Establishment and characterization of oviductal organoids from farm and companion animals†.

Organoid technology has provided a unique opportunity to study early human development and decipher various steps involved in the pathogenesis of disease. The technology is already used in clinics to improve human patient outcomes. However, limited knowledge of the methodologies required to establish organoid culture systems in domestic animals has slowed the advancement and application of organoid technology in veterinary medicine. This is particularly true for the field of reproduction and the application of assisted reproductive technologies (ART). Here, we have developed a platform to grow oviductal organoids from five domestic species-bovine, porcine, equine, feline, and canine. The organoids were grown progressively from single cells derived from the enzymatic digestion of freshly collected infundibular/fimbrial samples. The addition of WNT, TGFß, BMP, ROCK, and Notch signaling pathway activators or inhibitors to the organoid culture medium suggested remarkable conservation of the molecular signals involved in oviductal epithelial development and differentiation across species. The gross morphology of organoids from all the domestic species was initially similar. However, some differences in size, complexity, and growth rate were subsequently observed and described. After 21 days, well-defined and synchronized motile ciliated cells were observed in organoids. Histopathologically, oviductal organoids mimicked their respective native tissue. In summary, we have carried out a detailed cross-species comparison of oviductal organoids, which would be valuable in advancing our knowledge of oviduct physiology and, potentially, help in increasing the success of ART.

Conception and early pregnancy in the mare: lipidomics the unexplored frontier.

Lipids are dynamic biological molecules that play key roles in metabolism, inflammation, cell signalling and structure. They are biologically significant in the physiology of conception and reproduction. Many of the mechanisms surrounding equine conception and the early feto-maternal dialogue are yet to be understood at a biochemical level. Recently, lipidomic technologies have advanced considerably and analytical strategies have been enhanced and diversified. Consequently, in-depth lipidomic exploration now has the potential to reveal new lipid biomarkers and biochemical relationships that improve our understanding of the processes leading to efficient and successful reproduction. This review considers the role of lipids in conception and establishment of pregnancy, providing new insights into the enigmatic pathways governing early reproductive physiology of the mare. Lay summary: This paper discusses the role that lipids play in the very early stages of pregnancy in the mare. Lipids are microscopic non-soluble molecules that are important components of living cells. The manuscript discusses how lipids influence the reproductive cycle of mares, including ovulation and the detailed biological process of becoming pregnant. It explains how lipids are identified in a laboratory setting with a newly developing technology known as 'lipodomics'. The technology may lead to a more detailed understanding of how mares become pregnant. The focus of the paper is on mare reproduction, but it also draws on similarities with reproduction in other mammals. Remarkably there are gaps in much of our knowledge about the finer details of pregnancy in the horse, and the paper summarises what we already know about lipids, highlighting areas for further research.

Nicotinic acid supplementation at a supraphysiological dose increases the bioavailability of NAD+ precursors in mares.

NAD+ deficiency has recently been linked with increased occurrences of congenital abnormalities and embryonic death in human and animal subjects. Early embryonic death is a major component of pregnancy loss in mares and very little is known regarding the requirement for NAD+ in horses. The aim of this study was to quantify NAD+ and its metabolites in the plasma and urine of mares after orally administering an acute dose of nicotinic acid and determine the absorption, metabolism and excretion of this essential precursor for NAD+ biosynthesis. Nicotinic acid (5 g per os) was administered to four mares via a dosing syringe. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6 and 22 h, and urine samples were collected at 0, 3, 6 and 22 h. The samples were processed and analysed by mass spectrometry. A general additive model was applied to all metabolite concentration values followed by a post-hoc multiple comparisons test. Nicotinic acid was rapidly absorbed into peripheral blood within 15 min of administration and the concentrations of nicotinic acid, nicotinamide (NAM), nicotinuric acid, nicotinic acid mononucleotide and nicotinic acid adenine dinucleotide (NaAD) increased significantly in plasma at 30 min. The concentrations of NAM, nicotinic acid riboside and NaAD increased significantly in urine at 3 h. The levels of NAM and NaAD remained significantly elevated in plasma at 22 h, sixfold and ninefold greater, respectively, than the basal levels at 0 h. While the extracellular levels of NAD+ in the samples remained undetected, the large, sustained elevation of NaAD levels in plasma indicates that the NAD+ levels were boosted within the cellular compartments. The results show that nicotinic acid supplementation increases the bioavailability of NAD+ precursors in mares, which is proposed to be beneficial during periods of peak NAD+ demand, such as during early embryo development.

Pyrantel resistance in two herds of donkey in the UK.

Resistance to currently available anthelmintics is a serious phenomenon which is prevalent globally. Cyathostomins are one of the major parasites, and are of primary concern in donkeys. There have been reports of emerging resistance to pyrantel, but the status of pyrantel resistance in donkey populations in the UK is largely unknown. This report investigates pyrantel resistance in two geographically isolated donkey herds in the South West of England. The first herd had suspected pyrantel resistance, with already established resistance to other anthelmintics. In the second herd the efficacy of pyrantel was not suspected at the time the study took place. Faecal Egg Count Reduction Test (FECRT) was carried out, revealing large scale resistance. Eighty one percent of the first herd and 73% of the second herd had a FEC of less than 95% after treatment, and anthelmintic resistance was confirmed using the World Association for the Advancement of Veterinary Parasitology guidelines. These findings indicate that anthelmintic resistance to pyrantel exists in both tested donkey populations and illustrate the continuing development of resistance through different classes of chemotherapeutics.

Is HIV Painful? An Epidemiologic Study of the Prevalence and Risk Factors for Pain in HIV-infected Patients.

OBJECTIVES: To evaluate the prevalence, impact, and risk factors for pain among a cohort of human immunodeficiency virus (HIV)-infected adults treated with combination antiretroviral therapy if indicated according to current guidelines. METHODS: This was a cross-sectional epidemiological observational study. All patients attending 1 HIV-outpatient center in the United Kingdom in a 10-month period were eligible. Patients completed a validated questionnaire enquiring about demographics, HIV factors, and symptoms of pain. RESULTS: Of 1050 eligible participants, 859 (82%) completed a questionnaire. The 1-month period prevalence of pain lasting >1 day was 62.8% among whom 63% reported current pain. The prevalence of pain at most anatomic sites was broadly similar to that observed in population studies using the same questionnaires except that we found considerably higher rates of foot/ankle pain. The median duration of pain was 3 years (range, 0 to 51 y) and the median pain score was 5.0 on an 11-point visual analogue score. Over 40% of people in pain had consulted their primary care physician and >20% were taking analgesics daily. Independent risk factors for current pain were older age (P=0.001), time since diagnosis of HIV infection (P=0.001), and receipt of a protease inhibitor-based regimen (P=0.04). DISCUSSION: Pain, and notably foot/ankle pain, is common among adults living with prevalent HIV and is associated with substantial morbidity and health care utilization.

The changing spectrum of rheumatic disease in HIV infection.

BACKGROUND: Rheumatic manifestations were described soon after human immunodeficiency virus (HIV) was discovered. Since however, combination anti-retroviral therapy (cART) has revolutionized the course of the infection. Less clear is what effect cART has had on rheumatic manifestations. SOURCES OF DATA: References were retrieved from the PubMed database using keywords including: 'HIV' and 'arthritis'; 'myalgia'; 'arthralgia' and other disease-specific terms, e.g. 'rheumatoid arthritis'. AREAS OF AGREEMENT: Musculoskeletal pain was common in HIV and increased with AIDS. Immune restoration inflammatory syndrome on initiation of cART causes de novo autoimmune inflammatory rheumatic disorders. Seronegative inflammatory arthritis with/without axial involvement has been reported widely with HIV. AREAS OF CONTROVERSY: It is unclear if HIV causes these conditions, creates an environmental milieu supportive of these conditions or acts as a marker of other risk factors. It is unclear what effect cART has had on these conditions. GROWING POINTS: Variable diagnostic classification criteria have caused this literature to be poorly comparable. AREAS TIMELY FOR DEVELOPING RESEARCH: High-quality controlled epidemiological studies using standardized criteria are needed among cART users. Treatment of active autoimmune disease in HIV patients needs to be evaluated formally.

Psychological symptoms in women in a primary care setting in Tamil Nadu.

BACKGROUND: Common mental disorders, especially depression, are likely to increase as a result of globalization and industrialization and it is likely that the resultant burden of care will increase proportionately. Women have a higher prevalence of depression and also carry the burden of caring for the affected individuals. AIM: To study the psychological symptoms with possible common mental disorders in a primary care setting. METHODS: One hundred two women of Tamil ethnicity were approached to take part in answering the Self-Report Questionnaire (SRQ). The mean age of cases and non-cases were 39 years and 33 years, respectively. RESULTS: Nearly three-fifths scored above the cut-off point. Age, physical illness and chronic pain were found to be important factors in the genesis of depression in particular. CONCLUSION: These findings have major implications for any preventative or intervention strategies.