Patient-reported outcomes of laparoscopic magnetic sphincter augmentation for gastro-oesophageal reflux disease.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) is a chronic progressive disease, associated with substantial clinical and economic burden. Proton pump inhibitors (PPIs) are considered first-line treatment; however, there are concerns around the long-term impact of their usage. Surgical treatment with Nissen fundoplication can be considered but, because of the potential side effects, few patients undergo surgery and there remains a substantial therapeutic gap within the current treatment pathway. Laparoscopic magnetic sphincter augmentation (MSA) using the LINX® device is an alternative surgical approach. METHODS: The objective of this study was to investigate patient-reported outcomes following laparoscopic MSA surgery using the LINX® device in a UK setting. A retrospective questionnaire obtained data regarding postoperative symptoms, medication use and patient satisfaction. RESULTS: Out of 131 patients surveyed, 97 responses were received, with a minimum follow-up time of 1 year. In those who reported heartburn and regurgitation preoperatively, improvement was reported in 93% (84/90) and 90% (86/96) of patients, respectively. Eighty-eight per cent (73/83) of patients were able to completely stop or reduce their medication by at least 75%. Seventy-seven per cent (73/95) of patients were "very satisfied" or "satisfied". CONCLUSIONS: This study is the first to present patient-reported outcomes of MSA using the LINX® device for patients with GORD in the UK. It demonstrates that the device has favourable outcomes and could effectively bridge the current therapeutic gap that exists between PPI medication and Nissen fundoplication.

Loss of DRAK2 signaling enhances allogeneic transplant survival by limiting effector and memory T cell responses.

Here, we demonstrate that loss of DRAK2 signaling significantly promotes the acceptance of allogeneic engraftment in two separate transplant models without promoting generalized immunosuppression. Drak2-/- T cells failed to reject allogeneic tumors, and were defective in rejecting Balb/C allogeneic skin grafts on C57BL6/J recipients. A significant fraction of alloreactive Drak2-/- T cells underwent apoptosis following activation, whereas enforced expression of Bcl-xL in Drak2-/- T cells restored allograft rejection. Formation of allogeneic memory was also greatly hampered in T cells lacking the Drak2 gene. Adoptive transfer of memory T cells from Drak2-/- mice failed to promote the rejection of allogeneic tumors, and such cells led to significantly delayed rejection of skin allografts in the Balb/C->C57BL/6J model. Costimulatory blockade by in vivo administration of Cytotoxic T-Lymphocyte Antigen 4 fusion protein (CTLA4-Ig) synergized with the DRAK2 deficiency and led to long-term allogeneic skin graft acceptance. Overall, these results demonstrate that DRAK2 plays an important role in primary and memory T cell responsiveness to allografts. Because previous studies have demonstrated that a loss of DRAK2 does not negatively impact antiviral immunity, the studies here underscore the potential utility of pharmacological blockade of DRAK2 to achieve transplant maintenance without the imposition of generalized immunosuppression.

Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy.

BACKGROUND: Despite the predominance of extensive disease in children with ulcerative colitis, data concerning severe paediatric ulcerative colitis are sparse. We reviewed rates and predictors of response to intravenous-corticosteroid therapy in a single-centre cohort with long-term follow-up. METHODS: 99 children (49% males; age 2-17 years) were hospitalised (1991-2000) for treatment of severe ulcerative colitis (90% extensive; 49% new onset ulcerative colitis). Clinical, laboratory and radiographic data were reviewed. A population-based subset was used to assess incidence. Predictors of corticosteroid response were analysed using univariate and multivariate analyses at days 3 and 5 of therapy. Colectomy rates were calculated using Kaplan-Meier survival analyses. RESULTS: 28% (95% CI, 23 to 34%) of children with ulcerative colitis resident in the Greater Toronto Area required admission for intravenous corticosteroid therapy, of whom 53 (53%; 95% CI, 44 to 63%) responded. Several predictors were associated with corticosteroid failure, but in multivariable modelling only C-reactive protein [OR = 3.5 (1.4 to 8.4)] and number of nocturnal stools [OR = 3.2 (1.6 to 6.6)] remained significant at both days 3 and 5. The Pediatric Ulcerative Colitis Activity Index (PUCAI), Travis and Lindgren's indices strongly predicted non-response. Radiographically, the upper range of colonic luminal width was 40 mm in children younger than 11 years versus 60 mm in older patients. Cumulative colectomy rates at discharge, 1 year and 6 years were 42%, 58% and 61%, respectively. CONCLUSIONS: Children with ulcerative colitis commonly experience at least one severe exacerbation. Response to intravenous corticosteroids is poor. The PUCAI, determined at day 3 (>45 points) should be used to screen for patients likely to fail corticosteroids and at day 5 (>70 points) to dictate the introduction of second-line therapies.

Comparison of sevoflurane and isoflurane in dogs anaesthetised for clinical surgical or diagnostic procedures.

OBJECTIVES: To assess attributes of sevoflurane for routine clinical anaesthesia in dogs by comparison with the established volatile anaesthetic isoflurane. METHODS: One hundred and eight dogs requiring anaesthesia for elective surgery or diagnostic procedures were studied. The majority was premedicated with 0.03 mg/kg of acepromazine and 0.01 mg/kg of buprenorphine or 0.3 mg/kg of methadone before induction of anaesthesia with 2 to 4 mg/kg of propofol and 0.5 mg/kg of diazepam. They were randomly assigned to receive either sevoflurane (group S, n=50) or isoflurane (group I, n=58) in oxygen and nitrous oxide for maintenance of anaesthesia. Heart rate, respiratory rate, indirect arterial blood pressure, haemoglobin saturation, vaporiser settings, end-tidal carbon dioxide and anaesthetic concentration and oesophageal temperature were measured. Recovery was timed. Data were analysed using analysis of variance and non-parametric tests. RESULTS: Heart rate (85 to 140/minute), respiratory rate (six to 27/minute) and systolic arterial blood pressure (80 to 150 mmHg) were similar in the two groups. End-tidal carbon dioxide between 30 and 60 minutes (group S 6.4 to 6.6 and group I 5.8 to 5.9 per cent) and vaporiser settings throughout (group S 2.1 to 2.9 and group I 1.5 to 1.5 per cent) were higher in group S. There was no difference in time to head lift (18+/-16 minutes), sternal recumbency (28+/-22 minutes) or standing (48+/-32 minutes). No adverse events occurred. CLINICAL SIGNIFICANCE: Sevoflurane appeared to be a suitable volatile anaesthetic for maintenance of routine clinical anaesthesia in dogs.

An analysis of dietary micronutrient intakes in two age groups of black South African women.

OBJECTIVE: To assess micronutrient intake of black women living in Mangaung, South Africa. SUBJECTS AND METHOD: A sample of 500 pre-menopausal black South African women (496 qualified to participate) from two age groups (25-34 and 35-44 years) were selected randomly in Mangaung, the black residential area of Bloemfontein. A validated Quantitative Food Frequency Questionnaire (QFFQ) was used to determine dietary intake of participants. Data were categorized into the two age groups. Median micronutrient intakes were compared to the Recommended Dietary Allowance (RDA) and Adequate Intake (AI). The prevalence of women with intakes < or = 67% of the RDA was calculated. RESULTS: Median calcium and vitamin D intakes were lower than the AI. Of all women, 46.2% to 62.2% consumed < or = 67% of the RDA for total iron, selenium, folate and vitamin C, and more than 94% consumed < or = 67% of the RDA for selenium. At least 25% of all women consumed < or = 67% of the RDA for vitamin A and E. The vitamin B6 intake of older women was inadequate and a fairly large percentage of the total sample consumed < or = 67% of the RDA. CONCLUSION: Generally, micronutrient intakes were adequate in this population. Attention should be given to those micronutrients where median intakes were < or = 67% of the RDA and those that were not at or above the respective AI in these groups of women.

Role of video capsule endoscopy in patients with constitutional mismatch repair deficiency (CMMRD) syndrome: report from the International CMMRD Consortium.

BACKGROUND AND STUDY AIMS: Constitutional mismatch repair deficiency (CMMRD) syndrome, also known as biallelic mismatch repair deficiency (BMMRD) syndrome is a rare autosomal-recessive genetic disorder that has a high mortality due to malignancy in childhood and early adulthood. The small bowel phenotype in CMMRD is not well described and surveillance protocols for small bowel cancer have not been well established. This study was conducted to evaluate the usefulness and clinical impact of video capsule endoscopy (VCE) for small bowel surveillance. PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International CMMRD Consortium database. Treating physicians were contacted and VCE report data were extracted using a standardized template. RESULTS: Among 58 patients included in the database, 38 VCE reports were collected from 17 patients. Polypoid lesions were first detected on VCE at a median age of 14 years (range: 4 - 17). Of these, 39 % in 7 patients (15/38) showed large polypoid lesions (> 10 mm) or multiple polyps that prompted further investigations. Consequently, three patients were diagnosed with small bowel neoplasia including one patient with adenocarcinoma. Small bowel neoplasia and/or cancer were confirmed histologically in 35 % of the patients (6/17) who had capsule surveillance and the lesions in half of these patients were initially visualized on VCE. Multiple polyps were identified on eight VCEs that were completed on three patients. Ten VCEs (28 %) were incomplete due to slow bowel transit; none required capsule removal. CONCLUSIONS: Small bowel surveillance in patients with CMMRD should be initiated early in life. VCE has the potential to detect polyps; however, small bowel neoplasias are often proximal and can be missed, emphasizing the importance of concurrent surveillance with other modalities. MEETING PRESENTATIONS: Digestive Disease Week 2017 and World Congress of Pediatric Gastroenterology, Hepatology and Nutrition 2016.

FADD self-association is required for stable interaction with an activated death receptor.

Receptor-mediated programmed cell death proceeds through an activated receptor to which the death adaptor FADD and the initiator procaspases 8 and/or 10 are recruited following receptor stimulation. The adaptor FADD is responsible for both receptor binding and recruitment of the procaspases into the death-inducing signaling complex. Biochemical dissection of the FADD death effector domain and functional replacement with a coiled-coil motif demonstrates that there is an obligatory FADD self-association via the DED during assembly of the death-inducing signaling complex. Using engineered oligomerization motifs with defined stoichiometries, the requirement for FADD self-association through the DED can be separated from the caspase-recruitment function of the domain. Disruption of FADD self-association precludes formation of a competent signaling complex. On this basis, we propose an alternative architecture for the FADD signaling complex in which FADD acts as a molecular bridge to stitch together an array of activated death receptors.

Myonuclear apoptosis in dystrophic mdx muscle occurs by perforin-mediated cytotoxicity.

Myonuclear apoptosis is an early event in the pathology of dystrophin-deficient muscular dystrophy in the mdx mouse. However, events that initiate apoptosis in muscular dystrophy are unknown, and whether elimination of apoptosis can ameliorate subsequent muscle wasting remains a major question. We have tested the hypothesis that cytotoxic T-lymphocytes initiate myonuclear apoptosis in dystrophic muscle, and examined whether perforin-mediated cytotoxicity plays a role in the pathophysiology of muscular dystrophy. Mdx mice showed muscle invasion by cytotoxic T cells and helper T cells at the onset of histologically detectable muscle fiber pathology. At this time, perforin-expressing cells were also present at elevated concentration. Mdx mice depleted of CD8(+) cells showed a significant reduction of apoptotic myonuclei concentration and a reduction in necrosis, judged by macrophage invasion of muscle fibers. Double-mutant mice, deficient in dystrophin and perforin, showed nearly complete absence of myonuclear apoptosis, and a significant reduction in the concentration of macrophages in the connective tissue surrounding muscle fibers. However, muscle fiber invasion by macrophages was not reduced significantly in double mutant mice. Thus, cytotoxic T-lymphocytes contribute significantly to apoptosis and necrosis in mdx dystrophy, and perforin-mediated killing is primarily responsible for myonuclear apoptosis.

Modulation of monocyte functions by muramyl tripeptide phosphatidylethanolamine in a phase II study in patients with metastatic melanoma.

BACKGROUND: Muramyl tripeptide phosphatidylethanolamine (MTP-PE) is a synthetic analogue of muramyl dipeptide (MDP), a component of bacterial cell walls that has potent in vitro monocyte-activating properties. We conducted a phase II clinical trial of MTP-PE in 30 patients with metastatic melanoma. PURPOSE: Our purpose was to define a clinical response rate for this agent in patients with advanced melanoma and to evaluate the agent's immunomodulatory properties. METHODS: Patients were randomly assigned to 1- or 4-mg dose levels of MTP-PE and received the drug intravenously once a week for 12-24 weeks. Immunological monitoring consisted of measurement of plasma tumor necrosis factor-alpha (TNF-alpha), neopterin, interleukin-1-beta, interleukin-6 (IL-6), and beta 2-microglobulin levels; phenotyping analysis of expression of human HLA-DR, CD-14 on mononuclear cells; and measurement of in vitro monocyte cytotoxicity against SKMel28 targets cells. RESULTS: MTP-PE was well tolerated; fever and chills were the major toxic effects. Plasma TNF-alpha levels increased 16-fold 2 hours after the first MTP-PE treatment. Increases in TNF-alpha levels after MTP-PE administration continued through week 12, but changes were of a lower magnitude after week 1. Plasma neopterin levels were significantly increased 24 hours after treatment at weeks 1, 6, and 12. A marked increase in IL-6 and a modest rise in beta 2-microglobulin levels were also seen at week 1. No significant changes from baseline IL-1 beta were observed. In the cytotoxicity assay, monocyte cytotoxic activity was significantly increased at weeks 4 and 6. Surface immuno-phenotyping revealed a consistent transient reduction in the number of circulating monocytes 2 hours after MTP-PE was administered. In addition, we observed a down-regulation (i.e., a decrease) in the expression of Leu M3 and HLA-DR on monocytes, 2 hours after MTP-PE treatment, followed by a recovery 24 hours after treatment. No objective clinical responses were seen in this advanced disease population. CONCLUSIONS: We conclude that MTP-PE has pleiotropic and potentially beneficial biologic effects and that further clinical investigations of MTP-PE are justified. IMPLICATIONS: In view of the clear immunomodulatory actions seen in our study and in earlier clinical trials, we believe that MTP-PE deserves further study in the adjuvant setting.

Training non-physicians to do endoscopy: Feasibility, effectiveness and cost-effectiveness.

Colorectal cancer (CRC) is one of the most common cancers in women and men worldwide. Training non-physicians including nurses, nurse practitioners, and physician assistants to perform endoscopy can provide the opportunity to expand access to CRC screening as demand for endoscopic procedures continues to grow. A formal program, incorporating didactic instruction and hands-on practice in addition to oversight, is required to train non-physicians to perform endoscopy as safely and effectively as physicians. Additionally, the context in which the non-physician endoscopy program is organized will dictate key program characteristics including remuneration, participant recruitment and professional and legal considerations. This review explores the evidence in support of non-physician based endoscopy, potential challenges in implementing non-physician endoscopy and requirements for a high-quality program to support training and implementation.

Cell-mediated cytotoxicity in perforin-less mice.

We have used a perforin-less (PO) mouse to explore alternate CTL-mediated lytic pathways. PO mice are unable to overcome an infection with LCMV in vivo. Nevertheless, splenocytes from infected mice show vigorous, antigen-specific cytotoxicity that requires the presence of the Fas antigen on target cells. The Fas lytic pathway is virtually indistinguishable, in terms of kinetics and magnitude of cytotoxicity, from perforin/granzyme-mediated lysis. It is rapidly induced in CTL upon occupation of the TcR, and requires protein synthesis for full expression. Upon removal of the activating signal, the capacity for fas-mediated lysis rapidly disappears. PO mice infected with LCMV also undergo what appears to be a CD8-mediated immunopathology, and rarely live beyond one month. The precise basis of this pathology is unknown at present. Given the widespread distribution of Fas in mice, particularly on inflamed tissues, the complete failure to clear virus from any tissue or organ is surprising.

A family history study of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by unexplained, disabling fatigue and is associated with high rates of comorbid depression. While the aetiology is unknown, findings from recent twin surveys suggest that genetic factors may be relevant to prolonged fatigue states (> 1 month). To date, however, there has been no exploration of the role of familial/genetic factors in operationally defined CFS. The aims of the present study were: (i) to examine whether CFS is familial by comparing the rates of CFS in the first-degree relatives of CFS cases and medical control subjects; and (ii) to determine whether the high rate of comorbid depression in CFS is reflected in a greater familial loading for affective disorder. Twenty-five CFS cases and 36 medical control subjects were assessed for fatigue symptoms based on the Centre for Disease Control (CDC) criteria for CFS, and for lifetime psychiatric symptoms using the Schedule for Schizophrenia and Affective Disorders-Lifetime Version. Informant family history was obtained regarding first-degree relatives using the CDC criteria and the Family History Research Diagnostic Criteria. In addition, informant history was supplemented by sending a questionnaire to first-degree relatives. There were significantly higher rates of CFS in the relatives of CFS cases compared with the relatives of control subjects. The rate of depression in the CFS cases was similar to previous studies but did not appear to reflect a greater familial loading for depression when compared with control subjects. However, these analyses were complicated by higher than expected rates of depression in the control group. These findings suggest that familial factors are important in the aetiology of chronic fatigue syndrome.

The use of explant lens culture to assess cataractogenic potential.

Explanted cultures of crystalline lenses have been used to investigate mechanisms of xenobiotic-induced cataract formation. However, very few studies have utilized mechanistic information to predict the cataractogenic potential of structurally diverse xenobiotics. The present investigation outlines how visual assessment of lens clarity, biochemical endpoints of toxicity, and mechanisms of lenticular opacity formation can be used to select compounds with a lower probability of causing cataract formation in vivo. The rat lens explant culture system has been used to screen thiazolidinediones against ciglitazone for their direct cataractogenic potential in vitro. The two compounds that were selected as development candidates (englitazone and darglitazone) did not produce cataracts in rats exposed daily for 3 months. The culture system has also been used to illustrate that the lens is capable of metabolizing compounds to reactive intermediates. In this example, the toxicity of S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a model cataractogen, was attenuated by inhibiting lenticular cysteine conjugate beta-lyase metabolism using aminooxyacetic acid. Finally, this model was used retrospectively to investigate the cataractogenic potential of CJ-12,918 and CJ-13,454 in rats. These compounds showed differences in the incidence of cataract formation in vivo based on differences in hepatic metabolism and penetration of parent drug and metabolites into the lens. The rank order of cataractogenic potential in vitro correlated better with in vivo results when an induced S9 microsomal fraction was added to the culture media. However, the model did not correctly predict the cataractogenic potential of ZD2138, a structurally similar compound. These studies illustrate the use of explant culture to assess mechanisms of cataract formation and outline its use and limitations for predicting cataractogenic potential in vivo.

Enhanced recovery of cryopreserved islets using SIS.

Although cryopreservation of pancreatic islets would add flexibility to transplantation, the recoveries are only 60% to 90% and function is decreased. Islets are multicellular structures approximately 50 to 250 microm in diameter organized into a network of cells and vascular channels. Due to this complexity, islets are more susceptible to damage during cryopreservation than an individual cell. This study investigated porcine small intestinal submucosa (SIS) as a matrix to support islets recovery and function post-thaw. Groups of frozen/thawed human islets (150 IE/condition; n = 4 preparations) were cultured for 5 weeks in plates containing noncoated Biopore membrane inserts alone or inserts covered with SIS. Islets were placed directly on the insert post-thaw (SIS(1)), or cultured overnight in standard plates, washed, and then transferred to the SIS (SIS(2)). Function was assessed by determining glucose-stimulated release of insulin, which was measured by radioimmunoassay. Analysis of basal insulin secretion showed time and treatment to be significantly different (P =.0043 and P =.0123, respectively) but without an interaction (P >.05). The two SIS treatments were not significantly different (P >.05); however, both SIS(1) and SIS(2) were significantly different from controls (P =.0108 and P =.0420, respectively). Similar results were obtained for stimulation indices; time and treatment were significantly different (P =.0161 and P =.0264, respectively) but not an interaction (P >.05). The two SIS treatments were not significantly different (P =.05); however, both SIS(1) and SIS(2) differed from controls (P =.0248 and P =.0407, respectively). The results indicate that SIS enables frozen-thawed islets to exhibit superior post-thaw function compared with a non-SIS-supported condition.

Improved in vitro function of islets using small intestinal submucosa.

Transplantation of human pancreatic islets has been demonstrated to be a viable alternative to exogenous insulin therapy for diabetes mellitus. However, optimum results require transplantation of islets from two to three pancreas donors after a minimum number of days in culture. This implies that a substantial part of the transplanted islet mass may be nonfunctional. This study investigates the ability of an optimized technique to retain islet function using porcine-derived small intestinal submucosa (SIS) during in vitro culture. Groups of purified human islets were cultured for 3 weeks in modified standard islet culture conditions of CMRL = 1066 tissue culture medium supplemented with 25 mmol/L HEPES, penicillin/streptomycin, and a commercial insulin-transferin-selenium (ITS) supplement. Islets (50 to 200 IE/condition; n = 5 preparations) were cultured in plates containing noncoated Biopore membrane inserts alone, or on inserts that had been covered with SIS. Function was assessed by static incubation with low (4 mmol/L), or high (20 mmol/L) glucose at the end of each week. Glucose-stimulated release of human insulin was measured by radioimmunoassay (Linco, St. Charles, Missouri). Remaining islets were stained and evaluated visually. Neither culture condition resulted in significantly different basal secretion until week 3 (P =.05). However, by the end of week 2 and for the duration of the experiment thereafter, SIS-treated islets exhibited a higher SI (P <.05). At the end of the experiment, islets cultured on the SIS exhibited excellent morphology, with greater than 90% staining positive with Dithizone. Islets cultured on the inserts alone lost their initial morphology, becoming "loose" in appearance. The results of this study indicate that SIS enables enhanced function of islets in vitro as compared to non-SIS supported culture conditions.

Enhanced length of stay management through monitoring of discharge planning parameters.

Traditional data collection in discharge planning programs has been largely retrospective, measuring the patient's length of stay and unnecessary hospital days at the point of discharge. Although the data collection is useful, it does not lend itself to corrective actions on a concurrent basis. Carney Hospital has developed a data base that monitors patient status daily in order to identify when a length of stay problem is developing and when corrective actions are succeeding. The Patient Tracking System is an interactive computer report utilized by Continuing Care staff, Utilization Review staff, and clinical managers on the patient care units. It is a caseload register that operates from the admission transfer discharge (A/T/D) system of the hospital and sorts inpatients by discharge planning status, length of stay, discharge planning worker, and nursing unit. It is the basis for a weekly management review that identifies numbers of patients and average length of stay to date of key groups of patients proven to impact the overall length of stay in the hospital. Carney Hospital has successfully utilized this system to alert managers to any length of stay "creep," to identify the sources of the length-of-stay problem, and to mobilize key personnel to take corrective actions. The system is easy to use and is an effective length-of-stay management tool.

Dispositional differences in critical thinking related to gender and academic major.

Dispositional differences among several university majors and across gender were examined in this exploratory study, using Facione's California Critical Thinking Disposition Inventory. Participants were 334 baccalaureate undergraduates (121 males, 213 females) enrolled in majors classified as practice disciplines (i.e., nursing, education, business) and nonpractice disciplines (i.e., English, history, psychology). A MANCOVA with grade point average as a covariate was conducted for majors, indicating significant main effects for major. Highest scores generally were found in English, psychology, and nursing. When majors were grouped into practice and nonpractice disciplines, nonpractice had generally higher disposition scores, and female scores in both practice and nonpractice disciplines were higher than males on Open-Mindedness and Maturity.

Blue light from individual light masks directed at a single eye advances the breeding season in mares.

REASONS FOR PERFORMING STUDY: Artificial lighting is commonly used to advance the breeding season in horses. Light masks have been developed that direct light at a single eye to inhibit the production of melatonin, the decoder of photoperiod for seasonally breeding animals. OBJECTIVES: To investigate whether low-intensity blue light from light masks was effective at advancing the breeding season in mares. STUDY DESIGN: Controlled experiment. METHODS: Data on reproductive activity was collected from 3 groups of mares maintained on Kentucky horse farms under various lighting conditions between 20 November 2011 and 10 February 2012: 59 nonpregnant, healthy Thoroughbred mares were used. On 1 December 2011, Group 1 (n = 16) was housed indoors under barn lighting (250 Lux) until 23.00 h daily. Group 2 (n = 25) wore light masks programmed to turn on from 16.30 h until 23.00 h daily and was maintained outdoors. Group 3 (n = 19) was maintained outdoors under the natural photoperiod as control. At 2-week intervals, rectal ultrasound examinations were performed and blood was collected for progesterone analysis. Oestrous cyclicity was defined as the presence of follicles >20 mm diameter detected in conjunction with serum progesterone >1 ng/ml and confirmation of ovulation by transrectal ultrasound examination. RESULTS: On 10 February, the number of mares exhibiting oestrous cyclicity was 14/16 (87.5%) in Group 1; 20/25 (80%) in Group 2; and 4/19 (21%), in Group 3. Pairwise comparison of groups revealed no difference in the number of cycling mares between Groups 1 and 2 (χ(2) test, P = 0.3348) whereas differences were observed between Groups 1 and 3 (χ(2) test, P<0.0001) and Groups 2 and 3 (χ(2) test, P<0.0003). CONCLUSIONS: Low-intensity blue light to a single eye from a light mask is an effective alternative to maintenance of mares indoors under lights for advancing the breeding season. Mobile light therapy for horses could have economic benefits for the breeder by reducing the costs of maintaining mares indoors, and welfare benefits for horses by permitting outdoor maintenance.

Blue light from light-emitting diodes directed at a single eye elicits a dose-dependent suppression of melatonin in horses.

The production of melatonin during night-time hours decodes day length for seasonally breeding animals. The use of artificial light to advance the breeding season in mares is common practice within the equine industry. Four healthy Thoroughbred mares were used to evaluate the minimum intensity of light required to inhibit serum melatonin. Mares were fitted with indwelling jugular catheters and using a crossover design blood samples were collected following 1h exposure to light (barn lighting approximately 200 lux), dark (<0.1 lux), and 3, 10, 50, and 100 lux intensities. The light source was a light-emitting diode (LED; 468 nm) directed at either a single eye or both eyes. All treatments, except the sample collected after 1 h exposure to light, occurred during the dark phase of the 24 h cycle. Serum melatonin levels were determined by radioimmunoassay. Two-way repeated measures ANOVA revealed that there was no difference between the level of melatonin inhibition achieved when light was administered to one or two eyes (P = 0.7028). One-way ANOVA of melatonin levels at light intensities of 10, 50 and 100 lux were significantly different to dark (P < 0.05) and not different to light (P > 0.05) intensities. There was no difference between melatonin levels at 3 lux (P > 0.05) and dark intensities. The threshold level of low wavelength light required to inhibit melatonin production in the horse lies between 3 and 10 lux. Melatonin inhibition can be achieved by exposing a single eye to low wavelength blue light. This is a novel finding with important implications for management of artificial lighting regimens in horses.