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Background There is a limited literature describing the oral microbiome and its diagnostic potential in paediatric inflammatory bowel disease [IBD]. Methods We examined the dorsum tongue microbiome by V1–V2 sequencing in a cohort of 156 treatment-naïve children diagnosed with IBD compared to 102 healthy control children. Microbiome changes over time following treatment were examined in a subset of patients and associations between IBD diagnosis and dysbiosis were explored. Results Analysis of community structure of the microbiome in tongue samples revealed that IBD samples diverged significantly from healthy control samples [PERMANOVA p  = 0.0009] and exhibited a reduced abundance of Clostridia in addition to several major oral genera [ Veillonella , Prevotella and Fusobacterium species] with an increased abundance of streptococci. This dysbiosis was more marked in patients with severe disease. Higher levels of the potential pathobionts Klebsiella and Pseudomonas spp. were also associated with IBD. In terms of predicted functions, the IBD oral microbiome was potentially more acidogenic and exhibited reduced capacity for B vitamin biosynthesis. We used a machine learning approach to develop a predictive model of IBD which exhibited a mean-prediction AUC [area under the ROC curve] of 0.762. Finally, we examined a subset of 53 patients following 12 months of therapy and could show resolution of oral dysbiosis as demonstrated by a shift towards a healthy community structure and a significant reduction in oral dysbiosis. Conclusion Oral dysbiosis found in children with IBD is related to disease severity and resolves over time following successful IBD treatment. [ABSTRACT FROM AUTHOR]

Inferences made from molecular data support regional stock assessment goals by providing insights into the genetic population dynamics of enigmatic species. Population genomics metrics, such as genetic diversity and population connectivity, serve as useful proxies for species health and stability. Sleeper sharks (genus Somniosus) are ecologically important deep-sea predators, estimated to reach ages of 250 to 300 yr and taking decades to reach sexual maturity. The subgenus Somniosus (Somniosus) is comprised of 3 species: S. pacificus , S. microcephalus , and S. antarcticus. Given the life history strategy of somniosids, they are vulnerable to overfishing and population declines. Further, data to assess the stocks of these species are limited. To address this deficiency, we used the reduced representation library method Restriction-site Associated DNA sequencing (RADseq) to conduct phylogenomic and population genomics analyses, providing novel information for use in stock assessments. Our results strongly support the species status of S. microcephalus (N = 79), but recover S. antarcticus (N = 2) intermixed within the S. pacificus (N = 170) clade. Population genomics analyses reveal genetic homogeneity within S. pacificus and S. microcephalus , and estimates of effective population size were in the hundreds for both species. Kinship analysis identified 2 first-degree relative pairs within our dataset (1 within each species). Our results contribute new information for stock assessments of these uniquely long-lived species by providing the strongest molecular evidence to date for the synonymization of S. antarcticus and S. pacificus , as well as estimating population genomic metrics for each supported species within the Somniosus (Somniosus) subgenus. [ABSTRACT FROM AUTHOR]

Littoral cell angiomas are uncommon primary splenic haemangiomas with rare malignant potential. We report a case of a 76-year-old male with an incidental solitary littoral cell angioma found within an accessory spleen. We provide an overview of the literature of littoral cell angiomas and highlight the diagnostic challenge and treatment of this important differential for general surgeons caring for patients with splenic masses. This is the first case to describe primary resection of a littoral cell angioma with splenic preservation. [ABSTRACT FROM AUTHOR]

Approximately two-thirds of hospital admissions are older adults and almost half of these are likely to have some form of dementia. People with dementia are not only at an increased risk of adverse outcomes once admitted, but the unfamiliar environment and routinised practices of the wards and acute care can be particularly challenging for them, heightening their confusion, agitation and distress further impacting the ability to optimise their care. It is well established that a person-centred care approach helps alleviate some of the unfamiliar stress but how to embed this in the acute-care setting remains a challenge. In this article, we highlight the challenges that have been recognised in this area and put forward a set of evidence-based 'pointers for service change' to help organisations in the delivery of person-centred care. The DEMENTIA CARE pointers cover areas of: dementia awareness and understanding, education and training, modelling of person-centred care by clinical leaders, adapting the environment, teamwork (not being alone), taking the time to 'get to know', information sharing, access to necessary resources, communication, involving family (ask family), raising the profile of dementia care, and engaging volunteers. The pointers extend previous guidance, by recognising the importance of ward cultures that prioritise dementia care and institutional support that actively seeks to raise the profile of dementia care. The pointers provide a range of simple to more complex actions or areas for hospitals to help implement person-centred care approaches; however, embedding them within the organisational cultures of hospitals is the next challenge. [ABSTRACT FROM AUTHOR]

This article explores an interesting episode in the history of time, health, and modernity: Britain's 1908 and 1909 Daylight Saving Time (DST) Bills. While the original DST scheme was unsuccessful, the discussions surrounding its implementation reveal tensions central to early twentieth century modernity, namely between industrial time and 'natural' bodily rhythms. This article argues that DST was essentially a public health measure aimed at improving the conditions of indoor workers like shop girls and clerks through government regulation of the private time of the labouring classes. Drawing on the extensive evidence provided to two House of Commons Special Committees, this article reveals how DST debates drew together contemporary discussions around sunlight therapy, night work, and the importance of regular sleeping and eating to tackle Britain's endemic urban diseases like consumption and anaemia. I suggest that the idea of bodily rhythms was increasingly important in medical thinking in this period and that the study of rhythmicity points to the potential for incorporating temporality as an analytical category in medical history. [ABSTRACT FROM AUTHOR]

Purpose: The physician voice is crucial to shaping health policy and public health guidelines, particularly during COVID-19. However, there are gaps in health policy and advocacy education within graduate medical education. This study sought to characterise the impact of a virtual COVID-19 focused advocacy day among medical trainees in Massachusetts.Study Design: The half-day event featured speakers drawn from government relations experts, physician advocates, and state and federal legislators as well as breakout discussions among attendees. A 25-question Redcap survey and list of resources/opportunities for continued advocacy was administered to all participants at event's conclusion on 19 May 2020.Results: There were 60 responses from 141 participants (43% response rate). One-third reported no prior formal health policy instruction, and over half reported getting information from news publications, social media and peers. 58% believed physician involvement in advocacy to be 'extremely important' prior to COVID-19; 83% believed the same after onset of COVID-19 (p<0.0001). The most common barriers to advocacy engagement were lack of time and knowledge. Most attendees felt participation increased their knowledge and likelihood to engage in the COVID-19 response, imparted useful skills/knowledge for continued advocacy, increased their interest in future similar events, and that such events should be available to all trainees.Conclusions: Trainees recognise the importance of health policy and advocacy and value opportunities to gain the necessary skills/knowledge to effect tangible change. Virtual advocacy days can be replicated nationwide to help trainees learn about advocacy efforts and find their legislative voices during COVID-19 and beyond. [ABSTRACT FROM AUTHOR]

Background A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. Methods Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. Results About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95–100) to 100% and specificity from 99% (95% CI 97–100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76–87) to 94% (95% CI 89–98) and specificity ranging from 76% (95% CI 70–82) to 92% (95% CI 88–96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. Conclusions People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people. Trial Registration NCT04509713 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: Atypical antipsychotic drugs are frequently used in the treatment of serious mental illness (SMI), specifically schizophrenia and bipolar disorder. Adherence to these prescribed drug regimens is a challenge to successful treatment with these drugs. For some of the more common drugs in this class, novel turbidimetric immunoassays have been developed for therapeutic drug monitoring (TDM) to aid in the management of patients prescribed these drugs. Methods: Immunoassays for aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, and risperidone were set up at 2 centers: Johns Hopkins Hospital (JHH) on the Roche Cobas® c501, and the Hospital of the University of Pennsylvania (HUP) on the Beckman AU480. Assay imprecision, limit of quantification (LOQ), functional sensitivity, linearity, and recovery were assessed. Remnant clinical samples were obtained from a reference laboratory (ARUP), and immunoassay results were compared with those obtained by LC–MS/MS. Results: Imprecision at both sites for all analytes and concentrations tested was <10%. The manufacturer's LOQ was confirmed for each assay, and the functional sensitivity for each assay was found to be lower than the LOQ. All assays were found to be linear over the measuring range, with recoveries ranging from 91% to 123%. For method comparison, Deming regression slopes were found to be between 0.84 to 1.28. Conclusion: The immunoassays evaluated here are suitable for quantifying drug concentrations to be used in TDM for all 6 drugs. Commercialization of these assays will enable increased access for TDM in psychiatric patient management. [ABSTRACT FROM AUTHOR]

Quantifying vertical distributions of pelagic predators elucidates pelagic ecosystem structure and informs fisheries management. In the tropical South Atlantic Ocean, the recently designated large-scale marine protected area around Ascension Island hosts diverse pelagic predators for which basin-specific vertical habitat information is minimal or absent. We used pop-up satellite archival tags to analyse vertical habitat use in 12 species (bigeye tuna Thunnus obesus , blue marlin Makaira nigricans , blue shark Prionace glauca , dolphinfish Coryphaena hippurus , Galapagos shark Carcharhinus galapagensis , oceanic whitetip Carcharhinus longimanus , sailfish Istiophorus albicans , silky shark Carcharhinus falciformis , swordfish Xiphias gladius , tiger shark Galeocerdo cuvier , wahoo Acanthocybium solandri , and yellowfin tuna Thunnus albacares) and quantify parameters (temperature, dissolved oxygen, diel cycles, lunar phase) known to constrain vertical movements. Predator depth distributions varied widely, and classification trees grouped predators into four clades: (i) primarily epipelagic; (ii) partial thermocline use; (iii) oscillatory diving with thermocline/sub-thermocline use; and (iv) extensive use of sub-thermocline waters. Vertical habitat differences were linked to thermal physiology and foraging ecology, and species-specific physical constraints from other ocean basins were largely conserved in the South Atlantic. Water column features defined species-specific depth distributions, which can inform fisheries practices and bycatch risk assessments and population estimates. [ABSTRACT FROM AUTHOR]

Animal-borne telemetry devices have become a popular and valuable means for studying the cryptic lives of cetaceans. Evaluating the effect of capture, handling and tagging procedures remains largely unassessed across species. Here, we examine the effect of capture, handling and tagging activities on an iconic Arctic cetacean, the narwhal (Monodon monoceros), which has previously been shown to exhibit an extreme response to extended capture and handling. Using accelerometry-derived metrics of behaviour, including activity level, energy expenditure and swimming activity, we quantify the post-release responses and time to recovery of 19 individuals following capture and tagging activities considering the intrinsic covariates of sex and individual size and the extrinsic covariates of handling time and presence of a 'bolt-on' satellite telemetry device. From accelerometer-derived behaviour, most narwhals appeared to return to mean baseline behaviour (recovery) within 24 hours after release, which was supported by longer-term measures of diving data. None of the covariates measured, however, had an effect on the time individuals took to recover following release. Using generalized additive models to describe changes in behaviour over time, we found handling time to be a significant predictor of activity levels, energy expenditure and swimming behaviour following release. Individuals held for the longest period (>40 min) were found to display the largest effect in behaviour immediately following release with respect to swimming behaviour and activity levels. We also found some support for relationships between activity levels, energy expenditure and swimming activity and two other covariates: sex and the attachment of a bolt-on configuration satellite tags. Our results indicate that narwhals recover relatively quickly following capture, handling and tagging procedures, but we suggest that researchers should minimize handling time and further investigation is needed on how to mitigate potential effects of bolt-on satellite tags in these sensitive species. [ABSTRACT FROM AUTHOR]

Objective: The genetic testing for hereditary breast cancer that is most helpful in high-risk women is underused. Our objective was to quantify the risk factors for heritable breast and ovarian cancer contained in the electronic health record (EHR), to determine how many women meet national guidelines for referral to a cancer genetics professional but have no record of a referral.Methods and Materials: We reviewed EHR records of a random sample of women to determine the presence and location of risk-factor information meeting National Comprehensive Cancer Network (NCCN) guidelines for a further genetic risk evaluation for breast and/or ovarian cancer, and determine whether the women were referred for such an evaluation.Results: A thorough review of the EHR records of 299 women revealed that 24 (8%) met the NCCN criteria for referral for a further genetic risk evaluation; of these, 12 (50%) had no referral to a medical genetics clinic.Conclusions: Half of the women whose EHR records contain risk-factor information meeting the criteria for further genetic risk evaluation for heritable forms of breast and ovarian cancer were not referred. [ABSTRACT FROM AUTHOR]

Surveillance of animal movements using electronic tags (i.e., biotelemetry) has emerged as an essential tool for both basic and applied ecological research and monitoring. Advances in animal tracking are occurring simultaneously with changes to technology, in an evolving global scientific culture that increasingly promotes data sharing and transparency. However, there is a risk that misuse of biotelemetry data could increase the vulnerability of animals to human disturbance or exploitation. For the most part, telemetry data security is not a danger to animals or their ecosystems, but for some high-risk cases, as with species' with high economic value or at-risk populations, available knowledge of their movements may promote active disturbance or worse, potential poaching. We suggest that when designing animal tracking studies it is incumbent on scientists to consider the vulnerability of their study animals to risks arising from the implementation of the proposed program, and to take preventative measures. [ABSTRACT FROM AUTHOR]

Introduction The ability to predict risk for poor outcomes in Crohn's disease [CD] would enable early treatment intensification. We aimed to identify children with CD with complications at baseline and throughout the study period who are at risk for surgery 2 years from diagnosis. Methods Newly diagnosed children with CD were enrolled into a prospective, multicentre inception cohort. Disease characteristics and serological markers were obtained at baseline and week 12 thereafter. Outcome data including disease activity, therapies, complications and need for surgery were collected until the end of 104 weeks. A chi-square automatic interaction detection [CHAID] algorithm was used to develop a prediction model for early surgery. Results Of 285 children enrolled, 31 [10.9%] required surgery within 2 years. Multivariate analysis identified stricturing disease at baseline (odds ratio [OR] 5.26, 95% confidence interval [CI] 2.02–13.67 [ p = 0.001]), and Paediatric Crohn's Disease Activity Index [PCDAI] >10 at week 12 (OR 1.06, 95% CI 1.02–1.10 [ p = 0.005]) as key predictors for early surgery. CHAID demonstrated that absence of strictures at diagnosis [7.6%], corticosteroid-free remission at week 12 [4.1%] and early immunomodulator therapy [0.8%] were associated with the lowest risk of surgery, while stricturing disease at diagnosis [27.1%, p < 0.001] or elevated PCDAI at week 12 [16.7%, p = 0.014] had an increased risk of surgery at follow-up. Anti-OmpC status further stratified high-risk patients. Discussion A risk algorithm using clinical and serological variables at diagnosis and week 12 can categorize patients into high- and low-risk groups from diagnosis. [ABSTRACT FROM AUTHOR]

Background and Aim Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. Methods This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. Results Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. Conclusions High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome. [ABSTRACT FROM AUTHOR]

Background: Exclusive enteral nutrition [EEN] and corticosteroids [CS] induce similar rates of remission in mild to moderate paediatric Crohn's disease [CD], but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes. Methods: We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications [fibrostenotic disease, penetrating disease, and active perianal disease] and growth were recorded throughout the study. A propensity score analysis was performed. Results: A total of 147 children [mean age 12.9 ± 3.2 years], treated by EEN [n = 60] or CS [n = 87] were included. New complications developed in 13.7% of CS [12/87] versus 11.6% of EEN [7/60], = 0.29. Remission was achieved in 41/87 [47%] in CS and 38/60 [63%] EEN, p = 0.036. Median time to relapse did not differ [14.4 ± 1 months with CS, 16.05 ± 1.1 EEN, p = 0.28]. Mean height Z scores decreased from Week 0 to Week 78 with CS [-0.34 ± 1.1 to -0.51 ± 1.2, p = 0.01], but not with EEN [-0.32 ± 1.1 to -0.22 ± 0.9, p = 0.56]. In a propensity score analysis, EEN was superior to CS for inducing remission [p = 0.05] and trended to superiority for height Z score [p = 0.055]. Conclusions: Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD. [ABSTRACT FROM AUTHOR]

Background: Breast reconstruction is an important component of multidisciplinary breast cancer management. The practice of breast reconstruction after mastectomy has evolved significantly in the past decade as a result of both increasing mastectomy rates and advances in reconstructive strategy. These changes have significantly influenced the contemporary surgical management of breast cancer. The aim of this study was to examine trends in breast reconstruction after mastectomy in an Irish population. Methods: Data were reviewed from a database of all patients who had mastectomy with or without breast reconstruction at Galway University Hospital, a tertiary breast cancer referral centre, between 2004 and 2014. Trends in breast reconstruction after mastectomy were explored with respect to patient demographics, clinicopathological features, and neoadjuvant and adjuvant therapy. Results: Of 1303 patients who underwent mastectomy during interval studied, 706 (54.2 per cent) had breast reconstruction after mastectomy. In 629 patients (89·1 per cent), breast reconstruction was performed in the immediate setting. Reconstruction rates increased over time from 20·5 per cent in 2004 to 44·7 per cent in 2014. Reconstruction was more commonly performed in younger patients and those with benign, in situ and early‐stage disease. A negative relationship between radiotherapy and reconstruction was observed. A pedicled flap with or without an implant was the most commonly used reconstructive approach in patients receiving radiotherapy. Conclusion: Breast reconstruction after mastectomy has become the standard of care in the surgical treatment of breast cancer. Recent trends show a transition favouring implant‐based approaches. [ABSTRACT FROM AUTHOR]

Background Evidence suggests that the medical profession is reluctant to report mental ill-health despite its high prevalence. Aims To compare differential reporting patterns in the incidence of work-related mental ill-health (WRMIH) affecting doctors with selected comparison occupational groups, as determined by surveillance by general practitioners (GPs), specialist psychiatrists and occupational physicians (OPs). Methods New cases of medically reported WRMIH were reported prospectively between 2006 and 2009 by GPs, psychiatrists and OPs as part of The Health and Occupation Research (THOR) network. For GP and psychiatry reporting schemes, incidence rates (IRs) for doctors, nurses, teachers, corporate managers and protective service workers were calculated using information from the Labour Force Survey as the denominator. In OP surveys, participating reporters provided denominator information to calculate IRs for doctors, nurses and teachers. Results Average annual IRs expressed per 100 000 person/years employed as reported by GPs, psychiatrists and OPs, respectively, were: doctors (309, 971, 430), nurses (891, 208, 670), teachers (1040, 136, 210) and for GPs and psychiatrists, respectively, were: protective service workers (1432, 721) and corporate managers (428, 90). Psychiatrists reported a higher incidence of WRMIH in doctors, whereas GPs reported higher incidences of WRMIH in other occupations (chi-squared test, P < 0.001). Conclusions The distribution of the incidence of new cases reported across different schemes suggests a differential reporting pattern of WRMIH in doctors. The higher IR for doctors in psychiatrist-reported WRMIH could be due to factors such as disease severity and bypassing formal referral channels. [ABSTRACT FROM AUTHOR]

Electronic tags are significantly improving our understanding of aquatic animal behavior and are emerging as key sources of information for conservation and management practices. Future aquatic integrative biology and ecology studies will increasingly rely on data from electronic tagging. Continued advances in tracking hardware and software are needed to provide the knowledge required by managers and policymakers to address the challenges posed by the world's changing aquatic ecosystems. We foresee multiplatform tracking systems for simultaneously monitoring the position, activity, and physiology of animals and the environment through which they are moving. Improved data collection will be accompanied by greater data accessibility and analytical tools for processing data, enabled by new infrastructure and cyberinfrastructure. To operationalize advances and facilitate integration into policy, there must be parallel developments in the accessibility of education and training, as well as solutions to key governance and legal issues. [ABSTRACT FROM AUTHOR]

Reduced physical functioning is common following resections for esophageal cancer; however, objective data on physical performance outcomes in this cohort are rare. The aim of this study was to assess the physical performance and health related quality of life (HRQOL) of disease free survivors and compare findings in a case matched noncancer control group. Twenty-five males (mean (±SD) aged 63 (±6) years) who were over 6 months postesophagectomy and disease-free were compared with 25 controls (60 ± 6 years). Physical functioning was assessed through hand grip strength (dynamometry), exercise capacity (incremental shuttle walk test), physical activity levels (RT3 accelerometer), and body composition (bio-electrical impedance analysis). Health-related quality of life was measured using the EORTCQLQ-C30 questionnaire. Esophageal cancer survivors demonstrated significantly lower fitness (P < 0.001) and time spent in moderate (P < 0.001) and vigorous (P < 0.001) intensity physical activity compared with controls. Global health status and quality of life were similar in both groups (P = 0.245); however, physical and role functioning domains were lower in the cancer survivors (P < 0.001, and P = 0.001, respectively). These data show that disease-free survivors of curative esophageal cancer treatment demonstrate a significant compromise in physical functioning compared with controls, thus highlighting the multiple, complex rehabilitative needs of this cohort. [ABSTRACT FROM AUTHOR]

The Global Polio Eradication Initiative (GPEI) has been in operation since 1988, now spends $1 billion annually, and operates through thousands of staff and millions of volunteers in dozens of countries. It has brought polio to the brink of eradication. After eradication is achieved, what should happen to the substantial assets, capabilities, and lessons of the GPEI? To answer this question, an extensive process of transition planning is underway. There is an absolute need to maintain and mainstream some of the functions, to keep the world polio-free. There is also considerable risk-and, if seized, substantial opportunity-for other health programs and priorities. And critical lessons have been learned that can be used to address other health priorities. Planning has started in the 16 countries where GPEI's footprint is the greatest and in the program's 5 core agencies. Even though poliovirus transmission has not yet been stopped globally, this planning process is gaining momentum, and some plans are taking early shape. This is a complex area of work-with difficult technical, financial, and political elements. There is no significant precedent. There is forward motion and a willingness on many sides to understand and address the risks and to explore the opportunities. Very substantial investments have been made, over 30 years, to eradicate a human pathogen from the world for the second time ever. Transition planning represents a serious intent to responsibly bring the world's largest global health effort to a close and to protect and build upon the investment in this effort, where appropriate, to benefit other national and global priorities. Further detailed technical work is now needed, supported by broad and engaged debate, for this undertaking to achieve its full potential. [ABSTRACT FROM AUTHOR]

Background Postgraduate education, training and clinical governance in occupational medicine (OM) require easily accessible yet rigorous, research and evidence-based tools based on actual clinical practice. Aims To develop and evaluate an online resource helping physicians develop their OM skills using their own cases of work-related ill-health (WRIH). Methods WRIH data reported by general practitioners (GPs) to The Health and Occupation Research (THOR) network were used to identify common OM clinical problems, their reported causes and management. Searches were undertaken for corresponding evidence-based and audit guidelines. A web portal entitled Electronic, Experiential, Learning, Audit and Benchmarking (EELAB) was designed to enable access to interactive resources preferably by entering data about actual cases. EELAB offered disease-specific online learning and self-assessment, self-audit of clinical management against external standards and benchmarking against their peers' practices as recorded in the research database. The resource was made available to 250 GPs and 224 occupational physicians in UK as well as postgraduate OM students for evaluation. Results Feedback was generally very favourable with physicians reporting their EELAB use for case-based assignments. Comments such as those suggesting a wider range of clinical conditions have guided further improvement. External peer-reviewed evaluation resulted in accreditation by the Royal College of GPs and by the Faculties of OM (FOM) of London and of Ireland. Conclusions This innovative resource has been shown to achieve education, self-audit and benchmarking objectives, based on the participants' clinical practice and an extensive research database. [ABSTRACT FROM AUTHOR]

Background Primary care is one of the key environments in which to target public health and sedentary behaviours are increasing being linked to several adverse health outcomes. The aim of this study was to determine the prevalence and correlates of sedentary behaviour in an adult primary care population. Methods The International Physical Activity Questionnaire was used to collect data on the weekday sitting of participants. Stratified random sampling based on urban/rural location and deprivation was used to identify three primary care centres from which the sample was drawn. Results Data were collected from 885 participants (96.7% response rate) of whom 64% (n = 565) were female and 36% (n = 320) were male. The mean age was 42 (SD 14.2). Overall 48% (n = 418) of participants sat for >4 h daily with a median sitting time of 240 min (IQR 150-480). Attendance at the urban non-deprived primary care centre (B = 0.237, P < 0.001), male gender (B = 0.284, P < 0.001), overweight/obesity (B = 0.081, P = 0.048) and having a disability or injury limiting physical activity (B = 0.093, P = 0.028) were associated with higher sitting times. Conclusion This study established the factors that influence sedentary behaviours in the primary care population which can help inform the development and targeting of promotional strategies. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence of psoriasis in an IBD cohort with reference to clinical characteristics and anti-TNFα use. Methods: Patients with psoriasis and IBD were retrospectively identified from the IBD database at Tallaght Hospital from 2000 to 2015. Pertinent clinical data were obtained from patients notes including anti-TNFα exposure. Prevalence rates of genuine and reactive psoriasis were calculated and compared using Student's T-test. A P values of<0.05 was considered significant. Results: In total, 1384 IBD patients were identified. The overall prevalence rate of IBD and psoriasis was 2.4% (n=33), with 1.8% (n=25) in the Crohn's disease group and 0.6% (n=8) in the ulcerative colitis group. Within the psoriasis group, 24% (n=8 of 33) had reactive psoriasis. The prevalence rates of psoriasis in the non-biological and biological cohorts were similar 2.5% (25 of 981) and 2% (8 of 403), respectively. There was no significant association with reactive psoriasis and disease type. There was a trend towards higher rates of reactive psoriasis Adalimumab users, 3.6% (6 of 166) vs. 0.8% (2 of 237), OR=4.283, P=0.077, 95% CI 0.854-21.483 in infliximab users. In addition, in our cohort, smoking was not associated with any form of psoriasis in IBD, OR=1.377, 95% CI 0.061-3.087, P=0.437. Conclusion: In our large study, the prevalence rate of reactive psoriasis was similar to the background rate of psoriasis in the overall IBD cohort (2.0 vs. 2.4%). A 2% prevalence rate represents a common adverse event that clinicians should be aware of. [ABSTRACT FROM AUTHOR]

In plants movement of the endoplasmic reticulum (ER) is dependent on the actin cytoskeleton. However little is known about proteins that link the ER membrane and the actin cytoskeleton. Here we identified a novel protein, NETWORKED 3B (NET3B), which is associated with the ER and actin cytoskeleton in vivo. NET3B belongs to a superfamily of plant specific actin binding proteins, the NETWORKED family. NET3B associates with the actin cytoskeleton in vivo through an N-terminal NET actin binding (NAB) domain, which has been well-characterized in other members of the NET family. A three amino acid insertion, Val-Glu-Asp, in the NAB domain of NET3B appears to lower its ability to localize to the actin cytoskeleton compared with NET1A, the founding member of the NET family. The C-terminal domain of NET3B links the protein to the ER. Overexpression of NET3B enhanced the association between the ER and the actin cytoskeleton, and the extent of this association was dependent on the amount of NET3B available. Another effect of NET3B overexpression was a reduction in ER membrane diffusion. In conclusion, our results revealed that NET3B modulates ER and actin cytoskeleton interactions in higher plants. [ABSTRACT FROM AUTHOR]

Evidence is accumulating for molecular microcompartments formed when proteins interact in localized domains with the cytoskeleton, organelle surfaces, and intracellular membranes. To understand the potential functional significance of protein microcompartmentation in plants, we studied the interaction of the glycolytic enzyme fructose bisphosphate aldolase with actin in Arabidopsis thaliana. Homology modelling of a major cytosolic isozyme of aldolase, FBA8, suggested that the tetrameric holoenzyme has two actin binding sites and could therefore act as an actin-bundling protein, as was reported for animal aldolases. This was confirmed by in vitro measurements of an increase in viscosity of F-actin polymerized in the presence of recombinant FBA8. Simultaneously, interaction with F-actin caused noncompetitive inhibition of aldolase activity. We did not detect co-localization of an FBA8-RFP fusion protein, expressed in an fba8-knockout background, with the actin cytoskeleton using confocal laser-scanning microscopy. However, we did find evidence for a low level of interaction using FRET-FLIM analysis of FBA8-RFP co-expressed with the actinbinding protein GFP-Lifeact. Furthermore, knockout of FBA8 caused minor alterations of guard cell actin cytoskeleton morphology and resulted in a reduced rate of stomatal closure in response to decreased humidity. We conclude that cytosolic aldolase can be microcompartmented in vivo by interaction with the actin cytoskeleton and may subtly modulate guard cell behaviour as a result. [ABSTRACT FROM AUTHOR]

Esophageal cancer is a serious malignancy often treated with multimodal interventions and complex surgical resection. As treatment moves to centers of excellence with emphasis on enhanced recovery approaches, the role of the physiotherapist has expanded. The aim of this review is to discuss the rationale behind both the evolving prehabilitative role of the physiotherapist and more established postoperative interventions for patients with esophageal cancer. While a weak association between preoperative cardiopulmonary fitness and post-esophagectomy outcome is reported, cardiotoxicity during neoadjuvant chemotherapy and/or radiotherapy may heighten postoperative risk. Preliminary studies suggest that prehabilitative inspiratory muscle training may improve postoperative outcome. Weight and muscle loss are a recognized sequelae of esophageal cancer and the functional consequences of this should be assessed. Postoperative physiotherapy priorities include effective airway clearance and early mobilization. The benefits of respiratory physiotherapy post-esophagectomy are described by a small number of studies, however, practice increasingly recognizes the importance of early mobilization as a key component of postoperative recovery. The benefits of exercise training in patients with contraindications to mobilization remain to be explored. While there is a strong basis for tailored physiotherapy interventions in the management of patients with esophageal cancer, this review highlights the need for studies to inform prehabilitative and postoperative interventions. [ABSTRACT FROM AUTHOR]

Pathological and clinical studies implicate antibody-dependent mechanisms in the immunopathogenesis of multiple sclerosis. We tested this hypothesis directly by investigating the ability of patient-derived immunoglobulins to mediate demyelination and axonal injury in vitro. Using a myelinating culture system, we developed a sensitive and reproducible bioassay to detect and quantify these effects and applied this to investigate the pathogenic potential of immunoglobulin G preparations obtained from patients with multiple sclerosis (n = 37), other neurological diseases (n = 10) and healthy control donors (n = 13). This identified complement-dependent demyelinating immunoglobulin G responses in approximately 30% of patients with multiple sclerosis, which in two cases was accompanied by significant complement-dependent antibody mediated axonal loss. No pathogenic immunoglobulin G responses were detected in patients with other neurological disease or healthy controls, indicating that the presence of these demyelinating/axopathic autoantibodies is specific for a subset of patients with multiple sclerosis. Immunofluorescence microscopy revealed immunoglobulin G preparations with demyelinating activity contained antibodies that specifically decorated the surface of myelinating oligodendrocytes and their contiguous myelin sheaths. No other binding was observed indicating that the response is restricted to autoantigens expressed by terminally differentiated myelinating oligodendrocytes. In conclusion, our study identifies axopathic and/or demyelinating autoantibody responses in a subset of patients with multiple sclerosis. This observation underlines the mechanistic heterogeneity of multiple sclerosis and provides a rational explanation why some patients benefit from antibody depleting treatments. [ABSTRACT FROM AUTHOR]

Objective: To provide a targeted portrait of socioeconomic disparities in health care quality in four countries and how those disparities have changed over time.Design: Within each country, comparisons between the highest and lowest quintiles of socioeconomic status were made to determine if disparities exist and if any observed disparities have been decreasing over a 5-year period.Setting: Small geographic areas in Canada, England, New Zealand and the United States.Data Sources: Data were obtained by working with national health statistics agencies in each country.Results: There were socioeconomic disparities in health care quality and health status for most of the indicators studied in all four countries. The analysis included nine quality indicators in four countries, for a total of thirty-six observations. Twenty-six observations had a ratio of highest to lowest socioeconomic quintile of <0.95 or >1.05. These disparities generally persisted over time. The relative difference between the highest and lowest quintile decreased over time in eight of the twenty-one observations with time-series data available.Conclusion: The fact that disparities in a variety of indicators exist in four very different health systems underscores the importance of factors common to the four systems or factors outside the health system. Some successful strategies for reducing disparities could potentially be learned from the few examples of success in these countries. [ABSTRACT FROM AUTHOR]

Background Information on sickness absence (SA) duration in general practice is difficult to record. The duration of absence certified by general practitioners (GPs) can be viewed as a prognosis for return to work. The Health and Occupation Research network in General Practice (THOR-GP) collects SA information from GPs associated with cases of work-related ill-health. A sample of these cases is followed up 1 year retrospectively to gather information on the duration of absence. Aims To examine the extent of the underestimation of SA in routinely reported data and to investigate how well GPs predict patients' return to work. Methods THOR-GPs submit case and SA information using a web-based form. GPs who submitted selected cases were asked about the total number of days of SA and whether the patient had returned to work. Results THOR-GPs' routine SA data collection underestimated absence duration by 61%. According to the retrospective data, a much larger proportion of periods of absence due to work-related mental ill-health developed into long-term SA (60%) than episodes attributed to musculoskeletal disorders (32%). In over half the reported cases, the return to work was longer than the GP initially predicted. Conclusions THOR-GP prospectively reported SA data underestimated the total length of absence; however, these data can examine the episodic rates of absence within different groups. More accurate longitudinal data can be collected retrospectively. GPs' ability to predict the length of time a patient will be away from work is important to enable treatment and rehabilitation planning in order to decrease the likelihood of a patient falling into long-term SA. [ABSTRACT FROM AUTHOR]

Arabidopsis synaptotagmin 1 (SYT1) is localized on the endoplasmic reticulum-plasma membrane (ER-PM) contact sites in leaf and root cells. The ER-PM localization of Arabidopsis SYT1 resembles that of the extended synaptotagmins (E-SYTs) in animal cells. In mammals, E-SYTs have been shown to regulate calcium signaling, lipid transfer, and endocytosis. Arabidopsis SYT1 was reported to be essential for maintaining cell integrity and virus movement. This study provides detailed insight into the subcellular localization of SYT1 and VAP27-1, another ER-PM-tethering protein. SYT1 and VAP27-1 were shown to be localized on distinct ER-PM contact sites. The VAP27-1-enriched ER-PM contact sites (V-EPCSs) were always in contact with the SYT1-enriched ER-PM contact sites (S-EPCSs). The V-EPCSs still existed in the leaf epidermal cells of the SYT1 null mutant; however, they were less stable than those in the wild type. The polygonal networks of cortical ER disassembled and the mobility of VAP27-1 protein on the ER-PM contact sites increased in leaf cells of the SYT1 null mutant. These results suggest that SYT1 is responsible for stabilizing the ER network and V-EPCSs. [ABSTRACT FROM AUTHOR]

The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18 575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. [ABSTRACT FROM AUTHOR]

Background. Reduced participation in physical activity and increased time spent in sedentary behavior are associated with overweight, chronic disease, and disability. In order to optimize recommendations and interventions to increase physical activity and reduce sedentary behavior in children with cerebral palsy (CP), knowledge of their physical activity and sedentary behavior is needed. Objectives. The aim of this study was to describe light, moderate, and vigorous physical activity and sedentary behavior in preadolescent children with and without CP and compare physical activity and sedentary behavior between the 2 groups. Design. This was a cross-sectional study of 33 children, aged 6 to 10 years, with CP (Gross Motor Function Classification System [GMFCS] levels I-III) and 33 age- and sex-matched children with typical development. Methods. Physical activity was measured using the RT3 accelerometer over 7 days. Results. Children with CP spent more time in sedentary behavior and accumulated less total activity, moderate activity, vigorous activity, and sustained bouts of moderate-to-vigorous activity (MVPA). They also accumulated a fewer number of bouts of MVPA and vigorous activity, despite spending a similar amount of time in each bout. Limitations. The small number of children in GMFCS levels II and III did not allow for adjustment for GMFCS level when comparing physical activity between children with and without CP. Conclusions. Preadolescent children with CP spent less time in moderate and vigorous activity and more time in sedentary behavior than children with typical development. Children with CP also accumulated less continuous MVPA and vigorous activity as a result of achieving fewer sustained bouts of MVPA and vigorous activity throughout the day. [ABSTRACT FROM AUTHOR]

Background: The Health and Occupation Research (THOR) network in the UK and the Republic of Ireland (ROI) is an integrated system of surveillance schemes collecting work-related ill-health (WRIH) data since 1989. In addition to providing information about disease incidence, trends in incidence and the identification of new hazards, THOR also operates an ad hoc data enquiry service enabling interested parties to request information about cases of WRIH reported to THOR. Aims: To examine requests for information made to a network of surveillance schemes for WRIH in the UK. Methods: Analysis via SPSS of data requests received by THOR between 2002 and 2014. Results: A total of 631 requests were received by THOR between 2002 and 2014. Requests were predominantly submitted by participating THOR physicians (34%) and the main THOR funder--the UK Health & Safety Executive (HSE) (31%). The majority (67%) of requests were for information about work-related respiratory or skin disease with relatively few requests for other diagnoses, such as musculoskeletal or mental ill-health. Requests frequently related to a specific industry and/or occupation (42%) and/or a specific causal agent (58%). Conclusions: Data collected by occupational disease surveillance systems such as THOR are an extremely useful source of information, the use of which extends beyond informing government on disease incidence and trends in incidence. The data collected provide a framework that can assist a wide range of enquirers with clinical diagnoses, identification of suspected causative agents/exposures and to highlight growing risks in particular industrial and occupational sectors. [ABSTRACT FROM AUTHOR]

Background Accurate workplace injury data are useful in the prioritization of prevention strategies. In the UK, physicians report workplace ill-health data within The Health and Occupation Research (THOR) network, including injury case reports. Aims To compare workplace injury data reported by occupational physicians (OPs) and general practitioners (GPs) to THOR. Methods Injury cases reported by OPs and GPs, reported to THOR between 2006 and 2012 were analysed. Demographics, industrial groups, nature of injury, kind of accident and site of injury were compared. Data on sickness absence for workplace injuries reported by GPs were investigated. Results In total, 2017 workplace injury cases were reported by OPs and GPs. Males were more likely to sustain a workplace accident than females. Sprains and strains were reported most often, with the upper limbs being affected most frequently. Slips, trips and falls were identified as important causal factors by both OPs and GPs. Psychological injuries also featured in THOR reporting, with a higher proportion reported by OPs (21%) than by GPs (3%). The proportion of people classified as 'unfit' by GPs reduced following the introduction of the 'fit' note. Conclusions THOR reports returned by OPs and GPs provide a valuable source of information of workplace injury data, and complement other sources of information, such as the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations and the Labour Force Survey. [ABSTRACT FROM AUTHOR]

Two studies evaluated sorting and feeding zilpaterol hydrochloride (ZH) on feedlot performance and carcass characteristics in randomized block-designed finishing trials. In Exp. 1 (initial BW 342 ± 10 kg, n = 1,000), 5 treatments included an unsorted non-ZH fed negative control (-CON), an unsorted ZH fed positive control (+CON), and 3 treatments in which the heaviest 20% within the pen were sorted and marketed 28 d early and the remaining 80% were fed ZH. The 20% were identified at the beginning (EARLY), 100 d from slaughter (MIDDLE), or 50 d from slaughter (LATE). Because of sorting, the remaining steers in sorted treatments were fed 14 d longer than -CON and +CON. Average days on feed for control treatments were 165 and 173 d for the EARLY, MIDDLE, and LATE treatments. In Exp. 2 (initial BW 376 ± 29 kg, n = 1,400), 4 treatments included -CON; +CON; an early weight sort fed ZH (1-SORT) with the heaviest 20% identified at d 1 and sorted 50 d from harvest and marketed 14 d before -CON and +CON, with the remaining 80% of the pen fed 7 d longer than -CON and +CON; and a 4-way sort 50 d from harvest fed ZH (4-SORT) with steers sorted into HEAVY, MIDHEAVY, MID-LIGHT, and LIGHT groups marketed -14, 0, +7, and +28 d from -CON and +CON, respectively. Average days on feed for control treatments were 154 and 157 d for the 1-SORT and 159 d for 4-SORT. Steers were fed Zilmax at 8.3 mg/kg DM for 20 d followed by a 3 d withdrawal. In Exp. 1, steers fed +CON had 13 kg greater (P < 0.01) HCW than steers fed -CON. Steers sorted EARLY, MIDDLE, and LATE had 28, 25, and 24 kg heavier (P < 0.01) HCW than -CON steers, respectively. Carcass weight SD was greater (P = 0.01) for +CON than -CON but was not different (P = 0.17) between -CON and ZH sorted treatments. Percentage of overweight carcasses (454 kg) was greater (P ≤ 0.05) in sorted treatments than in -CON. In Exp. 2, HCW for +CON was 15 kg heavier (P < 0.01) than that for -CON, and HCW for 4-SORT was greater (P < 0.02) than that for +CON. Carcass weight SD was not different (P > 0.10) between +CON and -CON, whereas carcass weight SD of 4-SORT was reduced (P < 0.01) compared with that of -CON and +CON. Steers fed ZH had a greater percentage of carcasses over 454 kg than steers fed -CON (P < 0.01). Although not statistically different (P = 0.27), the percentage of carcasses over 454 kg was reduced by 28% for 4-SORT compared with +CON. Feeding ZH increases carcass weight, but sorting reduces variation, allowing further increases in carcass weight while minimizing overweight carcasses. [ABSTRACT FROM AUTHOR]

The white shark, Carcharodon carcharias, is both one of the largest apex predators in the world and among the most heavily protected marine fish. Population genetic diversity is in part shaped by recent demographic history and can thus provide information complementary to more traditional population assessments, which are difficult to obtain for white sharks and have at times been controversial. Here, we use the mitochondrial control region and 14 nuclear-encoded microsatellite loci to assess white shark genetic diversity in 2 regions: the Northwest Atlantic (NWA, N = 35) and southern Africa (SA, N = 131). We find that these 2 regions harbor genetically distinct white shark populations (ΦST = 0.10, P < 0.00001; microsatellite FST = 0.1057, P < 0.021). M-ratios were low and indicative of a genetic bottleneck in the NWA (M-ratio = 0.71, P < 0.004) but not SA (M-ratio = 0.85, P = 0.39). This is consistent with other evidence showing a steep population decline occurring in the mid to late 20th century in the NWA, whereas the SA population appears to have been relatively stable. Estimates of effective population size ranged from 22.6 to 66.3 (NWA) and 188 to 1998.3 (SA) and evidence of inbreeding was found (primarily in NWA). Overall, our findings indicate that white population dynamics within NWA and SA are determined more by intrinsic reproduction than immigration and there is genetic evidence of a population decline in the NWA, further justifying the strong domestic protective measures that have been taken for this species in this region. Our study also highlights how assessment of genetic diversity can complement other sources of information to better understand the status of threatened marine fish populations. [ABSTRACT FROM AUTHOR]

Background: In 2010, the fit note replaced the sick note to help focus on what people are capable of doing, rather than signing patients 'off sick'. Aims: To compare proportions of work-related ill-health issued with sickness certification pre- and post-fit note introduction and assess sickness absence trends. Methods: General practitioners (GPs) report data on work-related ill-health and sickness absence via The Health and Occupation Research network in General Practice. The proportion of cases issued with sickness certification 4 years before and 3 years after the fit note introduction were compared. Changes in certification incidence rate ratios were measured over time. Results: Participating GPs reported 5517 cases of work-related ill-health. Pre-fit note introduction 50% of cases were certified sick. There was no change in the proportion of cases certified sick in the first year post-fit note, despite 13% of cases classified as 'maybe fit'. However, in the second year, the proportion of cases certified sick had reduced significantly (41%) and a larger proportion (19%) was advised on workplace adjustments. In the third year post-introduction, there was a slight rise in the proportion of cases certified sick; therefore, although there was a fall of 2% per annum in certification rates, this was not significant. Conclusions: In the first year post-fit note introduction, modifications to work were recommended for people who would previously have been declared fit. Trends analyses showed a slight decrease in the certification rate, possibly indicating GPs will become more practised in advising on workplace adjustments. [ABSTRACT FROM AUTHOR]

Plant-parasitic cyst nematodes synthesize and secrete effector proteins that are essential for parasitism. One such protein is the 10A07 effector from the sugar beet cyst nematode, Heterodera schachtii , which is exclusively expressed in the nematode dorsal gland cell during all nematode parasitic stages. Overexpression of H. schachtii 10A07 in Arabidopsis thaliana produced a hypersusceptible phenotype in response to H. schachtii infection along with developmental changes reminiscent of auxin effects. The 10A07 protein physically associates with a plant kinase and the IAA16 transcription factor in the cytoplasm and nucleus, respectively. The interacting plant kinase (IPK) phosphorylates 10A07 at Ser-144 and Ser-231 and mediates its trafficking from the cytoplasm to the nucleus. Translocation to the nucleus is phosphorylation dependent since substitution of Ser-144 and Ser-231 by alanine resulted in exclusive cytoplasmic accumulation of 10A07. IPK and IAA16 are highly upregulated in the nematode-induced syncytium (feeding cells), and deliberate manipulations of their expression significantly alter plant susceptibility to H. schachtii in an additive fashion. An inactive variant of IPK functioned antagonistically to the wild-type IPK and caused a dominant-negative phenotype of reduced plant susceptibility. Thus, exploitation of host processes to the advantage of the parasites is one mechanism by which cyst nematodes promote parasitism of host plants. [ABSTRACT FROM AUTHOR]

Aging is associated with alterations in glucose metabolism and sarcopenia that jointly contribute to a higher risk of developing type 2 diabetes. Because aging is considered as a state of low-grade inflammation, in this study we examined whether older, healthy (lean, community-dwelling) participants have altered signaling flux through toll-like receptor 4 (TLR4), a key mediator of innate and adaptive immune responses. We also examined whether a 4-month aerobic exercise program would have an anti-inflammatory effect by reducing TLR4 expression and signaling. At baseline, muscle TLR4, nuclear factor κB p50 and nuclear factor κB p65 protein content, and c-Jun N-terminal kinase phosphorylation were significantly elevated in older versus young participants. The plasma concentration of the TLR4 agonist lipopolysaccharide and its binding protein also were significantly elevated in older participants, indicative of metabolic endotoxemia, which is a recently described phenomenon of increased plasma endotoxin level in metabolic disease. These alterations in older participants were accompanied by decreased insulin sensitivity, quadriceps muscle volume, and muscle strength. The exercise training program increased insulin sensitivity, without affecting quadriceps muscle volume or strength. Muscle TLR4, nuclear factor κB, and c-Jun N-terminal kinase, and plasma lipopolysaccharide and lipopolysaccharide binding protein were not changed by exercise. In conclusion, insulin resistance and sarcopenia of aging are associated with increased TLR4 expression/signaling, which may be secondary to metabolic endotoxemia. [ABSTRACT FROM PUBLISHER]

Analyzes exons commonly deleted in deletion-type Duchenne muscular dystrophy (DMD), using duplex polymerase-chain-reaction protocols on single lymphocytes and blastomeres from embryos. Amplification results from single lymphocytes; Signals for DMD exons produced by embryos; Suitability of the method for preimplantation genetic diagnosis.

The microtubule plus-end tracking proteins (+TIPs) END BINDING1b (EB1b) and SPIRAL1 (SPR1) are required for normal cell expansion and organ growth. EB proteins are viewed as central regulators of +TIPs and cell polarity in animals; SPR1 homologs are specific to plants. To explore if EB1b and SPR1 fundamentally function together, we combined genetic, biochemical, and cell imaging approaches in Arabidopsis thaliana. We found that eb1b-2 spr1-6 double mutant roots exhibit substantially more severe polar expansion defects than either single mutant, undergoing right-looping growth and severe axial twisting instead of waving on tilted hard-agar surfaces. Protein interaction assays revealed that EB1b and SPR1 bind each other and tubulin heterodimers, which is suggestive of a microtubule loading mechanism. EB1b and SPR1 show antagonistic association with microtubules in vitro. Surprisingly, our combined analyses revealed that SPR1 can load onto microtubules and function independently of EB1 proteins, setting SPR1 apart from most studied +TIPs in animals and fungi. Moreover, we found that the severity of defects in microtubule dynamics in spr1 eb1b mutant hypocotyl cells correlated well with the severity of growth defects. These data indicate that SPR1 and EB1b have complex interactions as they load onto microtubule plus ends and direct polar cell expansion and organ growth in response to directional cues. [ABSTRACT FROM AUTHOR]