| 1. |
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| 2. |
- Zhang, Q, et al.
(author)
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Recessive inborn errors of type I IFN immunity in children with COVID-19 pneumonia
- 2022
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:8
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Journal article (peer-reviewed)abstract
- Recessive or dominant inborn errors of type I interferon (IFN) immunity can underlie critical COVID-19 pneumonia in unvaccinated adults. The risk of COVID-19 pneumonia in unvaccinated children, which is much lower than in unvaccinated adults, remains unexplained. In an international cohort of 112 children (<16 yr old) hospitalized for COVID-19 pneumonia, we report 12 children (10.7%) aged 1.5–13 yr with critical (7 children), severe (3), and moderate (2) pneumonia and 4 of the 15 known clinically recessive and biochemically complete inborn errors of type I IFN immunity: X-linked recessive TLR7 deficiency (7 children) and autosomal recessive IFNAR1 (1), STAT2 (1), or TYK2 (3) deficiencies. Fibroblasts deficient for IFNAR1, STAT2, or TYK2 are highly vulnerable to SARS-CoV-2. These 15 deficiencies were not found in 1,224 children and adults with benign SARS-CoV-2 infection without pneumonia (P = 1.2 × 10−11) and with overlapping age, sex, consanguinity, and ethnicity characteristics. Recessive complete deficiencies of type I IFN immunity may underlie ∼10% of hospitalizations for COVID-19 pneumonia in children.
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| 3. |
- Garcia-Garcia, A, et al.
(author)
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Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
- 2023
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:5
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Journal article (peer-reviewed)abstract
- X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
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| 4. |
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| 5. |
- Campbell, TM, et al.
(author)
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Respiratory viral infections in otherwise healthy humans with inherited IRF7 deficiency
- 2022
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 219:7
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Journal article (peer-reviewed)abstract
- Autosomal recessive IRF7 deficiency was previously reported in three patients with single critical influenza or COVID-19 pneumonia episodes. The patients’ fibroblasts and plasmacytoid dendritic cells produced no detectable type I and III IFNs, except IFN-β. Having discovered four new patients, we describe the genetic, immunological, and clinical features of seven IRF7-deficient patients from six families and five ancestries. Five were homozygous and two were compound heterozygous for IRF7 variants. Patients typically had one episode of pulmonary viral disease. Age at onset was surprisingly broad, from 6 mo to 50 yr (mean age 29 yr). The respiratory viruses implicated included SARS-CoV-2, influenza virus, respiratory syncytial virus, and adenovirus. Serological analyses indicated previous infections with many common viruses. Cellular analyses revealed strong antiviral immunity and expanded populations of influenza- and SARS-CoV-2–specific memory CD4+ and CD8+ T cells. IRF7-deficient individuals are prone to viral infections of the respiratory tract but are otherwise healthy, potentially due to residual IFN-β and compensatory adaptive immunity.
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| 6. |
- Bilterys, T., et al.
(author)
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Relationship, differences, and agreement between objective and subjective sleep measures in chronic spinal pain patients with comorbid insomnia: a cross-sectional study
- 2023
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In: Pain. - 0304-3959. ; 164:9, s. 2016-2028
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Journal article (peer-reviewed)abstract
- Sleep disturbances are one of the most frequent reported problems in people with nonspecific chronic spinal pain (nCSP) and presents an additional treatment challenge. Interventions targeting sleep problems are mainly based on subjective sleep complaints and do not take objective sleep into consideration. The aim of this cross-sectional study was to evaluate the relationship and conformity between self-reported and objectively measured sleep parameters (ie, questionnaire vs polysomnography and actigraphy). The baseline data of 123 people with nCSP and comorbid insomnia who are participating in a randomized controlled trial were analyzed. Pearson correlations were used to investigate the relationship between objective and subjective sleep parameters. Differences between objective and subjective sleep parameters were analyzed using t tests. Bland-Altman analyses were performed to quantify and visualize agreement between the different measurement methods. Except for the significant moderate correlation between perceived time in bed (TIB) and actigraphic TIB (r = 0.667, P < 0.001), all other associations between subjective and objective measures were rather weak (r < 0.400). Participants underestimated their total sleep time (TST) (mean difference [MD] = -52.37 [-67.94, -36.81], P < 0.001) and overestimated sleep onset latency (SOL) (MD = 13.76 [8.33, 19.20], P < 0.001) in general. The results of this study suggest a discrepancy (differences and lack of agreement) between subjective and objective sleep parameters in people with nCSP and comorbid insomnia. No or weak associations were found between self-reported sleep and objectively measured sleep. Findings suggest that people with nCSP and comorbid insomnia tend to underestimate TST and overestimate SOL. Future studies are necessary to confirm our results.
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| 7. |
- Fernandez-de-las-Penas, C., et al.
(author)
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Phenotyping Post-COVID Pain as a Nociceptive, Neuropathic, or Nociplastic Pain Condition
- 2022
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:10
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Journal article (peer-reviewed)abstract
- Pain after an acute Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) condition (post-COVID pain) is becoming a new healthcare emergency. Precision medicine refers to an evidence-based method of grouping patients based on their diagnostic/symptom presentation and then tailoring specific treatments accordingly. Evidence suggests that post-COVID pain can be categorized as nociceptive (i.e., pain attributable to the activation of the peripheral receptive terminals of primary afferent neurons in response to noxious chemical, mechanical, or thermal stimuli), neuropathic (i.e., pain associated with a lesion or disease of the somatosensory nervous system and limited to a "neuroanatomically plausible" distribution of the system), nociplastic (i.e., pain arising from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain), or mixed type (when two pain phenotypes co-exist). Each of these pain phenotypes may require a different treatment approach to maximize treatment effectiveness. Accordingly, the ability to classify post-COVID pain patients into one of these phenotypes would likely be critical for producing successful treatment outcomes. The 2021 International Association for the Study of Pain (IASP) clinical criteria and grading system provide a framework for classifying pain within a precision pain medicine approach. Here we present data supporting the possibility of grouping patients with post-COVID pain into pain phenotypes, using the 2021 IASP classification criteria, with a specific focus on nociplastic pain, which is probably the primary mechanism involved in post-COVID pain. Nociplastic pain, which is usually associated with comorbid symptomology (e.g., poor sleep quality, fatigue, cognitive-emotional disturbances, etc.) and is considered to be more difficult to treat than other pain types, may require a more nuanced multimodal treatment approach to achieve better treatment outcomes.
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| 8. |
- Leemans, L., et al.
(author)
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Do psychological factors relate to movement-evoked pain in people with musculoskeletal pain? A systematic review and meta-analysis
- 2022
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In: Brazilian Journal of Physical Therapy. - : Elsevier BV. - 1413-3555. ; 26:6
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Journal article (peer-reviewed)abstract
- Background: A growing body of evidence has demonstrated the importance of implementing movement-evoked pain in conventional pain assessments, with a significant role for psychologi-cal factors being suggested. Whether or not to include these factors in the assessment of move-ment-evoked pain has not yet been determined.Objectives: The aim of this systematic review is to explore the association between psychologi-cal factors and movement-evoked pain scores in people with musculoskeletal pain.Methods: For this systematic review with meta-analysis, four electronic databases (PubMed, Medline, WOS, and Scopus) were searched. Cross-sectional studies, longitudinal cohort studies, and randomized controlled trials investigating the association between movement-evoked pain and psychological factors in adults with musculoskeletal pain were considered. Meta-analysis was conducted for outcomes with homogeneous data from at least 2 studies. Fischer-Z transfor-mations were used as the measure of effect. Quality of evidence was assessed using the National Institutes of Health's Quality assessment tool for observational cohort and cross-sectional studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Results: Meta-analyses and grading the quality of evidence revealed moderate evidence for a relation between movement-evoked pain and depressive symptoms (Fisher-z=0.27; 95%CI: 0.17, 0.36; 5 studies (n=440)), pain-related fear (Fisher-z=0.35; 95%CI: 0.26, 0.44; 6 studies (n=492)), and pain catastrophizing (Fisher-z=0.47; 95%CI: 0.36, 0.58; 4 studies (n=312)) in people with musculoskeletal pain.Conclusions: Movement-evoked pain is weakly to moderately associated to depressive symp-toms, pain-related fear, and pain catastrophizing in people with musculoskeletal pain.(c) 2022 Associa4ao Brasileira de Pesquisa e Pos-Gradua4ao em Fisioterapia. Published by Elsevier Espana, S.L.U. All rights reserved.
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| 9. |
- Mucciola, R., et al.
(author)
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Neutron capture and total cross-section measurements on Mo-94'95'96 at n_TOF and GELINA
- 2023
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In: 15th International Conference on Nuclear Data for Science and Technology, ND2022. - : EDP Sciences.
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Conference paper (peer-reviewed)abstract
- Capture and total cross section measurements for 94'95'96 MO have been performed at the neutron time -of-flight facilities, n_TOF at CERN and GELINA at JRC-Geel. The measurements were performed using isotopically enriched samples with an enrichment above 95% for each of the (94'95'96)M0 isotopes. The capture measurements were performed at n_TOF using C6D6 detectors and a new sTED detector. The transmission measurements were performed at a 10 m station of GELINA using a Li-6 glass neutron detector. Preliminary results of these measurements are presented.
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| 10. |
- Van Looveren, E., et al.
(author)
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The Association between Sleep and Chronic Spinal Pain: A Systematic Review from the Last Decade
- 2021
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 10:17
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Journal article (peer-reviewed)abstract
- Chronic spinal pain, including both neck and low back pain, is a common disabling disorder in which sleep problems are frequently reported as a comorbidity. The complex processes of both sleep and chronic pain seem to have overlapping mechanisms, which may explain their often established bidirectional relationship. This systematic review aims to investigate the assumed association between sleep and chronic spinal pain by providing an overview of the literature from the last decade. Eligible studies were obtained by searching four databases (PubMed, Embase, Web of Science, and PsycARTICLES). Articles were found relevant if they included a human adult population and investigated the possible association between sleep parameters and chronic spinal pain. Only studies published after January 2009 were included, as this review aimed to provide an update of a previous literature overview on this topic. The quality of the studies was assessed by risk of bias and level of evidence. A total of twenty-seven studies (6 cohort, 5 case-control, and 16 cross-sectional studies) were included in this systematic review. The methodological quality of these studies was low to moderate. The majority of studies reported weak to moderate evidence for an association between sleep parameters and chronic spinal pain, with more severe pain accompanied by more disturbed sleep. Addressing frequently reported sleep problems in chronic spinal pain patients therefore appears to be a necessary complement to pain management to achieve optimal treatment outcomes.
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| 11. |
- Bilterys, T., et al.
(author)
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Predictors for physical activity and its change after active physical therapy in people with spinal pain and insomnia: Secondary analysis of a randomized controlled trial
- 2022
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In: Brazilian Journal of Physical Therapy. - : Elsevier BV. - 1413-3555. ; 26:6
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Journal article (peer-reviewed)abstract
- Background: In healthy people and people with nonspecific chronic spinal pain (nCSP) and/or insomnia, participation in physical activity on a regular basis has several physical and psychological health benefits. However, people with chronic conditions often tend to reduce physical activity participation which can lead to deconditioning over time. Currently, there are no known predictors for an (in)active lifestyle (before and after physical therapy treatment) in people with chronic spinal pain and comorbid insomnia. Objective: To examine predictors of pre-treatment moderate-to-vigorous physical activity (MVPA) and to examine determinants for a change in MVPA in response to 14-weeks of active physical therapy treatment in people with nonspecific chronic spinal pain (nCSP) and comorbid insomnia. Methods: Baseline data and post-treatment data were analyzed for 66 participants. A linear multiple regression analysis was conducted to examine which factors predict MVPA at baseline. Linear mixed-effects modeling was used to identify determinants for change in MVPA in response to an active physical therapy treatment. Results: Physical fatigue (b = -0.9; 95%CI: -1.59, -0.15), less limitations in functioning as a result of emotional problems (b = 0.1; 95%CI: 0.03, 0.10), mental fatigue (b = -1.0; 95%CI: -1.67, -0.43), lower general sleep quality (b= 0.7; 95%CI: 0.22, 1.17), and body mass index (b = -0.5; 95%CI: -0.93, -0.16) were significant predictors of baseline MVPA. The regression model explained 33.3% of the total variance in baseline MVPA. The change of MVPA in response to the treatment ranged from a decrease of 17.5 to an increase of 16.6 hours per week. No determinants for change in MVPA after treatment could be identified. Conclusion: People with nCSP and comorbid insomnia are more likely to engage in MVPA if they report, at baseline, lower sleep quality, fewer limitations in functioning resulting from emotional problems, lower body mass index, as well as less physical and mental fatigue.
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| 12. |
- Colonna, N., et al.
(author)
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The fission experimental programme at the CERN n_TOF facility : status and perspectives
- 2020
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 56:2
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Research review (peer-reviewed)abstract
- Neutron-induced fission reactions play a crucial role in a variety of fields of fundamental and applied nuclear science. In basic nuclear physics they provide important information on properties of nuclear matter, while in nuclear technology they are at the basis of present and future reactor designs. Finally, there is a renewed interest in fission reactions in nuclear astrophysics due to the multi-messenger observation of neutron star mergers and the important role played by fission recycling in r-process nucleosynthesis. Although studied for several decades, many fundamental questions still remain on fission reactions, while modern applications and the development of more reliable nuclear models require high-accuracy and consistent experimental data on fission cross sections and other fission observables. To address these needs, an extensive fission research programme has been carried out at the n_TOF neutron time-of-flight facility at CERN during the last 18 years, taking advantage of the high energy resolution, high luminosity and wide energy range of the neutron beam, as well as of the detection and data acquisition systems designed for this purpose. While long-lived isotopes are studied on the 185 m long flight-path, the recent construction of a second experimental area at a distance of about 19 m has opened the way to challenging measurements of short-lived actinides. This article provides an overview of the n_TOF experimental programme on neutron-induced fission reactions along with the main characteristics of the facility, the various detection systems and data analysis techniques used. The most important results on several major and minor actinides obtained so far and the future perspectives of fission measurements at n_TOF are presented and discussed.
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| 19. |
- Goudman, L, et al.
(author)
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Exploration of the Supraspinal Hypotheses about Spinal Cord Stimulation and Dorsal Root Ganglion Stimulation: A Systematic Review
- 2021
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In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:13
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Journal article (peer-reviewed)abstract
- Despite the established efficacy and effectiveness of Spinal Cord Stimulation (SCS), there is still no consensus on the supraspinal mechanisms of action of this therapy. The purpose of this study was to systematically review previously raised hypotheses concerning supraspinal mechanisms of action of SCS based on human, animal and computational studies. Searches were conducted using four electronic databases (PubMed, EMBASE, SCOPUS and Web of Science), backward reference searching and consultation with experts. The study protocol was registered prior to initiation of the review process (PROSPERO CRD42020161531). A total of 54 publications were included, 21 of which were animal studies, and 33 were human studies. The supraspinal hypotheses (n = 69) identified from the included studies could be categorized into six groups concerning the proposed supraspinal hypothesis, namely descending pathways (n = 24); ascending medial pathway (n = 13); ascending lateral pathway (n = 10); affective/motivational influences (n = 8); spinal–cerebral (thalamic)-loop (n = 3) and miscellaneous (n = 11). Scientific support is provided for the hypotheses identified. Modulation of the descending nociceptive inhibitory pathways, medial and lateral pathways were the most frequently reported hypotheses about the supraspinal mechanisms of action of SCS. These hypotheses were mainly supported by studies with a high or moderate confidence in the body of evidence.
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| 20. |
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| 23. |
- Huysmans, E., et al.
(author)
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Exploring Associations between Healthcare Use and Demographics, Pain and Pain Cognitions in People Scheduled for Surgery for Lumbar Radiculopathy: A Cross-Sectional Study
- 2023
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 12:1
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Journal article (peer-reviewed)abstract
- This cross-sectional study explored associations between demographics, pain intensity and cognitions on the one hand and healthcare use (HCU) on the other hand in people undergoing surgery for lumbar radiculopathy. HCU during the 2 months preceding surgery was evaluated using a retrospective questionnaire. Demographics included sex, age and level of education and equivalent income. Back and leg pain intensity were evaluated using a visual analogue scale. Pain cognitions were assessed with the Tampa scale of kinesiophobia, the pain catastrophizing scale and the pain vigilance and awareness questionnaire. The sample comprised 120 participants (52% males; 49 years (Quartile (Q)1-Q3: 37.3-57.43)). The number of visits to the general practitioner was associated with sex (incidence rate ratio (IRR) for males = 0.811; p = 0.050), pain catastrophizing (IRR = 1.010; p = 0.041), pain magnification (IRR = 1.058; p = 0.004) and leg pain intensity (IRR = 1.004; p = 0.038). The number of neurosurgeon visits was associated with level of education (IRR moderate education = 1.518; p = 0.016 (reference: low education)). Receiving zero physiotherapy visits was associated with higher back pain intensity (Beta = 0.018; p = 0.028). Highest level of analgesics used was associated with sex (IRR for males = 0.502; p = 0.047) and leg pain (IRR = 1.014; p = 0.034). Only the association between general practitioner visits and pain magnification remained significant in multivariable analyses (IRR = 1.061; p = 0.033). The results suggest a rather indirect relationship between HCU and demographics, pain intensity and cognitions, involving a potential interplay between several patient- and healthcare system-related factors.
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| 24. |
- Van Looveren, E., et al.
(author)
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Combining Cognitive Behavioral Therapy for Insomnia and Chronic Spinal Pain Within Physical Therapy: A Practical Guide for the Implementation of an Integrated Approach
- 2022
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In: Physical Therapy. - : Oxford University Press (OUP). - 1538-6724 .- 0031-9023. ; 102:8
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Journal article (peer-reviewed)abstract
- Most people who have nonspecific chronic spinal pain (nCSP) report comorbid insomnia. However, in current treatment strategies for nCSP, insomnia is usually not addressed. Considering the bidirectional interaction between pain and sleep and its underlying psychophysiological mechanisms, insomnia may increase the risk of developing adverse physical and psychological health outcomes and should thus no longer be left untreated. As suggested by previous pilot studies, adding cognitive behavioral therapy for insomnia to the contemporary evidence-based biopsychosocial physical therapy approach may also improve pain outcomes in nCSP. This manuscript aims to provide practical guidelines on hybrid physical therapy, including the combination of the following components: (1) pain neuroscience education (eg, to reconceptualize pain) and cognition-targeted exercise therapy (eg, graded exposure to functional daily life movements), and (2) cognitive behavioral therapy for insomnia (sleep psychoeducation, behavioral and cognitive therapy, correction of sleep hygiene, and relaxation therapy) can be deployed for the management of patients who have chronic spinal pain. Impact. Due to the major impact sleep disturbances have on pain and disability, insomnia as a comorbidity should no longer be ignored when treating patients with chronic spinal pain. © The Author(s) 2022. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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