A Critical Reappraisal of the Bleeding Time.

Seminars in Thrombosis and Hemostasis (STH) celebrates 50 years of publishing in 2024. To celebrate this landmark event, STH is republishing some archival material. This manuscript represents the second most highly cited paper ever published in STH. The manuscript published without an abstract, and essentially represented a State of the Art Review on the bleeding time, a relatively invasive procedure that required an incision on the skin or earlobe of a patient, and timing how long it took for the incision to stop bleeding. The bleeding time test was first described in 1901 by the French physician Milian, who presented three studies of bleeding from stab wounds made in the fingertips of healthy and diseased subjects. In 1910, Duke observed the duration of bleeding from small incisions of the ear lobe, and pointed out that the duration of bleeding was increased in instances of reduced platelet counts. The test was subsequently repeatedly modified, and numerous variants of the test, including semiautomated methods, were described by several workers. The most frequently utilised test reflected one described by Ivy and coworkers, who shifted the location of the incision to the volar aspect of the forearm and applied a blood pressure cuff to the arm to maintain a standard venous pressure. The bleeding time has been proposed for use as a diagnostic test for platelet-related bleeding disorders, a measure of efficacy in various forms of therapy, and as a prognosticator of abnormal bleeding. The authors to the current review reevaluated the bleeding time literature using methods to assess the performance of the test in 1990, locating 862 printed documents that discussed the bleeding time, the majority in peer-reviewed professional journals. As this is a republication of archival material, transformed into a modern format, we apologise in advance for any errors introduced during this transformation.

Circulating cell-free endometrial DNA level is unaltered during menstruation and in endometriosis.

STUDY QUESTION: Is circulating cell-free DNA (cirDNA) from the endometrium elevated during menstruation and in endometriosis? SUMMARY ANSWER: Endometrial cirDNA does not increase during menstruation and is not elevated in endometriosis. WHAT IS KNOWN ALREADY: Changes in cirDNA associated with common benign conditions are a potential source of false positives in cancer diagnostic applications, but also present an opportunity for biomarker development for diseases such as endometriosis. Elevated cirDNA has been reported in endometriosis patients compared to healthy community controls, but no difference in total or endometrial cirDNA has been found between patients with endometriosis and patients with other gynaecological conditions. Likewise, menstruation is a potential driver of changes in cirDNA levels and tissue profile, but total and endothelial cirDNA do not increase during menstruation. STUDY DESIGN, SIZE, DURATION: For endometriosis comparisons, 59 participants with surgically confirmed endometriosis and 27 laparoscopic patients without endometriosis (hospital controls) were prospectively recruited, while 25 healthy community participants (healthy controls) were recruited in a university setting. Total and endometrial cirDNA and cirDNA fragmentation were measured across the three groups. For menstrual comparisons, 36 matched non-menstruating and menstruating samples were collected from healthy women recruited within a university setting, and the endometrial cirDNA was compared between the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: cirDNA was extracted from venous blood plasma then quantitated by quantitative PCR of ALU repetitive element (115 bp) and TP53 gene sequence (105 bp) for total concentration. cirDNA derived from the endometrium was quantitated by methylation-specific droplet digital PCR of a FAM101A region (69 bp) after bisulfite conversion of the DNA. A cirDNA size fragmentation ratio was obtained by quantifying a long segment of ALU repetitive element (247 bp) and expressing the amount relative to the 115 bp ALU target. MAIN RESULTS AND THE ROLE OF CHANCE: No differences in cirDNA level were found in any comparison populations in this study. Mean total cirDNA was unchanged between healthy controls (ALU-115-3.31 ng/ml; TP53-2.73 ng/ml), hospital controls (ALU-115-3.47 ng/ml; TP53-2.83 ng/ml) and endometriosis patients (ALU-115-3.35 ng/ml; TP53-2.66 ng/ml). Likewise, endometrial cirDNA was unchanged between healthy controls (18.3 copies/ml), hospital controls (20.6 copies/ml) and endometriosis patients (22 copies/ml). Endometrial cirDNA did not change during menstruation (non-menstruating: 38 copies/ml; menstruating: 33 copies/ml). Irrespective of endometriosis diagnosis, blood from patients undergoing laparoscopy (hospital controls: 0.77; endometriosis patients: 0.79), had a significantly higher cirDNA size ratio than community-recruited healthy controls (0.64), indicating increased abundance of long cirDNA fragments. LIMITATIONS, REASONS FOR CAUTION: It was not possible to completely match the age, BMI and parity between the three cohorts investigated, however of these, only age has been shown to influence circulating DNA levels and not within the age range of our cohort. Blood from community-recruited healthy women and women undergoing laparoscopy was collected via antecubital vein venepuncture (processed within 3 h) and with either peripheral cannula or venepuncture (processed within 6 h), respectively, which could potentially impact the size distribution of circulating DNA fragments. For the collection of non-menstruating phase blood samples, we did not differentiate between follicular phase, ovulation and luteal phase. Thus, only the mensturating samples were collected at a consistent phase, and any fluctuations in cirDNA that occur at the other phases may have obscured small changes during menstruation. WIDER IMPLICATIONS OF THE FINDINGS: There is no evidence that cirDNA has potential as a diagnostic biomarker for endometriosis. Endometriosis, representing a common benign gynaecological condition, and menstruation, representing a normal physiological occurrence in women, should not affect methylation-based diagnostics in other disease areas, including oncology. STUDY FUNDING/COMPETING INTEREST(S): N.L.Y.: Australian Government Research Training Program (RTP) Stipend through The University of New South Wales, Translational Cancer Research Network PhD Scholarship Top-Up Award via the Cancer Institute NSW, Beth Yarrow Memorial Award in Medical Science, UNSW Completion Scholarship; C.E.H.: Gynaecological Oncology Fund of the Royal Hospital for Women; K.W.: Ovarian Cancer Research Foundation and CAMILLA AND MARC. C.E.F.: UNSW Women's Wellbeing Academy and the Australian Human Rights Institute. We declare the following competing interest: K.W. holds stock in Guardant Health, Exact Sciences and Epigenomics AG. No other authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.

Maternal periconceptional and first trimester protein restriction in beef heifers: effects on placental parameters and fetal and neonatal calf development.

Few studies have investigated the effects of nutrition during the periconception and early gestation periods on fetal and placental development in cattle. In this study, nulliparous yearling heifers (n=360) were individually fed a diet high or low in protein (HPeri and LPeri) beginning 60 days before conception. From 24 to 98 days after conception, half of each treatment group was changed to the alternative high- or low-protein diet (HPost and LPost) yielding four groups in a 2×2 factorial design. A subset of heifers (n=46) was necropsied at 98 days after conception and fetoplacental development assessed. Placentome number and volume decreased in response to LPeri and LPost diets respectively. Absolute lung, pancreas, septum and ventricle weights decreased in LPost versus HPost fetuses, whereas the post-conception diet altered absolute and relative liver and brain weights depending on sex. Similarly, changes in fetal hepatic gene expression of factors regulating growth, glucose output and lipid metabolism were induced by protein restriction in a sex-specific manner. At term, neonatal calf and placental measures were not different. Protein restriction of heifers during the periconception and early gestation periods alters fetoplacental development and hepatic gene expression. These changes may contribute to functional consequences for progeny, but this may not be apparent from gross morphometry at birth.

Morphometric and gene expression analyses of stromal expansion during development of the bovine fetal ovary.

During ovarian development stroma from the mesonephros penetrates and expands into the ovarian primordium and thus appears to be involved, at least physically, in the formation of ovigerous cords, follicles and surface epithelium. Cortical stromal development during gestation in bovine fetal ovaries (n=27) was characterised by immunohistochemistry and by mRNA analyses. Stroma was identified by immunostaining of stromal matrix collagen type I and proliferating cells were identified by Ki67 expression. The cortical and medullar volume expanded across gestation, with the rate of cortical expansion slowing over time. During gestation, the proportion of stroma in the cortex and total volume in the cortex significantly increased (P<0.05). The proliferation index and numerical density of proliferating cells in the stroma significantly decreased (P<0.05), whereas the numerical density of cells in the stroma did not change (P>0.05). The expression levels of 12 genes out of 18 examined, including osteoglycin (OGN) and lumican (LUM), were significantly increased later in development (P<0.05) and the expression of many genes was positively correlated with other genes and with gestational age. Thus, the rate of cortical stromal expansion peaked in early gestation due to cell proliferation, whilst late in development expression of extracellular matrix genes increased.

Peri-conception and first trimester diet modifies reproductive development in bulls.

Nutritional perturbation during gestation alters male reproductive development in rodents and sheep. In cattle both the developmental trajectory of the feto-placental unit and its response to dietary perturbations is dissimilar to that of these species. This study examined the effects of dietary protein perturbation during the peri-conception and first trimester periods upon reproductive development in bulls. Nulliparous heifers (n=360) were individually fed a high- or low-protein diet (HPeri and LPeri) from 60 days before conception. From 24 until 98 days post conception, half of each treatment group changed to the alternative post-conception high- or low-protein diet (HPost and LPost) yielding four treatment groups in a 2×2 factorial design. A subset of male fetuses (n=25) was excised at 98 days post conception and fetal testis development was assessed. Reproductive development of singleton male progeny (n=40) was assessed until slaughter at 598 days of age, when adult testicular cytology was evaluated. Low peri-conception diet delayed reproductive development: sperm quality was lowered during pubertal development with a concomitant delay in reaching puberty. These effects were subsequent to lower FSH concentrations at 330 and 438 days of age. In the fetus, the low peri-conception diet increased the proportion of seminiferous tubules and decreased blood vessel area in the testis, whereas low first trimester diet increased blood vessel number in the adult testis. We conclude that maternal dietary protein perturbation during conception and early gestation may alter male testis development and delay puberty in bulls.

Complications of external cephalic version: a retrospective analysis of 1121 patients at a tertiary hospital in Sydney.

OBJECTIVE: To report the complication rate associated with external cephalic version (ECV) at term. DESIGN: Single-centre retrospective study. SETTING: A major tertiary hospital in Sydney, Australia. POPULATION OR SAMPLE: All women who underwent an ECV at Royal Prince Alfred Hospital from 1995-2013 were included. METHODS: ECV was attempted on all consenting women with a breech presentation at term in the absence of contraindications. Complications were classified as minor (transient cardiotocography abnormalities, ruptured membranes, small antepartum haemorrhage) or serious (fetal death, placental abruption, fetal distress requiring emergency caesarean section, fetal bone injury, cord prolapse). ECV success rates and rate of reversion to breech were recorded. MAIN OUTCOME MEASURES: The primary outcome was the incidence of serious complications. Secondary outcome measures were the rate of minor complications and reversion to breech. RESULTS: Of 1121 patients that underwent ECV, five (0.45%) experienced a serious complication. There was one placental abruption, one emergency caesarean section for fetal distress and two cord prolapses. There was one fetal death attributable to a successful ECV. Forty-eight women (4.28%) experienced a minor complication. Reversion to the breech occurred in sixteen patients (3.32%). CONCLUSION: ECV at term is associated with a low rate of serious complications. TWEETABLE ABSTRACT: Study of 1121 consecutive ECV attempts shows low rate of complications although one fetal death reported.

[Problematic Internet use, time spent online and personality traits]. / Utilisation problématique d'Internet, temps passé en ligne et traits de personnalité.

BACKGROUND: Internet addiction or problematic Internet use is a recent and increasingly recognized disorder which has been consistently associated with many psychiatric disorders, adding to the documented negative consequences of problematic Internet use. However, very few studies have examined the relationship between problematic Internet use and personality traits and none in a French sample. Moreover, those which have evaluated this relationship have mainly been conducted on small samples. OBJECTIVE: The main goal of our study was to explore the relationship between problematic Internet use, time spent online and personality traits in a French sample, taking into account the presence of depressive symptoms, and gender. METHODS: A sample of 276 participants aged from 18 to 50 (M=28; SD=8.9) completed a questionnaire assessing problematic Internet use, time spent online, the presence of ten personality traits and depressive symptoms. RESULTS: Our results revealed significant differences between genders. Among men, problematic Internet use was associated with personality clusters A and B while in women no cluster or personality traits were associated. Time spent online was predicted by schizoid personality traits among men and avoidant personality traits among women. DISCUSSION: Our results indicate that cluster A (schizoid and schizotypal) and cluster B traits (borderline and antisocial) play a more important role in problematic Internet use than cluster C traits among men. Differences between men and women regarding the relationships between personality traits, time online and problematic Internet use may be related to differences in the activities engaged in by men and women online. We observed that communication websites use was more prevalent among women while erotic, gambling and shopping websites use was more prevalent among men suggesting that the characteristics of problematic Internet use may vary according to gender. CONCLUSION: Few studies have examined the relationship between problematic Internet use, time spent online and personality traits, and none among a French sample. These results suggest the importance of assessing the impact of personality traits on Internet use, particularly on time spent online, by differentiating results in terms of gender and online activities.

Feasibility Assessment of a Novel Isolation Care Tent in Uganda During the 2022 Sudan ebolavirus Outbreak.

This case study describes a feasibility assessment of a novel isolation care tent used in health facilities in Uganda during the 2022 Sudan ebolavirus outbreak. The Isolation System for Treatment and Agile Response to High-Risk Infections Model 1B (ISTARI 1B) is a single-occupancy, portable, negative-pressure isolation tent designed for the safe delivery of standard care to patients with a communicable disease, including Ebola disease (Sudan). At the request of the Uganda Ministry of Health, the Makerere University Infectious Diseases Institute and University of Nebraska Medical Center partnered to evaluate 7 health facilities across 4 districts in Uganda for infrastructure, case management, and infection prevention and control (IPC) capacity relevant to isolation care and ISTARI 1B use. A 3-day workshop was held with IPC leaders to provide familiarization and hands-on experience with the ISTARI 1B, delineate appropriate use scenarios in Ugandan healthcare settings, contextualize ISTARI 1B use in case management and IPC workflows, develop a framework for site assessment and implementation readiness, and consider ongoing monitoring, assessment, and intervention tools. Workshop participants performed a comprehensive site assessment and mock deployment of the ISTARI 1B. In this case study, we describe lessons learned from health facility assessments and workshop outcomes and offer recommendations to support successful ISTARI 1B implementation. Use scenarios and implementation strategies were identified across facility levels, including tools for site assessment, training, risk communication, and ongoing quality and safety monitoring.

Experiences of Users with an Online Self-Guided Mental Health Training Program Using Gamification.

Young adulthood is a period of high risk for the development of mental health concerns. Increasing well-being among young adults is important to prevent mental health concerns and their consequences. Self-compassion has been identified as a modifiable trait with the potential to protect against mental health concerns. An online self-guided mental health training program using gamification was developed and the user experience was evaluated in a 6-week experimental design. During this period, 294 participants were allocated to use the online training program via a website. User experience was assessed via self-report questionnaires, and interaction data for the training program were also collected. Results showed that those who completed the intervention (n= 47) visited the website on average 3.2 days a week, with a mean of 45.8 interactions during the 6 weeks. Participants report positive user experiences of the online training, on average a System Usability Scale Brooke (1) score of 79.1 (out of 100) at the end-point. Participants showed positive engagement with story elements of the training, based on an average score of 4.1 (out of 5) in the evaluation of the story at the end-point. This study found the online self-compassion intervention for youth to be acceptable, although some features seem preferred by users as compared to others. Gamification in the form of a guiding story and a reward structure seemed to be a promising element for successfully motivating participants and serving as a guiding metaphor for self-compassion.

Morphological classification of bovine ovarian follicles.

Follicle classification is an important aid to the understanding of follicular development and atresia. Some bovine primordial follicles have the classical primordial shape, but ellipsoidal shaped follicles with some cuboidal granulosa cells at the poles are far more common. Preantral follicles have one of two basal lamina phenotypes, either a single aligned layer or one with additional layers. In antral follicles <5 mm diameter, half of the healthy follicles have columnar shaped basal granulosa cells and additional layers of basal lamina, which appear as loops in cross section ('loopy'). The remainder have aligned single-layered follicular basal laminas with rounded basal cells, and contain better quality oocytes than the loopy/columnar follicles. In sizes >5 mm, only aligned/rounded phenotypes are present. Dominant and subordinate follicles can be identified by ultrasound and/or histological examination of pairs of ovaries. Atretic follicles <5 mm are either basal atretic or antral atretic, named on the basis of the location in the membrana granulosa where cells die first. Basal atretic follicles have considerable biological differences to antral atretic follicles. In follicles >5 mm, only antral atresia is observed. The concentrations of follicular fluid steroid hormones can be used to classify atresia and distinguish some of the different types of atresia; however, this method is unlikely to identify follicles early in atresia, and hence misclassify them as healthy. Other biochemical and histological methods can be used, but since cell death is a part of normal homoeostatis, deciding when a follicle has entered atresia remains somewhat subjective.

Physiology: does gut hormone PYY3-36 decrease food intake in rodents?

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.

[Therapeutic alliance in psychotherapy: the contribution of empirical research]. / L'alliance thérapeutique en psychothérapie: apports de la recherche empirique.

INTRODUCTION: The therapeutic alliance in psychotherapy refers to the quality of the relationship between therapist and patient, as well as their agreement upon the aims and tasks of the treatment. This concept is widely used in clinical settings and, since the validation of a number of instruments, has become the focus of much research. However, the quantity of experimental evidence now available impedes the dissemination of these findings among clinicians in a concise manner. LITERATURE FINDINGS: The present paper aimed to provide a review of the literature reporting experimental evidence focusing on the therapeutic alliance. In order to do this, findings were organized around four main issues: the relationship between the therapeutic alliance and clinical outcome; the evolution of the therapeutic alliance over time; the mechanism of action by which the therapeutic alliance encourages change, and finally the factors that have been shown to influence the creation and evolution of the alliance. DISCUSSION: This review reveals that the therapeutic alliance is to this day one of the most investigated factors of psychotherapy. The therapeutic alliance enables change to take place during psychotherapy and, along with a number of specific factors, appears to be important for clinical outcome. Over time, the therapeutic alliance has been seen to evolve and several patterns have been identified. A number of characteristics inherent to the patient, the therapist, and even their interaction have been reported to influence the development and strength of the therapeutic alliance. Several hypotheses have been put forward to account for the mechanism by which the therapeutic alliance encourages change. CONCLUSION: The area of research regarding the therapeutic alliance remains dynamic. Despite the present body of knowledge surrounding this concept, a number of research questions await further investigation.

Characterizing a body positive online forum: Resistance and pursuit of appearance-ideals.

The body positive movement emerged in response to pressure to pursue the unattainable thin ideal, and promotes a more accepting stance towards the body. To date, however, little is known regarding the nature of online body positive content. Using publicly available data from a large online discussion platform (Reddit), all the forums to which commenters on a body acceptance forum (N = 1262) had also contributed were identified. For each pairing of 50 representative forums (i.e., a large number and proportion of body acceptance commenters), the commenter-overlap between the two forums was used to compute a network model, to detect communities of body acceptance commenters. By manually reviewing the topics of each community's forums, the shared interests of these commenters were identified. The majority of commenters (86 %) contributed to forums relating to women, feminism, relationships and support, and mental health. Large proportions of the commenters also revealed an interest in topics including body weight/shape, eating, exercise, and cosmetics. These findings confirm that original feminist tenets of body positivity remain present. However, our findings also suggest the existence of a sizeable subgroup interacting with topics related to the thin ideal, perhaps illustrating a gradual absorption of the body positive movement into mainstream culture.

Quantification of viable granulosa cells in murine ovarian follicles.

Ovarian follicle growth and oocyte maturation depend on the viability of granulosa cells (GC). We quantified GC in whole mouse follicles. Single follicles were isolated from adult mouse ovaries and stained with DAPI or Live-Dead stain before fixation. An objective image analysis protocol for counting fluorescent labeled GC was developed that used Image J software to measure GC cytoplasmic and nuclear areas. These data were compared to the number of GC obtained by disaggregating 96 follicles with enzymes to produce a suspension of GC, which then was stained with trypan blue and assessed using a hemocytometer. We found a linear relation between GC/follicle and follicle diameter. Viability of GC/follicle ranged from 40 ± 11 to 72 ± 7%. The coefficient of variation for image analysis of DAPI stained GC by different assessors was 4%, but the number of GC obtained from image analysis was approximately 50% less than from disaggregated follicles. The number of GC in intact mouse follicles was greater than the number reported earlier for fixed ovarian sections. We found that the number of GC was less in fluorescence labeled follicles; it is possible that the three-dimensional structure of the intact follicles obscured the fluorescent signal. Direct quantification of viable GC isolated from follicles appears to be the most accurate method.

Supplementation of rangeland primiparous Bos indicus x Bos taurus beef heifers during lactation. 1. Effects on dam milk production and liveweight, bull calf growth, live carcass characteristics and metabolic hormone concentrations.

The practice of feeding replacement-breeding bulls on high energy diets after weaning to meet liveweight (LW) and carcass expectations between 18 and 24 months of age negatively affects reproductive potential. This experiment reports upon the effects of an alternative management strategy aimed at improving calfhood nutrition in rangeland-reared bulls to enhance LW and live carcass characteristics at 2 years. Following artificial insemination (AI cohort; n = 26), or natural mating, subsequent to the addition of bulls at 39 d post-AI (NM cohort; n = 36), primiparous Santa Gertrudis heifers grazing rangeland pastures with bull calf progeny were allocated at parturition to receive either nil supplement (control; CON) or provided with unrestricted access to a pelleted vegetable protein meal-based supplement containing 35% CP (SUPP) until weaning at 199 ± (SD) 26 d. The mean estimated pellet consumption by SUPP heifers during lactation was 2.6 ± (SEM) 0.5 kg DM daily. Grazing diet quality measurements indicated nutritional restriction of CON heifers until at least 115 d of lactation. This was confirmed by lower blood urea nitrogen concentrations at 88 d (P < 0.001) and greater mean NEFA (P < 0.001) concentrations. Rainfall during mid-lactation subsequently improved grazing diet quality; thus the CON heifers experienced moderate nutritional restriction across lactation, but sufficient to reduce milk yield by 1.6 kg/d (P < 0.001) and maternal LW at weaning by 18.4 kg (P < 0.001). Bulls reared by SUPP heifers were 17.5 kg heavier at weaning (P = 0.001) and had elevated IGF-I and leptin concentrations between 4 and 4.5 months of age (P < 0.05). Effects on metabolic hormones during calfhood were cohort specific, with greater concentrations of IGF-I confined to AISUPP bulls and NMSUPP bulls demonstrating greater concentrations of leptin. Bulls were amalgamated at weaning and grazed common pastures without supplementation until the experiment concluded at 675 d. Pre-weaning plane of nutrition did not affect the LW, carcass fat depth, IGF-I or leptin concentrations of bulls after weaning. Mean eye muscle area (EMA) was greater in SUPP compared to CON bulls (68.5 ± 0.9 cm2vs 65.2 ± 0.9 cm2; P < 0.05) and AISUPP bulls tended to have greater EMA (P = 0.06) than AICON bulls from 495 d of age. Thus when primiparous heifers experience moderate nutritional restriction during lactation, supplementation may have persistent effects upon increasing carcass muscle characteristics of bull progeny.

Supplementation of rangeland primiparous Bos indicus x Bos taurus beef heifers during lactation. 2. Effects upon the reproductive development of bull calf progeny.

This experiment evaluated the effect of pre-weaning plane of nutrition of dams upon reproductive development in Bos indicus x Bos taurus bull offspring reared under extensively managed conditions in the northern Australia rangelands. Following artificial insemination (AI cohort; n = 26), or natural mating (NM cohort; n = 36), grazing primiparous heifers received either nil supplement (Control; CON), thereby experiencing a moderate nutritional restriction, or were provided a protein supplement (SUPP) between parturition and weaning at mean age 199 ± (SD) 26 d. Bull progeny grazed rangeland pastures without supplementation from weaning until the experiment concluded at 675 d. At 120 ± 3 d and 140 d ± 10 d age, within the AI and NM cohort, respectively, bull calves were subjected to a GnRH challenge (1.5 µg/kg of body weight i.m.). Jugular blood samples collected immediately before and at 60 min after administration of GnRH were analysed for LH, FSH, testosterone and inhibin concentrations. Overall mean concentrations of testosterone in SUPP bulls were greater in both the AI cohort (P = 0.05) and the NM cohort (P = 0.06). At 60 d intervals during the post-weaning period, scrotal circumference (SC) was measured and semen collected to assess concentration, progressive motility and morphology of sperm. Bulls reared by SUPP heifers had greater (P = 0.05) SC at 375 d and tended to have greater (P = 0.09) mean percentage of morphologically normal sperm (PNS). Within the NM cohort, NMSUPP bulls had greater (P = 0.04) overall mean SC and tended (P = 0.07) to demonstrate both greater progressive motility and PNS. A greater incidence of sperm morphological abnormalities, associated with sexual immaturity, were observed in CON bulls. Consequently, NMCON bulls demonstrated delayed (P = 0.03) age of sexual maturity as compared to NMSUPP bulls. In summary, improving the plane of nutrition supplied to Bos indicus x Bos taurus bulls between parturition and weaning via moderate supplementation of grazing dams reduces age at sexual maturity with consequent economic advantages to the producer.

Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis.

OBJECTIVE: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor ß (TGFß)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. METHODS: A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. RESULTS: We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFß signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. CONCLUSIONS: We provide new insights into defects in early insulin signalling, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFß ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.