Ivermectin performance in horses diagnosed with equine endocrine disorders.

Anthelmintic performance against equine cyathostomins can be evaluated by two different non-terminal measures; the Fecal Egg Count Reduction Test (FECRT) and the Egg Reappearance Period (ERP). Most available FECRT and ERP data have been determined in populations of young horses, and very little information is available from mature and senior horses. Furthermore, it is unknown how commonly occurring equine endocrine disorders such as Insulin dysregulation (ID) and Pituitary pars intermedia dysfunction (PPID) may interfere with these measurements, but it has been suggested that horses with these conditions could be more susceptible to parasitic infections. A research population of senior horses and horses with or without PPID, ID, or both were enrolled in this study. All strongylid egg count positive horses were included in an ivermectin (200 µg/kg) efficacy study. These were distributed among the following groups: ID: six, PPID: three, PPID and ID: seven, and healthy controls: three. Strongylid fecal egg counts were determined on the day of ivermectin administration, at two weeks post deworming, and on weekly intervals until eight weeks post treatment. Determination of FECRT and ERP were carried out following World Association for the Advancement of Veterinary Parasitology guidelines. Results revealed high ivermectin efficacy with mean egg count reduction at 99.7% or above in all groups at two weeks post treatment. Egg reappearance was documented at six and seven weeks in the ID and PPID/ID groups, respectively, whereas the PPID and healthy control groups both had ERP at 8 weeks. Statistical analysis found no significant differences in egg count levels between groups during the study. The expected ERP for ivermectin is 8-10 weeks, meaning that two of the groups displayed shortened ERPs. However, due to the small group sizes, these data should be interpreted with caution. Nonetheless, results do indicate a need for further investigation of the possible influence of endocrine disorders on anthelmintic performance in horses.

The impact of market integration on arranged marriages in Matlab, Bangladesh.

Success in marriage markets has lasting impacts on women's wellbeing. By arranging marriages, parents exert financial and social powers to influence spouse characteristics and ensure optimal marriages. While arranging marriages is a major focus of parental investment, marriage decisions are also a source of conflict between parents and daughters in which parents often have more power. The process of market integration may alter parental investment strategies, however, increasing children's bargaining power and reducing parents' influence over children's marriage decisions. We use data from a market integrating region of Bangladesh to (a) describe temporal changes in marriage types, (b) identify which women enter arranged marriages and (c) determine how market integration affects patterns of arranged marriage. Most women's marriages were arranged, with love marriages more recent. We found few predictors of who entered arranged vs. love marriages, and family-level market integration did not predict marriage type at the individual level. However, based on descriptive findings, and findings relating women's and fathers' education to groom characteristics, we argue that at the society-level market integration has opened a novel path in which daughters use their own status, gained via parental investments, to facilitate good marriages under conditions of reduced parental assistance or control.

Emotional and informational social support from health visitors and breastfeeding outcomes in the UK.

BACKGROUND: Shorter breastfeeding duration is associated with detrimental consequences for infant health/development and maternal health. Previous studies suggest social support is essential in maintaining breast/chest-feeding and helping to improve general infant feeding experiences. Public health bodies therefore work to support breastfeeding in the UK, yet UK breastfeeding rates continue to be one of the lowest globally. With this, a better understanding of the effectiveness and quality of infant feeding support is required. In the UK, health visitors (community public health nurses specialising in working with families with a child aged 0-5 years) have been positioned as one of the key providers of breast/chest-feeding support. Research evidence suggests that both inadequate informational support and poor/negative emotional support can lead to poor breastfeeding experiences and early breastfeeding cessation. Thus, this study tests the hypothesis that emotional support from health visitors moderates the relationship between informational support and breastfeeding duration/infant feeding experience among UK mothers. METHODS: We ran cox and binary logistic regression models on data from 565 UK mothers, collected as part of a 2017-2018 retrospective online survey on social support and infant feeding. RESULTS: Informational support, compared to emotional support, was a less important predictor of both breastfeeding duration and experience. Supportive emotional support with unhelpful or absent informational support was associated with the lowest hazard of breastfeeding cessation before 3 months. Results for breastfeeding experience followed similar trends, where positive experience was associated with supportive emotional and unhelpful informational support. Negative experiences were less consistent; however, a higher probability of negative experience was found when both types of support were reported as unsupportive. CONCLUSIONS: Our findings point to the importance of health visitors providing emotional support to bolster the continuation of breastfeeding and encourage a positive subjective experience of infant feeding. The emphasis of emotional support in our results encourages increased allocation of resources and training opportunities to ensure health visitors are able to provide enhanced emotional support. Lowering health visitors caseloads to allow for personalised care is just one actionable example that may improve breastfeeding outcomes in the UK.

Effect of aging on monocyte phagocytic and inflammatory functions, and on the ex vivo inflammatory responses to lipopolysaccharide, in horses.

Studies investigating age-related changes in the function of monocytes are currently limited for horses. Thus, the main goal of this study was to determine the effect of aging on monocyte phagocytic capacity and pro-inflammatory cytokine responses to bacterial lipopolysaccharide (LPS). A second goal of this work was to examine the effect of aging on the inflammatory cytokine responses to LPS in a whole blood ex vivo model. Seven healthy young adult (4-6 years of age) and seven healthy senior horses (>20 years of age) were enrolled. Phagocytosis of E. coli, and pro-inflammatory cytokine (TNFα) responses to LPS, were measured in monocytes by flow cytometry. Gene expressions of pro-inflammatory cytokines (TNFα, IL-1ß, IL-6, IL-8, IL-18, CCL-5, CCL-2) were measured in peripheral blood mononuclear cells (PBMCs) and whole blood by RT-qPCR post incubation for 2 h or 6 h with a low (0.01 µg/mL) or a high (1 µg/mL) dose of LPS. Two sets of statistical models were applied to compare the age groups, one adjusted, and one unadjusted for the horses' body condition scores (BCS). The percentage of monocytes that phagocytosed E. coli after 2 h of incubation was significantly lower in senior compared to young adult horses in the BCS-adjusted model. In the senior group, the expression of IL-1ß in 2 h-0.01 µg/mL LPS-stimulated PBMCs was significantly higher than in the young adult group (BCS-adjusted and unadjusted models). In senior horses, expressions of IL-8 and IL-6 in whole blood samples stimulated for 6 h with 0.01 µg/mL LPS and for 2 h with 1 µg/mL LPS, respectively, were significantly lower than in young adult horses (BCS-adjusted models). The results of this study suggest that the phagocytic function of monocytes, as well as their IL-1ß response to LPS may be altered in senior horses. In addition, the whole blood IL-8 and IL-6 gene expression responses to LPS may be insufficient in senior horses. While investigation of the effect of BCS on monocyte functions and whole blood pro-inflammatory LPS-responses was not a major goal of this work, it appears that adiposity may play a role in innate immune cell function, as significant differences between the age groups were often not apparent until the models were adjusted for BCS.

The differential role of practical and emotional support in infant feeding experience in the UK.

Social support is a known determinant of breastfeeding behaviour and is generally considered beneficial. However, social support encompasses a myriad of different supportive acts, providing scope for diverse infant feeding outcomes. Given the vulnerability of postpartum mental health, this paper aims to explore both how support prolongs breastfeeding and which forms of support promote the positive experience of all infant feeding. Using survey data collected online from 515 UK mothers with infants aged 0-108 weeks, Cox regression models assessed the relationship between receiving different types of support, support need and breastfeeding duration. Quasi-binomial logistic regression models assessed the relationship between receiving support, infant feeding mode and maternal experience of infant feeding. Rates of negative infant feeding experience indicate the widespread need for support: e.g. 38% of currently, 47% of no longer and 31% of never breastfeeding women found infant feeding stressful. Overall, practical support via infant feeding broadly predicted shorter breastfeeding durations and poorer feeding experience; results in relation to other forms of support were more complex. Our findings indicate different forms of support have different associations with infant feeding experience. They also highlight the wide range of individuals beyond the nuclear family on which postpartum mothers in the UK rely. This article is part of the theme issue 'Multidisciplinary perspectives on social support and maternal-child health'.

Characterization of the in situ immunological responses to vaccine adjuvants.

Adjuvants are included with many inactivated and some modified live vaccines to enhance immune responses to specific antigens. While early vaccines relied exclusively upon aluminum salts, still the major adjuvant used in human vaccines, other adjuvant products are used in veterinary medicine. In addition to enhancing antigen presentation, adjuvants can also enhance the development of specific immune responses. Thus, alum adjuvants often preferentially stimulate humoral immune responses. By contrast, lipid-based adjuvants are often more effective at stimulating cell-mediated immune responses. Metastim(®) is a lipid-based adjuvant reported to elicit both humoral and cellular immune responses, though the mechanism responsible for this activity remains unclear. In this study, we compared the ability of equine influenza virus vaccines containing either saline or Metastim(®) or an aluminum phosphate adjuvant to stimulate antigen presenting cell function in vivo. Six ponies were intradermally inoculated with inactivated equine influenza (KY97) mixed with either adjuvant or saline. Multiple sites were injected so that biopsies could be collected at different times post injection. The 4mm punch biopsies were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated from 2mm punch biopsies for the determination of gene expression by real-time PCR. H&E staining revealed a variety of cells recruited to the injection sites, including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR analysis of the injection site confirmed this cellular infiltration and identified increased expression of activation markers. Both vaccines also stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing Metastim(®) elicited significantly higher gene expression of interferon-γ, IL-12, CD4 and CD83 compared to alum (p<0.05). While the greater induction of IFNγ-related gene expression indicates that Metastim(®) can elicit Th-1 immune responses more effectively than the aluminum salt, there was also evidence of Th2 cytokine induction.

The effect of passively acquired antibodies on Lawsonia intracellularis infection and immunity in the horse.

REASONS FOR PERFORMING STUDY: Multiple hypotheses into the age-based susceptibility of animals to Lawsonia intracellularis exist, including the decline of passively acquired antibodies. OBJECTIVES: To determine whether the decline in passively acquired antibodies in horses is responsible for the age predilection of equine proliferative enteropathy (EPE). Additional objectives included examination of various risk factors for the development of EPE as well as the determination of naturally occurring attack rates for clinical and subclinical EPE. STUDY DESIGN: Prospective, multifarm field study. METHODS: A total of 369 mare and foal pairs from 15 central Kentucky Thoroughbred farms were used in this study, which took place from January 2012 to February 2013. Serum samples were collected from mares and foals within 48 h of parturition, and then monthly from foals to February of their yearling year. Lawsonia intracellularis-specific antibodies were measured using an enzyme-linked immunosorbent assay. RESULTS: No effect of passively acquired antibodies on the occurrence of presumptive clinical or subclinical EPE was noted. In total, 5.3% and 6.3% of seropositive horses developed presumptive clinical or subclinical EPE, respectively. In multiple logistic regression models, colts were at a significantly greater risk than fillies of developing presumptive clinical EPE (odds ratio [OR] 5.468, 95% confidence interval [CI] 1.134-26.362, P = 0.034) or a combination of either presumptive clinical or subclinical EPE (OR 3.861, 95% CI 1.461-10.206, P = 0.006) while foals that were weaned in September or beyond were at a lower risk of developing presumptive EPE (OR = 0.281, 95% CI 0.0807-0.981, P = 0.05). CONCLUSIONS: This is the first study to show that passively acquired antibodies to L. intracellularis do not have an effect on the occurrence of clinical or subclinical EPE. A number of novel findings, including identification of the disease rate among naturally exposed horses, warrant additional work as they may help to identify potential risk factors for L. intracellularis exposure and/or the reservoir host(s) of the bacterium.

Adaptation and validation of a bacteria-specific enzyme-linked immunosorbent assay for determination of farm-specific Lawsonia intracellularis seroprevalence in central Kentucky Thoroughbreds.

REASONS FOR PERFORMING STUDY: Lawsonia intracellularis is the causative agent of equine proliferative enteropathy (EPE), a disease for which no large-scale seroprevalence studies have been conducted. OBJECTIVES: To validate and use an equine-specific enzyme-linked immunosorbent assay (ELISA) for L. intracellularis to determine the seroprevalence of L. intracellularis on numerous farms. METHODS: An ELISA, in which purified antigen was used, was adapted from previous work in swine. A total of 337 Thoroughbreds from 25 central Kentucky farms were enrolled and monthly serum samples collected from August 2010 to January/February 2011. Samples were screened for L. intracellularis-specific antibodies using a modified ELISA. Farms were classified into one of 3 groups based on 3 year prior history with EPE. RESULTS: The ELISA intra-assay coefficient of variation (CV) was 6.73 and inter-assay CV was 9.60. An overall seroprevalence of 68% was obtained, with farm-specific seroprevalances ranging from 14 to 100%. A significant difference was found in the average seroprevalence (P<0.05) on farms with a confirmed recent history of EPE cases. Additionally, both lower average ELISA unit (EU) values (P = 0.079) and maximum EU values (P = 0.056) were detected on farms with no recent EPE history when compared to the other groups. A bimodal exposure distribution to L. intracellularis was detected in the fall and winter months. CONCLUSIONS: Recent history of EPE was associated with higher average seroprevalence indicating increased exposure on farms with prior cases of EPE. Seasonally bimodal exposure was also observed. POTENTIAL RELEVANCE: The adapted ELISA appears to be useful for determination of L. intracellularis-specific antibody levels. The high farm-specific seroprevalences and bimodal distribution of exposure to L. intracellularis were unexpected and suggest that farms with a previous history of EPE remain at risk due to heightened exposure levels beyond early winter.

Characterization of the interferon gamma response to Lawsonia intracellularis using an equine proliferative enteropathy challenge (EPE) model.

Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanlings, in particular, appear to be most at risk for infection, though the reasons for their particular susceptibility is unknown. Using an infectious challenge model for EPE, we demonstrate that EPE, like porcine proliferative enteropathy, can exhibit three clinical forms: classical, subclinical and acute. Out of six pony weanlings, one developed signs of classic EPE, one developed acute EPE, and two developed subclinical EPE. Attempts to induce pharmacological stress through the use of dexamethasone failed to have any effect on outcome. Peripheral blood cells collected from those weanlings that developed clinical EPE exhibited decreased expression of interferon-gamma (IFN-γ) following in vitro stimulation with L. intracellularis. By contrast, those weanlings that did not develop clinical disease generated a robust IFN-γ response. These results indicate IFN-γ likely plays a significant role in protection from disease caused by L. intracellularis in the equid.

Posterior calcaneal osteotomy with wedge: cadaver testing of a new procedure for insufficiency of the posterior tibial tendon.

Insufficiency of the posterior tibial tendon is challenging to treat. When the deformity is flexible, treatment options have included tendon transfer, often combined with a medial slide calcaneal osteotomy and/or a lengthening of the lateral column. Posterior calcaneal osteotomy has been shown to give correction, although not full correction. Lengthening of the lateral column also has been shown to give correction and has been used in the more severe flexible deformities, but it involves either fusion of the calcaneocuboid joint or risk of arthritis at this joint. An osteotomy combining the calcaneal medial slide with a lengthening of the lateral column at the same osteotomy site has been tested in the laboratory. This combined osteotomy provides a lengthening of the lateral column, but it is positioned away from the calcaneocuboid joint. In this study, the osteotomy was compared with a medial slide calcaneal osteotomy and an Evans lengthening of the lateral column, using a cadaver flatfoot model. Radiographic measurements were made to evaluate correction of the planovalgus deformity after each of these procedures. There was statistically significant improved correction with the new osteotomy compared with that in a standard medial slide, and correction was comparable to that in the lengthening of the lateral column. This combined osteotomy may be a reasonable alternative when more correction is desired than can be obtained from a medial slide alone and when the surgeon wishes to avoid an osteotomy near the calcaneocuboid joint.

Bilateral posterior fracture-dislocation of the shoulders: management by bilateral shoulder hemiarthroplasties.

Bilateral posterior fracture-dislocation of the shoulders is rare, with only 26 reported cases in the literature. We present the case of a patient who sustained bilateral posterior fracture-dislocations after a first time seizure. Due to significant articular surface involvement, bilateral hemiarthroplasties were performed. The literature on this injury and current treatment options is also reviewed.

Purification and characterization of a novel tyrosyl-aminopeptidase from human osteoclastomas.

1. An aminopeptidase that preferentially releases tyrosine residues from synthetic substrates has been purified from human osteoclastomas. This enzyme also hydrolyses dipeptides having an N-terminal tyrosine and a hydrophobic carboxy-terminal amino acid. 2. The tyrosyl-aminopeptidase consists of two identical subunits with M(r)s of about 100,000. 3. The enzyme is a metallopeptidase and is inhibited by chelating agents, chloromethylketone analogues of hydrophobic amino acids, and bestatin.

Purification and characterization of a tripeptidyl peptidase I from human osteoclastomas: evidence for its role in bone resorption.

Tripeptidyl peptidase I (EC 3.4.14.9), which cleaves tripeptides from the N-terminus of synthetic substrates, has been purified from human osteoclastomas (a bone tumor containing large numbers of normal osteoclasts). The enzyme has an M(r) of 48 kDa but forms aggregates with an M(r) of about 700 kDa. The tripeptidyl peptidase has an acidic pH optimum (approximately pH 5.0), suggesting that it has a lysosomal localization and prefers substrates with a hydrophobic amino acid in the P1 position. There is an absolute requirement for a nonsubstituted N-terminus. The enzyme is inhibited by reagents which modify serine and histidine residues. Lysosomal tripeptidyl peptidase is known to be capable of cleaving Gly-Pro-X triplets from synthetic collagen-like polypeptides. Ala-Ala-Phe-CH2Cl, a potent inhibitor of osteoclastoma tripeptidyl peptidase, inhibits osteoclastic bone resorption in an in vitro test system. This suggests that tripeptidyl peptidase I, secreted by osteoclasts, is involved at some stage in the degradation of bone collagen.

Determination of loading parameters in the canine hip in vivo.

The loading parameters in the canine hip were determined from multiple studies, involving the collection of kinematic and force plate data in vivo joint reaction force from an instrumented hip replacement prosthesis, and in vivo femoral cortical bone strain gauge data in different dogs. In the middle of the stance phase of gait the canine femur was flexed 110 degrees with respect to the pelvis and formed a 20 degree angle relative to the floor. At this point in the gait cycle, a line passing from the superior to the inferior aspect of the pubic symphysis was parallel to the floor. The joint reaction force measurements showed that the net force vector during midstance was directed inferiorly, posteriorly, and laterally, with a peak magnitude of up to 1.65 times the body weight. A torsional moment of 1.6 N m is exerted about the femoral shaft. In vivo strain data showed that during gait peak compressive strains of -300 to -502 microstrain were produced on the medial aspect of the femoral cortex and peak tensile strains of +250 to +458 midstrain were produced on the femoral cortex. At the midstance phase of gait, principal cortical bone strains were rotated up to 29 degrees relative to the long axis of the femur, suggesting torsional loads on the femur. These data in combination provide valuable insights on the loading parameters of the canine hip which can be used in future applications of the canine as a model for evaluating mechanically based phenomena such as bone ingrowth and remodeling or hip prostheses.

Degradation of bone matrix proteins by osteoclast cathepsins.

1. The degradation of the bone matrix proteins osteocalcin, osteonectin and alpha 2HS-glycoprotein by human cathepsins B and L and human osteoclastoma cathepsins has been investigated. 2. Intermediate degradation products (M(r) > 12 kDa) were not observed during the digestion of alpha 2HS-glycoprotein and osteonectin by cathepsins B and L although they were observed with some of the osteoclastoma cathepsins. Most of the osteoclastoma cathepsins were capable of degrading these two proteins to small peptides at comparable rates. 3. Each cathepsin produced a different pattern of osteocalcin degradation products. 4. The extensive range of non-collagenous proteins in bone matrix may necessitate the production by osteoclasts of cathepsins with different specificities during bone resorption.

Human osteoclastomas contain multiple forms of cathepsin B.

During bone resorption, the osteoclast secretes hydrolytic enzymes into the sealing zone which it creates between itself and the bone surface. Since this environment is acidic, proteinases active at low pH must therefore be responsible for degrading the bone matrix, which is largely composed of type I collagen. To investigate these enzymes, we have used human osteoclastomas as the starting material. Sequential chromatography on S-Sepharose, phenyl-Sepharose, heparin-Sepharose and Sephacryl S-200HR resulted in the separation of six cysteine proteinase activities. These proteinases have Mr values ranging from 20,000 to 42,000. The pH profiles of activity showed optima between 3.5-6.0 for both synthetic substrates and type I collagen. All the proteinases were able to degrade soluble and insoluble type I collagen. The kinetics of hydrolysis using Z-Phe-Arg-NHMec and Bz-Phe-Val-Arg-NHMec as substrates resulted in values within the range expected for cathepsin B. The six activities were all inhibited by the cysteine proteinase inhibitors antipain, chymostatin, leupeptin and E-64. The rate constants of inactivation using Z-Phe-Tyr-(O-t-Bu)CHN2 were also similar to the published rates for cathepsin B. Antibodies to cathepsin B reacted with all activities. These antibodies localised the enzyme activities to the osteoclast within the tumour. Northern blotting using a cDNA probe to cathepsin B revealed three species of mRNA transcripts. These results suggest that multiple forms of cathepsin B-like proteinases are involved in osteoclastic bone resorption.

A program to teach house calls for the elderly to fourth-year medical students.

The authors report on the development, implementation, and evaluation of a curriculum to teach house calls for the elderly to fourth-year medical students. A faculty committee drew up a statement of philosophy: developed attitude, knowledge, and skill objectives: and specified required educational experiences for the curriculum. which was incorporated into a required eight-week rotation in ambulatory medicine. In 1985 and 1986, 18 students completed the new curriculum at three different clinic sites and made a total of 167 documented house calls. Prerotation and postrotation measurement of the students' attitudes documented a significantly (p less than .003) more favorable attitude toward house calls after completion of the curriculum. The students further indicated that they were more likely after the curriculum than before it to provide house calls as part of their future medical practice. The students' evaluation of the curriculum provided information on the relative effectiveness of teaching strategies used in the curriculum and documented the success of the curriculum in transmitting knowledge about the homebound elderly.

Comparison of schizophrenics and normals on a visual search task.

The response times of 16 paranoids, 16 nonparanoids and 16 normals were compared on a search task which required subjects to identify target letters embedded in displays of varying numbers of non-targets. The rate on increase in response times with increased numbers of letters displayed was not markedly different for the various groups, although a derived measure of decision and response-selection time indicated that normals selected responses more rapidly. When compared with normals, schizophrenics seemed to experience more difficulty in response selection and decision than in processing visual stimulus information.