracranial stenosis. Recently, RNF213 has been identified as a susceptibility gene in the development of this condition. Pulmonary hypertension is a rare progressive vasculopathy with an unknown etiology. The co-occurrence of pulmonary hypertension and Moyamoya disease has been described in four patients; however, whether this co-occurrence represents a chance association or a common vascular pathology has remained unknown. Here, we report two unrelated male patients who presented during their childhood with dyspnea on exertion. Systemic vascular imaging studies revealed the presence of pulmonary hypertension and Moyamoya disease in both patients. Medical exome sequencing revealed that both patients had a homozygous mutation for p.Arg4810Lys in RNF213. We suggest that homozygosity in RNF213 may lead to a novel entity involving the brain and lung. Interestingly, when present in a heterozygous state, this mutation causes a classic cerebral vascular disease, Moyamoya disease. In the homozygous state, the exact same mutation led to Moyamoya disease with extracranial systemic vasculopathy in at least two patients. From a clinical standpoint, cerebrovascular or pulmonary vascular investigations may be warranted in patients with pulmonary hypertension or Moyamoya disease, respectively. © 2016 Wiley Periodicals, Inc.


Effects of topical human amniotic fluid and human serum in a mouse model of keratoconjunctivitis sicca.
To compare the effects of topical human amniotic fluid (HAF), topical human serum (HS), and topical artificial tears in a mouse model of dry eye. Thirty C57BL/6 mice were divided into 3 treatment groups: HAF, HS, and preservative-free artificial tears. Dry eye was induced by an injection of botulinum toxin B (BTX-B) into the lacrimal gland. Tear production and ocular surface fluorescein staining were evaluated in each mouse at 6 time points during a 4-week period. Goblet cell density was assessed in stained histological sections. Apoptotic keratocytes were evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling test assay. A significant decrease in tear production was observed 3 days after BTX-B injection in all groups. At week 1, the HAF and HS groups had improved tear production compared with the control group (P < 0.001 and P = 0.003, respectively). HAF had a significantly improved fluorescein staining score compared with the HS (P = 0.043) and control (P = 0.007) groups at week 2. Goblet cell density was significantly decreased in the control group compared with the HAF and HS groups (P < 0.001). No difference in the amount of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive keratocytes was observed among the groups. HAF was superior to HS and artificial tears for improving corneal staining within 2 weeks of therapy in this induced mouse model of keratoconjunctivitis sicca. Clinical studies are needed to ascertain the benefits of these therapies in patients with ocular surface disorders associated with dry eye.


Depression burden, self-help interventions, and side effect experience in women receiving treatment for breast cancer.
To describe effects of a set of Self-Help Intervention Project (SHIP) interventions with self-reported depression burden on the side effect experience of women receiving treatment for breast cancer. Repeated measures, experimental design. Outpatient sites at a regional cancer center, private practices, and health maintenance organizations. 169 women who completed data at all three data-collection points were used to answer the research questions. Following random assignment, individuals in the treatment group participated in five different, but complementary, self-help interventions for six weeks. The control group received the usual care. Variables were measured at baseline after radiation, chemotherapy, or hormone therapies were started to allow for the side effects to emerge at six to eight weeks after treatment and three months following time 2. Depression burden, fatigue burden, pain burden, nausea burden, difficulty concentrating burden, anxiety burden, number of side effects, severity of side effects, and participation in the interventions. Self-reported depression burden was found to significantly influence severity of side effects, number of side effects, and the burdens of fatigue, difficulty concentrating, and anxiety. Depression burden did not significantly influence the side effect burdens of nausea or pain. Depression burden interacted with the self-help interventions over time for the side effect of fatigue, but the intervention effect on pain burden and nausea burden was not influenced by depression burden over time. No significant intervention effects were found for the burden of difficulty concentrating or anxiety, the number of side effects, or perceived severity of side effects. The interventions significantly reduced the fatigue, pain, and nausea burden in women with breast cancer. The interventions were particularly helpful, relative to their fatigue experience, for women reporting a high level of depression burden. Findings also contribute to conceptual clarification of essential aspects of the side effect experience and provide a basis for measure and intervention refinement. Every woman who is undergoing cancer treatment should be assessed for depression and depression burden. Self-help interventions are effective and convenient treatments that reduce side effects and promote quality of life in women with breast cancer.


Thought suppression induces intrusion in naturally occurring negative intrusive thoughts.
It has been hypothesized that personally relevant negative intrusive thoughts may be the direct precursors of obsessional thinking. Efforts made to suppress or neutralize are said to be involved in the transition between 'normal' and 'abnormal' intrusive thoughts. In order to test this hypothesis, naturally occurring intrusive thoughts were identified in non-clinical subjects, some of whom were asked to suppress these thoughts during an experimental period. The occurrence and characteristics of the target intrusive thoughts during suppression and a subsequent non-suppression period were assessed. The results indicate that (i) suppression can result in increased intrusion; and (ii) that distraction can play an important moderating role. It is suggested that, in suppression experiments, the effects of self-monitoring per se may have been underestimated. Motivated and intrusion-focussed monitoring of consciousness may be as important as suppression, given that obsessional patients tend to be constantly vigilant for the occurrence of obsessional thinking.


Defining how multiple lipid species interact with inward rectifier potassium (Kir2) channels.
Protein-lipid interactions are a key element of the function of many integral membrane proteins. These potential interactions should be considered alongside the complexity and diversity of membrane lipid composition. Inward rectifier potassium channel (Kir) Kir2.2 has multiple interactions with plasma membrane lipids: Phosphatidylinositol (4, 5)-bisphosphate (PIP2) activates the channel; a secondary anionic lipid site has been identified, which augments the activation by PIP2; and cholesterol inhibits the channel. Molecular dynamics simulations are used to characterize in molecular detail the protein-lipid interactions of Kir2.2 in a model of the complex plasma membrane. Kir2.2 has been simulated with multiple, functionally important lipid species. From our simulations we show that PIP2 interacts most tightly at the crystallographic interaction sites, outcompeting other lipid species at this site. Phosphatidylserine (PS) interacts at the previously identified secondary anionic lipid interaction site, in a PIP2 concentration-dependent manner. There is interplay between these anionic lipids: PS interactions are diminished when PIP2 is not present in the membrane, underlining the need to consider multiple lipid species when investigating protein-lipid interactions.


Unravelling bacteriophage ϕ11 requirements for packaging and transfer of mobile genetic elements in Staphylococcus aureus.
Bacteriophages play a major role in spreading mobile genetic elements (MGEs)-encoded genes among bacterial populations. In spite of this, the molecular requirements for building phage transducing particles have not been completely deciphered. Here, we systematically inactivated each ORF from the packaging and lysis modules of the staphylococcal phage ϕ11, used as a model for the Siphoviridae phages infecting Gram-positive bacteria, and determined their functional role in transferring different MGEs including plasmids, staphylococcal pathogenicity islands (SaPIs) and the phage itself. In a previous report, we identified seven of these ORFs as being required for the production of functional phage or SaPI particles. In this report, we have completed the mutational analysis and have identified and characterized 15 additional phage-encoded proteins required for the production of mature phage, SaPI, or transducing particles. Apart from these, we have not yet ascertained any specific function for the six remaining ϕ11 genes, though they are highly conserved among the staphylococcal bacteriophages. To the best of our knowledge, this study represents the first systematic deletion analysis of all the ORFs comprising the morphogenetic and lysis modules of a phage, clearly defining the molecular requirements involved in phage-mediated MGEs transfer.


Mechanisms of Drug Deposition in Hair and Issues for Hair Testing.
The purpose of this review is to provide a summary of the knowledge of the mechanisms by which drugs deposit into hair. While much work and many reviews have been produced on methods of analysis of drugs in hair, a smaller body of work and fewer reviews have concentrated on the biochemical mechanisms by which drugs deposit and are retained in hair. Proposed mechanisms are discussed with various studies that have been used to elucidate these mechanisms. While multiple mechanisms are likely involved in the deposition and retention of drugs in hair, melanin and various interactions with melanin including potential covalent linkage of drug with melanin appear to dominate the scheme of interactions. The implications of these interactions are discussed with particular emphasis on the potential difficulties in distinguishing internal deposition from external contamination and the appropriateness of manufacturing control materials. The potential for hair testing to be truly reflective of endogenous deposition may hinge on the ability to isolate and analyze melanin adducts of drugs that would be indicative of endogenous drug deposition during hair growth and active melanogenesis.


Recruitment, retention, and compliance results from a probability study of children's environmental health in economically disadvantaged neighborhoods.
The School Health Initiative: Environment, Learning, and Disease (SHIELD) study used a probability sample of children (second through fifth grades) from two low-income and racially mixed neighborhoods of Minneapolis, Minnesota, to assess childhood environmental health. Children were eligible to participate in SHIELD regardless of whether they or their families spoke a foreign language, their household had a telephone, or they were enrolled in a special education program. The overall enrollment rate in year 1 was 57%, with a substantial disparity between children from English-speaking (42%) versus non-English-speaking (71%) families. At the end of year 1, 85% were retained in the study. A relatively high percentage of children provided the two requested blood (82%) and urine (86%) samples in year 1, and 90% provided a valid spirometry sample. Eighty-two percent provided both requested volatile organic chemical badge samples, and both time-activity logs were obtained from 66%. However, only 32% provided both peak flow measurements. All percentages increased for those participating in the second year of the study. Results indicate that a school-based research design makes it feasible and practical to conduct probability-based assessments of children's environmental health in economically disadvantaged and ethnically diverse neighborhoods. There is an ongoing need, however, to improve understanding of the cultural, economic, psychologic, and social determinants of study participation among this population.


Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries.
Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 - 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest-of-the-world (RoW). Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 ± 3.4 mSv (RoW 11.4 ± 4.3 mSv; P < 0.001) and of PET was 2.6 ± 1.5 mSv (RoW 3.8 ± 2.5 mSv; P < 0.001). The mean effective doses of SPECT and PET differed between European regions (P < 0.001 and P = 0.002, respectively). The mean quality score was 6.2 ± 1.2, which was higher than the RoW score (5.0 ± 1.1; P < 0.001). Adherence to best practices did not differ significantly among the European regions (range 6 to 6.4; P = 0.73). Of the best practices, stress-only imaging and weight-adjusted dosing were the least commonly used. In Europe, the mean effective dose from nuclear cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in relation to the best practice quality score. A possible reason for the differences between Europe and the RoW could be the safety culture fostered by actions under the Euratom directives and the implementation of diagnostic reference levels. Stress-only imaging and weight-adjusted activity might be targets for optimization of European nuclear cardiology practice.


Reclining chairs reduce pain from gurneys in older emergency department patients: a randomized controlled trial.
Pain related to the gurney is a frequent complaint of older emergency department (ED) patients. The authors hypothesized that these patients may have less pain and higher satisfaction if allowed to sit in a reclining hospital chair. A single-blind, randomized controlled trial was performed. Patients 65 years old or older who were able to sit upright, transfer, and engage in normal conversation were eligible. Severely ill or cognitively impaired patients were excluded. Patients were randomized to either remain on the gurney or transfer to the chair after initial evaluation. Patients reported pain at arrival (t0), at one hour (t1), and at two hours (t2) using a 0-10 pain scale, and satisfaction at study completion on a 0-10 scale. The primary outcome was a decrease in pain between t0 and t1 or no pain at both t0 and t1. This outcome was analyzed using a 95% confidence interval for the difference between proportions; exclusion of zero was considered significant. Sixty-six patients in each group were enrolled. There was no difference in demographics between groups, but the chair patients were more likely to have pain at t0 than the gurney patients. More chair patients than gurney patients had a successful primary outcome (97% vs. 76%, 21% difference, 95% CI=10% to 32%). The mean satisfaction score was higher in the chair group than in the gurney group (8.1 vs. 6.0, 2.1 difference, 95% CI=1.4% to 2.8%). The simple modification of allowing older ED patients to sit in reclining chairs resulted in less pain and higher satisfaction.


Genome-wide comparative analysis of metacaspases in unicellular and filamentous cyanobacteria.
Cyanobacteria are an ancient group of photoautotrophic prokaryotes with wide variations in genome size and ecological habitat. Metacaspases (MCAs) are cysteine proteinases that have sequence homology to caspases and play essential roles in programmed cell death (PCD). MCAs have been identified in several prokaryotes, fungi and plants; however, knowledge about cyanobacterial metacaspases still remains obscure. With the availability of sequenced genomes of 33 cyanobacteria, we perform a comparative analysis of metacaspases and explore their distribution, domain structure and evolution. A total of 58 putative MCAs were identified, which are abundant in filamentous diazotrophic cyanobacteria and Acaryochloris marina MBIC 11017 and absent in all Prochlorococcus and marine Synechococcus strains, except Synechococcus sp. PCC 7002. The Cys-His dyad of caspase superfamily is conserved, while mutations (Tyr in place of His and Ser/Asn/Gln/Gly instead of Cys) are also detected in some cyanobacteria. MCAs can be classified into two major families (alpha and beta) based on the additional domain structure. Ten types and a total of 276 additional domains were identified, most of which involves in signal transduction. Apoptotic related NACHT domain was also found in two cyanobacterial MCAs. Phylogenetic tree of MCA catalytic P20 domains coincides well with the domain structure and the phylogenies based on 16s rRNA. The existence and quantity of MCA genes in unicellular and filamentous cyanobacteria are a function of the genome size and ecological habitat. MCAs of family alpha and beta seem to evolve separately and the recruitment of WD40 additional domain occurs later than the divergence of the two families. In this study, a general framework of sequence-structure-function connections for the metacaspases has been revealed, which may provide new targets for function investigation.


Cost-effectiveness analysis of periacetabular osteotomy.
A lack of long-term outcomes data following periacetabular osteotomy makes it difficult for surgeons to recommend the most appropriate procedure to young patients who might be candidates for a joint-preserving procedure. In this study, we compared the cost-effectiveness of periacetabular osteotomy with total hip arthroplasty in terms of cost per quality-adjusted life year for the young adult. A decision model was constructed for a cost-utility analysis of periacetabular osteotomy compared with total hip arthroplasty. Outcome probabilities and effectiveness were derived from the literature. Effectiveness was expressed in quality-adjusted life years gained. Cost data were compiled and verified from our institution. Costs and utilities were discounted in accord with the United States Panel on Cost-Effectiveness in Health and Medicine. Principal outcome measures were average incremental costs, incremental effectiveness, incremental quality-adjusted life years, and net health benefits. Multivariate sensitivity analysis was used to assess the contribution of included variables in the model's outcomes. For Tönnis grade-1 coxarthrosis, periacetabular osteotomy dominates with an average incremental cost-effectiveness of $7856 per quality-adjusted life year and an average incremental effectiveness of 0.15. For Tönnis grade-2 coxarthrosis, periacetabular osteotomy is, on the average, more cost-effective than total hip arthroplasty with an incremental cost-effectiveness of $824 per quality-adjusted life year, but it is less effective than total hip arthroplasty, on the average, with an incremental effectiveness of -1.4 quality-adjusted life years. Periacetabular osteotomy becomes more cost-effective at a longevity of 5.5 years for Tönnis grade-1 coxarthrosis and 18.25 years for Tönnis grade-2 coxarthrosis. In Tönnis grade-3 coxarthrosis, total hip replacement becomes the dominant treatment strategy. Periacetabular osteotomy is, on the average, more cost-effective in Tönnis grade-1 and grade-2 coxarthrosis, while it is both more costly and less effective in Tönnis grade-3 coxarthrosis. These findings can inform clinical decision-making in the absence of long-term data. On the basis of this model, periacetabular osteotomy is preferable to total hip arthroplasty in Tönnis grade-1 and grade-2 coxarthrosis when the patient is sufficiently young and when functionality in sports is important.


Is visual evaluation of aneurysm coiling a reliable study end point? Systematic review and meta-analysis.
Angiographic occlusion as a surrogate marker of satisfactory aneurysm treatment is commonly used in clinical trials although some pitfalls have to be considered. To investigate the inter-rater reliability of visual rating of aneurysm occlusion as study end point, we performed a systematic review and meta-analysis. Electronic databases (MEDLINE, EMBASE, PubMed, and the Cochrane Library) were searched up to June 2014. Assessment of risk for bias was based on the Quality Appraisal Tool for Studies of Diagnostic Reliability and the Guidelines for Reporting Reliability and Agreement studies. Inter-rater reliability estimates were pooled across studies using meta-analysis, and the influence of several factors (eg, imaging methods, grading scales, and occlusion rate) was tested with meta-regression. From 1193 titles, 644 abstracts and 87 full-text versions were reviewed. Twenty-six articles met the inclusion criteria and provided 77 reliability estimates. Twenty-one different rating scales were used, and statistical analysis varied. Mean inter-rater agreement of the pooled studies was substantial (κ=0.65; 95% confidence interval, 0.60-0.69). Reliability varied significantly as a function of imaging methods, grading scales, occlusion rates, and their interaction. Observer agreement substantially increased with increasing occlusion rate in digital subtraction angiography but not in MR angiography. Reliability was higher in studies using 2- or 3-value grading scales than in studies with 4-value grading scales. There is significant heterogeneity between studies evaluating the reliability of visual evaluation of aneurysm coiling. On the basis of our analysis, we found that the combination of magnetic resonance angiography, 3-value grading scale, and 2 trained raters seems most promising for usage as surrogate study end points.


[Remote sensing monitoring and pre-alarming of algal blooms in Taihu Lake].
The explosive growth of algae in inland water bodies is one of the major water environmental problems in China, and it's very important to monitor the dynamic of algae in both temporal and spatial scales. In the present paper, a model, which was used to extract the algae information from the water body of Taihu Lake using MODIS data, was established based on the remote sensing index and image false color composite methods. Using this model, we studied the algae explosive growth formation process between March and May in 2007. Through the analysis of the temporal and spatial distribution features of the algae outbreak between the spring and summer seasons, an early warning method of algal blooms was proposed, that is, when the MODIS green index mainly concentrated in the range between 0. 6 and 0. 8, the water body of Taihu Lake can be considered to have been in the early alarming stage of algal blooms.


Stepping Into and Out of the Void: Funding Dynamics of Human Embryonic Stem Cell Research in California, Sweden, and South Korea.
Nonprofit organizations and philanthropists stepped into a funding void caused by controversies over public funding of human embryonic stem cell (hESC) research. Based on interviews of 83 representatives of 53 funders, we examine the motivations and accountability structures of public agencies, corporations, fundraising dependent nonprofit organizations and philanthropic organizations that funded hESC research in three jurisdictions: California, Sweden, and South Korea. While non-traditional forms of funding are essential in the early stages of research advancement, they are unreliable for the long timeframes necessary to advance cell therapies. Such funding sources may enter the field based on high expectations, but may exit just as rapidly based on disappointing rates of progress.


Dimorphic effects of transforming growth factor-β signaling during aortic aneurysm progression in mice suggest a combinatorial therapy for Marfan syndrome.
Studies of mice with mild Marfan syndrome (MFS) have correlated the development of thoracic aortic aneurysm (TAA) with improper stimulation of noncanonical (Erk-mediated) TGFβ signaling by the angiotensin type I receptor (AT1r). This correlation was largely based on comparable TAA modifications by either systemic TGFβ neutralization or AT1r antagonism. However, subsequent investigations have called into question some key aspects of this mechanism of arterial disease in MFS. To resolve these controversial points, here we made a head-to-head comparison of the therapeutic benefits of TGFβ neutralization and AT1r antagonism in mice with progressively severe MFS (Fbn1(mgR/mgR) mice). Aneurysm growth, media degeneration, aortic levels of phosphorylated Erk and Smad proteins and the average survival of Fbn1(mgR/mgR) mice were compared after a ≈3-month-long treatment with placebo and either the AT1r antagonist losartan or the TGFβ-neutralizing antibody 1D11. In contrast to the beneficial effect of losartan, TGFβ neutralization either exacerbated or mitigated TAA formation depending on whether treatment was initiated before (postnatal day 16; P16) or after (P45) aneurysm formation, respectively. Biochemical evidence-related aneurysm growth with Erk-mediated AT1r signaling, and medial degeneration with TGFβ hyperactivity that was in part AT1r dependent. Importantly, P16-initiated treatment with losartan combined with P45-initiated administration of 1D11 prevented death of Fbn1(mgR/mgR) mice from ruptured TAA. By demonstrating that promiscuous AT1r and TGFβ drive partially overlapping processes of arterial disease in MFS mice, our study argues for a therapeutic strategy against TAA that targets both signaling pathways although sparing the early protective role of TGFβ.


Seeing with the eyes shut: neural basis of enhanced imagery following Ayahuasca ingestion.
The hallucinogenic brew Ayahuasca, a rich source of serotonergic agonists and reuptake inhibitors, has been used for ages by Amazonian populations during religious ceremonies. Among all perceptual changes induced by Ayahuasca, the most remarkable are vivid "seeings." During such seeings, users report potent imagery. Using functional magnetic resonance imaging during a closed-eyes imagery task, we found that Ayahuasca produces a robust increase in the activation of several occipital, temporal, and frontal areas. In the primary visual area, the effect was comparable in magnitude to the activation levels of natural image with the eyes open. Importantly, this effect was specifically correlated with the occurrence of individual perceptual changes measured by psychiatric scales. The activity of cortical areas BA30 and BA37, known to be involved with episodic memory and the processing of contextual associations, was also potentiated by Ayahuasca intake during imagery. Finally, we detected a positive modulation by Ayahuasca of BA 10, a frontal area involved with intentional prospective imagination, working memory and the processing of information from internal sources. Therefore, our results indicate that Ayahuasca seeings stem from the activation of an extensive network generally involved with vision, memory, and intention. By boosting the intensity of recalled images to the same level of natural image, Ayahuasca lends a status of reality to inner experiences. It is therefore understandable why Ayahuasca was culturally selected over many centuries by rain forest shamans to facilitate mystical revelations of visual nature.


Non-asbestos-related malignant pleural mesothelioma.
Malignant pleural mesothelioma (MPM) is an uncommon tumor derived from mesothelial lining cells. MPM has been described as an insidious neoplasm because of its long latency period. The tumor is typically found in patients several decades after asbestos exposure. We herein describe a 26-year-old patient with MPM who presented with pleural effusion. The patient had not been exposed to asbestos or erionite. There are few case reports of non-asbestos-related MPM in young patients. We report this case to remind physicians to consider MPM in the differential diagnosis of pleural effusion in young patients without exposure to asbestos or erionitis.


The smell of environmental change: Using floral scent to explain shifts in pollinator attraction.
As diverse environmental changes continue to influence the structure and function of plant-pollinator interactions across spatial and temporal scales, we will need to enlist numerous approaches to understand these changes. Quantitative examination of floral volatile organic compounds (VOCs) is one approach that is gaining popularity, and recent work suggests that floral VOCs hold substantial promise for better understanding and predicting the effects of environmental change on plant-pollinator interactions. Until recently, few ecologists were employing chemical approaches to investigate mechanisms by which components of environmental change may disrupt these essential mutualisms. In an attempt to make these approaches more accessible, we summarize the main field, laboratory, and statistical methods involved in capturing, quantifying, and analyzing floral VOCs in the context of changing environments. We also highlight some outstanding questions that we consider to be highly relevant to making progress in this field.


Magnetic resonance imaging: improved patient tolerance utilizing medical hypnosis.
Magnetic Resonance Imaging (MRI) is a medical diagnostic procedure which requires a patient to be placed supine into the cylindrical bore of a powerful magnet for approximately one hour. The patient's arms are usually against the sides of the magnet bore with a 3" to 10" space between the patient's face and the top of the magnet bore. This enclosure induces panic and claustrophobic responses in 1% to 10% of the patients undergoing the MRI procedure. There have been many failed diagnostic studies due to patient intolerance, and there are reports of procedure-induced claustrophobia. We describe the hypnotic procedure utilized to reduce anxiety and panic for successful completion of MRI scans. Medical hypnosis has been an effective intervention in ten patients, permitting completion of their diagnostic procedure.


The Daily Relationship Between Aspects of Food Insecurity and Medication Adherence Among People Living with HIV with Recent Experiences of Hunger.
Limited access to resources can significantly impact health behaviors. Previous research on food insecurity and HIV has focused on establishing the relationship between lacking access to nutritious food and antiretroviral (ARV) medication non-adherence in a variety of social contexts. This study aims to determine if several aspects of food insecurity co-occur with missed doses of medication on a daily basis among a sample of people living with HIV who have recently experienced hunger. The current study utilized a prospective, observational design to test the daily relationship between food insecurity and medication non-adherence. Participants were followed for 45 days and completed daily assessments of food insecurity and alcohol use via interactive text message surveys and electronic medication adherence monitoring using the Wisepill. Fifty-nine men and women living with HIV contributed a total of 2,655 days of data. Results showed that severe food insecurity (i.e., hunger), but not less severe food insecurity (i.e., worrying about having food), significantly predicted missed doses of medication on a daily level. Daily alcohol use moderated this relationship in an unexpected way; when individuals were hungry and drank alcohol on a given day, they were less likely to miss a dose of medication. Among people living with HIV with recent experiences of hunger, this study demonstrates that there is a daily relationship between hunger and non-adherence to antiretroviral therapy. Future research is needed to test interventions designed to directly address the daily relationship between food insecurity and medication non-adherence.


The pregnane X receptor regulates gene expression in a ligand- and promoter-selective fashion.
Recent studies have revealed that pregnane X receptor (PXR) can function as a master regulator to control the expression of phase I and phase II drug-metabolizing enzymes, as well as members of the drug transporter family, including multiple drug resistance (MDR) 1, which has a major role in multidrug resistance. Previously, we have demonstrated that steroid/xenobiotics metabolism by tumor tissue through the PXR-cytochrome P-450 3A (CYP3A) pathway might play an important role in endometrial cancer. In this study, we examined which endocrine-disrupting chemicals (EDCs) and anticancer agents might be ligands for PXR and whether these chemicals enhanced PXR-mediated transcription through two different PXR-responsive elements (PXREs), CYP3A4 and MDR1, in endometrial cancer cell lines. Some steroids/EDCs strongly activated PXR-mediated transcription through the CYP3A4-responsive element compared with the MDR1-responsive element, whereas these steroids/EDCs also enhanced the CYP3A4 expression compared with the MDR1 expression. In contrast, the anticancer agents, cisplatin and paclitaxel, strongly activated PXR-mediated transcription through the MDR1-responsive element compared with the CYP3A4-responsive element, whereas these drugs also enhanced the MDR1 expression compared with the CYP3A4 expression. We also analyzed how these ligands regulated PXR-mediated transcription through two different PXREs. In the presence of PXR ligands, there was no difference in the DNA binding affinity of the PXR/retinoid X receptor heterodimer to each PXRE, but there were different interactions of the coactivator to each PXR/PXRE complex. These data suggested that PXR ligands enhanced PXR-mediated transcription in a ligand- and promoter-dependent fashion, which in turn differentially regulated the expression of individual PXR targets, especially CYP3A4 and MDR1.


Association between hyperglycemia at admission during hospitalization for acute myocardial infarction and subsequent diabetes: insights from the veterans administration cardiac care follow-up clinical study.
Among patients with acute myocardial infarction (AMI) without known diabetes, hyperglycemia at admission is common and associated with worse outcomes. It may represent developing diabetes, but this association is unclear. Therefore, we examined the association between hyperglycemia (≥140 mg/dL) at admission and evidence of diabetes among patients with AMI without known diabetes within 6 months of their hospitalization. We studied a national cohort of consecutive patients with AMI without known diabetes presenting at 127 Veterans Affairs hospitals between October 2005 and March 2011. Evidence of diabetes either at discharge or in the following 6 months was ascertained using diagnostic codes, medication prescriptions, and/or elevated hemoglobin A1c. Association between hyperglycemia at admission and evidence of diabetes was evaluated using regression modeling. Among 10,499 patients with AMI without known diabetes, 98% were men and 1,761 (16.8%) had hyperglycemia at admission. Within 6 months following their index hospitalization, 208 patients (11.8%) with hyperglycemia at admission had evidence of diabetes compared with 443 patients (5.1%) without hyperglycemia at admission (P < 0.001). After multivariable adjustment, hyperglycemia at admission was significantly associated with subsequent diabetes odds ratio 2.56 (95% CI 2.15-3.06). Among those with new evidence of diabetes, 41% patients (267 of 651) had a hemoglobin A1c ≥6.5% without accompanying diagnostic codes or medication prescriptions, suggesting they had unrecognized diabetes. Hyperglycemia at admission occurred in one of six patients with AMI without known diabetes and was significantly associated with new evidence of diabetes in the 6 months following hospitalization. In addition, two of five patients with evidence of diabetes were potentially unrecognized. Accordingly, diabetes-screening programs for hyperglycemic patients with AMI may be an important component of optimal care.


Conducting polymers and the bioanalytical sciences: new tools for biomolecular communication. A review.
This review covers the evolution of conducting polymers and their use in the bioanalytical sciences. It is the controlled dynamic behaviour of these unique materials that enables such diverse and high-level performance to be achieved. The construction and application of conducting polymers for use as biosensors are the particular emphasis of this paper. Biocompatibility is briefly discussed.


The Impacts of Climate Change on Ticks and Tick-Borne Disease Risk.
Ticks exist on all continents and carry more zoonotic pathogens than any other type of vector. Ticks spend most of their lives in the external environment away from the host and are thus expected to be affected by changes in climate. Most empirical and theoretical studies demonstrate or predict range shifts or increases in ticks and tick-borne diseases, but there can be a lot of heterogeneity in such predictions. Tick-borne disease systems are complex, and determining whether changes are due to climate change or other drivers can be difficult. Modeling studies can help tease apart and understand the roles of different drivers of change. Predictive models can also be invaluable in projecting changes according to different climate change scenarios. However, validating these models remains challenging, and estimating uncertainty in predictions is essential. Another focus for future research should be assessing the resilience of ticks and tick-borne pathogens to climate change.


Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain.
This report identifies evidence of partially functional cerebral regions in catastrophically injured brains. To study five patients in a persistent vegetative state (PVS) with different behavioural features, we employed [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET), MRI and magnetoencephalographic (MEG) responses to sensory stimulation. Each patient's brain expressed a unique metabolic pattern. In three of the five patients, co-registered PET/MRI correlate islands of relatively preserved brain metabolism with isolated fragments of behaviour. Two patients had suffered anoxic injuries and demonstrated marked decreases in overall cerebral metabolism to 30-40% of normal. Two other patients with non-anoxic, multifocal brain injuries demonstrated several isolated brain regions with relatively higher metabolic rates, that ranged up to 50-80% of normal. Nevertheless, their global metabolic rates remained <50% of normal. MEG recordings from three PVS patients provide clear evidence for the absence, abnormality or reduction of evoked responses. Despite major abnormalities, however, these data also provide evidence for localized residual activity at the cortical level. Each patient partially preserved restricted sensory representations, as evidenced by slow evoked magnetic fields and gamma band activity. In two patients, these activations correlate with isolated behavioural patterns and metabolic activity. Remaining active regions identified in the three PVS patients with behavioural fragments appear to consist of segregated corticothalamic networks that retain connectivity and partial functional integrity. A single patient who suffered severe injury to the tegmental mesencephalon and paramedian thalamus showed widely preserved cortical metabolism, and a global average metabolic rate of 65% of normal. The relatively high preservation of cortical metabolism in this patient defines the first functional correlate of clinical- pathological reports associating permanent unconsciousness with structural damage to these regions. The specific patterns of preserved metabolic activity identified in these patients do not appear to represent random survivals of a few neuronal islands; rather they reflect novel evidence of the modular nature of individual functional networks that underlie conscious brain function. The variations in cerebral metabolism in chronic PVS patients indicate that some cerebral regions can retain partial function in catastrophically injured brains.


Sequence of a staphylococcal gene, vat, encoding an acetyltransferase inactivating the A-type compounds of virginiamycin-like antibiotics.
The Staphylococcus aureus plasmids, pIP680 and pIP1156, which confer resistance to A-type compounds of virginiamycin-like antibiotics (Vml: streptogramin A, pristinamycin IIA, virginiamycin M) and to synergistic mixtures of the A and B compounds of Vml antibiotics, were shown to direct the modification of A-type compounds by acetylation. The vat gene, encoding the acetyltransferase modifying A-type compounds, was isolated from plasmid pIP680 and sequenced. This gene potentially encodes a 219-amino-acid (aa) protein, VAT, of 24 330 Da showing at least 38% aa identity with two chloramphenicol acetyltransferases encoded by cat genes isolated from Escherichia coli and Agrobacterium tumefaciens. Resistance to A-type compounds of Vml antibiotics conferred to S. aureus by vat was not expressed in E. coli, although a protein having a M(r) similar to that encoded by this gene was detected in E. coli minicells. The vat gene was detected by the polymerase chain reaction in two chromosomally located staphylococcal conjugative elements and in the conjugative plasmid, pIP1156, conferring resistance to A-type compounds.


Conditional cross-design synthesis estimators for generalizability in Medicaid.
While much of the causal inference literature has focused on addressing internal validity biases, both internal and external validity are necessary for unbiased estimates in a target population of interest. However, few generalizability approaches exist for estimating causal quantities in a target population that is not well-represented by a randomized study but is reflected when additionally incorporating observational data. To generalize to a target population represented by a union of these data, we propose a novel class of conditional cross-design synthesis estimators that combine randomized and observational data, while addressing their estimates' respective biases-lack of overlap and unmeasured confounding. These methods enable estimating the causal effect of managed care plans on health care spending among Medicaid beneficiaries in New York City, which requires obtaining estimates for the 7% of beneficiaries randomized to a plan and 93% who choose a plan, who do not resemble randomized beneficiaries. Our new estimators include outcome regression, propensity weighting, and double robust approaches. All use the covariate overlap between the randomized and observational data to remove potential unmeasured confounding bias. Applying these methods, we find substantial heterogeneity in spending effects across managed care plans. This has major implications for our understanding of Medicaid, where this heterogeneity has previously been hidden. Additionally, we demonstrate that unmeasured confounding rather than lack of overlap poses a larger concern in this setting.


Incorporation of rhodopsin in laterally structured supported membranes: observation of transducin activation with spatially and time-resolved surface plasmon resonance.
Rhodopsin-transducin coupling was used as an assay to investigate a laterally patterned membrane reconstituted with a receptor and its G protein. It served as a model system to show the feasibility to immobilize G protein-coupled receptors on solid supports and investigate receptor activation and interaction with G proteins by one-dimensional imaging surface plasmon resonance. Supported membranes were formed by the self-assembly of lipids and rhodopsin from detergent solution onto functionalized gold surfaces. They formed micrometer-sized alternating regions of pure fluid phospholipid bilayers separated by bilayers composed of an outer phospholipid leaflet on a gold-attached inner thiolipid. Rhodopsin was found to incorporate preferentially into the phospholipid bilayer regions, whereas transducin was uniformly distributed over the entire outer surface of the supported patterned membrane. The influence of rhodopsin on the dark binding of transducin to lipid membranes was described quantitatively and compared with previously published data. Coupling reactions with transducin resembled closely the native system, indicating that the native functionality of rhodopsin was preserved in the supported membranes. The spatially varying properties of the membranes resulted in a pattern of rhodopsin activity on the surface. This combination of techniques is very promising for the investigation of the lateral diffusion of transducin, can be extended to include signalling proteins downstream of the G protein, and may be applied to functional screening of other G protein-coupled receptors. In the future, it may also serve as a basis for constructing biosensors based on receptor proteins.


The gut bacterium Extibacter muris produces secondary bile acids and influences liver physiology in gnotobiotic mice.
Extibacter muris is a newly described mouse gut bacterium which metabolizes cholic acid (CA) to deoxycholic acid (DCA) via 7α-dehydroxylation. Although bile acids influence metabolic and inflammatory responses, few in vivo models exist for studying their metabolism and impact on the host. Mice were colonized from birth with the simplified community Oligo-MM12 with or without E. muris. As the metabolism of bile acids is known to affect lipid homeostasis, mice were fed either a low- or high-fat diet for eight weeks before sampling and analyses targeting the gut and liver. Multiple Oligo-MM12 strains were capable of deconjugating primary bile acids in vitro. E. muris produced DCA from CA either as pure compound or in mouse bile. This production was inducible by CA in vitro. Ursodeoxycholic, chenodeoxycholic, and β-muricholic acid were not metabolized under the conditions tested. All gnotobiotic mice were stably colonized with E. muris, which showed higher relative abundances after HF diet feeding. The presence of E. muris had minor, diet-dependent effects on Oligo-MM12 communities. The secondary bile acids DCA and surprisingly LCA and their taurine conjugates were detected exclusively in E. muris-colonized mice. E. muris colonization did not influence body weight, white adipose tissue mass, liver histopathology, hepatic aspartate aminotransferase, or blood levels of cholesterol, insulin, and paralytic peptide (PP). However, proteomics revealed shifts in hepatic pathways involved in amino acid, glucose, lipid, energy, and drug metabolism in E. muris-colonized mice. Liver fatty acid composition was substantially altered by dietary fat but not by E. muris.In summary, E. muris stably colonized the gut of mice harboring a simplified community and produced secondary bile acids, which affected proteomes in the liver. This new gnotobiotic mouse model can now be used to study the pathophysiological role of secondary bile acids in vivo.


Associations between Obesity and Adverse Childhood Experiences in the United States.
Background: Obesity leads to serious health consequences in children and is potentially associated with increased adverse childhood experiences (ACEs). Nationally representative studies examining associations between obesity and ACEs are lacking. Therefore, we aimed to determine the relationship between ACEs and childhood obesity. Methods: We performed a retrospective cross-sectional study of children 10-17 years of age, who participated in the 2018 National Survey of Children's Health (NSCH), a national population-based survey. Obesity was determined by CDC definitions using BMI calculated by the NSCH from self-reported height/weight. Logistic regression, adjusted for key sociodemographic factors, determined differences in rates of ACEs between children with obesity (BMI ≥95th percentile) and those without (BMI <95th percentile). Results: Weighted NSCH data included 29,696,808 children 10-17 years of age, 15% with obesity. Obesity was associated with having more ACEs compared to other children (p < 0.01). In adjusted analyses, children with obesity were more likely than other children to report most ACEs, including food/housing insecurity [adjusted odds ratio (aOR) 1.64, confidence interval (95% CI) 1.26-2.13], parental divorce [1.67 (1.32-2.13)], witnessing physical violence [1.49 (1.03-2.16)], be a victim of violence [1.99, (1.27-3.12)], or live with a person with drug/alcohol abuse [1.65, (1.24-2.2)]. Children with obesity were also more likely to report ≥4 ACEs compared to other children (p < 0.001). Conclusion: Children with obesity are more likely to report ACEs overall and have more ACEs compared to other children. Obesity negatively affects child health; in combination with ACEs, health outcomes of children may be disproportionately affected, highlighting the importance of preventive screening and social interventions in childhood.


Global report on preterm birth and stillbirth (6 of 7): ethical considerations.
Despite the substantial global burden of preterm and stillbirth, little attention has been given to the ethical considerations related to research and interventions in the global context. Ethical dilemmas surrounding reproductive decisions and the care of preterm newborns impact the delivery of interventions, and are not well understood in low-resource settings. Issues such as how to address the moral and cultural attitudes surrounding stillbirths, have cross-cutting implications for global visibility of the disease burden. This analysis identifies ethical issues impacting definitions, discovery, development, and delivery of effective interventions to decrease the global burden of preterm birth and stillbirth. This review is based on a comprehensive literature review; an ethical analysis of other articles within this global report; and discussions with GAPPS's Scientific Advisory Council, team of international investigators, and a community of international experts on maternal, newborn, and child health and bioethics from the 2009 International Conference on Prematurity and Stillbirth. The literature review includes articles in PubMed, Academic Search Complete (EBSCO), and Philosopher's Index with a range of 1995-2008. Advancements in discovery science relating to preterm birth and stillbirth require careful consideration in the design and use of repositories containing maternal specimens and data. Equally important is the need to improve clinical translation from basic science research to delivery of interventions, and to ensure global needs inform discovery science agenda-setting. Ethical issues in the development of interventions include a need to balance immediate versus long-term impacts--such as caring for preterm newborns rather than preventing preterm births. The delivery of interventions must address: women's health disparities as determinants of preterm birth and stillbirth; improving measurements of impact on equity in coverage; balancing maternal and newborn outcomes in choosing interventions; and understanding the personal and cross-cultural experiences of preterm birth and stillbirth among women, families and communities. Efforts to improve visibility, funding, research and the successful delivery of interventions for preterm birth and stillbirth face a number of ethical concerns. Thoughtful input from those in health policy, bioethics and international research ethics helped shape an interdisciplinary global action agenda to prevent preterm birth and stillbirth.


Robustness of analyses of imaging data.
Successful classifications of reflectance and vibrational data are to a large extent dependent upon robustness of input data. In this study, a well-known geostatistical approach, variogram analysis, was described and its robustness was assessed through comprehensive evaluation of 3,200 variogram settings. High-resolution hyperspectral imaging data were acquired from greenhouse maize plants, and the robustness (radiometric repeatability) of three variogram parameters (nugget, sill, and range) was examined when generated from imaging data collected from two different sets of plants and with imaging data collected on seven different days in two years. Robustness of variogram parameters was compared with average reflectance values in six spectral bands, three standard vegetation indices (NDVI, SI, and PRI), and PCA scores from principal component analysis.


Stereotactic fractionated radiotherapy and LINAC radiosurgery in the treatment of vestibular schwannoma-report about both stereotactic methods from a single institution.
To evaluate tumor control and side effects associated with radiosurgery (RS) and stereotactic fractionated radiotherapy (SFR) for vestibular schwannomas (VSs) in a group of patients treated at the same institution. Between May 1997 and June 2007, 115 consecutive cases of VS were treated in our department. The SFR group (47 patients), including larger tumors (maximum diameter >1.5 cm), received a total dose of 54 Gy at 1.8 Gy per fraction. The RS group (68 patients, maximum diameter <1.5 cm) received a total dose of 12 Gy at the 100% isodose. Evaluation included serial imaging tests (magnetic resonance imaging) and neurologic and functional hearing examinations. The tumor control rate was 97.9% in the SFR group for a mean follow-up time of 32.1 months and 98.5% in the RS group for a mean follow-up time of 30.1 months. Hearing function was preserved after RS in 85% of the patients and after SFR in 79%. Facial and trigeminal nerve function remained mostly unaffected after SFR. After RS, new trigeminal neuropathy occurred in 9 of 68 patients (13%). A high tumor control rate and low number of side effects are registered after SFR and RS of VS. These results confirm that considering tumor diameter, both RS and SFR are good treatment modalities for VS.


Advances in treatment techniques: arc-based and other intensity modulated therapies.
Treatment planning and radiation delivery techniques have advanced significantly during the past 2 decades. The development of the multileaf collimator has changed the scope of radiotherapy. The dynamic conformal arc technique emerged from traditional cone-based conformal arc therapies, which aim to improve target dose uniformity and reduce normal tissue doses. With dynamic conformal arc, the multileaf collimator aperture is shaped dynamically to conform to the target. With the advent of intensity-modulated radiotherapy (IMRT), the concept of arc therapy in combination with IMRT has enabled better-quality dose distributions and more efficient delivery. Helical tomotherapy has been developed to treat targets sequentially by modulating the beam intensity in each "slice" of the patient. Helical tomotherapy offers improved dose distributions for complicated treatments, such as whole-body radiation. Intensity-modulated arc therapy has been studied to modulate fluences in a cone beam rather than fan beam geometry to improve delivery efficiency. This article reviews arc-based IMRT, intensity-modulated arc therapy, and helical tomotherapy techniques. We compare the dosimetric results reported in the literature for each technique in various treatment sites. We also review the application of these techniques in specialized clinical procedures including total marrow irradiation, simultaneous treatment of multiple brain metastases, dose painting, simultaneous integrated boost, and stereotactic radiosurgery.


Mitochondrial vesicles: an ancient process providing new links to peroxisomes.
The fate and function of mitochondria and peroxisomes are tightly coupled. Their biogenesis is linked through common transcriptional pathways, and their growth and division is mediated by common fission machinery. Recently, these two organelles have been linked in a much more direct manner, where mitochondrial derived vesicles deliver specific cargo into a population of peroxisomes. There are a number of concepts that emerge from this observation, including the idea that mitochondria are able to segregate their contents into vesicles and that vesicles may represent a new mechanism for mitochondrial communication with peroxisomes, and potentially other intracellular organelles. By considering the function of their bacterial relatives, we can develop hypothesis about the origin and mechanism of mitochondrial vesicle formation. The vesicles released from bacteria have numerous functions in signaling within the colony and mediating host infection. Therefore, the first observation that the mitochondria form vesicles that are transported within the cell defines a new, evolutionarily conserved process in mitochondrial cell biology and dynamics. This review will explore the mechanism and function of mitochondrial vesicle transport with an eye toward the evolutionary implications of this new pathway in cell biology.


A novel TBK1 mutation in a family with diverse frontotemporal dementia spectrum disorders.
Mutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The phenotype is highly variable and has been associated with behavioral variant FTD, primary progressive aphasia, and pure ALS. We describe the clinical, anatomical, and pathological features of a patient who developed corticobasal syndrome (CBS)/progressive nonfluent aphasia (PNFA) overlap. The patient presented with progressive speech difficulties and later developed an asymmetric akinetic-rigid syndrome. Neuroimaging showed asymmetrical frontal atrophy, predominantly affecting the right side. There was a strong family history of neurodegenerative disease with four out of seven siblings developing either dementia or ALS in their 50s and 60s. The patient died at the age of 71 and the brain was donated for postmortem analysis. Histopathological examination showed frontotemporal lobar degeneration TDP-43 type A pathology. Genetic screening did not reveal a mutation in the GRN, MAPT, or C9orf72 genes, but exome sequencing revealed a novel p.E703X mutation in the TBK1 gene. Although segregation data were not available, this loss-of-function mutation is highly likely to be pathogenic because it is predicted to disrupt TBK1/optineurin interaction and impair cellular autophagy. In conclusion, we show that TBK1 mutations can be a cause of an atypical parkinsonian syndrome and screening should be considered in CBS patients with a family history of dementia or ALS.


A phase II study evaluating the effect of tamoxifen on DNA repair in melanoma patients treated with dacarbazine.
The addition of tamoxifen to dacarbazine containing chemotherapy regimens used in the treatment of melanoma, has been shown to increase response rates, but the mechanism of any interaction is uncertain. The object of this study was to determine whether the addition of tamoxifen to dacarbazine, would modify DNA repair in-vivo and cause an increase in O6-meG adducts in peripheral blood leucocytes. This would provide some insight into the nature of the interaction between these two drugs. Twenty three patients with metastatic malignant melanoma received dacarbazine (DTIC) 1 g/m2 every three weeks for a maximum of six cycles. Tamoxifen 20 mg daily, was started after the first cycle of chemotherapy and then taken continuously during the treatment. Adduct levels after the second cycle of treatment were significantly higher than those after the first cycle (p = 0.0001). A similar rise however, was also produced when a cohort of patients were given dacarbazine without tamoxifen during the second cycle of treatment. This study did not show an additional increase of O6-meG adducts when tamoxifen was administered and therefore this mechanism does not support a postulated interaction between tamoxifen and dacarbazine. This is in agreement with the recent randomised study which did not show any significant increase in response rate with the addition of tamoxifen.


Estrogen regulation and ion dependence of taurine uptake by MCF-7 human breast cancer cells.
It has been reported that estrogen receptor-positive MCF-7 cells express TauT, a Na(+)-dependent taurine transporter. However, there is a paucity of information relating to the characteristics of taurine transport in this human breast cancer cell line. Therefore, we have examined the characteristics and regulation of taurine uptake by MCF-7 cells. Taurine uptake by MCF-7 cells showed an absolute dependence upon extracellular Na(+). Although taurine uptake was reduced in Cl(-) free medium a significant portion of taurine uptake persisted in the presence of NO(3) (-). Taurine uptake by MCF-7 cells was inhibited by extracellular beta-alanine but not by L-alanine or L-leucine. 17β-estadiol increased taurine uptake by MCF-7 cells: the V(max) of influx was increased without affecting the K(m). The effect of 17β-estradiol on taurine uptake by MCF-7 cells was dependent upon the presence of extracellular Na(+). In contrast, 17β-estradiol had no significant effect on the kinetic parameters of taurine uptake by estrogen receptor-negative MDA-MB-231 cells. It appears that estrogen regulates taurine uptake by MCF-7 cells via TauT. In addition, Na(+)-dependent taurine uptake may not be strictly dependent upon extracellular Cl(-).


Feeling but not caring: empathic alteration in narcissistic men with high psychopathic traits.
Psychopathy is a personality disorder characterized by specific interpersonal-affective deficits and social deviance often marked by reduced empathy and decreased affective response to the suffering of others. However, recent findings in community samples suggest that the somatosensory resonance to other's pain measured with electroencephalography (EEG) is increased by psychopathic traits. This study aimed at comparing both the response to physical pain and the observation of pain being inflicted to another person in individuals with clinically significant psychopathic traits, namely patients with severe narcissistic personality disorder (NPD, n=11), and community controls (CC, n=13). The gating of somatosensory responses to a tactile steady-state stimulation (25 Hz) during the observation of pain-evoking and non-painful visual stimuli of hands was measured using EEG. Pain thresholds were assessed with a quantitative sensory testing (QST) battery. NPD compared with CC subjects showed similar thermal pain thresholds, but significantly higher pain pressure thresholds (PPT). Significantly greater somatosensory gating (SG) during the anticipation and the observation of pain in others was observed in NPD compared with CC subjects, but this difference was not associated with differences in self-pain perception. SG to pain observation was positively correlated with the Impulsivity-Egocentricity (IE) dimension of psychopathy. These findings demonstrated a stronger somatosensory resonance in the high psychopathic trait NPD group that suggests an increased somatic representation of observed pain despite lower dispositional empathy.


Design of miniaturized illumination for transvaginal co-registered photoacoustic and ultrasound imaging.
A novel lens-array based illumination design for a compact co-registered photoacoustic/ultrasound transvaginal probe has been demonstrated. The lens array consists of four cylindrical lenses that couple the laser beams into four 1-mm-core multi-mode optical fibers with optical coupling efficiency of ~87%. The feasibility of our lens array was investigated by simulating the lenses and laser beam profiles using Zemax. The laser fluence on the tissue surface was experimentally measured and was below the American National Standards Institute (ANSI) safety limit. Spatial distribution of hemoglobin oxygen saturation (sO2) of a mouse tumor was obtained in vivo using photoacoustic measurements at multiple wavelengths. Furthermore, benign and malignant ovaries were imaged ex vivo and evaluated histologically. The co-registered images clearly showed different patterns of blood vasculature. These results highlight the clinical potential of our system for noninvasive photoacoustic and ultrasound imaging of ovarian tissue and cancer detection and diagnosis.


Update on the Japanese guidelines for the use of infliximab and etanercept in rheumatoid arthritis.
Application of biological agents targeting tumor necrosis factor-alpha (TNF-alpha) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). The introduction of infliximab in 2003 and etanercept in 2005 in Japan had a significant impact on both Japanese rheumatologists and RA patients, although serious adverse effects such as bacterial pneumonia, tuberculosis and Pneumocystis jiroveci pneumonia are significant concerns. Based on the data from post-marketing surveillance in Japan and accumulating evidence worldwide, the Internal Medicine Rheumatology Study Group of the Ministry of Health, Labor and Welfare (MHLW), Japan, has updated the guidelines for the use of anti-TNF-alpha agents for RA, which were subsequently approved by the Board of Japan College of Rheumatology (JCR). In the present revised guidelines, we combined the guidelines for use of each of infliximab and etanercept together with some modifications and precautions, paying special attention to serious adverse reactions. Although it is still controversial whether the use of TNF-alpha blocking agents per se increases the risk of infection or not, bacterial pneumonia, regardless of the pathogens, is the most frequent complications in RA. The risk factors associated with pneumonia identified in the post-marketing surveillance of infliximab in Japan are presented in this guideline. The diagnostic algorithm is also designed for early diagnosis and treatment of pulmonary lesions seen during the treatment of biological agents. Preventive measures and precautions against tuberculosis, another frequent and significant complication in Japan, are also described. Furthermore, risk factors for developing Pneumocystis pneumonia, which uniquely occurs at 30- to 50-fold frequency under TNF-alpha blockade therapy in Japan, are described here and its preventive measures are discussed. It is stressed that secondary-care rheumatologists should be better familiarized with the proper use of TNF-alpha blocking agents and be alert to any adverse events for a better management of RA patients.


Induction of miR-132 and miR-212 Expression by Glucagon-Like Peptide 1 (GLP-1) in Rodent and Human Pancreatic β-Cells.
Better understanding how glucagon-like peptide 1 (GLP-1) promotes pancreatic β-cell function and/or mass may uncover new treatment for type 2 diabetes. In this study, we investigated the potential involvement of microRNAs (miRNAs) in the effect of GLP-1 on glucose-stimulated insulin secretion. miRNA levels in INS-1 cells and isolated rodent and human islets treated with GLP-1 in vitro and in vivo (with osmotic pumps) were measured by real-time quantitative PCR. The role of miRNAs on insulin secretion was studied by transfecting INS-1 cells with either precursors or antisense inhibitors of miRNAs. Among the 250 miRNAs surveyed, miR-132 and miR-212 were significantly up-regulated by GLP-1 by greater than 2-fold in INS-1 832/3 cells, which were subsequently reproduced in freshly isolated rat, mouse, and human islets, as well as the islets from GLP-1 infusion in vivo in mice. The inductions of miR-132 and miR-212 by GLP-1 were correlated with cAMP production and were blocked by the protein kinase A inhibitor H-89 but not affected by the exchange protein activated by cAMP activator 8-pCPT-2'-O-Me-cAMP-AM. GLP-1 failed to increase miR-132 or miR-212 expression levels in the 832/13 line of INS-1 cells, which lacks robust cAMP and insulin responses to GLP-1 treatment. Overexpression of miR-132 or miR-212 significantly enhanced glucose-stimulated insulin secretion in both 832/3 and 832/13 cells, and restored insulin responses to GLP-1 in INS-1 832/13 cells. GLP-1 increases the expression of miRNAs 132 and 212 via a cAMP/protein kinase A-dependent pathway in pancreatic β-cells. Overexpression of miR-132 or miR-212 enhances glucose and GLP-1-stimulated insulin secretion.


Validation of cleaning procedures used in an Italian Hospital Pharmacy for antineoplastic drug decontamination: a new tool for industrial hygiene.
Current Italian regulations and procedures for surface decontamination of antineoplastic drugs (ADs) are not clear. Therefore, most hospital pharmacies follow internal procedures as an interpretation of the recommended handling guidelines. Our study compared 7 different cleaning procedures after controlled contamination of the work surface of a biological safety cabinet workbench in an Italian hospital oncology pharmacy (HOP) to determine which of them is more efficient and practical. Moreover, in order to approximate operative routine and improve risk awareness, cleaning procedures were carried out by the personnel that usually operate in the HOP. Measured quantities, i.e. a drop (100 μL) of 5-FluoroUracil, IPhosfamide, CycloPhosphamide and Gemcitabine, were deposited on the work surface within precisely delimited areas. Following the wipe-test analysis using UPLC-MS/MS, the cleaning efficacy was calculated based on the ratio of the residual concentration of the AD, after the cleaning procedure, to the concentration of each AD before the procedure. Tested cleaning procedures were: 1) Hypo-Chlor®, hot water and Farmecol70®; 2) Hypo-Chlor® and hot water; 3) Farmecol70®; 4) Surfa'Safe SH® and hot water; 5) Amuchina® 10%, hot water and Farmecol70®; 6) Incidin® Oxyfoam and hot water; 7) liquid Marseille soap, hot water and Farmecol70®. Within the studied HOP, the Marseille soap was evaluated to be the optimal choice due to its efficacy, low cost, and the very short contact time needed before rinsing. The application of the protocol for procedure validation suggested here could be used in every HOP as a reliable industrial hygiene tool to demonstrate the validity of the chosen cleaning procedure.


Integration of indocyanine green videoangiography with operative microscope: augmented reality for interactive assessment of vascular structures and blood flow.
Preservation of adequate blood flow and exclusion of flow from lesions are key concepts of vascular neurosurgery. Indocyanine green (ICG) fluorescence videoangiography is now widely used for the intraoperative assessment of vessel patency. Here, we present a proof-of-concept investigation of fluorescence angiography with augmented microscopy enhancement: real-time overlay of fluorescence videoangiography within the white light field of view of conventional operative microscopy. The femoral artery was exposed in 7 anesthetized rats. The dissection microscope was augmented to integrate real-time electronically processed near-infrared filtered images with conventional white light images seen through the standard oculars. This was accomplished by using an integrated organic light-emitting diode display to yield superimposition of white light and processed near-infrared images. ICG solution was injected into the jugular vein, and fluorescent femoral artery flow was observed. Fluorescence angiography with augmented microscopy enhancement was able to detect ICG fluorescence in a small artery of interest. Fluorescence appeared as a bright-green signal in the ocular overlaid with the anatomic image and limited to the anatomic borders of the femoral artery and its branches. Surrounding anatomic structures were clearly visualized. Observation of ICG within the vessel lumens permitted visualization of the blood flow. Recorded video loops could be reviewed in an offline mode for more detailed assessment of the vasculature. The overlay of fluorescence videoangiography within the field of view of the white light operative microscope allows real-time assessment of the blood flow within vessels during simultaneous surgical manipulation. This technique could improve intraoperative decision making during complex neurovascular procedures.


Neuroimaging of multimodal sensory stimulation in amyotrophic lateral sclerosis.
Structural and functional imaging techniques were combined to investigate sensory system function in amyotrophic lateral sclerosis (ALS). Functional MRI (fMRI) was used to investigate cortical activity during visual, auditory and somatosensory stimulation in 14 ALS patients and 18 control subjects. Changes in amplitude, latency and duration of the blood oxygen level dependent response were modelled. Furthermore, diffusion tensor imaging was used to investigate changes in white matter networks. During visual stimulation, fMRI demonstrated a decreased response in secondary visual areas in ALS, possibly related to demyelination of sensory nerve fibres. Increasing brain activity in associative cortices was linked to a decrease in physical functioning and might represent a compensatory process. Additionally, reduced white matter functioning became evident for fibres projecting to the extrastriate visual cortex. For auditory stimulation, a delayed response in secondary auditory areas probably linked to prolonged nerve conductance time and an altered cortical pattern in areas involved in target processing/detection became evident in ALS patients. Structural white matter changes in the primary and secondary auditory cortices were observed. For somatosensory stimulation, a prolonged/reduced response in sensory integration areas of the parietal lobe was observed, perhaps linked to the reduced visceral inflow due to immobility. Multiparametric MRI suggests a progressive functional deficit in secondary/higher order sensory processing areas in ALS, probably associated with reduction of re-afferent information flow due to progressive immobility. The changes described might also represent an expression of the disease process itself. Evidence for compensatory processes in multimodal associative cortices was found.


Sickness absence of lead workers and controls.
Certificated sickness rates and levels of lead exposure of 955 men who worked in a lead accumulator factory during a period of seven years (1965-72) were examined. The men were divided by department into four exposure groups; a second division into three groups was made, based on the mean of each man's blood lead measurements during the study period. Absences showed no age pattern, but men who left during the seven years of observation (ex-workers) had had a higher absence rate (842 spells/1000 man years) than those still employed in 1972 (535 spells/1000 man years). There was no significant difference in absence rates or lengths of absences between differently exposed departments either for all causes or for a selected group of potentially lead-induced causes. However, the proportion of potentially lead-induced absences was significantly higher in ex-workers (12-2%) than in current workers (7-4%). Similar analysis showed no significant differences in absence rates of men with different blood lead levels. It was concluded that higher levels of lead exposure did not seem to be associated with higher rates of absence or longer absences either for all causes of absence combined or for those causes which might be attributable to lead.


Preeclampsia prediction with blood pressure measurements: A global external validation of the ALSPAC models.
The prediction of preeclampsia in pregnancy has resulted in a plethora of prognostic models. Yet, very few make it past the development stage and most fail to influence clinical practice. The timely identification of high-risk pregnant women could deliver a tailored antenatal care regimen, particularly in low-resource settings. This study externally validated and calibrated previously published models that predicted the risk of preeclampsia, based on blood pressure (BP) at multiple time points in pregnancy, in a geographically diverse population. The prospective INTERBIO-21st Fetal Study included 3,391 singleton pregnancies from Brazil, Kenya, Pakistan, South Africa, Thailand and the UK, 2012-2018. Preeclampsia prediction was based on baseline characteristics, BP and deviation from the expected BP trajectory at multiple time points in pregnancy. The prediction rules from the Avon Longitudinal Study of Parents and Children (ALSPAC) were implemented in the INTERBIO-21st cohort. Model discrimination was similar to the development cohort. Performance was best with baseline characteristics and a BP measurement at 34 weeks' gestation (AUC 0.85, 95 % CI 0.80-0.90). The ALSPAC models largely overestimated the true risk of preeclampsia incidence in the INTERBIO-21st cohort. After recalibration, these prediction models could potentially serve as a risk stratifying tool to help identify women who might benefit from increased surveillance during pregnancy.


"I think this is the only challenge… the stigma" Stakeholder perceptions about barriers to Antenatal care (ANC) and Prevention of mother-to-child transmission (PMTCT) uptake in Kano state, Nigeria.
Despite the progress made so far in reducing mother-to-child transmission (MTCT), Nigeria still contributes significantly to the global burden of new pediatric HIV infections. The elimination target for MTCT has not been reached and the decline in new infections among all Global Plan countries from 2009 to 2015 was lowest in Nigeria. This qualitative study explores the barriers to uptake of prevention of mother-to-child transmission (PMTCT) intervention in Kano, the second most populous state in Nigeria. Key informant interviews (KIIs) were conducted among twelve stakeholders who were purposively selected based on their knowledge and involvement in PMTCT program activities in the state. The KII guide explored the status and challenges of PMTCT uptake in Kano state. Qualitative data analysis was managed using NVIVO 11 software and themes were analyzed using thematic analysis. We found that the key barriers to uptake of PMTCT identified by stakeholders cut across the domains of the socio-ecological model. These include-fear of stigma associated with being seen accessing HIV related services, low male partner involvement, socio-cultural beliefs about the dangers of hospital-based delivery, poor attitude of health workers, distance/cost to facilities, issues with availability of HIV test kits and poor organization of health services. The implementation of effective PMTCT programs would require innovative strategies that leverage improvement of Antenatal care (ANC) uptake as an entry point for PMTCT. In addition, sustaining engagement in care requires creating a supportive stigma-free environment in the community as well as spousal support to ensure women can navigate the socio-cultural barriers that limit access to health services.


Opening wedge osteotomy for distal radius malunion: dorsal or palmar approach?
Background There are various technical variations to consider when performing a corrective osteotomy of a distal radius malunion. We chose two of the more commonly reported techniques and compared the results of volar (palmar) osteotomy and fixation with dorsal osteotomy and fixation. Method Within a continuous cohort of patients who had undergone corrective osteotomy for a malunited Colles fracture, two groups could be identified retrospectively. In 8 patients a dorsal approach was used. A structural trapezoidal graft, subtending the amount of correction, was inserted into the osteotomy gap and stabilization was performed with a thin round-hole mini-fragment plate. In 14 patients a palmar approach and a palmar fixed-angle plate was used for correction of the malunion and for angular stable rigid fixation of the two fragments. The osteotomy gap was loosely filled with nonstructural cancellous bone chips. A retrospective comparison of the two groups was performed to see whether the outcome was affected by the use of either operative technique.The demographics, the preoperative amount of deformity, range of motion, pain, and force were comparable for both groups. All osteotomies healed without loss of correction. After a minimal follow-up of one year, radiographic appearance, objective functional parameters were assessed and subjective data (Disabilities of the Arm, Shoulder, and Hand [DASH] score and special pain and function questionnaire) obtained. Results These data did not show statistical difference for the two groups except for the amount of final wrist flexion. This parameter was significantly better in patients who had palmar approaches and fixed-angle plates. Conclusion Corrective osteotomies of distal radius malunions can be done in either way. It might result in some better flexion, if performed volarly.


Valine pyrrolidide preserves intact glucose-dependent insulinotropic peptide and improves abnormal glucose tolerance in minipigs with reduced beta-cell mass.
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation. However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced beta-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)-treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg). VP did not significantly affect levels of intact GLP-1 but increased levels of intact GIP (from 4543 +/- 1880 to 9208 +/- 3267 pM x min; P <.01), thus improving glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 +/- 480 to 1582 +/- 353 mM x min; P =.05). VP did not increase insulin levels during the oral glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 +/- 42 to 192 +/- 108; P <.05), but not after NIA + STZ, possibly because of less residual insulin secretory capacity in these animals. GIP seems to contribute to the antihyperglycemic effect of VP in this model; however, additional mechanisms for the effect of DPPIV inhibition cannot be excluded. The authors conclude that DPPIV inhibitors may be useful to treat type 2 diabetes, even when this is due to reduced beta-cell mass.


Ecological risk assessment and its application to elasmobranch conservation and management.
Ecological risk assessments (ERAs) are employed to quantify and predict the vulnerability of a particular species, stock or population to a specific stressor, e.g. pollution, harvesting, climate change, by-catch. Data generated from ERAs are used to identify and prioritize species for implementation of effective conservation and management strategies. At this time, ERAs are of particular importance to elasmobranchs, given the ecological importance and documented global population declines of some elasmobranch species. Here, ERAs as a tool for elasmobranch conservation and management are reviewed and a theoretical roadmap provided for future studies. To achieve these goals, a brief history of ERAs and approaches used within them (in the context of elasmobranchs) are given, and a comprehensive review conducted of all ERA studies associated with elasmobranchs published between 1998 and 2011. The hazards assessed, species evaluated and methodological approaches taken are recorded. Chronological and geographical patterns suggest that this tool has grown in popularity as a commercial fishery management instrument, while also signalling a recent precautionary approach to elasmobranch management in commercial fisheries globally. The analysis demonstrates that the predominant parameters incorporated in previous ERAs are largely based on life-history characteristics, and sharks have received the majority of attention; batoids (including skates) have received less attention. Recreational fishing and habitat degradation are discussed as hazards which warrant future investigation through ERA. Lastly, suggestions are made for incorporating descriptive ecological data to aid in the continued development and evolution of this management tool as it applies to future elasmobranch conservation.


EEG feature selection using mutual information and support vector machine: A comparative analysis.
The large number of methods for EEG feature extraction demands a good choice for EEG features for every task. This paper compares three subsets of features obtained by tracks extraction method, wavelet transform and fractional Fourier transform. Particularly, we compare the performance of each subset in classification tasks using support vector machines and then we select possible combination of features by feature selection methods based on forward-backward procedure and mutual information as relevance criteria. Results confirm that fractional Fourier transform coefficients present very good performance and also the possibility of using some combination of this features to improve the performance of the classifier. To reinforce the relevance of the study, we carry out 1000 independent runs using a bootstrap approach, and evaluate the statistical significance of the F(score) results using the Kruskal-Wallis test.


Rationale for immune-based therapies in Merkel polyomavirus-positive and -negative Merkel cell carcinomas.
Merkel cell carcinoma (MCC) is a rare but often deadly skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). Polyomavirus T-antigen oncoproteins are persistently expressed in virus-positive MCCs (˜80% of cases), while remarkably high numbers of tumor-associated neoantigens are detected in virus-negative MCCs, suggesting that both MCC subsets may be immunogenic. Here we review mechanisms by which these immunogenic tumors evade multiple levels of host immunity. Additionally, we summarize the exciting potential of diverse immune-based approaches to treat MCC. In particular, agents blocking the PD-1 axis have yielded strikingly high response rates in MCC as compared with other solid tumors, highlighting the potential for immune-mediated treatment of this disease.