Galactorrhea: Rapid Evidence Review.

Galactorrhea is the production of breast milk that is not the result of physiologic lactation. Milky nipple discharge within one year of pregnancy and the cessation of breastfeeding is usually physiologic. Galactorrhea is more often the result of hyperprolactinemia caused by medication use or pituitary microadenomas, and less often hypothyroidism, chronic renal failure, cirrhosis, pituitary macroadenomas, hypothalamic lesions, or unidentifiable causes.

Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing.

Diagnostic whole genome sequencing (WGS) is increasingly used in rare diseases. However, standard, semi-automated WGS analysis may overlook diagnoses in complex disorders. Here, we show that specialist multidisciplinary analysis of WGS, following an initial 'no primary findings' (NPF) report, improves diagnostic rates and alters management.

Characterization of Retronasal Airflow Patterns during Intraoral Fluid Discrimination Using a Low-Cost, Open-Source Biosensing Platform.

Nasal airflow plays a critical role in olfactory processes, and both retronasal and orthonasal olfaction involve sensorimotor processes that facilitate the delivery of volatiles to the olfactory epithelium during odor sampling. Although methods are readily available for monitoring nasal airflow characteristics in laboratory and clinical settings, our understanding of odor sampling behavior would be enhanced by the development of inexpensive wearable technologies. Thus, we developed a method of monitoring nasal air pressure using a lightweight, open-source brain-computer interface (BCI) system and used the system to characterize patterns of retronasal airflow in human participants performing an oral fluid discrimination task.

Development of a Bioactive Polymeric Drug Eluting Coronary Stent Coating Using Electrospraying.

Drug-eluting stents are now routinely used in the treatment of acute coronary syndromes caused by coronary artery disease. Whilst the sustained release of anti-proliferative drugs from these devices has greatly reduced the need for repeat revascularisation procedures, this approach is not suitable for all patients and appears to delay regrowth of the endothelium, necessitating the use of prolonged dual anti-platelet therapy. Although the development of more advanced stent platforms and drug coatings has produced modest improvements in performance, these devices have not fully addressed the limitations experienced with their first-generation counterparts.

Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance.

In this study, we developed a predictive model of in vivo stent based drug release and distribution that is capable of providing useful insights into performance. In a combined mathematical modelling and experimental approach, we created two novel sirolimus-eluting stent coatings with quite distinct doses and release kinetics. Using readily measurable in vitro data, we then generated parameterised mathematical models of drug release.

In vitro studies on space-conforming self-assembling silk hydrogels as a mesenchymal stem cell-support matrix suitable for minimally invasive brain application.

Advanced cell therapies require robust delivery materials and silk is a promising contender with a long clinical track record. Our aim was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix that would allow future minimally invasive brain application. We used sonication energy to programme the transition of silk (1-5% w/v) secondary structure from a random coil to a stable β-sheet configuration.

Modelling the Impact of Atherosclerosis on Drug Release and Distribution from Coronary Stents.

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES.

The brain on stress: Insight from studies using the Visible Burrow System.

The discovery of adrenal steroid receptors outside of the hypothalamus in the hippocampus and other forebrain regions catalyzed research on the effects of stress upon cognitive function, emotions and self-regulatory behaviors as well as the molecular, cellular and neuroanatomical mechanisms underlying acute and chronic stress effects on the brain. Indeed, this work has shown that the brain is a plastic and vulnerable organ in the face of acute and chronic stress. The insight that Bob and Caroline Blanchard had in developing and interpreting findings using the Visible Burrow System model made an enormous contribution to the current view that the human brain is very sensitive to the social environment and to agonistic interactions between individuals.

Mast cells promote blood brain barrier breakdown and neutrophil infiltration in a mouse model of focal cerebral ischemia.

Blood brain barrier (BBB) breakdown and neuroinflammation are key events in ischemic stroke morbidity and mortality. The present study investigated the effects of mast cell deficiency and stabilization on BBB breakdown and neutrophil infiltration in mice after transient middle cerebral artery occlusion (tMCAo). Adult male C57BL6/J wild type (WT) and mast cell-deficient (C57BL6/J Kit(Wsh/Wsh) (Wsh)) mice underwent tMCAo and BBB breakdown, brain edema and neutrophil infiltration were examined after 4 hours of reperfusion.

Catecholamine mapping within nucleus accumbens: differences in basal and amphetamine-stimulated efflux of norepinephrine and dopamine in shell and core.

The nucleus accumbens is believed to play a critical role in mediating the behavioral responses to rewarding stimuli. Although most studies of the accumbens focus on dopamine, it receives afferents from many other nuclei, including noradrenergic cell groups in the brainstem. We used in vivo microdialysis to measure extracellular levels of both norepinephrine and dopamine in the accumbens shell and core.

Trends of reproductive hormones in male rats during psychosocial stress: role of glucocorticoid metabolism in behavioral dominance.

Stress in socially subordinate male rats, associated with aggressive attacks by dominant males, was studied in a group-housing context called the visible burrow system (VBS). It has been established that subordinate males have reduced serum testosterone (T) and higher corticosterone (CORT) relative to dominant and singly housed control males. The relationship of the decreased circulating T levels in subordinate males to changes in serum LH concentrations has not been evaluated previously.

Animal models of social stress: effects on behavior and brain neurochemical systems.

Social interactions serve as an evolutionarily important source of stress, and one that is virtually ubiquitous among mammalian species. Animal models of social stress are varied, ranging from a focus on acute, intermittent, or chronic exposure involving agonistic behavior, to social isolation. The relative stressfulness of these experiences may depend on the species, sex, and age of the subjects, and subject sex also appears to influence the value of hypothalamic--pituitary--adrenal (HPA) axis activity as a general criterion for stress response: higher glucocorticoid levels are typically found in dominant females in some species.

Chronic social stress reduces dendritic arbors in CA3 of hippocampus and decreases binding to serotonin transporter sites.

Male rats housed in mixed-sex groups in a visible burrow system (VBS) form a dominance hierarchy in which subordinate animals show stress-related changes in behavior, endocrine function and neurochemistry. Dominants also appear to be moderately stressed compared to controls, although these animals do not develop the more pronounced behavioral and physiological deficits seen in the subordinates. In the present study, we examined the effects of chronic psychosocial stress on the morphology of Golgi-impregnated CA3 pyramidal neurons.

Corticosterone and phenytoin reduce neuronal nitric oxide synthase messenger RNA expression in rat hippocampus.

The production and release of the corticosteroids, namely the glucocorticoids and the mineralocorticoids, are regulated by various stimuli, including stress. Previous studies from our laboratory have shown that chronic exposure to stress or to stress levels of glucocorticoids produces atrophy of the apical dendrites of CA3 pyramidal neurons in the hippocampus. This stress-induced dendritic remodeling is blocked by the anti-epileptic drug phenytoin, which suppresses glutamate release, and also by N-methyl-D-aspartate receptor antagonists.

Behavioral and endocrine change following chronic predatory stress.

Adult male rats showed very high levels of crouching when exposed to a cat, with suppression of the nondefensive behaviors (e.g., lying, locomotion, rearing) that were shown by toy cat-exposed controls.

Prevention of stress-induced morphological and cognitive consequences.

Atrophy and dysfunction of the human hippocampus is a feature of aging in some individuals, and this dysfunction predicts later dementia. There is reason to believe that adrenal glucocorticoids may contribute to these changes, since the elevations of glucocorticoids in Cushing's syndrome and during normal aging are associated with atrophy of the entire hippocampal formation in humans and are linked to deficits in short-term verbal memory. We have developed a model of stress-induced atrophy of the hippocampus of rats at the cellular level, and we have been investigating underlying mechanisms in search of agents that will block the atrophy.

Decreased 5-HT1A and increased 5-HT2A receptor binding after chronic corticosterone associated with a behavioural indication of depression but not anxiety.

The effects of chronic corticosterone treatment (100 mg pellet implanted for 1 week) were assessed in animal tests of anxiety, exploration and motor activity, and changes in binding to 5-HT1A and 5-HT2A receptors, and the 5-HT transporter, were measured. At the end of the week's treatment, the corticosterone concentration was significantly elevated and there were significant decreases in adrenal, thymus and body weights. However, there were no changes in the measures of anxiety in the social interaction test or on trials 1 and 2 of the elevated plus-maze.

Chronic social stress alters levels of corticotropin-releasing factor and arginine vasopressin mRNA in rat brain.

In the visible burrow system model of chronic social stress, male rats housed in mixed-sex groups quickly form a dominance hierarchy in which the subordinates appear to be severely stressed. A subgroup of subordinates have an impaired corticosterone response after presentation of a novel restraint stressor, leading to their designation as nonresponsive subordinates. To examine the mechanism underlying the blunted corticosterone response in these animals, in situ hybridization histochemistry was used to quantify corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) mRNA expression in the brain.

Tianeptine treatment induces regionally specific changes in monoamines.

Tianeptine is an atypical tricyclic antidepressant that facilitates serotonin (5-HT) reuptake. Tianeptine (10 mg/kg) or saline was administered intraperitoneally to male rats daily for 4 days. Monoamine levels were measured in micropunches of discrete brain nuclei that are implicated in mood and cognition.

Effects of chronic social stress on tyrosine hydroxylase mRNA and protein levels.

Males housed in mixed sex groups quickly form dominance hierarchies; subordinates can be further subdivided into stress responsive subordinates (SRS) and non-responsive subordinates (NRS) based on corticosterone responses to a novel stressor. Tyrosine hydroxylase (TH) mRNA levels measured with in situ hybridization were elevated in locus coeruleus (LC) of NRS compared to singly or pair-housed controls; NRS also had higher TH levels than dominants. TH protein levels determined by immunoautoradiography were also higher in LC of NRS and SRS versus pair-housed controls.

Serotonin receptor binding in a colony model of chronic social stress.

Male rats housed in mixed-sex groups quickly established dominance hierarchies in which subordinates appeared severely stressed. Subordinate rats had elevated basal corticosterone (CORT) levels relative to dominants and individually housed controls. Several subordinates had blunted CORT responses to a novel stressor, leading to the classification of subordinates as either stress-responsive or nonresponsive.

Short-term fluoxetine treatment alters monoamine levels and turnover in discrete brain nuclei.

The effects of short-term fluoxetine administration on monoamine levels and turnover were assessed in discrete brain nuclei. Adult male rats received fluoxetine HCl (10 mg/kg) or saline injections intraperitoneally for 4 days and monoamine levels determined by high performance liquid chromatography. The major metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), was decreased by fluoxetine treatment in the ventromedial hypothalamic nucleus (VMN), the lateral hypothalamic area and the CA1 region of the hippocampus.