Transverse sectioning in the evaluation of skin biopsy specimens from alopecic dogs.

OBJECTIVES: Transverse sectioning of skin biopsy specimens has revolutionised assessment of human alopecia by demonstration of every hair in each specimen, allowing quantitative evaluation of follicular activity. Since only vertical sectioning is performed routinely in veterinary laboratories, we aimed to determine whether transverse sectioning was a valuable technique in assessment of canine alopecia. METHODS: Paired vertical and transverse sections of biopsy specimens from 31 alopecic dogs were examined independently in triplicate in random order and blinded to previous diagnosis using a standard check-list proforma. Assessments of key features (follicular activity [anagen/telogen], infundibular hyperkeratosis, sebaceous gland abnormalities, pigment clumping, dermal inflammation) by each sectioning method were compared. RESULTS: In the 31 cases, (atrophic [n = 13], dysplastic [n = 12], inflammatory diseases [n = 6]), follicular inactivity scores (median, [lower-upper quartile]) in transverse sections significantly exceeded those in vertical sections (transverse 4 [3-5], vertical 3 [2-4]). Agreement between the two sectioning planes was moderate for infundibular hyperkeratosis (kappa = 0.5210) and dermal inflammation (0.4351), fair for sebaceous gland abnormalities (0.3966) and pigment clumping (0.2197), but slight for follicular activity (0.1041). Vertical sectioning demonstrated diagnostically important epidermal pathology (n = 2) and dermal thinning (n = 3) whereas transverse sectioning enhanced assessment of hair growth phase (n = 11), follicular structure and architecture (n = 11), and focal luminal or mural folliculitides (n = 3). CLINICAL SIGNIFICANCE: Transverse sectioning confers significant benefits and complements traditional vertical sectioning in the histological assessment of canine hair follicle diseases, particularly when subtle abnormalities comprise distorted compound follicle architecture, hair cycle arrest or when relatively few adnexal structures are affected.

High-throughput analysis suggests differences in journal false discovery rate by subject area and impact factor but not open access status.

BACKGROUND: A low replication rate has been reported in some scientific areas motivating the creation of resource intensive collaborations to estimate the replication rate by repeating individual studies. The substantial resources required by these projects limits the number of studies that can be repeated and consequently the generalizability of the findings. We extend the use of a method from Jager and Leek to estimate the false discovery rate for 94 journals over a 5-year period using p values from over 30,000 abstracts enabling the study of how the false discovery rate varies by journal characteristics. RESULTS: We find that the empirical false discovery rate is higher for cancer versus general medicine journals (p = 9.801E-07, 95% CI: 0.045, 0.097; adjusted mean false discovery rate cancer = 0.264 vs. general medicine = 0.194). We also find that false discovery rate is negatively associated with log journal impact factor. A two-fold decrease in journal impact factor is associated with an average increase of 0.020 in FDR (p = 2.545E-04). Conversely, we find no statistically significant evidence of a higher false discovery rate, on average, for Open Access versus closed access journals (p = 0.320, 95% CI - 0.015, 0.046, adjusted mean false discovery rate Open Access = 0.241 vs. closed access = 0.225). CONCLUSIONS: Our results identify areas of research that may need additional scrutiny and support to facilitate replicable science. Given our publicly available R code and data, others can complete a broad assessment of the empirical false discovery rate across other subject areas and characteristics of published research.

Juvenile-onset and adult-onset demodicosis in dogs in the UK: prevalence and breed associations.

OBJECTIVES: To explore epidemiological features of demodicosis relevant to UK veterinary general practitioners. Breed risk factors were proposed as distinct between juvenile-onset and adult-onset disease. MATERIALS AND METHODS: The study used anonymised clinical data on dogs under primary veterinary care at practices enrolled in the UK VetCompass Programme. Case inclusion required recording of a final demodicosis diagnosis for a dermatological condition that was present during the 2013 study period. Risk factor analysis used multivariable logistic regression modelling. RESULTS: In dogs aged <2 years (juvenile-onset), the 1-year period prevalence was 0.48% (95% confidence interval: 0.45 to 0.52). Compared with crossbred dogs, seven breeds showed increased odds of diagnosis with demodex: British bulldog, Staffordshire bull terrier, Chinese shar-pei, dogue de Bordeaux, pug, French bulldog and boxer. Additionally, six breeds showed reduced odds of juvenile demodicosis: Lhasa apso, bichon frise, Labrador retriever, German shepherd dog, shih-tzu and Chihuahua. In dogs aged >4 years (adult-onset), the 1-year period prevalence was 0.05% (95% confidence interval: 0.0.04 to 0.06). Six breeds showed increased odds of demodicosis compared with crossbred dogs: Chinese shar-pei, shih-tzu, West Highland white terrier, pug, boxer and Border terrier. CLINICAL SIGNIFICANCE: Juvenile-onset demodicosis is much more common (about 10 times higher) than the adult-onset form. Knowledge of the predisposed breeds for these two presentations can assist with diagnosis and support the concept of distinct aetiopathogenetic phenotypes.

The impact of airborne pollution on atopic dermatitis: a literature review.

The increasing prevalence of atopic dermatitis (AD) parallels a global rise in industrialization and urban living over recent decades. This shift in lifestyle is accompanied by greater cutaneous exposure to environmental pollutants during the course of daily activities. The objectives of this review are to highlight the effects of airborne pollution on epidermal barrier function, examine evidence on the relationship between pollutants and AD, synthesize a proposed mechanism for pollution-induced exacerbation of AD, and identify potential methods for the reduction and prevention of pollutant-induced skin damage. The literature review was done by searching the PubMed, Embase and Google Scholar databases. Inclusion criteria were in vitro and animal studies, clinical trials and case series. Non-English-language publications, review articles and case reports were excluded. Pollutants induce cutaneous oxidative stress and have been shown to damage skin barrier integrity by altering transepidermal water loss, inflammatory signalling, stratum corneum pH and the skin microbiome. AD represents a state of inherent barrier dysfunction, and both long- and short-term pollutant exposure have been linked to exacerbation of AD symptoms and increased AD rates in population studies. Airborne pollutants have a detrimental effect on skin barrier integrity and AD symptoms, and appear to pose a multifaceted threat in AD through several parallel mechanisms, including oxidative damage, barrier dysfunction, immune stimulation and propagation of the itch-scratch cycle. Future research is needed to elucidate specific mechanisms of pollution-induced epidermal barrier dysfunction and to identify efficacious methods of skin barrier repair and protection against pollutant-driven damage.

Correction: Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Correction for 'Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions' by J. A. Perlinger et al., Environ. Sci.: Processes Impacts, 2018, 20, 195-209.

Prognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer.

BACKGROUND: Despite rising incidence rates of colorectal malignancies, only a few prognostic tools have been implemented in proven clinical routine. Cell division and proliferation play a significant role in malignancies. In terms of colorectal cancer, the impact of proliferation associated proteins is controversially debated. The aim of our study was to examine the expression of topoisomerase II α and minichromosome maintenance protein 6 and to correlate these findings with the clinical data. METHODS: Tissue samples of 619 patients in total were stained using the antibodies Ki-S4 and Ki-MCM6 targeting topoisomerase II α as well as minichromosome maintenance protein 6. The median rate of proliferation was correlated with clinical and follow up data. RESULTS: The expression rate of minichromosome maintenance protein 6 is significantly higher than the proportion of topoisomerase II α in tumour cells (p < 0.001). A high expression of both proteins coincides with a beneficial outcome for the patient, indicating a favourable prognostic marker (p < 0.001 and p = 0.008). CONCLUSIONS: We have demonstrated that high expression rates of proliferative markers is linked to a beneficial patient outcome. According to the general opinion, a high expression rate correlates with a poor patient outcome. In this study, we were able to refute this assertion.

Responses of deposition and bioaccumulation in the Great Lakes region to policy and other large-scale drivers of mercury emissions.

Mercury (Hg) emissions pose a global problem that requires global cooperation for a solution. However, neither emissions nor regulations are uniform world-wide, and hence the impacts of regulations are also likely to vary regionally. We report here an approach to model the effectiveness of regulations at different scales (local, regional, global) in reducing Hg deposition and fish Hg concentrations in the Laurentian Great Lakes (GL) region. The potential effects of global change on deposition are also modeled. We focus on one of the most vulnerable communities within the region, an Indigenous tribe in Michigan's Upper Peninsula (UP) with a high fish consumption rate. For the GL region, elements of global change (climate, biomass burning, land use) are projected to have modest impacts (<5% change from the year 2000) on Hg deposition. For this region, our estimate of the effects of elimination of anthropogenic emissions is a 70% decrease in deposition, while our minimal regulation scenario increases emissions by 35%. Existing policies have the potential to reduce deposition by 20% with most of the reduction attributable to U.S. policies. Local policies within the Great Lakes region show little effect, and global policy as embedded in the Minamata Convention is projected to decrease deposition by approximately 2.8%. Even within the GL region, effects of policy are not uniform; areas close to emission sources (Illinois, Indiana, Ohio, Pennsylvania) experience larger decreases in deposition than other areas including Michigan's UP. The UP landscape is highly sensitive to Hg deposition, with nearly 80% of lakes estimated to be impaired. Sensitivity to mercury is caused primarily by the region's abundant wetlands. None of the modeled policy scenarios are projected to reduce fish Hg concentrations to the target that would be safe for the local tribe. Regions like Michigan's UP that are highly sensitive to mercury deposition and that will see little reduction in deposition due to regulations require more aggressive policies to reduce emissions to achieve recovery. We highlight scientific uncertainties that continue to limit our ability to accurately predict fish Hg changes over time.

Fully robotic da Vinci Ivor-Lewis esophagectomy in four-arm technique-problems and solutions.

The aim of this technical note is a step-by-step description of a fully robotic abdominothoracic esophagectomy with an intrathoracic esophagogastrostomy. We report on our technique and short-term results of 75 patients undergoing an Ivor-Lewis esophagectomy using a fully robotic 4-arm approach in the abdominal and thoracic phase with a hand-sewn intrathoracic anastomosis. There are several important steps and differences to consider compared to the conventional minimal invasive approach (patient's positioning, anaesthesiological set up, port placement, gastric conduit pull up, technique of esophagostrostomy). Mean operative time was 392 minutes (240-610) with a 94% R0 resection status. Conversion to open procedure occurred in 2 (2.6%) in the abdominal, and 14 (18.2%) in the thoracic phase. Main reasons for conversion were problems during the lifting of the gastric conduit and difficulties in the construction of the esophagogastrostomy. The rate dropped during the last 20 patients (1/20 (10%). Our results suggest that the reported technique is safe and feasible. It satisfies the oncological principles and provides the advantages of robotic assisted minimal invasive surgery.

Clinical and pathological features of hair coat abnormalities in curly coated retrievers from UK and Sweden.

OBJECTIVES: To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden. MATERIALS AND METHODS: Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology. Blood was collected for haematological, biochemical and endocrine assays. RESULTS: Of 90 dogs surveyed, 39 had current or previous episodes of symmetrical, non-pruritic alopecia and or frizzy coat changes, usually affecting caudal thighs, axillae, dorsum and neck before 18 months of age; 23 dogs had a waxing/waning course. Examined dogs generally matched the pattern described in questionnaires. Hair shaft anomalies comprised occasional distorted anagen bulbs (10 dogs) and transverse fractures (8 dogs). Vertical histopathological sections showed infundibular hyperkeratosis (28 of 30 sections) and low-grade pigment clumping (17 of 30). Subtle telogenisation of hair follicles was unequivocally confirmed by transverse histomorphometric analyses. CLINICAL SIGNIFICANCE: The follicular dysplasia of curly coated retriever reported here is similar to that of Irish water spaniels and Chesapeake Bay retrievers but distinct from that of Portuguese water dogs. The genetic basis requires further assessment.

Hope thinking and past trauma mediate the relationships of body mass index with perceived mental health treatment need and mental health treatment use.

UNLABELLED: Greater body mass is associated with a greater risk of mental health conditions and more frequent mental health treatment use. However, factors that might influence perceived mental health treatment need and mental health treatment use among those of greater weight, including hope thinking, trauma history and perceived mental health treatment stigma, are not well understood. OBJECTIVE: The objective of this study was to determine if hope thinking, trauma history and/or perceived mental health treatment stigma mediate the relationships of body mass index [BMI] with perceived mental health treatment need and mental health treatment use. METHOD: Primary care clinic patients in the Midwest United States (N = 196; BMI range = 18.5 to 47.0, mean = 29.26 ± 6.61, median = 27.90) were recruited to complete a battery of self-report measures that assessed perceived mental health treatment need, mental health treatment use, hope thinking (Trait Hope Scale), trauma history (a single-item traumatic event history screen from the posttraumatic stress disorder module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), and perceived mental health treatment stigma (Stigma Scale for Receiving Psychological Help). RESULTS: Reduced hope thinking and a greater incidence of past trauma accounted for greater perceived mental health treatment need and greater mental health treatment use among those of greater BMI. BMI was not related to perceived unmet mental health treatment need. CONCLUSION: Increased perceived mental health treatment need and mental health treatment use among those of greater BMI may be explained by lower hope thinking and a greater incidence of trauma in this population. Heavier patients may benefit from interventions designed to augment hope and address traumatic histories.

Ciclosporin modulates the responses of canine progenitor epidermal keratinocytes (CPEK) to toll-like receptor agonists.

Toll-like receptor (TLR) 2 dependent pathways have an important role in the antimicrobial defense of human keratinocytes, and various factors and compounds have been shown to affect those pathways. Investigating Toll-like receptor function in canine keratinocytes and the potential for their modulation is of similar relevance in dogs due to the frequency of staphylococcal skin infections in this species, particularly in the context of canine atopic dermatitis. This pilot study hypothesized that ciclosporin would have a modulatory effect on the cytokine and TLR mRNA expression of canine progenitor epidermal keratinocytes in response to TLR2 agonists. No detectable up-regulation of TLR2, TLR4, IL-8 and TNF-α mRNA was detected following exposure to FSL-1, Pam3CSK4 and staphylococcal peptidoglycan (PGN). Ciclosporin alone did not alter the expression levels of these transcripts but in the presence of ciclosporin, TNF-α mRNA expression was upregulated in response to all three agonists and both TNF-α and IL-8 transcript abundance was increased in response to Pam3CSK4. The enhanced responsiveness of canine keratinocytes to TLR2 agonists in response to ciclosporin may imply that administration of this drug might enhance the innate immune barrier of skin.

Primary care veterinary usage of systemic glucocorticoids in cats and dogs in three UK practices.

OBJECTIVES: To describe systemic glucocorticoid usage in cats and dogs by three primary care -veterinary practices in England and to ascertain risk factors for clinical use. To evaluate consistency of prescribing patterns across clinics. To validate a merged database of primary veterinary clinical data as a functional tool for clinical epidemiological research. METHODS: A merged database was established from clinical data on 31,273 cat and dog consultations with pharmacotherapy from three veterinary practices in England. Descriptive statistics described systemic glucocorticoid drug use in cats and dogs while mixed-effects logistic regression modelling evaluated risk factors. Individual clinic usage was compared. RESULTS: Overall, 1877 (16·68%) cat consultations and 2913 (14·55%) dog consultations resulted in systemic glucocorticoid therapy. Cats received higher parenteral (P<0·0001) and oral (P<0·0001) dose levels than dogs. Pathophysiological indication, age, skin condition, sex and clinic attended were significant risk factors for glucocorticoid prescription. Clinics varied widely in their odds of systemic glucocorticoid usage (P<0·0001). CLINICAL SIGNIFICANCE: An evidence base for systemic glucocorticoid prescribing by primary care small animal practices in England is provided. Clinic attended was a significant risk factor, indicating wide variation in prescribing patterns between clinics. A merged primary care veterinary clinical database was effective for epidemiological research.

Evaluation of mucosal bacteria and histopathology, clinical disease activity and expression of Toll-like receptors in German shepherd dogs with chronic enteropathies.

The pathogenesis of chronic enteropathies in dogs likely involves an interaction between the intestinal immune system and luminal intestinal bacteria. German shepherd dogs (GSD) are particularly predisposed to chronic enteropathies. The present study sought to evaluate expression patterns of certain pattern recognition receptors of the innate immunity (Toll-like receptors, TLR), clinical disease activity and histopathological severity in GSD with chronic enteropathies. Mucosal biopsies were collected from the duodenum, colon and ileum of 13 affected GSD and 10 healthy greyhounds as controls. Dogs were objectively assessed using published scoring systems for clinical and histological severity of disease. Diversity of the duodenal microbiota was assessed by construction of 16S rRNA gene libraries. Expression of TLR2, TLR4, TLR5 and TLR9 in biopsies of the duodenum, ileum and colon was assessed by quantitative real-time PCR. TLR4 expression was increased in all intestinal segments in GSD, however, TLR5 expression was very low compared to the healthy dogs. The microbiota in the duodenum of GSDs was significantly different to that of the greyhounds, with an over-representation of 16S rRNA gene sequences belonging to the classes of Bacilli, and Erysipelotrichi, and to the orders of Lactobacillales, Actinomycetales and Erysipelotrichales. These findings could point to a distinct pathogenesis of chronic enteropathies in GSD, with differentially high and low expression of TLR4 and TLR5, respectively, and increased proportions of specific members of the Lactobacillales potentially playing a role.

Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study.

BACKGROUND: Microtubule-associated protein tau (MAPT) has been associated with several neurodegenerative disorders including forms of parkinsonism and Parkinson disease (PD). We evaluated the association of the MAPT region with PD in a large cohort of familial PD cases recruited by the GenePD Study. In addition, postmortem brain samples from patients with PD and neurologically normal controls were used to evaluate whether the expression of the 3-repeat and 4-repeat isoforms of MAPT, and neighboring genes Saitohin (STH) and KIAA1267, are altered in PD cerebellum. METHODS: Twenty-one single-nucleotide polymorphisms (SNPs) in the region of MAPT on chromosome 17q21 were genotyped in the GenePD Study. Single SNPs and haplotypes, including the H1 haplotype, were evaluated for association to PD. Relative quantification of gene expression was performed using real-time RT-PCR. RESULTS: After adjusting for multiple comparisons, SNP rs1800547 was significantly associated with PD affection. While the H1 haplotype was associated with a significantly increased risk for PD, a novel H1 subhaplotype was identified that predicted a greater increased risk for PD. The expression of 4-repeat MAPT, STH, and KIAA1267 was significantly increased in PD brains relative to controls. No difference in expression was observed for 3-repeat MAPT. CONCLUSIONS: This study supports a role for MAPT in the pathogenesis of familial and idiopathic Parkinson disease (PD). Interestingly, the results of the gene expression studies suggest that other genes in the vicinity of MAPT, specifically STH and KIAA1267, may also have a role in PD and suggest complex effects for the genes in this region on PD risk.

The relative health related quality of life of veterans with Parkinson's disease.

OBJECTIVES: To use databases of the US Veterans Health Administration (VHA) to describe the impact of Parkinson's disease on health related quality of life (HRQoL) of veterans; to compare the HRQoL of veterans with Parkinson's disease with that of veterans reporting eight other neurological or chronic conditions; and to estimate the unique effect of Parkinson's disease on HRQoL. METHODS: Respondents to the VHA 1999 large national health survey of veteran enrollees with a diagnosis of Parkinson's disease in VHA treatment files for the fiscal years 1997-1999 were identified by merging databases. The survey incorporated the Veterans SF-36, a well validated generic measure of HRQoL and functional status. This was used to compare patient groups. Mean physical (PCS) and mental (MCS) component summary scores were calculated for Parkinson's disease and eight other diseases by multivariable regressions that adjusted for age, sex, race, education, and 15 mental and physical co-morbid conditions that were self reported in the survey. RESULTS: Of 887 775 survey respondents, 14 530 (1.64%) had a Parkinson's disease diagnosis. Controlling for sociodemographic factors and co-morbidities, veterans with Parkinson's disease had PCS and MCS below veterans with angina/coronary heart disease, arthritis, chronic low back pain, congestive heart failure, diabetes, and stroke. Veterans with spinal cord injury reported slightly lower PCS than veterans with Parkinson's disease (32.38 v 32.72; 0.03 of 1 SD). Veterans with depression reported markedly lower MCS than veterans with Parkinson's disease (35.94 v 41.48; 0.55 of 1 SD). The unique effect of having Parkinson's disease on HRQoL was to lower PCS and MCS by 4.10 and 3.42 points (0.41 and 0.34 of 1 SD), respectively. CONCLUSIONS: The analysis quantifies the negative impact of Parkinson's disease on HRQoL, after controlling for sociodemographic factors and co-morbidities. Compared with eight other chronic conditions, Parkinson's disease imposes a relatively heavy burden on US veterans in the VHA health care system.