Towards a phylogenetic framework for the evolution of shakes, rattles, and rolls in Myiarchus tyrant-flycatchers (Aves: Passeriformes: Tyrannidae).
A phylogeny of 19 of the 22 currently recognized species of Myiarchus tyrant-flycatchers is presented. It is based on 842bp of mitochondrial DNA (mtDNA) sequences from the ATPase subunit 8 and ATPase subunit 6 genes. Except for the morphologically distinct M. semirufus, mtDNAs of the remaining 18 species fall into either of two clades. One comprises predominantly Caribbean and Central and North American taxa (Clade I), and the other is of predominantly South American taxa (Clade II). The phylogeny is only very broadly concordant with some vocal characters and also with the limited morphological diversity for which the group is well known. Paraphyly in several species (M. swainsoni, M. tuberculifer, M. ferox, M. phaeocephalus, M. sagrae, M. stolidus) suggests that morphological evolution, albeit resulting in limited morphological diversity, has been more rapid than that of mtDNA, or that current taxonomy is faulty, or both. A South American origin for Myiarchus is likely. Dispersal and vicariance both appear to have been involved in generating the present-day distribution of some species. Relatively recent dispersal events out of South America are inferred to have brought species of Clades I and II into broad sympatry. Jamaica has been colonized independently at least twice by members of Clades I and II. The phylogeny brings a historical perspective that in turn suggests that ecological study of closely related species from within each major clade where they are sympatric will be especially rewarding.


Social networks, mobility, and political participation: The potential for women's self-help groups to improve access and use of public entitlement schemes in India.
Women's self-help groups (SHGs) have increasingly been used as a vehicle for social, political, and economic empowerment as well as a platform for service delivery. Although a growing body of literature shows evidence of positive impacts of SHGs on various measures of empowerment, our understanding of ways in which SHGs improve awareness and use of public services is limited. To fill this knowledge gap, this paper first examines how SHG membership is associated with political participation, awareness, and use of government entitlement schemes. It further examines the effect of SHG membership on various measures of social networks and mobility. Using data collected in 2015 across five Indian states and matching methods to correct for endogeneity of SHG membership, we find that SHG members are more politically engaged. We also find that SHG members are not only more likely to know of certain public entitlements than non-members, they are significantly more likely to avail of a greater number of public entitlement schemes. Additionally, SHG members have wider social networks and greater mobility as compared to non-members. Our results suggest that SHGs have the potential to increase their members' ability to hold public entities accountable and demand what is rightfully theirs. An important insight, however, is that the SHGs themselves cannot be expected to increase knowledge of public entitlement schemes in absence of a deliberate effort to do so by an external agency.


6,11-Dioxobenzo[f]pyrido[1,2-a]indoles Kill Mycobacterium tuberculosis by Targeting Iron-Sulfur Protein Rv0338c (IspQ), A Putative Redox Sensor.
Screening of a diversity-oriented compound library led to the identification of two 6,11-dioxobenzo[f]pyrido[1,2-a]indoles (DBPI) that displayed low micromolar bactericidal activity against the Erdman strain of Mycobacterium tuberculosis in vitro. The activity of these hit compounds was limited to tubercle bacilli, including the nonreplicating form, and to Mycobacterium marinum. On hit expansion and investigation of the structure activity relationship, selected modifications to the dioxo moiety of the DBPI scaffold were either neutral or led to reduction or abolition of antimycobacterial activity. To find the target, DBPI-resistant mutants of M. tuberculosis Erdman were raised and characterized first microbiologically and then by whole genome sequencing. Four different mutations, all affecting highly conserved residues, were uncovered in the essential gene rv0338c (ispQ) that encodes a membrane-bound protein, named IspQ, with 2Fe-2S and 4Fe-4S centers and putative iron-sulfur-binding reductase activity. With the help of a structural model, two of the mutations were localized close to the 2Fe-2S domain in IspQ and another in transmembrane segment 3. The mutant genes were recessive to the wild type in complementation experiments and further confirmation of the hit-target relationship was obtained using a conditional knockdown mutant of rv0338c in M. tuberculosis H37Rv. More mechanistic insight was obtained from transcriptome analysis, following exposure of M. tuberculosis to two different DBPI; this revealed strong upregulation of the redox-sensitive SigK regulon and genes induced by oxidative and thiol-stress. The findings of this investigation pharmacologically validate a novel target in tubercle bacilli and open a new vista for tuberculosis drug discovery.


Participant-Centric Initiatives and Medical Research: Scoping Review Protocol.
Significant advances in digital technologies have meant that health care data can be collected, stored, transferred, and analyzed for research purposes more easily than ever before. Participant-centric initiatives (PCI) are defined as "tools, programs, and projects that empower participants to engage in the research process" using digital technologies and have the potential to provide a number of benefits to both participants and researchers, including the promotion of public trust in medical research, improved quality of research, increased recruitment and retention, and improved health care delivery. The main objective of this scoping review is to describe the extent and range of PCIs across the United Kingdom, United States, and Japan that are designed to facilitate medical research. The methodological framework described by Levac et al will be applied to this scoping review. We will search electronic databases (MEDLINE, EMBASE, PsychINFO, Cumulative Index to Nursing, and Allied Health Literature and CiNii), grey literature sources, Internet search engines (Google and Bing), and hand search key journals and reference lists of relevant articles. All digital tools and programs will be eligible for inclusion if there is a description of key features and functions that fall within the parameters of a PCI. Only those that play a role in medical research will be included. Preliminary searches conducted in MEDLINE and EMBASE retrieved 1820 and 2322 results, respectively. The scoping review will be completed by January 2018. The scoping review will be the first to map the extent and range of PCIs currently available across the United Kingdom, United States, and Japan, and will be the first review to contribute to a better understanding of what PCIs patients may benefit from. Researchers and practitioners will be able to use information in this review as a guide for patients and also as a guide for the development of future tools and programs. The results will be disseminated through a peer-reviewed publication and conference presentations.


Communicating with parents about vaccination: a framework for health professionals.
A critical factor shaping parental attitudes to vaccination is the parent's interactions with health professionals. An effective interaction can address the concerns of vaccine supportive parents and motivate a hesitant parent towards vaccine acceptance. Poor communication can contribute to rejection of vaccinations or dissatisfaction with care. We sought to provide a framework for health professionals when communicating with parents about vaccination. Literature review to identify a spectrum of parent attitudes or 'positions' on childhood vaccination with estimates of the proportion of each group based on population studies. Development of a framework related to each parental position with determination of key indicators, goals and strategies based on communication science, motivational interviewing and valid consent principles. Five distinct parental groups were identified: the 'unquestioning acceptor' (30-40%), the 'cautious acceptor' (25-35%); the 'hesitant' (20-30%); the 'late or selective vaccinator' (2-27%); and the 'refuser' of all vaccines (<2%). The goals of the encounter with each group will vary, depending on the parents' readiness to vaccinate. In all encounters, health professionals should build rapport, accept questions and concerns, and facilitate valid consent. For the hesitant, late or selective vaccinators, or refusers, strategies should include use of a guiding style and eliciting the parent's own motivations to vaccinate while, avoiding excessive persuasion and adversarial debates. It may be necessary to book another appointment or offer attendance at a specialised adverse events clinic. Good information resources should also be used. Health professionals have a central role in maintaining public trust in vaccination, including addressing parents' concerns. These recommendations are tailored to specific parental positions on vaccination and provide a structured approach to assist professionals. They advocate respectful interactions that aim to guide parents towards quality decisions.


Evaluation of the efficacy and safety of adjuvant treatment to levodopa therapy in Parkinson s disease patients with motor complications.
One of the complications of long-term treatment of Parkinson's disease (PD) with levodopa is the development of motor complications. Generally, when motor complications develop, clinicians add in an additional drug (to the levodopa regimen) from one of three other classes of anti-Parkinsonian treatments (dopamine agonists, catechol-O-methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs)). However, despite trials having shown that these drugs are beneficial compared to placebo, it remains unclear as to the best way to treat patients experiencing motor complications and whether one class of drug is more effective than another. This meta-analysis aims to assess more reliably the benefits and risks of the three classes of drugs (dopamine agonists, COMTIs and MAOBIs) currently used as adjuvant treatment to levodopa in PD patients suffering from motor complications. The three drug classes were compared with the aim of determining whether one class of drug provides better symptomatic control than another. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications. Randomised trials comparing an orally administered dopamine agonist, COMTI or MAOBI versus placebo, both on a background of levodopa therapy, in PD patients experiencing motor complications. Two authors independently extracted data on off-time, levodopa dose, motor complications, side-effects, treatment concordance, clinician-rated disability, mortality, quality of life and health economic data. Forty-four eligible trials, involving 8436 participants were identified. Compared to placebo, adjuvant therapy significantly reduced off-time (-1.05 hours/day, 95% confidence interval (CI) -1.19 to -0.90; P<0.00001), the required levodopa dose (-55.65 mg/day, CI -62.67 to -48.62; P<0.00001) and improved UPDRS scores (UPDRS ADL score: -1.31 points, CI -1.62 to -0.99; P<0.00001; UPDRS motor score: -2.84 points, CI -3.36 to -2.32; P<0.00001; UPDRS total score: -3.26 points, CI -4.52 to -2.00; P<0.00001). However, dyskinesia (odds ratio (OR) 2.50, CI 2.21 to 2.84; P<0.00001) and side-effects including constipation (OR 3.19, CI 2.17 to 4.68; P<0.00001), dizziness (OR 1.57, CI 1.30 to 1.90; P<0.00001), dry mouth (OR 2.33, CI 1.22 to 4.47; P=0.01), hallucinations (OR 2.16, CI 1.70 to 2.74; P<0.00001), hypotension (OR 1.47, CI 1.18 to 1.83; P=0.0007), insomnia (OR 1.38, CI 1.09 to 1.74; P=0.007), nausea (OR 1.78, CI 1.53 to 2.07; P<0.00001), somnolence (OR 1.87, CI 1.40 to 2.51; P<0.0001) and vomiting (OR 2.56, CI 1.67 to 3.93; P<0.0001) were all increased with adjuvant therapy.Indirect comparisons of the three drug classes suggested that dopamine agonists were more efficacious in reducing off-time (dopamine agonist: -1.54 hours/day; COMTI: -0.83 hours/day; MAOBI: -0.93 hours/day; test for heterogeneity between drug classes P=0.0003) and levodopa dose (dopamine agonist: -116 mg/day; COMTI: -52 mg/day; MAOBI: -29 mg/day; test for heterogeneity between drug classes P<0.00001). UPDRS scores also improved more with dopamine agonists than with COMTI or MAOBI (UPDRS total scores - dopamine agonist: -10.01 points versus COMTI: -1.46 points versus MAOBI: -2.20 points; test for heterogeneity between drug classes P<0.00001), although more dyskinesia were seen with dopamine agonists (OR 2.70) and COMTI (OR 2.50) than with MAOBI (OR 0.94) (test for heterogeneity between drug classes P=0.009). Although the increase in the overall incidence of side-effects was generally more marked with dopamine agonists (OR 1.52) and COMTI (OR 2.0) than with MAOBI (OR 1.32), heterogeneity between drug classes was only of borderline significance (P=0.07). Compared to placebo, adjuvant therapy reduces off-time, levodopa dose, and improves UPDRS scores in PD patients who develop motor complications on levodopa therapy. However, this is at the expense of increased dyskinesia and numerous other side-effects. Indirect comparisons suggest that dopamine agonist therapy may be more effective than COMTI and MAOBI therapy, which have comparable efficacy. However, as indirect comparisons should be interpreted with caution, direct head-to-head randomised trials assessing the impact of these different drug classes on overall patient-rated quality of life are needed.


Bullying in school and cyberspace: Associations with depressive symptoms in Swiss and Australian adolescents.
Cyber-bullying (i.e., bullying via electronic means) has emerged as a new form of bullying that presents unique challenges to those victimised. Recent studies have demonstrated that there is a significant conceptual and practical overlap between both types of bullying such that most young people who are cyber-bullied also tend to be bullied by more traditional methods. Despite the overlap between traditional and cyber forms of bullying, it remains unclear if being a victim of cyber-bullying has the same negative consequences as being a victim of traditional bullying. The current study investigated associations between cyber versus traditional bullying and depressive symptoms in 374 and 1320 students from Switzerland and Australia respectively (52% female; Age: M = 13.8, SD = 1.0). All participants completed a bullying questionnaire (assessing perpetration and victimisation of traditional and cyber forms of bullying behaviour) in addition to scales on depressive symptoms. Across both samples, traditional victims and bully-victims reported more depressive symptoms than bullies and non-involved children. Importantly, victims of cyber-bullying reported significantly higher levels of depressive symptoms, even when controlling for the involvement in traditional bullying/victimisation. Overall, cyber-victimisation emerged as an additional risk factor for depressive symptoms in adolescents involved in bullying.


MACRA 2.0: are you ready for MIPS?
The annual cost of healthcare delivery in the USA now exceeds US$3 trillion. Fee for service methodology is often implicated as a cause of this exceedingly high figure. The Affordable Care Act created the Center for Medicare and Medicaid Innovation (CMMI) to pilot test value based alternative payments for reimbursing physician services. In 2015, the Medicare Access and CHIP Reauthorization Act (MACRA) was passed into law. MACRA has dramatic implications for all US based healthcare providers. MACRA permanently repealed the Medicare Sustainable Growth Rate so as to stabilize physician part B Medicare payments, consolidated pre-existing federal performance programs into the Merit based Incentive Payments System (MIPS), and legislatively mandated new approaches to paying clinicians. Neurointerventionalists will predominantly participate in MIPS. MIPS unifies, updates, and streamlines previously existing federal performance programs, thereby reducing onerous redundancies and overall administrative burden, while consolidating performance based payment adjustments. While MIPS may be perceived as a straightforward continuation of fee for service methodology with performance modifiers, MIPS is better viewed as a stepping stone toward eventually adopting alternative payment models in later years. In October 2016, the Centers for Medicare and Medicaid Services (CMS) released a final rule for MACRA implementation, providing greater clarity regarding 2017 requirements. The final rule provides a range of options for easing MIPS reporting requirements in the first performance year. Nonetheless, taking the newly offered 'minimum possible' approach toward meeting the requirements will still have negative consequences for providers.


Chlamydia pneumoniae infection and lung cancer risk: a meta-analysis.
Chlamydia pneumoniae (C. pneumoniae) is a common cause of acute respiratory infection and has been hypothesised to cause several chronic diseases, including lung cancer. Numbers studies were conducted to analyse the association between C. pneumoniae infection and risk of lung cancer, but no clear consensus had been found. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Embase, Web of Science and CNKI were searched; Data were extracted and analysed independently by two investigators. Ultimately, 12 studies, involving 2595 lung cancer cases and 2585 controls from four prospective studies and eight retrospective studies were included. Overall, people exposed to C. pneumoniae infection had an odds ratio (OR) of 1.48 (95% confidence interval (CI), 1.32-1.67) for lung cancer risk, relative to those not exposed. C. pneumoniae infection was clearly identified as a risk factor for lung cancer in both prospective studies (OR, 1.16; 95% CI, 1.00-1.36) and retrospective studies (OR, 2.17; 95% CI, 1.79-2.63) and in both IgA ≥ 16 cutoff group (OR, 1.22; 95% CI, 1.06-1.41) and the IgA ≥ 64 cutoff group (OR, 2.35; 95% CI, 1.88-2.93). In conclusion, C. pneumoniae infection is associated with an increased risk for lung cancer, higher titre may be a better predictor of lung cancer risk.


Advancing Genomics through the Global Invertebrate Genomics Alliance (GIGA).
The Global Invertebrate Genomics Alliance (GIGA), a collaborative network of diverse scientists, marked its second anniversary with a workshop in Munich, Germany, where international attendees focused on discussing current progress, milestones and bioinformatics resources. The community determined the recruitment and training talented researchers as one of the most pressing future needs and identified opportunities for network funding. GIGA also promotes future research efforts to prioritize taxonomic diversity and create new synergies. Here, we announce the generation of a central and simple data repository portal with a wide coverage of available sequence data, via the compagen platform, in parallel with more focused and specialized organism databases to globally advance invertebrate genomics. Therefore this article serves the objectives of GIGA by disseminating current progress and future prospects in the science of invertebrate genomics with the aim of promotion and facilitation of interdisciplinary and international research.


Accelerated resolution therapy: an innovative mental health intervention to treat post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is a disabling trauma and stress-related disorder that may occur after a person experiences a traumatic event, and evokes a combination of intrusion and avoidance symptoms, negative alterations in cognitions and mood, and alterations in arousal and reactivity. Accelerated resolution therapy (ART) is an emerging psychotherapy that provides fast and lasting resolution for mental health problems such as PTSD. ART has been shown to achieve a positive result in one to five sessions, typically over a 2-week period, and requires no homework, skills practice or repeated exposure to targeted events. Initial research, including one randomised control trial, has demonstrated that ART interventions can significantly reduce symptoms of psychological trauma in both civilians and US service members and veterans. These results suggest that ART be considered as either a primary treatment option or for refractory PTSD in those with a suboptimal response to endorsed first-line therapies. Conservative estimates indicate substantial potential cost savings in PTSD treatment. Despite the need for more definitive clinical trials, there is increasing interest in ART in the USA, including in the US Army. The growing positive empirical evidence is compelling, and there appears to be sufficient evidence to warrant UK researchers undertaking ART research. The armed forces offer the potential for comparative international trials. However, equally important are veterans, emergency services personnel and those subjected to violence. ART appears to also have application in other conditions, including depression, anxiety disorders, and alcohol or drug misuse. ART can potentially help personnel traumatised by the unique challenges of war and conflict zones by providing brief psychotherapy in a readily accessible and culturally competent manner. ART facilitates the provision of interventions and resolutions in theatre, thus enhancing forces' fighting capability.


Methanol formation from CO2 catalyzed by Fe3S4{111}: formate versus hydrocarboxyl pathways.
Carbon capture and utilisation is one of the most promising techniques to minimize the impact of the increasing amount of carbon dioxide in the atmosphere. Recently, the mineral greigite was shown to be capable of catalysing CO2 conversion, leading to useful small organic molecules. Here, we have carried out a systematic study of the adsorption and selective reduction of CO2 on the Fe3S4{111} surface. We have considered both formate and hydrocarboxyl key intermediates, leading to different reaction pathways via Eley-Rideal and Langmuir-Hinshelwood mechanisms, and we have built a kinetic model considering the wide range of intermediates in the reaction network. Our results show that the mechanism to produce formic acid takes place via formate intermediate mostly on FeA sites, while methanol is formed via hydrocarboxyl intermediates on FeB sites. From the kinetic model, we have derived a reaction constant comparison and determined the limiting step rates. The overall process takes place under very mild conditions, requiring only a small energy input that might come from a chemiosmotic potential.


Correlation between clinical and magnetic resonance imaging findings in the treatment of anterior disc displacement.
This study aimed to compare the agreement of clinical examination and magnetic resonance imaging (MRI) results before and after the treatment of nonreduction temporomandibular joint (TMJ) disc displacement. The study group consisted of 22 patients, each with anterior disc displacement without reduction in at least one TMJ. Diagnosis was performed clinically and with MRI prior to treatment. All patients received the same treatment protocol, consisting of occlusal appliance therapy and exercise for a period of 24 weeks. By the end of treatment, clinical and imaging examinations were repeated and the results subjected to statistical analysis. Before treatment, MRI and clinical examinations matched in 35 of 44 joints (79.5%). On the basis of the kappa index, the agreement between clinical and imaging examinations was moderate (mean kappa index = 0.59, P = .0001). After treatment, these examinations matched in only 16 of 44 cases (36%) and the agreement was poor. Clinical criteria do not necessarily correlate with MRI findings in the postoperative period in patients treated for TMJ anterior disc displacement.


Diallyl sulfide as a potential dietary agent to reduce TNF-α- and histamine-induced proinflammatory responses in A7r5 cells.
Oxidative stress-aggravated chronic inflammatory diseases of the airway are well documented; hence, treatment with antioxidants to ameliorate oxidative stress might be an effective strategy to reduce airway complications. The aim of this study was to investigate the effect and molecular mechanism of diallyl sulfide (DAS), which is a natural organosulfuric compound found in garlic, on the inhibition of tumor necrosis factor-alpha (TNF-α)- or histamine-induced inflammation in rat aortic smooth muscle A7r5 cells. A7r5 cells were coincubated with DAS before exposure to TNF-α or histamine. DAS significantly blocked the accumulation of the nuclear p65 protein in TNF-α-induced A7r5 cells by attenuating the TNF-α receptor complex through the dissociation of the TNF receptor-associated death domain and TNF receptor-associated factor 2. Moreover, DAS inhibited histamine-induced inflammation by decreasing reactive oxygen species (ROS) levels by enhancing the nuclear factor-erythroid 2-related factor 2-related antioxidative enzyme. DAS also inhibited inflammation by suppressing interleukin-1β and TNF-α through the inhibition of ROS-induced PI3K/Akt and the downstream NF-κB and activator protein-1. Our results demonstrate that DAS is a potential phytochemical to inhibit TNF-α- and histamine-induced inflammation, suggesting that DAS might be an effective dietary agent for the prevention of oxidative stress-induced inflammation of the airway.


Monolithic molecularly imprinted cryogel for lysozyme recognition.
The application of molecularly imprinted polymers in the selective adsorption of macromolecules such as proteins by monolithic protein-imprinted columns requires a macroporous structure, which can be provided by cryogelation at low temperature in which the formation of ice crystals gives a porous structure to the molecularly imprinted polymer. In this study, we applied this technique to synthesize lysozyme-imprinted polyacrylamide cryogels containing 8% w/v of total monomers and 0.3% w/v of lysozyme. The synthesized cryogel was sponge-like and elastic with very fast swelling and reshaping properties, showing a swelling ratio of 24.5 ± 3 and gel fraction yield of about 72%. It showed an imprinting effect of 1.58 and a separation factor of 1.37 for cytochrome c as the competing protein. Adsorption studies on the cryogel revealed that it follows the Langmuir isotherm, with a maximum theoretical adsorption capacity of 36.3 mg lysozyme per gram of cryogel. Additionally, it was shown that a salt-free rebinding solution at low flow rate and pH = 7.0 is favorable for lysozyme rebinding. This kind of monolithic column promises a wide range of application in separation of various biomolecules due to its preparation simplicity, good rebinding characteristics, and macroporosity.


Long-term effects of perinatal nutrition on T lymphocyte kinetics in young Gambian men.
Nutritional status is highly dependent on season in countries such as The Gambia. In a rural Gambian setting, individuals born during periods of seasonal nutritional deprivation ("hungry seasons") are susceptible to mortality from infectious diseases in adult life. We investigated the hypothesis that impaired immunocompetence in those born in the hungry season results from an underlying defect in immunologic memory, similar to the immunosenescence of old age, which is likely to be reflected in the phenotype and kinetics of T lymphocytes in young adults. T cell phenotype in terms of CD3, CD4, CD8, CD45RA, and CD45R0 expression and in vivo dynamics measured by stable isotope labeling of T cell subsets combined with gas chromatography-mass spectrometry and frequency of T cell receptor excision circles were measured in 25 young (18-24-y-old) Gambian men. Thirteen of these 25 men were exposed to perinatal malnutrition as defined by birth season and birth weight. In persons born in the hungry season with low birth weight, no differences in the proportions of memory or naive T cells were found. Kinetic analysis showed higher proliferation rates in memory (CD45R0(+)) subsets of T cells than in naïve (CD45R0(-)) cells, which is consistent with previous studies, but no evidence was found for an effect of birth weight or season on T lymphocyte proliferation and disappearance rates. No significant correlations were found between in vivo T cell kinetics and frequency of T cell receptor excision circles. Only absolute numbers of granulocytes were elevated in those born in the nutritionally deprived season. In healthy young Gambian men, T lymphocyte homeostasis is extremely robust regardless of perinatal nutritional compromise.


Arabidopsis U2AF65 Regulates Flowering Time and the Growth of Pollen Tubes.
During pre-mRNA splicing, U2 small nuclear ribonucleoprotein auxiliary factor 65 (U2AF65) interacts with U2AF35 and splicing factor 1 (SF1), allowing for the recognition of the 3'-splice site by the ternary complex. The functional characterization of U2AF65 homologs has not been performed in Arabidopsis thaliana yet. Here, we show that normal plant development, including floral transition, and male gametophyte development, requires two Arabidopsis U2AF65 isoforms (AtU2AF65a and AtU2AF65b). Loss-of-function mutants of these two isoforms displayed opposite flowering phenotypes: atu2af65a mutants showed late flowering, whereas atu2af65b mutants were characterized by slightly early flowering, as compared to that in the wild-type (Col-0) plants. These abnormal flowering phenotypes were well-correlated with the expression patterns of the flowering time genes such as FLOWERING LOCUS C (FLC) and FLOWERING LOCUS T (FT). However, the two atu2af65 mutants did not display any morphological abnormalities or alterations in abiotic stress tests. Double mutation of the AtU2AF65a and AtU2AF65b genes resulted in non-viable seeds due to defective male gametophyte. In vitro pollen germination test revealed that mutations in both AtU2AF65a and AtU2AF65b genes significantly impaired pollen tube growth. Collectively, our findings suggest that two protein isoforms of AtU2AF65 are differentially involved in regulating flowering time and display a redundant role in pollen tube growth.


Pneumonia among children under five in Uganda: symptom recognition and actions taken by caretakers.
Pneumonia is a leading cause of death among children under five years of age. Pneumonia deaths could be averted if caretakers recognized the danger signs and sought appropriate treatment promptly. We interviewed 278 caretakers in Mukono district Uganda, whose under-five children had suffered from probable pneumonia two weeks prior to the evaluation. Through structured questionnaires we assessed caretaker's knowledge about danger signs among under-five children with pneumonia and the actions taken to manage probable pneumonia using descriptive statistics. We also conducted in-depth interviews with caretakers and community health workers. Lower chest wall in drawing (a pneumonia specific danger sign) was mentioned by only 9.4% of the caretakers. Among the Integrated Management of Childhood Illnesses (IMCI) standard general danger signs, inability to feed was the most commonly cited danger sign (37.8%) followed by incessant vomiting (10.1%). No caretaker mentioned all the four standard general danger signs. In terms of actions taken, most caretakers offered drinks (49.6%) and traditional herbs (45.3%) while, 31.7% gave antibiotics. Caretaker's knowledge about danger signs was inadequate in relation to the IMCI guidelines. Caretakers used both modern and traditional forms of treatment to manage pneumonia. Comprehensive interventions geared at increasing symptom recognition and improving health-seeking behavior are needed to reverse this trend.


Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation.
End-stage renal disease (ESRD) requires for its treatment permanent dialysis or kidney transplantation (KT). KT is the best clinical treatment, however, the early function of the allograft varies depending on multiple factors associated with cold ischemia time (CIT) and the allograft rejection process. It is known that serum creatinine is an insensitive and late marker for predicting graft recovery after KT, mainly in patients with delayed graft function (DGF). Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal nephron and it is one of the most promising novel biomarkers for acute kidney injury (AKI) and chronic kidney disease (CKD). NGAL has been proposed to be a predictor of organ recovery from DGF after KT from donors after cardiac death. Because nonrenal diseases can also induce NGAL, more information is necessary to validate the sensitivity and specificity of urine and plasma NGAL in clinical samples. The exosomes are vesicles released into the urine from the kidney epithelium and they have been proposed as better source to explore as biomarker of renal dysfunction. The molecular composition of the urinary exosomes could be representative of the physiological or physiopathologic condition of the urinary system. We propose that determination of NGAL in urinary exosomes is a better predictor of kidney dysfunction after KT than other urinary fractions. We analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16-60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD). The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three patient developed DGF. Using Western blot analysis, NGAL was detectable in the cellular and exosomal fraction of the urine. The exosomes expressed higher levels of NGAL than the cellular fraction. The expression of NGAL was observed from the first day after transplantation. In the cellular fraction of the urine, no significant differences of NGAL were observed between the patients. However, the median of NGAL expression in the exosomes fraction was significantly higher in DD patient, from the first day after KT (P < .05). Moreover, we noticed that NGAL expression in exosomes remained elevated in the patients with DGF compared with non-DGF patients (P < .05). Considering the highest abundance of NGAL in the urinary exosomes and its correlation with DGF patients, we suggest the exosomal fraction as a more sensitive substrate to evaluate early biomarkers of DGF after KT.


Portulaca oleracea L. prevents lipopolysaccharide-induced passive avoidance learning and memory and TNF-α impairments in hippocampus of rat.
There is a growing body of evidence that neuroinflammation can impair memory. It has been indicated that Portulaca oleracea Linn. (POL), possess anti-inflammatory activity and might improve memory disruption caused by inflammation. In this study the effect of pre-treatment with the hydro-alcoholic extract of POL on memory retrieval investigated in lipopolysaccharide (LPS) treated rats. Male Wistar rats (200-220g) received either a control diet or a diet containing of POL (400mg/kg, p.o.) for 14days. Then, they received injections of either saline or LPS (1mg/kg, i.p.). In all the experimental groups, 4h following the last injection, passive avoidance learning (PAL) and memory test was performed. The retention test was done 24h after the training and then the animals were sacrificed. Hippocampal TNF-α levels measured using ELISA as one criteria of LPS-induced neuroinflammation. The results indicated that LPS significantly impaired PAL and memory and increased TNF-α levels in hippocampus tissue. Pre-treatment with POL improved memory in control rats and prevented memory and TNF-α deterioration in LPS treated rats. Taken together, the results of this study suggest that the hydro-alcoholic extract of POL may improve memory deficits in LPS treated rats, possibly via inhibition of TNF-α and anti-inflammatory activity.


UV and X-ray sensitivity of Candida albicans laboratory strains and mutants having chromosomal alterations.
Utilization of L-sorbose, D-arabinose or primary fluconazole resistance in Candida albicans are controlled by copy number of specific chromosomes. On the other hand, spontaneous morphological mutants have a wide range of chromosomal alterations. We have investigated the UV and X-ray sensitivity of these mutants, as well as C. albicans laboratory strains. While L-sorbose utilizing mutants had normal sensitivities, a large subclass of D-arabinose utilizing mutants was abnormally sensitive to UV. Spontaneous morphological mutants responded differently, an expected result because of the heterogeneous nature of their electrophoretic karyotypes. We suggest that the differences in UV and X-ray sensitivity are due to gene imbalance caused by some chromosomal alterations. In this respect, the radiation sensitivity is similar to other features impaired by changes in chromosomes, but is unlike the acquisition of the ability to utilize alternative nutrients or the acquisition of resistance to fluconazole. Our studies also revealed that strains of C. albicans heterozygous for the mating type loci exhibited the same X-ray sensitivity as homozygous or hemizygous strains, a finding which is in contrast to the properties of Saccharomyces cerevisiae, where heterozygous strains are more resistant. This feature of C. albicans strains may be indicative of an inefficient repair system that may be related to inefficiency of mating.


The role of target distinctiveness in infant perseverative reaching.
From a dynamic systems perspective, perseverative errors in infancy arise from the interaction of the perceptual cues with the memory of previous actions. To evaluate this account, we tested 9-month-old infants in a task in which they reached for two targets. Experimenters repeatedly cued the first target, which always matched the background (A), and then cued the second target, which varied in its distinctiveness (B). We predicted that a sufficiently distinctive B target would lessen perseverative responding. Results showed that infants perseverated when reaching for two identical targets, but that they made nonperseverative responses when reaching in the presence of a highly distinctive B target. Reach direction on each trial was jointly determined by the distinctiveness of the target, the immediately preceding perceptual events, and the history of reaches in the task.


Deep brain stimulation for chronic pain: a systematic review and meta-analysis.
Deep brain stimulation (DBS) has shown promise in effectively treating chronic pain. This study aimed to assess the efficacy of DBS in this context. We conducted a systematic literature search using PubMed, Scopus, and Web of Science, following the PRISMA guidelines. A well-constructed search strategy was utilized. Our literature search identified two groups of subjects: one group underwent DBS specifically for chronic pain treatment (DBS-P), while the second group received DBS for other indications (DBS-O), such as Parkinson's disease or dystonia, with pain perception investigated as a secondary outcome in this population. Meta-analysis was performed using R version 4.2.3 software. Heterogeneity was assessed using the tau^2 and I^2 indices, and Cochran's Q-test was conducted. The analysis included 966 patients in 43 original research studies with chronic pain who underwent DBS (340 for DBS-P and 625 for DBS-O). Subgroup analysis revealed that DBS-P exhibited a significant effect on chronic pain relief, with a standardized mean difference (SMD) of 1.65 and a 95% confidence interval (CI) of [1.31; 2.00]. Significant heterogeneity was observed among the studies, with an I^2 value of 85.8%. However, no significant difference was found between DBS-P and DBS-O subgroups. Subgroup analyses based on study design, age, pain diseases, and brain targets demonstrated varying levels of evidence for the effectiveness of DBS across different subgroups. Additionally, meta-regression analyses showed no significant relationship between age or pain duration and DBS effectiveness for chronic pain. These findings significantly contribute to the expanding body of knowledge regarding the utility of DBS in the management of chronic pain. The study underscores the importance of conducting further research to enhance treatment outcomes and elucidate patient-specific factors that are associated with treatment response. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=428442, identifier CRD42023428442.


Isolation from a shea cake digester of a tannin-degrading Streptococcus gallolyticus strain that decarboxylates protocatechuic and hydroxycinnamic acids, and emendation of the species.
A facultatively anaerobic, mesophilic, non-motile, non-sporulating bacterium, designated strain B7, was isolated from an anaerobic digester fed with shea cake rich in tannins and aromatic compounds, after enrichment on tannic acid. The coccoid cells (less than 2 microm in diameter) occurred in pairs or short chains and stained gram-positive. Strain B7 fermented a wide range of carbohydrates (cellobiose, fructose, galactose, glucose, lactose, maltose, mannitol, melibiose, raffinose and trehalose), grew optimally at pH 7.0 and had a G+C content of 40.4+/-0.3 mol%. Strain B7 was closely related to Streptococcus gallolyticus ACM 3611T, a member of the Streptococcus bovis rRNA cluster, with a sequence similarity of 98% and a DNA hybridization value of 86 mol%. Isolate B7 hydrolysed tannic acid and decarboxylated gallic acid to pyrogallol, traits also observed in S. gallolyticus ACM 3611T. In addition, both strains decarboxylated protocatechuic acid to catechol, p-coumaric acid to 4-vinylphenol, caffeic acid to 4-vinylcatechol and ferulic acid to 4-vinylguaiacol. An unsubstituted para-hydroxyl group on the benzene ring was required for decarboxylation. Glucose addition markedly increased the conversion rate. As these traits were not described previously, emendation of the description of the species Streptococcus gallolyticus is proposed.


Identification of a novel lipopolysaccharide core biosynthesis gene cluster in Bordetella pertussis, and influence of core structure and lipid A glucosamine substitution on endotoxic activity.
Lipopolysaccharide (LPS), also known as endotoxin, is one of the main constituents of the gram-negative bacterial outer membrane. Whereas the lipid A portion of LPS is generally considered the main determinant for endotoxic activity, the oligosaccharide moiety plays an important role in immune evasion and the interaction with professional antigen-presenting cells. Here we describe a novel four-gene cluster involved in the biosynthesis of the Bordetella pertussis core oligosaccharide. By insertionally inactivating these genes and studying the resulting LPS structures, we show that at least two of the genes encode active glycosyltransferases, while a third gene encodes a deacetylase also required for biosynthesis of full-length oligosaccharide. In addition, we demonstrate that mutations in the locus differentially affect LPS and whole-cell endotoxic activities. Furthermore, while analyzing the mutant LPS structures, we confirmed a novel modification of the lipid A phosphate with glucosamine and found that inactivation of the responsible glycosyltransferase reduces the endotoxic activity of the LPS.


Inferring the popularity of an opinion from its familiarity: a repetitive voice can sound like a chorus.
Despite the importance of doing so, people do not always correctly estimate the distribution of opinions within their group. One important mechanism underlying such misjudgments is people's tendency to infer that a familiar opinion is a prevalent one, even when its familiarity derives solely from the repeated expression of 1 group member. Six experiments demonstrate this effect and show that it holds even when perceivers are consciously aware that the opinions come from 1 speaker. The results also indicate that the effect is due to opinion accessibility rather than a conscious inference about the meaning of opinion repetition in a group. Implications for social consensus estimation and social influence are discussed.


Functional role of the supplementary and pre-supplementary motor areas.
The supplementary motor complex consists of the supplementary motor area, the supplementary eye field and the pre-supplementary motor area. In recent years, these areas have come under increasing scrutiny from cognitive neuroscientists, motor physiologists and clinicians because they seem to be crucial for linking cognition to action. However, theories regarding their function vary widely. This Review brings together the data regarding the supplementary motor regions, highlighting outstanding issues and providing new perspectives for understanding their functions.


Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands.
Serotonin (5-HT) is a monoamine neurotransmitter that plays an important role in physiological functions. 5-HT has been implicated in sleep, feeding, sexual behavior, temperature regulation, pain, and cognition as well as in pathological states including disorders connected to mood, anxiety, psychosis and pain. 5-HT1A receptors have for a long time been considered as an interesting target for the action of antidepressant drugs. It was postulated that postsynaptic 5-HT1A agonists could form a new class of antidepressant drugs, and mixed 5-HT1A receptor ligands/serotonin transporter (SERT) inhibitors seem to possess an interesting pharmacological profile. It should, however, be noted that 5-HT1A receptors can activate several different biochemical pathways and signal through both G protein-dependent and G protein-independent pathways. The variables that affect the multiplicity of 5-HT1A receptor signaling pathways would thus result from the summation of effects specific to the host cell milieu. Moreover, receptor trafficking appears different at pre- and postsynaptic sites. It should also be noted that the 5-HT1A receptor cooperates with other signal transduction systems (like the 5-HT1B or 5-HT2A/2B/2C receptors, the GABAergic and the glutaminergic systems), which also contribute to its antidepressant and/or anxiolytic activity. Thus identifying brain specific molecular targets for 5-HT1A receptor ligands may result in a better targeting, raising a hope for more effective medicines for various pathologies.


Re-Irradiation of Hepatocellular Carcinoma: Clinical Applicability of Deformable Image Registration.
This study aimed to evaluate whether the deformable image registration (DIR) method is clinically applicable to the safe delivery of re-irradiation in hepatocellular carcinoma (HCC). Between August 2010 and March 2012, 12 eligible HCC patients received re-irradiation using helical tomotherapy. The median total prescribed radiation doses at first irradiation and re-irradiation were 50 Gy (range, 36-60 Gy) and 50 Gy (range, 36-58.42 Gy), respectively. Most re-irradiation therapies (11 of 12) were administered to previously irradiated or marginal areas. Dose summation results were reproduced using DIR by rigid and deformable registration methods, and doses of organs-at-risk (OARs) were evaluated. Treatment outcomes were also assessed. Thirty-six dose summation indices were obtained for three OARs (bowel, duodenum, and stomach doses in each patient). There was no statistical difference between the two different types of DIR methods (rigid and deformable) in terms of calculated summation ΣD (0.1 cc, 1 cc, 2 cc, and max) in each OAR. The median total mean remaining liver doses (M(RLD)) in rigid- and deformable-type registration were not statistically different for all cohorts (p=0.248), although a large difference in M(RLD) was observed when there was a significant difference in spatial liver volume change between radiation intervals. One duodenal ulcer perforation developed 20 months after re-irradiation. Although current dose summation algorithms and uncertainties do not warrant accurate dosimetric results, OARs-based DIR dose summation can be usefully utilized in the re-irradiation of HCC. Appropriate cohort selection, watchful interpretation, and selective use of DIR methods are crucial to enhance the radio-therapeutic ratio.


Humoral immune response to chlamydial genital infection of mice with the agent of mouse pneumonitis.
The objective of this study was to characterize the humoral immune response to chlamydial genital infection of mice with the mouse pneumonitis agent (MoPn). With an enzyme-linked immunoabsorbent assay, immunoglobulin G antibodies to MoPn were first detected in plasma by day 14. Peak plasma antibody concentrations were reached by day 49, and this response did not decline significantly throughout the 300-day monitoring period. Immunoglobulin A against MoPn could first be detected in pooled vaginal washes by day 21 after infection and had reached peak concentrations by day 28, but anti-MoPn immunoglobulin G was not consistently present in secretions. The antibody response in secretions had declined slightly by day 300. Immunoblot analysis revealed that the early phase of the plasma antibody response to MoPn as a result of genital infection was against lipopolysaccharide, the major outer membrane protein, and a 62-kilodalton (kDa) protein. In secretions, early-phase immunoglobulin A antibodies were directed to the major outer membrane protein and lipopolysaccharide. Late reactions to 15-, 22-, and 83-kDa proteins in plasma were noted. Late reactions to the 62-kDa protein in secretions were also noted. The cause of these late responses remains unexplained. When mice were challenged intravaginally with MoPn at 50-day intervals after the primary infection, it was found that mice inoculated on day 100 or after were susceptible to reinfection. Susceptibility could not be related to a decline in the antibody concentration in plasma or secretions or in the antibody response to specific components of MoPn as measured by immunoblot analysis.


Annexin 1 and melanocortin peptide therapy for protection against ischaemic-reperfusion damage in the heart.
Cardiovascular disease is a major cause of mortality within the western world affecting 2.7 million British people. This review highlights the beneficial effects of naturally occurring hormones and their peptides, in myocardial ischaemic-injury (MI) models, a disease pathology in which cytokines and neutrophils play a causal role. Here we discuss two distinct classes of endogenous peptides: the steroid inducible annexin 1 and the melanocortin peptides. Annexin 1 and the melanocortins counteract the most important part of the host inflammatory response, namely, the process of leukocyte extravasation, as well as release of proinflammatory mediators. Their biological effects are mediated via the seven transmembrane G-protein-coupled receptors, the fMLP receptor family (or FPR), and the melanocortin receptors, respectively. Pharmacological analysis has demonstrated that the first 24 amino acids of the N-terminus (termed Ac2-26) are the most active region. Both exogenous annexin 1 and its peptides demonstrate cardioprotectiveness and continuing work is required to understand this annexin 1/FPR relationship fully. The melanocortin peptides are derived from a precursor molecule called the POMC protein. These peptides display potent anti-inflammatory effects in human and animal models of disease. In MI, the MC3R has been demonstrated to play an important role in mediating the protective effects of these peptides. The potential anti-inflammatory role for endogenous peptides in cardiac disease is in its infancy. The inhibition of cell migration and release of cytokines and other soluble mediators appears to play an important role in affording protection in ischaemic injury and thus may lead to potential therapeutic targets.


Phage-display-guided nanocarrier targeting to atheroprone vasculature.
In regions of the circulation where vessels are straight and unbranched, blood flow is laminar and unidirectional. In contrast, at sites of curvature, branch points, and regions distal to stenoses, blood flow becomes disturbed. Atherosclerosis preferentially develops in these regions of disturbed blood flow. Current therapies for atherosclerosis are systemic and may not sufficiently target these atheroprone regions. In this study, we sought to leverage the alterations on the luminal surface of endothelial cells caused by this atheroprone flow for nanocarrier targeting. In vivo phage display was used to discover unique peptides that selectively bind to atheroprone regions in the mouse partial carotid artery ligation model. The peptide GSPREYTSYMPH (PREY) was found to bind 4.5-fold more avidly to the region of disturbed flow and was used to form targeted liposomes. When administered intravenously, PREY-targeted liposomes preferentially accumulated in endothelial cells in the partially occluded carotid artery and other areas of disturbed flow. Proteomic analysis and immunoblotting indicated that fibronectin and Filamin-A were preferentially bound by PREY nanocarriers in vessels with disturbed flow. In additional experiments, PREY nanocarriers were used therapeutically to deliver the nitric oxide synthase cofactor tetrahydrobiopterin (BH4), which we have previously shown to be deficient in regions of disturbed flow. This intervention increased vascular BH4 and reduced vascular superoxide in the partially ligated artery in wild-type mice and reduced plaque burden in the partially ligated left carotid artery of fat fed atheroprone mice (ApoE(-/-)). Targeting atheroprone sites of the circulation with functionalized nanocarriers provides a promising approach for prevention of early atherosclerotic lesion formation.


The aetiology of adult burns in the Western Cape, South Africa.
Rural to urban migration to major cities in South Africa continues to lead to the proliferation of informal settlements. There is little recent published data on the epidemiology of adult burns in the Western Cape, South Africa. A retrospective review of patients on the Burn Unit database was undertaken, looking at patients admitted to the Burn Unit between January 2003 and December 2008. This study discusses the characteristics and outcome of patients who were treated at the Tygerburg Burn unit. A total of 1908 patients were admitted to the burn unit during the 6 year period under review. Most fatal injuries occurred in the 20-40 year age group. Injuries due to shack fires and fuel stoves comprised 21% (399) of all admissions. Mortality due to these injuries comprised 28% (137) of total mortality. Gas stoves accounted for 24% with kerosene stoves accounting for 71% of injuries. The burn death rate in this study (25%) was found to have increased dramatically from the last audit done from 1986 to 1995 in which a burn death rate of 7.5% was observed. Reasons for this are explored. It is likely that those with HIV/AIDS have poorer outcomes. Shack fires and injuries due to fuel stoves are a common reason for admission to the burn unit and mostly involve young male individuals. Other research from the Southern African region does not mention shack fires as a separate entity making it difficult to obtain an accurate idea of the scale of the problem. Their injuries are severe with a high mortality. The use of kerosene stoves are a major contributing factor. Recommendations include enforceable legislation to promote safer stove design, research into safer bio fuels and materials for building shacks as well promoting fire safety among schoolchildren in the community. Further research is needed to determine the impact of HIV/AIDS on the outcome of acute burns within the Southern African region.


Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation.
During muscle regeneration, the mechanism integrating environmental cues at the chromatin of muscle progenitors is unknown. We show that inflammation-activated MKK6-p38 and insulin growth factor 1 (IGF1)-induced PI3K/AKT pathways converge on the chromatin of muscle genes to target distinct components of the muscle transcriptosome. p38 alpha/beta kinases recruit the SWI/SNF chromatin-remodeling complex; AKT1 and 2 promote the association of MyoD with p300 and PCAF acetyltransferases, via direct phosphorylation of p300. Pharmacological or genetic interference with either pathway led to partial assembly of discrete chromatin-bound complexes, which reflected two reversible and distinct cellular phenotypes. Remarkably, PI3K/AKT blockade was permissive for chromatin recruitment of MEF2-SWI/SNF complex, whose remodeling activity was compromised in the absence of MyoD and acetyltransferases. The functional interdependence between p38 and IGF1/PI3K/AKT pathways was further established by the evidence that blockade of AKT chromatin targets was sufficient to prevent the activation of the myogenic program triggered by deliberate activation of p38 signaling.


Opioid-Free Total Intravenous Anesthesia Improves Postoperative Quality of Recovery after Ambulatory Gynecologic Laparoscopy.
Gynecological laparoscopic surgery is commonly performed on an ambulatory basis under general anesthesia. The postoperative quality of recovery (QOR) should be considered one of the principal endpoints after ambulatory surgery. Total intravenous anesthesia (TIVA) with opioids is known to improve postoperative QOR after ambulatory surgery. However, opioids can be associated with an increased incidence of postoperative complications, which can affect postoperative QOR. The primary aim of this study was to compare the patient recovery using the QOR-40 at 24 h postoperative in ambulatory gynecological laparoscopy between opioid-free (OF) TIVA and opioid-based TIVA. A prospective, randomized, controlled, comparative study was conducted at the day surgery center. Eighty females were included in the study. They were randomized into two equal groups: OF TIVA group with dexmedetomidine and propofol or opioid-based TIVA (O) group with fentanyl and propofol. The primary outcome was QOR-40 at 24 h postoperative, and the secondary outcomes were postoperative numerical rating scale (NRS), time to first rescue analgesia, number of rescue tramadol analgesia, and the incidence of postoperative nausea and vomiting. A statistically significant difference in total QOR-40 score at 24 h postoperative was observed between the groups (median [range] QOR-40 of 182.0 [164.0-192.0] in the OF TIVA group and 170.0 [156.0-185.0] in the O group; P = 0.03). OF group had significantly lower time to first rescue analgesia, maximum NRS pain scores, number of rescue tramadol analgesia, and ondansetron use. OF TIVA significantly improves postoperative QOR in patients undergoing ambulatory gynecological laparoscopic surgery.


Insulitis in human type 1 diabetes: The quest for an elusive lesion.
The histopathology of type 1 diabetes is defined by a decreased β-cell mass in association with insulitis, a characteristic lymphocytic infiltration limited to the islets of Langerhans and prominent in early stage disease in children. A cytotoxic T-cell mediated destruction of insulin-producing β-cells is thought to be initiated by an unknown (auto)antigen, leading to the destruction > 75% of β-cell mass at clinical diagnosis. Although considered to be pathognomonic for recent onset disease, insulitis has only been described in approximately 150 cases over the past century. This review describes the quest for this elusive lesion and gives its incidence in various patient subpopulations stratified for age of onset and duration of the disease. It discusses recent new insights into the regenerative capacity of the β-cell mass in the pre-clinical stages of the disease and relates these findings to the inflammatory processes within the islet tissue.


[Prevention of dyslexia – short-term and intermediate effects of promoting phonological awareness and letter-sound correspondence with at-risk preschool children].
This study assesses the short-term and intermediate effects of preschool training stimulating phonological awareness and letter-sound correspondence for children at risk of developing dyslexia. Moreover, we examined whether training reduced the frequency of subsequent dyslexic problems. 25 children at risk of developing dyslexia were trained with Hören, Lauschen, Lernen 1 und 2 (Küspert & Schneider, 2008; Plume & Schneider, 2004) by their kindergarten teachers and were compared with 60 untrained at-risk children. The training revealed a significant short-term effect: The phonological awareness of trained at-risk children increased significantly over that of untrained at-risk children. However, there were no differences in phonological awareness, spelling, and reading ability between the first-graders in the training and control group. Furthermore, reading problems were reduced in the training group. In the future, phonological awareness as well as additional predictors should be included when identifying children vulnerable to developing dyslexia. Moreover, in order to prevent dyslexia, additional prerequisite deficits need to be identified, alleviated, and their effects evaluated.


Nonsyndromic craniosynostosis in Vietnam: initial surgical outcomes of subspecialty mentorship.
There is a global deficit of pediatric neurosurgical care, and the epidemiology and overall surgical care for craniosynostosis is not well characterized at the global level. This study serves to highlight the details and early surgical results of a neurosurgical educational partnership and subsequent local scale-up in craniosynostosis correction. A prospective case series was performed with inclusion of all patients undergoing correction of craniosynostosis by extensive cranial vault remodeling at Children's Hospital 2, Ho Chi Minh City, Vietnam, between January 1, 2015, and December 31, 2019. A total of 76 patients were included in the study. The group was predominantly male, with a male-to-female ratio of 3.3:1. Sagittal synostosis was the most common diagnosis (50%, 38/76), followed by unilateral coronal (11.8%, 9/76), bicoronal (11.8%, 9/76), and metopic (7.9%, 6/76). The most common corrective technique was anterior cranial vault remodeling (30/76, 39.4%) followed by frontoorbital advancement (34.2%, 26/76). The overall mean operative time was 205.8 ± 38.6 minutes, and the estimated blood loss was 176 ± 89.4 mL. Eleven procedures were complicated by intraoperative durotomy (14.5%, 11/76) without any damage of dural venous sinuses or brain tissue. Postoperatively, 4 procedures were complicated by wound infection (5.3%, 4/76), all of which required operative wound debridement. There were no neurological complications or postoperative deaths. One patient required repeat reconstruction due to delayed intracranial hypertension. There was no loss to follow-up. All patients were followed at outpatient clinic, and the mean follow-up period was 32.3 ± 18.8 months postoperatively. Surgical care for pediatric craniosynostosis can be taught and sustained in the setting of collegial educational partnerships with early capability for high surgical volume and safe outcomes. In the setting of the significant deficit in worldwide pediatric neurosurgical care, this study provides an example of the feasibility of such relationships in addressing this unmet need.


Somatostatin analog inhibits afferent response to rectal distention in diarrhea-predominant irritable bowel patients.
Irritable bowel syndrome (IBS) patients exhibit enhanced sensitivity to rectal distention. The somatostatin analog reduces perception of rectal distention in healthy volunteers without modifying rectal resistance. We evaluated whether octreotide has similar effects on rectal perception and resistance in diarrhea-prone IBS patients. Octreotide (100 micrograms s.c.) and placebo were injected in double-blind fashion in eight IBS patients. Rectal balloons measured volumes that evoked increasing levels of perception and intrarectal pressures. After placebo, threshold perception, pressure, urgency and maximal tolerated volume were reported at 18 +/- 5, 46 +/- 8, 72 +/- 7 and 102 +/- 10 ml by the IBS patients, values less than we have observed in healthy volunteers. With octreotide, these sensations were perceived at higher volumes (40 +/- 10, 89 +/- 16, 167 +/- 20 and 202 +/- 25 ml, P < .05) that approximated responses in healthy volunteers. IBS patients exhibited higher rectal pressures at each volume and showed a trend to higher rectal resistance (0.13 +/- 0.02 mmHg/ml) than we have observed in healthy volunteers. These abnormalities were normalized by octreotide. Octreotide did not block the rectoanal inhibitory reflex confirming a lack of effect on local rectal reflex arcs. As with healthy volunteers, IBS patients with diarrhea experience reduced perception of rectal distention after octreotide. Octreotide also reduces elevated rectal pressures in IBS patients, in contrast to healthy volunteers. Thus, octreotide shows potential therapeutic benefit in IBS via dual effects on visceral afferent pathways and rectal wall stiffness.


Light Pollution: Outdoor lighting is a growing threat to astronomy.
There have been major qualitative and quantitative changes in outdoor lighting technology in the last decade. The level of skylight caused by outdoor lighting systems is growing at a very high rate, about 20 percent per year nationwide. In addition, the spectral distribution of man-made light pollution may change in the next decade from one containing a few mercury lines to one containing dozens of lines and a significantly increased continuum level. Light pollution is presently damaging to some astronomical programs, and it is likely to become a major factor limiting progress in the next decade. Suitable sites in the United States for new dark sky observing facilities are very difficult to find. Some of the increase in outdoor illumination is due to the character of national growth and development. Some is due to promotional campaigns, in which questionable arguments involving public safety are presented. There are protective measures which might be adopted by the government; these would significantly aid observational astronomy, without compromising the legitimate outdoor lighting needs of society. Observatories should establish programs to routinely monitor sky brightness as a function of position, wavelength, and time. The astronomical community should establish a mechanism by which such programs can be supported and coordinated.


Prevalence and Genomic Structure of Bacteriophage phi3 in Human-Derived Livestock-Associated Methicillin-Resistant Staphylococcus aureus Isolates from 2000 to 2015.
Whereas the emergence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex 398 (CC398) in animal husbandry and its transmission to humans are well documented, less is known about factors driving the epidemic spread of this zoonotic lineage within the human population. One factor could be the bacteriophage phi3, which is rarely detected in S. aureus isolates from animals but commonly found among isolates from humans, including those of the human-adapted methicillin-susceptible S. aureus (MSSA) CC398 clade. The proportion of phi3-carrying MRSA spa-CC011 isolates, which constitute presumptively LA-MRSA within the multilocus sequence type (MLST) clonal complex 398, was systematically assessed for a period of 16 years to investigate the role of phi3 in the adaptation process of LA-MRSA to the human host. For this purpose, 632 MRSA spa-CC011 isolates from patients of a university hospital located in a pig farming-dense area in Germany were analyzed. Livestock-associated acquisition of MRSA spa-CC011 was previously reported as having increased from 1.8% in 2000 to 29.4% in 2014 in MRSA-positive patients admitted to this hospital. However, in this study, the proportion of phi3-carrying isolates rose only from 1.1% (2000 to 2006) to 3.9% (2007 to 2015). Characterization of the phi3 genomes revealed 12 different phage types ranging in size from 40,712 kb up to 44,003 kb, with four hitherto unknown integration sites (genes or intergenic regions) and several modified bacterial attachment (attB) sites. In contrast to the MSSA CC398 clade, phi3 acquisition seems to be no major driver for the readaptation of MRSA spa-CC011 to the human host.


The Importance of Intra-Organizational Networking for Younger Versus Older Workers: Examining a Multi-Group Mediation Model of Individual Task Performance Enhancement.
The purpose of this paper is to investigate the effect of intra-organizational networking on individual task performance, via employability. Moreover, this study also examines whether this relationship differs for younger (<40 years) versus older employees (≥40 years). A self-report questionnaire was distributed among a sample of employees working in a range of different types of organizations (n = 374). We conclude that employability fully mediates the relationship between intra-organizational networking and individual task performance. However, this mediation effect did not vary between younger and older employees. This study extends past research by applying a human capital perspective (in particular, social capital) and life-span development frameworks for explaining employability and task performance enhancement across one's working life. It provides useful insights for stimulating career development and individual performance growth, by means of social capital, herewith increasing the individual employee's chance to survive in nowadays' labor markets.


Why first-level health workers fail to follow guidelines for managing severe disease in children in the Coast Region, the United Republic of Tanzania.
To determine why health workers fail to follow integrated management of childhood illness (IMCI) guidelines for severely ill children at first-level outpatient health facilities in rural areas of the United Republic of Tanzania. Retrospective and prospective case reviews of severely ill children aged < 5 years were conducted at health facilities in four districts. We ascertained treatment and examined the characteristics associated with referral, conducted follow-up interviews with parents of severely ill children, and gave health workers questionnaires and interviews. In total, 502 cases were reviewed at 62 facilities. Treatment with antimalarials and antibiotics was consistent with the diagnosis given by health workers. However, of 240 children classified as having 'very severe febrile disease', none received all IMCI-recommended therapies, and only 25% of severely ill children were referred. Lethargy and anaemia diagnoses were independently associated with referral. Most (91%) health workers indicated that certain severe conditions can be managed without referral. The health workers surveyed rarely adhered to IMCI treatment and referral guidelines for children with severe illness. They administered therapy based on narrow diagnoses rather than IMCI classifications, disagreed with referral guidelines and often considered referral unnecessary. To improve implementation of IMCI, attention should focus on the reasons for health worker non-adherence.


Biological Soil Crusts as Ecosystem Engineers in Antarctic Ecosystem.
Biological soil crusts (BSC) are considered as pivotal ecological elements among different ecosystems of the world. The effects of these BSC at the micro-site scale have been related to the development of diverse plant species that, otherwise, might be strongly limited by the harsh abiotic conditions found in environments with low water availability. Here, we describe for the first time the bacterial composition of BSCs found in the proximities of Admiralty Bay (Maritime Antarctica) through 16S metabarcoding. In addition, we evaluated their effect on soils (nutrient levels, enzymatic activity, and water retention), and on the fitness and performance of Colobanthus quitensis, one of the two native Antarctic vascular plants. This was achieved by comparing the photochemical performance, foliar nutrient, biomass, and reproductive investment between C. quitensis plants growing with or without the influence of BSC. Our results revealed a high diversity of prokaryotes present in these soil communities, although we found differences in terms of their abundances. We also found that the presence of BSCs is linked to a significant increase in soils' water retention, nutrient levels, and enzymatic activity when comparing with control soils (without BSCs). In the case of C. quitensis, we found that measured ecophysiological performance parameters were significantly higher on plants growing in association with BSCs. Taken together, our results suggest that BSCs in Antarctic soils are playing a key role in various biochemical processes involved in soil development, while also having a positive effect on the accompanying vascular flora. Therefore, BSCs would be effectively acting as ecosystem engineers for the terrestrial Antarctic ecosystem.


Two to tango: regulation of Mammalian iron metabolism.
Disruptions in iron homeostasis from both iron deficiency and overload account for some of the most common human diseases. Iron metabolism is balanced by two regulatory systems, one that functions systemically and relies on the hormone hepcidin and the iron exporter ferroportin, and another that predominantly controls cellular iron metabolism through iron-regulatory proteins that bind iron-responsive elements in regulated messenger RNAs. We describe how the two distinct systems function and how they "tango" together in a coordinated manner. We also highlight some of the current questions in mammalian iron metabolism and discuss therapeutic opportunities arising from a better understanding of the underlying biological principles.


Tyrosine hydroxylase regulation in adult rat striatum following short-term neonatal exposure to manganese.
Manganese (Mn) is an essential trace element required for a range of physiological processes, but Mn can also be neurotoxic especially during development. Excess levels of Mn accumulate preferentially in the striatum and can induce a syndrome called manganism, characterized by an initial stage of psychiatric disorder followed by motor impairment. In the present study, we investigated the effects of Mn exposure on the developing dopaminergic system, specifically tyrosine hydroxylase (TH) protein and phosphorylation levels in the striatum of rats. Neonatal rats were exposed to Mn intraperitoneally (ip) from post-natal day 8 up to day 12 (PND8-12). Striatal tissue was analysed on PND14 or PND70, to detect either short-term or long-term effects induced by Mn exposure. There was a dose dependent increase in TH protein levels in the striatum at PND14, reaching significance at 20 mg kg(-1) Mn, and this correlated with an increase in TH phosphorylation at serines 40, 31 and 19. However, in the striatum at PND70, a time by which Mn levels were no longer elevated, there was a dose dependent decrease in TH protein levels, reaching significance at 20 mg kg(-1) Mn, and this correlated with TH phosphorylation at Ser40 and Ser19. There was however a significant increase in phosphorylation of TH at serine 31 at 20 mg kg(-1) Mn, which did not correlate with TH protein levels. Taken together our findings suggest that neonatal Mn exposure can have both short-term and long-term effects on the regulation of TH in the striatal dopaminergic system.


Assessment of intracranial collaterals on CT angiography in anterior circulation acute ischemic stroke.
Intracranial collaterals influence the prognosis of patients treated with intravenous tissue plasminogen activator in acute anterior circulation ischemic stroke. We compared the methods of scoring collaterals on pre-tPA brain CT angiography for predicting functional outcomes in acute anterior circulation ischemic stroke. Two hundred consecutive patients with acute anterior circulation ischemic stroke treated with IV-tPA during 2010-2012 were included. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff system, Maas system, the modified Tan scale, and the Alberta Stroke Program Early CT Score 20-point methodology. Good and extremely poor outcomes at 3 months were defined by modified Rankin Scale scores of 0-1 and 5-6 points, respectively. Factors associated with good outcome on univariable analysis were younger age, female sex, hypertension, diabetes mellitus, atrial fibrillation, small infarct core (ASPECTS ≥8), vessel recanalization, lower pre-tPA NIHSS scores, and good collaterals according to Tan methodology, ASPECTS methodology, and Miteff methodology. On multivariable logistic regression, only lower NIHSS scores (OR, 1.186 per point; 95% CI, 1.079-1.302; P = .001), recanalization (OR, 5.599; 95% CI, 1.560-20.010; P = .008), and good collaterals by the Miteff method (OR, 3.341; 95% CI, 1.203-5.099; P = .014) were independent predictors of good outcome. Poor collaterals by the Miteff system (OR, 2.592; 95% CI, 1.113-6.038; P = .027), Maas system (OR, 2.580; 95% CI, 1.075-6.187; P = .034), and ASPECTS method ≤5 points (OR, 2.685; 95% CI, 1.156-6.237; P = .022) were independent predictors of extremely poor outcomes. Only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke. However, poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals.


Mechanisms of antibody binding to a protein.
The mechanisms of antibody binding to a protein were studied by an analysis of specific amino acid residues critical to nine antigenic sites on myohemerythrin. Rabbit antisera to the whole protein were assayed for binding to more than 1500 distinct peptide analogs differing from the protein sequence by single amino acid replacements. The results, combined with information from the three-dimensional crystallographic structure, were used to evaluate probable mechanisms of antibody binding at individual sites. The data from all sites examined indicate that initial binding to solvent-exposed amino acid residues may promote local side-chain displacements and thereby allow the participation of other, previously buried, residues.


Electrocatalytic generation of H2 from neutral water in acetonitrile using manganese polypyridyl complexes with ligand assistance.
A Mn(i) tris(2-pyridylmethyl)amine complex fac-[Mn(κ3-tpa) (CO)3]+OTf- carries out electrocatalytic hydrogen evolution from neutral water in acetonitrile. Bulk electrocatalytic studies showed that the catalyst functions with a moderate Faradaic efficiency and turn over frequency. DFT computations support the role of the tpa ligand as a shuttle to transfer of protons to the metal center.


Clinical Hypnosis for Chronic Pain in Outpatient Integrative Medicine: An Implementation and Training Model.
Introduction: Clinical hypnosis for pain management cultivates specific skills to enhance general self-regulation and address pain. Hypnosis is well suited to integrative medicine settings; however, questions persist about its feasibility. This article describes a financially viable hypnosis practice model implemented in an integrative medicine clinic, providing initial feasibility data about rates of referral, participation, reimbursement, and provider retention. The specific processes required to establish and implement hypnosis services were detailed, including instruction in billing, reimbursement data, and a training model to enhance reach of services. Materials and methods: Insurer reimbursement data and operational costs were examined from three hypnosis groups conducted between September 2017 and March 2018. Furthermore, information on referral patterns and enrollment in treatment was collected from program initiation in September 2017 to January 2019. Provider retention in training with the expansion of supervision in the program's second year was also examined. Results: Of 258 individuals referred to hypnosis, 124 (48%) enrolled in group treatment. Analysis of insurer reimbursement over a subset of enrollees from three completed groups (N = 26) indicated an average collection of $95.85 per patient per session, equating to $706.86 per patient for the eight-session treatment. This extrapolates to $4,926.82 in total per seven-person group for the entirety of the eight-session treatment. After an annual training workshop, provider retention significantly increased (to 81% of eligible trained providers) with the initiation of twice-monthly clinical supervision focusing on transitioning from training to practice. Conclusion: This analysis indicates that a training- and practice-based research model of clinical hypnosis is feasible and financially sustainable in an integrative medicine setting.


Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy.
C1-inhibitor (C1-INH) is a serine protease inhibitor regulating the complement, kinin-kallikrein, coagulation, and fibrinolytic systems. Hereditary angioedema (HAE) is caused by an inherited deficiency of C1-INH characterized by sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. The optional therapy for the acute management of HAE is administration of human C1-INH (hC1-INH) concentrate. However, hC1-INH is not available in many countries, in which case fresh frozen plasma is an alternative. To summarize our experience with hC1-INH concentrate in patients with HAE. Clinical and laboratory information on the effectiveness and safety of hC1-INH administered to relieve 468 acute edematous attacks in 61 patients with HAE was analyzed. Severe abdominal or subcutaneous attacks and laryngeal edema were consistently relieved by the administration of 500 U hC1-INH concentrate. Symptoms improved within 15 to 60 minutes of administration. Progression of the attacks was never observed, and there were no recurrent attacks within 72 hours. hC1-INH concentrate requirements did not change after repeated use. hC1-INH concentrate proved effective in the management of 94 attacks in 22 children and 6 attacks in 4 pregnant women. Adverse reactions, viral infections, and antibody formation against the purified protein did not occur. The administration of hC1-INH concentrate in HAE is highly effective and safe for the treatment of acute attacks and short-term prophylaxis and in pediatric patients and pregnant women. Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis.


End-digit preference in blood pressure recordings of patients with ischaemic heart disease in primary care.
End-digit preference describes the disproportionate selection of specific end digits. The rounding of figures might lead to either an under- or over-recording of blood pressure (BP) and a lack of accuracy and reliability in treatment decisions. A total of 85 000 BP values taken from computerised general practice records of ischaemic heart disease patients in England between 2001 and 2003 were examined. Zero preference accounts for 64% of systolic and 59% of diastolic readings, compared with an expected frequency of 10% (P<0.000001). Even numbers are more frequently seen than odd numbers. In all, 64% of nonzero systolic recordings and 65% of diastolic recordings ended in even numbers, compared with expected proportions of 44% (P<0.0001). Among the nonzero even numbers, eight is the most frequently observed: 28% of systolic and 31% of diastolic recordings compared with an expected proportion of 25% (P<0.0001). Among the five nonzero odd numbers, five is the most frequently observed end digit, representing 59% systolic and 62% of diastolic compared with an expected level of 20% (P<0.00001). English general practice displays marked end-digit preference. This is strongly for the end-digit zero. However, there is more use of other end-digits, notably 8 and 5. This bias potentially carries important treatment consequences for this high-risk population.


Food variety and dietary diversity scores in children: are they good indicators of dietary adequacy?
To assess whether a food variety score (FVS) and/or a dietary diversity score (DDS) are good indicators of nutrient adequacy of the diet of South African children. Secondary data analyses were undertaken with nationally representative data of 1-8-year-old children (n = 2200) studied in the National Food Consumption Study in 1999. An average FVS (mean number of different food items consumed from all possible items eaten) and DDS (mean number of food groups out of nine possible groups) were calculated. A nutrient adequacy ratio (NAR) is the ratio of a subject's nutrient intake to the estimated average requirement calculated using the Food and Agriculture Organization/World Health Organization (2002) recommended nutrient intakes for children. The mean adequacy ratio (MAR) was calculated as the sum of NARs for all evaluated nutrients divided by the number of nutrients evaluated, expressed as a percentage. MAR was used as a composite indicator for micronutrient adequacy. Pearson correlation coefficients between FVS, DDS and MAR were calculated and also evaluated for sensitivity and specificity, with MAR taken as the ideal standard of adequate intake. The relationships between MAR and DDS and between anthropometric Z-scores and DDS were also evaluated. The children had a mean FVS of 5.5 (standard deviation (SD) 2.5) and a mean DDS of 3.6 (SD 1.4). The mean MAR (ideal = 100%) was 50%, and was lowest (45%) in the 7-8-year-old group. The items with the highest frequency of consumption were from the cereal, roots and tuber group (99.6%), followed by the 'other group' (87.6%) comprising items such as tea, sugar, jam and sweets. The dairy group was consumed by 55.8%, meat group by 54.1%, fats by 38.9%, other vegetables by 30.8%, vitamin-A-rich by 23.8%, other fruit by 22%, legumes and nuts by 19.7% and eggs by 13.3%. There was a high correlation between MAR and both FVS (r = 0.726; P < 0.0001) and DDS (r = 0.657; P < 0.0001), indicating that either FVS or DDS can be used as an indicator of the micronutrient adequacy of the diet. Furthermore, MAR, DDS and FVS showed significant correlations with height-for-age and weight-for-age Z-scores, indicating a strong relationship between dietary diversity and indicators of child growth. A DDS of 4 and an FVS of 6 were shown to be the best indicators of MAR less than 50%, since they provided the best sensitivity and specificity. Either FVS or DDS can be used as a simple and quick indicator of the micronutrient adequacy of the diet.


The butyrophilin (BTN) gene family: from milk fat to the regulation of the immune response.
Butyrophilins (BTN) belong to the immunoglobulin (Ig) superfamily of transmembrane proteins. These molecules are of increasing interest to immunologists, as they share a structural homology with B7 family members at the extracellular domain level. Moreover, a role of these molecules has been suggested in the negative regulation of lymphocyte activation for almost all the BTN that have been studied. In addition, the expression of some BTN family members has been reported to be associated with autoimmune diseases. Over the last few years, the number of BTN and BTN-like members has greatly increased. In this study, the butyrophilin family in mammals has been revisited, using phylogenetic analysis to identify all the family members and the phylogenetic relations among them, and to establish a standard nomenclature. Fourteen BTN groups were identified that are not all conserved between mammalian species. In addition, an overview of expression profiles and functional BTN data demonstrates that these molecules represent a new area of investigation for the design of future strategies in the modulation of the immune system.


Visuotopic reorganization in the primary visual cortex of adult cats following monocular and binocular retinal lesions.
The effect of discrete monocular retinal lesions on the representation of the visual field in the primary visual area (V1) was investigated in adult cats. Lesions were created using argon lasers, 8 d to 4(1/2) months prior to electrophysiological recording. This produced lesion projection zones (LPZs) in V1, 1.6-9.5 mm wide, that were deprived of their normal input from one eye, but that received a normal input from the other eye. Nevertheless, at the majority of recording sites within these zones neuronal responses were elicited by stimulation of the lesioned eye, with receptive fields being displaced onto regions of retina surrounding the lesion, while receptive fields determined through stimulation of the normal eye followed the normal visuotopic organization of V1. However, neuronal responses to stimulation of the lesioned eye within the LPZs were characterized by rapid habituation and unusually low firing rates in comparison with responses to stimulation of the normal eye. Stimulation of the normal eye temporarily marked the responsiveness of neurons within the LPZ to stimulation of the lesioned eye. The proportion of neurons responsive to stimulation of the lesioned eye was higher just inside the borders of the LPZs than at the centers of these zones. However, neurons responsive to stimulation of the test eye were found up to 3.6 mm from the perimeter of the LPZs, and therefore the shifts in the visuotopic map caused by retinal lesions cannot be explained solely on the basis of the normal scatter of receptive fields and point-image size in V1. The proportion of cells responsive to stimulation of the lesioned eye was highest in the infragranular layers, and lowest in the supragranular layers. By combining a restricted lesion of one eye with laser photocoagulation of the optic disc of the other eye, the effects of the normal eye on the lesion-induced visuotopic reorganization were also investigated. Neither chronic nor acute deactivation produced any discernible further changes in visuotopy or in the characteristics of neuronal responses to stimulation of the eye with the discrete lesions. Our findings show that the representations of the two eyes in adult visual cortex are capable of independent reorganization. These findings parallel those of work in auditory cortex, suggesting that topographic reorganization in primary sensory areas of adult cortex may be governed by similar mechanisms.


Gardening by the psychomyiid caddisfly Tinodes waeneri: evidence from stable isotopes.
Sedentary species face a trade-off between the benefits of exploiting food close to their homes and the cost of defending it. In aquatic systems, it has been suggested that some sedentary grazers can increase the range of circumstances under which they are at an advantage over mobile grazers by enhancing food resources within their feeding territories through 'gardening'. We examined this for the retreat-building sedentary larvae of the caddis Tinodes waeneri, which are often dominant in the littoral of lakes. We hypothesised that T. waeneri gardens by fertilising its retreat (a fixed 'gallery' on which algae and other microorganisms grow), and that gardening would be more important in lower productivity lakes. We tested this by analysing the carbon and nitrogen stable isotope ratios of larvae, their galleries and the general background epilithon, collected from rocks in the littoral zones of six lakes spread across a natural nutrient gradient. We found evidence of nutrient recycling within the Tinodes gallery community in all lakes. Galleries were (15)N-depleted compared to the epilithon, suggesting that algae on galleries preferentially assimilated (14)N from larval excretions that were themselves (15)N-depleted relative to the larval food source. Mixing model results indicate that galleries formed an important larval carbon and nitrogen source, with mean gallery dietary contributions of over 40% in at least one sample period in all lakes studied. Gallery contributions were greater between April and October than in January and, contrary to our initial hypothesis, greater in the more productive lakes of those surveyed. Nevertheless, T. waeneri galleries do act as a fertilised garden. 'Gardening' appears to be widespread in this species, and may affect productivity and patterns of nitrogen retention within the stony littoral of lakes.


Connecting Families to Their Health Record and Care Team: The Use, Utility, and Impact of a Client/Family Health Portal at a Children's Rehabilitation Hospital.
Health care portals have the potential to provide consumers with timely, transparent access to health care information and engage them in the care process. The objective was to examine the use, utility, and impact on engagement in care and caregiver-provider communication of a client/family portal providing access to electronic health records (EHRs) and secure, 2-way e-messaging with care providers. We conducted a prospective, mixed-methods study involving collection of caregivers' portal usage information over a 14-month period (from portal introduction in January 2015 to the end of the study period in March 2016), a Web-based survey for caregivers administered after a minimum of 2 months' exposure to the portal and repeated 2 months later, and focus groups or individual interviews held with caregivers and service providers at the same points in time. The survey assessed caregivers' perceptions of the utility of and satisfaction with the EHR and e-messaging, and the portal's impact on client engagement and perceptions of caregiver-provider communication. A total of 18 caregivers (parents) completed surveys and 6 also took part in focus groups or interviews. In addition, 5 service providers from different disciplines took part in focus groups or interviews. Although usage patterns varied, the typical pattern was a steady level of use (2.5 times a month over an average of 9 months), which is higher than typically reported use. The portal pages most frequently accessed were the home page, health record main page, appointment main page, and reports main page. The Web-based survey captured caregivers' perceptions of usefulness of and satisfaction with the EHR and portal messaging, as well as the portal's impact on their engagement in care and perceptions of caregiver-provider communication. The surveys indicated a moderate degree of utility of and satisfaction with the portal features, and a low but emerging impact on engagement in care and caregiver-provider communication (survey scales measuring these outcomes displayed excellent internal consistency, with Cronbach alpha ranging from .89 to .95). Qualitative themes from focus groups and interviews supported and extended the survey findings. Caregivers and service providers saw appreciable information benefits and provided recommendations to increase portal use and utility. Caregivers focused on the scope of organizational adoption of the portal system and indicated their hopes for the future of the portal, whereas service providers were concerned about how to best manage their investment of time and effort in preparing client-friendly reports and messaging clients via the portal. Overall, the findings show the promise of the portal and the need for ongoing evaluation to show the portal's ultimate potential in enhancing engagement in care and communication with care providers.


Antioxidant systems and anoxia tolerance in a freshwater turtle Trachemys scripta elegans.
The effects of anoxic submergence (20 h at 5 degrees C) and subsequent 24 h aerobic recovery on the antioxidant systems of six organs were examined in freshwater turtles, Trachemys scripta elegans. Both xanthine oxidase and xanthine dehydrogenase were detected in turtle tissues with xanthine oxidase composing 36-75% of the total activity. Turtle organs displayed high constitutive activities of catalase (CAT), superoxide dismutase (SOD), and alkyl hydroperoxide reductase (AHR). Measurements of lipid peroxidation damage products (conjugated dienes, lipid hydroperoxides, thiobarbituric acid reactive substances) showed minimal changes during anoxia or recovery suggesting that natural anoxic-aerobic transitions occur without the free radical damage that is seen during ischemia-reperfusion in mammals. Anoxia exposure led to selected decreases in enzyme activities in organs, consistent with a reduced potential for oxidative damage during anoxia: SOD decreased in liver by 30%, CAT decreased in heart by 31%, CAT and total glutathione peroxidase (GPOX) decreased in kidney (by 68 and 41%), and CAT and SOD decreased in brain (by 80 and 15%). AHR, however, increased 2 and 3.5 fold during anoxia in heart and kidney respectively. Most anoxia-induced changes were reversed during aerobic recovery although brain enzyme activities remained suppressed. Some specific changes occurred during the recovery period: SOD increased from controls in heart by 45%, AHR increased to 200 and 168% of control values in red and white muscle respectively, and total GPOX decreased from controls in heart and white muscle by 75 and 77% respectively. The results show that biochemical adaptation for natural anoxia tolerance in turtles includes well-developed antioxidant defenses that minimize or prevent damage by reactive oxygen species during the reoxygenation of organs after anoxic submergence.


Deep RNA sequencing reveals the smallest known mitochondrial micro exon in animals: The placozoan cox1 single base pair exon.
The phylum Placozoa holds a key position for our understanding of the evolution of mitochondrial genomes in Metazoa. Placozoans possess large mitochondrial genomes which harbor several remarkable characteristics such as a fragmented cox1 gene and trans-splicing cox1 introns. A previous study also suggested the existence of cox1 mRNA editing in Trichoplax adhaerens, yet the only formally described species in the phylum Placozoa. We have analyzed RNA-seq data of the undescribed sister species, Placozoa sp. H2 ("Panama" clone), with special focus on the mitochondrial mRNA. While we did not find support for a previously postulated cox1 mRNA editing mechanism, we surprisingly found two independent transcripts representing intermediate cox1 mRNA splicing stages. Both transcripts consist of partial cox1 exon as well as overlapping intron fragments. The data suggest that the cox1 gene harbors a single base pair (cytosine) micro exon. Furthermore, conserved group I intron structures flank this unique micro exon also in other placozoans. We discuss the evolutionary origin of this micro exon in the context of a self-splicing intron gain in the cox1 gene of the last common ancestor of extant placozoans.