Insights for disease modeling from single-cell transcriptomics of iPSC-derived Ngn2-induced neurons and astrocytes across differentiation time and co-culture.

BACKGROUND: Trans-differentiation of human-induced pluripotent stem cells into neurons via Ngn2-induction (hiPSC-N) has become an efficient system to quickly generate neurons a likely significant advance for disease modeling and in vitro assay development. Recent single-cell interrogation of Ngn2-induced neurons, however, has revealed some similarities to unexpected neuronal lineages. Similarly, a straightforward method to generate hiPSC-derived astrocytes (hiPSC-A) for the study of neuropsychiatric disorders has also been described. RESULTS: Here, we examine the homogeneity and similarity of hiPSC-N and hiPSC-A to their in vivo counterparts, the impact of different lengths of time post Ngn2 induction on hiPSC-N (15 or 21 days), and the impact of hiPSC-N/hiPSC-A co-culture. Leveraging the wealth of existing public single-cell RNA-seq (scRNA-seq) data in Ngn2-induced neurons and in vivo data from the developing brain, we provide perspectives on the lineage origins and maturation of hiPSC-N and hiPSC-A. While induction protocols in different labs produce consistent cell type profiles, both hiPSC-N and hiPSC-A show significant heterogeneity and similarity to multiple in vivo cell fates, and both more precisely approximate their in vivo counterparts when co-cultured. Gene expression data from the hiPSC-N show enrichment of genes linked to schizophrenia (SZ) and autism spectrum disorders (ASD) as has been previously shown for neural stem cells and neurons. These overrepresentations of disease genes are strongest in our system at early times (day 15) in Ngn2-induction/maturation of neurons, when we also observe the greatest similarity to early in vivo excitatory neurons. We have assembled this new scRNA-seq data along with the public data explored here as an integrated biologist-friendly web-resource for researchers seeking to understand this system more deeply: https://nemoanalytics.org/p?l=DasEtAlNGN2&g=NES . CONCLUSIONS: While overall we support the use of the investigated cellular models for the study of neuropsychiatric disease, we also identify important limitations. We hope that this work will contribute to understanding and optimizing cellular modeling for complex brain disorders.

Sensor-Based Quantification of Peanut Disease Defoliation Using an Unmanned Aircraft System and Multispectral Imagery.

Early leaf spot (Passalora arachidicola) and late leaf spot (Nothopassalora personata) are two of the most economically important foliar fungal diseases of peanut, often requiring seven to eight fungicide applications to protect against defoliation and yield loss. Rust (Puccinia arachidis) may also cause significant defoliation depending on season and location. Sensor technologies are increasingly being utilized to objectively monitor plant disease epidemics for research and supporting integrated management decisions. This study aimed to develop an algorithm to quantify peanut disease defoliation using multispectral imagery captured by an unmanned aircraft system. The algorithm combined the Green Normalized Difference Vegetation Index and the Modified Soil-Adjusted Vegetation Index and included calibration to site-specific peak canopy growth. Beta regression was used to train a model for percent net defoliation with observed visual estimations of the variety 'GA-06G' (0 to 95%) as the target and imagery as the predictor (train: pseudo-R2 = 0.71, test k-fold cross-validation: R2 = 0.84 and RMSE = 4.0%). The model performed well on new data from two field trials not included in model training that compared 25 (R2 = 0.79, RMSE = 3.7%) and seven (R2 = 0.87, RMSE = 9.4%) fungicide programs. This objective method of assessing mid-to-late season disease severity can be used to assist growers with harvest decisions and researchers with reproducible assessment of field experiments. This model will be integrated into future work with proximal ground sensors for pathogen identification and early season disease detection.[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

RENEB Inter-Laboratory Comparison 2021: The Gene Expression Assay.

Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios.

Interprofessional communication in the hospital setting : a systematic review of the qualitative literature.

Communication plays a key role in the provision of safe patient care, and miscommunication in healthcare can lead to avoidable patient harm or mortality. Interprofessional communication (IPCom) can be challenging due to differences in training, education and roles between healthcare professions. The aim of this systematic review was to synthesize the qualitative evidence regarding healthcare providers' perceptions of interprofessional communication in the hospital setting. Four databases (PubMed, CINAHL, Web of Science, and Embase) were searched for studies that met the inclusion criteria. Eighteen studies were identified as suitable for inclusion in the review and were examined using thematic synthesis. Thematic synthesis led to the development of five descriptive themes: 1) 'Hierarchy", 2) "Interprofessional Ethos," 3) "Healthcare Environment," 4) "Personal Factors" and 5) "Methods of Communication," and two overarching analytical themes: "Barriers to Communication" and "Facilitators to Communication." Personal factors, such as strong interprofessional relationships, were found to be important facilitators to IPCom, while organizational factors, such as challenging and hierarchical working environments, were found to pose barriers to IPCom.

Inter-laboratory comparison of gene expression biodosimetry for protracted radiation exposures as part of the RENEB and EURADOS WG10 2019 exercise.

Large-scale radiation emergency scenarios involving protracted low dose rate radiation exposure (e.g. a hidden radioactive source in a train) necessitate the development of high throughput methods for providing rapid individual dose estimates. During the RENEB (Running the European Network of Biodosimetry) 2019 exercise, four EDTA-blood samples were exposed to an Iridium-192 source (1.36 TBq, Tech-Ops 880 Sentinal) at varying distances and geometries. This resulted in protracted doses ranging between 0.2 and 2.4 Gy using dose rates of 1.5-40 mGy/min and exposure times of 1 or 2.5 h. Blood samples were exposed in thermo bottles that maintained temperatures between 39 and 27.7 °C. After exposure, EDTA-blood samples were transferred into PAXGene tubes to preserve RNA. RNA was isolated in one laboratory and aliquots of four blinded RNA were sent to another five teams for dose estimation based on gene expression changes. Using an X-ray machine, samples for two calibration curves (first: constant dose rate of 8.3 mGy/min and 0.5-8 h varying exposure times; second: varying dose rates of 0.5-8.3 mGy/min and 4 h exposure time) were generated for distribution. Assays were run in each laboratory according to locally established protocols using either a microarray platform (one team) or quantitative real-time PCR (qRT-PCR, five teams). The qRT-PCR measurements were highly reproducible with coefficient of variation below 15% in ≥ 75% of measurements resulting in reported dose estimates ranging between 0 and 0.5 Gy in all samples and in all laboratories. Up to twofold reductions in RNA copy numbers per degree Celsius relative to 37 °C were observed. However, when irradiating independent samples equivalent to the blinded samples but increasing the combined exposure and incubation time to 4 h at 37 °C, expected gene expression changes corresponding to the absorbed doses were observed. Clearly, time and an optimal temperature of 37 °C must be allowed for the biological response to manifest as gene expression changes prior to running the gene expression assay. In conclusion, dose reconstructions based on gene expression measurements are highly reproducible across different techniques, protocols and laboratories. Even a radiation dose of 0.25 Gy protracted over 4 h (1 mGy/min) can be identified. These results demonstrate the importance of the incubation conditions and time span between radiation exposure and measurements of gene expression changes when using this method in a field exercise or real emergency situation.

Where next for youth mental health services in Ireland?

To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.

Validating Baboon Ex Vivo and In Vivo Radiation-Related Gene Expression with Corresponding Human Data.

The research for high-throughput diagnostic tests for victims of radio/nuclear incidents remains ongoing. In this context, we have previously identified candidate genes that predict risk of late-occurring hematologic acute radiation syndrome (HARS) in a baboon model. The goal of the current study was to validate these genes after radiation exposure in humans. We also examined ex vivo relative to in vivo measurements in both species and describe dose-response relationships. Eighteen baboons were irradiated in vivo to simulate different patterns of partial- or total-body irradiation (TBI), corresponding to an equivalent dose of 2.5 or 5 Sv. Human in vivo blood samples were obtained from patients exposed to different dose ranges: diagnostic computerized tomography (CT; 0.004-0.018 Sv); radiotherapy for prostate cancer (0.25-0.3 Sv); and TBI of leukemia patients (2 × 1.5 or 2 × 2 Sv, five patients each). Peripheral whole blood of another five baboons and human samples from five healthy donors were cultivated ex vivo and irradiated with 0-4 Sv. RNA was isolated pairwise before and 24 h after irradiation and converted into cDNA. Gene expression of six promising candidate genes found previously by us in a baboon model ( WNT3, POU2AF1, CCR7, ARG2, CD177, WLS), as well as three genes commonly used in ex vivo whole blood experiments ( FDXR, PCNA, DDB2) was measured using qRT-PCR. We confirmed the six baboon candidate genes in leukemia patients. However, expression for the candidate gene FDXR showed an inverse relationship, as it was downregulated in baboons and upregulated in human samples. Comparisons among the in vivo and ex vivo experiments revealed the same pattern in both species and indicated peripheral blood cells to represent the radiation-responsive targets causing WNT3 and POU2AF1 gene expression changes. CCR7, ARG2, CD177 and WLS appeared to be altered due to radiation-responsive targets other than the whole blood cells. Linear dose-response relationships of FDXR, WNT3 and POU2AF1 using human ex vivo samples corresponded with human in vivo samples, suggesting that ex vivo models for in vivo dose estimates can be used over a wide dose range (0.001-5 Sv for POU2AF1). In summary, we validated six baboon candidate genes in humans, but the FDXR measurements underscored the importance of independent assessments even when candidates from animal models have striking gene sequence homology to humans. Since whole blood cells represented the same radiation-responsive targets for FDXR, WNT3 and POU2AF1 gene expression changes, ex vivo cell culture models can be utilized for in vivo dose estimates over a dose range covering up to 3.5 log scales. These findings might be a step forward in the development of a gene expression-based high-throughput diagnostic test for populations involved in large-scale radio/nuclear incidents.

Routine use of PICO dressings may reduce overall groin wound complication rates following peripheral vascular surgery.

BACKGROUND: Approximately 19% of morbidity in peripheral vascular surgery is attributable to wound complications, which can result in delayed healing, and also arterial or graft infection leading to limb loss and even mortality in extreme cases. AIM: To determine whether groin wound complications were reduced following the routine introduction of PICO negative pressure wound therapy dressings in patients who underwent peripheral vascular surgery. METHODS: Patients who underwent peripheral vascular surgery from 2011 to 2016 were identified and divided into PICO and non-PICO groups. Patient, procedure and wound characteristics were tabulated and analysed. Patients were followed-up for at least six weeks postoperatively. Wound complication rates, infection confirmed by microbiology, and requirement for re-admission due to wound complications were noted. Basic cost analysis was performed. FINDINGS: In total, 151 patients were analysed (N = 73 PICO, N = 78 non-PICO). No difference in age (P = 0.862), body mass index (P = 0.673), diabetes (P = 0.339), pre-operative albumin (P = 0.196), use of drain (P = 0.343) and history of meticillin-resistant Staphylococcus aureus (P = 0.281) was observed between groups. The PICO group contained more smokers than the non-PICO group (45% vs 29%, P = 0.034). Wound complications were seen in 8% (N = 6) of the PICO group and 19% (N = 15) of the non-PICO group (P = 0.042). No significant difference in infection was found between the two groups (3% vs 6%, P = 0.249), but fewer seromas were observed when PICO dressings were used (1.4% vs 7.7%, P = 0.069). Haematoma (2.7% vs 3.8%, P = 0.531) and dehiscence rates (1.4% vs 1.3%, P = 0.735) were similar between the two groups. CONCLUSIONS: Routine use of PICO dressings is associated with a reduction in wound complication rates following peripheral vascular surgery, and is cost-effective.

Description and outcome evaluation of Jigsaw: an emergent Irish mental health early intervention programme for young people.

OBJECTIVES: Jigsaw is an early intervention mental health service developed by Headstrong which provides support to young people, aged 12-25 years, in 10 communities across Ireland. This study aimed to profile young people who availed of Jigsaw, in one calendar year, and to provide evidence that Jigsaw's model facilitates the reduction of psychological distress. METHODS: Participants were 2420 young people who received support, directly or indirectly, from Jigsaw. Demographic details, including age, gender, presenting issues and referral pathways, captured on the Jigsaw Data System were described and psychological distress was assessed using the Clinical Outcomes in Routine Evaluation (CORE) questionnaires. RESULTS: A gender balance was almost observed and the majority of participants were between 15 and 17 years old. The most common presenting issue was anxiety and the most common referral sources were self, parent, general practitioner, school and Adult Mental Health Services (AMHS). Participants reported high levels of psychological distress pre-intervention and levels were significantly lower post intervention. CONCLUSIONS: Although a lack of control group limits interpretation of the study findings, this study provides emerging evidence that Jigsaw is an accessible and effective service which plays a key role in the continuum of mental health care for young people in Ireland.

Comparison of the prognostic accuracy of scoring systems, cardiopulmonary exercise testing, and plasma biomarkers: a single-centre observational pilot study.

BACKGROUND: Current approaches to risk assessment before major surgery have important limitations. The aim of this pilot study was to compare predictive accuracy of preoperative scoring systems, plasma biomarkers, and cardiopulmonary exercise testing (CPET) for complications after major non-cardiac surgery. METHODS: Single-centre, observational study of patients aged ≥40 yr undergoing major elective non-cardiac surgery. Before surgery, risk scores were calculated and blood samples collected for measurement of plasma biomarkers. Patients underwent CPET for measurement of anaerobic threshold (AT) and peak oxygen consumption ( peak). After surgery, patients were followed for 28 days to evaluate complications and major adverse cardiac events (MACE). Data are presented as area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals. RESULTS: A total of 100 patients were recruited between April 2009 and October 2010; 17 of whom did not proceed to surgery. CPET variables suggested good predictive accuracy for MACE [AT: AUROC 0.83 (0.69-0.96); peak AUROC 0.81 (0.69-0.96)] and poor predictive accuracy for all complications [AT: AUROC 0.64 (0.52-0.77); peak AUROC 0.64 (0.52-0.77)]. There was a trend towards predictive accuracy of the plasma biomarkers B-type natriuretic peptide and estimated glomerular filtration rate (calculated from serum creatinine) for MACE but not all complications. C-reactive protein, ASA score, and revised cardiac risk index had little or no predictive value. CONCLUSIONS: These pilot data suggest that CPET and plasma biomarkers may improve risk assessment before surgery. Only large clinical studies can confirm this observation and define the optimal use of these tests in clinical practice.

First observation of African tigerfish Hydrocynus vittatus predating on barn swallows Hirundo rustica in flight.

A population of African tigerfish Hydrocynus vittatus from the Schroda Dam, actively prey on barn swallows Hirundo rustica in flight. This behaviour was discovered during a radio telemetry study and documented using a motion picture video camera. These results show that an avivorous diet is a part of the feeding biology of H. vittatus, and may occur in other populations.

Responsivity to criminogenic need in forensic intellectual disability services.

BACKGROUND: Research has shown for some time that addressing criminogenic need is one of the crucial aspects of reducing reoffending in all types of offenders. Criminogenic need such as anger or inappropriate sexual interest is considered to be crucial in the commission of the offence. The aim of the present study is to investigate the extent to which forensic services address the needs of those accepted into services. METHOD: This study reviews the treatment for 197 offenders with intellectual disability accepted into a range of services. Participants' case files were examined to ascertain the extent to which need was addressed through recognised therapies. A standard pro forma was used on which we had established good reliability across four research assistants. RESULTS: The most frequently referred problems were violence and sexual offending. Specialist forensic intellectual disability community services were significantly more likely to provide treatment specifically designed to address index behaviours when compared to generic community services and secure services. CONCLUSIONS: Various possible explanations of these findings are explored including staffing levels, diagnosed mental illness, expertise of staff and clarity of purpose in services.

Hybrid repair of a symptomatic thoracic intra-mural haematoma.

INTRODUCTION: The repair of thoracic aortic pathology by open techniques is associated with high morbidity and mortality. METHODS: We describe the first case of hybrid thoracic aortic repair performed in Ireland for a symptomatic thoracic intramural haematoma. CONCLUSION: Hybrid repair with extra-anatomical aortic visceral revascularisation and subsequent thoracic endograft exclusion offers an attractive alternative method of repair for thoracic aortic pathology.

Reproductive seasonality and the effect of the GnRH agonist deslorelin as a contraceptive in captive male Black Flying-foxes (Pteropus alecto).

Effective contraception would enhance genetic management of captive Pteropus species, which typically breed well in captivity. Male reproductive seasonality was monitored (15-mo interval) in captive P. alecto (6 controls and 5 treated with 4.7 mg deslorelin). In untreated males, there were seasonal changes in testicular volume, body weight and testosterone secretion; testicular volume and body weight peaked in February and March, respectively, whereas testosterone concentration remained >5 ng/ml before rising (P < 0.001) to 24.9 ± 3.6 ng/ml (mean ± SEM) in April. However, there was no corresponding change in sperm quality, and seminal vesicle gland (SVG) secretions remained present in ejaculates. In treated males, testosterone concentration had an initial 'flare' response (mean ± SEM peak: 19.95 ± 3.27 ng/ml) before declining (P < 0.001) by 32 d to basal levels, where it remained. In these males, there was reduced sperm motility after 1 mo (P < 0.001) and the absence of SVG secretions after 4 mo. However, aspermic ejaculates were first recorded 5 mo post-treatment. At 10 mo after treatment, spermatogenesis was still disrupted, when membrane-intact, but non-motile sperm were present in two individuals. Motile sperm were first recovered from one of these males 13 mo after deslorelin treatment. We concluded that captive P. alecto males: (a) had seasonal reproductive changes in testicular volume, body weight and testosterone secretion; (b) produced motile, membrane-intact sperm and SVG secretions throughout the year; and (c) had a rapid decline in testosterone concentration and consequent suppression of testicular function for at least 5 mo following deslorelin administration.

An analysis of vascular surgery in elderly patients to determine whether age affects treatment strategy.

OBJECTIVES: The incidence of arterial disease increases with age. Increasing life expectancy in the western world will intensify demands on vascular surgeons with regard to increasing caseload, expanding patient selection criteria, and more complex and minimally-invasive treatment options. We analysed our arterial cases over the past 31 years (n = 6,144) and compared our methods of intervention and complication rates in the elderly population (>75) with the younger cohort, in order to determine whether age should influence our management strategies. METHODS: Data were collected prospectively on all arterial cases from 1978 to 2009. Methods of intervention and corresponding complication rates in the over and under 75-year-old cohorts were analyzed utilizing Fisher's exact test to calculate two-sided p values, relative risks and 95% confidence intervals. RESULTS: Endovascular management has evolved to become the first line approach for all arterial cases (except carotid disease). Age was a significant risk factor for death and MI for the open procedures of AAA repair (p = 0.049 and p = 0.007, respectively), aorto-bifemoral reconstruction (p < 0.0001 and p = 0.006) and lower limb bypass (p = 0.01 and p < 0.001). For endovascular procedures, age did not impact on MI rate for EVAR (p = 0.78) or death rates for EVAR (p = 0.46), iliac angioplasty (p = 0.62) or lower limb angioplasty (p = 0.29). CONCLUSION: A paradigm shift has occurred towards endovascular management of aortic, iliac and femoral arterial disease. Whilst patient age >75 significantly impacts on complication rates from index open vascular procedures, age does not impact upon complication rates of corresponding endovascular procedures. We, therefore, recommend an endovascular approach be adopted as first line for all patients, regardless of patient age.

Splenic mass with remote trauma history: a management dilemma.

BACKGROUND: Delayed presentation of splenic trauma is a well described entity. METHOD: We report two patients who presented with splenic abnormality found incidentally on imaging for other medical problems. A remote history of splenic trauma was elicited during clinical evaluation; 18 months in one patient and 11 years in the second patient. Both patients underwent surgical exploration. CONCLUSIONS: Radiological investigations could not reassure us that the splenic abnormalities were benign, and their management was the subject of some debate.

ACE up the sleeve - are vascular patients medically optimized?

OBJECTIVE: To examine the current medical management of arteriopathic patients attending a vascular surgical service at a university teaching hospital over a 6-month period. The prescribing of antiplatelets, statins, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers and beta-blockers was specifically examined. Vascular patients are often under the care of multiple specialties, and therefore the influence of different medical specialties on the patients' medical management was also examined. DESIGN: Between January and June 2009, data were recorded on sequential patients with arterial disease attending the vascular surgical service. Patients' demographics, type of arterial disease, medical consultations within the previous 12 months, and current medications were recorded. RESULTS: The study included 180 patients with a mean age of 69 years (39-88 years). All but 4% were taking an antiplatelet or anticoagulant, predominantly aspirin. There were 86% taking a statin, 44% taking a beta-blocker, and 51% taking an ACE inhibitor. Suboptimal prescription of ACE inhibitors and beta-blockers was evident regardless of the type of medical consultations in the previous year. No specialty group differed significantly from vascular surgeons in their prescribing pattern. CONCLUSIONS: While almost all arteriopaths receive some form of antiplatelet and statin in line with clinical evidence, ACE inhibitors and beta-blockers appear to be under-prescribed in this arteriopathic population. We conclude that opportunity exists for vascular surgeons to embrace recent guidelines and lead the way in both surgical and medical optimization of arteriopathic patients through improving links with primary care physicians or taking greater responsibility themselves for the medical as well as the surgical care of their arteriopathic patients.

Epidemiology of Soybean Rust in Soybean Sentinel Plots in Florida.

Since its discovery in the southeastern United States in 2004, soybean rust (SBR) has been variable from year to year. Caused by Phakopsora pachyrhizi, SBR epidemics in Florida are important to understand, as they may serve as an inoculum source for other areas of the country. This study examined the first disease detection date, incidence, and severity of SBR in relation to environmental data, growth stage, and maturity group (MG3, MG5, MG7) in soybean sentinel plots (225 m2) across north Florida from 2005 through 2008. The majority (91%) of the initial infections were observed in MG5 and MG7 soybeans, with plots not becoming infected until growth stage R4 or later. Precipitation was the principle factor affecting disease progress, where disease increased rapidly after rain events and was suppressed during dry periods. On average, plots became infected 30 days earlier in 2008 than 2005. In 2008, there was a significant increase in disease incidence and severity associated with the occurrence of Tropical Storm Fay, which deposited up to 380 mm of rainfall in north Florida. The results of this study indicate that climatic and environmental factors are important in determining the development of SBR in north Florida.

T-box 2 represses NDRG1 through an EGR1-dependent mechanism to drive the proliferation of breast cancer cells.

T-box 2 (TBX2) is a transcription factor involved in mammary development and is known to be overexpressed in a subset of aggressive breast cancers. TBX2 has previously been shown to repress growth control genes such as p14(ARF) and p21(WAF1/cip1). In this study we show that TBX2 drives proliferation in breast cancer cells and this is abrogated after TBX2 small interfering RNA (siRNA) knockdown or after the expression of a dominant-negative TBX2 protein. Using microarray analysis we identified a large cohort of novel TBX2-repressed target genes including the breast tumour suppressor NDRG1 (N-myc downregulated gene 1). We show that TBX2 targets NDRG1 through a previously undescribed mechanism involving the recruitment of early growth response 1 (EGR1). We show EGR1 is required for the ability of TBX2 to repress NDRG1 and drive cell proliferation. We show that TBX2 interacts with EGR1 and that TBX2 requires EGR1 to target the NDRG1 proximal promoter. Abrogation of either TBX2 or EGR1 expression is accompanied by the upregulation of cell senescence and apoptotic markers. NDRG1 can recapitulate these effects when transfected into TBX2-expressing cells. Together, these data identify a novel mechanism for TBX2-driven oncogenesis and highlight the importance of NDRG1 as a growth control gene in breast tissue.