| 1. |
- Björnsson, Jon Mar, et al.
(författare)
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Reduced proliferative capacity of hematopoietic stem cells deficient in hoxb3 and hoxb4
- 2003
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 23:11, s. 3872-3883
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Tidskriftsartikel (refereegranskat)abstract
- Several homeobox transcription factors, such as HOXB3 and HOXB4, have been implicated in regulation of hematopoiesis. In support of this, studies show that overexpression of HOXB4 strongly enhances hematopoietic stem cell regeneration. Here we find that mice deficient in both Hoxb3 and Hoxb4 have defects in endogenous hematopoiesis with reduced cellularity in hematopoietic organs and diminished number of hematopoietic progenitors without perturbing lineage commitment. Analysis of embryonic day 14.5 fetal livers revealed a significant reduction in the hematopoietic stem cell pool, suggesting that the reduction in cellularity observed postnatally is due to insufficient expansion during fetal development. Primitive Lin(-) Scal(+) c-kit(+) hematopoietic progenitors lacking Hoxb3 and Hoxb4 displayed impaired proliferative capacity in vitro. Similarly, in vivo repopulating studies of Hoxb3/Hoxb4-deficient hematopoietic cells resulted in lower repopulating capability compared to normal littermates. Since no defects in homing were observed, these results suggest a slower regeneration of mutant HSC. Furthermore, treatment with cytostatic drugs demonstrated slower cell cycle kinetics of hematopoietic stem cells deficient in Hoxb3 and Hoxb4, resulting in increased tolerance to antimitotic drugs. Collectively, these data suggest a direct physiological role of Hoxb4 and Hoxb3 in regulating stem cell regeneration and that these genes are required for maximal proliferative response.
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| 2. |
- Hultström, Michael, 1978-, et al.
(författare)
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Dehydration is associated with production of organic osmolytes and predicts physical long-term symptoms after COVID-19 : a multicenter cohort study
- 2022
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Ingår i: Critical Care. - : Springer Nature. - 1364-8535 .- 1466-609X. ; 26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We have previously shown that iatrogenic dehydration is associated with a shift to organic osmolyte production in the general ICU population. The aim of the present investigation was to determine the validity of the physiological response to dehydration known as aestivation and its relevance for long-term disease outcome in COVID-19.METHODS: The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental.RESULTS: Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern.CONCLUSIONS: Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID.TRIAL REGISTRATION: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).
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| 3. |
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| 4. |
- Larsson, Ellinor, 1982-
(författare)
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Promoting social activities and participation among seniors : exploring and evaluating social and Internet-based occupational therapy interventions
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionThe use of technology and Internet-based activities (IBAs) is increasing in society. However, seniors with limited experiences with the Internet can experience restricted participation in meaningful activities that are dependent on the Internet. Also, social transitions during aging might lead to reduced social activities and social contacts and to increased experiences of loneliness, all of which might have negative health implications. Therefore, there is a need to advance the knowledge of how occupational therapists can support seniors’ use of IBAs and create opportunities for social contacts and social activities during aging.AimThe overall aim of this thesis is to increase the knowledge of how Internet-based activities influence seniors’ participation in society, how seniors experience and are influenced by support from a social Internet-based occupational therapy intervention, and how different aspects of this intervention can contribute to healthy ageing.MethodsIn study I, seniors’ experiences of IBAs were explored and described through interviews with 10 seniors (66–82 years old) that were analyzed with the constant comparative method. In study II, a multiple case study with five seniors (65–85 years old) was used to explore the design of an Internet-based occupational therapy social intervention program and how it influenced social activities and social contacts among the participants. The qualitative and quantitative data from multiple sources were analyzed by pattern matching. In study III, an explorative randomized crossover study with an AB/BA design was conducted with 30 seniors (61–89 years old) who were vulnerable to loneliness and who participated in the intervention program. The quantitative data were analyzed with parametric and non-parametric statistics. In study IV, a qualitative interview study was conducted to collect the experiences of 15 seniors (66–87 years old) from the previous intervention process in study III. The interviews were analyzed with the constant comparative method. All participants in studies I–IV were community-dwelling, retired seniors without home-care services. ResultsComplex interactions of different aspects influence seniors’ possibilities and preferences for taking part in IBAs. The performance of IBAs yielded different experiences of participation in society (study I). The initial explorative results indicated that the client-centered and individually adapted intervention program supports participation in social IBAs (SIBAs) and other social contexts (study II). After participation in the intervention program, the experiences of loneliness significantly decreased, and satisfaction with social contacts on the Internet increased for one group (study III). If an individual’s requirements are met during the intervention process, experiences of habitual SIBA usage, increased self-reliance, and enriched social contacts and social activities both on and off the Internet might be facilitated (study IV).ConclusionThis thesis provides knowledge of how social support, experiences of and accessibility to technology, life-changing events, and identified meaningfulness with online activities influence the motivation to participate in social and Internet-based activities. The occupational therapist should address the individual’s perspective in the intervention program so as to adapt the intervention and to support experiences of satisfactory participation and enhanced social activities and social contacts for seniors. In addition, healthy aging might be supported by the intervention program due to the reduction in loneliness and increased participation in social activities and society. Further evaluation of the framework and content of the intervention program for seniors with restricted participation in IBAs and SIBAs and high levels of loneliness is suggested.
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| 5. |
- Ternesten-Hasséus, Ewa, 1956, et al.
(författare)
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Capsaicin sensitivity in patients with chronic cough-- results from a cross-sectional study.
- 2013
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Ingår i: Cough (London, England). - : Springer Science and Business Media LLC. - 1745-9974. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A subgroup of patients with chronic cough is recognised as having airway symptoms resulting exposure to chemicals and scents related to enhanced cough sensitivity to inhaled capsaicin. Sensory hyperreactivity, which has an estimated prevalence of more than 6%, is one possible explanation for the symptoms experienced by these patients. We hypothesized that a number of patients diagnosed with chronic unexplained cough also have coughing provoked by chemical irritants associated with augmented capsaicin cough reaction, but the extent of such a relation is not known. One aim of the present study was to analyse cough sensitivity to inhaled capsaicin in patients with chronic unexplained cough. Another aim was to compare capsaicin sensitivity in individuals with chemically induced coughing (the chemical-sensitive group) to capsaicin sensitivity in those without such chemical sensitivity (non-sensitive group). METHODS: Fifty-six participants from an earlier cross-sectional study of 62 patients with chronic unexplained cough were asked to participate in this study: 33 were chemical-sensitive and 23 were non-sensitive. Each participant visited the clinic once and performed a capsaicin inhalation test with one of two inhalation devices. The number of coughs, induced airway symptoms, and spirometry results were recorded. RESULTS: Thirty-nine of the invited patients participated in the study, with 32 in the chemical-sensitive group (21 women, 11 men), and 7 in the non-sensitive group (4 women, 3 men). The chemical-sensitive patients coughed significantly more on inhaling capsaicin, and had significantly more other airway symptoms compared to those in the non-sensitive group. Women coughed significantly more than men after receiving the higher concentration of capsaicin. CONCLUSIONS: Environmental irritants often trigger chronic unexplained cough. The current findings confirm that this sensitivity is related to enhanced capsaicin cough sensitivity and indicates more involvement of airway sensory nerves in the pathophysiology of the disease than in cough without evident trigger factors.
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| 6. |
- Wallin, Ewa, et al.
(författare)
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Acute brain lesions on magnetic resonance imaging in relation to neurological outcome after cardiac arrest
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:5, s. 625-647
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Magnetic resonance imaging (MRI) of the brain including diffusion-weighted imaging (DWI) is reported to have high prognostic accuracy in unconscious post-cardiac arrest (CA) patients. We documented acute MRI findings in the brain in both conscious and unconscious post-CA patients treated with target temperature management (TTM) at 32-34°C for 24 h as well as the relation to patients' neurological outcome after 6 months.METHODS:A prospective observational study with MRI was performed regardless of the level of consciousness in post-CA patients treated with TTM. Neurological outcome was assessed using the Cerebral Performance Categories scale and dichotomized into good and poor outcome.RESULTS:Forty-six patients underwent MRI at 3-5 days post-CA. Patients with good outcome had minor, mainly frontal and parietal, lesions. Acute hypoxic/ischemic lesions on MRI including DWI were more common in patients with poor outcome (P = 0.007). These lesions affected mostly gray matter (deep or cortical), with or without involvement of the underlying white matter. Lesions in the occipital and temporal lobes, deep gray matter and cerebellum showed strongest associations with poor outcome. Decreased apparent diffusion coefficient, was more common in patients with poor outcome.CONCLUSIONS:Extensive acute hypoxic/ischemic MRI lesions in the cortical regions, deep gray matter and cerebellum detected by visual analysis as well as low apparent diffusion coefficient values from quantitative measurements were associated with poor outcome. Patients with good outcome had minor hypoxic/ischemic changes, mainly in the frontal and parietal lobes.
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| 7. |
- Wallin, Ewa, et al.
(författare)
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Acute brain lesions on MRI in relation to neurological outcome 6 months after cardiac arrest treated with hypothermia.
- 2015
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 96:Suppl1, s. 147-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Aim of the study: To document the acute magnetic resonance imaging (MRI) findings on the brain in cardiac arrest (CA) patients treated with therapeutic hypothermia (TH) and their relation to patients’ neurological outcome after 6 months.Method: A prospective observational study with MRI was performed regardless the level of consciousness in 56 post-CA patients treated with TH.Results: MRI of the brain was obtained at a median of 4 days (3-13 days). At 6 months, 32/56 had survived with good neurological outcome. The MMSE was performed in 28/32 (88%) patients with a median of 28 (24-30). Acute ischemic lesions were found on diffusion-weighted MRI (DWI) in 34 (61%) patients and were more common in patients with poor outcome (p=0.006). Acute ischemic injuries affected mostly gray matter, deep or cortical and with or without involvement of the underlying white matter. Very few lesions were pure white matter lesions. Lesions in the occipital and temporal lobes, deep gray matter and cerebellum were most associated with poor outcome. Reductions in the apparent diffusion coefficient (ADC) were more common in patients with poor outcome, particularly in the occipital lobes. None of the patients with an ADC below 600x10-6 mm2/s in any region survived to 6 months.Conclusions: In visual analyses of acute MRI, extensive acute lesions were found in the cortical regions and gray matter and were associated with poor outcome. In ADC measurements, low values were associated with poor outcome. Patients with good outcome showed a minor pathological pattern mainly in the frontal and parietal lobes.
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| 8. |
- Wallin, Ewa, et al.
(författare)
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Relationship of acute brain lesions on MRI after cardiac arrest treated with hypothermia to neurological outcome 6 months later
- 2016
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Ingår i: Insights into Imaging 7:Suppl 1, 2016. - : Springer.
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Konferensbidrag (refereegranskat)abstract
- Relationship of acute brain lesions on MRI after cardiac arrest treated with hypothermia to neurological outcome 6 months later,Purpose: To document the acute MRI findings in the brain of post-cardiac arrest (CA) patients treated with therapeutic hypothermia and their relationship to patient outcome after 6 months.Methods and Materials: MRI was performed prospectively 3-13 days (median 4) after CA in 56 patients regardless of the level of consciousness in three hospitals. The images were interpreted visually by two neuroradiologists. Apparent diffusion coefficient (ADC) was measured in predetermined areas in cerebral white matter, deep grey matter, cerebellar grey and white matter and the brainstem. Outcome was assessed using the Cerebral Performance Categories Scale (CPC ) and dichotomized into good and poor outcome.Results: Acute hypoxic lesions on diffusion-weighted MRI (DWI) were more common in patients with poor outcome (p=0.006) and affected mostly grey matter, deep or cortical, with or without involvement of underlying white matter. Pure white matter lesions were very few. Lesions in the occipital and temporal lobes, deep white matter and cerebellum were most associated with poor outcome. Reductions in the ADC, particularly in the occipital lobes, were more common in patients with poor outcome. None of the patients with an ADC below 604-678 x10-6 mm2/s (variation depending on the equipment and technique) in any region survived to 6 months.Conclusion: Extensive acute lesions in cortical regions and deep grey matter in visual analysis and regions with an ADC under the level 600-680 x10-6 mm2/s are associated with poor outcome. Lesions are fewer and mainly situated in the frontal and parietal lobes in patients with good outcome.
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| 9. |
- Bark, Lovisa, et al.
(författare)
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Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19.
- 2023
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Ingår i: Scientific reports. - : Springer Nature. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3-6months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3-6months after ICU discharge was associated to the development of mild cognitive dysfunction (p=0.01), especially in women (p=0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p=0.009), physical fatigue (p=0.004), mental fatigue (p=0.001), and reduced motivation (p=0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p=0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.Trial registration The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).
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| 10. |
- Bickham, S., et al.
(författare)
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Low cutoff G.657-compatible fiber for data center interconnects operating in the 1064 and 1310 nm windows
- 2020
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11286
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Konferensbidrag (refereegranskat)abstract
- Optical interconnects in data centers have traditionally used 850 nm GaAs-based vertical-cavity surface-emitting lasers (VCSELs) in combination with multimode fiber, having a reach up to 100 m in length. Longer links typically use standard single-mode fiber in conjunction with either InP-based edge-emitting lasers or silicon photonic transmitters operating in the 1310 nm or 1550 nm window. Single-mode GaAs-based VCSELs operating at 1064 nm offer another path for achieving longer system reach. Potential advantages of these VCSELs include better power efficiency, modulation speeds reaching 50 Gbps and large-scale fabrication volumes. The longer wavelength is also beneficial due to the lower attenuation and chromatic dispersion of optical fibers at that wavelength. However, one practical issue for single-mode transmission is that the G.657 standard for single-mode fiber requires that the 22-meter cable cutoff wavelength be less than 1260 nm, and these fibers are typically few-moded at 1064 nm. The large differences between the group velocities of the LP01 and LP11 modes can lead to degradation of the system performance due to multi-path interference if the higher order modes are present. To resolve this quandary, we have designed and validated the performance of a new optical fiber which is single-moded at wavelengths less than 1064 nm, but also has G.657-compliant mode field diameter and dispersion characteristics that enable it to be used in the 1310 nm window.
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