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| 2. |
- Strandberg, B., et al.
(författare)
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Near-threshold π-photoproduction on the deuteron
- 2020
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Ingår i: Physical Review C. - 2469-9985. ; 101:3
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Tidskriftsartikel (refereegranskat)abstract
- The first experimental investigation of the near-threshold cross section for incoherent π-photoproduction on the deuteron γd→π-pp is presented. The experimental technique involved detection of the ≈131 MeV γ ray resulting from the radiative capture of photoproduced π-in the target. The total cross section was measured using an unpolarized tagged-photon beam, a liquid-deuterium target, and three very large NaI(Tl) spectrometers. The data are compared to theoretical models that give insight into the elementary reaction γn→π-p and pion-nucleon and nucleon-nucleon final-state interactions.
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| 3. |
- Umek, T., et al.
(författare)
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Oligonucleotides Targeting DNA Repeats Downregulate Huntingtin Gene Expression in Huntington's Patient-Derived Neural Model System
- 2021
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Ingår i: Nucleic Acid Therapeutics. - : Mary Ann Liebert Inc. - 2159-3337 .- 2159-3345. ; 31:6, s. 443-456
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is one of the most common, dominantly inherited neurodegenerative disorders. It affects the striatum, cerebral cortex, and other subcortical structures leading to involuntary movement abnormalities, emotional disturbances, and cognitive impairments. HD is caused by a CAG center dot CTG trinucleotide-repeat expansion in exon 1 of the huntingtin (HTT) gene leading to the formation of mutant HTT (mtHTT) protein aggregates. Besides the toxicity of the mutated protein, there is also evidence that mtHTT transcripts contribute to the disease. Thus, the reduction of both mutated mRNA and protein would be most beneficial as a treatment. Previously, we designed a novel anti-gene oligonucleotide (AGO)-based strategy directly targeting the HTT trinucleotide-repeats in DNA and reported downregulation of mRNA and protein in HD patient fibroblasts. In this study, we differentiate HD patient-derived induced pluripotent stem cells to investigate the efficacy of the AGO, a DNA/Locked Nucleic Acid mixmer with phosphorothioate backbone, to modulate HTT transcription during neural in vitro development. For the first time, we demonstrate downregulation of HTT mRNA following both naked and magnetofected delivery into neural stem cells (NSCs) and show that neither emergence of neural rosette structures nor self-renewal of NSCs is compromised. Furthermore, the inhibition potency of both HTT mRNA and protein without off-target effects is confirmed in neurons. These results further validate an anti-gene approach for the treatment of HD.
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- Hathaway, Cassandra A., et al.
(författare)
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Prolactin and risk of epithelial ovarian cancer
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 30:9, s. 1652-1659
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer.Methods: Weconducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype.Results: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (Ptrend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97–1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74–2.58; Ptrend = 0.32 and OR = 1.41; 95% CI = 0.93–2.13; Ptrend = 0.08, respectively; Pheterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56–4.59; Ptrend < 0.01 and OR = 0.90; 95% CI = 0.58–1.40; Ptrend = 0.98, respectively; Pheterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis.Conclusions: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2.Impact: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.
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| 6. |
- Holmström, Oscar, et al.
(författare)
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A novel deep learning-based point-of-care diagnostic method for detecting Plasmodium falciparum with fluorescence digital microscopy.
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malaria remains a major global health problem with a need for improved field-usable diagnostic tests. We have developed a portable, low-cost digital microscope scanner, capable of both brightfield and fluorescence imaging. Here, we used the instrument to digitize blood smears, and applied deep learning (DL) algorithms to detect Plasmodium falciparum parasites.METHODS: Thin blood smears (n = 125) were collected from patients with microscopy-confirmed P. falciparum infections in rural Tanzania, prior to and after initiation of artemisinin-based combination therapy. The samples were stained using the 4',6-diamidino-2-phenylindole fluorogen and digitized using the prototype microscope scanner. Two DL algorithms were trained to detect malaria parasites in the samples, and results compared to the visual assessment of both the digitized samples, and the Giemsa-stained thick smears.RESULTS: Detection of P. falciparum parasites in the digitized thin blood smears was possible both by visual assessment and by DL-based analysis with a strong correlation in results (r = 0.99, p < 0.01). A moderately strong correlation was observed between the DL-based thin smear analysis and the visual thick smear-analysis (r = 0.74, p < 0.01). Low levels of parasites were detected by DL-based analysis on day three following treatment initiation, but a small number of fluorescent signals were detected also in microscopy-negative samples.CONCLUSION: Quantification of P. falciparum parasites in DAPI-stained thin smears is feasible using DL-supported, point-of-care digital microscopy, with a high correlation to visual assessment of samples. Fluorescent signals from artefacts in samples with low infection levels represented the main challenge for the digital analysis, thus highlighting the importance of minimizing sample contaminations. The proposed method could support malaria diagnostics and monitoring of treatment response through automated quantification of parasitaemia and is likely to be applicable also for diagnostics of other Plasmodium species and other infectious diseases.
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| 8. |
- Mendham, Amy E., et al.
(författare)
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Sarcopenia in older black South African women and relationships with physical activity and protein intake
- 2020
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Ingår i: 13th European Nutrition Conference, FENS 2019, 15–18 October 2019, Malnutrition in an Obese World: European Perspectives. - : Cambridge University Press. ; , s. E150-E150
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: South Africa (SA) is a developing country with an ageing population. Adequate nutrition and physical activity (PA) protect against the loss of muscle mass and physical function, both of which are important components of sarcopenia. This study aimed to measure the prevalence of sarcopenia in older black SA women and investigate its associations with PA and protein intake.Materials and Methods: Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic questionnaires, 24 h urine collection (estimate protein intake), venous blood (hs-C-reactive protein (hs-CRP) and ferritin), functional tests (grip strength, 3 m timed-up-and-go (TUG), 10 m walk test) and PA monitoring (activPAL). Dual-energy x-ray absorptiometry whole-body scans assessed fat and fat-free soft tissue mass (FFSTM).Results: According to the European Working group on Sarcopenia in Older People (EWGSOP)2, 2.5% (n = 3) had confirmed sarcopenia of a low severity based on normal physical function. Of the total cohort, 9% (n = 11) had low grip strength, 22.1% (n = 27) had a low appendicular skeletal muscle index (ASMI), and no women had low TUG (s) or gait speed (m/s). Higher ASMI was associated with lower hs-CRP (p = 0.05; Rho = -0.209) and higher ferritin (Rho = 0.252; p = 0.019), grip strength (kg, Rho = 0.223; p = 0.015), and gait speed (m/s, Rho = 0.180; p = 0.050). Protein intake suggested intake of 41.8g/day/ or 0.51 g/kg of body mass/day. Higher total protein intake (g/24h), was associated with higher FFSTM (kg) and ASMI (p < 0.001). PA outcomes were not correlated with FFSTM or ASMI (p > 0.05), however, there was a strong positive correlation of TUG (s) and gait speed (m/s) with time spent: 1) stepping per day (min) and; 2) at a high cadence (> 100 steps/min) (all p < 0.01). Daily step count was 7137 ± 3233 (mean ± Standard deviation), with 97.9 ± 38.7 min of total time spent stepping and 12.6 ± 16.8 min spent stepping at a high cadence (> 100 steps/min). Of note, 13.9% (n = 17) of women were completing > 10,000 steps/day.Discussion: Based on the EWGSOP2 criteria, there is a low prevalence of sarcopenia in older black SA women, explained by the maintenance of strength and physical function that directly related to PA, especially that performed at higher intensities. In contrast, low muscle mass was relatively prevalent (22.1%) and was associated with low dietary protein and not PA. Notably, it may be important to review the cut-points of EWGSOP2 criteria to be specific to the older SA women from disadvantaged communities.
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| 9. |
- Mendham, Amy E., et al.
(författare)
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Sarcopenic Obesity in Africa: A Call for Diagnostic Methods and Appropriate Interventions
- 2021
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- This perspective aims to highlight the lack of current knowledge on sarcopenic obesity in Africa and to call for diagnostic methods and appropriate interventions. Sarcopenic obesity has been defined as obesity that occurs in combination with low muscle mass and function, which is typically evident in older adults. However, there has been no clear consensus on population-specific diagnostic criterion, which includes both gold-standard measures that can be used in a more advanced health care system, and surrogate measures that can be used in low-income settings with limited resources and funding. Importantly, low and middle-income countries (LMICs) across Africa are in an ongoing state of economic and social transition, which has contributed to an increase in the aging population, alongside the added burden of poverty, obesity, and associated co-morbidities. It is anticipated that alongside the increased prevalence of obesity, these countries will further experience an increase in age-related musculoskeletal diseases such as sarcopenia. The developmental origins of health and disease (DOHaD) approach will allow clinicians and researchers to consider developmental trajectories, and the influence of the environment, for targeting high-risk individuals and communities for treatment and/or prevention-based interventions that are implemented throughout all stages of the life course. Once a valid and reliable diagnostic criterion is developed, we can firstly assess the prevalence and burden of sarcopenic obesity in LMICs in Africa, and secondly, develop appropriate and sustainable interventions that target improved dietary and physical activity behaviors throughout the life course.
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| 10. |
- Mendham, Amy E., et al.
(författare)
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Understanding factors associated with sarcopenic obesity in older African women from a low-income setting : a cross-sectional analysis
- 2021
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: High rates of food insecurity, obesity and obesity-related comorbidities in ageing South African (SA) women may amplify the risk of developing sarcopenic obesity. This study aimed to investigate the prevalence and correlates of sarcopenic obesity and its diagnostic components [grip strength, appendicular skeletal muscle mass (ASM) and body mass index (BMI)] in older SA women from a low-income setting.Methods: This cross-sectional study recruited black SA women between the ages of 60–85 years (n = 122) from a low-income community. Testing included a fasting blood sample (markers of cardiometabolic risk, HIV), whole body and regional muscle and fat mass (dual-energy absorptiometry x-ray), anthropometry, blood pressure, functional movement tests, current medication use, demographic and health questionnaires, physical activity (PA; accelerometery), household food insecurity access scale, and a one-week quantified food frequency questionnaire. Foundation for the National Institutes of Health (FNIH) criteria (grip strength and ASM, adjusted for BMI) were used to classify sarcopenia. Participants with sarcopenia alongside a BMI of > 30.0 kg/m2 were classified as having sarcopenic obesity. Prevalence using other criteria (European Working Group on Sarcopenia in Older People, Asian Working Group for Sarcopenia and the International Working Group for Sarcopenia) were also explored.Results: The prevalence of sarcopenia was 27.9%, which comprised of sarcopenia without obesity (3.3%) and sarcopenic obesity (24.6%). Other classification criteria showed that sarcopenia ranged from 0.8–14.7%, including 0.8–9.8% without obesity and 0–4.9% with sarcopenic obesity. Using multivariate-discriminant analysis (OPLS-DA) those with sarcopenic obesity presented with a descriptive profile of higher C-reactive protein, waist circumference, food security and sedentary time than women without sarcopenic obesity (p = 0.046). A similar profile described women with low BMI-adjusted grip strength (p < 0.001).Conclusions: The majority of women with sarcopenia were also obese (88%). We show a large discrepancy in the diagnostic criteria and the potential for significantly underestimating the prevalence of sarcopenia if BMI is not adjusted for. The main variables common to women with sarcopenic obesity were higher food security, lower PA and chronic inflammation. Our data highlights the importance of addressing obesity within these low-income communities to ensure the prevention of sarcopenic obesity and that quality of life is maintained with ageing.
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