Peripartum issues in the inflammatory arthritis patient: A survey of the RAPPORT registry.

Childbearing women with rheumatoid (RA) and psoriatic arthritis (PsA) have significant peripartum issues. A retrospective anonymous RedCAP survey of peripartum period in females with RA/PsA in the RAPPORT registry was performed. Completed analyses included descriptive statistics, Chi-square and Fisher's exact test. 162 patients (133 RA/29 PsA) completed the survey (103 women having 234 pregnancies), 164 pregnancies occurring before and 70 pregnancies occurring after diagnosis. Pregnancy outcomes from 103 patients included: 96% live births, 1.9% stillbirths, 23% miscarriages, and 15% therapeutic abortions. A third of patients had fewer children than desired due to disease activity, medications and other reasons. For 63 pregnancies after diagnosis: (1) 49% of pregnancies received pre-conception counseling; (2) 65% described good disease control during pregnancy but 74% flared in the first 3 months postpartum; (3) 79% of pregnancies discontinued IA medications; (4) 35% of pregnancies occurred on biologic therapy at or prior to conception. Gestational age at time of delivery was 37-40 weeks in 58% (33/57) post-arthritis vs 66% (83/126) pre-arthritis pregnancies. No statistically significant differences occurred between pregnancies before or after RA/PsA diagnosis for: pregnancy planning, fertility treatment, pregnancy and labour/delivery complications, birth defect frequency or neonatal complications. Neonatal ICU admissions were significantly lower in pre- compared to post-arthritis pregnancies (3.2% vs 14.5%). No pregnancy complications were noted in 24/54 pregnancies on medications compared to 6/9 pregnancies not on medications. The impact of RA/PsA before, during and after pregnancy varied considerably in this cohort emphasizing the importance of informed-decision making at all stages.

Comparison of the utility of clinical breast examination and MRI in the surveillance of women with a high risk of breast cancer.

AIM: To review surveillance magnetic resonance imaging (MRI) and clinical breast examinations (CBE) performed for women at high risk of breast cancer in order to determine recall and cancer-detection rates. MATERIALS AND METHODS: Data were collected on all surveillance MRI examinations performed at St James's Hospital in 2016 for women at high risk of developing breast cancer. Data collected included age, indication for MRI, MRI score, ultrasound indications and scores, and histology findings. Ultrasound scores were recorded from CBEs that received a score of ≥3. RESULTS: A total of 385 breast surveillance MRI examinations and CBEs were performed for women at high risk of breast cancer. A recall rate of 11.2% was documented for breast MRI examinations, whereas a recall rate of 6.2% was identified for CBEs. The biopsy rate was 6.2% for MRI and 0.2% for CBE. The cancer detection rate was 1.6% or 16 per 1,000 for MRI screening and 0% for CBE. CONCLUSION: The high cancer detection rate in the present study supports the unparalleled sensitivity of breast MRI surveillance. Furthermore, the present study did not identify any breast cancers through CBE, suggesting it is not a critical component of the surveillance programme of high-risk women. The current UK guidelines recommending a target recall rate of 7% were not met in the present study or by other studies in the literature, collectively suggesting the guidelines may not be reflective of what is attainable in clinical practice.

Optimisation and validation of a PCR to detect viable Tenacibaculum maritimum in salmon skin tissue samples.

A PCR protocol was optimised and validated for the detection of viable Tenacibaculum maritimum cells in salmon skin tissue. Viability conventional (vPCR) and quantitative PCR (v-qPCR) assays both had a limit of detection of 103 CFU mL-1 viable cells. The v-qPCR assay showed a linear quantification over 4 log units. Conventional vPCR showed complete signal suppression when only dead cells were present at concentrations lower than 106 CFU mL-1. While the v-qPCR did not result in complete suppression when only dead cells were present, a method was developed to determine if viable cells were present based on the % Δ in cycle threshold (Ct) value. The procedure was validated for high-throughput processing and an enrichment protocol was validated to reliably detect low concentrations of viable cells both with and without a high background of dead cells. Performing this protocol on naturally infected tissues showed that vPCR and v-qPCR reduced the potential for false positives compared to using conventional PCR and qPCR. The optimised protocol developed for this study provides an efficient, reliable and robust alternative for the detection of viable T. maritimum in skin tissue.

What investigations are needed to optimally monitor for malignancies in SLE?

OBJECTIVE: The overall cancer incidence risk in systemic lupus erythematosus (SLE) is approximately 15%-20% more than in the general population. Nevertheless, to date, the optimal malignancy screening measures in SLE remain undefined. Our objective is to determine what investigations are needed to optimally monitor for malignancies in SLE in order to inform upcoming Canadian Rheumatology Association recommendations. METHODS: We conducted a systematic search looking at three scientific sources, Embase, Medline and Cochrane, in an attempt to identify cancer screening recommendations for patients with SLE. We used a filter for observational studies and included articles published in 2000 and onward. RESULTS: The initial search strategy led to 986 records. After removal of duplicates and articles unrelated to SLE, we were left with 497 titles. From those, 79 research articles on cancer incidence in SLE were isolated and reviewed. Of the 79 original research papers, 25 offered screening recommendations, 14 suggested additional cancer screening whereas 11 studies simply promoted adherence to general population screening measures. The suggestions for more rigorous screening included recommending human papilloma virus testing in addition to routine cervical screening, and/or that cervical screening should be performed annually and/or suggested urine cancer screening in SLE patients with a history of cyclophosphamide exposure. CONCLUSIONS: We found no original research studies directly comparing cancer screening strategies in SLE. Generally, authors recommend adherence to general population screening measures, particularly cervical screening. This, possibly with adding targeted screening in special cases (e.g. annual urine cytology in patients with prior cyclophosphamide exposure, and considering existing lung cancer screening guidelines for past heavy smokers), may be a reasonable approach for cancer screening in SLE.

Effect of biologics on depressive symptoms in patients with psoriasis: a systematic review.

BACKGROUND: Twenty to fifty percent of patients with psoriasis have depressive symptoms. OBJECTIVE: To describe the effects of biologics (tumour necrosis factor inhibitors [TNFi] or interleukin 12/23 inhibitors [IL-12/23i]) on depressive symptoms in patients with psoriasis. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) examining the effects of biologics on depressive symptoms in adults with psoriasis. RESULTS: Of the 305 publications identified, three RCTs were included in a systematic review. In a trial evaluating ustekinumab, mean change in Hospital and Anxiety Depression Rating Scale at 24 weeks from baseline was 3.1 with ustekinumab (P < 0.001) vs. 0.21 with placebo (not significant). In a trial evaluating adalimumab, mean change in Zung Self-Rating Depression Scale at 12 weeks from baseline was -6.7 with adalimumab vs. -1.5 with placebo. In a trial evaluating etanercept, the between-group difference at 12 weeks in Beck Depression Inventory Scale was 1.8 (95% CI: 0.6, 2.90) in favour of etanercept over placebo. Limitations are that diagnostic criteria for depression were not used and scales and data from individual RCTs could not be combined. CONCLUSION: Adalimumab, etanercept and ustekinumab were associated with statistically significant reductions in depressive symptom scores using various scales in patients with moderate-to-severe psoriasis.

New Zealand juvenile oyster mortality associated with ostreid herpesvirus 1-an opportunistic longitudinal study.

During the 2010-11 summer outbreak of ostreid herpesvirus 1 (OsHV-1) in New Zealand, an opportunistic longitudinal field study was conducted. OsHV-1 PCR-negative oyster spat (Crassostrea gigas) were relocated to an OsHV-1 PCR-positive area of the North Island of New Zealand that was experiencing juvenile oyster mortalities. Over a period of 13 d, spat were monitored for mortality, sampled for histopathology, and tested for the presence of OsHV-1 using real time PCR and Vibrio culture. Histopathology showed some evidence of tissue pathology; however, no consistent progressive pathology was apparent. Field mortalities were evident from Day 6 on. After 5 and 7 d of exposure, 83 and 100% of spat, respectively, tested positive for the virus by real time PCR. Vibrio species recovered during the longitudinal study included V. splendidus and V. aestuarianus. This study offers insight into the rapidity of onset and virulence of the virus in naïve oyster spat in New Zealand waters.

Development and validation of a real-time PCR assay for the detection of Aeromonas salmonicida.

A real-time PCR assay using a molecular beacon was developed and validated to detect the vapA (surface array protein) gene in the fish pathogen, Aeromonas salmonicida. The assay had 100% analytical specificity and analytical sensitivities of 5 ± 0 fg (DNA), 2.2 × 10(4) ± 1 × 10(4) CFU g(-1) (without enrichment) and 40 ± 10 CFU g(-1) (with enrichment) in kidney tissue. The assay was highly repeatable and proved to be robust following equivalency testing using a different real-time PCR platform. Following analytical validation, diagnostic specificity was determined using New Zealand farmed Chinook salmon, Oncorhynchus tshawytscha (Walbaum), (n = 750) and pink shubunkin, Carassius auratus (L.) (n = 157). The real-time PCR was run in parallel with culture and all fish tested were found to be negative by both methods for A. salmonicida, resulting in 100% diagnostic specificity (95% confidence interval). The molecular beacon real-time PCR system is specific, sensitive and a reproducible method for the detection of A. salmonicida. It can be used for diagnostic testing, health certification and active surveillance programmes.

Issues influencing the decision to have upper limb surgery for people with tetraplegia.

STUDY DESIGN: Grounded theory. OBJECTIVES: To explore to better understand the decision-making process of people with tetraplegia regarding reconstructive upper limb (UL) surgery. SETTING: New Zealand. METHODS: In-depth interviews with 22 people with tetraplegia, 10 of whom had UL surgery and 12 had not. Verbatim transcripts were analysed using constructivist grounded theory. RESULTS: The primary reason for having reconstructive UL surgery was to improve independence and return to previous pastimes. Reasons not to have surgery were hope for further recovery or cure, and inadequate physical environment or social supports while rehabilitating. In addition, women identified the temporary loss of independence and need for increased care while rehabilitating as issues. Importantly, these issues were not static, often changing in importance or relevance over time. CONCLUSIONS: The moment of making the decision for reconstructive UL surgery is elusive; therefore, multiple offers of surgery at different timeframes in an individual's life are required. In addition, flexibility in timing for surgery would allow for surgery to better coordinate with an individual's goals and priorities.

Development and validation of real-time PCR for the detection of Yersinia ruckeri.

Yersiniosis (enteric red mouth disease) is a contagious bacterial disease caused by Yersinia ruckeri, which primarily affects salmonids. A real-time PCR assay using a molecular beacon has been developed and validated to improve the detection of the causative biotypes of Y. ruckeri. The assay, which targets the glnA (glutamine synthetase) gene, proved to have 100% analytical specificity and analytical sensitivities of 5 fg and 3 × 10(3) CFU g(-1) for DNA and seeded kidney tissue, respectively. The assay was highly repeatable with low % CV for intra- and inter-run experiments, and the optimized parameters transferred easily between different real-time PCR platforms. Following analytical validation, diagnostic specificity was determined using New Zealand farmed Chinook salmon (n = 750) from 10 farms during 2007/08. The real-time PCR was run in parallel with the bacterial culture detection method, and all fish tested were found to be negative by both methods for Y. ruckeri, resulting in 100% diagnostic specificity (95% confidence interval). The molecular beacon real-time PCR system is specific, sensitive, reproducible and a rapid method for the detection of Y. ruckeri and has the potential to be used for routine diagnostic testing, health certification and active surveillance programmes.

Development of real-time PCR assays for detection of megalocytiviruses in imported ornamental fish.

Megalocytiviruses have been associated globally with severe systemic disease and economic loss in farmed food fish and ornamental fish. The viruses have been spread internationally by translocation of live fish. In New Zealand, megalocytiviruses are regarded as exotic. A potential pathway for introduction has been identified, namely imported ornamental fish. In the present study, real-time PCR assays were developed for detection of megalocytiviruses using a conserved major capsid protein gene. A SYBR green assay was developed to target all known megalocytiviruses. A second real-time PCR assay using a molecular beacon was developed to specifically target gourami, Trichogaster trichopterus, iridovirus, a species of iridovirus previously linked to ornamental fish imports in Australia. The analytical sensitivity for the SYBR green and molecular beacon assays were 10 and 100 fg, respectively. The analytical specificity of the real-time PCR assays determined using genomic DNA templates from three target viruses, 12 non-target viruses and 25 aquatic bacterial species were 100%. The intra-run and inter-run coefficients of variation of both assays were <5%. The real-time PCR assays developed in this study provide rapid, sensitive, and specific detection of megalocytiviruses and gourami iridovirus.

Outbreaks of pleuritis and peritonitis in calves associated with Pasteurella multocida capsular type B strain.

CASE HISTORY: Three dairy calf-rearing properties experienced high mortality in calves during 2008 and 2009. Affected calves were aged 13-18 weeks (Farm I), 6 months (Farm II), and 2-11 weeks (Farm III), and the mortality rate was 22/175 (13%), 5/80 (6%), and 60/900 (7%), respectively. CLINICAL AND LABORATORY FINDINGS: Affected calves rapidly became moribund, were in respiratory distress, and had a fever (40-41°C). Post-mortem examination of nine calves revealed fibrinopurulent pleuritis, pericarditis, and peritonitis. This was confirmed histopathologically on tissues from three calves, one from each farm; aggregates of small Gram-negative coccobacilli were evident on Gram stain. Pasteurella multocida was cultured from tissues from affected calves on the three farms, and PCR of DNA extracted from tissue samples amplified cap-sular type B-specific DNA. Multi-locus sequence typing (MLST) demonstrated that all capsular type B isolates belonged to the same sequence type (ST), ST62, but did not belong to serotype B:2, the only B serotype classified as causing haemorrhagic septicaemia by the Office International des Epizooties (OIE). DIAGNOSIS: Pleuritis and peritonitis due to infection with P. multocida capsular type B strain. CLINICAL RELEVANCE: Haemorrhagic septicaemia was excluded as a cause of disease from the three farms, however P. multocida was the primary agent in the affected calves. It is possible the agent has been present in New Zealand for some time but not reported, as there had been no transfer of animals between affected farms. Emergence of the syndrome could potentially be a result of factors other than just the presence of the organism, such as changing management. The syndrome described may be of increasing importance in the future.

Upper limb reconstructive surgery uptake for persons with tetraplegia in New Zealand: a retrospective case review 2001-2005.

STUDY DESIGN: Retrospective case series. OBJECTIVE: To describe the uptake of upper limb surgery by individuals with tetraplegia in New Zealand (NZ). SETTING: New Zealand. METHODS: The clinical notes of all individuals who sustained a cervical spinal cord injury between 1 January 2001 and 31 December 2005 were retrospectively reviewed for those who met the clinical criteria to undergo upper limb surgery. Cases were cross-referenced to the hand surgery record to determine the uptake of upper limb surgery in this cohort. RESULTS: The uptake of upper limb surgery for people with tetraplegia in NZ was 44% of the eligible cohort and 59% of those assessed for surgery. This is notably higher than the reported proportion in other developed countries. The data also suggested that women and those who identified as NZ Maori were less likely to undergo upper limb surgery than were men and those of NZ European ethnicity. CONCLUSION: Utilization of upper limb surgery in the eligible tetraplegic population in NZ was high. However, it seemed that some groups were less likely to undergo surgery. Further research into the factors that affect an individual's decision to undergo upper limb surgery could explain the observed pattern.

Addressing species specific metabolism and solubility issues in a quinoline series of oral PDE4 inhibitors.

Species specific conversion of the lead PDE4 inhibitor 1 to the quinolone 3 was identified as the major route of metabolism in the cynomolgus monkey. Modification of the template to give the cinnoline 9 retained potency and selectivity, and greatly improved the pharmacokinetic profile in the cynomolgus monkey compared with 1. Additional SAR studies aimed at improving the solubility of 9 are also described.

Metals tolerance in moderately thermophilic isolates from a spent copper sulfide heap, closely related to Acidithiobacillus caldus, Acidimicrobium ferrooxidans and Sulfobacillus thermosulfidooxidans.

Selective enrichments enabled the recovery of moderately thermophilic isolates with copper bioleaching ability from a spent copper sulfide heap. Phylogenetic and physiological characterization revealed that the isolates were closely related to Sulfobacillus thermosulfidooxidans, Acidithiobacillus caldus and Acidimicrobium ferrooxidans. While isolates exhibited similar physiological characteristics to their corresponding type strains, in general they displayed similar or greater tolerance of high copper, zinc, nickel and cobalt concentrations. Considerable variation was found between species and between several strains related to S. thermosulfidooxidans. It is concluded that adaptation to metals present in the bioleaching heap from which they were isolated contributed to but did not entirely explain high metals tolerances. Higher metals tolerance did not confer stronger bioleaching performance, suggesting that a physical, mineralogical or chemical process is rate limiting for a specific ore or concentrate.

Minimizing macrovessel signal in cerebral perfusion imaging using independent component analysis.

The pronounced susceptibility effect of macrovessels in MR bolus-tracking studies induces spots of artificially high blood flow and volume in perfusion parameter images. These high-intensity regions impede the detection of perfusion changes and lead to elevated perfusion parameters in adjacent tissues. The purpose of this work was to explore postprocessing methods to reduce the influence of macrovessel signal in dynamic MRI. After data reduction was performed with the use of a principal component analysis (PCA), an independent component analysis (ICA) was applied to separate signal components of different compartments. Based on this decomposition, the dynamic time series were reconstructed with minimized contributions of macrovessel signal and noise. The influence of the temporal resolution and signal-to-noise ratio (SNR) of the source data were investigated by means of a simulation study. A region-of-interest (ROI)-based analysis of corrected and uncorrected in vivo data demonstrated that the influence of arteries and veins was reduced at least by 50%, while gray matter (GM) and white matter (WM) tissues were nearly unaffected by the correction process. Hemodynamic parameter images of the cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated from corrected and uncorrected scans. The corrected parameter images showed a clearly reduced macrovessel signal and an improved perceptibility of microvascular perfusion changes compared to the uncorrected ones.

Nickel and cobalt phytoextraction by the hyperaccumulator Berkheya coddii: implications for polymetallic phytomining and phytoremediation.

We investigated the potential of the South African high-biomass Ni hyperaccumulator Berkheya coddii to phytoextract Co and/or Ni from artificial metalliferous media. Plant accumulation of both metals from single-element substrates indicate that the plant/media metal concentration quotient (bioaccumulation coefficient) increases as total metal concentrations increase. Cobalt was readily taken up by B. coddii with and without the presence of Ni. Nickel uptake was, however, inhibited by the presence of an equal concentration of Co. Bioaccumulation coefficients of Ni and Co for the single element substrates (total metal concentration of 1000 micrograms g-1) were 100 and 50, respectively. Cobalt phytotoxicity was observed above a total Co concentration in plant growth media of 20 micrograms g-1. Elevated Co concentrations significantly decreased the biomass production of B. coddii without affecting the bioaccumulation coefficients. The mixed Ni-Co substrate produced bioaccumulation coefficients of 22 for both Ni and Co. Cobalt phytotoxicity in mixed Ni-Co substrate occurred above a total Co concentration of 15 micrograms g-1. When grown in the presence of both Ni and Co, the bioaccumulation coefficients of each metal were reduced, as compared to single-element substrate. This may indicate competition for binding sites in the root zone. The interference relationship between Ni and Co uptake demonstrated by B. coddii suggests a significant limitation to phytoextraction where both metals are present.

Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene.

We analysed the CACNA1A gene, located on chromosome 19p13, in three unrelated families and one sporadic case with episodic ataxia type 2 (EA-2). In two of the families and the sporadic patient, novel truncating mutations, which disrupt the reading frame and result in a premature stop of the CACNA1A protein, were identified in exons 14, 16 and 26. In the remaining family, a novel missense mutation (H253Y) was found. Of the twenty two EA-2 mutations identified thus far, including those of the present study, seventeen are truncating mutations and five are missense mutations, all resulting in an EA-2 clinical phenotype.

Improved diffusion-weighted single-shot echo-planar imaging (EPI) in stroke using sensitivity encoding (SENSE).

Diffusion-weighted single-shot EPI (sshEPI) is one of the most important tools for the diagnostic assessment of stroke patients, but it suffers from well known artifacts. Therefore, sshEPI was combined with SENSitivity Encoding (SENSE) to further increase EPI's potential for stroke imaging. Eight healthy volunteers and a consecutive series of patients (N = 8) with suspected stroke were examined with diffusion-weighted SENSE-sshEPI using different reduction factors (1.0 < or = R < or = 3.0). Additionally, a high-resolution diffusion-weighted SENSE-sshEPI scan was included. All examinations were diagnostic and of better quality than conventional sshEPI. No ghostings or aliasing artifacts were discernible, and EPI-related image distortions were markedly diminished. Chemical shift artifacts and eddy current-induced image warping were still present, although to a markedly smaller extent. Measured direction-dependent diffusion-coefficients and isotropic diffusion values were comparable to previous findings but showed less fluctuation. We have demonstrated the technical feasibility and clinical applicability of diffusion-weighted SENSE-sshEPI in patients with subacute stroke. Because of the faster k-space traversal, this novel technique is able to reduce typical EPI artifacts and increase spatial resolution while simultaneously remaining insensitive to bulk motion.

Mutational analysis in X-linked spondyloepiphyseal dysplasia tarda.

Spondyloepiphyseal dysplasia tarda (SEDT) is an X-linked recessive disorder characterized by short stature due to defective growth of the vertebral bodies. In addition, deformities of the femoral heads result in early onset secondary osteoarthritis of the hips. The disorder affects males only with heterozygous female carriers showing no consistent abnormalities. The gene causing SEDT, which is located on Xp22.12-p22.31, consists of 6 exons of which only exons 3, 4, 5, and 6 are translated to yield an 140 amino acid protein, referred to as SEDLIN. SEDLIN mutations have been observed in SEDT patients, and we have undertaken studies to characterize such mutations in four unrelated SEDT kindreds by DNA sequence analysis. We identified two nonsense and two intragenic deletional frameshift mutations. The nonsense mutations occurred in exons 4 (TGG-->TGA, Trp70Stop) and 6 (CGA-->TGA, Arg122Stop). Both of the intragenic deletions, which were approximately 750 bp and 1300-1445 bp in size, involved intron 5 and part of exon 6 and resulted in frameshifts that lead to premature termination (Stop) signals. Thus, all four mutations are predicted to result in truncated proteins. The results of our study expand the spectrum of SEDLIN mutations associated with SEDT, and this will help to elucidate further the role of this novel protein in the etiology of this form of osteochondrodysplasia.

Interstitial deletion 4q32-34 with ulnar deficiency: 4q33 may be the critical region in 4q terminal deletion syndrome.

We report on an infant with Robin sequence; mild developmental delay; a left ulnar ray defect with absent ulna and associated metacarpals, carpals and phalanges; and a right ulnar nerve hypoplasia. He had a de novo interstitial deletion of 4q32-->q34. The critical region involved in the 4q terminal deletion syndrome may be 4q33. This conclusion was suggested by showing that del(4)(q31qter), del(4)(q32qter), and del(4)(q33qter) result in a similarly severe phenotype. In addition, we propose that genes for distal arm development, in particular for development of the left ulnar ray, central nervous system development, and cleft lip and palate, may be located at 4q33.