BRD1+/- MINIPIGS—A LARGE NON-PRIMATE MODEL OF HUMAN
Here, I present an update on my work, including preliminary data from our minipig model that hints at behavioral changes and altered cerebral cholesterol and steroid biosynthesis.
As we have recently shown that ~15% of GWAS risk loci in major psychiatric disorders harbor genes that encode nuclear receptors or their co-regulators, we argue that our BRD1+/- minipig model broadly represent psychiatric genetic risk and thus holds promising translational value to psychiatry.
Keywords: Psychiatry, psychology and mental health, Animal models/disease models, Genetic engineering
Disentangling the gender-related differences in depressive disorders: The role of estrogen
Shokouh Arjmand, Department of Clinical Medicine, Translational Neuropsychiatry Unit
G. Wegener, Department of Clinical Medicine; A. M. Landau, Department of Clinical Medicine; S. Joca, Department of Biomedicine; H. K. Müller, Department of Clinical Medicine; R. Andreatini, Universidade Federal do Paraná;
Major depressive disorder (MDD) is the most prevalent psychiatric disorder globally, affecting almost 300 million people of different ages. Depression leads to dramatic
functional impairment, disability, and low quality of life. MDD affects twice as many women as men; an epidemiological observation that points to a crucial role of hormonal disparities and the associated biological consequences in the pathophysiology of depression.
Mounting evidence has indicated that the response to ketamine can largely depend on sex, suggesting that ketamine, our only currently approved rapid-acting antidepressant, and estrogen receptors can interact. Using FSL rats, a selectively-bred animal model of depression, in a preclinical setting, molecular and behavioral consequences of this
crosstalk will be investigated. The primary purposes are to explore how estrogen pulls the strings behind depression and how ketamine influences estrogen receptors. The underlying mechanisms of mood regulation by estrogens will also be explored. We will further delve into how ketamine may alter depressive-like behaviors via interacting with estrogen receptors, both the nuclear receptors and membrane estrogen receptors in silico and in vitro, to alleviate depressive symptoms swiftly. The possible interaction site of ketamine will be predicted using reverse docking and molecular dynamics simulation, and will further be confirmed by site directed mutagenesis, and alanine scanning. After being subjected to depression and anxiety-related behavioral tests, molecular correlates of this proposed interaction by use of qRT-PCR and western blotting will be identified.
Keywords: Psychiatry, psychology and mental health, Pharmacology, Animal models/disease models
Organ specific adverse effects after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy - A scoping review
Rogini Balachandran, Department of Clinical Medicine,
LZ. Mogensen, Department of Surgery Aarhus University Hospital;
P. Christensen, Department of Surgery Aarhus University Hospital, Department of Clinical Medicine Aarhus University, Danish Cancer Society Centre for Research on Survivorship and Late Adverse Effects after Cancer in the Pelvis Organs Aarhus University Hospital;
HV. Thaysen, Department of Surgery Aarhus University Hospital, Department of Clinical Medicine Aarhus University;
LH. Iversen, Department of Surgery Aarhus University Hospital, Department of Clinical Medicine Aarhus University
Aim: We conducted a review in order to describe type and extent of organ specific adverse effects after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) for gastrointestinal (GI) cancers and pseudomyxoma peritonei (PMP).
Method: In November 2020, a systematic literature search was done using 6 databases.
We categorized organ specific adverse effects into gastrointestinal dysfunction, urological dysfunction, sexual dysfunction, pain and others. We extracted data on type and extent of these over short-term (0-5 months following surgery), medium-term (6-11 months) and long-term (>=12 months).
Results: In total, we screened 2451 papers. 18 studies fulfilled the eligibility criteria and the studies reported on a total of 2081 patients. The majority of studies reported an increase in organ specific adverse effects 3-6 months after surgery. A return to preoperative level differed within the domains. Diarrhea was still worse 12 months after surgery compared to preoperatively and improved later only. For constipation, symptoms improved shortly after surgery. Sexual dysfunction did not seem to improve long-term. Only one study reported on urological and stoma-related dysfunction. In the remaining domains regarding organ specific adverse effects, a return to preoperative level happened within the first year of surgery.
Conclusion: This review showed an increase in organ specific adverse effects 3-6 months after surgery. A return to preoperative level differed within the domains. Furthermore, this review demonstrated a lack of knowledge on urological dysfunction, sexual dysfunction and stoma-related issues.
Keywords: Reviews and meta-analyses, Gastrointestinal surgery, Other
Being well? Description of existential well-being and suffering in the transition from hospital to home care in older patients and their relatives: a meta-
ethnography
Aline Dragosits, Department of Public Health, Nursing and Healthcare
Bente Martinsen1, Ann Hemingway2, Annelise Norlyk1
1. Section for Nursing and Health care, Department of Public Health, Aarhus University
2. Faculty of Health & Social Sciences, Bournemouth University
Background: The transition from hospital to home care means a change in needs, health status and definition of oneself in an unfamiliar social context, especially for older patients.
Their relatives play an important role during this process, as older patients often leave the hospital with ongoing care needs. Previous studies point to the fact that the transition often creates a feeling of discontinuity of care as well as being left alone. This causes suffering, which effects the well-being of the older patients and their relatives.
Objective: The aim of this meta-ethnography is to gain an in-depth understanding of older patients and their relatives’ description of well-being and suffering in relation to the
transition from hospital to home care.
Method: The study follows a meta-ethnographic approach, which synthesizes qualitative primary research in order to reinterpret the primary findings. A systematic literature search was conducted using Pubmed, Embase, CINAHL, APA PsycInfo and Scopus databases.
Inclusion criteria were empirical phenomenological studies focusing on the hospital to home transition, published in English, Danish or German within the last ten years. Nine phenomenological studies were included.
Perspective: In order to gain an in-depth understanding of the different levels of suffering and well-being and how they are intertwined, the analysis will follow Galvin and Todres (2013) humanizing framework of care. This framework is led by an existential well-being theory, where well-being is a sense of homecoming (dwelling) as well as a possibility (mobility).
This project has received funding from the European Union’s H2020-MSCA-ITN-2018 programme
Keywords: Reviews and meta-analyses, Qualitative research, Other
Diagnostic accuracy of radiography, digital breast tomosynthesis (DBT), micro-CT and ultrasound for margin assessment during breast surgery: A systematic review and meta-analysis
Irina Palimaru Manhoobi, Department of Clinical Medicine, Department of Radiology, Aarhus University Hospital
I. P. Mahoobi MD, Department of Radiology, Aarhus University Hospital; A. Bodilsen MD PhD, Department of Abdominal Surgery, Aarhus University Hospital; J. Nijkamp PhD, Danish center for Particle Therapy, Aarhus University Hospital, Department of Clinical Medicine, Aarhus University; A. Pareek MD PhD, Department of Radiology, North Zealand Hospital; T.
Tramm MD PhD, Department of Pathology, Aarhus University Hospital; S. Redsted MD, Department of Radiology, Aarhus University Hospital; P. Christiansen MD DMSc, Department of Plastic and Breast Surgery, Aarhus University Hospital.
Background:
Achieving adequate resection margins in breast conserving surgery is challenging and often demands more than one surgical procedure. We evaluated pooled diagnostic sensitivity, and specificity of radiological methods for intraoperative margin assessment to reduce repeat surgery rate.
Methods:
We included studies using radiography, digital breast tomosynthesis (DBT), micro-CT, and ultrasound for intraoperative margin assessment with the histological assessment as the reference method. A systematic search was performed in PubMed, Embase, Cochrane Library, Scopus, and Web of Science. Two investigators screened the studies for eligibility criteria and extracted data of the included studies independently. The quality assessment on diagnostic accuracy studies (QUADAS)-2 tool was used. A bivariate random effect model was used to calculate pooled sensitivity and specificity of the index tests in the meta-analysis.
Results:
The systematic search resulted in screening of 798 unique records. Twenty-two articles with 29 index test methods were selected for meta-analysis. Pooled sensitivity and specificity and area under the curve were calculated for each of the 4 subgroups in the meta-analysis respectively: Radiography; 52%, 77%, 60%, DBT; 67%, 76%, 76%, micro-CT;
68%, 69%, 72%, and ultrasound; 72%, 78%, 80%.
Conclusion:
Ultrasound showed the highest and radiography the lowest diagnostic performance for intraoperative margin assessment. However, the heterogeneity between studies was high
and the subgroups small. The radiological methods for margin assessment need further improvement to provide reliable guidance to prevent repeat surgeries in primary breast cancer.
Keywords: Reviews and meta-analyses, Oncology, Medical technology and diagnostic techniques