Objective In screening for small-for-gestational age (SGA) using third-trimester antenatal ultrasound, there are concerns about the low detection rates and potential for harm caused by both false-negative and false-positive screening results. Using a selective third-trimester ultrasound screening program, this study aimed to investigate the incidence of adverse perinatal outcomes among cases with (i) false-negative compared with true-positive SGA diagnosis and (ii) false-positive compared with true-negative SGA diagnosis. Methods This prospective cohort study was nested within the UK-based DESiGN trial, a prospective multicenter cohort study of singleton pregnancies without antenatally detected fetal anomalies, born at > 24 + 0 to < 43 + 0 weeks' gestation. We included women recruited to the baseline period, or control arm, of the trial who were not exposed to the Growth Assessment Protocol (GAP) intervention and whose birth outcomes were known. Stillbirth and major neonatal morbidity were the two primary outcomes. Minor neonatal morbidity was considered a secondary outcome. Suspected SGA was defined as an estimated fetal weight (EFW) < 10th percentile, based on the Hadlock formula and fetal growth charts. Similarly, SGA at birth was defined as birth weight (BW) < 10th percentile, based on UK population references. Maternal and pregnancy characteristics and perinatal outcomes were reported according to whether SGA was suspected antenatally or not. Unadjusted and adjusted logistic regression models were used to quantify the differences in adverse perinatal outcomes between the screening results (false negative vs true positive and false positive vs true negative). Results In total, 165 321 pregnancies were included in the analysis. Fetuses with a false-negative SGA screening result, compared to those with a true-positive result, were at a significantly higher risk of stillbirth (adjusted OR (aOR), 1.18 (95% CI, 1.07-1.31)), but at lower risk of major (aOR, 0.87 (95% CI, 0.83-0.91)) and minor (aOR, 0.56, (95% CI, 0.54-0.59)) neonatal morbidity. Compared with a true-negative screening result, a false-positive result was associated with a lower BW percentile (median, 18.1 (interquartile range (IQR), 13.3-26.9)) vs 49.9 (IQR, 30.3-71.7)). A false-positive result was also associated with a significantly increased risk of stillbirth (aOR, 2.24 (95% CI, 1.88-2.68)) and minor neonatal morbidity (aOR, 1.60 (95% CI, 1.51-1.71)), but not major neonatal morbidity (aOR, 1.04 (95% CI, 0.98-1.09)). Conclusions In selective third-trimester ultrasound screening for SGA, both false-negative and false-positive results were associated with a significantly higher risk of stillbirth, when compared with true-positive and true-negative results, respectively. Improved SGA detection is needed to address false-negative results. It should be acknowledged that cases with a false-positive SGA screening result also constitute a high-risk population of small fetuses that warrant surveillance and timely birth. (c) 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

In today's complex healthcare landscape, exacerbated by resource constraints at various levels, optimization of health professionals' roles is becoming increasingly paramount. Interprofessional collaboration, underpinned by role recognition and teamwork, leads to improved patient and organizational outcomes. Hospital pharmacists play a pivotal role in multidisciplinary teams, and it is imperative to understand multidisciplinary viewpoints on hospital pharmacists' roles to guide role prioritization and organizational efficiency. However, no study extensively investigated multidisciplinary views on values of diverse pharmacist roles in tertiary settings. This study aims to address this gap by examining non-pharmacist health professionals' views on hospital pharmacists' roles, recognizing their specialized niches as a crucial step towards optimizing their roles and services in Australia and internationally. Multiple focus group discussions and interviews were held via a virtual conferencing platform. Study participants were recruited using the study investigators' professional networks who were non-pharmacist health professionals with experience working with pharmacists in hospital settings. Data were collected from transcripts of the focus group recordings, which were later summarized using descriptive statistics and thematic analysis. Overarching themes were categorized and mapped against work system models to conceptualize organizational implications of multidisciplinary feedback, linking them to patient and organizational outcomes. Twenty-seven health professionals participated across focus groups and interviews, with the majority of professions being doctors and nurses. Three major themes were identified as follows: (i) overarching perceptions regarding hospital pharmacists; (ii) professional niches of hospital pharmacists; and (iii) future opportunities to optimize hospital pharmacy services. Valued professional niches included patient and health professional educators, transition-of-care facilitators, and quality use of medicines analysts. The study highlights critical insights into hospital pharmacists' roles in Australia, identifying their niche expertise as vital to healthcare efficiency and success. Based on multidisciplinary feedback, the study advocates for strategic role optimization and targeted research for enhanced clinical, economic, and organizational outcomes.

ABSTRACTObjectiveTo identify the clinical characteristics and patterns of ultrasound use amongst pregnancies with an antenatally unidentified small‐for‐gestational‐age (SGA) fetus, compared with those in which SGA is identified, to understand how to design interventions that improve antenatal SGA identification.MethodsThis was a prospective cohort study of singleton, non‐anomalous SGA (birth weight < 10th centile) neonates born after 24 + 0 gestational weeks at 13 UK sites, recruited for the baseline period and control arm of the DESiGN trial. Pregnancy with antenatally unidentified SGA was defined if there was no scan or if the final scan showed estimated fetal weight (EFW) at the 10th centile or above. Identified SGA was defined if EFW was below the 10th centile at the last scan. Maternal and fetal sociodemographic and clinical characteristics were studied for associations with unidentified SGA using unadjusted and adjusted logistic regression models. Ultrasound parameters (gestational age at first growth scan, number and frequency of ultrasound scans) were described, stratified by presence of indication for serial ultrasound. Associations of unidentified SGA with absolute centile and percentage weight difference between the last scan and birth were also studied on unadjusted and adjusted logistic regression, according to time between the last scan and birth.ResultsOf the 15 784 SGA babies included, SGA was not identified antenatally in 78.7% of cases. Of pregnancies with unidentified SGA, 47.1% had no recorded growth scan. Amongst 9410 pregnancies with complete data on key maternal comorbidities and antenatal complications, the risk of unidentified SGA was lower for women with any indication for serial scans (adjusted odds ratio (aOR), 0.56 (95% CI, 0.49–0.64)), for Asian compared with white women (aOR, 0.80 (95% CI, 0.69–0.93)) and for those with non‐cephalic presentation at birth (aOR, 0.58 (95% CI, 0.46–0.73)). The risk of unidentified SGA was highest among women with a body mass index (BMI) of 25.0–29.9 kg/m2 (aOR, 1.15 (95% CI, 1.01–1.32)) and lowest in those with underweight BMI (aOR, 0.61 (95% CI, 0.48–0.76)) compared to women with BMI of 18.5–24.9 kg/m2. Compared to women with identified SGA, those with unidentified SGA had fetuses of higher SGA birth‐weight centile (adjusted odds for unidentified SGA increased by 1.21 (95% CI, 1.18–1.23) per one‐centile increase between the 0th and 10th centiles). Duration between the last scan and birth increased with advancing gestation in pregnancies with unidentified SGA. SGA babies born within a week of the last growth scan had a mean difference between EFW and birth‐weight centiles of 19.5 (SD, 13.8) centiles for the unidentified‐SGA group and 0.2 (SD, 3.3) centiles for the identified‐SGA group (adjusted mean difference between groups, 19.0 (95% CI, 17.8–20.1) centiles).ConclusionsUnidentified SGA was more common amongst women without an indication for serial ultrasound, and in those with cephalic presentation at birth, BMI of 25.0–29.9 kg/m2 and less severe SGA. Ultrasound EFW was overestimated in women with unidentified SGA. This demonstrates the importance of improving the accuracy of SGA screening strategies in low‐risk populations and continuing performance of ultrasound scans for term pregnancies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Background In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus (“hypogastric plexus”) and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming “ascending nerves” or “shunt fascicles” running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width. Aim To identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon. Methods Human colonic segments were obtained with informed consent, from adult patients undergoing elective surgery ( n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves. Results The rectosigmoid and rectal specimens had 6–11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1–3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres. Conclusion Ascending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200.

Background Admission to hospital introduces risks for people with Parkinson’s disease in maintaining continuity of their highly individualized medication regimens, which increases their risk of medication errors. This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual’s symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome. Objective To determine the occurrence and identify factors that contribute to Parkinson’s medication errors in Australian hospitals. Methods A retrospective discharge diagnosis code search identified all admissions for people with Parkinson’s disease to three tertiary metropolitan hospitals in South Australia, Australia over a 3-year period. Of the 405 case notes reviewed 351 admissions met our inclusion criteria. Results Medication prescribing (30.5%) and administration (85%) errors during admission were extremely common, with the most frequent errors related to administration of levodopa preparations (83%). A higher levodopa equivalent dosage, patients with a modified swallowing status or nil by mouth order during admission, and patients who did not have a pharmacist led medication history within 24 hours of admission had significantly higher rates of medication errors. Conclusions This study identified 3 major independent factors that increased the risk of errors during medication management for people with Parkinson’s disease during hospitalization. Thus, targeting these areas for preventative interventions have the greatest chance of producing a clinically meaningful impact on the number of hospital medication errors occurring in the Parkinson’s population.

Background : Since the emergence of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) in late December 2019, there has been increasing recognition of the pro-thrombotic risk this virus can cause as part of Coronavirus disease 2019 (Covid-19). Aims : To assess if the rate of PTE was increased in those with COVID-19 in both critical care and ward patients. To assess the effect of right heart strain or requirement for critical care on mortality. Methods : We reviewed all computed tomography pulmonary angiograms (CTPA) performed in Scotland between 23 rd March and 31 st May 2020 (1st wave) and identified those inpatients with COVID-19 using either classical radiological appearances, or positive COVID-19 polymerase chain reaction swab. 3401 CTPAs were reviewed. 192 were positive for PTE in patients with evidence of COVID-19 either real-time polymerase chain reaction (RT-PCR) swab positive for SARS-CoV-2 [ n = 104] or having radiological changes consistent with COVID-19 [ n = 88]). The total number of hospital admissions in Scotland between 23 rd March 2020 and 31 st May 2020 with COVID-19 was 5195. The incidence of PTE during this time was 3.7% in all patients admitted to all hospitals in Scotland with COVID-19 during this period. 475 hospitalised patients were managed in critical care (both level 2 and level 3 care), in whom the incidence of PTE was 6% ( n = 29). 4720 patients required ward based care alone and the incidence of PTE was 3.5% ( n = 163). This compares to the national pre-Covid rate of 1%. There was increased risk of death with right heart strain (25/52 vs 128/140[ P < 0.01]) and in critical care (15/29 vs 146/163[ P < 0.01]). Conclusions : In this national study, we have demonstrated an increased risk of pulmonary thromboembolism in both critical care and ward based environments.

Autophagic dysregulation and lysosomal impairment have been implicated in the pathogenesis of Parkinson's disease, partly due to the identification of mutations in multiple genes involved in these pathways such as GBA, SNCA, ATP13a2 (also known as PARK9), TMEM175 and LRRK2. Mutations resulting in lysosomal dysfunction are proposed to contribute to Parkinson's disease by increasing α-synuclein levels, that in turn may promote aggregation of this protein. Here, we used two different genetic models–one heterozygous for a mutated form of the GBA protein (D409V), and the other heterozygous for an ATP13a2 loss-of-function mutation, to test whether these mutations exacerbate the spread of α-synuclein pathology following injection of α-synuclein preformed fibrils in the olfactory bulb of 12-week-old mice. Contrary to our hypothesis, we found that mice harboring GBA D409V+/− and ATP13a2+/− mutations did not have exacerbated behavioral impairments or histopathology (α-synuclein, LAMP2, and Iba1) when compared to their wildtype littermates. This indicates that in the young mouse brain, neither the GBA D409V mutation or ATP13a2 loss-of-function mutation accelerate the spread of α-synuclein pathology. As a consequence, we postulate that these mutations increase Parkinson's disease risk only by acting in one of the initial, upstream events in the Parkinson's disease pathogenic process. Further, the mutations, and the molecular pathways they impact, appear to play a less important role once the pathogenic process has been triggered and therefore do not specifically influence α-synuclein pathology spread.

The repurposing of drugs developed to treat type 2 diabetes for the treatment of Parkinson's disease (PD) was encouraged by the beneficial effect exerted by the glucagon-like peptide 1 (GLP-1) analogue exenatide in a phase 2 clinical trial. The effects of GLP-1 analogues have been investigated extensively using rodent toxin models of PD. However, many of the toxin-based models used lack robust α-synuclein (α-syn) pathology, akin to the Lewy bodies and neurites seen in PD. One prior study has reported a protective effect of a GLP-1 analogue on midbrain dopamine neurons following injection of α-syn preformed fibrils (PFF) into the striatum. Here, we used olfactory bulb injections of PFF as a model of prodromal PD and monitored the effect of a long-acting GLP-1 analogue on the propagation of α-syn pathology in the olfactory system. Thirteen weeks after PFF injection, mice treated with long-acting the GLP-1 analogue had a significant increase in pathological α-syn in brain regions connected to the olfactory bulb, accompanied by signs of microglia activation. Our results suggest that the nature of the neuronal insult and intrinsic properties of the targeted neuronal population markedly influence the effect of GLP-1 analogues.

Current treatments for Parkinson’s disease (PD) provide only symptomatic relief, with no disease-modifying therapies identified to date. Repurposing FDA-approved drugs to treat PD could significantly shorten the time needed for and reduce the costs of drug development compared with conventional approaches. We developed an efficient strategy to screen for modulators of β-glucocerebrosidase (GCase), a lysosomal enzyme that exhibits decreased activity in patients with PD, leading to accumulation of the substrate glucosylceramide and oxidized dopamine and α-synuclein, which contribute to PD pathogenesis. Using a GCase fluorescent probe and affinity-based fluorescence polarization assay, we screened 1280 structurally diverse, bioactive, and cell-permeable FDA-approved drugs and found that the antipsychotic quetiapine bound GCase with high affinity. Moreover, quetiapine treatment of induced pluripotent stem cell–derived (iPSC-derived) dopaminergic neurons from patients carrying mutations in GBA1 or LRRK2 led to increased wild-type GCase protein levels and activity and partially lowered accumulation of oxidized dopamine, glucosylceramide, and α-synuclein. Similarly, quetiapine led to activation of wild-type GCase and reduction of α-synuclein in a GBA mutant mouse model (Gba1D409V/+ mice). Together, these results suggest that repurposing quetiapine as a modulator of GCase may be beneficial for patients with PD exhibiting decreased GCase activity.

The protein alpha-synuclein (asyn) is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinson’s disease (PD); yet, a functional role for asyn in neurons is not clearly established. We have previously shown that asyn expression is up-regulated following viral infection in neurons and is critical for host immune responses to RNA virus infections. Here, we investigate the mechanisms underlying asyn-dependent immune responses to RNA virus infection in the brain. Using asyn knock-out (KO) mice and human neuronal models, we show that asyn is required for expression of the full repertoire of interferon-stimulated genes (ISGs) in neurons following acute RNA virus infection. Furthermore, treatment of asyn KO human neurons with poly I:C or type I interferon also fail to induce expression of the full complement of ISGs suggesting that asyn plays an important role in modulating neuronal innate immune responses. In brain tissue, asyn-dependent ISG expression is independent of microglia activation and supports activation of infiltrating lymphocytes following viral challenge. We also show that virus infections lead to accumulation of phosphorylated S129 asyn in human and non-human primate neuronal tissues. In a model of pS129 asyn pathology, we found that infection with West Nile virus increases microglia activation but does not significantly alter pS129 asyn pathology in the mouse model. Taken together, our results establish asyn as a novel, neuron-specific modulator of innate immunity by a mechanism that promotes interferon-stimulated gene expression and links responses to virus infection with formation of phosphorylated S129-asyn in neuronal tissue.

Hyposmia is evident in over 90% of Parkinson's disease (PD) patients. A characteristic of PD is intraneuronal deposits composed in part of α-synuclein fibrils. Based on the analysis of post-mortem PD patients, Braak and colleagues suggested that early in the disease α-synuclein pathology is present in the dorsal motor nucleus of the vagus, as well as the olfactory bulb and anterior olfactory nucleus, and then later affects other interconnected brain regions. Here, we bilaterally injected α-synuclein preformed fibrils into the olfactory bulbs of wild type male and female mice. Six months after injection, the anterior olfactory nucleus and piriform cortex displayed a high α-synuclein pathology load. We evaluated olfactory perceptual function by monitoring odor-evoked sniffing behavior in a plethysmograph at one-, three- and six-months after injection. No overt impairments in the ability to engage in sniffing were evident in any group, suggesting preservation of the ability to coordinate respiration. At all-time points, females injected with fibrils exhibited reduced odor detection sensitivity, which was observed with the semi-automated plethysmography apparatus, but not a buried pellet test. In future studies, this sensitive methodology for assessing olfactory detection deficits could be used to define how α-synuclein pathology affects other aspects of olfactory perception and to clarify the neuropathological underpinnings of these deficits.

Epidemiological studies suggest a link between type-2 diabetes and Parkinson's disease (PD) risk. Treatment of type-2 diabetes with insulin sensitizing drugs lowers the risk of PD. We previously showed that the insulin sensitizing drug, MSDC-0160, ameliorates pathogenesis in some animal models of PD. MSDC-0160 reversibly binds the mitochondrial pyruvate carrier (MPC) protein complex, which has an anti-inflammatory effect and restores metabolic deficits. Since PD is characterized by the deposition of α-synuclein (αSyn), we hypothesized that inhibiting the MPC might directly inhibit αSyn aggregation in vivo in mammals. To answer if modulation of MPC can reduce the development of αSyn assemblies, and reduce neurodegeneration, we treated two chronic and progressive mouse models; a viral vector-based αSyn overexpressing model and a pre-formed fibril (PFF) αSyn seeding model with MSDC-0160. These two models present distinct types of αSyn pathology but lack inflammatory or autophagy deficits. Contrary to our hypothesis, we found that a modulation of MPC in these models did not reduce the accumulation of αSyn aggregates or mitigate neurotoxicity. Instead, MSDC-0160 changed the post-translational modification and aggregation features of αSyn. These results are consistent with the lack of a direct effect of MPC modulation on synuclein clearance in these models.

Loss of dopaminergic neurons in the substantia nigra (SN) is one of the pathological hallmarks in Parkinson's disease (PD). This neuron loss is accompanied by reduced protein and activity levels of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. Reduced nigral brain-derived neurotrophic factor (BDNF) has been postulated to contribute to the loss of nigral dopaminergic neurons in PD by causing a lack of trophic support. Prior to this nigral cell loss many patients develop non-motor symptoms such as hyposmia, constipation and orthostatic hypotension. We investigated how TH, BDNF and BDNF related receptors are altered in the SN, olfactory bulb, adrenal glands and colon (which are known to be affected in PD) using rotenonetreated rats. Rotenone was administered to Sprague-Dawley rats at a dose of 2.75 mg/kg, 5 days/week for 4 weeks, via intraperitoneal injections. Rats underwent behavioural testing, and tissues were collected for western blot and ELISA analysis. This rotenone treatment induced reduced rears and distance travelled in the rearing and open field test, respectively but caused no impairments in forced movement (rotarod test). The SN had changes consistent with a pro-apoptotic state, such as increased proBDNF but no change in TH; whereas, the colon had significantly reduced TH and increased sortilin. Thus, our results indicate further investigation is warranted for this rotenone-dosing paradigm's capacity for reproducing the early stage of PD, as we observed impairments in voluntary movement and pathology in the colon without overt motor symptoms or nigral dopaminergic loss.

While people are often aware of the motor symptoms in Parkinson's disease (PD), few know of the many non-motor symptoms, which patients report have a greater impact on their quality of life. Gastrointestinal (GI) dysfunction is one of the most common non-motor symptoms, which can occur at any stage of PD, even years prior to diagnosis, and can affect all sections along the GI tract causing a range of symptoms including drooling, gastroparesis and constipation. We have investigated whether a neurotoxin model of PD induced by rotenone, a mitochondrial complex I inhibitor, is capable of reproducing the GI dysfunction seen clinically. Sprague-Dawley rats were administered 2.75 mg/kg rotenone, 5 days/week for 4 weeks, via intraperitoneal injection. Rats underwent behavioural testing, including the one-hour stool and gastric emptying tests before GI contents and tissues were collected for microbiota and histological analysis. Rats exposed to rotenone had more days with evidence of diarrhoea and significantly delayed gastric emptying, reproducing the clinical symptom of gastroparesis. Microbiota analysis revealed alterations in the small intestine and colon of rotenone-treated rats, relatively consistent with changes described in PD patients. Histological analysis demonstrated mucosal thickening and goblet cell hyperplasia in the colon of rotenone rats, which may be an adaptive response to the toxin or changes in GI microbiota. Our results indicate that rotenone may be a good model for investigating the mechanisms involved with Parkinson's GI symptoms and for screening potential therapeutic options as it is capable of recapitulating some key GI changes that occur during PD progression. (C) 2018 Elsevier B.V. All rights reserved.

Parkinson’s disease (PD) is a common neurodegenerative disease worldwide. While the typical motor symptoms of PD are well known, the lesser known non-motor symptoms can also greatly impact the patient’s quality of life. These symptoms often appear before motor impairment, therefore identifying biomarkers that may predict PD risk or pathology has been a major and challenging endeavour. Given that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH) occurs in PD, the expression and accompanying post-translational changes in TH during PD progression could yield insight into the disruption of cellular signalling occurring in the CNS, and also in peripheral tissues wherein catecholamine function plays a role. Furthermore, changes in expression and phosphorylation of TH in the brain and periphery can potentially reveal how TH stability and function are compromised in PD. As such, these changes can reveal how catecholamine synthesis capacity is gradually compromised and how changes in cellular signalling may govern the functional status of remaining catecholaminergic neurons. This review summarises the findings of clinical PD and neurotoxin models of PD that assessed TH expression or phosphorylation in catecholaminergic pathways in the brain and relevant peripheral tissues. We propose that establishing similar changes in TH expression and function in the CNS and periphery of established neurotoxin models can be a potential reference for comparison to changes in TH in human peripheral tissues. These changes in TH expression and phosphorylation may have predictive validity to estimate risk of PD progression before motor impairment is evident.

We hypothesize that Parkinson's disease (PD) pathogenesis can be divided into three temporal phases. During the first phase, 'triggers', such as viral infections or environmental toxins, spark the disease process in the brain and/or peripheral tissues. Triggers alone, however, may be insufficient, requiring 'facilitators' like peripheral inflammation for PD pathology to develop. Once the disease manifests, 'aggravators' spur further neurodegeneration and exacerbate symptoms. Aggravators are proposed to include impaired autophagy and cell-to-cell propagation of α-synuclein pathology. We believe clinical trials need to consider these three phases and target potential therapies at the appropriate stage of the disease process in order to be effective.

A growing body of evidence suggests that neurohypophyseal hormones like oxytocin are able to modulate drug taking and susceptibility to addiction through interactions with a number of key neurobiological systems that are implicated in addiction processes. This chapter will describe the synthesis and role of these hormones and will examine the advantages and disadvantages of the methods of detection of oxytocin and vasopressin in humans. It will also describe the evidence relating to the relationship between peripheral and central concentrations of oxytocin and vasopressin. Lastly, it will highlight the relationship between the neurohypophyseal hormones and drugs of abuse. All studies associating neurohypophyseal hormones with behaviour rely upon accurate quantitation of peptide concentrations. Following extensive discussion in the field, the debate is ongoing as to which are the most appropriate methods for sample collection and analysis. This chapter will pull together the evidence in order to provide a current overview of the options and opportunities.

The non-motor symptoms of Parkinson's disease are often under-recognised and undertreated. Constipation is exceedingly common in Parkinson's disease, reportedly affecting up to 70% of patients. Pharmacists are ideally positioned to screen patients with Parkinson's disease for and to optimise management. This review will describe the evidence base for the use of different treatments in the of in patients with Parkinson's PubMed, Embase and Web of Science were searched using the following search terms: constipation OR gastrointestinal dysfunction OR slow colonic transit OR defecatory dysfunction OR slow motility AND OR management OR therapy AND Parkinson* disease. The literature indicates macrogol is a safe and effective treatment for in Parkinson’s disease; it should be considered a first line treatment and can be recommended by the pharmacist over-the-counter. Pharmacists can provide information regarding fibre supplementation with psyllium, which may be effective and can be initiated early. Lubiprostone appears to be a promising option, but larger and longer trials are warranted. Although many commonly employed treatments for have not been evaluated for efficacy in Parkinson's disease, pharmacists can utilise available data to make evidence-based recommendations to optimise of and improve patient quality of life. Keywords: Constipation, Parkinson’s disease, Treatment, Non-motor, Pharmacy practice