Schistosoma japonicum: the design and experimental evaluation of a multivalent DNA vaccine.
The aim of this study was to construct and evaluate the immunity efficacy of the DNA multivalent vaccine pVIVO(2)SjFABP-23. The vaccine was constructed and produced as follows. Forty BALB/c mice were divided into four groups designated pVIVO(2), pVIVO(2)Sj23, pVIVO(2)SjFABP and pVIVO(2)SjFABP-23. Each mouse was immunized with 100 mug of the corresponding plasmid DNA by intramuscular injection. 28 days post-vaccination, the mice were challenged with S. japonicum cercariae, and the worm and egg burdens were determined 42 days post-challenge. Serum samples were collected from all the mice before and after vaccination and at the end of the experiment, and used for antibody detection. The IFN-gamma and IL-4 levels were quantified in the supernatants of specifically stimulated spleen cells. The number of worms was reduced by 52%, 40% and 42% in mice respectively immunized with pVIVO(2)SjFABP-23, pVIVO(2)Sj23 or pVIVO(2)SjFABP. A respective 61%, 38% and 39% egg reduction was determined relative to those mice that only received the empty pVIVO2 plasmid. pVIVO(2)SjFABP-23 immunization increased IgG levels against SWAP and SEA. Increased IFN-gamma levels were detected in the supernatant of specific stimulated spleen cells from mice immunized with the 3 different constructs. The multivalent DNA vaccine developed induced higher levels of protection than the two monovalent tested vaccines.


Molecular phylodynamics of the heterosexual HIV epidemic in the United Kingdom.
The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses originating among immigrants from sub-Saharan Africa. The high rate of HIV evolution, combined with the availability of a very high density sample of viral sequences from routine clinical care has allowed the phylodynamics of the epidemic to be investigated for the first time. Sequences of the viral protease and partial reverse transcriptase coding regions from 11,071 patients infected with HIV of non-B subtypes were studied. Of these, 2774 were closely linked to at least one other sequence by nucleotide distance. Including the closest sequences from the global HIV database identified 296 individuals that were in UK-based groups of 3 or more individuals. There were a total of 8 UK-based clusters of 10 or more, comprising 143/2774 (5%) individuals, much lower than the figure of 25% obtained earlier for men who have sex with men (MSM). Sample dates were incorporated into relaxed clock phylogenetic analyses to estimate the dates of internal nodes. From the resulting time-resolved phylogenies, the internode lengths, used as estimates of maximum transmission intervals, had a median of 27 months overall, over twice as long as obtained for MSM (14 months), with only 2% of transmissions occurring in the first 6 months after infection. This phylodynamic analysis of non-B subtype HIV sequences representing over 40% of the estimated UK HIV-infected heterosexual population has revealed heterosexual HIV transmission in the UK is clustered, but on average in smaller groups and is transmitted with slower dynamics than among MSM. More effective intervention to restrict the epidemic may therefore be feasible, given effective diagnosis programmes.


The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia.
We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of pancreatitis, thrombosis, hyperammonemia and central neurotoxicity and their association with asparaginase activity levels. Eighty-nine patients were treated according to the Dutch Childhood Oncology Group Acute Lymphoblastic Leukemia 10 medium-risk intensification protocol, which includes 15 doses of PEGasparaginase (2,500 IU/m(2)) over 30 weeks. Erwinia asparaginase (20,000 IU/m(2)) was administered when allergy to or silent inactivation of PEGasparaginase occurred. Triglyceride, cholesterol and ammonia levels increased rapidly in children treated with PEGasparaginase and remained temporarily elevated, but normalized after administration of the last asparaginase dose. Among the patients treated with PEGasparaginase, hypertriglyceridemia and hypercholesterolemia (grade 3/4) were found in 47% and 25%, respectively. The correlation between PEGasparaginase activity levels and triglyceride levels was strongest at week 5 (Spearman correlation coefficient = 0.36, P = 0.005). The triglyceride levels were higher in children ≥ 10 years old than in younger patients (<10 years old) after adjustment for type of asparaginase preparation: median 4.9 mmol/L versus 1.6 mmol/L (P<0.001). In patients receiving Erwinia asparaginase, triglyceride levels increased in the first weeks as well, but no grade 3/4 dyslipidemia was found. Hyperammonemia (grade 3/4) was only found in patients treated with Erwinia asparaginase (9%). Thrombosis occurred in 4.5%, pancreatitis in 7%, and central neurotoxicity in 9% of patients using either of the two agents; these toxicities were not related to levels of asparaginase activity or to triglyceride levels. In conclusion, severe dyslipidemia occurred frequently, but was temporary and was not associated with relevant clinical events and should not, therefore, be considered a reason for modifying asparaginase treatment. Dyslipidemia was the only toxicity related to levels of asparaginase activity.


Coalescent inferences in conservation genetics: should the exception become the rule?
Genetic estimates of effective population size (Ne) are an established means to develop informed conservation policies. Another key goal to pursue the conservation of endangered species is keeping the connectivity across fragmented environments, to which genetic inferences of gene flow and dispersal greatly contribute. Most current statistical tools for estimating such population demographic parameters are based on Kingman's coalescent (KC). However, KC is inappropriate for taxa displaying skewed reproductive variance, a property widely observed in natural species. Coalescent models that consider skewed reproductive success-called multiple merger coalescents (MMCs)-have been shown to substantially improve estimates of Ne when the distribution of offspring per capita is highly skewed. MMCs predictions of standard population genetic parameters, including the rate of loss of genetic variation and the fixation probability of strongly selected alleles, substantially depart from KC predictions. These extended models also allow studying gene genealogies in a spatial continuum, providing a novel theoretical framework to investigate spatial connectivity. Therefore, development of statistical tools based on MMCs should substantially improve estimates of population demographic parameters with major conservation implications.


Risk Factors for Wound Infections after Deformity Correction Surgery in Neuromuscular Scoliosis.
This study aims to elucidate surgical risk factors in neuromuscular scoliosis (NMS) with respect to wound site infection after spinal fusion. A retrospective review was performed of all patients treated surgically for NMS between January 2008 and December 2016 (minimum 6 months' follow-up). A sub-cohort of 60 patients with minimum 2 years of follow-up data was also analyzed. In 102 patients (53 boys and 49 girls), the mean age at surgery was 14.0 years (SD ±2.7). Mean follow-up was 2.53 years (±1.66), and mean time to presentation of infection was 2.14 months (±4.95). The overall perioperative complication rate was 26.5%, with 14.7% of patients developing deep wound infection. Gram-negative bacteria were responsible for 60% of infections; 20% were Gram positive, and 20% involved both types. Pulmonary comorbidities (p = 0.007), pre- to postoperative increase in weight (p = 0.010), exaggerated lumbar lordosis at follow-up (p = 0.008), history of seizures (p = 0.046), previous myelomeningocele repair (p = 0.046), and previous operations (p = 0.013) were significant risk factors for infection. Our data suggest that in the pediatric population treated surgically for NMS, wound infection is strongly associated with postoperative increase in body weight, residual lumbar lordosis, pulmonary comorbidity, history of myelomeningocele repair, seizures, and previous operations.


Effects of habitat and season on competitive interactions between roach (Rutilus rutilus) and perch (Perca fluviatilis).
The competitive interactions between two distantly related fish species, roach (Rutilus rutilus) and perch (Perca fluviatilis), were studied in enclosures in two habitats. In the open water habitat dominated by small planktonic prey perch grew more slowly and altered its diet from zooplankton to benthic macroinvertebrates when in the presence of roach. No effect, however, of perch on roach was observed. This was probably caused by the higher foraging efficiency of roach on zooplankton (laboratory experiments) and to the presence of a resource utilizable only by roach, bluegreen algae/detritus. In the littoral habitat no interspecific effects were detected even though resources were more limiting. This was probably a consequence of the higher densities of chironomids, on which perch fed more efficiently than roach, and of the presence of bluegreen algae/detritus. Roach, which consumed a larger spectrum of food types than perch, as a result was less affected by competition. The distributions of the species in the lake corresponded to what could be predicted from experiments. The degree of resource limitation varied with season and was highest in summer, while no resource limitation was observed in spring. This variation in resource limitation is probably caused by the increased metabolic demands of the fish in summer.


Molecular functions of thyroid hormones and their clinical significance in liver-related diseases.
Thyroid hormones (THs) are potent mediators of several physiological processes, including embryonic development, cellular differentiation, metabolism, and cell growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate the biological functions of T3 via transcriptional regulation. TRs generally form heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3 stimulation. Research over the past few decades has revealed that disruption of cellular TH signaling triggers chronic liver diseases, including alcoholic or nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model experiments and epidemiologic studies to date imply close associations between high TH levels and prevention of liver disease. Moreover, several investigations spanning four decades have reported the therapeutic potential of T3 analogs in lowering lipids, preventing chronic liver disease, and as anticancer agents. Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of TH actions is critical for the treatment of significant public health issues. Here, we have reviewed recent studies focusing on the roles of THs and TRs in several disorders, in particular, liver diseases. We also discuss the potential therapeutic applications of THs and underlying molecular mechanisms.


ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.
Here we investigate how ß-adrenergic stimulation of the heart alters regulation of ryanodine receptors (RyRs) by intracellular Ca(2+) and Mg(2+) and the role of these changes in SR Ca(2+) release. RyRs were isolated from rat hearts, perfused in a Langendorff apparatus for 5 min and subject to 1 min perfusion with 1 µM isoproterenol or without (control) and snap frozen in liquid N2 to capture their phosphorylation state. Western Blots show that RyR2 phosphorylation was increased by isoproterenol, confirming that RyR2 were subject to normal ß-adrenergic signaling. Under basal conditions, S2808 and S2814 had phosphorylation levels of 69% and 15%, respectively. These levels were increased to 83% and 60%, respectively, after 60 s of ß-adrenergic stimulation consistent with other reports that ß-adrenergic stimulation of the heart can phosphorylate RyRs at specific residues including S2808 and S2814 causing an increase in RyR activity. At cytoplasmic [Ca(2+)] <1 µM, ß-adrenergic stimulation increased luminal Ca(2+) activation of single RyR channels, decreased luminal Mg(2+) inhibition and decreased inhibition of RyRs by mM cytoplasmic Mg(2+). At cytoplasmic [Ca(2+)] >1 µM, ß-adrenergic stimulation only decreased cytoplasmic Mg(2+) and Ca(2+) inhibition of RyRs. The Ka and maximum levels of cytoplasmic Ca(2+) activation site were not affected by ß-adrenergic stimulation. Our RyR2 gating model was fitted to the single channel data. It predicted that in diastole, ß-adrenergic stimulation is mediated by 1) increasing the activating potency of Ca(2+) binding to the luminal Ca(2+) site and decreasing its affinity for luminal Mg(2+) and 2) decreasing affinity of the low-affinity Ca(2+)/Mg(2+) cytoplasmic inhibition site. However in systole, ß-adrenergic stimulation is mediated mainly by the latter.


The shape of things to come: exploring goal-directed prospection.
Through the ability to preview the future (i.e., prospection), people can anticipate how best to think, feel and act in just about any setting. But exactly what factors determine the contents of prospection? Extending research on action identification and temporal construal, here we explored how action goals and temporal distance modulate the characteristics of future previews. Participants were required to imagine travelling to Egypt (in the near or distant future) to climb or photograph a pyramid. Afterwards, to probe the contents of prospection, participants provided a sketch of their imaginary experience. Results elucidated the impact of goal type and temporal distance on mental imagery. While a climbing goal prompted participants to draw a larger pyramid in the near than distant future, a photographic goal influenced only the compositional complexity of the sketches. These findings reveal how action goals and temporal distance shape the contents of future simulations.


Tree carbon allocation explains forest drought-kill and recovery patterns.
The mechanisms governing tree drought mortality and recovery remain a subject of inquiry and active debate given their role in the terrestrial carbon cycle and their concomitant impact on climate change. Counter-intuitively, many trees do not die during the drought itself. Indeed, observations globally have documented that trees often grow for several years after drought before mortality. A combination of meta-analysis and tree physiological models demonstrate that optimal carbon allocation after drought explains observed patterns of delayed tree mortality and provides a predictive recovery framework. Specifically, post-drought, trees attempt to repair water transport tissue and achieve positive carbon balance through regrowing drought-damaged xylem. Furthermore, the number of years of xylem regrowth required to recover function increases with tree size, explaining why drought mortality increases with size. These results indicate that tree resilience to drought-kill may increase in the future, provided that CO2 fertilisation facilitates more rapid xylem regrowth.


Adult-onset opsoclonus-myoclonus syndrome.
BACKGROUND Little is known about adult-onset opsoclonus-myoclonus syndrome (OMS) outside of individual case reports. OBJECTIVE To describe adult-onset OMS. DESIGN Review of medical records (January 1, 1990, through December 31, 2011), prospective telephone surveillance, and literature review (January 1, 1967, through December 31, 2011). SETTING Department of Neurology, Mayo Clinic, Rochester, Minnesota. PATIENTS Twenty-one Mayo Clinic patients and 116 previously reported patients with adult-onset OMS. MAIN OUTCOME MEASURES Clinical course and longitudinal outcomes. RESULTS The median age at onset of the 21 OMS patients at the Mayo Clinic was 47 years (range, 27-78 years); 11 were women. Symptoms reported at the first visit included dizziness, 14 patients; balance difficulties, 14; nausea and/or vomiting, 10; vision abnormalities, 6; tremor/tremulousness, 4; and altered speech, 2. Myoclonus distribution was extremities, 15 patients; craniocervical, 8; and trunk, 4. Cancer was detected in 3 patients (breast adenocarcinoma, 2; and small cell lung carcinoma, 1); a parainfectious cause was assumed in the remainder of the patients. Follow-up of 1 month or more was available for 19 patients (median, 43 months; range, 1-187 months). Treatment (median, 6 weeks) consisted of immunotherapy and symptomatic therapy in 16 patients, immunotherapy alone for 2, and clonazepam alone for 1. Of these 19 patients, OMS remitted in 13 and improved in 3; 3 patients died (neurologic decline, 1; cancer, 1; and myocardial infarction, 1). The cause of death was of paraneoplastic origin in 60 of 116 literature review patients, with the most common carcinomas being lung (33 patients) and breast (7); the most common antibody was antineuronal nuclear antibody type 2 (anti-Ri, 15). Other causes were idiopathic in origin, 38 patients; parainfectious, 15 (human immunodeficiency virus, 7); toxic/metabolic, 2; and other autoimmune, 1. Both patients with N -methyl-D-aspartate receptor antibody had encephalopathy. Improvements were attributed to immunotherapy alone in 22 of 28 treated patients. CONCLUSIONS Adult-onset OMS is rare. Paraneoplastic and parainfectious causes (particularly human immunodeficiency virus) should be considered. Complete remission achieved with immunotherapy is the most common outcome.


Hypertrophic cardiomyopathy-causing Asp175asn and Glu180gly Tpm1 mutations shift tropomyosin strands further towards the open position during the ATPase cycle.
To understand the molecular mechanism by which the hypertrophic cardiomyopathy-causing Asp175Asn and Glu180Gly mutations in α-tropomyosin alter contractile regulation, we labeled recombinant wild type and mutant α-tropomyosins with 5-iodoacetamide-fluorescein and incorporated them into the ghost muscle fibers. The orientation and mobility of the probe were studied by polarized fluorimetry at different stages of the ATPase cycle. Multistep alterations in the position and mobility of wild type tropomyosin on the thin filaments during the ATP cycle were observed. Both mutations were found to shift tropomyosin strands further towards the open position and to change the affinity of tropomyosin for actin, with the effect of the Glu180Gly mutation being greater than Asp175Asn, showing an increase in the binding strong cross-bridges to actin during the ATPase cycle. These structural changes to the thin filament are likely to underlie the observed increased Ca(2+)-sensitivity caused by these mutations which initiates the disease remodeling.


Ultrastructural analysis and residual DNA evaluation of rabbit vein scaffold.
To investigate the ultrastructural characteristics and analysis of residual DNA in scaffold models, produced with decellularized vena cava in an experimental model with rabbits. Three groups were created for ultrastructural and residual DNA analysis: group 1 - control, consisting of samples of vena cava in natura; group 2 - SD, consisting of vein fragments submitted to 2% sodium deoxycholate decellularization by shaking (160rpm - Shaker News Brunswick Scientific®) for 1 hour at controlled temperature shaker at 37°C; group 3 - SDS, consisting of vein fragments submitted to 1% sodium dodecyl sulfate decellularization under the same previous condition, for 2 hours. The ultrastructural matrix of the blood vessel maintained its vintegrity after either decellularization models. The results of the two quantification methods demonstrated a significant decrease in the DNA content of the decellularized vena cava samples as compared to the control samples and, differed statistically from each other, p <0.05. The 2% DS protocol for vein decellularization, in this experimental model, was considered the best protocol because it presented less amount of residual DNA without causing substantial destruction of the extracellular matrix.


Effect of supervised students' involvement on diagnostic accuracy in hospitalized medical patients--a prospective controlled study.
During internships most medical students engage in history taking and physical examination during evaluation of hospitalized patients. However, the students' ability for pattern recognition is not as developed as in medical experts and complete history taking is often not repeated by an expert, so important clues may be missed. On the other hand, students' history taking is usually more extensive than experts' history taking and medical students discuss their findings with a Supervisor. Thus the effect of student involvement on diagnostic accuracy is unclear. We therefore compared the diagnostic accuracy for patients in the medical emergency department with and without student involvement in the evaluation process. Patients in the medical emergency department were assigned to evaluation by either a supervised medical student or an emergency department physician. We only included patients who were admitted to our hospital and subsequently cared for by another medical team on the ward. We compared the working diagnosis from the emergency department with the discharge diagnosis. A total of 310 patients included in the study were cared for by 41 medical students and 21 emergency department physicians. The working diagnosis was changed in 22% of the patients evaluated by physicians evaluation and in 10% of the patients evaluated by supervised medical students (p = .006). There was no difference in the expenditures for diagnostic procedures, length of stay in the emergency department or patient comorbidity complexity level. Involvement of closely supervised medical students in the evaluation process of hospitalized medical patients leads to an improved diagnostic accuracy compared to evaluation by an emergency department physician alone.


RHOA-FAK is a required signaling axis for the maintenance of KRAS-driven lung adenocarcinomas.
Non-small cell lung cancer (NSCLC) often expresses mutant KRAS together with tumor-associated mutations of the CDKN2A locus, which are associated with aggressive, therapy-resistant tumors. Here, we unravel specific requirements for the maintenance of NSCLC that carries this genotype. We establish that the extracellular signal-regulated kinase (ERK)/RHOA/focal adhesion kinase (FAK) network is deregulated in high-grade lung tumors. Suppression of RHOA or FAK induces cell death selectively in mutant KRAS;INK4A/ARF-deficient lung cancer cells. Furthermore, pharmacologic inhibition of FAK caused tumor regression specifically in the high-grade lung cancer that developed in mutant Kras;Cdkn2a-null mice. These findings provide a rationale for the rapid implementation of genotype-specific targeted therapies using FAK inhibitors in patients with cancer. Targeted therapies are effective for only a small fraction of patients with cancer. We report that FAK inhibitors exert potent antitumor effects in NSCLCs that express mutant KRAS in association with INK4A/ARF deficiency. These results reveal a novel genotype-specific vulnerability of cancer cells that can be exploited for therapeutic purposes.


Random-walk access times on partially disordered complex networks: an effective medium theory.
An analytic effective medium theory is constructed to study the mean access times for random walks on hybrid disordered structures formed by embedding complex networks into regular lattices, considering transition rates F that are different for steps across lattice bonds from the rates f across network shortcuts. The theory is developed for structures with arbitrary shortcut distributions and applied to a class of partially disordered traversal enhanced networks in which shortcuts of fixed length are distributed randomly with finite probability. Numerical simulations are found to be in excellent agreement with predictions of the effective medium theory on all aspects addressed by the latter. Access times for random walks on these partially disordered structures are compared to those on small-world networks, which on average appear to provide the most effective means of decreasing access times uniformly across the network.


Epidemic History and Iatrogenic Transmission of Blood-borne Viruses in Mid-20th Century Kinshasa.
The human immunodeficiency virus type 1 (HIV-1) pandemic was ignited in Léopoldville (now known as Kinshasa), in the former Belgian Congo. Factors that jump-started its early expansion remain unclear. Nonlethal hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV-1) can be used to investigate past iatrogenic transmission. We undertook a cross-sectional study of elderly inhabitants of Kinshasa, with serological assays, amplification, and sequencing. Risk factors were assessed through logistic regression. Phylogenetic methods reconstructed the genetic history of HCV. A total of 217 of 839 participants (25.9%) were HCV seropositive; 26 (3.1%) were HTLV-1-seropositive. Amplification products were obtained from 118 HCV-seropositive participants; subtypes 4k (in 47 participants) and 4r (in 38) were most common. Independent risk factors for HCV subtype 4r seropositivity were intramuscular tuberculosis therapy, intravenous injections at hospital A, intravenous injections before 1960, and injections at a colonial-era venereology clinic. Intravenous injections at hospital B and antimalarials were associated with HCV subtype 4k seropositivity. Risk factors for HTLV-1 seropositivity included intravenous injections at hospitals C or D and transfusions. Evolutionary analysis of viral sequences revealed independent exponential amplification of HCV subtypes 4r and 4k from the 1950s onward. Iatrogenic transmission of HCV and HTLV-1 occurred in mid-20th century Kinshasa, at the same time and place HIV-1 emerged. Iatrogenic routes may have contributed to the early establishment of the pandemic.


Evaluation of paired-end sequencing strategies for detection of genome rearrangements in cancer.
Paired-end sequencing is emerging as a key technique for assessing genome rearrangements and structural variation on a genome-wide scale. This technique is particularly useful for detecting copy-neutral rearrangements, such as inversions and translocations, which are common in cancer and can produce novel fusion genes. We address the question of how much sequencing is required to detect rearrangement breakpoints and to localize them precisely using both theoretical models and simulation. We derive a formula for the probability that a fusion gene exists in a cancer genome given a collection of paired-end sequences from this genome. We use this formula to compute fusion gene probabilities in several breast cancer samples, and we find that we are able to accurately predict fusion genes in these samples with a relatively small number of fragments of large size. We further demonstrate how the ability to detect fusion genes depends on the distribution of gene lengths, and we evaluate how different parameters of a sequencing strategy impact breakpoint detection, breakpoint localization, and fusion gene detection, even in the presence of errors that suggest false rearrangements. These results will be useful in calibrating future cancer sequencing efforts, particularly large-scale studies of many cancer genomes that are enabled by next-generation sequencing technologies.


Acceptance of Minimally Invasive Dentistry Among US Dentists in Public Health Practices.
Little is known about use or acceptance of minimally invasive dentistry (MID) in the USA, particularly in public health settings. The purpose of this study was to assess opinions concerning MID among dentists in public-health practices. A cross-sectional study was conducted to assess the views of dentists in public-health practices concerning MID using an online survey instrument among National Network for Oral Health Access (NNOHA) and American Association of Community Dental Programs (AACDP) members. Specific questions focused on diagnostic and preventive techniques, and whether MID was considered to meet the standard of care in the US Results: Overall, 86% believed that MID met the standard of care for primary teeth, and 77% did so for permanent teeth. The majority of respondents also agreed that fluoride varnish prevents caries and atraumatic restorative techniques (ART) are an effective caries treatment for children and adults. According to logistic regression results, dentists who had continuing education courses in MID and agreed that ART was an effective treatment for adults were more likely to report that MID met the standard of care for permanent teeth. Subjects who believed that fluoride varnish was effective as caries prevention for children were more likely to view MID as meeting the standard of care for primary teeth. There appears to be a paradigm shift toward a MID philosophy, and most responding public health dentists believed that MID meets the standard of care for primary and permanent teeth in the US.


Ovotestes suggest cryptic genetic influence in a reptile model for temperature-dependent sex determination.
Sex determination and differentiation in reptiles is complex. Temperature-dependent sex determination (TSD), genetic sex determination (GSD) and the interaction of both environmental and genetic cues (sex reversal) can drive the development of sexual phenotypes. The jacky dragon (Amphibolurus muricatus) is an attractive model species for the study of gene-environment interactions because it displays a form of Type II TSD, where female-biased sex ratios are observed at extreme incubation temperatures and approximately 50 : 50 sex ratios occur at intermediate temperatures. This response to temperature has been proposed to occur due to underlying sex determining loci, the influence of which is overridden at extreme temperatures. Thus, sex reversal at extreme temperatures is predicted to produce the female-biased sex ratios observed in A. muricatus. The occurrence of ovotestes during development is a cellular marker of temperature sex reversal in a closely related species Pogona vitticeps. Here, we present the first developmental data for A. muricatus, and show that ovotestes occur at frequencies consistent with a mode of sex determination that is intermediate between GSD and TSD. This is the first evidence suggestive of underlying unidentified sex determining loci in a species that has long been used as a model for TSD.


Dual functionality of cis-regulatory elements as developmental enhancers and Polycomb response elements.
Developmental gene expression is tightly regulated through enhancer elements, which initiate dynamic spatio-temporal expression, and Polycomb response elements (PREs), which maintain stable gene silencing. These two cis-regulatory functions are thought to operate through distinct dedicated elements. By examining the occupancy of the Drosophila pleiohomeotic repressive complex (PhoRC) during embryogenesis, we revealed extensive co-occupancy at developmental enhancers. Using an established in vivo assay for PRE activity, we demonstrated that a subset of characterized developmental enhancers can function as PREs, silencing transcription in a Polycomb-dependent manner. Conversely, some classic Drosophila PREs can function as developmental enhancers in vivo, activating spatio-temporal expression. This study therefore uncovers elements with dual function: activating transcription in some cells (enhancers) while stably maintaining transcriptional silencing in others (PREs). Given that enhancers initiate spatio-temporal gene expression, reuse of the same elements by the Polycomb group (PcG) system may help fine-tune gene expression and ensure the timely maintenance of cell identities.


An international survey of aquaponics practitioners.
Aquaponics, a combination of fish farming and soilless plant farming, is growing in popularity and gaining attention as an important and potentially more sustainable method of food production. The aim of this study was to document and analyze the production methods, experiences, motivations, and demographics of aquaponics practitioners in the United States (US) and internationally. The survey was distributed online using a chain sampling method that relied on referrals from initial respondents, with 809 respondents meeting the inclusion criteria. The majority of respondents were from the US (80%), male (78%), and had at least a high school degree (91%). The mean age of respondents was 47±13 years old. Most respondents (52%) had three years or less of aquaponics experience. Respondents typically raised tilapia or ornamental fish and a variety of leafy green vegetables, herbs, and fruiting crops. Respondents were most often motivated to become involved in aquaponics to grow their own food, for environmental sustainability reasons, and for personal health reasons. Many respondents employed more than one method to raise crops, and used alternative or environmentally sustainable sources of energy, water, and fish feed. In general, our findings suggest that aquaponics is a dynamic and rapidly growing field with participants who are actively experimenting with and adopting new technologies. Additional research and outreach is needed to evaluate and communicate best practices within the field. This survey is the first large-scale effort to track aquaponics in the US and provides information that can better inform policy, research, and education efforts regarding aquaponics as it matures and possibly evolves into a mainstream form of agriculture.


Polyamine metabolism in a member of the phylum Microspora (Encephalitozoon cuniculi): effects of polyamine analogues.
The uptake, biosynthesis and catabolism of polyamines in the microsporidian parasite Encephalitozoon cuniculi are detailed with reference to the effects of oligoamine and arylamine analogues of polyamines. Enc. cuniculi, an intracellular parasite of mammalian cells, has both biosynthetic and catabolic enzymes of polyamine metabolism, as demonstrated in cell-free extracts of mature spores. The uptake of polyamines was measured in immature, pre-emergent spores isolated from host cells by Percoll gradient. Spermine was rapidly taken up and metabolized to spermidine and an unknown, possibly acetamidopropanal, by spermidine/spermine N(1)-acetyltransferase (SSAT) and polyamine oxidase (PAO). Most of the spermidine and the unknown product were found in the cell incubation medium, indicating they were released from the cell. bis(Ethyl) oligoamine analogues of polyamines, such as SL-11144 and SL-11158, as well as arylamine analogues [BW-1, a bis(phenylbenzyl) 3-7-3 analogue] blocked uptake and interconversion of spermine at micromolar levels and, in the case of BW-1, acted as substrate for PAO. The Enc. cuniculi PAO activity differed from that found in mammalian cells with respect to pH optimum, substrate specificity and sensitivity to known PAO inhibitors. SL-11158 inhibited SSAT activity with a mixed type of inhibition in which the analogue had a 70-fold higher affinity for the enzyme than the natural substrate, spermine. The interest in Enc. cuniculi polyamine metabolism and the biochemical effects of these polyamine analogues is warranted since they cure model infections of Enc. cuniculi in mice and are potential candidates for human clinical trials.


Crush Injury to the Hand Following Epileptic Seizure Leading to Compartment Syndrome.
Compartment syndrome of the forearm or leg has been well documented in the literature. However, there have been few published reports of hand compartment syndrome. We hereby present the first reported case in the literature of hand compartment syndrome secondary to an epileptic seizure. A 50-year old gentleman with known epilepsy presented to the Emergency Department following a witnessed tonic-clonic seizure. The patient's chief complaints were a grossly swollen and excruciatingly painful dominant right hand. Examination revealed severely reduced range of motion and neurovascular compromise. An emergency decompression fasciotomy was performed in the operating theatre, where severe oedema was noted with viable muscle throughout. Compartment syndrome can occur in any muscle compartment of the body, including in the hand. Any crush injury to the hand should trigger a high index of suspicion by the clinician to enable prompt recognition of this surgical emergency and initiate timely management.


Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation.
Mutations in the genes for amyloid precursor protein (APP) and presenilins (PS1, PS2) increase production of beta-amyloid 42 (Abeta42) and cause familial Alzheimer's disease (FAD). Transgenic mice that express FAD mutant APP and PS1 overproduce Abeta42 and exhibit amyloid plaque pathology similar to that found in AD, but most transgenic models develop plaques slowly. To accelerate plaque development and investigate the effects of very high cerebral Abeta42 levels, we generated APP/PS1 double transgenic mice that coexpress five FAD mutations (5XFAD mice) and additively increase Abeta42 production. 5XFAD mice generate Abeta42 almost exclusively and rapidly accumulate massive cerebral Abeta42 levels. Amyloid deposition (and gliosis) begins at 2 months and reaches a very large burden, especially in subiculum and deep cortical layers. Intraneuronal Abeta42 accumulates in 5XFAD brain starting at 1.5 months of age (before plaques form), is aggregated (as determined by thioflavin S staining), and occurs within neuron soma and neurites. Some amyloid deposits originate within morphologically abnormal neuron soma that contain intraneuronal Abeta. Synaptic markers synaptophysin, syntaxin, and postsynaptic density-95 decrease with age in 5XFAD brain, and large pyramidal neurons in cortical layer 5 and subiculum are lost. In addition, levels of the activation subunit of cyclin-dependent kinase 5, p25, are elevated significantly at 9 months in 5XFAD brain, although an upward trend is observed by 3 months of age, before significant neurodegeneration or neuron loss. Finally, 5XFAD mice have impaired memory in the Y-maze. Thus, 5XFAD mice rapidly recapitulate major features of AD amyloid pathology and may be useful models of intraneuronal Abeta42-induced neurodegeneration and amyloid plaque formation.


Sialyltransferase7A, a Klf4-responsive gene, promotes cardiomyocyte apoptosis during myocardial infarction.
Myocardial infarction (MI) is one major cause of heart failure through its induction of cardiomyocyte death. However, the molecular mechanisms associated with MI-induced cardiomyocyte apoptosis in the context of sialylation of heart are not yet understood. In this study, we found that sialyltransferase7A (Siat7A), one of the members of sialyltransferase family, was significantly increased in the ischemic myocardium, as well as in the human cardiomyocyte cell line AC16 under hypoxic condition. The Sialyl-Tn antigen (Neu5Acα2-6GalNAc-O-Ser/Thr) synthesized by Siat7A also increased in the AC16 cardiomyocytes following hypoxic stimulus. Increased Siat7A promoted cardiomyocyte apoptosis. The knockdown of Siat7A expression reduced cardiomyocyte apoptosis in both of vivo and vitro. Furthermore, the decreased extracellular signal-regulated kinase ERK1 and ERK2 (ERK1/2) activity was involved in the Siat7A-induced cardiomyocyte apoptosis. Notably, we showed that Krüppel-like factor 4 (Klf4), one of the transcription factors, specifically bound to the Siat7A promoter by ChIP assays. Deletion and mutagenesis analysis identified that Klf4 could transactivate the Siat7A promoter region (nt -655 to -636 bp). The upregulated Siat7A expression, which was paralleled by the increased Klf4 in the ischemic myocardium, contributed to cardiomyocyte apoptosis. Our study suggests Siat7A could be a valuable target for developing treatments for MI patients.


Reduced biomass burning emissions reconcile conflicting estimates of the post-2006 atmospheric methane budget.
Several viable but conflicting explanations have been proposed to explain the recent ~8 p.p.b. per year increase in atmospheric methane after 2006, equivalent to net emissions increase of ~25 Tg CH4 per year. A concurrent increase in atmospheric ethane implicates a fossil source; a concurrent decrease in the heavy isotope content of methane points toward a biogenic source, while other studies propose a decrease in the chemical sink (OH). Here we show that biomass burning emissions of methane decreased by 3.7 (±1.4) Tg CH4 per year from the 2001-2007 to the 2008-2014 time periods using satellite measurements of CO and CH4, nearly twice the decrease expected from prior estimates. After updating both the total and isotopic budgets for atmospheric methane with these revised biomass burning emissions (and assuming no change to the chemical sink), we find that fossil fuels contribute between 12-19 Tg CH4 per year to the recent atmospheric methane increase, thus reconciling the isotopic- and ethane-based results.


Association of coffee and caffeine intake with the risk of Parkinson disease.
The projected expansion in the next several decades of the elderly population at highest risk for Parkinson disease (PD) makes identification of factors that promote or prevent the disease an important goal. To explore the association of coffee and dietary caffeine intake with risk of PD. Data were analyzed from 30 years of follow-up of 8004 Japanese-American men (aged 45-68 years) enrolled in the prospective longitudinal Honolulu Heart Program between 1965 and 1968. Incident PD, by amount of coffee intake (measured at study enrollment and 6-year follow-up) and by total dietary caffeine intake (measured at enrollment). During follow-up, 102 men were identified as having PD. Age-adjusted incidence of PD declined consistently with increased amounts of coffee intake, from 10.4 per 10,000 person-years in men who drank no coffee to 1.9 per 10,000 person-years in men who drank at least 28 oz/d (P<.001 for trend). Similar relationships were observed with total caffeine intake (P<.001 for trend) and caffeine from non-coffee sources (P=.03 for trend). Consumption of increasing amounts of coffee was also associated with lower risk of PD in men who were never, past, and current smokers at baseline (P=.049, P=.22, and P=.02, respectively, for trend). Other nutrients in coffee, including niacin, were unrelated to PD incidence. The relationship between caffeine and PD was unaltered by intake of milk and sugar. Our findings indicate that higher coffee and caffeine intake is associated with a significantly lower incidence of PD. This effect appears to be independent of smoking. The data suggest that the mechanism is related to caffeine intake and not to other nutrients contained in coffee. JAMA. 2000;283:2674-2679.


Enhancing nitrogen removal efficiency in a dyestuff wastewater treatment plant with the IFFAS process: the pilot-scale and full-scale studies.
The activated sludge (AS) process is widely applied in dyestuff wastewater treatment plants (WWTPs); however, the nitrogen removal efficiency is relatively low and the effluent does not meet the indirect discharge standards before being discharged into the industrial park's WWTP. Hence it is necessary to upgrade the WWTP with more advanced technologies. Moving bed biofilm processes with suspended carriers in an aerobic tank are promising methods due to enhanced nitrification and denitrification. Herein, a pilot-scale integrated free-floating biofilm and activated sludge (IFFAS) process was employed to investigate the feasibility of enhancing nitrogen removal efficiency at different hydraulic retention times (HRTs). The results showed that the effluent chemical oxygen demand (COD), ammonium nitrate (NH4+-N) and total nitrogen (TN) concentrations of the IFFAS process were significantly lower than those of the AS process, and could meet the indirect discharge standards. PCR-DGGE and FISH results indicated that more nitrifiers and denitrifiers co-existed in the IFFAS system, promoting simultaneous nitrification and denitrification. Based on the pilot results, the IFFAS process was used to upgrade the full-scale AS process, and the effluent COD, NH4+-N and TN of the IFFAS process were 91-291 mg/L, 10.6-28.7 mg/L and 18.9-48.6 mg/L, stably meeting the indirect discharge standards and demonstrating the advantages of IFFAS in dyestuff wastewater treatment.


Expression of visinin-like protein-3 in mouse kidney.
In renal proximal brush borders the Na/Pi cotransporter NaPi-IIa is part of a heteromultimeric complex including the PDZ proteins PDZK1 and NHERF1, which interact with the C terminus of NaPi-IIa. In this study, a yeast two-hybrid screen against the N terminus of the Na/Pi cotransporter NaPi-IIa was performed. Thereby we identified visinin-like protein-3 (VILIP-3), a member of neuronal calcium sensors. In this study, expression and protein localization of VILIP-3 in the mouse kidney was performed by immunofluorescence and RT-PCR using laser-assisted microdissected nephron segments. VILIP-3 was found to be abundant in distal and collecting ducts where it partly colocalized with calbindin D28K. In addition VILIP-3 was observed in the brush borders of proximal tubular S1 and S3 segments of both superficial and deep nephrons.


Enzymatic activities of allergen extracts from three species of dust mites and cockroaches commonly found in Korean home.
Allergen extracts from dust mites and cockroaches commonly found in Korean homes were used to evaluate their enzymatic activity as they are believed to influence allergenicity. Allergen extracts were prepared from 3 dust mite species (Dermatophagoides farinae, D. pteronyssinus, and Tyrophagus putrescentiae) and 3 cockroach species (Blattella germanica, Periplaneta americana, and P. fuliginosa) maintained in the Korea National Arthropods of Medical Importance Resource Bank. Proteins were extracted in PBS after homogenization using liquid nitrogen. The activities of various enzymes were investigated using the API Zym system. No significant difference in phosphatase, lipase, or glycosidase activity was observed among the 6 allergen extracts, but much difference was observed in protease activity. Protease activity was assessed in more detail by gelatin zymography and the EnzChek assay. Extract from T. putrescentiae showed the highest protease activity, followed by those of the cockroach extracts. Extracts from D. farinae and D. pteronyssinus showed only weak protease activity. Gelatinolytic activity was detected mainly in a 30-kDa protein in D. farinae, a 28-kDa protein in D. pteronyssinus, a > 26-kDa protein in T. putrescentiae, a > 20-kDa protein in B. germanica, and a > 23-kDa protein in P. americana and P. fuliginosa. The information on various enzymatic activities obtained in this study may be useful for future studies. In particular, the strong protease activity found in cockroach extracts could contribute to sensitization to cockroach allergens, which is known to be associated with the development of asthma.


Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice.
Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD.


Strength-dependent perturbation of whole-brain model working in different regimes reveals the role of fluctuations in brain dynamics.
Despite decades of research, there is still a lack of understanding of the role and generating mechanisms of the ubiquitous fluctuations and oscillations found in recordings of brain dynamics. Here, we used whole-brain computational models capable of presenting different dynamical regimes to reproduce empirical data's turbulence level. We showed that the model's fluctuations regime fitted to turbulence more faithfully reproduces the empirical functional connectivity compared to oscillatory and noise regimes. By applying global and local strength-dependent perturbations and subsequently measuring the responsiveness of the model, we revealed each regime's computational capacity demonstrating that brain dynamics is shifted towards fluctuations to provide much-needed flexibility. Importantly, fluctuation regime stimulation in a brain region within a given resting state network modulates that network, aligned with previous empirical and computational studies. Furthermore, this framework generates specific, testable empirical predictions for human stimulation studies using strength-dependent rather than constant perturbation. Overall, the whole-brain models fitted to the level of empirical turbulence together with functional connectivity unveil that the fluctuation regime best captures empirical data, and the strength-dependent perturbative framework demonstrates how this regime provides maximal flexibility to the human brain.


Electrical Impedance Tomography: a new study method for neonatal Respiratory Distress Syndrome?
Treatment of cardiorespiratory system diseases is a procedure that usually demands data collection on terms of the anatomy and the operation of the organs that are under study. Electrical Impedance Tomography (EIT) is an alternative approach, in comparison to existing techniques. With EIT electrodes are placed in the perimeter of the human body and images of the estimated organ are reconstructed, using the measurement of its impendence (or resistance) distribution and determining its alteration through time, while at the same time the patient is not exposed to ionizing radiation. Its clinical use presupposes the correct placement of the electrodes over the perimeter of the human body, the rapid data collection and electrical safety. It is a low cost technique and it is implemented near the patient. It is able to determine the distribution of ventilation, blood supply, diffused or localized lung defects, but it can also estimate therapeutic interventions or alteration to assisted ventilation of the neonate. EIT was developed at the beginning of the 1980s, but it has only recently begun to be implemented on neonates, and especially in the study of their respiratory system function. The low rate of image analysis is considered to be a drawback, but it is offset by the potential offered for the estimation of lungs' function (both under normal and pathological conditions), since ventilation and resistance are two quite similar concepts. In this review the most important studies about EIT are mentioned as a method of estimating respiratory distress syndrome in neonates. In terms of the above mentioned development, it is supposed that this technique will offer a great amount of help to the doctor in his / her estimations of the cardiorespiratory system and to his / her selection of the best intervening strategies.


Dietary β-glucans differentially modulate immune and stress-related gene expression in lymphoid organs from healthy and Aeromonas hydrophila-infected rainbow trout (Oncorhynchus mykiss).
Although β-glucans stimulating effects have already been demonstrated on the immune system of numerous animal species, available data remain relatively variable and more research should be done regarding the complexity of underlying mechanisms. In this context, the present study aimed to evaluate the stress and immune-related effects of dietary β-glucans (i.e. Macrogard®) by considering a number of influencing factors such as the dose (0, 0.1, 0.2 and 0.5% in food), feeding duration (15 versus 30 days), tissue (blood, kidney, spleen, gills) and infection status (healthy or infected). Blood parameters (lysozyme, ACH50 activities, leucocyte populations) and mRNA expression level of several immune- and stress-related genes (TFN-α1, IL-1β, IL10, COX-2, TGF-β, MC2R, HSP70) were measured. Our results suggest that spleen may be a highly responsive organ to dietary β-glucans both in healthy or infected fish, and that this organ may therefore significantly contribute to the immune reinforcement induced by such immunostimulatory diet. Our study further reveals that overdoses of β-glucans and/or prolonged medication can lead to a non-reactive physiological status and, consequently, to a poor immune response. All in all, the current data emphasizes the need for further extensive research in the field of dietary β-glucans as a preventive method for farmed fish protection.


The lived experience of new graduate nurses working in an acute care setting.
The high attrition rate of graduate nurses will exacerbate the current nursing shortage as Baby Boomer nurses (born between 1946 and 1964) retire, negatively affecting the quality of patient care and increasing employer costs. The purpose of this phenomenological study was to explore the lived experiences of new graduate nurses employed in an acute care setting in southwest Florida. This information provides further guidance to nurse educators as they develop curricula, support graduate nurses to transition into professional practice, and create strategies to increase retention. Ten participants who were traditional students in generic baccalaureate nursing programs, selected through purposeful and snowball sampling, were interviewed via open-ended questions. Using Colaizzi's classic phenomenological method of data analysis and NVivo 10 software, three over-arching themes emerged-knowledge, skills, and environment-which were interpreted in relation to graduates' lived experience. Recommendations include implementation of innovative initiatives that address new graduates' experience and increase retention.


Diffusional motion of redox centers in carbonate electrolytes.
Ferrocene (Fc) and N-(ferrocenylmethyl)-N,N-dimethyl-N-ethylammonium bistrifluoromethyl-sulfonimide (Fc1N112-TFSI) were dissolved in carbonate solvents and self-diffusion coefficients (D) of solutes and solvents were measured by (1)H and (19)F pulsed field gradient nuclear magnetic resonance (NMR) spectroscopy. The organic solvents were propylene carbonate (PC), ethyl methyl carbonate (EMC), and a ternary mixture that also includes ethylene carbonate (EC). Results from NMR studies over the temperature range of 0-50 °C and for various concentrations (0.25-1.7 M) of Fc1N112-TFSI are compared to values of D simulated with classical molecular dynamics (MD). The measured self-diffusion coefficients gradually decreased as the Fc1N112-TFSI concentration increased in all solvents. Since TFSI(-) has fluoromethyl groups (CF3), D(TFSI) could be measured separately and the values found are larger than those for D(Fc1N112) in all samples measured. The EC, PC, and EMC have the same D in the neat solvent mixture and when Fc is dissolved in EC/PC/EMC at a concentration of 0.2 M, probably due to the interactions between common carbonyl structures within EC, PC, and EMC. A difference in D (D(PC) < D(EC) < D(EMC)), and both a higher E(a) for translational motion and higher effective viscosity for PC in the mixture containing Fc1N112-TFSI reflect the interaction between PC and Fc1N112(+), which is a relatively stronger interaction than that between Fc1N112(+) and other solvent species. In the EC/PC/EMC solution that is saturated with Fc1N112-TFSI, we find that D(PC) = D(EC) = D(EMC) and Fc1N112(+) and all components of the EC/PC/EMC solution have the same E(a) for translational motion, while the ratio D(EC/PC/EMC)/D(Fc1N112) is approximately 3. These results reflect the lack of available free volume for independent diffusion in the saturated solution. The Fc1N112(+) transference numbers lie around 0.4 and increase slightly as the temperature is increased in the PC and EMC solvents. The trends observed for D from simulations are in good agreement with experimental results and provide molecular level understanding of the solvation structure of Fc1N112-TFSI dissolved in EC/PC/EMC.


Dysregulated bile acid synthesis, metabolism and excretion in a high fat-cholesterol diet-induced fibrotic steatohepatitis in rats.
Cholesterol over-intake is involved in the onset of nonalcoholic steatohepatitis (NASH), and hepatocellular bile acid (BA) accumulation correlates with liver injuries. However, how dietary cholesterol influences cholesterol and BA kinetics in NASH liver remains ambiguous and needs to be clarified. Molecular markers involved in cholesterol and BA kinetics were investigated at protein and mRNA levels in an already-established stroke-prone spontaneously hypertensive 5/Dmcr rat model with fibrotic steatohepatitis, by feeding a high fat-cholesterol (HFC) diet. Unlike the control diet, the HFC diet deposited cholesterol greatly in rat livers, where 3-hydroxy-3-methylglutaryl CoA reductase, low-density lipoprotein (LDL) receptor and LDL receptor-related protein-1 were expectedly downregulated, especially at 8 and 14 weeks, suggesting that cholesterol synthesis and uptake in response to cholesterol accumulation may not be disorganized. The HFC diet did not upregulate liver X receptor-α, conversely, it enhanced classic BA synthesis by upregulating cholesterol 7α-hydroxylase but downregulating sterol 12α-hydroxylase, and influenced alternative synthesis by downregulating sterol 27-hydroxylase but upregulating oxysterol 7α-hydroxylase, mainly at 8 and 14 weeks, indicating that there were different productions of primary BA species. Unexpectedly, no feedback inhibition of BA synthesis by farnesoid X receptor occurred. Additionally, the HFC diet impaired BA detoxification by UDP-glucuronosyltransferase and sulfotransferase 2A1, and decreased excretion by bile salt export pump at 8 and 14 weeks, although it induced compensatory export by multidrug resistance-associated protein-3. The disturbed BA detoxification may correlate with suppressed pregnane X receptor and constitutive androstane receptor. The HFC diet may accumulate BA in rat livers, which influences fibrotic steatohepatitis progression.


A tunable single-component warm white-light Sr3Y(PO4)3:Eu2+,Mn2+ phosphor for white-light emitting diodes.
The photoluminescence properties and energy transfer of the Eu(2+) and Mn(2+) co-doped Sr(3)Y(PO(4))(3) phosphors are investigated in detail. Two main emission bands attributed to the Eu(2+) and Mn(2+) ions are observed under UV light excitation via an efficient energy transfer process. When the Eu(2+) doping content is fixed, the emission chromaticity can be varied by simply adjusting the content of Mn(2+). The study of the behavior as a function of doping concentration indicates that the warm white-light can be obtained in a single host lattice. Furthermore, the analysis of the fluorescence decay curves based on the Inokuti-Hirayama theoretical model reveals that the dipole-quadrupole interaction is mainly responsible for the energy transfer mechanism from the Eu(2+) to Mn(2+) ions in the Sr(3)Y(PO(4))(3) phosphor. The developed phosphor exhibits a strong absorption in UV spectral region and white-light emission which may find utility as a single-component white-light-emitting UV-convertible phosphor in white LED devices.


Targeting factors for change: contraceptive counselling and care of female adolescents.
Sexual and reproductive health care should empower and enable all individuals to have a sex life that is as safe and pleasurable as possible. Achievement of this goal for adolescents is often impeded by regional and sociocultural barriers. To review global barriers to provision of effective counselling and care of adolescents seeking advice on contraception and sexual and reproductive health and identify elements of best practice that can be adapted to meet their needs at regional level. Experts with clinical experience and a scholarly background in the provision of contraceptive services to adolescents participated in a stepwise process of literature review and discussion according to the agreed objectives. The Global CARE (Contraception: Access, Resources, Education) group identified barriers to the access, availability and acceptance of contraception by adolescents, not only at the political and sociocultural level but also within health care practice. The group collected and summarized successful local strategies and tools suitable for adaptation in other regions. Elements of best practice for providing contraception regardless of setting or regional constraints, including required skills, knowledge, and attitudes, were also proposed. Sharing of evidence-based best practice in delivering contraceptive services, improvements in health care provider education, and sharing of experience between countries will hopefully help to overcome the barriers to appropriate and effective counselling and care of adolescents.


Glucose metabolism in critically ill patients: are incretins an important player?
Critical illness afflicts millions of people worldwide and is associated with a high risk of organ failure and death or an adverse outcome with persistent physical or cognitive deficits. Spontaneous hyperglycemia is common in critically ill patients and is associated with an adverse outcome compared to normoglycemia. Insulin is used for treating hyperglycemia in the critically ill patients but may be complicated by hypoglycemia, which is difficult to detect in these patients and which may lead to serious neurological sequelae and death. The incretin hormone, glucagon-like peptide (GLP) 1, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar characteristics and are, among other things, both characterized by different grades of systemic inflammation and insulin resistance. The GLP-1 might be a potential new treatment target in critically ill patients with stress-induced hyperglycemia.


The importance of bone biomarkers in the diagnosis of renal osteodystrophy.
To evaluate the association of serum biochemical markers in patients with chronic kidney disease (CKD) in Jamaica for early detection of renal osteodystrophy (ROD). The study contained two groups: CKD group (221) which consisted of adult patients, from dialysis units and renal clinics, with stage III to V CKD. The control group (237) had adult individuals, from the medical outpatient clinics, with mild and controlled chronic diseases and absence of renal failure. The patients in the study were between 18-80 years of age and gave informed consent to participate in the study. The differences in distribution of demographic, clinical and pathologic variables between the two groups were evaluated. Pearson's chi-squared test and Spearman' rho correlation coefficient test was used, with p < 0.01 considered statistically significant. Data analysis was conducted using the statistical package for the social sciences (SPSS) version 17.0. Among the 221 CKD patients in the study, 174 (78.7%) had ROD based on serum intact parathyroid hormone (iPTH) levels. The majority of patients in the control group did not have bone disease ie 95-96%. The majority of CKD patients (70.0%) had high-turnover (HTO) bone disease compared to 29.3% of patients with low-turnover (LTO) bone disease. Dialysis patients who had HTO bone disease compared with those with LTO had significantly higher levels of iPTH and total serum alkaline phosphatase (ALP). A similar relationship was observed among CKD patients not on dialysis. There was a significant individual variation in bone turnover biochemical markers. A total of 237 patients were recruited in the control group. Based on the levels of iPTH and tALP six of them were found to have bone disease. The majority of these patients with bone disease were diabetic (83.3%) while the other patient had cancer (16.7%). The six patients in the control group with bone disease were within the age cohort of 64-80 years, most of whom were 78 years old. A combination of serum biochemical markers might predict underlying renal osteodystrophy better that would individual biochemical markers. A predictive model using bone histology and biochemical markers can be developed in the future.


Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division.
Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons. Although CoMIC is potentiated by inhibition of Drp1 and occurs at the potential division spots contacting the endoplasmic reticulum, it appears on IMM independently of OMM. Intra-mitochondrial influx of Ca2+ induces and potentiates CoMIC, and leads to K+-mediated mitochondrial bulging and depolarization. Synergistically, optic atrophy 1 (Opa1) also regulates CoMIC via controlling Mic60-mediated OMM-IMM tethering. Therefore, we propose that CoMIC is a priming event for efficient mitochondrial division.


Computational modelling reveals distinct patterns of cognitive and physical motivation in elite athletes.
Effort can be perceived both cognitively and physically, but the computational mechanisms underlying the motivation to invest effort in each domain remain unclear. In particular, it is unknown whether intensive physical training is associated with higher motivation specific to that domain, or whether it is accompanied by corresponding changes in cognitive motivation. Here, we tested a group of elite Oxford University rowers, and compared their behaviour to matched non-athletic controls. We trained participants on two tasks involving cognitive or physical effort. They then decided between a baseline low level of effort for low reward, versus higher levels of effort for higher rewards. Separate choices were made for the cognitive and physical tasks, which allowed us to computationally model motivation in each domain independently. As expected, athletes were willing to exert greater amounts of physical effort than non-athletes. Critically, however, the nature of cognitive effort-based decisions was different between groups, with a concave pattern of effort discounting for athletes but a convex pattern for non-athletes. These data suggest that the greater physical drive in athletes is accompanied by fundamentally different patterns of cognitive effort discounting, and suggests a complex relationship between motivation in the two domains.


Infectious and autoantibody-associated encephalitis: clinical features and long-term outcome.
Pediatric encephalitis has a wide range of etiologies, clinical presentations, and outcomes. This study seeks to classify and characterize infectious, immune-mediated/autoantibody-associated and unknown forms of encephalitis, including relative frequencies, clinical and radiologic phenotypes, and long-term outcome. By using consensus definitions and a retrospective single-center cohort of 164 Australian children, we performed clinical and radiologic phenotyping blinded to etiology and outcomes, and we tested archived acute sera for autoantibodies to N-methyl-D-aspartate receptor, voltage-gated potassium channel complex, and other neuronal antigens. Through telephone interviews, we defined outcomes by using the Liverpool Outcome Score (for encephalitis). An infectious encephalitis occurred in 30%, infection-associated encephalopathy in 8%, immune-mediated/autoantibody-associated encephalitis in 34%, and unknown encephalitis in 28%. In descending order of frequency, the larger subgroups were acute disseminated encephalomyelitis (21%), enterovirus (12%), Mycoplasma pneumoniae (7%), N-methyl-D-aspartate receptor antibody (6%), herpes simplex virus (5%), and voltage-gated potassium channel complex antibody (4%). Movement disorders, psychiatric symptoms, agitation, speech dysfunction, cerebrospinal fluid oligoclonal bands, MRI limbic encephalitis, and clinical relapse were more common in patients with autoantibodies. An abnormal outcome occurred in 49% of patients after a median follow-up of 5.8 years. Herpes simplex virus and unknown forms had the worst outcomes. According to our multivariate analysis, an abnormal outcome was more common in patients with status epilepticus, magnetic resonance diffusion restriction, and ICU admission. We have defined clinical and radiologic phenotypes of infectious and immune-mediated/autoantibody-associated encephalitis. In this resource-rich cohort, immune-mediated/autoantibody-associated etiologies are common, and the recognition and treatment of these entities should be a clinical priority.


As diversity increases, people paradoxically perceive social groups as more similar.
With globalization and immigration, societal contexts differ in sheer variety of resident social groups. Social diversity challenges individuals to think in new ways about new kinds of people and where their groups all stand, relative to each other. However, psychological science does not yet specify how human minds represent social diversity, in homogeneous or heterogenous contexts. Mental maps of the array of society's groups should differ when individuals inhabit more and less diverse ecologies. Nonetheless, predictions disagree on how they should differ. Confirmation bias suggests more diversity means more stereotype dispersion: With increased exposure, perceivers' mental maps might differentiate more among groups, so their stereotypes would spread out (disperse). In contrast, individuation suggests more diversity means less stereotype dispersion, as perceivers experience within-group variety and between-group overlap. Worldwide, nationwide, individual, and longitudinal datasets (n = 12,011) revealed a diversity paradox: More diversity consistently meant less stereotype dispersion. Both contextual and perceived ethnic diversity correlate with decreased stereotype dispersion. Countries and US states with higher levels of ethnic diversity (e.g., South Africa and Hawaii, versus South Korea and Vermont), online individuals who perceive more ethnic diversity, and students who moved to more ethnically diverse colleges mentally represent ethnic groups as more similar to each other, on warmth and competence stereotypes. Homogeneity shows more-differentiated stereotypes; ironically, those with the least exposure have the most-distinct stereotypes. Diversity means less-differentiated stereotypes, as in the melting pot metaphor. Diversity and reduced dispersion also correlate positively with subjective wellbeing.


How does surgery compare to sham surgery or physiotherapy as a treatment for tendinopathy? A systematic review of randomised trials.
To assess the effectiveness of surgery on all tendinopathies by comparing it to no treatment, sham surgery and exercise-based therapies for both mid-term (12 months) and long-term (> 12 months) outcomes. Our literature search included EMBASE, Medline, CINAHL and Scopus. A combined assessment of internal validity, external validity and precision of each eligible study yielded its overall study quality. Results were considered significant if they were based on strong (Level 1) or moderate (Level 2) evidence. 12 studies were eligible. Participants had the following types of tendinopathy: shoulder in seven studies, lateral elbow in three, patellar in one and Achilles in one. Two studies were of good, four of moderate and six of poor overall quality. Surgery was superior to no treatment or placebo, for the outcomes of pain, function, range of movement (ROM) and treatment success in the short and midterm. Surgery had similar effects to sham surgery on pain, function and range of motion in the midterm. Physiotherapy was as effective as surgery both in the midterm and long term for pain, function, ROM and tendon force, and pain, treatment success and quality of life, respectively. We recommend that healthcare professionals who treat tendinopathy encourage patients to comply with loading exercise treatment for at least 12 months before the option of surgery is seriously entertained.


Anticipatory Vibrotactile Cueing Facilitates Grip Force Adjustment during Perturbative Loading.
Grip force applied to an object held between the thumb and index finger is automatically and unconsciously adjusted upon perception of an external disturbance to the object. Typically, this adjustment occurs within approximately 100 ms. Here, we investigated the effect of anticipatory vibrotactile cues prior to a perturbative force, which the central nervous system may use for rapid grip re-stabilization. We asked participants to grip and hold an instrumented, actuated handle between the thumb and index finger. Under computer control, the handle could suddenly be pulled away from a static grip and could independently provide vibration to the gripping fingers. The mean latency of corrective motor action was 139 ms. When vibrotactile stimulation was applied 50 ms before application of tractive force, the latency was reduced to 117 ms, whereas the mean latency of the conscious response to vibrotactile stimuli alone was 229 ms. This suggests that vibrotactile stimulation can influence reflex-like actions. We also examined the effects of anticipatory cues using a set of perturbative loads with different rising rates. As expected, facilitation of grip force adjustment was observed for moderate loads. In contrast, anticipatory cues had an insignificant effect on rapid loads that evoked an adjustment within 60-80 ms, which approaches the minimum latency of human grip adjustment. Understanding the facilitative effects of anticipatory cues on human reactive grip can aid the development of human-machine interfaces to enhance human behavior.


Quantitative three-dimensional imaging of live avian embryonic morphogenesis via micro-computed tomography.
Many clinically relevant congenital malformations arise during mid to late embryonic stages. This period is challenging to image quantitatively in live embryos, necessitating the use of multiple specimens with increased experimental variability. Here we establish X-ray and blood-pool computed tomography (CT) contrast agent toxicity and teratogenesis thresholds for 3D Micro-CT imaging of live avian embryos. Day 4 chick embryos micro-injected with Visipaque™ (VP) developed for an additional 6 days without defect. X-ray radiation up to 798 mGy was nontoxic. Peak average contrast of 1,060 HU occurred within 1 hr of imaging at 50 μm resolution. VP-enhanced contrast persisted past 24 hr with delayed accumulation in the allantois. Regional volumes of VP-injected embryos were statistically identical to those of fixed embryos perfused with osmium tetroxide. We further quantified longitudinal volumetric morphogenesis of the allantois over 30 hr. These results demonstrate the safety and efficacy of contrast enhanced quantitative micro-CT imaging for live embryos.


Restricted Access to Working Memory Does Not Prevent Cumulative Score Improvement in a Cultural Evolution Task.
Some theories propose that human cumulative culture is dependent on explicit, system-2, metacognitive processes. To test this, we investigated whether access to working memory is required for cumulative cultural evolution. We restricted access to adults' working-memory (WM) via a dual-task paradigm, to assess whether this reduced performance in a cultural evolution task, and a metacognitive monitoring task. In total, 247 participants completed either a grid search task or a metacognitive monitoring task in conjunction with a WM task and a matched control. Participants' behaviour in the grid search task was then used to simulate the outcome of iterating the task over multiple generations. Participants in the grid search task scored higher after observing higher-scoring examples, but could only beat the scores of low-scoring example trials. Scores did not differ significantly between the control and WM distractor blocks, although more errors were made when under WM load. The simulation showed similar levels of cumulative score improvement across conditions. However, scores plateaued without reaching the maximum. Metacognitive efficiency was low in both blocks, with no indication of dual-task interference. Overall, we found that taxing working-memory resources did not prevent cumulative score improvement on this task, but impeded it slightly relative to a control distractor task. However, we found no evidence that the dual-task manipulation impacted participants' ability to use explicit metacognition. Although we found minimal evidence in support of the explicit metacognition theory of cumulative culture, our results provide valuable insights into empirical approaches that could be used to further test predictions arising from this account.


Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer's disease.
Amyloid imaging studies of presymptomatic familial Alzheimer's disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer's disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer's disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network.


A vitamin-C-derived DNA modification catalysed by an algal TET homologue.
Methylation of cytosine to 5-methylcytosine (5mC) is a prevalent DNA modification found in many organisms. Sequential oxidation of 5mC by ten-eleven translocation (TET) dioxygenases results in a cascade of additional epigenetic marks and promotes demethylation of DNA in mammals1,2. However, the enzymatic activity and function of TET homologues in other eukaryotes remains largely unexplored. Here we show that the green alga Chlamydomonas reinhardtii contains a 5mC-modifying enzyme (CMD1) that is a TET homologue and catalyses the conjugation of a glyceryl moiety to the methyl group of 5mC through a carbon-carbon bond, resulting in two stereoisomeric nucleobase products. The catalytic activity of CMD1 requires Fe(II) and the integrity of its binding motif His-X-Asp, which is conserved in Fe-dependent dioxygenases3. However, unlike previously described TET enzymes, which use 2-oxoglutarate as a co-substrate4, CMD1 uses L-ascorbic acid (vitamin C) as an essential co-substrate. Vitamin C donates the glyceryl moiety to 5mC with concurrent formation of glyoxylic acid and CO2. The vitamin-C-derived DNA modification is present in the genome of wild-type C. reinhardtii but at a substantially lower level in a CMD1 mutant strain. The fitness of CMD1 mutant cells during exposure to high light levels is reduced. LHCSR3, a gene that is critical for the protection of C. reinhardtii from photo-oxidative damage under high light conditions, is hypermethylated and downregulated in CMD1 mutant cells compared to wild-type cells, causing a reduced capacity for photoprotective non-photochemical quenching. Our study thus identifies a eukaryotic DNA base modification that is catalysed by a divergent TET homologue and unexpectedly derived from vitamin C, and describes its role as a potential epigenetic mark that may counteract DNA methylation in the regulation of photosynthesis.


HIV donor funding has both boosted and curbed the delivery of different non-HIV health services in sub-Saharan Africa.
Donor funding for HIV programs has increased rapidly over the past decade, raising questions about whether other health services in recipient-country health systems are being crowded out or strengthened. This article--an investigation of the impacts of increased HIV donor funding on non-HIV health services in sub-Saharan Africa during 2003-10--provides evidence of both effects. HIV aid in some countries has crowded out the delivery of childhood immunizations, especially in countries with the lowest density of health care providers. At the same time, HIV aid may have positively affected some maternal health services, such as prenatal blood testing. These mixed results suggest that donors should be more attentive to domestic resource constraints, such as limited numbers of health workers; should integrate more fully with existing health systems; and should address these constraints up front to limit possible negative effects on the delivery of other health services.


Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation.
TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1's plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies.


Eagles enter rotor-swept zones of wind turbines at rates that vary per turbine.
There is increasing pressure on wind energy facilities to manage or mitigate for wildlife collisions. However, little information exists regarding spatial and temporal variation in collision rates, meaning that mitigation is most often a blanket prescription. To address this knowledge gap, we evaluated variation among turbines and months in an aspect of collision risk-probability of entry by an eagle into a rotor-swept zone (hereafter, "probability of entry"). We examined 10,222 eagle flight paths identified and recorded by an automated bird monitoring system at a wind energy facility in Wyoming, USA. Probabilities of entry per turbine-month combination were 4.03 times greater in some months than others, ranging 0.15 to 0.62. The overall probability of entry for the riskiest turbine (i.e., the one with the greatest probability of entry) was 2.39 times greater than the least-risky turbine. Our methodology describes large variation across turbines and months in the probability of entry. If subsequently combined with information on other sources of variation (i.e., weather, topography), this approach can identify risky versus safe situations for eagles under which cost of management, curtailment prescriptions, and collision risk can be simultaneously minimized.


Development of amyloid beta gold nanorod aggregates as optoacoustic probes.
Propagation of small amyloid beta (Aβ) aggregates (or seeds) has been suggested as a potential mechanism of Alzheimer's disease progression. Monitoring the propagation of Aβ seeds in an organism would enable testing of this hypothesis and, if confirmed, provide mechanistic insights. This requires a contrast agent for long-term tracking of the seeds. Gold nanorods combine several attractive features for this challenging task, in particular, their strong absorbance in the infrared (enabling optoacoustic imaging) and the availability of several established protocols for surface functionalisation. In this work, polymer-coated gold nanorods were conjugated with anti-Aβ antibodies and attached to pre-formed Aβ seeds. The resulting complexes were characterised for their optical properties by UV/Vis spectroscopy and multispectral optoacoustic tomography. The complexes retained their biophysical properties, i.e. their ability to seed Aβ fibril formation. They remained stable in biological media for at least 2 days and showed no toxicity to SH-SY5Y neuroblastoma cells up to 1.5 nM and 6 μM of gold nanorods and Aβ seeds, respectively. Taken together, this study describes the first steps in the development of probes for monitoring the spread of Aβ seeds in animal models.


Highly transparent supercapacitors based on ZnO/MnO2 nanostructures.
The recent rapid development of transparent electronics, notably displays and control circuits, requires the development of highly transparent energy storage devices, such as supercapacitors. The devices reported to date utilize carbon-based electrodes for high performance, however at the cost of their low transparency around 50%, insufficient for real transparent devices. To overcome this obstacle, in this communication highly transparent supercapacitors were fabricated based on ZnO/MnO2 nanostructured electrodes. ZnO served as an intrinsically transparent skeleton for increasing the electrode surface, while MnO2 nanoparticles were applied for high capacitance. Two MnO2 synthesis routes were followed, based on the reaction of KMnO4 with Mn(Ac)2 and PAH, leading to the synthesis of β-MnO2 with minority α-MnO2 nanoparticles and amorphous MnO2 with embedded β-MnO2, respectively. The devices based on such electrodes showed high capacitances of 2.6 mF cm-2 and 1.6 mF cm-2, respectively, at a scan rate of 1 mV s-1 and capacitances of 104 μF cm-2 and 204 μF cm-2 at a very high rate of 1 V s-1, not studied for transparent supercapacitors previously. Additionally, the Mn(Ac)2 devices exhibited very high transparencies of 86% vs. air, far superior to other transparent energy storage devices reported with similar charge storage properties. This high device performance was achieved with a non-acidic LiCl gel electrolyte, reducing corrosion and handling risks associated with conventional highly concentrated acidic electrolytes, enabling applications in safe, wearable, transparent devices.


Impact of fusion for adolescent idiopathic scoliosis on lung volume measured with computed tomography.
Although lung volume (LV) can be measured directly by computed tomography (CT), the literature regarding CT-assessed LV in adolescent idiopathic scoliosis (AIS) patients is limited, and the influence of posterior spinal fusion with instrumentation (PSF) on LV has not been established. This study aimed to identify factors associated with decreased LV after PSF in AIS patients. We retrospectively reviewed 111 consecutive AIS patients who were between 10 and 20 years of age and were treated by PSF at our facility. We assessed age at surgery, sex, height, body weight, Risser stage, Lenke classification, radiographic parameters, pulmonary function tests, and LV. Factors associated with a postoperative decrease in LV were identified by multivariable analysis. The mean total LV had increased at the 2-year follow-up, although marginally significant (p = .06), and there was a significant increase in the left LV (p = .01) but not the right LV (p = .25). We observed a postoperative reduction in total LV, defined as a total LV postoperative/preoperative ratio < 0.9, in 20 of the 111 patients (18.0%). Univariable analysis showed a significant correlation between ≥ 11 fusion levels and postoperative LV reduction (OR 3.11, 95% CI 1.13-8.57). This factor remained significant in the multivariable analysis, which yielded an adjusted OR of 2.82 (95% CI 1.01-7.93) for postoperative LV reduction in patients with ≥ 11 fusion levels. Our data suggest that a longer fusion area is associated with postoperative LV reduction. Therefore, avoidance of a longer fusion area of ≥ 11 will be preferable for preserving LV. These slides can be retrieved under Electronic Supplementary Material.


Long-term Impact of Mode of Delivery on Stress Urinary Incontinence and Urgency Urinary Incontinence: A Systematic Review and Meta-analysis.
Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) are associated with physical and psychological morbidity, and large societal costs. The long-term effects of delivery modes on each kind of incontinence remain uncertain. To investigate the long-term impact of delivery mode on SUI and UUI. We searched Medline, Scopus, CINAHL, and relevant major conference abstracts up to October 31, 2014, including any observational study with adjusted analyses or any randomized trial addressing the association between delivery mode and SUI or UUI ≥1 yr after delivery. Two reviewers extracted data, including incidence/prevalence of SUI and UUI by delivery modes, and assessed risk of bias. Pooled estimates from 15 eligible studies demonstrated an increased risk of SUI after vaginal delivery versus cesarean section (adjusted odds ratio [aOR]: 1.85; 95% confidence interval [CI], 1.56-2.19; I(2)=57%; risk difference: 8.2%). Metaregression demonstrated a larger effect of vaginal delivery among younger women (p=0.005). Four studies suggested no difference in the risk of SUI between spontaneous vaginal and instrumental delivery (aOR: 1.11; 95% CI, 0.84-1.45; I(2)=50%). Eight studies suggested an elevated risk of UUI after vaginal delivery versus cesarean section (aOR: 1.30; 95% CI, 1.02-1.65; I(2)=37%; risk difference: 2.6%). Compared with cesarean section, vaginal delivery is associated with an almost twofold increase in the risk of long-term SUI, with an absolute increase of 8%, and an effect that is largest in younger women. There is also an increased risk of UUI, with an absolute increase of approximately 3%. In this systematic review we looked for the long-term effects of childbirth on urinary leakage. We found that vaginal delivery is associated with an almost twofold increase in the risk of developing leakage with exertion, compared with cesarean section, with a smaller effect on leakage in association with urgency.


Performance Evaluation of Non-GPS Based Localization Techniques under Shadowing Effects.
Non-GPS localization has gained much interest from researchers and industries recently because GPS might fail to meet the accuracy requirements in shadowing environments. The two most common range-based non-GPS localization methods, namely Received Signal Strength Indicator (RSSI) and Angle-of-Arrival (AOA), have been intensively mentioned in the literature over the last decade. However, an in-depth analysis of the weighted combination methods of AOA and RSSI in shadowing environments is still missing in the state-of-the-art. This paper proposes several weighted combinations of the two RSSI and AOA components in the form of pAOA + qRSSI, devises the mathematical model for analyzing shadowing effects, and evaluates these weighted combination localization methods from both accuracy and precision perspectives. Our simulations show that increasing the number of anchors does not necessarily improve the precision and accuracy, that the AOA component is less susceptible to shadowing than the RSSI one, and that increasing the weight of the AOA component and reducing that of the RSSI component help improve the accuracy and precision at high Signal-to-Noise Ratios (SNRs). This observation suggests that some power control algorithm could be used to increase automatically the transmitted power when the channel experiences large shadowing to maintain a high SNR, thus guaranteeing both accuracy and precision of the weighted combination localization techniques.


The Practice of Hatha Yoga for the Treatment of Pain Associated with Endometriosis.
The aim of this study was to compare chronic pelvic pain, menstrual patterns, and quality of life (QoL) in two groups of women with endometriosis: those who did and those who did not participate in a specific 8-week yoga intervention. This was a randomized controlled trial. It was conducted at the University of Campinas Medical School, Campinas, SP, Brazil. Forty women were randomly divided into two groups: an intervention group of women who practiced yoga (n = 28), and a control group of women who did not practice yoga (n = 12). Participants attended 90-min scheduled yoga sessions twice a week for 8 weeks. Additionally, an Endometriosis Health Profile (EHP)-30 questionnaire was applied to evaluate women's QoL at admission and 2 months later upon completion of the yoga program. Menstrual and daily pain patterns were evaluated through a daily calendar (visual analog scale). The degree of daily pain was significantly lower among the women who practiced yoga compared with the non-yoga group (p = 0.0007). There was an improvement of QoL in both groups between baseline and the end of the study evaluation. In relation to EHP-30 domains, pain (p = 0.0046), impotence (p = 0.0006), well-being (p = 0.0009), and image (p = 0.0087) from the central questionnaire, and work (p = 0.0027) and treatment (p = 0.0245) from the modular questionnaire were significantly different between the study groups over time. There was no significant difference between the two groups regarding the diary of menstrual patterns (p = 0.96). Yoga practice was associated with a reduction in levels of chronic pelvic pain and an improvement in QoL in women with endometriosis.