What underlying mechanisms led the dissociative anesthetic ketamine to be clinically recognized as an antidepressant?

Ketamin har vært kjent i medisinsk praksis i flere tiår som et dissosiativt anestesimiddel. På 2000-tallet ble det observert at subanestetiske doser hadde en effekt på pasienter med depressive lidelser. Disse dosene hadde rask virkningstid og ble senere oppdaget å være fordelaktige fremfor SSRI-antidepressiver. I 2019 ble det godkjent at ketamin kunne brukes som medisin mot depresjon. Denne avhandlingen vil gi en kontekstuell bakgrunn av ketamin og dets utvikling til et klinisk viktig antidepressivt middel. Diskusjonsdelen vil ta for seg den underliggende mekanismen som utgjør denne effekten. Til tross for pågående forskning, forblir de nøyaktige prosessene når ketamin administreres i subanestetiske doser uklare på grunn av kompleksiteten til NMDA-reseptorene. Det antydes at ketamin modulerer glutamatnevrotransmisjon ved disse dosene, noe som fører til stimulering av AMPA-glutatreseptorene og deretter en økning av glutamatnivåene i hjernen. Denne mekanismen gjenoppretter synaptiske tilkoblinger i hjerneregioner som har muligens blitt dysregulert av depresjonen pasienten opplever. Imidlertid er det indikert motstridende funn og foreslåtte alternative mekanismer som gir uttrykk for at det kan være flere virkningsmekanismer som fører til ketamins antidepressive effekter.Ketamine has been used in medical practice for decades as a dissociative anesthetic. Research into its pharmacological properties began in the 2000s when it was observed that subanesthetic doses had a significant effect on patients with depressive disorders. These doses gave rapid-acting antidepressant responses and were later found to benefit individuals with treatment-resistant depression. In a recent significant development, ketamine was approved as a medication for depression in 2019. This thesis will provide a contextual background of ketamine and its progression from its origin to its current clinical relevance as an antidepressant. The discussion will focus on the underlying mechanism responsible for the antidepressant response. Despite ongoing research, the precise processes involved when ketamine is administered at subanesthetic doses remain elusive due to the complexity of the NMDA receptors. It is suggested that ketamine modulates glutamate neurotransmission at these doses, leading to the stimulation of AMPA glutamate receptor and subsequent increase of glutamate levels. This mechanism facilitates the restoration of synaptic connectivity in brain regions dysregulated by depression disorders. However, conflicting findings and proposed alternative mechanisms indicate the presence of multiple contributors to ketamine’s antidepressant effects

The Dilution Effect: A Barrier to Sustainable Consumption in B2B Markets? An Experimental Study of B2B Decision-Makers' Evaluation of a Sustainable Printer

Previous research indicates that individuals have a tendency to perceive sustainable and functional attributes as mutually exclusive, even if this perception does not objectively reflect reality. This misconception can lead them to prefer conventional products over green alternatives, under the belief that businesses prioritizing sustainability might compromise the functionality of the product. This perception has contributed to a discrepancy where individuals express a demand for green products, but this is not necessarily reflected in their purchasing decisions. In this research, we propose the psychological phenomenon known as the ‘dilution effect’ as a possible explanation for this misconception. It suggested that individuals may categorize the functional attribute of a product as ‘diagnostic’ or relevant information, while perceiving the sustainable attribute as ‘nondiagnostic’ information (irrelevant). As a result, when marketers present both attributes, the nondiagnostic information dilutes the diagnostic information, leading to the perception that the product’s functionality is diminished. We conduct a single study to investigate the presence of a dilution effect and a potential method to avoid it within the business-to-business (B2B) market by testing the relationship between communication types and brand attitude. We use an A/B/C monadic testing approach ( n = 100) and ask respondents to evaluate an advertisement of a fictional printer. We first examine the presence of the dilution effect by testing whether communicating a mix of unrelated functional and sustainable attributes lowers the brand attitude compared to the presentation of only the functional attribute. Within the same study, we also explore whether communicating that the sustainable benefits support the functional benefits can be a method to prevent decisions-makers from experiencing the dilution effect. Our findings challenge our predictions; in fact, they are inconsistent with our initial expectations. The results suggest that when companies in B2B markets communicate a mix of unrelated functional and sustainable, the effects of the functional attributes on brand attitude are higher than communication focusing only on functional benefits. Interestingly, communicated related benefits seems to result in the lowest brand attitude.nhhma

The Effects of Unfermented and Fermented Cow and Sheep Milk on the Gut Microbiota.

A variety of fermented foods have been linked to improved human health, but their impacts on the gut microbiome have not been well characterized. Dairy products are one of the most popular fermented foods and are commonly consumed worldwide. One area we currently lack data on is how the process of fermentation changes the gut microbiota upon digestion. What is even less well characterized are the possible differences between cow and other mammals' milks. Our aim was to compare the impact of unfermented skim milk and fermented skim milk products (milk/yogurt) originating from two species (cow/sheep) on the gut microbiome using a rat model. Male Sprague-Dawley rats were fed a dairy-free diet supplemented with one of four treatment dairy drinks (cow milk, cow yogurt, sheep milk, sheep yogurt) for 2 weeks. The viable starter culture bacteria in the yogurts were depleted in this study to reduce their potential influence on gut bacterial communities. At the end of the study, cecal samples were collected and the bacterial community profiles determined via 16S rRNA high-throughput sequencing. Fermentation status drove the composition of the bacterial communities to a greater extent than their animal origin. While overall community alpha diversity did not change among treatment groups, the abundance of a number of taxa differed. The cow milk supplemented treatment group was distinct, with a higher intragroup variability and a distinctive taxonomic composition. Collinsella aerofaciens was of particularly high abundance (9%) for this group. Taxa such as Firmicutes and Lactobacillus were found in higher abundance in communities of rats fed with milk, while Proteobacteria, Bacteroidetes, and Parabacteroides were higher in yogurt fed rats. Collinsella was also found to be of higher abundance in both milk (vs. yogurt) and cows (vs. sheep). This research provides new insight into the effects of unfermented vs. fermented milk (yogurt) and animal origin on gut microbial composition in a healthy host. A number of differences in taxonomic abundance between treatment groups were observed. Most were associated with the effects of fermentation, but others the origin species, or in the case of cow milk, unique to the treatment group. Future studies focusing on understanding microbial metabolism and interactions, should help unravel what drives these differences.fals

Incidence of newborn resuscitative interventions at birth and short-term outcomes: A regional population-based study

Objectives To determine the incidence and characteristics of resuscitative interventions at different gestational ages and short-term outcomes after resuscitation. Design, setting and patients A prospective observational study in an unselected population at Stavanger University Hospital, Norway, from October 2016 until September 2017. Interventions Using a data collection form and video recordings, we registered and analysed resuscitative interventions. Main outcome measures Incidence of continuous positive airway pressure (CPAP), positive pressure ventilation (PPV), intubation, chest compressions and intravenous fluid or epinephrine boluses. Short-term outcomes of resuscitated newborns. Results All 4693 newborns in the study period were included in the study. Two hundred and ninety-one (6.2%) newborns received interventions in the first minutes of life beyond drying and stimulation. PPV was provided in 170 (3.6%) while CPAP (without PPV) was provided in 121 (2.6%) newborns. Duration of PPV was median (IQR) 106 s (54–221). Intubations were performed in 19 (0.4%) newborns, with a mean (SD) intubation time of 47 (21) s. Ten (0.2%) newborns received chest compressions and epinephrine was administrated in three (0.1%) newborns. Sixty-three per cent of the treated newborns from 34 weeks’ gestational age were returned to parental care without further follow-up.publishedVersio

The Gut Microbiome Is Altered in Postmenopausal Women With Osteoporosis and Osteopenia

(c) 2020 The Author/sOsteoporosis and its precursor osteopenia are common metabolic bone diseases in postmenopausal women. A growing body of evidence suggests that the gut microbiota is involved in the regulation of bone metabolism; however, there are few studies examining how gut microbiomes in osteoporosis and osteopenia may differ from those in healthy individuals. The aim of this study was to characterize the diversity, composition, and functional gene potential of the gut microbiota of healthy, osteopenic, and osteoporotic women. Body composition, bone density, and fecal metagenomes were analyzed in 86 postmenopausal women. The women were classified as healthy, osteopenic, or osteoporotic based on T-scores. The taxonomic and functional gene compositions of the microbiome were analyzed using shotgun metagenomic sequencing. Both osteoporotic and osteopenic taxonomic compositions were found to be significantly different from healthy participants. Linear discriminant-analysis effect-size analyses identified that healthy participants had more unclassified Clostridia and methanogenic archaea (Methanobacteriaceae) than in both osteoporotic and osteopenic participants. Bacteroides was found to be more abundant in osteoporosis and osteopenia groups. Some KEGG pathways, including carbohydrate metabolism, biosynthesis of secondary metabolites, and cyanoamino acid metabolism, were found to be more abundant in both osteoporosis and osteopenia. These results show that osteoporosis and osteopenia alter the gut microbiome of postmenopausal women and identify potential microbial taxonomic and functional pathways that may be involved in this disease.fals

A randomised controlled study of low-dose high-frequency in-situ simulation training to improve newborn resuscitation

Positive pressure ventilation of the non-breathing newborn is a critical and time-sensitive intervention, considered to be the cornerstone of resuscitation. Many healthcare providers working in delivery units in high-resource settings have little opportunity to practise this skill in real life, affecting their performance when called upon to resuscitate a newborn. Low-dose, high-frequency simulation training has shown promise in low-resource settings, improving ventilation performance and changing practice in the clinical situation. We performed a randomised controlled study of low-dose, high-frequency simulation training for maintenance of ventilation competence in a multidisciplinary staff in a busy teaching hospital in Norway. We hypothesised that participants training according to a low-dose, high-frequency protocol would perform better than those training as they wished. Our results did not support this, although the majority of protocol participants were unable to achieve training targets. Subgroup analysis comparing no training to at least monthly training did identify a clear benefit to regular simulation practice. Simulated ventilation competence improved significantly for all participants over the course of the study. We conclude that frequent, short, simulation-based training can foster and maintain newborn ventilation skills in a multidisciplinary delivery unit staff in a high-resource setting.publishedVersio

Compliance with Guidelines and Efficacy of Heart Rate Monitoring during Newborn Resuscitation: A Prospective Video Study

Objective: Newborn resuscitation guidelines recommend initial assessment of heart rate (HR) and initiation of positive pressure ventilation (PPV) within 60 s after birth in non-breathing newborns. Pulse oximeter (PO) and electrocardiogram (ECG) are suggested methods for continuous HR monitoring during resuscitation. Our aim was to evaluate compliance with guidelines and the efficacy of PO versus ECG monitoring in real-life newborn resuscitations. Methods: In this prospective observational study, we video recorded resuscitations of newborns ≥34 weeks of gestation receiving PPV at birth. Results: 104 resuscitations were analysed. Median (IQR) time from birth to arrival at the resuscitation bay was 48 (22–68) s (n = 62), to initial HR assessment 70 (47–118) s (n = 61), and to initiation of PPV 78 (42–118) s (n = 62). Initial HR assessment (stethoscope or palpation) and initiation of PPV were achieved within 60 s for 35% of the resuscitated newborns. Time to initial HR assessment and initiating PPV was significantly longer following vaginal deliveries than caesarean sections: 84 (70–139) versus 44 (30–66) s (p < 0.001) and 93 (73–139) versus 38 (30–66) s (p < 0.001). Time from birth and sensor application to provision of a reliable HR signal from PO versus ECG was 348 (217–524) (n = 42) versus 174 (105–277) s (n = 30) (p < 0.001) and 199 (77–352) (n = 65) versus 16 (11–22) s (n = 52) (p < 0.001). Conclusion: Initial HR assessment and initiation of PPV were achieved within 60 s after birth in only 1/3 of newborn resuscitations. When applied for continuous HR monitoring, ECG was superior to PO in time to achieve reliable HR signals in real-life resuscitations.publishedVersio

Comparison of heart rate feedback from dry-electrode ecg, 3-lead ecg, and pulse oximetry during newborn resuscitation

Background: Assessment of heart rate (HR) is essential during newborn resuscitation, and comparison of dry-electrode ECG technology to standard monitoring by 3-lead ECG and Pulse Oximetry (PO) is lacking. Methods: NeoBeat, ECG, and PO were applied to newborns resuscitated at birth. Resuscitations were video recorded, and HR was registered every second. Results: Device placement time from birth was median (quartiles) 6 (4, 18) seconds for NeoBeat versus 138 (97, 181) seconds for ECG and 152 (103, 216) seconds for PO. Time to first HR presentation from birth was 22 (13, 45) seconds for NeoBeat versus 171 (129, 239) seconds for ECG and 270 (185, 357) seconds for PO. Proportion of time with HR feedback from NeoBeat during resuscitation from birth was 85 (69, 93)%, from arrival at the resuscitation table 98 (85, 100)%, and during positive pressure ventilation 100 (95, 100)%. For ECG, these proportions were, 25 (0, 43)%, 28 (0, 56)%, and 33 (0, 66)% and for PO, 0 (0, 16)%, 0 (0, 16)%, and 0 (0, 18)%. All p < 0.0001. Conclusions: NeoBeat was faster to place, presented HR more rapidly, and provided feedback on HR for a larger proportion of time during ongoing resuscitation compared to 3-lead ECG and PO.publishedVersio

The Relationship between Gram-Negative Colonisation and Bloodstream Infections in Neonates: A Systematic Review and Meta-Analysis.

OBJECTIVES: Neonates admitted to Neonatal Intensive Care Units (NICU) are at significant risk of developing bloodstream infections (BSIs). Gram-negative bacteria (GNB) both colonise and infect, but the association between these entities is unclear. By conducting a systematic literature review, we aimed to explore the impact of factors on the association between GN colonisation and GN-BSI at both baby level and unit level. METHODS: We searched Medline, Embase, and Cochrane Library. Observational cohort studies published after 2000 up to June 2016 reporting data on the total number of neonates (0-28 days) colonised with GNB assessed by rectal/skin swab culture and the total number of neonates with GN-BSI (same bacteria) were included. Studies were excluded if data on skin/rectal colonisation, neonates, and GNB could not been identified separately. The meta-analyses along with multivariate meta-regression with random-effect model were performed to investigate factors associated with the GN colonisation and GN-BSI at baby-level and unit-level. RESULTS: 27 studies fulfilled our inclusion criteria, 15 for the baby-level and 12 for the unit-level analysis. Study heterogeneity was high, with suboptimal overall quality of reporting assessed by the STROBE-NI statement (44.8% of items adequately reported). In 1,984 colonised neonates, 157 (7.9%) developed GN-BSI compared with 85 of 3,583 (2.4%) non-colonised neonates. Considerable heterogeneity across studies was observed. Four factors were included in the meta-regression model: Gross domestic product (GDP), pathogen, outbreak, and frequency of screening. There was no statistically significant impact of these factors on GN colonisation and GN-BSI in baby level. We were unable to perform the multivariate meta-regression due to the insufficient reported data for unit level. CONCLUSIONS: Study limitations include the small number and the high heterogeneity of the included studies. While this report shows a correlation between colonisation and BSI risk, this data currently doesn't support routinely screening for GNB. The analysis of large cohorts of colonised neonates with clinical outcomes is still needed to define the major determinants leading from colonisation to infection

Utvikling av Banestyring for Hydraulisk Offshorekran

Masteroppgave i mekatronikk - Universitetet i Agder, 2015(Konfidensiell til/confidential until 01.07.2020