Preliminary study of proton magnetic resonance spectroscopy to assess bone marrow adiposity in the third metacarpus or metatarsus in Thoroughbred racehorses.

BACKGROUND: Magnetic resonance spectroscopy (MRS) has been used to investigate metabolic changes within human bone. It may be possible to use MRS to investigate bone metabolism and fracture risk in the distal third metacarpal/tarsal bone (MC/MTIII) in racehorses. OBJECTIVES: To determine the feasibility of using MRS as a quantitative imaging technique in equine bone by using the 1H spectra for the MC/MTIII to calculate fat content (FC). STUDY DESIGN: Observational cross-sectional study. METHODS: Limbs from Thoroughbred racehorses were collected from horses that died or were subjected to euthanasia on racecourses. Each limb underwent magnetic resonance imaging (MRI) at 3 T followed by single-voxel MRS at three regions of interest (ROI) within MC/MTIII (lateral condyle, medial condyle, proximal bone marrow [PBM]). Percentage FC was calculated at each ROI. Each limb underwent computed tomography (CT) and bone mineral density (BMD) was calculated for the same ROIs. All MR and CT images were graded for sclerosis. Histology slides were graded for sclerosis and proximal marrow space was calculated. Pearson or Spearman correlations were used to assess the relationship between BMD, FC and marrow space. Kruskal-Wallis tests were used to check for differences between sclerosis groups for BMD or FC. RESULTS: Eighteen limbs from 10 horses were included. A negative correlation was identified for mean BMD and FC for the lateral condyle (correlation coefficient = -0.60, p = 0.01) and PBM (correlation coefficient = -0.5, p = 0.04). There was a significant difference between median BMD for different sclerosis grades in the condyles on both MRI and CT. A significant difference in FC was identified between sclerosis groups in the lateral condyle on MRI and CT. MAIN LIMITATIONS: Small sample size. CONCLUSIONS: 1H Proton MRS is feasible in the equine MC/MTIII. Further work is required to evaluate the use of this technique to predict fracture risk in racehorses.

RFWD3 modulates response to platinum chemotherapy and promotes cancer associated phenotypes in high grade serous ovarian cancer.

Background: DNA damage repair is frequently dysregulated in high grade serous ovarian cancer (HGSOC), which can lead to changes in chemosensitivity and other phenotypic differences in tumours. RFWD3, a key component of multiple DNA repair and maintenance pathways, was investigated to characterise its impact in HGSOC. Methods: RFWD3 expression and association with clinical features was assessed using in silico analysis in the TCGA HGSOC dataset, and in a further cohort of HGSOC tumours stained for RFWD3 using immunohistochemistry. RFWD3 expression was modulated in cell lines using siRNA and CRISPR/cas9 gene editing, and cells were characterised using cytotoxicity and proliferation assays, flow cytometry, and live cell microscopy. Results: Expression of RFWD3 RNA and protein varied in HGSOCs. In cell lines, reduction of RFWD3 expression led to increased sensitivity to interstrand crosslinking (ICL) inducing agents mitomycin C and carboplatin. RFWD3 also demonstrated further functionality outside its role in DNA damage repair, with RFWD3 deficient cells displaying cell cycle dysregulation, reduced cellular proliferation and reduced migration. In tumours, low RFWD3 expression was associated with increased tumour mutational burden, and complete response to platinum chemotherapy. Conclusion: RFWD3 expression varies in HGSOCs, which can lead to functional effects at both the cellular and tumour levels.

Point-of-care human milk concentration by passive osmosis: comprehensive analysis of fresh human milk samples.

OBJECTIVE: Preterm infants need enrichment of human milk (HM) for optimal growth. This study evaluated a novel, point-of-care human milk concentration (HMC) process for water removal from fresh HM samples by passive osmotic concentration. STUDY DESIGN: Nineteen fresh HM samples were concentrated by incubation with the HMC devices for 3 h at 4 °C. Pre- and post-concentration HM samples were compared by HM properties for: pH, osmolality, macronutrients, enzyme activity, bioactive, and total cell viability. RESULTS: Passive osmotic concentration reduced HM volume by an average of 16.3% ± 3.8% without a significant effect on pH or cell viability. Ten of the 41 HM components did not differ significantly (p > 0.05) between pre- and post-concentration samples. Twenty-three increased within the expected range by volume reduction. Six increased more than expected, two less than expected, and none decreased significantly. CONCLUSION: Passive osmotic concentration of fresh HM can concentrate HM components by selective removal of water. HM osmolality and pH remained within neonatal feeding parameters.

Maternal stress and breastfeeding outcomes in the NICU couplet care experience: a prospective cohort study.

OBJECTIVE: Couplet care is an innovative approach to provide postpartum care in the neonatal intensive care unit (NICU) with little known about its impact on infant feeding outcomes and maternal stress. STUDY DESIGN: We compared breastfeeding outcomes and maternal NICU-related stress among mother-infant dyads based on exposure to couplet care in a prospective cohort study. RESULT: Among 19 couplet-care exposed (CCE) dyads and 19 traditional postpartum care dyads, CCE mothers had lower self-reported stress related to parent-infant relationship as compared to traditional care (P < 0.001). CCE infants received relatively more feeds at the breast (P < 0.001), more breastmilk feeds (P = 0.002), and fewer feeds by staff (P < 0.001). Adjusted for gestational age, marital status, and infant length of stay, couplet care was associated with being in a higher tertile of percent breastmilk feeds (aOR 7.29, 95% CI 1.45-36.65). CONCLUSION: NICU couplet care was associated with improved parental stress and breastfeeding outcomes during hospitalization.

Establishing Neonate-specific Prognostic Markers in Acute Liver Failure: Admission Alpha Fetoprotein and Novel nALF Scores Predict Patient Outcomes.

OBJECTIVES: To develop neonate-specific prediction models for survival with native liver (SNL) in neonatal acute liver failure (ALF) and to determine if these prediction models have superior accuracy to existing models for older children with ALF. STUDY DESIGN: A single-center, retrospective chart review was conducted on neonates ≤ 30 days of life between 2005 and 2022 with ALF (INR ≥ 2 or prothrombin time [PT] ≥ 20s and liver dysfunction). Statistical analysis included comparison of patients by outcome of SNL and generalized linear modeling to derive prediction models. The predictive accuracy of variables was evaluated by receiver operating characteristic (ROC) analysis and Kaplan-Meier survival analysis. RESULTS: 51 patients met inclusion criteria. The most common causes of neonatal ALF included ischemia (22%), infection (20%), and gestational alloimmune liver disease (GALD) (16%). Overall SNL rate was 43% (n=22). AFP levels were higher in SNL patients (p=0.034) and differed more significantly by SNL status among non-GALD patients (n=21, p=0.001). An AFP < 4775 ng/mL had 75% sensitivity and 100% specificity to predict death or transplant in non-GALD patients with an area under the ROC curve (AUROC) of 0.81. A neonate-specific admission model (INR and ammonia) and peak model (PT and ammonia) also predicted SNL with good accuracy (AUROC = 0.73 and 0.82 respectively). CONCLUSIONS: We identified neonate-specific prognostic variables for SNL in ALF. Findings from our study may help early risk stratification to guide medical decision-making and consideration for liver transplantation.

Integrative multi-omics profiling in human decedents receiving pig heart xenografts.

In a previous study, heart xenografts from 10-gene-edited pigs transplanted into two human decedents did not show evidence of acute-onset cellular- or antibody-mediated rejection. Here, to better understand the detailed molecular landscape following xenotransplantation, we carried out bulk and single-cell transcriptomics, lipidomics, proteomics and metabolomics on blood samples obtained from the transplanted decedents every 6 h, as well as histological and transcriptomic tissue profiling. We observed substantial early immune responses in peripheral blood mononuclear cells and xenograft tissue obtained from decedent 1 (male), associated with downstream T cell and natural killer cell activity. Longitudinal analyses indicated the presence of ischemia reperfusion injury, exacerbated by inadequate immunosuppression of T cells, consistent with previous findings of perioperative cardiac xenograft dysfunction in pig-to-nonhuman primate studies. Moreover, at 42 h after transplantation, substantial alterations in cellular metabolism and liver-damage pathways occurred, correlating with profound organ-wide physiological dysfunction. By contrast, relatively minor changes in RNA, protein, lipid and metabolism profiles were observed in decedent 2 (female) as compared to decedent 1. Overall, these multi-omics analyses delineate distinct responses to cardiac xenotransplantation in the two human decedents and reveal new insights into early molecular and immune responses after xenotransplantation. These findings may aid in the development of targeted therapeutic approaches to limit ischemia reperfusion injury-related phenotypes and improve outcomes.

Patient and public involvement and engagement (PPIE): how valuable and how hard? An evaluation of ALL_EARS@UoS PPIE group, 18 months on.

BACKGROUND: ALL_EARS@UoS is a patient and public involvement and engagement (PPIE) group for people with lived experience of hearing loss. The purpose of the group is to share experiences of hearing loss and hearing healthcare, inform research and improve services for patients at University of Southampton Auditory Implant Service. A year after inception, we wanted to critically reflect on the value and challenges of the group. Four members of ALL_EARS@UoS were recruited to an evaluation steering group. This paper reports the evaluation of the group using the UK Standards for Public Involvement. METHODS: An anonymous, mixed-methods questionnaire was co-designed and shared with members of ALL_EARS@UoS using an online platform. The questionnaire was designed to capture satisfaction, individual feedback through free-text answers, and demographic information. Descriptive statistics have been used to express the satisfaction and demographic data. Reflexive thematic analysis has been used to analyse the free-text responses. Group engagement and activity data over time were monitored and collected. RESULTS: The questionnaire response rate was 61% (11/18). Areas identified as strengths were 'Communication' and 'Working together'. Five themes were developed from the thematic analysis; (1) Increased knowledge and awareness around the topic of hearing health for group members and wider society, (2) supporting research, (3) inclusivity within the group, (4) opportunity to make a difference for people in the future and (5) running of the group/group organisation. The data highlighted the value and challenges of PPIE. Members described feeling listened to and appreciation of being able to share experiences. Time of day and meeting format were identified as challenges as they affected who could attend the meetings. The ability to secure and maintain sufficient funding and time to support inclusive and diverse PPIE activities is a challenge for researchers. CONCLUSIONS: We have identified how PPIE added value to both group members and researchers, emphasising the true benefit of PPIE. We have highlighted challenges we are facing and our plan to tackle these. We aim to continue to develop and sustain a group that reflects the diversity of the Deaf/deaf or hard of hearing community and of our local community.

Genomic multidisciplinary teams: A model for navigating genetic mainstreaming and precision medicine.

AIM: Recent rapid advances in genomics are revolutionising patient diagnosis and management of genetic conditions. However, this has led to many challenges in service provision, education and upskilling requirements for non-genetics health-care professionals and remuneration for genomic testing. In Australia, Medicare funding with a Paediatric genomic testing item for patients with intellectual disability or syndromic features has attempted to address this latter issue. The Sydney Children's Hospitals Network - Westmead (SCHN-W) Clinical Genetics Department established Paediatric and Neurology genomic multidisciplinary team (MDT) meetings to address the Medicare-specified requirement for discussion with clinical genetics, and increasing genomic testing advice requests. METHODS: This SCHN-W genomic MDT was evaluated with two implementation science frameworks - the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) and GMIR - Genomic Medicine Integrative Research frameworks. Data from June 2020 to July 2022 were synthesised and evaluated, as well as process mapping of the MDT service. RESULTS: A total of 205 patients were discussed in 34 MDT meetings, facilitating 148 genomic tests, of which 73 were Medicare eligible. This was equivalent to 26% of SCHN-W genetics outpatient activity, and 13% of all Medicare-funded paediatric genomic testing in NSW. 39% of patients received a genetic diagnosis. CONCLUSION: The genomic MDT facilitated increased genomic testing at a tertiary paediatric centre and is an effective model for mainstreaming and facilitating precision medicine. However, significant implementation issues were identified including cost and sustainability, as well as the high level of resourcing that will be required to scale up this approach to other areas of medicine.

Creatine supplementation and resistance training to preserve muscle mass and attenuate cancer progression (CREATINE-52): a protocol for a double-blind randomized controlled trial.

BACKGROUND: Muscle mass is important for metastatic prostate cancer survival and quality of life (QoL). The backbone of treatment for men with metastatic castration sensitive prostate cancer (mCSPC) is androgen deprivation therapy (ADT) with an androgen signaling inhibitor. ADT is an effective cancer treatment, but it facilitates significant declines in muscle mass and adverse health outcomes important to mCSPC survivors, such as fatigue, and reductions in physical function, independence, insulin sensitivity, and QoL. In non-metastatic CSPC survivors, resistance training (RT) preserves muscle mass and improves these related health outcomes, but the biggest barrier to RT in CSPC survivors of all stages is fatigue. Creatine monohydrate supplementation coupled with RT (Cr + RT) may address this barrier since creatine plays a critical role in energy metabolism. Cr + RT in cancer-free older adults and other clinical populations improves muscle mass and related health outcomes. Evidence also suggests that creatine supplementation can complement cancer treatment. Thus, Cr + RT is a strategy that addresses gaps in survivorship needs of people with mCSPC. The purpose of this parallel, double-blind randomized controlled trial is to test the effects of 52-weeks of Cr + RT compared with placebo (PLA) and RT (PLA + RT) on muscle mass, other related health outcomes, and markers of cancer progression. METHODS: We will carry out this trial with our team's established, effective, home-based, telehealth RT program in 200 mCSPC survivors receiving ADT, and evaluate outcomes at baseline, 24-, and 52-weeks. RT will occur twice weekly with elastic resistance bands, and an established creatine supplementation protocol will be used for supplementation delivery. Our approach addresses a major facilitator to RT in mCSPC survivors, a home-based RT program, while utilizing a supervised model for safety. DISCUSSION: Findings will improve delivery of comprehensive survivorship care by providing a multicomponent, patient-centered lifestyle strategy to preserve muscle mass, improve health outcomes, and complement cancer treatment (NCT06112990).

Clinical outcomes following identification of an incidental p53 signature in the fallopian tube.

Fallopian tube pathology in patients with BRCA1 and BRCA2 mutations suggests a possible pathway to high grade serous ovarian carcinoma originates with a p53 signature, which is thought to represent a potential precursor to serous tubal intraepithelial carcinoma (STIC). The clinical implications of an isolated p53 signature in the average-risk population has not been well-established. This study aims to describe clinical outcomes in patients with incidentally noted p53 signature lesions. All patients diagnosed with a p53 signature lesion on final pathology from 2014 to 2022 were identified at a large academic institution. P53 signature is defined by our lab as morphologically normal to mildly atypical tubal epithelium with focal p53 over-expression on immunohistochemistry. Incidental p53 signature was defined as identification of a fallopian tube lesion excised for benign or unrelated indications in patients without a known hereditary disposition. Demographic, clinicopathologic, and genetic data were collected. A total of 127 patients with p53 signatures were identified. Thirty-six patients were excluded for established ovarian cancer or high-risk history leaving 91 total patients. Five patients (5.5%) developed a malignancy, none of which were ovarian or primary peritoneal, at the end of the eight and a half year follow up period. Twenty-four (26.4%) patients had salpingectomy without any form of oophorectomy at the time of initial surgery, while 67 (73.6%) patients had at least a unilateral oophorectomy at the time of their salpingectomy. Seven patients (7.7%) had additional surgery after p53 signature diagnosis; however, the final pathology yielded no evidence of malignancy in all these patients. After subsequent surgeries, 19 (20.9%) patients maintained their ovaries. The diagnosis of an incidental p53 signature was not associated with any primary peritoneal or ovarian cancer diagnoses during our follow up, and the majority of patients were managed conservatively by their providers with no further intervention after diagnosis.

Serving IPV Survivors in Culturally Diverse Communities: Perspectives From Current Service Providers.

This qualitative study examines current IPV service providers' perspectives on service delivery methods that best reach and serve IPV survivors from culturally diverse communities. Semi-structured interviews were conducted with 11 service providers, and transcripts were analyzed for themes related to service providers' experiences. Five themes emerged from the data that suggest best practices for reaching and serving survivors from culturally diverse backgrounds, including understanding survivors' backgrounds, promoting trust and inclusivity, building community relationships, providing culturally responsive education on IPV, and supporting current and future staff with training. Study findings provide implications for the education and training of future service providers.

Fenestrated endovascular aortic repair of a superior mesenteric artery aneurysm using carbon dioxide angiography and intravascular ultrasound.

Superior mesenteric artery aneurysms are rare; however, current guidelines suggest they all require repair due to the high rupture and mortality rates, and endovascular repair is an effective management strategy. Iodinated contrast traditionally used in endovascular repair can cause significant complications, including severe allergic reactions and contrast-induced nephropathy in patients with chronic renal disease. Therefore, other imaging methods should be used during endovascular procedures to reduce these risks. We describe a unique and innovative approach using carbon dioxide angiography and intravascular ultrasound during fenestrated endovascular repair of an uncommon superior mesenteric artery aneurysm in a patient with severe contrast allergies.

Pre-pregnancy BMI, rate of gestational weight gain, and preterm birth among US Pacific Islander individuals.

OBJECTIVE: The objective of this study was to examine the association between rate of gestational weight gain (GWG) and preterm birth (PTB) classified by pre-pregnancy BMI among Pacific Islander individuals in the United States. METHODS: Pacific Islander mothers (n = 55,975) and singleton infants (22-41 gestational weeks) without congenital anomalies were included using data from the National Center for Health Statistics (2014-2018). PTB was compared by pre-pregnancy BMI among women in each stratum of rate of GWG using Cox proportional hazards models. RESULTS: Compared with mothers with a rate of GWG within the guidelines, mothers with a rate of GWG below the guidelines and either pre-pregnancy underweight (adjusted hazard ratio [aHR] = 1.84, 95% CI: 1.10-3.06), healthy weight (aHR = 1.38, 95% CI: 1.15-1.65), obesity class I (aHR = 1.22, 95% CI: 0.97-1.52), or obesity class II (aHR = 1.43, 95% CI: 1.05-1.96) had an increased risk of PTB; mothers with a rate of GWG above the guidelines and either pre-pregnancy underweight (aHR = 1.57, 95% CI: 0.92-2.69) or obesity class II (aHR = 1.31, 95% CI: 0.98-1.76) had an increased risk of PTB. CONCLUSIONS: The association between rate of GWG below or above the guidelines and PTB differs by pre-pregnancy BMI among Pacific Islander individuals.

Compatibility of Various Hormones in Phytobase and HRT Heavy Cream Bases.

The release of United States Pharmacopeia Chapter <800> and the revisions to United States Pharmacopeia Chapter <795> (official November 1, 2023) indicates a changing regulatory climate and a trend towards increasingly high standards for the extension of beyond-use dates beyond the default recommended by the guidelines. Given the increased scrutiny and the additional requirements for establishing extended beyond-use dates, additional testing is required to help pharmacies provide the best formulations with scientifically robust data to support an extended beyond-use date for patient convenience. The objective of this study was to demonstrate the suitability of two vehicles, Phytobase and HRT Heavy, for compounded hormone therapy by evaluating the stability and antimicrobial effectiveness of the vehicles with common combinations of hormones.

Single cell RNA-sequencing of Ewing sarcoma tumors demonstrates transcriptional heterogeneity and clonal evolution.

Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients even prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. We also were able to identify the composition of the TME and molecularly dissect the transcriptional profile of circulating tumor cells in peripheral blood at the time of diagnosis.

Parent and grandparent neonatal intensive care unit visitation for preterm infants.

OBJECTIVE: Characterize family NICU visitation and examine associations with maternal health and social factors and infant health outcomes. STUDY DESIGN: Retrospective cohort study of 167 infants born ≤32 weeks at two urban NICUs 01/2019-03/2020. Average nurse-documented family member visitation and associations of visitation with maternal and infant factors and outcomes were compared. RESULTS: Mothers visited 4.4 days/week, fathers 2.6 days/week, and grandparents 0.4 days/week. Older maternal age, nulliparity, and non-English primary language were associated with more frequent family visitation. Mothers with depression or anxiety history visited less. Maternal depression and public insurance were associated with fewer father visits. Low parental visitation was associated with lower odds of feeding any maternal milk at discharge and low maternal visitation with 11.5% fewer completed infant subspecialty appointments in the year following discharge (95% CI -20.0%, -3.0%). CONCLUSION: Families with social disadvantage visited less often. Parental visitation was associated with infant feeding and follow-up.