A molecular assessment of Ostertagia leptospicularis and Spiculopteragia asymmetrica among wild fallow deer in Northern Ireland and implications for false detection of livestock-associated species.

BACKGROUND: Wild deer populations utilizing livestock grazing areas risk cross-species transmission of gastrointestinal nematode parasites (GINs), including GINs with anthelmintic resistance (AR) traits. Wild deer have been shown to carry problematic GIN species such as Haemonchus contortus and Trichostrongylus species in the UK, but the presence of livestock GINs in Northern Ireland deer populations is unknown. Also, is it not known whether AR traits exist among GINs of deer such as Ostertagia leptospicularis and Spiculopteragia asymmetrica in pastureland where anthelmintics are heavily used. METHODS: Adult-stage GIN samples were retrieved from Northern Irish wild fallow deer abomasa. Individual specimens were subject to a species-specific PCR analysis for common sheep and cattle GIN species with ITS-2 sequence analysis to validate species identities. In addition, the beta-tubulin gene was subject to sequencing to identify benzimidazole (BZ) resistance markers. RESULTS: ITS-2 sequencing revealed O. leptospicularis and S. asymmetrica, but species-specific PCR yielded false-positive hits for H. contortus, Teladorsagia circimcincta, Trichostrongylus axei, T. colubriformis, T. vitrinus and Ostertagia ostertagi. For beta-tubulin, O. leptospicularis and S. asymmetrica yielded species-specific sequences at the E198 codon, but no resistance markers were identified in either species at positions 167, 198 or 200 of the coding region. DISCUSSION: From this report, no GIN species of significance in livestock were identified among Northern Ireland fallow deer. However, false-positive PCR hits for sheep and cattle-associated GINs is concerning as the presence of deer species in livestock areas could impact both deer and livestock diagnostics and lead to overestimation of both GIN burden in deer and the role as of deer as drivers of these pathogens. ITS-2 sequences from both O. leptospicularis and S. asymmetrica show minor sequence variations to geographically distinct isolates. AR has been noted among GINs of deer but molecular analyses are lacking for GINs of wildlife. In producing the first beta-tubulin sequences for both O. leptospicularis and S. asymmetrica, we report no BZ resistance in this cohort. CONCLUSIONS: This work contributes to genetic resources for wildlife species and considers the implications of such species when performing livestock GIN diagnostics.

Understanding the role of wild ruminants in anthelmintic resistance in livestock.

Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the conditions under which wild ruminants can act as a source of helminths (including anthelmintic-resistant genotypes) for domestic ruminants, and vice versa, with the added possibility that wildlife could act as refugia for drug-susceptible genotypes and hence buffer the spread and development of resistance. Helminth infections cause significant productivity losses in domestic ruminants and a growing resistance to all classes of anthelmintic drug escalates concerns around helminth infection in the livestock industry. Previous research demonstrates that drug-resistant strains of the pathogenic nematode Haemonchus contortus can be transmitted between wild and domestic ruminants, and that gastro-intestinal nematode infections are more intense in wild ruminants within areas of high livestock density. In this article, the factors likely to influence the role of wild ruminants in helminth infections and anthelmintic resistance in livestock are considered, including host population movement across heterogeneous landscapes, and the effects of climate and environment on parasite dynamics. Methods of predicting and validating suspected drivers of helminth transmission in this context are considered based on advances in predictive modelling and molecular tools.

Role, Extent, and Impact of Comorbidity on Prognosis and Survival in Advanced Metastatic Melanoma: A Review.

Increased incidence of comorbidity in advanced metastatic melanoma (AMM) is emerging as an important factor in patient prognosis, treatment, and survival. This paper reviews the impact of comorbidities on the prognosis and survival outcomes of patients diagnosed with AMM. Our search initially yielded limited results. We then broadened our search to include breast, colorectal, and prostate cancer and covered malignancies in which screening (like melanoma) is associated with the detection of early-stage disease. Most studies showed that a higher prevalence of comorbidity was associated with more advanced cancer stage. Both treatment and survival of patients were influenced by age and the extent of comorbidity. Racial differences in survival were greatest for patients with no comorbidities and less evident at higher levels of comorbidity. Comorbid conditions showed differential effects for prognosis, treatment, and survival. Limited Information in the literature demonstrates that more research is warranted with respect to comorbidities and AMM.

Successful treatment of obesity and insulin resistance via ketogenic diet status post Roux-en-Y.

This is a single case of a 65-year-old American woman who presented with substantial weight gain and insulin resistance (IR) post-Roux-en-Y gastric bypass (RYGB) surgery. Before RYGB, she had reached 340 lbs (155 kg) and a body mass index (BMI) of 56.6 kg/m2 The surgery resulted in a 70 lbs (32 kg) weight loss, bringing her BMI, per cent total weight loss (%TWL) and per cent excess weight loss (%EWL) to 44.9 kg/m2, 20.6% and 36.8%, respectively. Unfortunately, her BMI would return to 53.6 kg/m2, nearly her pre-RYGB BMI. It was then she sought the guidance of a primary care physician with expertise in nutrition and medical management of obesity, who placed her on a ketogenic diet. One year later, she had lost 102 lbs (46.4 kg), resulting in a BMI, %TWL and %EWL of 36.6 kg/m2, 31.7%, and 63.1%, respectively, also further resulting in significant improvements of her inflammatory biomarkers. This case presentation will explore current literature, covering the effects of obesity on IR, pre-diabetes and other disease-provoking inflammatory biomarkers.

Previously misdiagnosed linear IgA dermatosis resolved with dapsone.

This is the case of a 25-year-old African American woman with a 3-week history of itching with burning, blistering lesions on her torso and extremities. Medical history was unremarkable. Medical treatments included three visits to urgent care, where she was treated with antivirals, oral and topical steroids, antibiotics and antifungals unsuccessfully. We performed a skin biopsy, and immunoflorescent studies revealed a linear deposition of IgA antigen at the basement membrane. The clinical diagnosis of linear IgA dermatosis (LAD) was established, with no eliciting cause, other than potential occupational exposure to Chlamydophila psittaci via her employment in a pet store. This is the first case to our knowledge to report such an association. However, confirmation of the exposure would only establish correlation, not causality. Resolution of symptoms and blisters was achieved with dapsone treatment. Accordingly, we highlight the crucial importance of reviewing exposures, along with the potential aetiology of LAD.

Atypical Presentation of Infective Endocarditis: A Case Report.

The American Heart Association defines Infective Endocarditis (IE) or bacterial endocarditis as an infection caused by bacteria that enter the bloodstream and settle in the heart lining, heart valve, or blood vessel [1]. IE is considered the fourth most common life-threatening infection syndrome after sepsis, pneumonia, and intra-abdominal abscess. In 2010, IE was associated with 1.58 million disability-adjusted life years, or years of healthy life lost, as a result of death and nonfatal illness and impairment [2,3]. The variability in clinical presentation of IE and the importance of early diagnosis require a diagnostic strategy that is prompt for disease detection and specific for its exclusion across all forms of the disease [2].

Oral Versus Topical Diclofenac Sodium in the Treatment of Osteoarthritis.

Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.

Exome sequencing a review of new strategies for rare genomic disease research.

The journey related to genomic information access and utilization by researchers and clinicians has barely begun to be travelled. There remains a broad horizon in the research and clinical arenas for fulfillment of that journey. Exciting is the potential depth and breadth of research, clinical applications, and more personalized medicine, that remain on the horizon. Exome sequencing has clarified the responsibilities of over 130 genes, greatly expanding the medical genetics database and enabling the development of orphan disease-based pharmaceuticals. Our research focus was to review >50 literature sources that related to rare genomic disease research and exome sequencing, as well as the new research and diagnostic strategies that were utilized. Using a systems approach, under discussion are ciliopathy, dermatology, otorhinolaryngology, immunology, gastroenterology, hematopoiesis, metabolic diseases, and the cardiovascular system. Also discussed are genetic, syndromic, and mitochondrial exome research. Recommendations for future research will also be discussed.