SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients.

Introduction: Successful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased organ donors over the last decade, there remains a considerable shortfall of suitable organs available for transplantation. Over half of UK donors are certified dead by neurological criteria following brain stem compression, which leads to severe physiological stress in the donor, combined with a hyperinflammatory state.

Defatting of donor transplant livers during normothermic perfusion-a randomised clinical trial: study protocol for the DeFat study.

Background: Liver disease is the third leading cause of premature death in the UK. Transplantation is the only successful treatment for end-stage liver disease but is limited by a shortage of suitable donor organs. As a result, up to 20% of patients on liver transplant waiting lists die before receiving a transplant.

The role of neuroestrogens in the estrogen-induced gonadotropin surge in male monkeys.

Neuroestrogens locally synthesized in the brain are known to play a role in sexual behaviors. However, the question of whether neuroestrogens are involved in the regulation of the gonadotropin-releasing hormone (GnRH) release is just emerging. Because previous studies in this lab indicate that neuroestradiol is also important for the pulsatile release as well as the surge release of GnRH in female rhesus monkeys, in the present study, we examined whether neuroestradiol plays a role in the estrogen-induced LH surge in orchidectomized (ORX) male rhesus monkeys.

Are vegans being overlooked in our prescribing practices: An orthopaedic perspective from Bristol, United Kingdom.

Aim: Bristol is considered the vegan capital of the UK. The UK vegan index reveals that Bristol has 360,000 Google searches each month for Vegan content. However, the possible animal source of the medications we prescribe is not commonly contemplated.

Exercise snacking to improve physical function in pre-frail older adult memory clinic patients: a 28-day pilot study.

Background: Finding innovative yet feasible ways of preventing physical and cognitive decline in those at risk is a critical global challenge, with exercise being championed as a key precursor to robust health in later life. Exercise snacking, here defined as short bouts of sporadic [muscle-strengthening] exercise, is one such strategy designed to overcome typical participation barriers observed in older adults. This study examined the acceptability of exercise snacking amongst pre-frail older adults and explored the efficacy of this approach in improving physical function.

Circulating cytokine levels in systemic sclerosis related interstitial lung disease and idiopathic pulmonary fibrosis.

Exploration of cytokine levels in systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is needed to find common and diverse biomolecular pathways. Circulating levels of 87 cytokines were compared amongst 19 healthy controls and consecutive patients with SSc-ILD (n = 39), SSc without ILD (n = 29), and IPF (n = 17) recruited from a Canadian centre using a log-linear model adjusted for age, sex, baseline forced vital capacity (FVC), and immunosuppressive or anti-fibrotic treatment at time of sampling. Also examined was annualized change in FVC.

Perioperative multimodal analgesic injection for patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion surgery.

Purpose: This retrospective cohort study compared postoperative as-needed (PRN) opioid consumption pre and postimplementation of a perioperative multimodal analgesic injection composed of ropivacaine, epinephrine, ketorolac, and morphine in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Secondary outcomes include pain score measurements, time to ambulation, length of stay, blood loss, 90-day complication rate, operating room time, nonopioid medication usage, and total inpatient medication cost before and after the initiation of this practice.

Methods: Consecutive patients weighing ≥ 20 kg who underwent PSF for a primary diagnosis of AIS between January 2017 and December 2020 were included.

Does transversus abdominis function correlate with prone plank and bench bridge holding time in club cricket players?

Background: Bridge and plank holding times are used to evaluate core stability. Transversus abdominis (TA) muscle function is assessed using ultrasound and also provides input on an individual's core stability.

Objectives: A correlation study comparing TA muscle function with bridge and plank holding time in club cricketers.

World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF) Core Set Development for Interstitial Lung Disease.

The World Health Organization (WHO) introduced the International Classification of Functioning, Disability, and Health (ICF) as a scientific method of disability data collection comprised of >1,200 categories describing the spectrum of impairment types (functional, symptoms-based and anatomical) under the bio-psycho-social model with consideration of and (pf). ICF Core Sets and ICF Checklists are streamlined disease-specific resources for clinical use, service provision, and for use in health economics and health policy. ICF can disclose strengths and weaknesses across multiple patient-reported outcome measures (PROMs) and help consolidate best-fitting question-items from multiple PROMs.

What is the purpose of clinical trial monitoring?

Background: The sources of information on clinical trial monitoring do not give information in an accessible language and do not give detailed guidance. In order to enable communication and to build clinical trial monitoring tools on a strong easily communicated foundation, we identified the need to define monitoring in accessible language.

Methods: In a three-step process, the material from sources that describe clinical trial monitoring were synthesised into principles of monitoring.

Key questions in marine mammal bioenergetics.

Bioenergetic approaches are increasingly used to understand how marine mammal populations could be affected by a changing and disturbed aquatic environment. There remain considerable gaps in our knowledge of marine mammal bioenergetics, which hinder the application of bioenergetic studies to inform policy decisions. We conducted a priority-setting exercise to identify high-priority unanswered questions in marine mammal bioenergetics, with an emphasis on questions relevant to conservation and management.

Physiological Characterization and Transcriptomic Properties of GnRH Neurons Derived From Human Stem Cells.

Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role in the regulation of reproductive function. In this study, we sought an efficient method for generating GnRH neurons from human embryonic and induced pluripotent stem cells (hESC and hiPSC, respectively). First, we found that exposure of primitive neuroepithelial cells, rather than neuroprogenitor cells, to fibroblast growth factor 8 (FGF8), was more effective in generating GnRH neurons.

Methane Emissions from Gathering Compressor Stations in the U.S.

Using results from a nationally representative measurement campaign at 180 gathering compressor stations conducted with nine industry partners, this study estimated emissions for the U.S. gathering sector, where sector-specific emission factors have not been previously available.

Role of Kisspeptin and NKB in Puberty in Nonhuman Primates: Sex Differences.

To understand the roles of kisspeptin and neurokinin B (NKB) in puberty and sex differences in their involvement, we conducted a series of experiments measuring the release of gonadotropin-releasing hormone (GnRH) and kisspeptin in the median eminence of the hypothalamus in male and female monkeys throughout sexual development. Results indicate that kisspeptin-10 and the NKB agonist, senktide, stimulated GnRH release in males and females at the prepubertal and pubertal stages, but females are much more sensitive to kisspeptin signaling than males. Moreover, throughout the progress of puberty, major remodeling of kisspeptin and NKB signaling pathways for the regulation of GnRH release takes place.

Pediatric Erythromelalgia and SCN9A Mutations: Systematic Review and Single-Center Case Series.

Objectives: To evaluate the clinical features of erythromelalgia in childhood associated with gain-of-function SCN9A mutations that increase activity of the Na1.7 voltage-gated sodium channel, we conducted a systematic review of pediatric presentations of erythromelalgia related to SCN9A mutations, and compared pediatric clinical presentations of symptomatic erythromelalgia, with or without SCN9A mutations.

Study Design: PubMed, Embase, and PsycINFO Databases were searched for reports of inherited erythromelalgia in childhood.

Role of Kisspeptin and Neurokinin B Signaling in Male Rhesus Monkey Puberty.

Despite the well-established concept that an increase in pulsatile GnRH release triggers puberty, the precise signaling mechanism responsible for the pubertal increase in GnRH release remains unclear. A recent study indicates that developmental changes in the network formation between kisspeptin and neurokinin B (NKB) signaling greatly contribute to the pubertal increase in GnRH release in female monkeys. It is, however, unknown whether similar developmental changes in the kisspeptin and NKB network are involved in male puberty.

Role of Kisspeptin and Neurokinin B in Puberty in Female Non-Human Primates.

In human patients, loss-of-function mutations in the genes encoding kisspeptin () and neurokinin B ( and their receptors ( and , respectively) result in an abnormal timing of puberty or the absence of puberty. To understand the neuroendocrine mechanism of puberty, we investigated the contribution of kisspeptin and NKB signaling to the pubertal increase in GnRH release using rhesus monkeys as a model. Direct measurements of GnRH and kisspeptin in the median eminence of the hypothalamus with infusion of agonists and antagonists for kisspeptin and NKB reveal that kisspeptin and NKB signaling stimulate GnRH release independently or collaboratively by forming kisspeptin and NKB neuronal networks depending on the developmental age.

Obligatory role of hypothalamic neuroestradiol during the estrogen-induced LH surge in female ovariectomized rhesus monkeys.

Negative and positive feedback effects of ovarian 17β-estradiol (E) regulating release of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) are pivotal events in female reproductive function. While ovarian feedback on hypothalamo-pituitary function is a well-established concept, the present study shows that neuroestradiol, locally synthesized in the hypothalamus, is a part of estrogen's positive feedback loop. In experiment 1, E benzoate-induced LH surges in ovariectomized female monkeys were severely attenuated by systemic administration of the aromatase inhibitor, letrozole.

Kisspeptin and Neurokinin B Signaling Network Underlies the Pubertal Increase in GnRH Release in Female Rhesus Monkeys.

Loss-of-function or inactivating mutations in the genes coding for kisspeptin and its receptor (KISS1R) or neurokinin B (NKB) and the NKB receptor (NK3R) in humans result in a delay in or the absence of puberty. However, precise mechanisms of kisspeptin and NKB signaling in the regulation of the pubertal increase in gonadotropin-releasing hormone (GnRH) release in primates are unknown. In this study, we conducted a series of experiments infusing agonists and antagonists of kisspeptin and NKB into the stalk-median eminence, where GnRH, kisspeptin, and NKB neuroterminal fibers are concentrated, and measuring GnRH release in prepubertal and pubertal female rhesus monkeys.

The Methylcytosine Dioxygenase Ten-Eleven Translocase-2 (tet2) Enables Elevated GnRH Gene Expression and Maintenance of Male Reproductive Function.

Reproduction depends on the establishment and maintenance of elevated GnRH neurosecretion. The elevation of primate GnRH release is accompanied by epigenetic changes. Specifically, cytosine residues within the GnRH gene promoter are actively demethylated, whereas GnRH mRNA levels and peptide release rise.

Impact of pulmonary disease on patient-reported outcomes and patient-performed functional testing in systemic lupus erythematosus.

Objectives: This study examines the effect of pulmonary disease on patient-reported outcomes (PROs) and patient-performed outcome (PPO) in systemic lupus erythematosus (SLE) patients at a single tertiary referral center.

Methods: Pulmonary function tests (PFTs), chest imaging, SLE-related damage, and disease activity were examined in 110 SLE patients. Presence was noted of abnormal PFTs, pleural disease, pulmonary hypertension (PH), pulmonary infarction, interstitial lung disease (ILD), and shrinking lung syndrome (SLS).

Neuroestradiol in the Stalk Median Eminence of Female Rhesus Macaques Decreases in Association With Puberty Onset.

In primates, despite the fact that GnRH neurons are mature at birth, a gonadal steroid independent central inhibition restrains the initiation of puberty. The neural substrates responsible for this central inhibition, however, are unclear. In this study, we tested the hypothesis that neuroestradiol release in the hypothalamus decreases prior to the pubertal increase in GnRH release.

Acute Influences of Bisphenol A Exposure on Hypothalamic Release of Gonadotropin-Releasing Hormone and Kisspeptin in Female Rhesus Monkeys.

Bisphenol A (BPA) is an industrial compound with pervasive distribution in the environments of industrialized countries. The U.S.

Prolonged infusion of estradiol benzoate into the stalk median eminence stimulates release of GnRH and kisspeptin in ovariectomized female rhesus macaques.

Our recent study indicates that a brief infusion (20 min) of estradiol (E2) benzoate (EB) into the stalk-median eminence (S-ME) stimulates GnRH release with a latency of approximately 10 minutes. In contrast to the effect induced by a brief infusion of EB, it has previously been shown that systemic EB administration suppresses release of GnRH, kisspeptin, and LH with a latency of several hours, which is known as the negative feedback action of E2. We speculated that the differential results by these 2 modes of EB administration are due to the length of E2 exposure.