| 1. |
- Ahl, Matilda, et al.
(författare)
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Immune response in blood before and after epileptic and psychogenic non-epileptic seizures
- 2023
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Ingår i: Heliyon. - : Elsevier. - 2405-8440. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory processes may provoke epileptic seizures and seizures may promote an immune reaction. Hence, the systemic immune reaction is a tempting diagnostic and prognostic marker in epilepsy. We explored the immune response before and after epileptic and psychogenic non-epileptic seizures (PNES). Serum samples collected from patients with videoEEG-verified temporal or frontal lobe epilepsy (TLE or FLE) or TLE + PNES showed increased interleukin-6 (IL-6) levels in between seizures (interictally), compared to controls. Patients with PNES had no increase in IL-6. The IL-6 levels increased transiently even further within hours after a seizure (postictally) in TLE but not in FLE patients. The postictal to interictal ratio of additionally five immune factors were also increased in TLE patients only. We conclude that immune factors have the potential to be future biomarkers for epileptic seizures and that the heterogeneity among different epileptic and non-epileptic seizures may be disclosed in peripheral blood sampling independent of co-morbidities.
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| 2. |
- Andersson, My, et al.
(författare)
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Improved interaction with collaborative robots - evaluation of event-specific haptic feedback in virtual reality
- 2024
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Ingår i: Procedia Computer Science. - : Elsevier. - 1877-0509. ; 232, s. 1055-1064
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Tidskriftsartikel (refereegranskat)abstract
- Industry 5.0 adopts a human-centric approach that views humans as a natural part of introducing new technology, such as collaborative robots. However, one of the main challenges in implementing collaborative robots is safety, including the sense of safety. Trust is also a primary challenge when establishing functional collaboration. Influencing factors includes experience and expertise, and research shows that Virtual Reality has the potential to perform such training. This research aims to investigate whether using virtual reality with appropriate feedback can be an effective platform for familiarization and training. In our experiment, we utilized haptic feedback from commercial Virtual Reality controllers to simulate physical interactions with collaborative robots. The experiment involved the participation of fifteen individuals. The results showed that participants regarded haptic feedback while moving as the most appropriate representation. This research aims to identify whether Virtual Reality with suitable feedback can serve as a familiarization and training platform.
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| 3. |
- Andersson, Thomas K., et al.
(författare)
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Perceptions of Experiences of Recovery After Pancreaticoduodenectomy-A Phenomenographic Interview Study
- 2022
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Ingår i: Cancer Nursing. - : Ovid Technologies (Wolters Kluwer Health). - 0162-220X .- 1538-9804. ; 45:3, s. 172-180
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Tidskriftsartikel (refereegranskat)abstract
- Background Pancreatic surgery in the context of enhanced recovery has mainly been evaluated using clinical variables. However, there is limited knowledge about patients' perceptions of recovery in this context. Hence, the aim of this study was to explore patients' perceptions of recovery after pancreatic surgery within an enhanced recovery program. Objective To explore the variations in patients' perceptions, a qualitatively designed study was undertaken. Methods Data in this phenomenographic study consisted of interviews with 19 patients at 4 to 6 weeks after surgery. Results Recovery after pancreatic surgery was classified into 5 categories, based on patients' perceptions: to be as before, affected by symptoms, physical activity, understanding the process, and facilitated by other people. Conclusion The study focused on various areas of recovery, which took place between the in-hospital and after-discharge phases. Physical experiences were found to disturb recovery, in contrast to social and emotional experiences, which facilitated recovery. Variations in perceptions of recovery suggest that care may need to be more individualized, both in the preoperative and the postoperative phase. Working with realistic expectations and early patient education might better prepare patients to continue working on their own recovery after discharge from the hospital. Implications for Practice Major cancer surgery needs to be perceived as a personal journey for the patient, even in enhanced recovery program care. Preoperative education is good, but adding continuous and individually adopted education during recovery is better. Knowledge about both hindering and facilitating factors for recovery is important for the healthcare personal.
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| 4. |
- Avdic, Una, et al.
(författare)
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Levetiracetam and N-Cadherin Antibody Alleviate Brain Pathology Without Reducing Early Epilepsy Development After Focal Non-convulsive Status Epilepticus in Rats
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Focal non-convulsive status epilepticus (fNCSE) is a neurological condition characterized by a prolonged seizure that may lead to the development of epilepsy. Emerging experimental evidence implicates neuronal death, microglial activation and alterations in the excitatory and inhibitory synaptic balance as key features in the pathophysiology following fNCSE. We have previously reported alterations in the excitatory adhesion molecule N-cadherin in rats with fNCSE originating from the hippocampus that subsequently also develop spontaneous seizures. In this study, fNCSE rats were treated intraperitoneally with the conventional anti-epileptic drug levetiracetam in combination with intraparenchymal infusion of N-cadherin antibodies (Ab) for 4 weeks post-fNCSE. The N-cadherin Ab was infused into the fornix and immunohistochemically N-cadherin Ab-stained neurons were detected within the dorsal hippocampal structures as well as in superjacent somatosensory cortex. Continuous levetiracetam treatment for 4 weeks post-fNCSE reduced microglia activation, including cell numbers and morphological changes, partly decreased neuronal cell loss, and excitatory post-synaptic scaffold protein PSD-95 expression in selective hippocampal structures. The additional treatment with N-cadherin Ab did not reverse neuronal loss, but moderately reduced microglial activation, and further reduced PSD-95 levels in the dentate hilus of the hippocampus. Despite the effects on brain pathology within the epileptic focus, neither monotherapy with systemic levetiracetam nor levetiracetam in combination with local N-cadherin Ab administration, reduced the amount of focal or focal evolving into bilateral convulsive seizures, seizure duration, or interictal epileptiform activity during 1 month of continuous electroenephalogram recordings within the hippocampus after fNCSE. Behavioral tests for spatial memory, anxiety, social interaction and anhedonia did not detect gross behavioral differences between fNCSE rats with or without treatment. The results reveal the refractory features of the present rodent model of temporal lobe epilepsy following fNCSE, which supports its clinical value for further therapeutic studies. We identify the persistent development of epilepsy following fNCSE, in spite of partly reduced brain pathology within the epileptic focus.
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| 5. |
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| 6. |
- Blohm, My, et al.
(författare)
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Relationship between surgical volume and outcomes in elective and acute cholecystectomy : nationwide, observational study
- 2023
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Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 110:3, s. 353-361
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High surgical volumes are attributed to improved quality of care, especially for extensive procedures. However, it remains unknown whether high-volume surgeons and hospitals have better results in gallstone surgery. The aim of this study was to investigate whether operative volume affects outcomes in cholecystectomies.METHODS: A registry-based cohort study was performed, based on the Swedish Registry of Gallstone Surgery. Cholecystectomies from 2006 to 2019 were included. Annual volumes for the surgeon and hospital were retrieved. All procedures were categorized into volume-based quartiles, with the highest group as reference. Low volume was defined as fewer than 20 operations per surgeon per year and fewer than 211 cholecystectomies per hospital per year. Differences in outcomes were analysed separately for elective and acute procedures.RESULTS: The analysis included 154 934 cholecystectomies. Of these, 101 221 (65.3 per cent) were elective and 53 713 (34.7 per cent) were acute procedures. Surgeons with low volumes had longer operating times (P < 0.001) and higher conversion rates in elective (OR 1.35; P = 0.023) and acute (OR 2.41; P < 0.001) operations. Low-volume surgeons also caused more bile duct injuries (OR 1.41; P = 0.033) and surgical complications (OR 1.15; P = 0.033) in elective surgery, but the results were not statistically significant for acute procedures. Low-volume hospitals had more bile duct injuries in both elective (OR 1.75; P = 0.002) and acute (OR 1.96; P = 0.003) operations, and a higher mortality rate after acute surgery (OR 2.53; P = 0.007).CONCLUSION: This study has demonstrated that operative volumes influence outcomes in cholecystectomy. The results indicate that gallstone surgery should be performed by procedure-dedicated surgeons at hospitals with high volumes of this type of benign surgery.
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| 7. |
- Dillner, Joakim, et al.
(författare)
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Antibodies to SARS-CoV-2 and risk of past or future sick leave
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n=15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.
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| 8. |
- Fagevik Olsén, Monika, 1964, et al.
(författare)
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Development of and adherence to an ERAS® and prehabilitation protocol for patients undergoing pancreatic surgery: An observational study
- 2023
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Ingår i: Scandinavian Journal of Surgery. - 1457-4969 .- 1799-7267. ; 112:4, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: There are still gaps in knowledge concerning the adherence to different multimodal pathways in pancreatic surgery. The aim of this trial was to explore and evaluate an Enhanced Recovery After Surgery (ERAS®) and prehabilitation protocol in patients undergoing open pancreatic surgery. Methods: Three groups of patients were included: two prospective series of 75 patients undergoing open pancreatic surgery following an ERAS® protocol with or without prehabilitation, and one group of 55 historical controls. Variables regarding adherence to, and effects of the protocols, were collected from the local database and the patients’ hospital records. Patients’ adherence to advice given pre-operatively was followed up using a study-specific questionnaire. Results: The patients reported high adherence to remembered advice given. The health care professionals’ adherence to the various parts of the concepts varied. ERAS® implementation resulted in more frequent gut motility stimulation (p < 0.001) and shorter duration of epidural anesthesia, site drains, and urinary catheter (p = 0.001). With prehabilitation, more patients were screened concerning nutritional status and prescribed preoperative training (p < 001). There was a significant change in weight before surgery, a shorter time to first flatus and a shorter length of stay after implementation of the concepts (p < 0.05). Complications were rare in all three groups and there were no significant differences between the groups. Conclusion: The implementation of an ERAS® and a prehabilitation protocol increased adherence to the protocols by both patients and healthcare professionals. An implementation of an ERAS® protocol with and without prehabilitation decreases length of stay and may decrease preoperative weight loss and time to bowel movement.
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| 9. |
- Gonzalez-Ramos, Ana, et al.
(författare)
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Human stem cell-derived GABAergic neurons functionally integrate into human neuronal networks
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Gamma-aminobutyric acid (GABA)-releasing interneurons modulate neuronal network activity in the brain by inhibiting other neurons. The alteration or absence of these cells disrupts the balance between excitatory and inhibitory processes, leading to neurological disorders such as epilepsy. In this regard, cell-based therapy may be an alternative therapeutic approach. We generated light-sensitive human embryonic stem cell (hESC)-derived GABAergic interneurons (hdIN) and tested their functionality. After 35 days in vitro (DIV), hdINs showed electrophysiological properties and spontaneous synaptic currents comparable to mature neurons. In co-culture with human cortical neurons and after transplantation (AT) into human brain tissue resected from patients with drug-resistant epilepsy, light-activated channelrhodopsin-2 (ChR2) expressing hdINs induced postsynaptic currents in human neurons, strongly suggesting functional efferent synapse formation. These results provide a proof-of-concept that hESC-derived neurons can integrate and modulate the activity of a human host neuronal network. Therefore, this study supports the possibility of precise temporal control of network excitability by transplantation of light-sensitive interneurons.
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| 10. |
- Gonzalez-Ramos, Ana, et al.
(författare)
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Transplantation of Human Stem Cell-Derived GABAergic Neurons into the Early Postnatal Mouse Hippocampus to Mitigate Neurodevelopmental Disorders
- 2022
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Ingår i: Journal of visualized experiments : JoVE. - : MyJove Corporation. - 1940-087X. ; :189
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Tidskriftsartikel (refereegranskat)abstract
- A reduced number or dysfunction of inhibitory interneurons is a common contributor to neurodevelopmental disorders. Therefore, cell therapy using interneurons to replace or mitigate the effects of altered neuronal circuits is an attractive therapeutic avenue. To this end, more knowledge is needed about how human stem cell-derived GABAergic interneuron-like cells (hdINs) mature, integrate, and function over time in the host circuitry. Of particular importance in neurodevelopmental disorders is a better understanding of whether these processes in transplanted cells are affected by an evolving and maturing host brain. The present protocol describes a fast and highly efficient generation of hdINs from human embryonic stem cells based on the transgenic expression of the transcription factors Ascl1 and Dlx2. These neuronal precursors are transplanted unilaterally, after 7 days in vitro, to the hippocampus of neonatal 2-day-old mice. The transplanted neurons disperse in the ipsi- and contralateral hippocampus of a mouse model of cortical dysplasia-focal epilepsy syndrome and survive for up to 9 months after transplantation. This approach allows for investigating the cellular identity, integration, functionality, and therapeutic potential of transplanted interneurons over an extended time in developing healthy and diseased brains.
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| 11. |
- Havervall, Sebastian, et al.
(författare)
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Robust humoral and cellular immune responses and low risk for reinfection at least 8 months following asymptomatic to mild COVID-19
- 2022
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 291:1, s. 72-80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Emerging data support detectable immune responses for months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, but it is not yet established to what degree and for how long protection against reinfection lasts.Methods: We investigated SARS-CoV-2-specific humoral and cellular immune responses more than 8 months post-asymptomatic, mild and severe infection in a cohort of 1884 healthcare workers (HCW) and 51 hospitalized COVID-19 patients. Possible protection against SARS-CoV-2 reinfection was analyzed by a weekly 3-month polymerase chain reaction (PCR) screening of 252 HCW that had seroconverted 7 months prior to start of screening and 48 HCW that had remained seronegative at multiple time points.Results: All COVID-19 patients and 96% (355/370) of HCW who were anti-spike IgG positive at inclusion remained anti-spike IgG positive at the 8-month follow-up. Circulating SARS-CoV-2-specific memory T cell responses were detected in 88% (45/51) of COVID-19 patients and in 63% (233/370) of seropositive HCW. The cumulative incidence of PCR-confirmed SARS-CoV-2 infection was 1% (3/252) among anti-spike IgG positive HCW (0.13 cases per 100 weeks at risk) compared to 23% (11/48) among anti-spike IgG negative HCW (2.78 cases per 100 weeks at risk), resulting in a protective effect of 95.2% (95% CI 81.9%-99.1%).Conclusions: The vast majority of anti-spike IgG positive individuals remain anti-spike IgG positive for at least 8 months regardless of initial COVID-19 disease severity. The presence of anti-spike IgG antibodies is associated with a substantially reduced risk of reinfection up to 9 months following asymptomatic to mild COVID-19.
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| 12. |
- Havervall, Sebastian, et al.
(författare)
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SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection
- 2022
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:1, s. e0262169-e0262169
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Tidskriftsartikel (refereegranskat)abstract
- Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p = 2*10−23 and 2*10−13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys
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| 13. |
- Hellström, Ann, 1959, et al.
(författare)
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Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity A Randomized Clinical Trial
- 2021
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Ingår i: JAMA Pediatrics. - : American Medical Association (AMA). - 2168-6203 .- 2168-6211. ; 175:4, s. 359-367
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP). OBJECTIVE To determine whether enteral supplementation with fatty acids from birth to 40 weeks' postmenstrual age reduces ROP in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Mega Donna Mega trial, a randomized clinical trial, was a multicenter study performed at 3 university hospitals in Sweden from December 15, 2016, to December 15, 2019. The screening pediatric ophthalmologists were masked to patient groupings. A total of 209 infants born at less than 27 weeks' gestation were tested for eligibility, and 206 infants were included. Efficacy analyses were performed on as-randomized groups on the intention-to-treat population and on the per-protocol population using as-treated groups. Statistical analyses were performed from February to April 2020. INTERVENTIONS Infants received either supplementation with an enteral oil providing AA (100mg/kg/d) and DHA (50mg/kg/d) (AA:DHA group) or no supplementation within 3 days after birth until 40 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES The primary outcomewas severe ROP (stage 3 and/or type 1). The secondary outcomes were AA and DHA serum levels and rates of other complications of preterm birth. RESULTS A total of 101 infants (58 boys [57.4%]; mean [SD] gestational age, 25.5 [1.5] weeks) were included in the AA:DHA group, and 105 infants (59 boys [56.2%]; mean [SD] gestational age, 25.5 [1.4] weeks) were included in the control group. Treatment with AA and DHA reduced severe ROP compared with the standard of care (16 of 101 [15.8%] in the AA:DHA group vs 35 of 105 [33.3%] in the control group; adjusted relative risk, 0.50 [95% CI, 0.28-0.91]; P =.02). The AA:DHA group had significantly higher fractions of AA and DHA in serum phospholipids compared with controls (overall mean difference in AA:DHA group, 0.82 mol% [95% CI, 0.46-1.18 mol%]; P <.001; overall mean difference in control group, 0.13 mol% [95% CI, 0.01-0.24 mol%]; P =.03). There were no significant differences between the AA:DHA group and the control group in the rates of bronchopulmonary dysplasia (48 of 101 [47.5%] vs 48 of 105 [45.7%]) and of any grade of intraventricular hemorrhage (43 of 101 [42.6%] vs 42 of 105 [40.0%]). In the AA:DHA group and control group, respectively, sepsis occurred in 42 of 101 infants (41.6%) and 53 of 105 infants (50.5%), serious adverse events occurred in 26 of 101 infants (25.7%) and 26 of 105 infants (24.8%), and 16 of 101 infants (15.8%) and 13 of 106 infants (12.3%) died. CONCLUSIONS AND RELEVANCE This study found that, compared with standard of care, enteral AA:DHA supplementation lowered the risk of severe ROP by 50% and showed overall higher serum levels of both AA and DHA. Enteral lipid supplementation with AA:DHA is a novel preventive strategy to decrease severe ROP in extremely preterm infants.
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| 14. |
- Hjorth, Olof, et al.
(författare)
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Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy
- 2022
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [11C]DASB and [11C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.
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| 15. |
- Hober, Sophia, Professor, 1965-, et al.
(författare)
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Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
- 2021
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Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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| 16. |
- Håkansson, Claes, et al.
(författare)
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Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience
- 2022
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Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 32, s. 1127-1134
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. Methods Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's kappa (dichotomized data), Cohen's kappa(w), and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as kappa/kappa(w) >= 0.80 and ICC >= 0.80 (significance level at 95% CI >= 0.65). Results Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's kappa. All raters achieved adequate agreement expressed as Cohen's kappa(w) and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. Conclusion We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences.
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| 17. |
- Ledri, Marco, et al.
(författare)
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Optogenetics for controlling seizure circuits for translational approaches
- 2023
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Ingår i: Neurobiology of Disease. - 0969-9961. ; 184, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- The advent of optogenetic tools has had a profound impact on modern neuroscience research, revolutionizing our understanding of the brain. These tools offer a remarkable ability to precisely manipulate specific groups of neurons with an unprecedented level of temporal precision, on the order of milliseconds. This breakthrough has significantly advanced our knowledge of various physiological and pathophysiological processes in the brain. Within the realm of epilepsy research, optogenetic tools have played a crucial role in investigating the contributions of different neuronal populations to the generation of seizures and hyperexcitability. By selectively activating or inhibiting specific neurons using optogenetics, researchers have been able to elucidate the underlying mechanisms and identify key players involved in epileptic activity. Moreover, optogenetic techniques have also been explored as innovative therapeutic strategies for treating epilepsy. These strategies aim to halt seizure progression and alleviate symptoms by utilizing the precise control offered by optogenetics. The application of optogenetic tools has provided valuable insights into the intricate workings of the brain during epileptic episodes. For instance, researchers have discovered how distinct interneuron populations contribute to the initiation of seizures (ictogenesis). They have also revealed how remote circuits in regions such as the cerebellum, septum, or raphe nuclei can interact with hyperexcitable networks in the hippocampus. Additionally, studies have demonstrated the potential of closed-loop systems, where optogenetics is combined with real-time monitoring, to enable precise, on-demand control of seizure activity. Despite the immense promise demonstrated by optogenetic approaches, it is important to acknowledge that many of these techniques are still in the early stages of development and have yet to reach potential clinical applications. The transition from experimental research to practical clinical use poses numerous challenges. In this review, we aim to introduce optogenetic tools, provide a comprehensive survey of their application in epilepsy research, and critically discuss their current potential and limitations in achieving successful clinical implementation for the treatment of human epilepsy. By addressing these crucial aspects, we hope to foster a deeper understanding of the current state and future prospects of optogenetics in epilepsy treatment.
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| 18. |
- Martin, Myriam, et al.
(författare)
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Methods for anti-factor VIII antibody levels in haemophilia A patients-validation of a multiplec immunoassay and comparability with assays measuring non-neutralising and neutralising antibodies (inhibitors)
- 2023
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Ingår i: Haemophilia. - : Wiley. - 1351-8216 .- 1365-2516. ; 29:1, s. 336-347
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe development of neutralising (inhibitors) and non-neutralising antibodies (NNAs) is a complication to factor replacement therapy in haemophilia. The diagnostic methods available lack standardisation, have high inter-laboratory variation, and false-negative as well as false-positive results may affect treatment. Both functional inhibitors and NNAs may be detected with higher reproducibility, sensitivity and specificity using the immunological Luminex xMAP-based fluorescence-immunoassay (xFLI).AimValidation of our xFLI and comparability with enzyme-linked immunosorbent assay (ELISA) and chromogenic Nijmegen-Bethesda assay (CBA) for anti-FVIII antibodies in haemophilia A (HA) patients.MethodsThe xFLI method was developed with full-length and B-domain deleted factor coupled to magnetic beads, optimised and validated for performance characteristics. Comparability with ELISA and CBA was evaluated in HA patient samples (n = 112), serial samples in six inhibitor patients and reference interval and decision-limits in healthy donors (n = 44).ResultsThe intra- and inter-assay precision (CV%) for the xFLI method was below 6% and detection limit (LLOQ) .084 ng/mL (NovoEight). All ELISA-positive samples were positive with either Advate or NovoEight. Additionally, 10.7%–14.3% were xFLI-positive and ELISA-negative. All but one CBA-positive sample was above 3SD with xFLI; one was between 2 and 3SD. 29.1% were xFLI-positive and CBA negative. The overall concordance between xFLI and ELISA was 82.1% and xFLI and CBA 77.9%.ConclusionThe anti-FVIII antibody xFLI method is adaptable to clinical practice and more sensitive and reproducible than ELISA and CBA. Actual NNA titers are determined to both full-length and B-domain deleted FVIII. The xFLI is thus valuable for confirmation of all anti-FVIII antibodies.
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| 19. |
- Raymond, Christopher, et al.
(författare)
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Inclusive conservation and the Post-2020 Global Biodiversity Framework : Tensions and prospects
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:3, s. 252-264
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Tidskriftsartikel (refereegranskat)abstract
- The draft Post-2020 Global Biodiversity Framework commits to achievement of equity and justice outcomes and represents a “relational turn” in how we understand inclusive conservation. Although “inclusivity” is drawn on as a means to engage diverse stakeholders, widening the framing of inclusivity can create new tensions with regard to how to manage protected areas. We first offer a set of tensions that emerge in the light of the relational turn in biodiversity conservation. Drawing on global case examples applying multiple methods of inclusive conservation, we then demonstrate that, by actively engaging in the interdependent phases of recognizing hybridity, enabling conditions for reflexivity and partnership building, tensions can not only be acknowledged but softened and, in some cases, reframed when managing for biodiversity, equity, and justice goals. The results can improve stakeholder engagement in protected area management, ultimately supporting better implementation of global biodiversity targets.
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| 20. |
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| 21. |
- Rudberg, Ann-Sofie, et al.
(författare)
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SARS-CoV-2 exposure, symptoms and seroprevalence in healthcare workers in Sweden.
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 may pose an occupational health risk to healthcare workers. Here, we report the seroprevalence of SARS-CoV-2 antibodies, self-reported symptoms and occupational exposure to SARS-CoV-2 among healthcare workers at a large acute care hospital in Sweden. The seroprevalence of IgG antibodies against SARS-CoV-2 was 19.1% among the 2149 healthcare workers recruited between April 14th and May 8th 2020, which was higher than the reported regional seroprevalence during the same time period. Symptoms associated with seroprevalence were anosmia (odds ratio (OR) 28.4, 95% CI 20.6-39.5) and ageusia (OR 19.2, 95% CI 14.3-26.1). Seroprevalence was also associated with patient contact (OR 2.9, 95% CI 1.9-4.5) and covid-19 patient contact (OR 3.3, 95% CI 2.2-5.3). These findings imply an occupational risk for SARS-CoV-2 infection among healthcare workers. Continued measures are warranted to assure healthcare workers safety and reduce transmission from healthcare workers to patients and to the community.
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| 22. |
- Sanna, Adriana, et al.
(författare)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype
- 2022
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Tidskriftsartikel (refereegranskat)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, MITF and SOX10, important in melanoma development and progression have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF methylated cultures were subdivided in two distinct subtypes. Examining mRNA levels of neural crest associated genes we found that one subtype had lost the expression of several lineage genes including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF methylated melanoma cells using CRISPR/Cas9 confirmed these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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| 23. |
- Sanna, Adriana, et al.
(författare)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype.
- 2022
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Ingår i: JCI insight. - : The American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Tidskriftsartikel (refereegranskat)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug-tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte-specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, microphthalmia-associated transcription factor (MITF) and SRY-box transcription factor 10 (SOX10), important in melanoma development and progression, have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation, and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF-methylated cultures were subdivided in 2 distinct subtypes. Examining mRNA levels of neural crest-associated genes, we found that 1 subtype had lost the expression of several lineage genes, including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF-methylated melanoma cells using CRISPR/Cas9 supported these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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| 24. |
- Sjöbom, Ulrika, et al.
(författare)
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Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial
- 2023
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Ingår i: Clinical Nutrition. - 0261-5614. ; 42:6, s. 962-971
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Tidskriftsartikel (refereegranskat)abstract
- Background & aim: Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources. Methods: Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (mmol l-1) units. Results: Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) mmol l-1, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05). Conclusions: Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed
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| 25. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study.
- 2023
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Ingår i: Obesity (Silver Spring, Md.). - 1930-739X. ; 31:8, s. 2171-2177
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this study was to investigate whether bariatric surgery is associated with substance use disorder (SUD) with substances other than alcohol.The prospective, controlled Swedish Obese Subjects study enrolled 2010 patients with obesity who underwent bariatric surgery (gastric bypass n=265; vertical banded gastroplasty n=1369; gastric banding n=376) and 2037 matched control individuals receiving usual obesity care. Participants with SUD other than alcohol use disorder were identified using International Statistical Classification of Diseases (ICD) codes from the Swedish National Patient Register (covering treatment in hospital but not primary care). Those with a history of non-alcohol SUD were excluded. Median follow-up was 23.8years.During follow-up, non-alcohol SUD incidence rates per 1000 person-years with 95% CI were 1.6 (0.8-3.1), 0.8 (0.5-1.2), 1.1 (0.5-2.2), and 0.6 (0.4-0.8) for gastric bypass, vertical banded gastroplasty, gastric banding, and control individuals, respectively. Only gastric bypass was associated with increased incidence of non-alcohol SUD (adjusted hazard ratio 2.54 [95% CI: 1.14-5.65], p=0.022) compared with control participants.Gastric bypass surgery was associated with increased risk of non-alcohol SUD, and this should be considered in long-term postoperative care.
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| 26. |
- Toh, KZX, et al.
(författare)
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Distal medium vessel occlusions in acute ischaemic stroke - Stent retriever versus direct aspiration: A systematic review and meta-analysis
- 2023
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Ingår i: European stroke journal. - : SAGE Publications. - 2396-9881 .- 2396-9873. ; 8:2, s. 434-447
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Tidskriftsartikel (refereegranskat)abstract
- Acute ischaemic stroke due to distal medium vessel occlusion (AIS-DMVO) causes significant morbidity. Endovascular thrombectomy advancement has made treating AIS-DMVO with stent retrievers (SR) and aspiration catheters (AC) possible, however the optimal technique remains unknown. We performed a systematic review and meta-analysis to investigate the efficacy and safety of SR use compared to purely AC use in patients with AIS-DMVO. Methods We systematically searched PubMed, Cochrane Library and EMBASE, from inception to 2nd September 2022, for studies comparing SR or primary combined (SR/PC) against AC in AIS-DMVO. We adopted the Distal Thrombectomy Summit Group’s definition of DMVO. Efficacy outcomes were functional independence (modified Rankin Scale (mRS) 0–2 at 90 days), first pass effect (modified Thrombolysis in Cerebral Infarction scale (mTICI) 2c-3 or expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2c-3 at first pass), successful final recanalisation (mTICI or eTICI 2b-3), and excellent final recanalisation (mTICI or eTICI 2c-3). Safety outcomes were symptomatic intracranial haemorrhage (sICH) and 90-day mortality. Results 12 cohort studies and 1 randomised-controlled trial were included, involving 1881 patients with 1274 receiving SR/PC and 607 receiving AC only. SR/PC achieved higher odds of functional independence (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.06–1.67) and lower odds of mortality (OR 0.69, 95% CI 0.50–0.94) than AC. Odds of successful/excellent recanalisation and sICH were similar between both groups. Stratified to compare only SR and only AC, the use of only SR, achieved significantly higher odds of successful recanalisation as compared to only AC (OR 1.80, 95% CI 1.17–2.78). Conclusion There is potential for efficacy and safety benefits in SR/PC use as compared to AC only in AIS-DMVO. Further trials are necessary to validate the efficacy and safety of SR use in AIS-DMVO.
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| 27. |
- Waloschková, Eliška, et al.
(författare)
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Human stem cell‐derived gabaergic interneurons establish efferent synapses onto host neurons in rat epileptic hippocampus and inhibit spontaneous recurrent seizures
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:24
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Tidskriftsartikel (refereegranskat)abstract
- Epilepsy is a complex disorder affecting the central nervous system and is characterised by spontaneously recurring seizures (SRSs). Epileptic patients undergo symptomatic pharmacolog-ical treatments, however, in 30% of cases, they are ineffective, mostly in patients with temporal lobe epilepsy. Therefore, there is a need for developing novel treatment strategies. Transplantation of cells releasing γ‐aminobutyric acid (GABA) could be used to counteract the imbalance between ex-citation and inhibition within epileptic neuronal networks. We generated GABAergic interneuron precursors from human embryonic stem cells (hESCs) and grafted them in the hippocampi of rats developing chronic SRSs after kainic acid‐induced status epilepticus. Using whole‐cell patch‐clamp recordings, we characterised the maturation of the grafted cells into functional GABAergic inter-neurons in the host brain, and we confirmed the presence of functional inhibitory synaptic connections from grafted cells onto the host neurons. Moreover, optogenetic stimulation of grafted hESC-derived interneurons reduced the rate of epileptiform discharges in vitro. We also observed decreased SRS frequency and total time spent in SRSs in these animals in vivo as compared to non-grafted controls. These data represent a proof‐of‐concept that hESC‐derived GABAergic neurons can exert a therapeutic effect on epileptic animals presumably through establishing inhibitory synapses with host neurons.
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