Extensive retreat and re-advance of the West Antarctic Ice Sheet during the Holocene.

To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters 1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so)2-4. Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today's grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance 5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss 6 on millennial timescales will depend on bedrock topography and mantle viscosity-parameters that are difficult to measure and to incorporate into ice-sheet models.

Kenyan palliative care providers' and leaders' perceptions of palliative care research needs and support to facilitate rigorous research.

BACKGROUND: Palliative care (PC) can reduce symptom distress and improve quality of life for patients and their families experiencing life-threatening illness. While the need for PC in Kenya is high, PC service delivery and research is limited. Qualitative research is needed to explore potential areas for PC research and support needed to enable that research. This insight is critical for informing a national PC research agenda and mobilizing limited resources for conducting rigorous PC research in Kenya. OBJECTIVES: To explore perceptions of priority areas for PC research and support needed to facilitate rigorous research from the perspective of Kenyan PC providers and leaders. METHODS: Focus groups (FGs) were conducted in November and December of 2018 using a semi-structured interview guide. FGs were audio-recorded, transcribed, and analyzed using a thematic content analysis approach. RESULTS: Three FGs were conducted (n = 22 participants). Ten themes related to PC research emerged, including research on: 1) beliefs about death, disease, and treatment to inform PC; 2) awareness about PC, 3) integration of PC within the health system; 4) understanding caregiver experiences and needs; 5) community health volunteers (CHVs) and volunteer programs; 6) evaluation of costs and benefits of PC; 7) treatment approaches, including complementary and alternative medicine (CAM) and advanced diagnostics at end of life; 8) other suggestions for research, 9) populations in need of PC research; and 10) resources for enabling research. CONCLUSIONS: Kenyan PC providers and leaders identified key areas requiring increased scientific inquiry and critical resources needed to enable this research. These findings can help to focus future PC research in Kenya and encourage funding agencies to prioritize the issues identified.

Addressing immediate public health needs as part of Afghan evacuees' resettlement to the United States during the COVID-19 pandemic.

OBJECTIVES: Since the removal of US troops from Afghanistan in 2021, the United States welcomed Afghan evacuees through Operation Allies Welcome. Using cell phone accessibility, the CDC Foundation worked with public-private partners to protect evacuees from the spread of COVID-19 and provide accessibility to resources. STUDY DESIGN: This was a mixed methods study. METHODS: The CDC Foundation activated its Emergency Response Fund to accelerate public health components of Operation Allies Welcome, including testing, vaccination, and COVID-19 mitigation and prevention. The CDC Foundation began the provision of cell phones to evacuees to ensure access to public health and resettlement resources. RESULTS: The provision of cell phones provided connections between individuals and access to public health resources. Cell phones provided means to supplement in-person health education sessions, capture and store medical records, maintain official resettlement documents, and assist in registration for state-administered benefits. CONCLUSIONS: Phones provided necessary connectivity to friends and family for displaced Afghan evacuees and higher accessibility to public health and resettlement resources. As many evacuees did not have access to US-based phone services upon entry, provision of cell phones and plans for a fixed amount of service time provided a helpful start in resettlement while also being a mechanism to easily share resources. Such connectivity solutions helped to minimize disparities among Afghan evacuees seeking asylum in the United States. Provision of cell phones by public health or governmental agencies can help to provide equitable resources to evacuees entering the United States for social connection, healthcare resources, and resources to assist in the process of resettlement. Further research is needed to understand the generalizability of these findings to other displaced populations.

An intra-action review conducted by the CDC Foundation during COVID-19 to evaluate emergency response procedures.

OBJECTIVES: During times of emergency response, the CDC Foundation leverages partnerships and relationships to better understand the situation and respond rapidly to save lives. As the COVID-19 pandemic began to unfold, an opportunity became clear to improve our work in emergency response through documentation of lessons learned and incorporating them into best practices. STUDY DESIGN: This was a mixed methods study. METHODS: The CDC Foundation Response, Crisis and Preparedness Unit conducted an internal evaluation via an intra-action review to evaluate and rapidly improve emergency response activities to provide effective and efficient response-related program management. RESULTS: The processes developed during the COVID-19 response to conduct timely and actionable reviews of the CDC Foundation's operations led to the identification of gaps in the work and management processes and to creation of subsequent actions to address these issues. Such solutions include surge hiring, establishing standard operating procedures for processes not yet documented, and creating tools and templates to streamline emergency response operations. CONCLUSIONS: The creation of manuals and handbooks, intra-action reviews, and impact sharing for emergency response projects led to actionable items meant to improve processes and procedures and the ability of the Response, Crisis and Preparedness Unit to quickly mobilize resources directed toward saving lives. These products are now open-source resources that can be used by other organizations to improve their own emergency response management systems.

Impact of fetal exposure to mycotoxins on longissimus muscle fiber hypertrophy and miRNA profile.

BACKGROUND: Longissimus muscle samples were collected from lambs exposed in utero to mycotoxins [E-, endophyte-free tall fescue seed without ergot alkaloids (negative control) or E + , endophyte-infected tall fescue seed containing ergot alkaloids] during mid-gestation (MID; E + /E-) or late-gestation (LATE; E-/E +) harvested at two developmental stages (FETAL, gestational d133) or (MAT, near maturity, 250 d of age; n = 3/treatment/developmental stage). Muscle samples were examined to determine the impact of in utero mycotoxin exposure on skeletal muscle fiber hypertrophy and the miRNA profile at FETAL and MAT. RESULTS: Longissimus weight was greater (P < 0.05) in E + /E- lambs compared to E-/E + lambs at MAT; however, FETAL longissimus weight did not differ (P > 0.10) between fescue treatments. Type I fiber cross sectional area was larger (P < 0.10) for E + /E- than E-/E + at MAT but did not differ (P > 0.10) between fescue treatments at FETAL. Type II fiber area was larger (P < 0.05) at MAT in E + /E- compared to E-/E + but did not differ (P < 0.05) between fescue treatments at FETAL. Cross-sectional Type I and Type II longissimus muscle fiber area increased (P < 0.05) from FETAL to MAT by 6.86-fold and 10.83-fold, respectively. The ratio of Type II:Type I muscle fibers was lower (P = 0.04) at MAT compared to FETAL. There were 120 miRNA differentially expressed (q < 0.05) between FETAL and MAT. Maternal fescue treatment did not alter (q > 0.05) expression of miRNAs in the longissimus muscle. miR-133, -29a, -22-3p, and -410-3p were identified as highly significant with a log2 fold change > 4. In vitro satellite cell cultures showed that selected miRNAs (miR-22-3p, 29a, 27a, and 133a) are differentially regulated during proliferation and differentiation indicating a role of miRNA in muscle hypertrophy. CONCLUSIONS: Exposure to mycotoxins did not alter fiber type but had long-term impacts on postnatal muscle hypertrophy and cross-sectional area. The miRNA profile of the longissimus was not altered by Maternal mycotoxin exposure at FETAL or MAT. Developmental age altered the miRNA transcriptome and mRNA expression of known genes related to muscle growth. These results indicate that Maternal exposure to E + fescue seed during LATE gestation can alter postnatal muscle hypertrophy in sheep; however, these changes are not regulated by the miRNA transcriptome of the longissimus muscle.

Role of family caregivers regarding sexual and reproductive health for women and girls with intellectual disability: A scoping review.

BACKGROUND: While people with intellectual disability (ID) face disparities relating to sexual and reproductive health (SRH) services, little is known about the role of family caregivers who assist women and girls with ID access SRH services. This scoping review examined the findings of studies to elucidate the role of family caregivers with regard to SRH for women and girls with ID. METHOD: We used Arksey and O'Malley's six-stage scoping framework, with Levac, Colquhoun and O'Brien's revisions, to evaluate identified sources. We searched three electronic databases, six ID journals and reference lists in full-text articles. Inclusion criteria included (1) primary and secondary source research studies in peer-reviewed journals; (2) published in English; (3) all research methodologies (i.e. qualitative, quantitative, mixed methods and systematic reviews or commentaries); (4) published between 2000 and 2016; and (5) studies from any country. RESULTS: The search yielded 2062 studies; 57 articles met inclusion criteria. Most studies employed purposive, convenience or criterion sampling. Participants included people with ID, family caregivers, paid caregivers and health-care professionals. Findings were summarised thematically: (1) menstruation and menopause; (2) vaccinations and preventive screenings; (3) supporting sexuality and healthy relationships; (4) coordinating with health-care providers and (5) contraception and sterilisation. CONCLUSIONS: Findings from this scoping review underscore the need for more and better-quality research, including how family caregivers assist women and girls with ID access perinatal and preventive SRH services and sexual abuse education. Family caregivers, women and girls with ID and health-care providers need increased access to information about SRH.

Change in multidimensional problems and quality of life over three months after HIV diagnosis: a multicentre longitudinal study in Kenya and Uganda.

BACKGROUND: Evidence on patient-reported outcomes of newly diagnosed HIV patients is scarce, and largely cross-sectional. This prospective cohort study describes the prevalence of, and changes in, patient-reported outcomes in the three months after HIV diagnosis, in 11 HIV outpatient centres in Kenya and Uganda. METHODS: Adults were recruited within 14 days of result, completing self-report measures four times at monthly intervals. Multilevel mixed-effects linear regression (quality of life continuous outcomes) and ordinal logistic regression (symptoms and concerns categorical outcomes) modelled change over time, with repeated observations grouped within individuals adjusted for demographic/clinical characteristics, and multiple imputation for missing data. RESULTS: 438 adults were enrolled and 234 (53·4%) initiated ART. Improvement was found for MOS-HIV physical health (from 46·3 [95% CI 45·1-47·3], to 53·7 [95% CI 52.8-54·6], p < 0.001), and mental health (from 46·4 [95% CI 45·5-47·3] to 54·5 [95% CI 53·7-55·4], p < 0.001). POS subscale 'interpersonal problems' improved but remained burdensome (OR = 0·91, 95% CI = 0·87-0·94, p < 0.001; 22·7% reported severe problems at final time point). The scores for the existential POS subscale (OR = 0·95, 95% CI = 0.90-1·00, p = 0.056) and physical/psychological problems POS subscale (OR = 0·97, 95% CI = 0.92-1·02, p = 0.259) did not improve. Participants who initiated ART had worsening physical/psychological (OR = 0·64, 95% CI = 0·41-0·99, p = 0·045) and interpersonal problems (OR = 0·64, 95% CI = 0·42-0·96, p = 0·033). CONCLUSION: Although some self-reported outcomes improve over time, burden of interpersonal problems remains substantial and existential concerns do not improve.

BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007).

This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.

Oncologists' and oncology nurses' attitudes and practices towards family involvement in cancer consultations.

Family members (FMs) regularly attend cancer consultations with patients, may assume an array of roles (e.g. emotional, informational) and their involvement may result in benefits and/or challenges. Little is currently known about how oncology health professionals (HPs) view FMs who accompany a patient in consultations. This study aimed to explore the attitudes and practices of Australian oncologists and oncology nurses regarding family involvement in consultations. Eleven oncologists and 10 nurses from a range of subspecialties and tumour streams participated in semi-structured interviews. Interviews were transcribed and qualitatively analysed using framework analysis methods. Five relevant themes were identified: (1) the varied and dynamic nature of family roles during consultations; (2) positivity towards FMs; (3) the benefits of family involvement to the FM themselves; (4) current HP practices to facilitate positive family involvement; and (5) the challenges of family involvement in consultations and HP practices to manage them. Overall, participants held mostly positive attitudes towards family involvement. Although they identified a number of challenges which can arise when family are involved, many noted these situations are the exception, that there are strategies which can help to overcome the challenges, and that the benefits of family involvement typically outweigh the costs.

Behavioural and cognitive outcomes in young children of mothers with intellectual impairments.

BACKGROUND: Despite an increase in international studies examining the experiences of parents with intellectual impairments and their children, few have utilised population-based data. This study investigated the behavioural and cognitive outcomes of 3-year-old US children of mothers with intellectual impairments compared with children of mothers without intellectual impairments. METHODS: This study employed a secondary analysis of the Fragile Families Child and Wellbeing Study, a longitudinal birth cohort study in the US. Our analytic sample included mothers with intellectual impairments (n = 263) and a comparison group of mothers without intellectual impairments (n = 1298), as well as each sampled mother's focal child. When weighted, Fragile Families is representative of all births in US cities with populations over 200 000. RESULTS: Children of mothers with intellectual impairments had poorer behavioural and cognitive outcomes in comparison to same-age children of mothers without intellectual impairments. Notably, however, children of mothers with intellectual impairments were not at increased risk of being aggressive unless their family income was below 200% of the federal poverty level. Further, families headed by mothers with intellectual impairments experienced multiple hardships related to socioeconomic factors, limited social supports and poor self-reported health. CONCLUSION: Appropriate policies and programmes must be developed and implemented to effectively support these families, such as increased financial benefits.

BSACI guideline for the management of chronic urticaria and angioedema.

This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web-based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research.

Obliquity-paced Pliocene West Antarctic ice sheet oscillations.

Thirty years after oxygen isotope records from microfossils deposited in ocean sediments confirmed the hypothesis that variations in the Earth's orbital geometry control the ice ages, fundamental questions remain over the response of the Antarctic ice sheets to orbital cycles. Furthermore, an understanding of the behaviour of the marine-based West Antarctic ice sheet (WAIS) during the 'warmer-than-present' early-Pliocene epoch ( approximately 5-3 Myr ago) is needed to better constrain the possible range of ice-sheet behaviour in the context of future global warming. Here we present a marine glacial record from the upper 600 m of the AND-1B sediment core recovered from beneath the northwest part of the Ross ice shelf by the ANDRILL programme and demonstrate well-dated, approximately 40-kyr cyclic variations in ice-sheet extent linked to cycles in insolation influenced by changes in the Earth's axial tilt (obliquity) during the Pliocene. Our data provide direct evidence for orbitally induced oscillations in the WAIS, which periodically collapsed, resulting in a switch from grounded ice, or ice shelves, to open waters in the Ross embayment when planetary temperatures were up to approximately 3 degrees C warmer than today and atmospheric CO(2) concentration was as high as approximately 400 p.p.m.v. (refs 5, 6). The evidence is consistent with a new ice-sheet/ice-shelf model that simulates fluctuations in Antarctic ice volume of up to +7 m in equivalent sea level associated with the loss of the WAIS and up to +3 m in equivalent sea level from the East Antarctic ice sheet, in response to ocean-induced melting paced by obliquity. During interglacial times, diatomaceous sediments indicate high surface-water productivity, minimal summer sea ice and air temperatures above freezing, suggesting an additional influence of surface melt under conditions of elevated CO(2).

A randomized controlled trial of postoperative analgesia following total knee replacement: transdermal Fentanyl patches versus patient controlled analgesia (PCA).

BACKGROUND: This randomized controlled trial compared a standard patient controlled analgesic (PCA) regime with a transdermal and oral Fentanyl regime for post-operative pain management in patients undergoing total knee replacement. METHODS: One hundred and ninety-six patients undergoing total knee replacement were recruited. Pre- and post-operatively Visual Analogue Score (VAS), Oxford Knee Score, Health Anxiety and Depression Score and Brief Pain Inventory Score were completed. According to the day 1, VAS score patients were randomly allocated to either a PCA regime or a Fentanyl transdermal/oral regime. Patient reported outcomes were measured until the patients were discharged. RESULTS: The results demonstrate that in terms of analgesic effect, day of discharge and side effect profile the two regimes are comparable. CONCLUSIONS: We conclude that a Fentanyl transdermal regime provides adequate analgesic effect comparable to a standard PCA regime in conjunction with a low side effect profile. Using a transdermal analgesic system provides efficient continuous delivery enabling a smooth transition from hospital to home within the first week. Transdermal Fentanyl provides an alternative analgesic regime that can provide an equivalent analgesic effect so as to enable a satisfactory outcome for the patient in terms of function and pain. LEVEL OF EVIDENCE: II.

Tumours with elevated levels of the Notch and Wnt pathways exhibit efficacy to PF-03084014, a γ-secretase inhibitor, in a preclinical colorectal explant model.

BACKGROUND: Dysregulation of the Notch pathway has been identified to play an important role in the development and progression of colorectal cancer (CRC). In this study, we used a patient-derived CRC explant model to investigate the efficacy of the clinical γ-secretase inhibitor (GSI) PF-03084014. METHODS: A total of 16 CRC explants were treated with PF-03084014. Knockdown of RBPjκ gene was used to determine the specificity of PF-03084014. Evaluation of the Notch and Wnt pathways in CRC explant tumours was performed by gene array and immunoblotting. RESULTS: We identified a subset of CRC tumours that exhibited elevations of the Notch and Wnt pathways sensitive to PF-03084014. Treatment with the GSI resulted in a significant reduction in cleaved Notch, Axin2 (Wnt-dependent gene) and active ß-catenin. In addition, knockdown of the RBPjκ gene showed that PF-03084014 has specificity for the Notch pathway in an HCT116 cell line xenograft model. Finally, an increase in apoptosis was observed in CRC001- and CRC021-sensitive tumours. CONCLUSION: This study provides evidence that inhibition of γ-secretase may be beneficial in a subset of patients with elevated levels of the Wnt and Notch pathways.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Africa: a report from the Global Opioid Policy Initiative (GOPI).

With nearly 1.1 billion inhabitants living in more than 50 countries, Africa is the world's poorest and most socioeconomically underdeveloped continent. Despite some advances for individual states, many African countries have very low opioid consumption and, overall, the continent has the lowest consumption per capita of any in the world. This article presents the findings of the first systematic study of the availability and accessibility of opioids for the management of cancer pain across the continent. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 25 of 52 countries, with 744 million of the region's 1127 million people (66%) covered by the survey. Many countries had severely restricted formularies of opioids and only 15 of 25 had morphine available in oral IR, CR and injectable formulations. Even when opioids are on formulary they are often unavailable, and access is significantly impaired by widespread over-regulation that is pervasive across the region.

Use of AgomiR and AntagomiR technologies to alter satellite cell proliferation in vitro, miRNA expression, and muscle fiber hypertrophy in intrauterine growth-restricted lambs.

Introduction: microRNAs (miRNAs) are small non-coding RNAs that work at the posttranscriptional level to repress gene expression. Several miRNAs are preferentially expressed in skeletal muscle and participate in myogenesis. This research was conducted to alter endogenous miRNA expression in skeletal muscle to promote muscle hypertrophy. Methods: Two experiments were conducted using mimic/agomiR or antagomir technologies to alter miRNA expression and examine changes in myoblast proliferation in vitro (experiment 1) and muscle hypertrophy in vivo (experiment 2). In vitro experiments found that antagomiR-22-3p and mimic-127 increased myoblast proliferation compared to other miRNA treatments or controls. These miRNA treatments, antagomiR-22-3p (ANT22) and agomiR-127 (AGO127), were then used for intramuscular injections in longissimus muscle. Results and discussion: The use of antagomiR or mimic/agomiR treatments down-regulated or up-regulated, respectively, miRNA expression for that miRNA of interest. Expression of predicted target KIF3B mRNA for miR-127 was up-regulated and ACVR2a mRNA was up-regulated for miR-22-3p. ANT22 injection also up-regulated the major regulator of protein synthesis (mTOR). Proteomic analyses identified 11 proteins for AGO127 and 9 proteins for ANT22 that were differentially expressed. Muscle fiber type and cross-sectional area were altered for ANT22 treatments to transition fibers to a more oxidative state. The use of agomiR and antagomir technologies allows us to alter miRNA expression in vitro and in vivo to enhance myoblast proliferation and alter muscle fiber hypertrophy in IUGR lambs during early postnatal growth.

Chronic preoperative pain and psychological robustness predict acute postoperative pain outcomes after surgery for breast cancer.

BACKGROUND: Few epidemiological studies have prospectively investigated preoperative and surgical risk factors for acute postoperative pain after surgery for breast cancer. We investigated demographic, psychological, pain-related and surgical risk factors in women undergoing resectional surgery for breast cancer. METHODS: Primary outcomes were pain severity, at rest (PAR) and movement-evoked pain (MEP), in the first postoperative week. RESULTS: In 338 women undergoing surgery, those with chronic preoperative pain were three times more likely to report moderate to severe MEP after breast cancer surgery (OR 3.18, 95% CI 1.45-6.99). Increased psychological 'robustness', a composite variable representing positive affect and dispositional optimism, was associated with lower intensity acute postoperative PAR (OR 0.63, 95% CI 0.48-0.82) and MEP (OR 0.71, 95% CI 0.54-0.93). Sentinel lymph node biopsy (SLNB) and intraoperative nerve division were associated with reduced postoperative pain. No relationship was found between preoperative neuropathic pain and acute pain outcomes; altered sensations and numbness postoperatively were more common after axillary sample or clearance compared with SLNB. CONCLUSION: Chronic preoperative pain, axillary surgery and psychological robustness significantly predicted acute pain outcomes after surgery for breast cancer. Preoperative identification and targeted intervention of subgroups at risk could enhance the recovery trajectory in cancer survivors.

miRNA transcriptome and myofiber characteristics of lamb skeletal muscle during hypertrophic growth1.

Postnatal muscle growth is achieved through hypertrophy of the muscle fibers and is impacted by the activity of satellite cells, the quiescent muscle stem cell. Several miRNAs are preferentially expressed in skeletal muscle and could provide a mechanism for increasing muscle hypertrophy through satellite cell proliferation and/or differentiation. The objectives of this study were to: 1) Characterize the miRNA transcriptome of the longissimus thoracis et lumborum muscle at several developmental timepoints [gestational d 85 (PN1), 110 (PN2), 133 (PN3), postnatal d 42 (PW1), 65 (PW2), 243 (MAT)] during muscle hypertrophy in lambs, and 2) examine miR-29a, identified in sequencing to be differentially regulated across development, loss of function on satellite cell proliferation and differentiation. Muscle fiber characteristics showed drastic increases (p < 0.0001) in fiber size and alterations in muscle fiber type occur during pre and postnatal development. miRNA sequencing comparisons were performed in developmental order (PN1 vs. PN2, PN2 vs. PN3, PN3 vs. PW1, PW1 vs. PW2, PW2 vs. MAT). There were 184 differentially expressed (P adj < 0.05) miRNA, 142 unique miRNA, from all 5 comparisons made. The transitional stage (PN3 vs. PW1) had the largest number (115) of differentially expressed miRNA. Inhibition of miR-29a in satellite cell culture increased (p < 0.05) cell proliferation and differentiation capacity. Characterization of the miRNA transcriptome provides valuable insights into the miRNA involved in muscle fiber hypertrophy and the potential importance of the transitional period.

Mycotoxin ingestion during late gestation alters placentome structure, cotyledon transcriptome, and fetal development in pregnant sheep.

Ergot alkaloids, a class of mycotoxins, induce vasoconstriction when consumed by animals and humans. Pregnant ewes (n = 16; 81.2 kg ± 7.7) were assigned fed endophyte-infected tall fescue seed (E+; 4.14 µg ergovaline + ergovalinine/g seed) or a control diet (CON; 0 µg ergovaline + ergovalinine) for increasing duration during late gestation (from gd86 to gd110 or gd133) to examine changes in placentome morphology and mRNA transcriptome, and fetal development. Exposure to E+ fescue reduced serum prolactin concentrations at gd110 and gd133 demonstrating treatment efficacy. For control ewes, cotyledon and total placentome weights decreased with advancing gestation due to remodeling of placental tissues; however, cotyledon and placentome weight did not change with advancing gestation in E+ fed ewes. Fetal brain sparing was evident in E+ exposed fetuses at gd110 and gd133 compared to CON, which demonstrates asymmetrical growth and intrauterine growth restriction. Mycotoxin exposure (E+) resulted in differential expression of 22 genes in the cotyledon tissue at gd110 but only one gene at gd133 compared to CON. These results suggest that the response to mycotoxin exposure in the pregnant sheep model has an immediate impact on placental remodeling and fetal development that persists throughout the duration of the exposure period.