Quantitative trait loci mapping of polyphenol metabolites from a 'Latham' x 'Glen Moy' red raspberry (Rubus idaeus L) cross.

OBJECTIVE: The objective of this study was to investigate the genetic control of polyphenol accumulation in red raspberry (Rubus idaeus L). METHODS: The levels of total anthocyanins and 37 individual polyphenol metabolites were measured over three years in a raspberry biparental mapping population. Quantitative trait loci (QTLs) for these traits were mapped onto a high-density SNP linkage map. RESULTS: At least one QTL was detected for each trait, with good consistency among the years. On four linkage groups (LG), there were major QTLs affecting several metabolites. On LG1, a QTL had large effects on anthocyanins and flavonols containing a rutinoside or rhamnose group. On LG4, a QTL had large effects on several flavonols and on LG5 and LG6 QTLs had large effects on ellagic acid derivatives. Smaller QTLs were found on LG2 and LG3. CONCLUSION: The identification of robust QTLs for key polyphenols in raspberry provides great potential for marker-assisted breeding for improved levels of potentially health beneficial components.

A retrospective review of pregnancies on biologics for the treatment of dermatological conditions.

Psoriasis often first presents in young adulthood, with the average age of diagnosis in women being 28 years, thus in the prime reproductive years. In addition, approximately 50% of pregnancies worldwide are unplanned. Although biologic therapies have revolutionized the treatment of moderate-to-severe psoriasis, there are no controlled studies of biologics in pregnant women. The increasing use of these agents in women of childbearing age highlights the need to further assess their safety during pregnancy. Postmarketing experience regarding the safety of these drugs is accumulating and being published, with largely reassuring results. We present our real-world experience of 17 pregnancies occurring in women on treatment with biologic agents for dermatological conditions to further add to the body of knowledge.

The causes of nail apparatus pigmentation presenting to a melanoma screening clinic a prospective study.

BACKGROUND: Advanced stage primary cutaneous malignant melanoma (PCMM) has a high mortality. PCMM may affect any area of the skin, including the nail apparatus (malignant melanoma or subungual melanoma). Although nail apparatus malignant melanoma (NAMM) is rare, delayed diagnosis carries a poor prognosis. AIM: The primary aim was to study the range of nail presentations and identify key patterns to aid in differential diagnosis. A secondary aim was to quantify the number of patients requiring surgery, indications for biopsy, and the incidence and characteristics of NAMM. METHODS: This was a prospective study of all referrals with nail apparatus pigmentation to a weekly dedicated melanoma screening clinic over a 6-month period. RESULTS: In total, 2246 patients were included. Of the 38 patients referred with nail pigmentation, 1 (2.6%) was diagnosed with NAMM and involved a fungating amelanotic lesion of the right hallux. The remaining patients were diagnosed with subungual haematoma (20/38; 52.6%), viral wart (2/38; 5.4%), acral fibrokeratoma (1/38; 2.6%), myxoid cyst (3/38; 7.9%), fungal nail infection (4/38; 10.5%), Pseudomonas nail infection (1/38; 2.6%), benign linear pigmentation (2/38, 5.3%), Bowen disease (1/38, 2.6%), psoriatic nail changes (2/38; 5.3%) and matrix malalignment (1/38; 2.6%). Of the eight patients (21.1%) who required surgery, five had a biopsy taken and three underwent surgery. Only 14 cases were followed up by Dermatology. NAMM accounted for 0.7% of all melanomas diagnosed. CONCLUSION: We illustrate the wide range of diagnoses for pigmented nail presentations and highlight the late presentation of advanced disease in a patient presenting with NAMM.

Plant exudates may stabilize or weaken soil depending on species, origin and time.

We hypothesized that plant exudates could either gel or disperse soil depending on their chemical characteristics. Barley (Hordeum vulgare L. cv. Optic) and maize (Zea mays L. cv. Freya) root exudates were collected using an aerated hydroponic method and compared with chia (Salvia hispanica L.) seed exudate, a commonly used root exudate analogue. Sandy loam soil was passed through a 500-µm mesh and treated with each exudate at a concentration of 4.6 mg exudate g-1 dry soil. Two sets of soil samples were prepared. One set of treated soil samples was maintained at 4°C to suppress microbial processes. To characterize the effect of decomposition, the second set of samples was incubated at 16°C for 2 weeks at -30 kPa matric potential. Gas chromatography-mass spectrometry (GC-MS) analysis of the exudates showed that barley had the largest organic acid content and chia the largest content of sugars (polysaccharide-derived or free), and maize was in between barley and chia. Yield stress of amended soil samples was measured by an oscillatory strain sweep test with a cone plate rheometer. When microbial decomposition was suppressed at 4°C, yield stress increased 20-fold for chia seed exudate and twofold for maize root exudate compared with the control, whereas for barley root exudate decreased to half. The yield stress after 2 weeks of incubation compared with soil with suppressed microbial decomposition increased by 85% for barley root exudate, but for chia and maize it decreased by 87 and 54%, respectively. Barley root exudation might therefore disperse soil and this could facilitate nutrient release. The maize root and chia seed exudates gelled soil, which could create a more stable soil structure around roots or seeds. HIGHLIGHTS: Rheological measurements quantified physical behaviour of plant exudates and effect on soil stabilization.Barley root exudates dispersed soil, which could release nutrients and carbon.Maize root and chia seed exudates had a stabilizing effect on soil.Physical engineering of soil in contact with plant roots depends on the nature and origin of exudates.

Melanoma diagnosis and management after the introduction of a pigmented lesion clinic in the Mid-West of Ireland.

BACKGROUND: A pigmented lesion clinic (PLC) was introduced and Consultant Dermatology posts were increased in the Mid-West of Ireland with the aim of improving early detection of melanoma. METHODS: We analysed retrospectively the invasive melanomas excised in the Mid-West of Ireland over a 2-year period prior to (2010-2011) and after (2013-2014) the advent of the PLC. RESULTS: The number of melanomas excised almost doubled from 54 (2010-2011) to 107 (2013-2014). There was a significant rise in the rate of excision biopsies performed by Dermatologists compared to non-dermatology clinicians from 19 to 56% (p < 0.0001). There was a significant difference in the diagnostic accuracy of excised melanomas by Dermatologists compared to non-dermatology clinicians during both time periods (2010-2011: p = 0.001; 2013-2014: p < 0.0001). There was a non-significant decrease in the median Breslow thickness of melanomas from 1.3 mm (0.6-2.6) (2010-2011) to 1.0 mm (0.5-2.3) (2013-2014) (n = 145, p = 0.48). CONCLUSION: The PLC has led to an increase in the number of melanomas excised by Dermatologists in the Mid-West of Ireland which has led to higher diagnostic accuracy.

An analysis of inpatient dermatologic consultations at University Hospital Limerick: inadequate infrastructure leads to acute skin failure.

BACKGROUND: Approximately 15-20 % of the general population have skin diseases and it is therefore clear that inpatients can also present with various skin conditions that require dermatology input and in some cases the primary reason for admission to hospital. Inpatient hospital care is more expensive than outpatient care. Recent trends are moving towards outpatient care, as there is huge pressure on hospital bed availability. AIMS: The main aim of this study was to analyse patients referred with dermatological complaints and how soon after admission, were patients assessed by the dermatology team. Most dermatologic work is outpatient based and inpatient workload can be underestimated. METHODS: We retrospectively reviewed our inpatient consultations with a total of 220 consultations (males 113, females 107) between August 2014 and April 2015, to document this significant area of work over an eight-month period. RESULTS: The services requesting consultations were mostly general medicine 45.9 % (101/220), surgery 25.4 % (56/220) and paediatrics 24 % (53/220). Dermatologist's diagnosis was different from the referral team diagnosis in 60 % (132/220) of consults, with prompt inpatient assessment by the dermatologist within 24 h of admission. Most common dermatoses diagnosed included eczema 21.8 % (48/220) and psoriasis 7.3 % (16/220). CONCLUSION: Timely diagnosis and inpatient care has important implications on appropriate treatment, duration of hospital stay and patient outcome.

A rapid marker ordering approach for high-density genetic linkage maps in experimental autotetraploid populations using multidimensional scaling.

KEY MESSAGE: The paper proposes and validates a robust method for rapid construction of high-density linkage maps suitable for autotetraploid species. Modern genotyping techniques are producing increasingly high numbers of genetic markers that can be scored in experimental populations of plants and animals. Ordering these markers to form a reliable linkage map is computationally challenging. There is a wide literature on this topic, but most has focussed on populations derived from diploid, homozygous parents. The challenge of ordering markers in an autotetraploid population has received little attention, and there is currently no method that runs sufficiently rapidly to investigate the effects of omitting problematic markers on map order in larger datasets. Here, we have explored the use of multidimensional scaling (MDS) to order markers from a cross between autotetraploid parents, using simulated data with 74-152 markers on a linkage group and also experimental data from a potato population. We compared different functions of the recombination fraction and LOD score to form the MDS stress function and found that an LOD2 weighting generally performed well, including when missing values and genotyping errors are present. We conclude that an initial analysis using unconstrained MDS gives a rapid method to detect and remove problematic markers, and that a subsequent analysis using either constrained MDS or principal curve analysis gives reliable marker orders. The latter approach is also particularly rapid, taking less than 10 s on a set of 258 markers compared to 6 days for the JoinMap software. This MDS approach could also be applied to experimental populations of diploid species.

Towards an understanding of the control of 'crumbly' fruit in red raspberry.

The genetic disorder known as 'crumbly' fruit is becoming a serious problem in the European raspberry industry. The study set out to examine the crumbly phenotype in a red raspberry mapping population under two environments (field and polytunnel) across six seasons in an effort to understand variability of the syndrome and to examine whether genetic factors were important and if so, whether QTL associated with the phenotype could be identified. This highlighted that seasonal, environmental (field or polytunnel) and genetic factors all influence the condition. Two QTL that are important for the genetic control of the condition have been located on linkage groups one and three, and an association with ripening time has been identified.

Safety of venous thromboembolism prophylaxis with fondaparinux in ischemic stroke.

INTRODUCTION: Unfractionated heparin (UFH), low molecular weight heparin or fondaparinux are recommended for venous thromboembolism (VTE) prophylaxis in acutely ill medical patients. There are limited data on the safety of fondaparinux for VTE prophylaxis in ischemic stroke. We examined adverse event frequency in hospitalized patients with ischemic stroke who received VTE prophylaxis with fondaparinux versus UFH. MATERIALS AND METHODS: We performed a propensity score matched analysis on a retrospective cohort of 644 consecutive patients with acute ischemic stroke receiving fondaparinux (n=322) or UFH (n=322) for VTE prophylaxis. Patients who received intravenous tPA and continuous intravenous infusions of UFH were excluded. The primary outcome was major hemorrhage (intracranial or extracranial) and the secondary outcome was total hemorrhage (major and minor hemorrhage) during hospitalization. We also examined the rate of symptomatic VTE. RESULTS: Mean age of the matched cohort was 71.3±14.1 years, median NIHSS score was 4 (IQR 1-11), median duration of anticoagulant exposure was 5 (IQR 3-8) days, and 98.1% received antiplatelet medications. In the matched cohort, there were less observed major hemorrhages in the fondaparinux group 1.2% (4/322) compared to UFH 3.7% (12/322), but this difference was not significant (OR=0.33, 95% CI 0.08-1.10, p=0.08). There were also no significant differences in total hemorrhage (p=0.15), intracranial hemorrhage (p=0.48), major extracranial hemorrhage (p=0.18) and symptomatic VTE (p=1.00) between the groups. CONCLUSIONS: Fondaparinux is not associated with increased hemorrhagic complications compared with UFH in patients with ischemic stroke. There were low rates of symptomatic VTE in both groups.

Low vitamin D level is associated with higher relapse rate in natalizumab treated MS patients.

BACKGROUND: Previous research suggested a relationship between low vitamin D and relapse rate. We examined whether vitamin D levels were associated with: 1) MS severity and 2) recent MS relapse activity, in patients treated with natalizumab. METHODS: All patients (n=118) were treated with natalizumab and were tested for vitamin D levels during the winter of 2009-10. Number of relapses during treatment with natalizumab was determined by retrospective chart review. MS severity was estimated with the Roxburgh's MS Severity Score (MSSS) at the time of the initial blood draw and 1 year preceding and following initial draws. Vitamin D levels of 50 nmol/L or greater were defined as normal. RESULTS: Patients with deficient vitamin D levels (DVD) totaled 45. Sixteen of the 26 patients with relapse in the year prior to the initial blood draw (4 patients had multiple relapses - all were in DVD) and 12 of 17 patients with relapse in the following year were in the DVD group. There was a significant difference between the normal vitamin D group (NVD) and DVD in MS relapse activity in the year prior (p=0.005) and following blood draw (p=0.006). There was no significant between group differences in MSSS at any time. CONCLUSIONS: Natalizumab treated patients with DVD were more likely to experience relapse and may experience more relapses than patients with NVD.

Towards an understanding of the nature of resistance to Phytophthora root rot in red raspberry.

A mapping population segregating for root rot resistance was screened under both field and glasshouse conditions over a number of seasons. Few correlations between field and glasshouse scores were significant. Final root rot scores were significantly negatively correlated with measures of root vigour. Two QTL associated with resistance were identified as were overlapping QTL for root vigour assessments. Markers significantly associated with the traits were used to identify BAC clones, which were subsequently sequenced to examine gene content. A number of genes were identified including those associated with stem cell identity, cell proliferation and elongation in the root zone, control of meristematic activity and organisation, cell signalling, stress response, sugar sensing and control of gene expression as well as a range of transcription factors including those known to be associated with defence. For marker-assisted breeding, the SSR marker Rub118b 110 bp allele from Latham was found in resistant germplasm but was not found in any of the susceptible germplasm tested.