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Background: Alcohol use disorder (AUD) is a chronic, relapsing disease, highly comorbid with anxiety and depression. The bed nucleus of the stria terminalis (BNST) and Crh+ neurons in this region play a key role in chronic ethanol‐induced increases in volitional intake, hypothesized to be driven by emergent negative affective behaviors. Excitatory N‐methyl‐d‐aspartate receptors (NMDARs) are a major target of ethanol, and chronic ethanol exposure has been shown to regulate NMDAR function and expression. Specifically, GluN2D subunit‐containing NMDARs have emerged as a target of interest due to their limited distribution and potential roles in affective behavior. Methods: Male and female mice underwent a home cage chronic drinking forced abstinence model (CDFA) to assess the impact of 1 day or 2 weeks of ethanol abstinence on BNST synaptic transmission and BNST Grin gene expression. Constitutive and conditional BNST GluN2D knockout mice were used to assess the impact of GluN2D deletion on continuous access ethanol intake as well as negative affect behaviors, using the open field, elevated zero maze, and forced swim tasks. Results: We report here that excitatory transmission undergoes time‐dependent upregulation in BNST Crh+ cells. Further, knockdown of dorsal BNST (dBNST) GluN2D expression significantly decreases ethanol intake in female, but not male, mice. While BNST Grin2b expression was significantly increased in protracted abstinence following CDFA, no differences in Grin2d expression were observed in the dBNST or dBNST Crh+ neurons. Finally, we find that deletion of GluN2D fails to alter negative affect in ethanol‐naïve female mice. Conclusions: These data suggest a role for BNST GluN2D‐containing NMDARs in ethanol drinking but not ethanol abstinence, highlighting sex differences and behavioral specificity. Overall, these data further suggest roles for BNST synaptic signaling in volitional ethanol intake that are partially independent of actions on affective behavior. [ABSTRACT FROM AUTHOR]

The IncHI1 self-transmissible plasmid pSf-R27 from Shigella flexneri 2a strain 2457T harbors sfh, a gene that codes for a protein with strong amino acid sequence homology to the global transcription regulator and nucleoid-associated protein H-NS and to its paralogue, StpA. Previously, we discovered that the expression of sfh mRNA is growth phase dependent such that in cultures growing in Lennox broth at 37[degree]C, the transcript is readily detectable in the early stages of exponential growth but is not detectable at the onset of stationary phase. In contrast, the Sfh protein is poorly expressed in early-exponential growth when sfh mRNA is abundant whereas it is expressed to a high level in early stationary phase, when sfh transcript expression is low (P. Deighan, C. Beloin, and C. J. Dorman, Mol. Microbiol. 48:1401-1416, 2003). This unusual pattern of reciprocal mRNA and protein expression is not due to growth phase-dependent effects on either mRNA or protein stability, nor is it due to the known abilities of the Sfh, StpA, and H-NS proteins to influence sfh gene expression. Instead, our data point to a blockade of sfh mRNA translation in early-exponential growth that is relieved as the culture enters the stationary phase of growth. Replacing the 5' end and translation initiation signals of the sfh mRNA with heterologous sequences did not alter the growth phase-dependent expression of the Sfh protein, suggesting that growth phase control of translation is intrinsic to another component of the message.

The need to engage students and staff effectively as partners in learning and teaching has been consistently emphasised in academic research and pedagogical practice. This article responds to this need by discussing the partnerships which were built in a creative education programme for educators from varied backgrounds, disciplines and institutions around the world at a leading Irish university. We discuss the different types of learning partnerships which are promoted during, outside and beyond the 'Educators Programme' and examine the pedagogical structures and processes which supported the development of partnership relationships. More specifically, we explain how the use of a Design Thinking methodology facilitated the formation of partnerships between programme facilitators and student-educators and also among student-educators, engaging them in i) collaborative learning ii) experiential learning, and iii) reflective practice. These processes were found to create an optimal environment for partnerships to grow. Psychological safety is presented as an essential foundational component for all of the above. Community of Practice is discussed as a positive outcome which naturally emerged from successful learning partnerships. Overall, it is argued that the successful learning partnerships built through the programme offered student-educators transformative learning experiences which empowered them to lead innovation and effect change in their teaching practice. This reflective case study contributes to discussions of the processes of building engagement and partnership between students and teachers and offers inspiration and practical ideas which can be applied in other local and international educational contexts. [ABSTRACT FROM AUTHOR]

Abstract Background HIV latency is an obstacle for the eradication of HIV from infected individuals. Stable post-integration latency is controlled principally at the level of transcription. The HIV trans-activating protein, Tat, plays a key function in enhancing HIV transcriptional elongation. The HIV core promoter is specifically required for Tat-mediated trans-activation of HIV transcription. In addition, the HIV core promoter has been shown to be a potential anti-HIV drug target. Despite the pivotal role of the HIV core promoter in the control of HIV gene expression, the molecular mechanisms that couple Tat function specifically to the HIV core promoter remain unknown. Results Using electrophoretic mobility shift assays (EMSAs), the TATA box and adjacent sequences of HIV essential for Tat trans-activation were shown to form specific complexes with nuclear extracts from peripheral blood mononuclear cells, as well as from HeLa cells. These complexes, termed pre-initiation complexes of HIV (PICH), were distinct in composition and DNA binding specificity from those of prototypical eukaryotic TATA box regions such as Adenovirus major late promoter (AdMLP) or the hsp70 promoter. PICH contained basal transcription factors including TATA-binding protein and TFIIA. A mutational analysis revealed that CTGC motifs flanking the HIV TATA box are required for Tat trans-activation in living cells and correct PICH formation in vitro. The binding of known core promoter binding proteins AP-4 and USF-1 was found to be dispensable for Tat function. TAR RNA prevented stable binding of PICH-2, a complex that contains the general transcription factor TFIIA, to the HIV core promoter. The impact of TAR on PICH-2 specifically required its bulge sequence that is also known to interact with Tat. Conclusion Our data reveal that CTGC DNA motifs flanking the HIV TATA box are required for correct formation of specific pre-initiation complexes in vitro and that these motifs are also required for Tat trans-activation in living cells. The impact of TAR RNA on PICH-2 stability provides a mechanistic link by which pre-initiation complex dynamics could be coupled to the formation of the nascent transcript by the elongating transcription complex. Together, these findings shed new light on the mechanisms by which the HIV core promoter specifically responds to Tat to activate HIV gene expression.

Paternal stress can induce long-lasting changes in germ cells potentially propagating heritable changes across generations. To date, no studies have investigated differences in transmission patterns between stress-resilient and stress-susceptible mice. We tested the hypothesis that transcriptional alterations in sperm during chronic social defeat stress (CSDS) transmit increased susceptibility to stress phenotypes to the next generation. We demonstrate differences in offspring from stressed fathers that depend on paternal category (resilient vs susceptible) and offspring sex. Importantly, artificial insemination (AI) reveals that sperm mediates some of the behavioral phenotypes seen in offspring. Using RNA-sequencing (RNA-seq), we report substantial and distinct changes in the transcriptomic profiles of sperm following CSDS in susceptible versus resilient fathers, with alterations in long noncoding RNAs (lncRNAs) predominating especially in susceptibility. Correlation analysis revealed that these alterations were accompanied by a loss of regulation of proteincoding genes by lncRNAs in sperm of susceptible males. We also identify several co-expression gene modules that are enriched in differentially expressed genes (DEGs) in sperm from either resilient or susceptible fathers. Taken together, these studies advance our understanding of intergenerational epigenetic transmission of behavioral experience. [ABSTRACT FROM AUTHOR]

Background Our Integrated Care Hub has been operating since mid-2017 providing patient-centred multidisciplinary team (MDT) care operating via a number of specialised care pathways. There has been an early emphasis on the response to crisis presentations and with the introduction of the Hub we now have an extensive and organised response to such presentations. We wanted to assess does this system result in earlier referral of the 'Crisis' patient to an Integrated Care Hub. Methods We performed a retrospective quantitative analysis of data comparing two time-periods January to June 2018 with January to April 2019 (year-to-date). The number and type of MDT contacts were classified into 4 categories: Immediate Crisis (would present to the Emergency Department within 48 hrs if not reviewed), Emerging Crisis (would present to the Emergency Department within 2 weeks if not reviewed), Stable Situation (needs optimisation), Stable Situation (no intervention). Data were extracted from File-Maker Pro. Results There were 424 MDT contacts in January-June 2018 compared with 658 MDT contacts in the year-to-date 2019. The number of patients in these time-periods presenting in 'Immediate Crisis' was reduced in the year-to-date 2019 - 4.41% when compared to the same time-period in 2018 – 11.79%. There was a similar reduction in 'Emerging' Crisis presentations in these time-periods: 15.65% in 2019 vs. 24.29% in 2018. While the patients attending that were classified as Stable Situation (needs optimisation) increased in 2019 compared to 2018 – 66.57% vs. 47.88%. Conclusion We can see from our data that the creation of our Integrated Care Hub has resulted in an increased demand for our service, however, interestingly we have found that the crisis patient load has, in fact, decreased. This suggests that we are influencing referral patterns by both recognising and intervening at an earlier stage to manage, stabilise and reverse crisis in these patients in an organised manner within the MDT. [ABSTRACT FROM AUTHOR]

Background Recent guidelines on diabetes management recommend individualisation of management particularly in those with frailty or significant co-morbidities. The aim of our audit was to assess diabetic control of residents in a long term care setting. Studies have shown that intensive control in an older population increases the risk of hypoglycaemia and does not necessarily improve clinical outcomes. There is also evidence that increased pill burden and hypoglycaemic events negatively affect quality of life among older people. Methods 176 nursing home residents were assessed. Detailed chart review was carried out on the 47 residents with a diagnosis of type 2 diabetes. Information collated included age, sex, diabetes type, frequency of blood sugar monitoring, weight, BMI, Clinical Frailty Scale, allocation of diabetic diet and treatments including insulin and oral hypoglycaemic agents. Diabetic control was assessed by HbA1c. Evidence of hypoglycaemia in the preceding four weeks was documented. Results Of 47 patients (33 female), average age was 79.8 years and median BMI was 25. 41/47 residents had a Clinical Frailty Score of 6 or greater. The median HbA1c overall was 44mmol/l (range was 29-116mmol/l). All patients were on a diabetic diet. 23/47 residents on oral hypoglycaemic agents and the median HbA1c of this group was 51mmol/l. 6/47 were on insulin. Sugars were checked weekly (daily in those on insulin) and HbA1c was checked in the previous 6 months in 36/47.There was 1 recorded hypoglycaemic episode. Conclusion Our data showed that long stay residents continue to have tight diabetic control despite low BMI, evidence of frailty, significant co morbidities and dependency. HbA1c can also decrease due to renal disease, weight loss and poor oral intake. In line with recent guidelines our data shows there is scope to rationalise diabetic treatment regimens with reduction in polypharmacy and improvement in quality of life. [ABSTRACT FROM AUTHOR]

Background Our Model 4 Hospital will open a Specialist Geriatric Ward in the coming months. This ward will focus on the provision of evidence-based care to confused and frail older adults. Careful selection of patients who would most benefit from this care will be vital to ensure success. We aim to determine the prevalence of frailty and confusion in our inpatient cohort to determine expected demand on this new service and to inform admission criteria. Methods All adult inpatients were screened for frailty (pre-admission status) using the Rockwood Clinical Frailty Scale (CFS). Point prevalence of confusion (combination of pre-existing dementia and incident delirium) was calculated by measuring 4AT scores on all adult inpatients (>16 years of age), with the exclusion of obstetric, paediatric, critical care and psychiatric wards. Eleven wards were visited by a team of six experienced geriatric practitioners during a one-week period in April 2019. Results In total, 257 patients were assessed. The median age was 74 years (16-99). The majority were male (54.9 %). 152 patients resided on a dedicated medical ward (59.1%). The point prevalence of pre-morbid frailty (CFS Score ≥ 5) was 39.9%. The point prevalence of confusion (4AT score ≥4) was 24.4%. Conclusion Our data show that frailty and delirium are highly prevalent in hospital inpatients. It is not feasible for this number of frail and confused patients to be cohorted in a single specialist area. It is therefore important that each hospital determine admission criteria to identify those at greatest need. Clearly, given the prevalence outlined here, there will be a large number of patients likely to benefit from but unable to access a Specialist Geriatric Ward. These wards therefore need to also serve as exemplars of best practice so that evidence-based care for this vulnerable cohort can be disseminated within an institution. [ABSTRACT FROM AUTHOR]

Background The Occupational Therapy (OT) service in the integrated care HUB team was established in January 2018. Prior to this, there was an established memory clinic, however with inconsistent access to OT. The streamlining and structuring of memory clinics further highlighted the need for post-diagnostic support for example individual sessions focusing on memory education and practical strategies to enable independence in daily activities. The integration of OT enabled person-centred strategies to be provided to individuals experiencing memory loss. Methods A retrospective analysis was completed comparing the number of OT memory patient contacts between January to June 2018 and November 2018 to April 2019 also reflecting the memory care pathway developed during this period. OT assessed all new patients experiencing memory difficulties that impacted on functional activities to initiate referral process. In April 2018, the Memory Technology Resource Room (MTRR) opened and the OT HUB using to facilitate patient contacts. The design/implementation of cognitive rehabilitation groups in May 2018 added another step to pathway. Dementia cafés were established in public cafés in the city and county area, sponsored by local care provider, also supported by HUB team. Feedback was gathered from surveys given to individuals, carers and HUB team in the Café and MTRR. Results From January to June 2018 there were 50 memory streamed patient contacts completed by the OT. From November 2018 to April 2019, 206 patient contacts were completed. These include both individual and group cognition focused sessions. Positive qualitative feedback was retrieved from attendees to MTRR and Café all indicating at least one positive outcome from post-diagnostic supports and services. Conclusion A multi-domain cognitive OT service when initiated by an integrated care HUB proves to be an effective and acceptable memory care pathway. The development of this holistic pathway enabled the person to be seen in the right place, at the right stage of their journey with memory difficulties. [ABSTRACT FROM AUTHOR]

Background The Inpatient rehabilitation service serves a population of 116,176 of whom 17,371 are aged 65yrs and over. Access to these units was traditionally via referral from the acute hospital sector with the minority of referrals coming from the community. Review of the existing rehabilitation pathway was undertaken and highlighted barriers of access to appropriate in-patient rehabilitation. The referral criteria were revised and an updated pathway was devised. Methods A quantitative retrospective review of all referrals received in four timeframes, commencing 1st July 2017 to date, was carried out. Each referral was classified into four subgroups: (1) Immediate Crisis (2) Emerging Crisis (3) Stable but Needs Optimisation (4) Stable and No in-patient Intervention required. The origin of the referral was also categorised into four subgroups: (1) Day Hospital (2) GP (3) AHP (4) Other. The Average Length of Stay (AvLoS) was calculated for, acute and community admissions, for each period breakdown. Results We compared 1st July 2017 to 31st December 2017 pre-establishment of the new referral pathway and the same six month period in 2018 post-establishment of the pathway. The new streamlined pathway facilitated improved access to in-patient rehabilitation from multiple sources and resulted in an increase in referrals from 25 to 79. Waiting time for admission was reduced from 37 days to 5 days. Community admissions increased from 16 to 48. There was no difference in AvLoS between the two time periods: Acute 22 & Community 17 to Acute 22.25 & Community 18. Conclusion This work highlights the effectiveness of an improved co-ordinated referral pathway, within an integrated care hub, from community to in-patient rehabilitation beds with improved accessibility and reduced waiting times. AvLoS figures suggest that appropriate patients were admitted to the rehabilitation units. Also, it confirms the efficiency of a patient centred approach in maximising appropriate services for Right Person, Right Place, Right Time. [ABSTRACT FROM AUTHOR]