| 1. |
- Patel, Y., et al.
(author)
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Virtual Ontogeny of Cortical Growth Preceding Mental Illness
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
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Journal article (peer-reviewed)abstract
- Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
- Schijven, Dick, et al.
(author)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Journal article (peer-reviewed)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 9. |
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| 10. |
- Potthast, W, et al.
(author)
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Relative movements between the tibia and femur induced by external plantar shocks are controlled by muscle forces in vivo.
- 2011
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In: Journal of Biomechanics. - : Elsevier BV. - 0021-9290 .- 1873-2380. ; 44:6, s. 1144-1148
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Journal article (peer-reviewed)abstract
- The purpose of this study was to investigate the role of muscle activation on the relative motion between tibia and femur. Impacts were initiated under the heels of four volunteers in three different activation levels of muscles crossing the extended knee joint: 0%, 30% and 60% of previously performed maximal voluntary isometric contractions. Impact forces were measured and tibial and femoral accelerations and displacements were determined by means of accelerometry. The accelerometers were mounted on the protruding ends of intracortical pins, inserted into the distal aspect of the femur and proximal aspect of the tibia. Under the 0%-condition the impact force (475±64N) led to 2.3±1.2mm knee compression and to 2.4±1.9mm medio-lateral and 4.4±1.1mm antero-posterior shear. The impact forces increased significantly with higher activation levels (619±33N (30%), 643±147N (60%)), while the knee compression (1.5±1.2, 1.4±1.3mm) and both medio-lateral shear (1.8±1.4, 1.5±1.1mm) and antero-posterior shear (2.6±1.3, 1.5±1.1mm) were significantly reduced. This study indicated that muscles are effective in controlling the relative motion between tibia and femur when the knee is subjected to external forces.
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| 11. |
- Potthast, W, et al.
(author)
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The influences of impact interface, muscle activity, and knee angle on impact forces and tibial and femoral accelerations occurring after external impacts
- 2010
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In: Journal of applied biomechanics. - : Human Kinetics. - 1065-8483 .- 1543-2688. ; 26:1, s. 1-9
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Journal article (peer-reviewed)abstract
- The purpose of this study was to quantify relative contributions of impact interface, muscle activity, and knee angle to the magnitudes of tibial and femoral accelerations occurring after external impacts. Impacts were initiated with a pneumatically driven impacter under the heels of four volunteers. Impact forces were quantified with a force sensor. Segmental accelerations were measured with bone mounted accelerometers. Experimental interventions were hard and soft shock interfaces, different knee angles (0°, 20°, 40° knee flexion), and muscular preactivation (0%, 30%, 60% of maximal voluntary contraction) of gastrocnemii, hamstrings, and quadriceps. Greater knee flexion led to lower impact forces and higher tibial accelerations. Increased muscular activation led to higher forces and lower tibial accelerations. The softer of the two shock interfaces under study reduced both parameters. The effects on accelerations and forces through the activation and knee angle changes were greater than the effect of interface variations. The hardness of the two shock interfaces explained less than 10% of the variance of accelerations and impact forces, whereas knee angle changes explained 25–29%, and preactivation changes explained 35–48% of the variances. It can be concluded that muscle force and knee joint angle have greater effects in comparison with interface hardness on the severity of shocks on the lower leg.
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| 12. |
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| 13. |
- van Rhee, Koen P., et al.
(author)
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Pooled Population Pharmacokinetic Analysis and Dose Recommendations for Ciprofloxacin in Intensive Care Unit Patients with Obesity
- 2024
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In: Journal of Clinical Pharmacology. - 0091-2700.
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Journal article (peer-reviewed)abstract
- Recent studies have explored the influence of obesity and critical illness on ciprofloxacin pharmacokinetics. However, variation across the subpopulation of individuals with obesity admitted to the intensive care unit (ICU) with varying renal function remains unexamined. This study aims to characterize ciprofloxacin pharmacokinetics in ICU patients with obesity and provide dose recommendations for this special population. Individual patient data of 34 ICU patients with obesity (BMI >30 kg/m2) from four studies evaluating ciprofloxacin pharmacokinetics in ICU patients were pooled and combined with data from a study involving 10 individuals with obesity undergoing bariatric surgery. All samples were collected after intravenous administration. Non-linear mixed effects modeling and simulation were used to develop a population pharmacokinetic model and describe ciprofloxacin exposure in plasma. Model-based dose evaluations were performed using a pharmacokinetic/pharmacodynamic target of AUC/MIC >125. The data from patients with BMI ranging from 30.2 to 58.1 were best described by a two-compartment model with first-order elimination and a proportional error model. The inclusion of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as a covariate on clearance reduced inter-individual variability from 57.3% to 38.5% (P <.001). Neither body weight nor ICU admission significantly influenced clearance or volume of distribution. Renal function is a viable predictor for ciprofloxacin clearance in ICU patients with obesity, while critical illness and body weight do not significantly alter clearance. As such, body weight and critical illness do not need to be accounted for when dosing ciprofloxacin in ICU patients with obesity. Individuals with CKD-EPI >60 mL/min/1.73 m2 may require higher dosages for the treatment of pathogens with minimal inhibitory concentration ≥0.25 mg/L.
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| 14. |
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| 15. |
- Ahle, Charlotte M., et al.
(author)
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Staphylococcus saccharolyticus : An Overlooked Human Skin Colonizer
- 2020
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In: Microorganisms. - : MDPI. - 2076-2607. ; 8:8
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Journal article (peer-reviewed)abstract
- Coagulase-negative staphylococcal species constitute an important part of the human skin microbiota. In particular, facultative anaerobic species such as Staphylococcus epidermidis and Staphylococcus capitis can be found on the skin of virtually every human being. Here, we applied a culture-independent amplicon sequencing approach to identify staphylococcal species on the skin of healthy human individuals. While S. epidermidis and S. capitis were found as primary residents of back skin, surprisingly, the third most abundant member was Staphylococcus saccharolyticus, a relatively unstudied species. A search of skin metagenomic datasets detected sequences identical to the genome of S. saccharolyticus in diverse skin sites, including the back, forehead, and elbow pit. Although described as a slow-growing anaerobic species, a re-evaluation of its growth behavior showed that S. saccharolyticus can grow under oxic conditions, and, in particular, in a CO2-rich atmosphere. We argue here that S. saccharolyticus was largely overlooked in previous culture-dependent and -independent studies, due to its requirement for fastidious growth conditions and the lack of reference genome sequences, respectively. Future studies are needed to unravel the microbiology and host-interacting properties of S. saccharolyticus and its role as a prevalent skin colonizer.
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| 16. |
- Arndt, A, et al.
(author)
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Asymmetrical loading of the human triceps surae: I. Mediolateral force differences in the Achilles tendon
- 1999
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In: Foot & ankle international. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 20:7, s. 444-449
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Journal article (peer-reviewed)abstract
- An in vitro experiment was designed to identify whether tensile force on different triceps surae components would result in nonhomogenous force distribution across the human Achilles tendon. Medial tendon forces were significantly higher than lateral (23.2 ± 6.6%; P ≤ 0.05) when only the gastrocnemius medialis was subjected to force. Lateral forces were significantly higher when both gastrocnemii (30.6 ± 16.5%) or all three muscles (20.7 ± 10.9%) were loaded. Experimental identification of force concentrations in the human Achilles tendon contributes to the understanding of the origin of its injury.
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| 17. |
- Arndt, A, et al.
(author)
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Asymmetrical loading of the human triceps surae: II. Differences in calcaneal moments
- 1999
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In: Foot & ankle international. - : SAGE Publications. - 1071-1007 .- 1944-7876. ; 20:7, s. 450-455
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Journal article (peer-reviewed)abstract
- An in vitro experimental study is presented investigating differences in moments calculated at the calcaneus, resulting from tensile forces input in various configurations of triceps surae muscles. Results indicated significantly higher values for plantarflexion moments when forces were input in both gastrocnemii than in the soleus ( P ≤ 0.05). Tensile force applied solely to the gastrocnemius lateralis produced a mean eversion moment at the calcaneus, whereas all other configurations demonstrated the expected inversion moment. An abduction moment was reported throughout. The presented data provides valuable input for optimizing future biomechanical models.
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| 18. |
- Brüggemann, A. Jelmer, et al.
(author)
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Patients’ silence towards the healthcare system after ethical transgressions by staff : associations with patient characteristics in a cross-sectional study among Swedish female patients
- 2012
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In: BMJ Open. - : BMJ. - 2044-6055. ; 2:6
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Journal article (peer-reviewed)abstract
- Objectives: To identify which patient characteristics are associated with silence towards the healthcare system after experiences of abusive or ethically wrongful transgressive behaviour by healthcare staff.Design: Cross-sectional questionnaire study using the Transgressions of Ethical Principles in Health Care Questionnaire.Setting: A women's clinic in the south of Sweden.Participants: Selection criteria were: consecutive female patients coming for an outpatient appointment, ≥18-year-old, with the ability to speak and understand the Swedish language, and a known address.Questionnaires were answered by 534 women (60%) who had visited the clinic, of which 293 were included in the present study sample.Primary outcome measure: How many times the respondent remained silent towards the healthcare system relative to the number of times the respondent spoke up.Results: Associations were found between patients’ silence towards the healthcare system and young age as well as lower self-rated knowledge of patient rights. Both variables showed independent effects on patients’ silence in a multivariate model. No associations were found with social status, country of birth, health or other abuse.Conclusions: The results offer opportunities for designing interventions to stimulate patients to speak up and open up the clinical climate, for which the responsibility lies in the hands of staff; but more research is needed.
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| 19. |
- Brüggemann, A. Jelmer
(author)
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Toward an Understanding of Abuse in Health Care : A Female Patient Perspective
- 2012
-
Doctoral thesis (other academic/artistic)abstract
- Background. High numbers of incidents of abuse in health care (AHC) have been reported by patients in Sweden. In questionnaire studies (n=9600), every fifth Swedish woman and every tenth Swedish man reported any lifetime experience of AHC, and a majority reported suffering from their experiences. Female patients with experiences of AHC described them as experiences of being nullified, and male patients as experiences of being mentally pinioned. Little is known about why AHC occurs and how it can prevail in a health care system that aims to relieve patients’ suffering.Aim. The overall aim of the thesis was to bring understanding to what AHC is and to start exploring what contributes to its occurrence, focusing on a female patient perspective.Methods. In study I, a concept analysis of AHC was conducted based on the concept’s appearance in scientific literature and through case studies. Also, AHC was demarcated against the related concepts patient dissatisfaction, medical error, and personal identity threat, in order to analyze differences and similarities with these concepts. For studies II and III the Transgressions of Ethical Principles in Health Care Questionnaire (TEP) was developed to measure to what extent female patients remain silent toward the health care system after having experienced abusive or wrongful ethical transgressions in the Swedish health care system. It was hypothesized that to a high degree female patients remain silent toward the health care system after such experiences, and this lack of feedback may in turn contribute to the hampering of structural change toward better encounters. The questionnaire was answered by female patients recruited at a women’s clinic in the south of Sweden (n=530). Study IV built on a constructed grounded theory design and included informants who reported experiences of AHC in TEP (n=12). The interviews focused on the informants’ stories of what contributed to their experiences of AHC.Results.Results. Based on the concept analysis, AHC was described as patients’ subjective experiences in health care of encounters devoid of care, in which they experienced suffering and loss of their human value. Study II showed that a majority of the female patients who perceived one or more transgressions as abusive or wrongful remained silent about at least one of them (70.3%). In 60% of all cases, patients remained silent about abusive or wrongful events. In study III it was examined whether patients remaining silent could be associated with any patient characteristics. Remaining silent was only found to be associated with younger age and a lower self-rated knowledge of patient rights. In study IV, female patients’ stories of what contributed to their experiences of AHC were analyzed. This was best characterized as a process where the patient loses power struggles. According to these patients, not only their vulnerability, but also their level of competence contributed to staff’s unintended use of domination techniques by which they felt abused.Conclusions. As AHC is defined from patients’ subjective experiences it is necessary for the prevention of AHC to listen to patients’ stories and complaints. The prevalence of female patients’ silence after abusive events could be worrying, as it constitutes a loss of essential feedback for the health care system. Patients do not bear responsibility for the quality of health care processes, but their knowledge may be very valuable for structural improvement of these processes and could be valued as such. Clinical interventions that stimulate these patients to speak up, accompanied by health care staff’s reflections on how to respond to patients speaking up, must therefore be explored.
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| 20. |
- Brüggemann, A. Jelmer, et al.
(author)
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What contributes to abuse in health care? : A grounded theory of female patients’ stories
- 2013
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In: International Journal of Nursing Studies. - : Elsevier BV. - 0020-7489 .- 1873-491X. ; 50:3, s. 404-412
-
Journal article (peer-reviewed)abstract
- BackgroundIn Sweden, 20% of female patients have reported lifetime experiences of abuse in any health care setting. Corresponding prevalence among male patients is estimated to be 8%. Many patients report that they currently suffer from these experiences. Few empirical studies have been conducted to understand what contributes to the occurrence of abuse in health care.ObjectivesTo understand what factors contribute to female patients’ experiences of abuse in health care.DesignConstructivist grounded theory approach.SettingsWomen's clinic at a county hospital in the south of Sweden.ParticipantsTwelve female patients who all had reported experiences of abuse in health care in an earlier questionnaire study.MethodsIn-depth interviews.ResultsThe analysis resulted in the core category, the patient loses power struggles, building on four categories: the patient's vulnerability, the patient's competence, staff's use of domination techniques, and structural limitations. Participants described how their sensitivity and dependency could make them vulnerable to staff's domination techniques. The participants’ claim for power and the protection of their autonomy, through their competence as patients, could catalyze power struggles.ConclusionsCentral to the participants’ stories was that their experiences of abuse in health care were preceded by lost power struggles, mainly through staff's use of domination techniques. For staff it could be important to become aware of the existence and consequences of such domination techniques. The results indicate a need for a clinical climate in which patients are allowed to use their competence.
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| 21. |
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| 22. |
- Brüggemann, Holger, et al.
(author)
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Pan-genome analysis of the genus Finegoldia identifies two distinct clades, strain-specific heterogeneity, and putative virulence factors
- 2018
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
-
Journal article (peer-reviewed)abstract
- Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen, associated with medical device-related infections. F. magna is the only described species of the genus Finegoldia. We report the analysis of 17 genomes of Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population can be divided into two distinct clades, with an average nucleotide identity of 90.7%. One clade contains strains of F. magna, whereas the other clade includes more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The latter species appears to be more abundant in the human microbiome. Surface structure differences between strains of F. magna and "F. nericia" were detected by microscopy. Strain-specific heterogeneity is high and previously identified host-interacting factors are present only in subsets of "F. nericia" and F. magna strains. However, all genomes encode multiple host factor-binding proteins such as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light of the genus Finegoldia and its ability to bind host components. Future research should explore if the genomic differences identified here affect the potential of different Finegoldia species and strains to cause opportunistic infections.
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| 23. |
- Brüggemann, Holger, et al.
(author)
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Staphylococcus saccharolyticus Isolated From Blood Cultures and Prosthetic Joint Infections Exhibits Excessive Genome Decay
- 2019
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 10
-
Journal article (peer-reviewed)abstract
- The slow-growing, anaerobic, coagulase-negative species Staphylococcus saccharolyticus is found on human skin and in clinical specimens but its pathogenic potential is unclear. Here, we investigated clinical isolates and sequenced the genomes of seven strains of S. saccharolyticus. Phylogenomic analyses showed that the closest relative of S. saccharolyticus is Staphylococcus capitis with an average nucleotide identity of 80%. Previously sequenced strains assigned to S. saccharoiyticus are misclassified and belong to S. capitis. Based on single nucleotide polymorphisms of the core genome, the population of S. saccharolyticus can be divided into two clades that also differ in a few larger genomic islands as part of the flexible genome. An unexpected feature of S. saccharolyticus is extensive genome decay, with over 300 pseudogenes, indicating ongoing reductive evolution. Many genes of the core metabolism are not functional, rendering the species auxotrophic for several amino acids, which could explain its slow growth and need for fastidious growth conditions. Secreted proteins of S. saccharolyticus were determined; they include stress response proteins such as heat and oxidative stress-related factors, as well as immunodominant staphylococcal surface antigens and enzymes that can degrade host tissue components. The strains secrete lipases and a hyaluronic acid lyase. Hyaluronidase as well as urease activities were detected in biochemical assays, with Glade-specific differences. Our study revealed that S. saccharolyticus has adapted its genome, possibly due to a recent change of habitat; moreover, the data imply that the species has tissue-invasive potential and might cause prosthetic joint infections.
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| 24. |
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| 25. |
- Davidsson, Sabina, 1972-, et al.
(author)
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Prevalence of Flp Pili-Encoding Plasmids in Cutibacterium acnes Isolates Obtained from Prostatic Tissue
- 2017
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In: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 8
-
Journal article (peer-reviewed)abstract
- Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C. acnes isolates. Genome sequencing of type II isolates identified large plasmids in several genomes. The plasmids are highly similar to previously identified linear plasmids of type I C. acnes strains associated with acne vulgaris. A PCR-based analysis revealed that 28.4% (21 out of 74) of all type II strains isolated from cancerous prostates carry a plasmid. The plasmid shows signatures for conjugative transfer. In addition, it contains a gene locus for tight adherence (tad) that is predicted to encode adhesive Flp (fimbrial low-molecular weight protein) pili. In subsequent experiments a tad locus-encoded putative pilin subunit was identified in the surface-exposed protein fraction of plasmid-positive C. acnes type II strains by mass spectrometry, indicating that the tad locus is functional. Additional plasmid-encoded proteins were detected in the secreted protein fraction, including two signal peptide-harboring proteins; the corresponding genes are specific for type II C. acnes, thus lacking from plasmid-positive type I C. acnes strains. Further support for the presence of Flp pili in C. acnes type II was provided by electron microscopy, revealing cell appendages in tad locus-positive strains. Our study provides new insight in the most prevalent prostatic subspecies of C. acnes, subsp. defendens, and indicates the existence of Flp pili in plasmid-positive strains. Such pili may support colonization and persistent infection of human prostates by C. acnes.
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| 26. |
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| 27. |
- Jägervall, C. D., et al.
(author)
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Patients’ experiences of orgasm changes and loss of ejaculation after radical prostatectomy
- 2016
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In: Läkartidningen. - 0023-7205. ; 113:36-37
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Journal article (peer-reviewed)abstract
- In this study we report on men’s experiences of orgasm changes and loss of ejaculation after radical prostatectomy. Ten men, all recruited through a Swedish hospital, were interviewed and data was analyzed using qualitative content analysis. The results showed that the experience of orgasm has weakened but that the loss of ejaculation was not perceived as a loss per se. However, the risk of urine release during orgasm was troublesome and inhibiting. These challenges were framed within an existential narrative about sexuality, as expressed in preoperative sexual farewell rituals and postoperative feelings of ambivalence and regret. These findings can be used in the design of patient information and for sexual rehabilitation treatment. © 2016, Swedish Medical Association. All rights reserved.
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| 28. |
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| 29. |
- Martial, Lisa C, et al.
(author)
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Dose Reduction of Caspofungin in Intensive Care Unit Patients with Child Pugh B Will Result in Suboptimal Exposure.
- 2016
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In: Clinical Pharmacokinetics. - : Springer Science and Business Media LLC. - 0312-5963 .- 1179-1926. ; 55:6, s. 723-733
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Caspofungin is an echinocandin antifungal agent used as first-line therapy for the treatment of invasive candidiasis. The maintenance dose is adapted to body weight (BW) or liver function (Child-Pugh score B or C). We aimed to study the pharmacokinetics of caspofungin and assess pharmacokinetic target attainment for various dosing strategies.METHODS: Caspofungin pharmacokinetic data from 21 intensive care unit (ICU) patients was available. A population pharmacokinetic model was developed. Various dosing regimens (loading dose/maintenance dose) were simulated: licensed regimens (I) 70/50 mg (for BW <80 kg) or 70/70 mg (for BW >80 kg); and (II) 70/35 mg (for Child-Pugh score B); and adapted regimens (III) 100/50 mg (for Child-Pugh score B); (IV) 100/70 mg; and (V) 100/100 mg. Target attainment based on a preclinical pharmacokinetic target for Candida albicans was assessed for relevant minimal inhibitory concentrations (MICs).RESULTS: A two-compartment model best fitted the data. Clearance was 0.55 L/h and the apparent volumes of distribution in the central and peripheral compartments were 8.9 and 5.0 L, respectively. The median area under the plasma concentration-time curve from time zero to 24 h on day 14 for regimens I-V were 105, 65, 93, 130, and 186 mg·h/L, respectively. Pharmacokinetic target attainment was 100 % (MIC 0.03 µg/mL) irrespective of dosing regimen but decreased to (I) 47 %, (II) 14 %, (III) 36 %, (IV) 69 %, and (V) 94 % for MIC 0.125 µg/mL.CONCLUSION: The caspofungin maintenance dose should not be reduced in non-cirrhotic ICU patients based on the Child-Pugh score if this classification is driven by hypoalbuminemia as it results in significantly lower exposure. A higher maintenance dose of 70 mg in ICU patients results in target attainment of >90 % of the ICU patients with species with an MIC of up to 0.125 µg/mL.
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| 30. |
- Mascalzoni, Deborah, 1973-, et al.
(author)
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Balancing scientific interests and the rights of participants in designing a recall by genotype study
- 2021
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In: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 29:7, s. 1146-1157
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Journal article (peer-reviewed)abstract
- Recall by genotype (RbG) studies aim to better understand the phenotypes that correspond to genetic variants of interest, by recruiting carriers of such variants for further phenotyping. RbG approaches pose major ethical and legal challenges related to the disclosure of possibly unwanted genetic information. The Cooperative Health Research in South Tyrol (CHRIS) study is a longitudinal cohort study based in South Tyrol, Italy. Demand has grown for CHRIS study participants to be enrolled in RbG studies, thus making the design of a suitable ethical framework a pressing need. We here report upon the design of a pilot RbG study conducted with CHRIS study participants. By reviewing the literature and by consulting relevant stakeholders (CHRIS participants, clinical geneticists, ethics board, GPs), we identified key ethical issues in RbG approaches (e.g. complexity of the context, communication of genetic results, measures to further protect participants). The design of the pilot was based on a feasibility assessment, the selection of a suitable test case within the ProtectMove Research Unit on reduced penetrance of hereditary movement disorders, and the development of appropriate recruitment and communication strategies. An empirical study was embedded in the pilot study with the aim of understanding participants' views on RbG. Our experience with the pilot study in CHRIS allowed us to contribute to the development of best practices and policies for RbG studies by drawing recommendations: addressing the possibility of RbG in the original consent, implementing tailored communication strategies, engaging stakeholders, designing embedded empirical studies, and sharing research experiences and methodology.
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| 31. |
- Mascalzoni, Deborah, 1973-, et al.
(author)
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Participant perspective on the recall-by-genotype research approach : a mixed-method embedded study with participants of the CHRIS study.
- 2023
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In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438.
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Journal article (peer-reviewed)abstract
- Recall-by-genotype (RbG) research recruits participants previously involved in genetic research based on their genotype. RbG enables the further study of a particular variant of interest, but in recalling participants, it risks disclosing potentially unwanted or distressing genetic information. Any RbG strategy must therefore be done in a manner that addresses the potential ethical and social issues. As part of an RbG pilot on the penetrance of Parkinson's disease variants, we conducted an empirical mixed-method study with 51 participants of the Cooperative Health Research in South Tyrol (CHRIS) study to understand participant views on RbG research approach. Participants were disclosed the disease under investigation but not the individual variant carrier status. Results showed that participants filtered the information received through personal experience and enacted mechanisms to address the concerns raised by invitation by resorting to personal resources and the support provided by experts. While the non-disclosure of the Parkin variant carrier status was deemed acceptable, disclosing the disease under study was important for participants. Participant preferences for disclosure of the disease under investigation and the carrier status varied according to how the knowledge of individual carrier status was perceived to impact the participant's life. This study provided insights into participant response to the RbG research approach, which are relevant for RbG policy development. A suitable communication strategy and granular options addressing preferences for invitation in the original informed consent are critical for an ethically informed RbG policy.
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| 32. |
- Quinones, Javier Pérez, et al.
(author)
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Self-assembled hyaluronic acid nanoparticles for controlled release of agrochemicals and diosgenin
- 2017
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In: Carbohydrate Polymers. - : ELSEVIER SCI LTD. - 0144-8617 .- 1879-1344. ; 173, s. 157-169
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Journal article (peer-reviewed)abstract
- Commercial sodium hyaluronate (HA) and synthetic hydrazide-modified HA were functionalized with diosgenin and two agrochemicals (brassinosteroids DI31 and S7) with degree of substitution ranging from 5.6 to 13.1%. The HA-steroid conjugates were studied with FTIR, H-1 NMR and differential scanning calorimetry. Dynamic light scattering revealed self-assembly of the HA-steroid conjugates into stable negatively charged nanoparticles of around 159 nm-441 nm in water, which after drying appeared as 140 nm-370 nm spherically shaped nanoparticles according to transmission electron microscopy. These nanoparticles exhibited almost constant release rates of steroids for the first 8 h, demonstrating sustained steroids delivery for 72 h in acidic medium. The nanoparticles formed from HA-steroid conjugates were not cytotoxic to human microvascular endothelial cells (HMVEC), while the HA- brassinosteroid nanoparticles showed in vitro agrochemical activity that was superior to the activity observed for the parent brassinosteroids DI31 and S7 at 10(-5) to 10(-7) mg mL(-1).
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| 33. |
- Sundkvist, Jonas, et al.
(author)
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Epidemiology, classification, treatment, and mortality of adult femoral neck and basicervical fractures: an observational study of 40,049 fractures from the Swedish Fracture Register
- 2021
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In: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 16:1
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Journal article (peer-reviewed)abstract
- Background: Although femoral neck fractures (FNFs) are common in orthopedic departments, optimal treatment methods remain in dispute. There are few large nationwide studies, including basicervical FNFs (bFNFs), on epidemiology, treatment, and mortality. This nationwide study aims to describe the epidemiology, fracture classification, current treatment regimens, and mortality of undisplaced and minimally displaced (Garden I-II, uFNF), displaced (Garden III-IV, dFNF) and bFNFs in adults. Methods: All FNFs, including bFNFs with a registered injury date between 1 April 2012 and 31 December 2020, were included in this observational study from the Swedish Fracture Register (SFR). Data on age, sex, injury mechanism, fracture classification, primary treatment, and seasonal variation were analyzed. Results: Some 40,049 FNFs were registered in the SFR. The mean age of the patients in the register was 80.3 (SD 11) years and 63.8% (25,567) were female. Of all FNFs, 25.0% (10,033) were uFNFs, 63.4% (25,383) dFNFs, and 11.6% (4,633) bFNFs. Non-surgical treatment was performed in 0.6% (261) of the patients. Internal fixation (IF) (84.7%) was the main treatment for uFNFs and arthroplasty (87.3%) for dFNFs. For bFNFs, IF (43.8%) and hip arthroplasty (45.9%) were performed equally often. Of the 33,105 patients with a 1-year follow-up mortality at 1-year was 20.6% for uFNF, 24.3% for dFNF, and 25.4% for bFNF. Conclusion: The main treatment of uFNFs is IF with screws or pins. Hip arthroplasty is the predominant treatment for dFNF. bFNF are more common than previously reported and treated with IF or arthroplasty, depending on patient age. These results may help health care providers, researchers and clinicians better understand the panorama of FNFs in Sweden.
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| 34. |
- Visnjevski, A, et al.
(author)
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Catalyzing a cycloaddition with molecularly imprinted polymers obtained via immobilized templates
- 2004
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In: Applied Catalysis A: General. - : Elsevier BV. - 0926-860X. ; 260:2, s. 169-174
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Journal article (peer-reviewed)abstract
- Polymeric catalysts to be applied in the Diels-Alder cycloaddition of hexachlorocyclopentadiene and maleic acid have been prepared via molecular imprinting with template molecules immobilized on silica particles. These enzyme mimicking polymers exhibit specific catalytic effects compared to non-imprinted control polymers or polymer-free solutions. It could be demonstrated that the activity of the molecularly imprinted material rises when increasing the temperature. By this means, the reduction of the activation energy (as expected for catalysts) from 63 to 55 kJ mol(-1) could be observed. Furthermore, the reaction was characterized based on the Michaelis-Menten model. For the diene compound a Michaelis constant of K-M = 5.8 mmol l(-1) and an effective reaction rate of r(max,eff) = 0.41 mumol l(-1) s(-1), leading to a reaction rate constant k(eff) = 1.1 x 10(-3) s(-1), were determined. (C) 2003 Elsevier B.V. All rights reserved.
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| 35. |
- Zbikowski, Anke, et al.
(author)
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Counteracting Abuse in Health Care : A Quantitative Evaluation of an Intervention with Forum Play for Staff
- 2014
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Other publication (other academic/artistic)abstract
- Objectives: In their lifetime, 13%–28% of female patients in the Nordic countries seeking gynecological health care have reported abuse by staff in a health care setting (AHC). Besides suffering, AHC can cause patients to avoid contacting the health care system. Thus, interventions are clearly needed. In this article, we report a drama intervention method among health care staff and study to what extent the intervention increased the staff’s awareness of AHC and their ability to take action against it.Design: Pre-/post-test measurement by means of self-reported questionnaires with a longterm follow-up one year after the intervention. Questionnaires were distributed at four measuring times.Setting: A women’s clinic in Sweden.Participants: All staff at the target clinic were invited to participate in the intervention and received the questionnaires (n=137). Of those 136 had the possibility to participate in the intervention. A total of 92 staff members (67%) returned at least two questionnaires. 76 (56%) participated in the intervention, of which 61 (80%) returned at least one questionnaire.Intervention: The drama intervention was based on Forum Play (FP), a form of improvised role-play based on the pedagogy of Augusto Boal. During one year, 2008–2009, 16 half-day FP workshops focusing on AHC were conducted at the target clinic. Participation was voluntary.Primary outcome measures: 1) The number of reported occasions when staff heard of or were involved in AHC. 2) FP participants’ self-reported ability to act in AHC-related situations.Results: No change could be seen in the number of occasions of AHC reported by staff between baseline and one year after the intervention. However, an increase of the participants’ ability to act in AHC-related situations was seen.Conclusions: Health care staff’s participation in FP workshops can increase their ability to take action in AHC situations, but probably does not affect their awareness of AHC.
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