Psychiatry NCHD referrals to the local emergency department in the context of an in-house primary care service.

OBJECTIVES: Patients with psychiatric illness are at increased risk of developing non-psychiatric medical illnesses. There have been positive reports regarding the integration of primary care services into mental health facilities. Here, we evaluate the appropriateness of psychiatry non-consultant hospital doctors (NCHD) transfers to the local emergency department (ED) in the context of an in-house primary care service. METHODS: We reviewed the inpatient transfers from St Patrick's University Hospital (SPUH) to the local ED at St James' Hospital (SJH) from 1 January 2016 to 31 December 2017. We used inpatient admission to SJH as our primary marker of an appropriate transfer. RESULTS: 246 inpatients were transferred from SPUH to the SJH ED for medical review in the years 2016 and 2017. 27 (11%) of these were referred to the ED by the primary care service. 51% of those referred were admitted with similar rates of admission for both general practitioner (n = 27, 54% admitted) and NCHD initiated referrals (n = 219, 51% admitted). Acute neurological illness, concern regarding a cardiac illness, and deliberate self-harm were the most common reasons for referral. CONCLUSION: Our primary finding is that, of those transferred to ED by either primary care or a psychiatry NCHD, a similar proportion was judged to be in need of inpatient admission. This indicates that as a group, psychiatry NCHD assessment of acuity and need for transfer was similar to that of their colleagues in primary care.

Proteomic and Transcriptomic Analyses in the Slipper Snail Crepidula fornicata Uncover Shell Matrix Genes Expressed During Adult and Larval Biomineralization.

The gastropod shell is a composite composed of minerals and shell matrix proteins (SMPs). SMPs have been identified by proteomics in many molluscs, but few have been studied in detail. Open questions include (1) what gene regulatory networks regulate SMP expression, (2) what roles individual SMPs play in biomineralization, and (3) how the complement of SMPs changes over development. These questions are best addressed in a species in which gene perturbation studies are available; one such species is the slipper snail, Crepidula fornicata. Here, SEM and pXRD analysis demonstrated that the adult shell of C. fornicata exhibits crossed lamellar microstructure and is composed of aragonite. Using high-throughput proteomics we identified 185 SMPs occluded within the adult shell. Over half of the proteins in the shell proteome have known biomineralization domains, while at least 10% have no homologs in public databases. Differential gene expression analysis identified 20 SMP genes that are up-regulated in the shell-producing mantle tissue. Over half of these 20 SMPs are expressed during development with two, CfSMP1 and CfSMP2, expressed exclusively in the shell gland. Together, the description of the shell microstructure and a list of SMPs now sets the stage for studying the consequences of SMP gene knockdowns in molluscs.

Sex Pheromone of the Introduced Pine Sawfly, Diprion similis, Revisited to Define a Useful Monitoring Lure: Deviating Chiral Composition and Behavioural Responses Compared to Earlier Reports.

Extracts of Diprion similis females contained about 15 ng of the sex pheromone precursor 3,7-dimethylpentadecan-2-ol per female. After derivatisation with (S)-2-acetoxypropanoyl chloride, we found that the major stereoisomer in the extract was (2S,3R,7R)-3,7-dimethylpentadecan-2-ol. Small amounts of other stereoisomers of 3,7-dimethylpentadecan-2-ol were also identified in the extract, namely 1% of (2R,3S,7S), 0.3% (2R,3R,7R) and 0.4% of (2R,3R,7S). An unknown fifth substance showed a very similar spectrum to 3,7-dimethylpentadecan-2-ol, both in SIM and full scan mode. None of the earlier suggested behavioural synergistic isomers ((2S,3S,7S), (2S,3S,7R) and (2S,3R,7S)) were detected in the extracts. In field tests in Ontario, Canada, the earlier identified main pheromone component, viz. the propanoate of (2S,3R,7R)-3,7-dimethylpentadecan-2-ol, was tested alone and in combination with other stereoisomers, earlier reported to be synergistic. No synergistic effects were detected and the threo four-isomer blend was as attractive as the pure main compound. Thus, one of the few examples of a diprionid sawfly using more than one substance in its sex pheromone could not be confirmed. The results also suggest that monitoring programs can use the more easily synthesized threo-blend without losing efficiency. Furthermore, the study suggests that other diprionid pheromones may benefit from a reinvestigation, to clarify possible synergistic effects of stereoisomers.

CNS Hypomyelination Disrupts Axonal Conduction and Behavior in Larval Zebrafish.

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, because of their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behavior. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias toward reorientation behavior instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high-frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.SIGNIFICANCE STATEMENT Myelination of CNS axons is essential for their health and function, and it is now clear that myelination is a dynamic life-long process subject to modulation by neuronal activity. However, it remains unclear precisely how changes to myelination affects animal behavior and underlying action potential conduction along axons in intact neural circuits. In recent years, zebrafish have been employed to study cellular and molecular mechanisms of myelination, because of their relatively simple, optically transparent, experimentally tractable vertebrate nervous system. Here we find that changes to myelination alter the behavior of young zebrafish and action potential conduction along individual axons, providing a platform to integrate molecular, cellular, and circuit level analyses of myelination using this model.

The nipple-areolar complex: comprehensive imaging review.

The nipple-areolar complex can be affected by a variety of benign and malignant entities that can present with non-specific symptoms. Benign pathologies commonly affecting the nipple-areolar complex include nipple calcifications, nipple adenoma, abscess of Montgomery tubercles, ductal ectasia, periductal mastitis, and papilloma. Malignant pathologies that affect the nipple-areolar complex include Paget's disease of the breast, ductal carcinoma in-situ, and invasive ductal carcinoma. Clinical history and examination, imaging, and tissue sampling when appropriate are co-dependent factors that guide the assessment of nipple-areolar pathologies. This article provides a review of the normal anatomy, common anatomical variants, benign and malignant pathologies, and imaging techniques to guide the diagnostic assessment of the nipple-areolar complex.

Fallout from the COVID-19 pandemic - should we prepare for a tsunami of post viral depression?

The current COVID-19 pandemic is not just a medical and social tragedy, but within the threat of the outbreak looms the potential for a significant and persistent negative mental health impact, based on previous experience with other pandemics such as Severe Acute Respiratory Syndrome (SARS) in 2003 and the earlier H1N1 outbreak of 1918. This piece will highlight the links between depression and viral illnesses and explore important overlaps with myalgic encephalomyelitis/chronic fatigue syndrome, potentially implicating inflammatory mechanisms in those exposed to a range of viral agents. While containment of psychological distress currently focuses on social anxiety and quarantine measures, a second wave of psychological morbidity due to viral illness may be imminent.

Mass and the Dangers of Syncope.

Introduction Syncope is defined as a transient, self-limited loss of consciousness with an inability to maintain postural tone that is followed by spontaneous recovery. We revisit situational syncope focusing on one situation, Mass. Methods We interrogated our electronic syncope database for key terms associated with situational syncope. From the most commonly encountered situation, Mass, we interrogated the results of tilt testing performed to identify evidence of orthostatic hypotension. Results There were 110 cases of situational syncope identified with 56.3% (n=62) taking place at mass. All had tilt table testing performed and 15.4% (n=17) had evidence of orthostatic hypotension. Conclusion The multiple sudden changes in position during mass from sitting to kneeling to standing can precipitate an episode of orthostatic hypotension. Consideration should be given as to whether it is safe for older mass goers to be subjected to such significant orthostatic stress.

Offering support to the general public by building CBT-based life skills: lessons learnt from an initial evaluation.

AimsCognitive behavioural therapy (CBT) is effective for symptoms of mild to moderate depression yet access to such therapy is frequently limited. An alternative to traditional ways of delivering CBT is lower intensity methods based on self-help principles, using written CBT resources, in a group or class setting. Aware, the Irish National charity providing support to people experiencing depression, has implemented a 6-week CBT-based group programme which has been independently evaluated to demonstrate its effectiveness using quantitative and qualitative measures. METHOD: Two outcome measures (the Patient Health Questionnaire - PHQ-9, and Generalised Anxiety Disorder - GAD-7) were completed and analysed using a matched pairs t-test in respect of all participants at three intervals across the programme. Qualitative feedback was also sought upon completion of the course and offered insight into significant change and individual impact of the programme. RESULTS: A total of 2289 individuals nationwide registered for the programme through the Aware website with 1885 completing the 6 weeks. There was an average attendance of 67% for the 6-week programme. Statistically significant reductions in terms of scores of depression and anxiety were seen upon completion but earlier trends towards improvement were noted. CONCLUSION: Completion of a 6-week Life Skills Programme has been associated with a reduction from moderately severe to mild scores in relation to both depressive and anxiety symptoms. Longitudinal follow-up will be required to determine if the effectiveness of the intervention is maintained but CBT-based group programmes may represent a useful alternative to traditional services to treat clinically significant depression.

Dedicated orthogeriatric service reduces hip fracture mortality.

BACKGROUND: Hip fracture is a common serious injury afflicting the geriatric population and is associated with poor clinical outcomes, functional and walking disabilities and high 1-year mortality rates. A multidisciplinary approach has been shown to improve outcomes of geriatric patients with fragility fracture. AIMS: We piloted a dedicated orthogeriatric service for hip fracture patients to determine if the service facilitated a change in major patient outcomes, such as mortality, length of stay and dependency. METHODS: A dedicated orthogeriatrics service for hip fracture was established as a collaborative project between the Department of Geriatric Medicine and Department of Orthopaedic Surgery at a university teaching hospital. Orthogeriatrics service data were collected prospectively on an orthogeriatric filemaker database from July 2011 to July 2012 (N = 206). Data were compared to previously recorded data (Irish Hip Fracture Database) on a cohort of hip fracture patients admitted to the same orthopaedic trauma unit from July 2009 to July 2010 (N = 248). RESULTS: Patients in the orthogeriatric service group experienced significant reductions in 1-year mortality (χ2 = 13.34, P < 0.001), length of acute hospital stay (U = -3.77, P < 0.001) and requirements for further rehabilitation (χ 2 = 26.59, P < 0.001). Patients in the pre-service establishment group were significantly more dependent following their fracture than the patients in the orthogeriatric service group (χ 2 = 5.34, P = 0.021). CONCLUSIONS: A multidisciplinary management approach to fragility fracture of the femoral neck that involves comprehensive geriatric assessment, daily medical involvement of a geriatric team and specialised follow-up assessment leads to a significant reduction in mortality and improved outcomes.

Dedicated Orthogeriatric Service Saves the HSE a Million Euro.

Hip fracture is common in older adults and is associated with high morbidity, mortality and significant health care costs. A pilot orthogeriatrics service was established in an acute hospital. We aimed to establish the cost effectiveness of this service. Length of hospital stay, discharge destination and rehabilitation requirements were analysed for a one year period and compared to patients who received usual care prior to the service. We calculated the costs incurred and savings produced by the orthogeriatric service. Median length of stay was reduced by 3 days (p < 0.001) saving €266,976. There was a 19% reduction in rehabilitation requirements saving €192,600. Median rehabilitation length of stay was reduced by 6.5 days saving €171,093. Reductions in long term care requirements led to savings of €10,934 per week. Costs to establish such a service amount to €171,564. The introduction of this service led to improved patient outcomes in a cost effective manner.

Older patient hospital admissions following primary care referral: the truth is in the referring.

BACKGROUND: Health information has a major role in the planning of future healthcare provision. With current reconfiguration and cost saving measures, further demands are being placed on acute hospitals. AIM: To examine the elderly admissions and the referral documentation of older patients admitted to a tertiary level hospital. METHODS: A retrospective analysis of primary care referral documentation for all acute admissions of patients over 75 years to University Hospital Limerick (UHL) over a 2-month period. Documentation was analysed on the basis of patient demographics, presenting complaint and referral source. Primary care referral documentation was then analysed on the basis of presenting complaint, patient demographics, referrer details, and the clinical information provided. RESULTS: Over the 2-month period there were a total of 381 elderly admissions through the Emergency department. The most common presenting complaint was with shortness of breath (21.5 %). 42.5 % of admissions were from a primary care setting. 31.1 % of referrals were typed and 47.0 % handwritten. Over 90 % of referrals contained the patient's name, date of birth and address. 98.7 % of referrals included a presenting complaint and 54 % included a past medical history. 20 % of referrals listed known drug allergies, while 9.3 % documented social history or baseline functional status. Referral letters from general practice and after-hour services were largely similar. CONCLUSIONS: Almost all primary care referrals included the required details as per recent HIQA guidelines. The further inclusion of optional information relating to patient social or functional status, which are of particular relevance to the older population may help patient management.

Temporal variability of glucocorticoid receptor activity is functionally important for the therapeutic action of fluoxetine in the hippocampus.

Previous studies have shown inconsistent results regarding the actions of antidepressants on glucocorticoid receptor (GR) signalling. To resolve these inconsistencies, we used a lentiviral-based reporter system to directly monitor rat hippocampal GR activity during stress adaptation. Temporal GR activation was induced significantly by acute stress, as demonstrated by an increase in the intra-individual variability of the acute stress group compared with the variability of the non-stress group. However, the increased intra-individual variability was dampened by exposure to chronic stress, which was partly restored by fluoxetine treatment without affecting glucocorticoid secretion. Immobility in the forced-swim test was negatively correlated with the intra-individual variability, but was not correlated with the quantitative GR activity during fluoxetine therapy; this highlights the temporal variability in the neurobiological links between GR signalling and the therapeutic action of fluoxetine. Furthermore, we demonstrated sequential phosphorylation between GR (S224) and (S232) following fluoxetine treatment, showing a molecular basis for hormone-independent nuclear translocation and transcriptional enhancement. Collectively, these results suggest a neurobiological mechanism by which fluoxetine treatment confers resilience to the chronic stress-mediated attenuation of hypothalamic-pituitary-adrenal axis activity.

Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity.

Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.

Characterizing the white matter hyperintensity penumbra with cerebral blood flow measures.

OBJECTIVE: White matter hyperintensities (WMHs) are common with age, grow over time, and are associated with cognitive and motor impairments. Mechanisms underlying WMH growth are unclear. We aimed to determine the presence and extent of decreased normal appearing white matter (NAWM) cerebral blood flow (CBF) surrounding WMHs to identify 'WM at risk', or the WMH CBF penumbra. We aimed to further validate cross-sectional finding by determining whether the baseline WMH penumbra CBF predicts the development of new WMHs at follow-up. METHODS: Sixty-one cognitively intact elderly subjects received 3 T MPRAGE, FLAIR, and pulsed arterial spin labeling (PASL). Twenty-four subjects returned for follow-up MRI. The inter-scan interval was 18 months. A NAWM layer mask, comprised of fifteen layers, 1 mm thick each surrounding WMHs, was generated for periventricular (PVWMH) and deep (DWMH) WMHs. Mean CBF for each layer was computed. New WMH and persistent NAWM voxels for each penumbra layer were defined from follow-up MRI. RESULTS: CBF in the area surrounding WMHs was significantly lower than the total brain NAWM, extending approximately 12 mm from both the established PVWMH and DWMH. Voxels with new WMH at follow-up had significantly lower baseline CBF than voxels that maintained NAWM, suggesting that baseline CBF can predict the development of new WMHs over time. CONCLUSIONS: A CBF penumbra exists surrounding WMHs, which is associated with future WMH expansion. ASL MRI can be used to monitor interventions to increase white matter blood flow for the prevention of further WM damage and its cognitive and motor consequences.

Assessing silver nanoparticles behaviour in artificial seawater by mean of AF4 and spICP-MS.

The use of nanotechnology-based products is constantly increasing and there are concerns about the fate and effect on the aquatic environment of antimicrobial products such as silver nanoparticles. By combining different characterization techniques (asymmetric flow field-flow fractionation, single particle ICP-MS, UV-Vis) we show that it is possible to assess in detail the agglomeration process of silver nanoparticles in artificial seawater. In particular we show that the presence of alginate or humic acid differentially affects the kinetic of the agglomeration process. This study provides an experimental methodology for the in-depth analysis of the fate and behaviour of silver nanoparticles in the aquatic environment.

Stress inoculation modeled in mice.

Stress inoculation entails intermittent exposure to mildly stressful situations that present opportunities to learn, practice and improve coping in the context of exposure psychotherapies and resiliency training. Here we investigate behavioral and hormonal aspects of stress inoculation modeled in mice. Mice randomized to stress inoculation or a control treatment condition were assessed for corticosterone stress hormone responses and behavior during open-field, object-exploration and tail-suspension tests. Stress inoculation training sessions that acutely increased plasma levels of corticosterone diminished subsequent immobility as a measure of behavioral despair on tail-suspension tests. Stress inoculation also decreased subsequent freezing in the open field despite comparable levels of thigmotaxis in mice from both treatment conditions. Stress inoculation subsequently decreased novel-object exploration latencies and reduced corticosterone responses to repeated restraint. These results demonstrate that stress inoculation acutely stimulates glucocorticoid signaling and then enhances subsequent indications of active coping behavior in mice. Unlike mouse models that screen for the absence of vulnerability to stress or presence of traits that occur in resilient individuals, stress inoculation training reflects an experience-dependent learning-like process that resembles interventions designed to build resilience in humans. Mouse models of stress inoculation may provide novel insights for new preventive strategies or therapeutic treatments of human psychiatric disorders that are triggered and exacerbated by stressful life events.