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1.
Sci Rep ; 14(1): 14139, 2024 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898030

RESUMO

Elevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI. We assessed the independent association of biomarkers with 1-year mortality and 6-12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01). Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8-8.8, p < 0.01; T-Tau 7.2-11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2-17.5, p < 0.01; T-Tau 8.7-12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8-9.4, p ≤ 0.05). Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores.


Assuntos
Biomarcadores , Lesões Encefálicas Traumáticas , Proteínas de Neurofilamentos , Ubiquitina Tiolesterase , Proteínas tau , Humanos , Lesões Encefálicas Traumáticas/sangue , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/diagnóstico , Biomarcadores/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Adulto , Proteínas de Neurofilamentos/sangue , Proteínas tau/sangue , Ubiquitina Tiolesterase/sangue , Proteína Glial Fibrilar Ácida/sangue , Idoso , Escala de Coma de Glasgow , Escala de Resultado de Glasgow
2.
RMD Open ; 10(2)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724261

RESUMO

OBJECTIVE: A comparison of cryoneurolysis or radio frequency (RF) with placebo in patients with facetogenic chronic low back pain (LBP) for patient global impression of change (PGIC), pain intensity, function and quality of life, with 1-year follow-up. DESIGN: Single-centre, single-blinded placebo-controlled randomised controlled trial. SETTING: Single-centre study. PARTICIPANTS: Inclusion from March 2020 to September 2022: consenting adults over 18 years of age, LBP>3 months, average Numeric Rating Scale LBP≥4 average last 14 days and a positive response to a diagnostic medial branch block (>50% pain reduction after 60 min). INTERVENTIONS: 120 patients were block randomised 1:1:1 to cryoneurolysis, RF or placebo of the medial branch nerves. Physical therapy was added after 4 weeks for all groups. MAIN OUTCOME MEASURES: Primary outcome was PGIC 4 weeks after the intervention. Secondary outcomes included pain intensity (Numeric Rating Scale, NRS), quality of life (Short Form 36, EQ-5D-5L), disability (Oswestry Disability Index), depression (Major Depression Inventory) and catastrophising (Pain Catastrophising Scale). Outcomes were measured at 4 weeks, 3, 6 and 12 months. RESULTS: There was no statistically significant difference in PGIC at 4 weeks between cryoneurolysis and placebo (risk ratio (RR) 2; 95% CI 0.75 to 5.33, p=0.17) and RF and placebo (RR 1.6; 95% CI 0.57 to 4.49, p=0.37), except PGIC for cryoneurolysis at 6-month follow-up (RR 5.1; 95% CI 1.20 to 22.03, p=0.03). No statistically significant differences were found in secondary follow-up endpoints. CONCLUSIONS: Denervation of the medial branch nerve by either cryoneurolysis or RF compared with placebo did not demonstrate significant improvement in PGIC, pain intensity, function and quality of life in patients with facetogenic chronic LBP at short-term or long-term follow-up. TRIAL REGISTRATION NUMBER: NCT04786145.


Assuntos
Dor Crônica , Dor Lombar , Medição da Dor , Qualidade de Vida , Ablação por Radiofrequência , Humanos , Dor Lombar/terapia , Dor Lombar/etiologia , Dor Lombar/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Ablação por Radiofrequência/métodos , Ablação por Radiofrequência/efeitos adversos , Dor Crônica/terapia , Dor Crônica/etiologia , Dor Crônica/psicologia , Resultado do Tratamento , Adulto , Método Simples-Cego , Criocirurgia/métodos , Idoso , Manejo da Dor/métodos
3.
Brain Spine ; 4: 102813, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681174

RESUMO

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

4.
Cell Rep Methods ; 4(3): 100731, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38490204

RESUMO

Systems vaccinology studies have identified factors affecting individual vaccine responses, but comparing these findings is challenging due to varying study designs. To address this lack of reproducibility, we established a community resource for comparing Bordetella pertussis booster responses and to host annual contests for predicting patients' vaccination outcomes. We report here on our experiences with the "dry-run" prediction contest. We found that, among 20+ models adopted from the literature, the most successful model predicting vaccination outcome was based on age alone. This confirms our concerns about the reproducibility of conclusions between different vaccinology studies. Further, we found that, for newly trained models, handling of baseline information on the target variables was crucial. Overall, multiple co-inertia analysis gave the best results of the tested modeling approaches. Our goal is to engage community in these prediction challenges by making data and models available and opening a public contest in August 2024.


Assuntos
Multiômica , Vacinas , Humanos , Vacinologia/métodos , Reprodutibilidade dos Testes , Simulação por Computador
5.
Acta Anaesthesiol Scand ; 68(5): 708-713, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38462487

RESUMO

BACKGROUND: A high proportion of patients who undergo surgery continue to suffer from moderate to severe pain in the early postoperative period despite advances in pain management strategies. Previous studies suggest that clonidine, an alpha2 adrenergic agonist, administered during the perioperative period could reduce acute postoperative pain intensity and opioid consumption. However, these studies have several limitations related to study design and sample size and hence, further studies are needed. AIM: To investigate the effect of a single intravenous (IV) dose of intraoperative clonidine on postoperative opioid consumption, pain intensity, nausea, vomiting and sedation after endometriosis and spine surgery. METHODS: Two separate randomised, blinded, placebo-controlled trials are planned. Patients scheduled for endometriosis (CLONIPAIN) will be randomised to receive either 150 µg intraoperative IV clonidine or placebo (isotonic saline). Patients undergoing spine surgery (CLONISPINE) will receive 3 µg/kg intraoperative IV clonidine or placebo. We aim to include 120 patients in each trial to achieve power of 90% at an alpha level of 0.05. OUTCOMES: The primary outcome is opioid consumption within the first three postoperative hours. Secondary outcomes include pain intensity at rest and during coughing, nausea, vomiting and sedation within the first two postoperative hours and opioid consumption within the first six postoperative hours. Time to discharge from the PACU will be registered. CONCLUSION: This study is expected to provide valuable information on the efficacy of intraoperative clonidine in acute postoperative pain management in patients undergoing endometriosis and spine surgery.


Assuntos
Clonidina , Endometriose , Feminino , Humanos , Clonidina/uso terapêutico , Analgésicos Opioides/uso terapêutico , Endometriose/cirurgia , Endometriose/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico , Náusea/tratamento farmacológico , Vômito/tratamento farmacológico , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
bioRxiv ; 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37693565

RESUMO

Computational models that predict an individual's response to a vaccine offer the potential for mechanistic insights and personalized vaccination strategies. These models are increasingly derived from systems vaccinology studies that generate immune profiles from human cohorts pre- and post-vaccination. Most of these studies involve relatively small cohorts and profile the response to a single vaccine. The ability to assess the performance of the resulting models would be improved by comparing their performance on independent datasets, as has been done with great success in other areas of biology such as protein structure predictions. To transfer this approach to system vaccinology studies, we established a prototype platform that focuses on the evaluation of Computational Models of Immunity to Pertussis Booster vaccinations (CMI-PB). A community resource, CMI-PB generates experimental data for the explicit purpose of model evaluation, which is performed through a series of annual data releases and associated contests. We here report on our experience with the first such 'dry run' for a contest where the goal was to predict individual immune responses based on pre-vaccination multi-omic profiles. Over 30 models adopted from the literature were tested, but only one was predictive, and was based on age alone. The performance of new models built using CMI-PB training data was much better, but varied significantly based on the choice of pre-vaccination features used and the model building strategy. This suggests that previously published models developed for other vaccines do not generalize well to Pertussis Booster vaccination. Overall, these results reinforced the need for comparative analysis across models and datasets that CMI-PB aims to achieve. We are seeking wider community engagement for our first public prediction contest, which will open in early 2024.

7.
Clin Neurol Neurosurg ; 233: 107933, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37591037

RESUMO

AIM: To compare the clinical outcome of single level cervical degenerative spine disease treated surgically with motion preserving anterior cervical disc arthroplasty versus anterior cervical discectomy and fusion (ACDF). METHODS: Patients treated with cervical disc arthroplasty at Aalborg University Hospital and ACDF at Aarhus University Hospital were matched 1:2. Primary outcome measures were Neck Disability Index (NDI), EQ-5D-3 L and Numeric rating scale (NRS) for arm- and neck pain. Data was collected by telephone interviews regarding present and retrospective data. RESULTS: 50 patients treated with cervical disc arthroplasty were matched to 100 ACDF patients covering November 2011 to December 2018. Mean improvements for NRS neck pain three-months postoperative, and NDI were significantly better in the cervical disc arthroplasty group, with intergroup differences of 1.56 (p = 0.02) and 5.01 (p = 0.01) respectively. A subgroup analysis of the half of the cohort with the longest follow-up (mean 7.6 years) showed, in favour of cervical disc arthroplasty, mean improvements of NDI: 8.80 (p = 0.00), EQ5D: - 0.19 (p = 0.04), NRS neck three months follow-up: 3.70 (p = 0.00) and long follow-up: 2.54 (p = 0.01) and NRS arm three months follow-up: 2.02 (p = 0.01). Radiologic examination indicated preserved mobility in 80% of the implanted protheses at 24-month post-surgical follow-up. CONCLUSION: Surgical treatment of one level degenerative cervical spine disease with cervical disc arthroplasty or anterior cervical discectomy and fusion has a similar good clinical outcome after a mean follow-up of 5.6 years. However, cervical disc arthroplasty displayed long-term superiority in the half of the cohort with the longest follow-up time averaging 7.6 years.

8.
Eur Psychiatry ; 66(1): e68, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37583088

RESUMO

In Denmark, a 10-year plan for psychiatry has been agreed on. The content of the plan was developed in collaboration between the Danish Health Authority and the Danish Authority for Social Services and Housing, and it involved many stakeholders. Recently, the government presented a planned investment that would increase the overall budget in Danish regions and municipalities by almost 20 percent over a 10-year period. Epidemiological research demonstrating shortened life expectancy and high levels of burden of disease for people with mental disorders contributed to emphasizing the need for improvement of psychiatric services. User organizations, trade unions, and scientific societies in the field of mental health were unified in a common organization, called the Psychiatry Alliance, and this alliance agreed on common action points and acted together to influence politicians. An assertive approach toward politicians and media was pivotal, and being a first mover and presenting tentative budgets was very influential.


Assuntos
Transtornos Mentais , Psiquiatria , Humanos , Transtornos Mentais/terapia , Saúde Mental , Dinamarca
9.
Nord J Psychiatry ; 77(7): 706-711, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37381680

RESUMO

PURPOSE: Cold water swimming (CWS) involves taking a regular dip in cold, natural waters throughout the winter. The evidence for the health benefits of CWS has been anecdotal, or from small-sample size studies. The available literature reports that CWS abolishes general tiredness, improves mood, boosts self-esteem and improves general well-being. However, research on the effects and safety of CWS as an add-on to the regular treatment of depression is limited. The aim of this study was to investigate whether it is possible and safe for patients with depression to participate in CWS. MATERIAL AND METHODS: The study was designed as an open-label feasibility study. All patients aged 20-69 years with a diagnosis of depression from an outpatient clinic were eligible for inclusion. The intervention consisted of twice-weekly, group-based CWS. RESULTS: Thirteen patients were initially recruited, and five patients participated on a regular basis. Although several patients had somatic comorbidities, all patients passed the somatic evaluation and were physically fit to participate in CWS. Patients who participated regularly in the CWS sessions had a well-being score of 39.2; at the end of the study, their score had increased to 54.0 and PSQI score at baseline was 10.4 (3.7); at the end of the study it was 8.0 ((3.7). CONCLUSION: This study indicates that it is possible and safe for patients with depression to participate in regular, supervised CWS. Furthermore, regular participation in CWS may improve sleep and well-being.


Assuntos
Depressão , Natação , Humanos , Depressão/terapia , Estudos de Viabilidade , Comorbidade , Água
10.
Acta Anaesthesiol Scand ; 67(8): 1085-1090, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37203222

RESUMO

BACKGROUND: Persistent opioid use following surgery is common especially in patients with preoperative opioid use. This study aims to determine the long-term effect of an individualised opioid tapering plan versus standard of care in patients with a preoperative opioid use undergoing spine surgery at Aarhus University Hospital, Denmark. METHODS: This is the 1-year follow-up of a prospective, single-centre, randomised trial of 110 patients who underwent elective spine surgery for degenerative disease. The intervention was an individualised tapering plan at discharge and telephone counselling 1 week after discharge, compared to standard of care. Postoperative outcomes after 1 year include opioid use, reasons for opioid use and pain intensity. RESULTS: The overall response rate to the 1-year follow-up questionnaire was 94% (intervention group 52/55 patients and control group 51/55 patients). Forty-two patients (proportion = 0.81, 95% CI 0.67-0.89) in the intervention group compared to 31 (0.61, 95% CI 0.47-0.73; p = .026) patients in the control group succeeded in tapering to zero 1 year after discharge (p = .026). One patient (0.02, 95% CI 0.01-0.13) in the intervention group compared to seven patients (0.14, 95% CI 0.07-0.26) in the control group were unable to taper to their preoperative dose 1 year after discharge (p = .025). Back/neck and radicular pain intensity was similar between study groups. CONCLUSION: These results suggest that an individualised tapering plan at discharge combined with telephone counselling 1 week after discharge can reduce opioid use 1 year after spine surgery.


Assuntos
Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Estudos Prospectivos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/induzido quimicamente , Coluna Vertebral/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Mar Pollut Bull ; 191: 114968, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37121189

RESUMO

A rapid increase in population size along with expansion in hotel investment have been identified as key drivers of marine pollution in Zanzibar coastal waters. A validated high-resolution hydrodynamic tracer model was used to estimate the dispersal and impact range of pollutants from the main hotel areas along the western coastline of Unguja Island. The model showed the highest impact of pollutants from land during the northeast monsoon season due to the weakening of the main current. Marine protected areas with short distances to hotel areas and weak tidal currents were more likely to be impacted by pollutants from land than the more remote areas with higher flushing in agreement with water quality and seagrass health measurements. Cumulative effects of pollutants instead of single sources are important to consider for integrated wastewater treatment plans and management strategies to reduce pollution for the protection of biodiversity and guide future monitoring.


Assuntos
Recifes de Corais , Poluentes Ambientais , Ecossistema , Hidrodinâmica , Tanzânia
12.
Acta Neurochir (Wien) ; 165(6): 1417-1425, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36790588

RESUMO

PURPOSE: Biochemical biomarkers to determine the injury severity and the potential for functional recovery of traumatic spinal cord injury (TSCI) are highly warranted; however, it remains to be clarified whether cerebrospinal fluid (CSF) or peripheral blood (PB) is the ideal sample media. This study aims to measure and compare biomarker concentrations in CSF and PB and to explore associations between biomarker concentrations and injury severity, i.e., American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, and biomarker concentrations and clinical outcome, i.e., AIS grade improvement and Spinal Cord Independent Measure version III (SCIM-III) score. METHODS: From 2018 to 2020, we conducted a single-center prospective pilot study of TSCI patients (n=15) and healthy controls (n=15). Sample collection and clinical outcome assessment were performed at median 13 h [IQR: 19], 9 days [IQR: 2], and 148 days [IQR: 49] after TSCI. Concentrations of neuron-specific enolase (NSE); glial fibrillary acid protein (GFAP); neurofilament light chain (NfL); interferon-γ (IFN-γ); interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13; and tumor necrosis factor α (TNF-α) were measured and associated to clinical outcomes. RESULTS: The biomarker concentrations were higher in CSF than PB. CSF concentrations of GFAP, NSE, IFN-y, TNF-a, IL-2, IL-12p70, IL-4, IL-10, and IL-13 and PB concentrations of GFAP and IFN-y were significantly associated with AIS grade, but not with AIS grade improvement or SCIM-III score. CONCLUSIONS: Our results support GFAP as a potential diagnostic biomarker that may be measured in CSF as well as PB.


Assuntos
Proteína Glial Fibrilar Ácida , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Biomarcadores , Proteína Glial Fibrilar Ácida/líquido cefalorraquidiano , Interleucina-10 , Interleucina-13 , Interleucina-2 , Interleucina-4 , Filamentos Intermediários , Projetos Piloto , Estudos Prospectivos , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/líquido cefalorraquidiano
13.
Ugeskr Laeger ; 185(3)2023 01 16.
Artigo em Dinamarquês | MEDLINE | ID: mdl-36760143

RESUMO

Intraoperative neuromonitoring (IONM) allows for a perioperative evaluation of the functional integrity of the spinal cord and nerve roots during intradural neurosurgery. This review examines established techniques as somatosensory evoked potentials and motor evoked potentials, as well as electromyography which all provide real-time feedback for the surgical team. IONM represents a valuable tool which can identify emerging neurological complications, and thus can be utilised to reduce the incidence of postoperative neurological deficits by timely interventions.


Assuntos
Transtornos Globais do Desenvolvimento Infantil , Neurocirurgia , Masculino , Criança , Humanos , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Procedimentos Neurocirúrgicos , Pais
14.
Brain Spine ; 2: 100906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248130

RESUMO

•Proteomics enable profiling of inflammatory responses after spinal cord injury.•Proteins are differentially expressed over time.•Proteins are differentially expressed in cerebrospinal fluid and peripheral blood.•A poor relationship exists between protein expression and neurological outcome.

15.
Acta Neurochir (Wien) ; 164(12): 3143-3153, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36190569

RESUMO

PURPOSE: Triggering of inflammatory responses and disruption of blood-spinal cord barrier (BSCB) integrity are considered pivotal events in the pathophysiology of traumatic spinal cord injury (TSCI). Yet, these events are poorly understood and described in humans. This study aims to describe inflammatory responses and BSCB integrity in human TSCI. METHODS: Fifteen TSCI patients and fifteen non-TSCI patients were prospectively recruited from Aarhus University Hospital, Denmark. Peripheral blood (PB) and cerebrospinal fluid (CSF) were collected at median day 0 [IQR: 1], median day 9 [IQR: 2], and median day 148 [IQR: 49] after injury. PB and CSF were analyzed for immune cells by flow cytometry, cytokines by multiplex immunoassay, and BSCB integrity by IgG Index. RESULTS: Eleven TSCI patients completed follow-up. Results showed alterations in innate and adaptive immune cell counts over time. TSCI patients had significantly increased cytokine concentrations in CSF at the first and second follow-up, while only concentrations of interleukin (IL)-4, IL-8, and tumor necrosis factor-α remained significantly increased at the third follow-up. In PB, TSCI patients had significantly increased IL-6, IL-8, and IL-10 concentrations and significantly decreased interferon-γ concentrations at the first follow-up. Results further showed increased IgG Index indicative of BSCB disruption in seven TSCI patients at the first follow-up, five TSCI patients at the second follow-up, and two patients at the third follow-up. CONCLUSIONS: Our results suggest that TSCI mainly triggers innate inflammatory responses that resolves over time, although with some degree of non-resolving inflammation, particularly in CSF. Our results cannot confirm BSCB disruption in all TSCI patients.


Assuntos
Citocinas , Traumatismos da Medula Espinal , Humanos , Imunoglobulina G , Inflamação , Projetos Piloto , Estudos Prospectivos
16.
Acta Neurochir (Wien) ; 164(7): 1883-1888, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35641649

RESUMO

PURPOSE: Incidental durotomy (ID) is one of the most common complications in degenerative surgery. Due to the negative consequences of ID, knowledge about incidence and risk factors is warranted. METHODS: A total of 1,139 surgical procedures for lumbar spinal stenosis (LS) and lumbar herniated disc (LDH) were included from the spine surgery database: DaneSpine. Uni- and multivariate analyses were performed for the assessment of possible risk factors. RESULTS: ID occurred in 10.4% of the surgical procedures. A multivariate regression analysis revealed an increased relative risk of ID by 2% per year of age, 58% by revision surgery, and 55% by decompression on multiple levels. CONCLUSION: In our single-centre cohort study, one in ten patients experiences an ID. Increasing age, revision surgery and decompression of multiple levels are risk factors of ID in degenerative surgery of the lumbar spine.


Assuntos
Deslocamento do Disco Intervertebral , Estenose Espinal , Estudos de Coortes , Constrição Patológica , Dura-Máter/cirurgia , Humanos , Incidência , Deslocamento do Disco Intervertebral/epidemiologia , Deslocamento do Disco Intervertebral/cirurgia , Complicações Intraoperatórias/epidemiologia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fatores de Risco , Estenose Espinal/cirurgia
17.
Reprod Toxicol ; 112: 23-35, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35595152

RESUMO

Induced pluripotent stem cell (iPSC) technology enabled the production of pluripotent stem cell lines from somatic cells from a range of known genetic backgrounds. Their ability to differentiate and generate a wide variety of cell types has resulted in their use for various biomedical applications, including toxicity testing. Many of these iPSC lines are now registered in databases and stored in biobanks such as the European Bank for induced pluripotent Stem Cells (EBiSC), which can streamline the quality control and distribution of these individual lines. To generate the quantities of cells for banking and applications like high-throughput toxicity screening, scalable and robust methods need to be developed to enable the large-scale production of iPSCs. 3D suspension culture platforms are increasingly being used by stem cell researchers, owing to a higher cell output in a smaller footprint, as well as simpler scaling by increasing culture volume. Here we describe our strategies for successful scalable production of iPSCs using a benchtop bioreactor and incubator for 3D suspension cultures, while maintaining quality attributes expected of high-quality iPSC lines. Additionally, to meet the increasing demand for "ready-to-use" cell types, we report recent work to establish robust, scalable differentiation protocols to cardiac, neural, and hepatic fate to enable EBiSC to increase available research tools.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Pluripotentes , Reatores Biológicos , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes/metabolismo
18.
Reprod Toxicol ; 111: 68-80, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35598806

RESUMO

Hepatocytes are of special interest in biomedical research for disease modelling, drug screening and in vitro toxicology. Human induced pluripotent stem cell (hiPSC)-derived hepatocytes could complement primary human hepatocytes due to their capability for large-scale expansion. In this study, we present an optimized protocol for the generation of hepatocyte-like cells (HLCs) from hiPSC in monolayer (2D) and suspension culture (3D) for production of organoids. A protocol was initially optimized in 2D using a gene edited CYP3A4 Nanoluciferase reporter hiPSC line for monitoring the maturity of HLCs and cryopreservation of definitive endoderm (DE) cells. The protocol was optimized for microwell cultures for high-throughput screening to allow for a sensitive and fast readout of drug toxicity. To meet the increasing demand of hepatic cells in biomedical research, the differentiation process was furthermore translated to scalable suspension-based bioreactors for establishment of hepatic organoids. In pilot studies, the technical settings have been optimized by adjusting the initial seeding density, rotation speed, inoculation time, and medium viscosity to produce homogeneous hepatic organoids and to maximize the biomass yield (230 organoids/ml). To speed up the production process, cryopreservation approaches for the controlled freezing of organoids were analysed with respect to cell recovery and marker expression. The results showed that cryopreserved organoids maintained their phenotype only when derived from hepatocyte progenitors (HPs) at day 8 but not from more mature stages. The establishment of robust protocols for the production of large batches of hepatocytes and hepatic organoids could substantially boost their use in biomedical and toxicology studies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Técnicas de Cultura de Células/métodos , Diferenciação Celular , Criopreservação , Hepatócitos , Humanos
19.
Acta Neurochir (Wien) ; 164(1): 25-32, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34671848

RESUMO

BACKGROUND: Spinal cord injury (SCI) is associated with substantial chronic morbidity and mortality. Routine imaging techniques such as T1- and T2-weighted magnetic resonance imaging (MRI) are not effective in predicting neurological deficiency grade or outcome. Diffusional kurtosis imaging (DKI) is an MR imaging technique that provides microstructural information about biological tissue. There are no longitudinal prospective studies assessing DKI metrics in acute traumatic SCI. Therefore, the purpose of this study was to establish a DKI protocol for acute SCI and correlate the DKI metrics to the functional neurological outcome of the patients. METHODS: Eight consecutive SCI patients referred to our institution with cervical SCI were included in the study. An acute diagnostic MRI scan was supplemented with a novel fast, mean kurtosis DKI protocol, which describes the average deviation from Gaussian diffusional along nine different directions. Mean kurtosis values were measured at the injury site and normalized to the mean kurtosis values of a non-injured site. At discharge form specialized rehabilitation, patients were evaluated using the Spinal Cord Independence Measure-III (SCIM-III). The DKI metrics and SCIM-III were analysed using Spearman's rank correlation. RESULTS: This pilot study found a significant correlation between decreasing mean kurtosis values at the injury site of the spinal cord and higher grade of disability measured by the SCIM-III (p = 0.002). CONCLUSION: This pilot study found that DKI may be a valuable tool as a prognostic marker in the acute phase of SCI.


Assuntos
Imagem de Tensor de Difusão , Traumatismos da Medula Espinal , Imagem de Difusão por Ressonância Magnética , Humanos , Projetos Piloto , Prognóstico , Estudos Prospectivos , Traumatismos da Medula Espinal/diagnóstico por imagem
20.
Integr Environ Assess Manag ; 18(4): 892-908, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34750976

RESUMO

Coastal waters are highly productive and diverse ecosystems, often dominated by marine submerged aquatic vegetation (SAV) and strongly affected by a range of human pressures. Due to their important ecosystem functions, for decades, both researchers and managers have investigated changes in SAV abundance and growth dynamics to understand linkages to human perturbations. In European coastal waters, monitoring of marine SAV communities traditionally combines diver observations and/or video recordings to determine, for example, spatial coverage and species composition. While these techniques provide very useful data, they are rather time consuming, labor-intensive, and limited in their spatial coverage. In this study, we compare traditional and emerging remote sensing technologies used to monitor marine SAV, which include satellite and occupied aircraft operations, aerial drones, and acoustics. We introduce these techniques and identify their main strengths and limitations. Finally, we provide recommendations for researchers and managers to choose the appropriate techniques for future surveys and monitoring programs. Integr Environ Assess Manag 2022;18:892-908. © 2021 SETAC.


Assuntos
Ecossistema , Plantas , Monitoramento Ambiental/métodos , Humanos , Tecnologia de Sensoriamento Remoto/métodos
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