“I smile, but Without Showing My Teeth”: The Lived Experience of Cleft, Lip, and Palate in Adults

Objective: To explore and describe the experience of growing up with unilateral cleft lip and palate (CLP) in adults. Design: Face-to-face interviews. Giorgi’s phenomenological method was used for analysis. Participants: Twenty-one (mean age: 40.8 years) adults treated for unilateral CLP during childhood and adolescence participated in the study. Results: Growing up with CLP meant to become aware of bodily otherness. The possible reactions from peers early in life complicated the striving for inclusion outside the close family. Being self-confident, clever in school, physically fit, and having trusted friends represented barriers against teasing and bullying. Nevertheless, the reflected image, in mirrors, windows, and photos, reminded the participants of the objectifying looks from others and often led to bodily adjustments that persisted into adulthood. The trajectory of treatment was not questioned during childhood, and the participants accepted the decisions on care made by experts and parents. Although problems related to the cleft could persist or return after the termination of ordinary treatment, a more hesitant view on the possible benefits of additional surgery was typical in adulthood. Conclusions: In retrospect, growing up with a unilateral CLP was found to have been an unquestioned part of the adult participants’ childhood, a burden that they feared would, to some extent, also be passed to their own children. However, the CLP had not prevented them from achieving goals and satisfaction in life. The occurrence of persisting psychological, functional, and esthetic challenges in adults suggests the need for an individualized, lifelong, and multidisciplinary perspective on CLP follow-up.publishedVersio

Per se limits: methods of defining cut-off values for zero tolerance

Establishment of cut-off values for per se legislation

Understanding of how the properties of medical grade lactide based copolymer scaffolds influence adipose tissue regeneration: Sterilization and a systematic in vitro assessment

Aliphatic polyesters are the synthetic polymers most commonly used in the development of resorbable medical implants/devices. Various three-dimensional (3D) scaffolds have been fabricated from these polymers and used in adipose tissue engineering. However, their systematic evaluation altogether lacks, which makes it difficult to select a suitable degradable polymer to design 3D resorbable implants and/or devices able to effectively mimic the properties of adipose tissue. Additionally, the impact of sterilization methods on the medical devices, if any, must be taken into account. We evaluate and compare five different medical-grade resorbable polyesters with l-lactide content ranging from 50 to 100 mol% and exhibiting different physiochemical properties depending on the comonomer (d-lactide, ε-caprolactone, glycolide, and trimethylene carbonate). The salt-leaching technique was used to prepare 3D microporous scaffolds. A comprehensive assessment of physical, chemical, and mechanical properties of the scaffolds was carried out in PBS at 37 °C. The cell-material interactions and the ability of the scaffolds to promote adipogenesis of human adipose tissue-derived stem cells were assessed in vitro. The diverse physical and mechanical properties of the scaffolds, due to the different composition of the copolymers, influenced human adipose tissue-derived stem cells proliferation and differentiation. Scaffolds made from polymers which were above their glass transition temperature and with low degree of crystallinity showed better proliferation and adipogenic differentiation of stem cells. The effect of sterilization techniques (electron beam and ethylene oxide) on the polymer properties was also evaluated. Results showed that scaffolds sterilized with the ethylene oxide method better retained their physical and chemical properties. Overall, the presented research provides (i) a detailed understanding to select a degradable polymer that has relevant properties to augment adipose tissue regeneration and can be further used to fabricate medical devices/implants; (ii) directions to prefer a sterilization method that does not change polymer properties.publishedVersio

Comparison of bone regenerative capacity of donor-matched human adipose–derived and bone marrow mesenchymal stem cells

Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(L-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated radiographically and histologically after 4, 12, and 24 weeks. In vitro, ASC and BMSC demonstrated mineralization. However, BMSC showed higher alkaline phosphatase activity than ASC. In vivo, human osteogenesis–related genes Runx2 and collagen type I were expressed in defects with scaffold/cells. Defects with scaffold/BMSC had higher cellular activity than defects with scaffold/ASC. Moreover, bone formation in defects with scaffold/BMSC was greater than in defects with scaffold/ASC, especially at the early time-point. These results suggest that although ASC have the potential to regenerate bone, the rate of bone regeneration with ASC may be slower than with BMSC. Accordingly, BMSC are more suitable for bone regenerative applications.publishedVersio

A clinical trial on the acute effects of methadone and buprenorphine on actual driving and cognitive function of healthy volunteers.

Aims: The present study assessed the acute effects of methadone and buprenorphine on actual on‐road driving performance and neurocognitive function. Methods: Methadone (5 and 10 mg per os) and buprenorphine (0.2 and 0.4 mg sublingual) were administered to 22 healthy volunteers in a five‐way, double‐blind, randomized, placebo‐controlled, double‐dummy, cross‐over study. Driving performance was assessed with an on‐road driving test. The primary outcome measure was standard deviation of lateral position (SDLP), a measure of road tracking control. Laboratory tests were used to measure cognitive function (e.g. reaction time and attention) and questionnaires were used to assess subjective measures of mood and sedation. Results: There was no significant main effect of treatment on SDLP. Yet, analysis of individual drug‐placebo contrast data revealed that buprenorphine 0.4 mg significantly increased SDLP. Driving impairment was mild and below the impairment threshold of a blood alcohol concentration of 0.5 mg ml−1. Four participants stopped their driving test while under the influence of either opioid due to sleepiness. Both opioids produced impairments of cognitive task performance and increased sleepiness particularly at the highest dose. Conclusions: Analgesic doses of buprenorphine produced mild impairing effects on driving and related cognitive skills, while methadone impaired cognitive task performance but not driving performance. Large individual variations were observed for both drugs. Patients should be informed about the possibility of driving impairment when initiating opioid treatment

Roadside survey of alcohol and drug use among Norwegian drivers in 2016-2017: A follow-up of the 2008-2009 survey

Objective: The objective of this study was to study the use of alcohol and drugs among the general driving population in the southeastern part of Norway and to compare the findings with the results from a similar roadside survey in 2008–2009. Methods: A roadside survey of drivers of cars, vans, motorcycles, and mopeds was performed from April 2016 to April 2017 in collaboration with the Mobile Police Service. Oral fluid was collected using the Quantisal device and analyzed for alcohol, illicit drugs, and psychoactive medicinal drugs. Age, sex, time, and geographical region were recorded. Results: Of the 5,556 drivers who were asked to participate in the study, 518 drivers (9.3%) declined to participate, and 4 samples contained insufficient volume of oral fluid to be analyzed; thus, 5,034 drivers were included. Fifteen drivers (0.3%) suspected by the police for driving under the influence of alcohol or drugs refused to participate in the study, so the alcohol and drug findings represent minimum values. The weighted prevalence of alcohol concentrations above the legal limit of 0.2 g/L was 0.2%, which is similar to the finding in the 2008–2009 survey. The weighted prevalences of medicinal drugs and illicit drugs were 3.0 and 1.7%, respectively; those numbers included more drugs than the 2008–2009 survey and are therefore not comparable. The most prevalent illicit and medicinal drugs were tetrahydrocannabinol (1.3%) and zopiclone (1.4%). The prevalences of benzodiazepines and amphetamines were significantly lower than detected in the 2008–2009 survey. Only one sample tested positive for a new psychoactive substance. Conclusions: The proportion of samples that tested positive for alcohol had not changed since 2008–2009, and the proportions that tested positive for benzodiazepines and amphetamines were lower. There are several possible reasons for the reduction: Implementation of legal limits for 28 drugs in 2012–2016, increased use of drug recognition tests, implementation of drug screening instruments, and automatic number plate recognition by the police since 2010; more focused enforcement of the driving under the influence (DUI) law; better information provided to drivers; and changes in drug prescriptions

Pharmacokinetics of single doses of methadone and buprenorphine in blood and oral fluid in healthy volunteers and correlation with effects on psychomotor and cognitive functions

PURPOSE: We aimed to study the pharmacokinetics of methadone and buprenorphine in blood and oral fluid after single-dose administration and investigate correlations between concentrations in blood and neurocognitive functions. METHODS: A 5-way, double-blind, randomized, placebo-controlled, double-dummy, crossover study was performed to study the pharmacokinetics and neurocognitive effects of methadone (5 and 10 mg per oral) and buprenorphine (0.2 and 0.4 mg sublingual) in 22 healthy volunteers. Blood and oral fluid were collected throughout the test days, and drug concentrations in both matrices were analyzed using ultrahigh-performance liquid chromatography-tandem mass spectrometry. On-road driving testing, neurocognitive computerized tests, and subjective questionnaires were performed. RESULTS: Large individual variations in concentrations of methadone and buprenorphine in blood and oral fluid, and accordingly oral fluid/blood drug concentration ratios, were observed. The mean ratio 6.5 hours after drug administration was 2.0 (range, 0.49-7.39) for methadone after both doses. Buprenorphine was not detected above the limit of quantification in blood after 6.5 hours. No significant correlation between methadone concentration in blood and effect was found. Significant correlations were found between buprenorphine concentration in blood and standard deviation of lateral position in the driving test and some measures of reaction time, divided attention, balance, alertness, contentedness. and sleepiness. CONCLUSIONS: Concentrations of methadone and buprenorphine in blood and oral fluid showed large interindividual variations. No concentration-effect correlations were found for methadone, whereas low to moderate correlations were observed between buprenorphine concentration and driving, psychomotor function, and subjective rating of sleep and alertness

Association between speeding and use of alcohol and medicinal and illegal drugs and involvement in road traffic crashes among motor vehicle drivers

Objective: The objective of this study was to study the association between self-reported road traffic crashes (RTCs) and recent use of alcohol and medicinal and illicit drug use and self-reported speeding in the previous 2 years. Methods: During the period from April 2016 to April 2017, drivers of cars, vans, motorcycles, and mopeds were stopped in a Norwegian roadside survey performed in collaboration with the police. Participation was voluntary and anonymous. The drivers were asked to deliver an oral fluid sample (mixed saliva), which was analyzed for alcohol and 39 illicit and medicinal drugs and metabolites. In addition, data on age, sex, and self-reported speeding tickets and RTCs during the previous 2 years were collected. Results: A total of 5,031 participants were included in the study, and 4.9% tested positive for the use of one or more illicit or medicinal drugs or alcohol. We found a significant, positive association between the use of cannabis and RTC involvement (odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.05–3.57; P = 0.035) and also between previous speeding tickets and RTC involvement (OR = 1.39; 95% CI, 1.08–1.80; P = 0.012). In addition, older age groups were found to have a significant, negative association with RTC involvement, with ORs equal to or less than 0.49, when using the age group 16–24 as reference. Conclusion: Speeding, as an indicator of risk behavior, and the use of cannabis were associated with previous RTC involvement, whereas increasing age was significantly associated with lower risk. This is consistent with previous studies on RTCs

Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison

Abstract Background Adipose-derived stem cells (ASCs) have been introduced as an alternative to bone marrow mesenchymal stem cells (BMSCs) for cell-based therapy. However, different studies comparing ASCs and BMSCs have shown conflicting results. In fact, harvesting ASCs and BMSCs from different individuals might influence the results, making comparison difficult. Therefore, this study aimed to characterize donor-matched ASCs and BMSCs in order to investigate proliferation, differentiation potential and possible effects of donor variation on these mesenchymal stem cells (MSCs). Methods Human bone marrow and adipose tissue samples were obtained from nine donors aged 8–14. ASCs and BMSCs were isolated and characterized based on expression of surface markers using flow cytometry. The proliferation up to 21 days was investigated. Multi-lineage differentiation was induced using osteogenic, chondrogenic and adipogenic differentiation media. Alkaline phosphatase (ALP) activity was monitored and collagen type I formation was evaluated by immunofluorescence staining. In vitro multi-potency was studied using tissue-specific stains and lineage-specific gene expression. In addition, the osteogenic lineage was evaluated at protein level. Results Isolated ASCs and BMSCs from all donors demonstrated morphologic and immunophenotypic characteristics of MSCs, with expression of MSCs markers and negative expression of hematopoietic markers. Unlike BMSCs, ASCs showed high expression of CD49d and low expression of Stro-1. In general, ASCs showed significantly higher proliferation and adipogenic capacity with more lipid vesicle formation and expression of the adipogenesis-related genes than BMSCs. In contrast, BMSCs showed significantly higher osteogenic and chondrogenic capacity compared to ASCs. BMSCs had earlier and higher ALP activity, calcium deposition, and expression of the osteogenesis- and chondrogenesis-related genes and the osteogenesis-related protein osteopontin. Proliferation and differentiation capacity of ASCs and BMSCs varied significantly among the donors. Conclusions ASCs and BMSCs showed tissue-specific differentiation abilities, but with significant variation between donors. The similarities and differences in the properties of ASCs and BMSCs should be taken into consideration when planning stem cell-based therapy