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Objectives To summarise the available data regarding the effect of hormone replacement therapy (HRT) on cognition and mood in women. Background Complaints of impaired cognition and mood are common in the peri-menopausal and menopausal period. There is debate as to whether HRT can ameliorate this phenomenon. Design A literature search of studies using electronic databases was conducted. Both randomised control trials and observational studies were included. Patients Perimenopausal and menopausal women. Results Due to the heterogenicity of results it is challenging to draw firm conclusions. The preparations used in many of the studies are older regimes no longer routinely used clinically. The notion of a ‘critical window’ for HRT is compelling, suggesting HRT has a positive impact on cognition when administered in the peri-menopausal or early postmenopausal period but may have negative effects on cognition in the older, postmenopausal woman. The evidence would seem to suggest importance of hormonal replacement in woman undergoing a surgical menopause, especially when young. It remains unclear for how long they ought to continue HRT though until at least the natural age of the menopause seems reasonable. Evidence for a positive effect of HRT on mood is more convincing, though possibly more efficacious in the younger age group. The effect of HRT on anxiety is less clear. Conclusions Further study, particularly focusing on the more contemporaneous HRT preparations, is warranted before evidence-based conclusions can be drawn.

Human immunodeficiency virus 1 (HIV-1) is a life-threatening pathogen that still lacks a curative therapy or vaccine. Despite the reduction in AIDS-related deaths achieved by current antiretroviral therapies, drawbacks including drug resistance and the failure to eradicate infection highlight the need to identify new pathways to target the infection. Circadian rhythms are endogenous 24-h oscillations which regulate physiological processes including immune responses to infection, and there is an emerging role for the circadian components in regulating viral replication. The molecular clock consists of transcriptional/translational feedback loops that generate rhythms. In mammals, BMAL1 and CLOCK activate rhythmic transcription of genes including the nuclear receptor REV-ERBα, which represses BMAL1 and plays an essential role in sustaining a functional clock. We investigated whether REV-ERB activity regulates HIV-1 replication and found REV-ERB agonists inhibited HIV-1 promoter activity in cell lines, primary human CD4 T cells and macrophages, whilst antagonism or genetic disruption of REV-ERB increased promoter activity. The REV-ERB agonist SR9009 inhibited promoter activity of diverse HIV-subtypes and HIV-1 replication in primary T cells. This study shows a role for REV-ERB synthetic agonists to inhibit HIV-1 LTR promoter activity and viral replication, supporting a role for circadian clock components in regulating HIV-1 replication.

IntroductionOlder patients undergoing cancer surgery are at increased risk of post-operative complications, prolonged hospital stay, and mortality. Identification of frailty can help predict patients at high risk of peri-operative complications and allow a collaborative, multidisciplinary team approach to their care. A survey was conducted to assess the confidence and knowledge of trainees in obstetrics and gynecology regarding identification and management of peri-operative issues encountered in frail gynecological oncology patients.MethodsA web-based survey was distributed via the Audit and Research in Gynaecological Oncology (ARGO) collaborative and UK Audit and Research Collaborative in Obstetrics and Gynaecology (UKARCOG) . The survey on the management of frail peri-operative patients was disseminated to doctors-in-training (trainees) working in obstetrics and gynecology in the United Kingdom (UK) and Ireland. Specialty (ST1–7), subspecialty, and general practice trainees, non-training grade doctors, and foundation year doctors currently working in obstetrics and gynecology were eligible. Consultants were excluded. Study data were collected using REDCAP software hosted at the University of Manchester. Responses were collected over a 6-week period between January and February 2020.ResultsOf the 666 trainees who participated, 67% (425/666) reported inadequate training in peri-operative management of frail patients. Validated frailty assessment tools were used by only 9% (59/638) of trainees and less than 1% (4/613) were able to correctly identify all the diagnostic features of frailty. Common misconceptions included the use of chronological age and gender in frailty assessments. The majority of trainees (76.5%, 448/586) correctly answered a series of questions relating to mental capacity; however, only 6% (36/606) were able to correctly identify all three diagnostic features of delirium. A total of 87% (495/571) of trainees supported closer collaboration with geriatricians and a multidisciplinary approach.ConclusionsObstetrics and gynecology trainees reported inadequate training in the peri-operative care of frail gynecological oncology patients, and overwhelmingly favored input from geriatricians. Routine use of validated frailty assessment tools may aid diagnosis of frailty in the peri-operative setting. There is an unmet need for formal education in the management of frail surgical patients within the UK and Irish obstetrics and gynecology curriculum.

Human immunodeficiency virus 1 (HIV-1) is a life-threatening pathogen that still lacks a curative therapy or vaccine. Despite the reduction in AIDS-related deaths achieved by current antiretroviral therapies, drawbacks including drug resistance and the failure to eradicate infection highlight the need to identify new pathways to target the infection. Circadian rhythms are endogenous 24-hour oscillations which regulate physiological processes including immune responses to infection, and there is an emerging role for the circadian components participating viral replication. The molecular clock consists of transcriptional/translational feedback loops that generate rhythms. In mammals, CLOCK and BMAL1 activate rhythmic transcription of genes including the nuclear receptor REV-ERBα, which represses BMAL1 and plays an essential role in sustaining a functional clock. We investigated whether REV-ERB activity regulates HIV-1 replication, and found REV-ERB agonists inhibited HIV-1 promoter activity in cell lines, primary human CD4 T cells and macrophages, whilst antagonism or genetic disruption of REV-ERB increased promoter activity. Furthermore, the REV-ERB agonist SR9009 inhibited promoter activity of different HIV-subtypes and HIV-1 replication in primary T cells. This study shows a role for REV-ERB synthetic ligands to inhibit HIV-1 LTR promoter activity and viral replication, supporting a role for circadian clock transcription factors in regulating HIV-1 replication.

Aims/Objectives/BackgroundThe Ottawa ankle rules (OAR) have been validated as a highly sensitive tool to rule out ankle fractures and reduce need for radiography. However, datasets validating OAR to date have excluded patients presenting ≥10 days post-injury and there is a need to ascertain if OAR can be safely used to rule out ankle fractures in this population.Methods/DesignPatients presenting with ankle injuries to an emergency department (ED) in England between June 2015 and November 2020 were identified retrospectively through a clinical-coding search. Patient records were used to confirm the number of days between injury and presentation; those who presented ≥10 days post-injury were included for further analysis. Data was collected from ED documentation including region of pain, bony tenderness and weight-bearing status. OAR were used to categorise patients as ‘Ottawa-positive’, ‘Ottawa-negative’ or insufficient documentation. It was recorded whether the patient underwent radiography and whether the formal radiograph report confirmed a clinically-significant fracture. Patients who didn’t undergo radiography and didn’t subsequently re-present were deemed not to have a fracture. Data collected for each patient was checked and agreed by two authors.Results/Conclusions6782 patients presented with ankle injuries, of which 126 patients presented ≥10 days post-injury. Of these 126 patients, 9 were Ottawa-positive, 90 were Ottawa-negative and 27 patients had insufficient documentation. 85 patients underwent radiography and 19 were found to have clinically-significant fractures. Of these fracture patients, 4 were Ottawa-positive and 15 were Ottawa-negative.Within our dataset, OAR demonstrated a sensitivity of 21.05%, specificity 93.75%, PPV 44.40% and NPV 83.30%. Using Fishers exact test, p=0.0658. OAR demonstrate poor sensitivity and cannot be safely used to rule out ankle fractures in patients who present ≥10 days post-injury. However, due to the p-value and low power there may be a risk of type 2 error and a larger study may prove otherwise.

Greater attention is now being given to the increasing popularity of the Internet as a communication tool, particularly social media and other forms of user-generated content (UGC). Social media websites, representing various forms of UGC, are also specifically gaining considerable attention from tourists and potential tourists. Now, tourists have the option of seeking information from “new media,” such as the Internet and social media, as well as traditional media, including films, television, books, magazines, and newspapers. Whereas both new and traditional media will play key roles in influencing the destination choices of tourists, research must also consider the influence of social groups that then translates through word of mouth (WOM). The youth and student travel market is a valuable segment of the overall tourism market, although it is often dismissed or ignored by tourism operators as youth tourists are wrongly perceived as having little financial value. This is, perhaps, because youth and student tourists are generally perceived as having a low income, and thus little disposable income to contribute towards travel. This research addresses this lack of attention by examining and exploring the international destination choice influencers of students with regard to peer and social pressure, traditional WOM, online social media platforms such as Facebook and Twitter, and other UGC websites. The research used a qualitative, focus group study strategy. The results found that all 24 university student participants indicated some level of apprehension about the reliability of information found on the Internet and social media in particular, and there were also varying degrees of reluctance to utilize social media as a credible destination information source. This contradicts previous research suggesting young people such as university students do not generally show concern about the credibility of information found in social media.