Carbohydrate pellets to assess insulin dysregulation in horses.

BACKGROUND: A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging. HYPOTHESIS/OBJECTIVES: To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets. ANIMALS: University and privately-owned horses and ponies (n = 157) comprised of 31 breeds and both sexes. METHODS: Multicenter cohort study. A custom-produced glycemic pellet was offered for free intake at 0.5 g/kg BW soluble carbohydrate and serum insulin and blood glucose concentrations measured before and after (60, 120, and 180 minutes) the pellets were offered. Pellet acceptance and intake time (those that finished within 10 minutes) were determined to assess palatability. RESULTS: The pellets were palatable to 132/157 animals, and ponies found the pellets more (P = .004) palatable than horses. The median intake time (4 [3-6] minutes) was positively correlated with acceptance grade (r = .51; P < .0001). Consumption of the pellets elicited peak blood glucose (6.6 [5.8-7.8] mmol/L) and serum insulin (40.5 [19-99.8] µIU/mL) responses at 120 minutes. At 120 minutes the optimal cut-off was 83 µIU/mL (95% CI: 70-99 µIU/mL) for the IMMULITE 2000XPi assay. CONCLUSIONS AND CLINICAL IMPORTANCE: The pellets were palatable and a suitable, novel carbohydrate source for the OGT.

Sphingolipidome of plasma, liver, and adipose tissues and its association with insulin response to oral glucose testing in Icelandic horses.

Insulin dysregulation (ID) is a determinant of equine metabolic syndrome. Among the sphingolipids, ceramides contribute to the development of ID; however, the cross talk between the liver and adipose tissue (AT) depots and the variation among AT depots in terms of ceramide metabolism are not well understood. We aimed to characterize the sphingolipidome of plasma, liver, and AT (nuchal, NUAT; subcutaneous, SCAT; omental, OMAT; retroperitoneal, RPAT) and their associations with insulin response to oral glucose testing (OGT) in normoinsulinemic and hyperinsulinemic horses. Plasma, liver, and AT samples were collected from 12 Icelandic horses upon euthanasia and analyzed by liquid chromatography-mass spectrometry. Eighty-four targeted compounds were effectively quantified. Comparing the AT depots, greater (false discovery rate, FDR < 0.05) ceramide, dihydroceramide, and sphingomyelin concentrations and lower glucosyl- and galactosyl-ceramides were found in RPAT and OMAT than in NUAT and SCAT. Hyperinsulinemic response to OGT was associated with sphingolipidome alterations primarily in the RPAT and OMAT, whereas the NUAT sphingolipidome did not show signs of ceramide accumulation, which was inconsistent with the previously proposed role of nuchal adiposity in ID. The plasma sphingolipidome was not significantly associated with the liver or AT sphingolipidomes, indicating that plasma profiles are determined by an interplay of various organs. Furthermore, hepatic sphingolipid profiles were not correlated with the profiles of AT depots. Finally, statistically valid partial least square regression models predicting insulin response were found in the plasma (Q2 = 0.58, R2 = 0.98), liver (Q2 = 0.64, R2 = 0.74), and RPAT (Q2 = 0.68, R2 = 0.79) sphingolipidome, but not in the other adipose tissues.

Doxycycline versus azithromycin for the treatment of anorectal Chlamydia trachomatis infection in women concurrent with vaginal infection (CHLAZIDOXY study): a multicentre, open-label, randomised, controlled, superiority trial.

BACKGROUND: Anorectal infections with Chlamydia trachomatis are commonly found in women. Although the efficacy of doxycycline and azithromycin is comparable in the treatment of urogenital infection, their efficacies toward anorectal infection remain unclear. We therefore aimed to compare a single dose of azithromycin with a 7-day course of doxycycline for the treatment of anorectal C trachomatis infection in women with concurrent vaginal infection. METHODS: We did a multicentre, open-label, randomised, controlled, superiority trial involving four sexually transmitted infection screening centres and three pregnancy termination centres in France. We included sexually active adult women (≥18 years) with a positive C trachomatis vaginal swab who agreed to provide self-collected anorectal swabs for C trachomatis detection. Participants were randomly assigned (1:1), using block sizes of six and eight and stratification by each investigating centre, to orally receive either azithromycin (a single 1-g dose, with or without food) or doxycycline (100 mg in the morning and evening at mealtimes for 7 days [ie, 100 mg of doxycycline twice per day for 7 days]). All laboratory staff who did the bacteriological analyses, but not the participants and the investigators, were masked to the treatment groups. The primary outcome was the microbiological anorectal cure rate defined as a C trachomatis-negative nucleic acid amplification test (NAAT) result in anorectal specimens 6 weeks after treatment initiation among women who had a baseline C trachomatis-positive anorectal NAAT result. The primary analysis was done in the modified intention-to-treat population, with multiple imputation, which included all women who underwent randomisation and had a C trachomatis-positive vaginal and anorectal NAAT result at baseline. Adverse events were reported in all women who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT03532464. FINDINGS: Between Oct 19, 2018, and April 17, 2020, we randomly assigned a total of 460 participants to either the doxycycline group (n=230) or the azithromycin group (n=230). Four (1%) of 460 participants were excluded because they refused to take doxycycline or were found to be ineligible after randomisation. Among the 456 participants, 357 (78%) had a concurrent C trachomatis-positive anorectal NAAT result at baseline; 184 (52%) of 357 were in the doxycycline group and 173 (48%) were in the azithromycin group (ie, the modified intention-to-treat population). Microbiological anorectal cure occurred in 147 (94%) of 156 participants in the doxycycline group (28 missing values) versus 120 (85%) of 142 in the azithromycin group (31 missing values; adjusted odds ratio with imputation of missing values 0·43 [95% CI 0·21-0·91]; p=0·0274). Reported adverse events possibly related to treatment were notified in 53 (12%) of 456 women: 24 (11%) of 228 in the doxycycline group and 29 (13%) of 228 in the azithromycin group. Gastrointestinal disorders were the most frequently occurring, in 43 (9%) of 456 women: 17 (8%) of 228 in the doxycycline group and 26 (11%) of 228 in the azithromycin group. INTERPRETATION: The microbiological anorectal cure rate was significantly lower among women who received a single dose of azithromycin than among those who received a 1-week course of doxycycline. This finding suggests that doxycycline should be the first-line therapy for C trachomatis infection in women. FUNDING: French Ministry of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Influence of Butorphanol, Buprenorphine and Levomethadone on Sedation Quality and Postoperative Analgesia in Horses Undergoing Cheek Tooth Extraction.

The aim of this prospective clinical trial was to compare the influence of butorphanol, buprenorphine and levomethadone on sedation quality and postoperative analgesia in horses undergoing cheek tooth extraction. Fifty horses were assigned to three groups prior to oral cheek tooth extraction. Horses were treated with acepromazine, followed by a detomidine bolus, one of the three opioids and both a nerve block and gingival anaesthesia. During the surgery, sedation was maintained with a detomidine constant rate infusion. After surgery, the quality of sedation, surgical conditions and severity of the extraction were assessed with a numerical rating scale. To evaluate differences in the quality of analgesia between the three treatments, postoperative pain was estimated with the Equine Utrecht University Scale for Facial Assessment of Pain. Additionally, several parameters that are associated with dental pain were added to this validated pain score, and blood samples were taken to measure serum cortisol. Our analysis showed lower pain scores and a greater analgesic effect with levomethadone and buprenorphine compared with butorphanol, with increased locomotor activity induced by buprenorphine. While cortisol values demonstrated higher response in horses treated with levomethadone and buprenorphine compared to butorphanol, these values could be biased by unrelated stressors.

Associations of plasma sphingolipid profiles with insulin response during oral glucose testing in Icelandic horses.

BACKGROUND: Sphingolipids modulate insulin sensitivity in mammals. Increased synthesis of ceramides is linked to decreased insulin sensitivity of tissues. Conversely, activation of the insulin signaling pathway can downregulate ceramide synthesis. Elucidating the association between sphingolipid metabolism and insulin response during oral glucose testing may help explain the pathophysiology of insulin dysregulation in horses. HYPOTHESES: Horses with insulin dysregulation will have a plasma sphingolipid profile characterized by increased ceramide concentrations. The plasma sphingolipid profile will have decreased ceramide concentrations after acute activation of the insulin signaling pathway by oral glucose testing. ANIMALS: Twelve Icelandic horses. METHODS: Horses were subjected to an oral glucose test (0.5 g/kg body weight glucose), with plasma insulin concentrations measured at 0, 30, 60, 120, 180, and 240 minutes postglucose administration. Plasma samples were collected at 0 and 120 minutes for sphingolipid profiling using a liquid chromatography-mass spectrometry-based metabolomics analysis. Eighty-three species of sphingolipids were detected, including 3-ketosphinganines, dihydroceramides, ceramides, dihydrosphingomyelins, sphingomyelins, galatosylceramides, glucosylceramides, lactosylceramides, and ceramide-1-phosphates. RESULTS: Glucose administration did not significantly alter plasma sphingolipid profiles. C22:0-ceramide, C24:1-ceramide, C23:0-ceramide, C16:1-sphingomyelin, C22:0-dihydroceramide, and C24:0-ceramide were positively correlated with the insulin response (area under the curve). CONCLUSION AND CLINICAL IMPORTANCE: Positive correlation between the insulin response and sphingolipid concentrations implies upregulated sphingolipid metabolism in insulin dysregulated horses. A high plasma ceramide concentration can indicate insulin dysregulation in horses.

Genotyping and follow-up of HR-HPV types detected by self-sampling in women from low socioeconomic groups not participating in regular cervical cancer screening in France.

BACKGROUND: HPV vaginal self-sampling can be an alternative for women refusing cytological screening. OBJECTIVES: To describe HR-HPV types in 35-69 years old women from low socioeconomic groups not attending regular cytological screening in Marseille, France. STUDY DESIGN: A cervical screening campaign using HR-HPV self-sampling including 22,702 women aged 35-69 years living in low socioeconomic districts of Marseille was organized. A cytological and/or histological follow-up was undertaken for a subset of women harboring HR-HPV types. Abbott RealTime High Risk HPV test was used for screening, while INNO-LiPA HPV Genotyping Extra assay was used for genotyping. RESULTS: 4245 self-samplings were performed (participation rate, 18.7%) out of which 609 (14.3%) were HR-HPV+ by the screening test including 114HPV 16 (18.7%), 41HPV 18 (6.7%), 454HR-HPVnon-16/18 (75.4%). A sample of 260 out of the 454HR-HPVnon-16/18 were genotyped by INNO-LiPA which revealed HPV52 (35%), 66 (22.6%), 51 (19.6%), 31 (15.7%), 39 (13%), 56 (10.4%), and 53, 35, 59, 33, 58, 82, 45, 68, 73 (<10% each). At month 12, a 2nd self-collection kit was sent to 274 of 609HR-HPV+ women who did not have a Pap-test previously performed on them. Of these 274 women, 130 provided a sample for HPV testing; one was uninterpretable, 56 were HPV negative, and 73 were HR-HPV+ (10HPV16+, 3HPV18+, 60HR-HPVnon-16/18+). Of the 345 women with cytological and/or histological follow-up 19 (5.5%) had ≥CIN2 lesions, (11 were HPV16+ and 8 were HR-HPVnon-16/18). CONCLUSION: This study illustrates the potential efficacy of self-sampling as a cancer screening strategy for socioeconomically deprived women who do not participate in regular Pap screening programs.