Dog leucocyte antigen (DLA) class II haplotypes and risk of canine diabetes mellitus in specific dog breeds.

BACKGROUND: Canine diabetes mellitus (DM) is a common endocrine disease in domestic dogs. A number of pathological mechanisms are thought to contribute to the aetiopathogenesis of relative or absolute insulin deficiency, including immune-mediated destruction of pancreatic beta cells. DM risk varies considerably between different dog breeds, suggesting that genetic factors are involved and contribute susceptibility or protection. Associations of particular dog leucocyte antigen (DLA) class II haplotypes with DM have been identified, but investigations to date have only considered all breeds pooled together. The aim of this study was to analyse an expanded data set so as to identify breed-specific diabetes-associated DLA haplotypes. METHODS: The 12 most highly represented breeds in the UK Canine Diabetes Register were selected for study. DLA-typing data from 646 diabetic dogs and 912 breed-matched non-diabetic controls were analysed to enable breed-specific analysis of the DLA. Dogs were genotyped for allelic variation at DLA-DRB1, -DQA1, -DQB1 loci using DNA sequence-based typing. Genotypes from all three loci were combined to reveal three-locus DLA class II haplotypes, which were evaluated for statistical associations with DM. This was performed for each breed individually and for all breeds pooled together. RESULTS: Five dog breeds were identified as having one or more DLA haplotype associated with DM susceptibility or protection. Four DM-associated haplotypes were identified in the Cocker Spaniel breed, of which one haplotype was shared with Border Terriers. In the three breeds known to be at highest risk of DM included in the study (Samoyed, Tibetan Terrier and Cairn Terrier), no DLA haplotypes were found to be associated with DM. CONCLUSIONS: Novel DLA associations with DM in specific dog breeds provide further evidence that immune response genes contribute susceptibility to this disease in some cases. It is also apparent that DLA may not be contributing obvious or strong risk for DM in some breeds, including the seven breeds analysed for which no associations were identified.

Feasibility and acceptability of a web-based HIV/STD prevention program for adolescent girls targeting sexual communication skills.

Adolescent girls are at substantial risk of sexually transmitted diseases including HIV. To reduce these risks, we developed Health Education And Relationship Training (HEART), a web-based intervention focused on developing sexual assertiveness skills and enhancing sexual decision-making. This study assessed the feasibility and acceptability of this new program and examined if perceived acceptability varied according to participant ethnicity, sexual orientation or sexual activity status. Participants were part of a randomized controlled trial of 222 10th-grade girls (Mage = 15.26). The current analyses included those in the intervention condition (n = 107; 36% white, 27% black and 29% Hispanic). HEART took approximately 45 min to complete and was feasible to administer in a school-based setting. Participants found the program highly acceptable: 95% liked the program and learned from the program, 88% would recommend the program to a friend and 94% plan to use what they learned in the future. The primary acceptability results did not vary by the ethnicity, sexual orientation or sexual activity status of participants, suggesting broad appeal. Results indicate that this new online program is a promising method to reach and engage adolescents in sexual health education.

The Genetic Basis of Pigmentation Differences Within and Between Drosophila Species.

In Drosophila, as well as in many other plants and animals, pigmentation is highly variable both within and between species. This variability, combined with powerful genetic and transgenic tools as well as knowledge of how pigment patterns are formed biochemically and developmentally, has made Drosophila pigmentation a premier system for investigating the genetic and molecular mechanisms responsible for phenotypic evolution. In this chapter, we review and synthesize findings from a rapidly growing body of case studies examining the genetic basis of pigmentation differences in the abdomen, thorax, wings, and pupal cases within and between Drosophila species. A core set of genes, including genes required for pigment synthesis (eg, yellow, ebony, tan, Dat) as well as developmental regulators of these genes (eg, bab1, bab2, omb, Dll, and wg), emerge as the primary sources of this variation, with most genes having been shown to contribute to pigmentation differences both within and between species. In cases where specific genetic changes contributing to pigmentation divergence were identified in these genes, the changes were always located in noncoding sequences and affected cis-regulatory activity. We conclude this chapter by discussing these and other lessons learned from evolutionary genetic studies of Drosophila pigmentation and identify topics we think should be the focus of future work with this model system.

MORTALITY DURING TREATMENT: FACTORS AFFECTING THE SURVIVAL OF OILED, REHABILITATED COMMON MURRES (URIA AALGE).

After major oil spills, hundreds to thousands of live stranded birds enter rehabilitative care. To target aspects of rehabilitative efforts for improvement and to evaluate which initial physical examination and biomedical parameters most effectively predict survival to release, medical records were examined from 913 Common Murres ( Uria aalge ; COMUs) oiled during the November 2001-January 2003 oil spill associated with the sunken S.S. Jacob Luckenbach off San Francisco, California, US. Results showed that 52% of all deaths occurred during the first 2 days of treatment. Birds stranding closest to the wreck had greater amounts of oil on their bodies than birds stranding farther away. More heavily oiled birds were in better clinical condition than birds with lesser amounts of oil, as shown by higher body mass (BM), packed cell volumes (PCV), total plasma protein (TP), and higher survival proportions. Additionally, BM, PCV, TP, and body temperature were positively correlated. For comparison, medical records from all nonoiled COMUs admitted for rehabilitation at the same facility during 2007-09 (n=468) were examined, and these variables were also found to be positively correlated. Oiled birds with BM under 750 g had approximately 5% lower PCV than BM-matched nonoiled COMUs. More heavily oiled COMUs may be in better condition than less oiled birds because heavily oiled birds must beach themselves immediately to avoid drowning and hypothermia, whereas lightly oiled birds may postpone beaching until exhausted due to extreme body catabolism. The strong relationship of PCV to BM regardless of oiling provides evidence that anemia commonly encountered in oiled seabirds may be a sequela to overall loss of body condition rather than solely due to toxic effects of oiling. Clinical information garnered in this study provides guidance for triage decisions during oil spills.

Association of Toll-like receptor 4 (TLR4) with chronic plaque type psoriasis and psoriatic arthritis.

Family studies have provided overwhelming evidence for an underlying genetic component to psoriasis. Toll-like receptors (TLRs) are key transmembrane proteins in both the innate and adaptive immune responses which are known to be integral processes in psoriasis. Recent functional studies support this notion having suggested a role for TLR4 in the pathogenesis of psoriasis. Furthermore a missense polymorphism in the TLR4 gene has been associated with a number of autoimmune conditions, including Crohn diseases, making TLR4 a viable candidate gene for investigation. The aim of this study was to investigate polymorphisms across the TLR4 region with a high-density single nucleotide polymorphism (SNP) panel in a large cohort of patients with chronic plaque type psoriasis. Twenty SNPs were successfully genotyped using Sequenom iPLEX Gold platform in 2826 UK chronic plaque type psoriasis patients including subgroup data on presence of confirmed psoriatic arthritis (n = 1839) and early-onset psoriasis (n = 1466) was available. Allele frequencies for psoriasis patients were compared against imputed Wellcome Trust Case Control Consortium controls (n = 4861). Significant association was observed between a missense variant rs4986790 of TLR4 (Asp229Gly) and plaque type psoriasis (p = 2 × 10(-4)) which was also notable in those with psoriatic arthritis (p = 2 × 10(-4)) and early-onset psoriasis (p = 8 × 10(-4)). We present data suggestive of an association between a functional variant and an intronic variant of TLR4 and chronic plaque type psoriasis and psoriatic arthritis. However, validation of this association in independent cohorts will be necessary.

Audit of the job satisfaction levels of the UK radiography and physics workforce in UK radiotherapy centres 2012.

OBJECTIVE: Workforce planning reports identify a staff shortfall that jeopardizes the ability of UK radiotherapy centres to meet future demands. Obtaining an understanding of the work experiences of radiotherapy professionals will support the development of strategies to increase job satisfaction, productivity and effectiveness. METHODS: A quantitative survey assessed job satisfaction, attitudes to incident reporting, stress and burnout, opportunities for professional development, workload, retention and turnover. Clinical oncologists were not included, as the Royal College of Radiologists, London, UK, had recently assessed their members' satisfaction. All questions were taken from validated instruments or adapted from the "UK National Health Service Staff Survey". RESULTS: The survey yielded 658 completed responses (approximately 16% response rate), from public and private sectors. Over a third (36%) of respondents were classified as satisfied for job satisfaction with 11% dissatisfied and the remaining 53% ambivalent. A significant proportion of clinical staff (37.5%) report high emotional exhaustion. Presenteeism was an issue with 42.4% attending work despite feeling unable to fulfil their role. CONCLUSION: Radiotherapy professionals are prone to the effects of compassion fatigue and burnout. Attention must be paid to workload and its impact on practitioners' job satisfaction. Professional development that is supported and informed by a performance development review is a simple and effective means of enhancing satisfaction. Individuals have a responsibility to themselves and their colleagues as their behaviours and attitudes influence job satisfaction. ADVANCES IN KNOWLEDGE: This work identifies areas for future research to enhance the professional resilience of practitioners, in order to provide high-quality treatments.

Monitoring of fungal loads in seabird rehabilitation centers with comparisons to natural seabird environments in northern California.

Aspergillosis remains a major cause of mortality in captive and rehabilitated seabirds. To date, there has been poor documentation of fungal (particularly Aspergillus spp.) burdens in natural seabird loafing and roosting sites compared with fungal numbers in rehabilitation or captive settings and the various microenvironments that seabirds are exposed to during the rehabilitation process. This study compares fungal, particularly Aspergillus spp., burdens potentially encountered by seabirds in natural and rehabilitation environments. Differences among the various microenvironments in the rehabilitation facility were evaluated to determine the risk of infection when seabirds are experiencing high stress and poor immune function. Aspergillus spp. counts were quantified in three wildlife rehabilitation centers and five natural seabird loafing and roosting sites in northern California using a handheld impact air sampler and a water filtration system. Wildlife rehabilitation centers demonstrated an increase in numbers of conidia of Aspergillus spp. and Aspergillus fumigatus in air and water samples from select aquatic bird rehabilitation centers compared with natural seabird environments in northern California. Various microenvironments in the rehabilitation facility were identified as having higher numbers of conidia of Aspergillus spp. These results suggest that periodic monitoring of multiple local areas, where the birds spend time in a rehabilitation facility, should be done to identify "high risk" sites, where birds should spend minimal time, or sites that should be cleaned more frequently or have improved air flow to reduce exposure to fungal conidia. Overall, these results suggest that seabirds may be more likely to encounter Aspergillus spp. in various microenvironments in captivity, compared with their native habitats, which could increase their risk of developing disease when in a debilitated state.

Characterization of CD4 and CD8 T cell responses in MuSK myasthenia gravis.

Muscle specific tyrosine kinase myasthenia gravis (MuSK MG) is a form of autoimmune MG that predominantly affects women and has unique clinical features, including prominent bulbar weakness, muscle atrophy, and excellent response to therapeutic plasma exchange. Patients with MuSK MG have predominantly IgG4 autoantibodies directed against MuSK on the postsynaptic muscle membrane. Lymphocyte functionality has not been reported in this condition. The goal of this study was to characterize T cell responses in patients with MuSK MG. Intracellular production of IFN-gamma, TNF-alpha, IL-2, IL-17, and IL-21 by CD4+ and CD8+ T cells was measured by polychromatic flow cytometry in peripheral blood samples from 11 Musk MG patients and 10 healthy controls. Only one MuSK MG patient was not receiving immunosuppressive therapy. Regulatory T cells (Treg) were also included in our analysis to determine if changes in T cell function were due to altered Treg frequencies. CD8+ T cells from MuSK MG patients had higher frequencies of polyfunctional responses than controls, and CD4+ T cells had higher IL-2, TNF-alpha, and IL-17. MuSK MG patients had a higher percentage of CD4+ T cells producing combinations of IFN-gamma/IL-2/TNF-gamma, TNF-alpha/IL-2, and IFN-gamma/TNF-alpha. Interestingly, Treg numbers and CD39 expression were not different from control values. MuSK MG patients had increased frequencies of Th1 and Th17 cytokines and were primed for polyfunctional proinflammatory responses that cannot be explained by a defect in CD39 expression or Treg number.

Is the decremental pattern in Lambert-Eaton syndrome different from that in myasthenia gravis?

OBJECTIVE: We reviewed our experience to determine if the decremental pattern during low frequency repetitive nerve stimulation (LF-RNS) distinguishes between the Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG). METHODS: LF-RNS studies were reviewed from 34 LEMS and 44 MG patients, 4 of whom had antibodies to muscle specific kinase (MuSK). In each train we calculated the ratio between the early and the later decrement. Receiver-operator characteristic curves were calculated to determine the ratio that best distinguished between LEMS and MG. RESULTS: The late decrement was more often greater in LEMS and the converse was true in MG, but with some overlap in values in individual patients. A late decrement more than 102% of the early decrement discriminated between LEMS and MG in 90% of studies. The decremental pattern in MG patients with MuSK antibodies resembled that in LEMS. CONCLUSION: When the decrement becomes progressively greater during low frequency RNS, the patient is more likely to have LEMS than MG, and in MG, is more likely to have MuSK antibodies. SIGNIFICANCE: A progressive decrement in patients otherwise felt to have MG should prompt further clinical, serological and electrodiagnostic tests. Further studies are needed to assess the decremental pattern in MuSK MG.

Assessment of plasma concentrations and potential adverse effects of doxycycline in cockatiels (Nymphicus hollandicus) fed a medicated pelleted diet.

Doxycycline hyclate was mixed with soybean oil and then added to a low-fat pelleted diet that contained approximately 2.4% fat, which produced a final diet that contained a calculated 6.4% fat and 300 mg doxycycline per kilogram of diet. The medicated diet was fed to 9 healthy adult cockatiels (Nymphicus hollandicus) for 47 days; a control group of 6 birds received the identical diet without doxycycline. Trough doxycycline plasma concentrations were measured 7 times during treatment and ranged from 0.98 to 3.83 microg/mL with an overall median of 2.09 microg/ mL. The birds were observed daily, weighed, and examined at least weekly, and selected plasma biochemical parameters were measured before treatment and at days 21 and 42. No adverse effects were noted, except one treatment bird became obese. This medicated diet may be suitable for treating spiral bacteria and Chlamydophila psittaci infections in cockatiels that will consume a pelleted diet.

Identifying host pathogenic pathways in bovine digital dermatitis by RNA-Seq analysis.

Digital dermatitis is a painful foot disease compromising welfare in dairy cattle. The disease has a complex multibacterial aetiology, but little is known about its pathogenesis. In this study, gene expression in skin biopsies from five bovine digital dermatitis lesions and five healthy bovine feet was compared using RNA-Seq technology. Differential gene expression was determined after mapping transcripts to the Btau 4.0 genome. Pathway analysis identified gene networks involving differentially expressed transcripts. Bovine digital dermatitis lesions had increased expression of mRNA for α2-macroglobulin-like 1, a protein potentially involved in bacterial immune evasion and bacterial survival. There was increased expression of keratin 6A and interleukin 1ß mRNA in bovine digital dermatitis lesions, but reduced expression of most other keratin and keratin-associated genes. There was little evidence of local immune reactions to the bacterial infection present in lesions.

Selection for axillary clearance in breast cancer (ultrasound negative, sentinel node positive patients have low rates of further metastases).

BACKGROUND: The aim of this study was to determine whether we could identify a subset of axillary clearance patients in whom the procedure yielded negative nodes and was therefore of no therapeutic benefit. METHODS: Over a three year period 138 patients underwent axillary clearance at our unit. The axillae of all patients were assessed preoperatively with clinical examination, ultrasound (USS) and FNAC if suspicious nodes identified. Patients with clinically malignant nodes or positive FNAC underwent axillary node clearance where appropriate, whilst completion axillary node clearance was performed in those who had no preoperative evidence of metastatic axillary disease but positive sentinel node biopsy (SNB)/axillary node sample (ANS). RESULTS: Of the 138 patients, the indications for axillary clearance were positive FNAC or clinically malignant nodes in 89 and positive SNB/ANS in the remaining 49. Patients with preoperative evidence of axillary metastases had significantly more positive nodes compared to those who underwent SNB and completion ANC 4.6 vs. 3.1 p = 0.037. Of the patients with ultrasonographically normal axillae but positive SNB, 8.7% had further nodal metastases at completion ANC. This was significantly less than in those with abnormal USS (negative FNAC) and positive SNB (41.7%); p = 0.033. CONCLUSIONS: Preoperative ultrasound in conjunction with FNAC and clinical judgement identifies most patients with positive axillary nodes and such patients have more widespread disease. The additional value of completion axillary ANC in patients with ultrasonographically normal axillae but positive SNB appears small as sentinel node 'biopsy' serves to clear the axilla of metastases in most of these patients.

Effects of freshwater housing and fluid types on aquatic bird serum electrolyte concentrations.

Recent seabird mass morbidity events have highlighted the need to elucidate the effects of freshwater and hypertonic saline use for fluid therapy and housing in captive aquatic birds. Serum electrolyte concentrations of northern fulmars (Fulmarus glacialis; n = 9), western grebes (Aechmophorus occidentalis; n = 6), and common murres (Uria aalge; n = 25) housed on freshwater while undergoing rehabilitation at the San Francisco Bay Oiled Wildlife Care and Education Center in Fairfield, California, were compared to reference intervals from free-ranging populations. Additionally, northern fulmars were given intermittent oral boluses of hypertonic saline. In birds housed on freshwater, there were significant decreases in serum sodium and chloride, with 44% of northern fulmars and 72% of common murres falling below the established reference interval. All of the western grebes were able to maintain serum sodium and chloride within the reference intervals. The significance of these findings reflect the behavior and natural history of the species studied. The physiologic regulation of salt by the salt glands, gastrointestinal tract, and renal systems of seabirds, along with their behavior and natural history, should be considered when working with these birds in a rehabilitation or captive setting. Salt supplementation is necessary for some species of seabirds. Monitoring of serum electrolytes should be used for individual animals or salt supplementation should be considered in holopelagic species.

Molecular sub-typing suggests that the environment of rehabilitation centers may be a potential source of Aspergillus fumigatus infecting rehabilitating seabirds.

Aspergillosis remains a major cause of infection-related avian mortality in birds that are debilitated and undergoing rehabilitation for release into the wild. This study was designed to understand the source of avian aspergillosis in seabirds undergoing rehabilitation at selected northern California aquatic bird rehabilitation centers. Air, surface and water sampling was performed between August 2007 and July 2008 in three such centers and selected natural seabird loafing sites. Average air Aspergillus fumigatus counts were at least nine times higher in samples obtained from the rehabilitation sites (M = 7.34, SD = 9.78 CFU/m(3)), when compared to those found at natural sites (M = 0.76, SD = 2.24 CFU/m(3)), t (205) = -5.99, P < 0.001. A total of 37 A. fumigatus isolates from birds with confirmed aspergillosis and 42 isolates from environmental samples were identified using both morphological and molecular methods, and subsequently sub-typed using an eight-locus microsatellite panel with the neighbor joining algorithm. Results of the study demonstrated the presence of five clonal groups, 13 genotypically related clusters, and 59 distinct genotypes. Six of the 13 genotypically related clusters contained matching genotypes between clinical isolates and local environmental isolates from the rehabilitation center in which these birds were housed. We present evidence that the environment of rehabilitation centers may be a source for A. fumigatus infection in rehabilitated seabirds.

Short-term survival and effects of transmitter implantation into western grebes using a modified surgical procedure.

Two pilot trials and one study in a closely related grebe species suggest that Western grebes (Aechmophorus occidentalis) will not tolerate intracoelomic transmitter implantation with percutaneous antennae and often die within days of surgery. Wild Western grebes (n = 21) were captured to evaluate a modified surgical technique. Seven birds were surgically implanted with intracoelomic transmitters with percutaneous antennae by using the modified technique (transmitter group), 7 received the same surgery without transmitter implantation (celiotomy group), and 7 served as controls (only undergoing anesthesia). Modifications included laterally offsetting the body wall incision from the skin incision, application of absorbable cyanoacrylate tissue glue to the subcutaneous space between the body wall and skin incisions, application of a waterproof sealant to the skin incision after suture closure, and application of a piece of porcine small intestine submucosa to the antenna egress. Survival did not differ among the 3 groups with 7 of 7 control, 6 of 7 celiotomy, and 6 of 7 transmitter birds surviving the 9-day study. Experimental birds were euthanized at the end of the study, and postmortem findings indicated normal healing. Significant differences in plasma chemistry or immune function were not detected among the 3 groups, and only minor differences were detected in red blood cell indices and plasma proteins. After surgery, the birds in the transmitter group spent more time preening tail feathers than those in the control and celiotomy groups. These results demonstrate that, in a captive situation, celiotomy and intracoelomic transmitter implantation caused minimal detectable homeostatic disturbance in this species and that Western grebes can survive implantation of intracoelomic transmitters with percutaneous antennae. It remains to be determined what potential this modified surgical procedure has to improve postoperative survival of Western grebes that are intracelomically implanted with transmitters with percutaneous antennae and released into the wild.

Trends in American Board of Psychiatry and Neurology specialties and neurologic subspecialties.

OBJECTIVE: To review the current status and recent trends in the American Board of Psychiatry and Neurology (ABPN) specialties and neurologic subspecialties and discuss the implications of those trends for subspecialty viability. METHODS: Data on numbers of residency and fellowship programs and graduates and ABPN certification candidates and diplomates were drawn from several sources, including ABPN records, Web sites of the Accreditation Council for Graduate Medical Education and the American Medical Association, and the annual medical education issues of the Journal of the American Medical Association. RESULTS: About four-fifths of neurology graduates pursue fellowship training. While most recent neurology and child neurology graduates attempt to become certified by the ABPN, many clinical neurophysiologists elect not to do so. There appears to have been little interest in establishing fellowships in neurodevelopmental disabilities. The pass rate for fellowship graduates is equivalent to that for the "grandfathers" in clinical neurophysiology. Lower percentages of clinical neurophysiologists than specialists participate in maintenance of certification, and maintenance of certification pass rates are high. CONCLUSION: The initial enthusiastic interest in training and certification in some of the ABPN neurologic subspecialties appears to have slowed, and the long-term viability of those subspecialties will depend upon the answers to a number of complicated social, economic, and political questions in the new health care era.