Pharmacists' perspectives on opioid stewardship challenges.

Objective: Pharmacists are in a distinctive position to champion opioid stewardship principles in communications with prescribers and patients. This effort is focused on elucidating perceived barriers to uphold these principles observed in pharmacy practice.

Design: Qualitative research study.

Adult medulloblastoma in an Australian population.

Medulloblastoma in adult patients is a rare condition with limited contemporary demographic and treatment outcome data available in an Australian population. We conducted a retrospective review of patterns of care and outcomes of adult patients diagnosed with medulloblastoma treated at major neuro-oncology centres across Australia between January 2010 and December 2019. A total of 80 patients were identified and the median follow-up after diagnosis was 59.

The impact of COVID-19 shielding on the wellbeing, mental health and treatment adherence of adults with cystic fibrosis.

People with cystic fibrosis (CF) were advised to undertake 'shielding' at home during the COVID-19 pandemic to reduce their risk of infection. We studied the impact shielding had on their wellbeing, mental health (GAD-7 and PHQ-9 scores) and adherence to treatment. 63 (46%) of 137 people surveyed responded (19 anonymously; 44 gave their identity).

Environmental epidemiology of Kawasaki disease: Linking disease etiology, pathogenesis and global distribution.

Background: The pathogenesis of Kawasaki disease (KD) is commonly ascribed to an exaggerated immunologic response to an unidentified environmental or infectious trigger in susceptible children. A comprehensive framework linking epidemiological data and global distribution of KD has not yet been proposed.

Methods And Findings: Patients with KD (n = 81) were enrolled within 6 weeks of diagnosis along with control subjects (n = 87).

Puberty onset is delayed following uteroplacental insufficiency and occurs earlier with improved lactation and growth for pups born small.

Being born small programs adult diseases later in life, with the early postnatal growth rate in growth-restricted offspring playing a role in the reduction of the risk of disease in adulthood. In addition, early postnatal growth is critical for puberty onset (PO). Using cross-fostering, we determined the effects of growth restriction and prenatal and postnatal environments on PO and sex steroids.

Cardiac macrophages and apoptosis after myocardial infarction: effects of central MR blockade.

After myocardial infarction (post-MI), inflammation and apoptosis contribute to progressive cardiac remodeling and dysfunction. Cardiac mineralocorticoid receptor (MR) and β-adrenergic signaling promote apoptosis and inflammation. Post-MI, MR activation in the brain contributes to sympathetic hyperactivity and an increase in cardiac aldosterone.

Embryo transfer cannot delineate between the maternal pregnancy environment and germ line effects in the transgenerational transmission of disease in rats.

Adverse conditions in utero can have transgenerational effects, in the absence of a subsequent insult. We aimed to investigate the contribution of the maternal pregnancy environment vs. germ line effects in mediating alterations to cardiorenal and metabolic physiology in offspring from mothers born small.

Growth restriction in the rat alters expression of metabolic genes during postnatal cardiac development in a sex-specific manner.

This study investigated the impact of uteroplacental insufficiency and growth restriction on the expression of genes related to mitochondrial biogenesis, glucose transport, and antioxidant defenses in cardiac tissue at embryonic day 20 (E20) and postnatal days 1, 7, and 35 in male and female Wistar rats (8-10 per group). Bilateral uterine vessel ligation to induce growth restriction (Restricted) or sham surgery was performed at pregnancy day 18. In male and female Controls, expression of most cardiac genes decreased during postnatal life, including genes involved in mitochondrial biogenesis regulation such as PGC-1α, NRF-2, and mtTFA and the glucose transporter GLUT-1 (P < 0.

Cardio-renal and metabolic adaptations during pregnancy in female rats born small: implications for maternal health and second generation fetal growth.

Intrauterine growth restriction caused by uteroplacental insufficiency increases risk of cardiovascular and metabolic disease in offspring. Cardio-renal and metabolic responses to pregnancy are critical determinants of immediate and long-term maternal health. However, no studies to date have investigated the renal and metabolic adaptations in growth restricted offspring when they in turn become pregnant.

The effect of water height on stride frequency, stride length and heart rate during water treadmill exercise.

Reasons For Performing Study: Water treadmill exercise is often incorporated into rehabilitation programmes for horses yet little is known about the biomechanical and physiological responses to water walking.

Objectives: To establish whether stride frequency (SF) reached steady state as a result of 6 introductory water treadmill sessions and then to investigate the effect of increasing water height on SF, stride length (SL) and heart rate (HR).

Methods: Nine horses with no previous experience of water treadmills completed 6 sessions of walking for between 15 and 30 min.

Progesterone withdrawal, and not increased circulating relaxin, mediates the decrease in myometrial relaxin receptor (RXFP1) expression in late gestation in rats.

In pregnant rats, a significant decrease in myometrial relaxin family peptide receptor 1 (RXFP1) expression, indicative of a functional relaxin withdrawal for activation of myometrial contractions, occurs in late gestation and during spontaneous labor. This coincides with the highest level of circulating relaxin and a decrease in progesterone. We investigated the potential regulatory role of these two systemic factors on myometrial RXFP1 expression by examining the effects of the antiprogestin RU486 and a monoclonal antibody against rat relaxin (MCA1) in pregnant rats.

Brain renin-angiotensin-aldosterone system and ventricular remodeling after myocardial infarct: a review.

After a myocardial infarct (MI), a variety of mechanisms contribute to progressive cardiac remodeling and dysfunction. Progressive activation of central sympathoexcitatory pathways appears to depend on a neuromodulatory pathway, involving local production of aldosterone and release of endogenous ouabain-like compounds ('ouabain') possibly from magnocellular neurons in the supraoptic and paraventricular nuclei. 'Ouabain' may lower the membrane potential of neurons and thereby enhance activity of angiotensinergic pathways.

Maternal progesterone treatment rescues the mammary impairment following uteroplacental insufficiency and improves postnatal pup growth in the rat.

Uteroplacental insufficiency in the rat reduces maternal progesterone and impairs mammary function and pup milk intake, compromising postnatal growth. We determined whether progesterone administration to rat dams progesterone-deficient following uteroplacental insufficiency improves lactation and pup growth. Uteroplacental insufficiency (Restriction) or sham surgery (Control) was performed on day 18 of pregnancy in WKY rats.

Gonadotrophin subunit and GnRH receptor gene expression in the pars distalis of the equine pituitary.

In the horse, pronounced changes in fertility occur annually in response to photoperiod. However, the mechanisms regulating gonadotrophin synthesis and release in this species remain unclear. Here, we investigated the expression of gonadotrophin subunits and GnRH receptor (GnRH-R) mRNA in the pituitary glands of Thoroughbred horses during the breeding (BS) and non-breeding (NBS) season.

Brain allopregnanolone in the fetal and postnatal rat in response to uteroplacental insufficiency.

Background/aims: Allopregnanolone suppresses central nervous system activity and has neuroprotective actions in hypoxia-induced brain injury. In pregnant sheep allopregnanolone concentrations are high during fetal life and decline rapidly after birth. We investigated brain allopregnanolone concentrations of fetal and postnatal rats derived from normal and growth restricted pregnancies.

Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats.

Impaired growth in utero predicts a low nephron number and high blood pressure later in life as does slowed or accelerated growth after a normal birth weight. We measured the effects of early postnatal growth restriction, with or without prenatal growth restriction, on blood pressure and nephron number in male rat offspring. Bilateral uterine artery and vein ligation were performed to induce uteroplacental insufficiency (Restricted) on day 18 of pregnancy.

Improved lactational nutrition and postnatal growth ameliorates impairment of glucose tolerance by uteroplacental insufficiency in male rat offspring.

Intrauterine growth restriction and accelerated postnatal growth predict increased risk of diabetes. Uteroplacental insufficiency in the rat restricts fetal growth but also impairs mammary development and postnatal growth. We used cross fostering to compare the influence of prenatal and postnatal nutritional restraint on adult glucose tolerance, insulin secretion, insulin sensitivity, and hypothalamic neuropeptide Y content in Wistar Kyoto rats at 6 months of age.

Relative contribution of the prenatal versus postnatal period on development of hypertension and growth rate of the spontaneously hypertensive rat.

1. To determine the relative roles of the prenatal and postnatal (preweaning) environment on the development of blood pressure and growth rate in the spontaneously hypertensive rat (SHR) of the Okamoto strain, we used combined embryo transfer and cross-fostering techniques between SHR and normotensive Wistar-Kyoto (WKY) rats to produce offspring whose development was examined during the first 20 weeks of life. 2.

Cognitive performance following modafinil versus placebo in sleep-deprived emergency physicians: a double-blind randomized crossover study.

Objectives: Modafinil has recently been approved for the treatment of shift work sleep disorder, making it potentially available for shift-working emergency physicians. The authors' objectives were to determine whether modafinil improved cognitive performance of emergency physicians following overnight shifts and to record symptoms and subjective evaluations of the effect of modafinil on the participants.

Methods: This was a randomized, double-blind, placebo-controlled crossover study that followed CONSORT guidelines.

Lack of evidence for a role for either the in utero or suckling periods in the exaggerated salt preference of the spontaneously hypertensive rat.

When offered as a choice with drinking water in two-bottle preference tests, the spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit a marked preference for saline solutions. While this behaviour is thought to be in part genetically determined, the role of environmental influences-in particular, perinatal ones-are poorly understood. In this study, we have used combined embryo transfer and cross-fostering techniques between SHR and normotensive Wistar Kyoto (WKY) rats to delineate the relative roles of the prenatal and postnatal, suckling environment on the exaggerated saline preference of male SHR and WKY offspring at 20 weeks of age.

Modafinil, sleep deprivation, and cognitive function in military and medical settings.

Military personnel of many professions, including health care workers, are routinely challenged with performing their duties during hours when the circadian rhythm is at its trough, namely, late night and early morning. Studies have shown that cognitive performance declines significantly during these hours. Although many pharmacologic agents have been studied in an attempt to find a safe medication to enhance alertness and cognitive function, no safe nonaddictive options have been identified.

Uteroplacental restriction in the rat impairs fetal growth in association with alterations in placental growth factors including PTHrP.

During pregnancy, parathyroid hormone-related protein (PTHrP) is one of many growth factors that play important roles to promote fetal growth and development, including stimulation of placental calcium transport. Angiotensin II, acting through the AT(1a) receptor, is also known to promote placental growth. We examined the effects of bilateral uterine artery and vein ligation (restriction), which mimics placental insufficiency in humans, on growth, intrauterine PTHrP, placental AT(1a), and pup calcium.

PTH/PTHrP receptor and mid-molecule PTHrP regulation of intrauterine PTHrP: PTH/PTHrP receptor antagonism increases SHR fetal weight.

Parathyroid hormone-related protein (PTHrP) has important roles in fetal growth and development through stimulation of placental calcium transport, vasodilatation of the uteroplacental vasculature and regulation of cellular growth and differentiation. The growth restricted spontaneously hypertensive rat (SHR) has reduced fetal plasma, placental and amniotic fluid PTHrP concentrations compared to its progenitor, the Wistar Kyoto (WKY) rat. The aim of this study was to determine whether intrauterine PTHrP infusions can restore PTHrP levels and promote SHR fetal growth.

Impaired mammary function and parathyroid hormone-related protein during lactation in growth-restricted spontaneously hypertensive rats.

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) during lactation, including stimulation of mammary and pup growth. As spontaneously hypertensive rat (SHR) pups are growth restricted compared with the control Wistar Kyoto (WKY), we examined the relative roles of pup suckling and maternal lactational environment on pup growth, mammary PTHrP, and milk PTHrP and calcium concentrations. SHR pups were lighter compared with the control from 6 days.