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1.	Gusdal, Annelie K, 1963-, et al. (författare) Voices on adherence to ART in Ethiopia and Uganda : a matter of choice or simply not an option? 2009 Ingår i: AIDS Care. - : Informa UK Limited. - 0954-0121 .- 1360-0451. ; 21:11, s. 1381-1387 Tidskriftsartikel (refereegranskat)abstract This paper explores HIV patients' adherence to antiretroviral treatment (ART) in resource-limited contexts in Uganda and Ethiopia, where ART is provided free of charge. Qualitative semi-structured interviews were conducted with 79 patients, 17 peer counselors, and 22 providers in ART facilities in urban and rural areas of Ethiopia and Uganda. Interviewees voiced their experiences of, and views on ART adherence both from an individual and a system level perspective. Two main themes emerged from the content analysis: "Patients' competing costs and systems' resource constraints'' and "Patients' trust in ART and quality of the patient-provider encounters.'' The first theme refers to how patients' adherence was challenged by difficulties in supporting themselves and their families, paying for transportation, for drug refill and follow-up as well as paying for registration fees, opportunistic infection treatment, and expensive referrals to other hospitals. The second theme describes factors that influenced patients' capacity to adhere: personal responsibility in treatment, trust in the effects of antiretroviral drugs, and trust in the quality of counseling. To grant patients a fair choice to successfully adhere to ART, transport costs to ART facilities need to be reduced. This implies providing patients with drugs for longer periods of time and arranging for better laboratory services, thus not necessitating frequent revisits. Services ought to be brought closer to patients and peripheral, community-based healthworkers used for drug distribution. There is a need for training providers and peer counselors, in communication skills and adherence counseling.
2.	Reimers, Eva, et al. (författare) Hedersproblematik är varken utmärkande eller exklusivt för islam 2022 Ingår i: Sydsvenska dagbladet. - Malmö. - 1652-814X. ; :2022-01-31 Tidskriftsartikel (populärvet., debatt m.m.)
3.	Sandestig, Anna, et al. (författare) Could Dissimilar Phenotypic Effects of ACTB Missense Mutations Reflect the Actin Conformational Change? : Two Novel Mutations and Literature Review 2018 Ingår i: Molecular Syndromology. - : S. Karger. - 1661-8769 .- 1661-8777. ; 9:5, s. 259-265 Tidskriftsartikel (refereegranskat)abstract The beta-actin gene encodes 1 of 6 different actin proteins. De novo heterozygous missense mutations in ACTB have been identified in patients with Baraitser-Winter syndrome (BRWS) and also in patients with developmental disorders other than BRWS, such as deafness, dystonia, and neutrophil dysfunction. We describe 2 different novel de novo missense ACTB mutations, c.208Camp;gt;G (p.Pro70Ala) and c.511Camp;gt;T (p.Leu171Phe), found by trio exome sequencing analysis of 2 unrelated patients: an 8-year-old boy with a suspected BRWS and a 4-year-old girl with unclear developmental disorder. The mutated residue in the first case is situated in the actin H-loop, which is involved in actin polymerization. The mutated residue in the second case (p.Leu171Phe) is found at the actin barbed end in the W-loop, important for binding to profilin and other actin-binding molecules. While the boy presented with a typical BRWS facial appearance, the girl showed facial features not recognizable as a BRWS gestalt as well as ventricular arrhythmia, cleft palate, thrombocytopenia, and gray matter heterotopia. We reviewed previously published ACTB missense mutations and ascertained that a number of them do not cause typical BRWS. By comparing clinical and molecular data, we speculate that the phenotypic differences found in ACTB missense mutation carriers might supposedly be dependent on the conformational change of ACTB.
4.	Bachrach-Lindström, Margareta, et al. (författare) Nutritional status and functional capacity after femoral neck fractures : a prospective randomized one-year follow-up study 2000 Ingår i: Aging. - 1945-4589. ; 12:5, s. 366-374 Tidskriftsartikel (refereegranskat)abstract The primary aim of this study was to evaluate the effect of two different surgical methods on nutritional status and functional capacity during the first postoperative year in patients with displaced femoral neck fractures. A further aim was to evaluate the effect of nutritional support. One hundred patients were randomly assigned to treatment with either primary total hip arthroplasty (THA) or osteosynthesis. Half of the patients in each treatment group received protein- and energy-enriched food in the hospital in addition to individual nutritional advice in order to optimize their intake of protein- and energy-rich food. Nutritional state and functional capacity were examined at baseline, one and three months, and one year after the operation. Pain was examined at three months and one year. The effect of nutritional intervention was equal within both surgical groups. Logistic regression showed that the dependent variable "living at one year" was significantly associated with serum albumin levels at one month. Advanced age, mental impairment and deteriorated nutritional status were predominant in the non-survivors. Overall, the primary THA group performed better compared with the osteosynthesis group concerning weight change over time, locomotion and pain. This study also showed that primary THA could safely be performed in the elderly without an increased postoperative mortality rate.
5.	Bergman, Annika, et al. (författare) A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques 2005 Ingår i: Familial Cancer. - : Springer. - 1389-9600 .- 1573-7292. ; 4:2, s. 89-96 Tidskriftsartikel (refereegranskat)abstract Dominant inheritance is presumed in 6-10% of breast and ovarian cancers. Mutations in BRCA1 and BRCA2 genes are the most commonly identified causative genes in such families. The frequency of mutation carriers with breast/ovarian cancer depends on the population studied, and display considerable variation that coincides with ethnic and geographical diversity. Mutation analyses were performed in 143 families registered at the Cancer Genetic Counseling Clinic of western Sweden. In a thorough mutation screening procedure, the entire BRCA1 and BRCA2 genes were analyzed using a combination of complementary mutation detection techniques. Mutations in either BRCA1 or BRCA2 were detected in 36% (52 out of 143) of all screened families. All families were clinically evaluated regarding age at diagnosis, type of cancer and number of cancer cases in the family. Among high-risk families, the mutation detection rate was 39% (46 out of 117). The detection rate observed among families with cases of ovarian cancer (42 out of 62, 68%), was substantially higher than in families with only breast cancer (10 out of 81, 12%). Age at ovarian cancer did not seem to have an effect on the detection rate. The analyses revealed 11 frameshift mutations, 4 nonsense mutations and 2 large deletions. Notably, the BRCA1 c.3171ins5 mutation accounted for 34 of 52 (65%) identified mutations. Seven mutations are novel: BRCA1c.409_410del; c.1912T>G; c.2228_2229del; c.3029delA; c.3433delA, a large deletion covering exons 1-3 of BRCA1and one BRCA2 mutation; BRCA2c.6287_6290del. We have shown that the founder mutation BRCA1 c.3171ins5 has a great influence on western Swedish breast/ovarian cancer families along with a high number of mutations unique for the region. In order to achieve a high mutation detection rate we suggest a combination of several detection techniques.
6.	Birzniece, Vita, et al. (författare) Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems. 2006 Ingår i: Brain Research Reviews. - : Elsevier BV. - 0165-0173 .- 1872-6321. ; 51:2, s. 212-239 Tidskriftsartikel (refereegranskat)
7.	Bjursell, Cecilia, 1971, et al. (författare) PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families. 2000 Ingår i: Human mutation. - 1098-1004 .- 1059-7794. ; 16:5, s. 395-400 Tidskriftsartikel (refereegranskat)abstract Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.
8.	Burström, Lage, et al. (författare) Musculoskeletal symptoms and exposure to whole-body vibration among open-pit mine workers in the arctic 2017 Ingår i: International Journal of Occupational Medicine and Environmental Health. - : Nofer Institute of Occupational Medicine. - 1232-1087 .- 1896-494X. ; 30:4, s. 553-564 Tidskriftsartikel (refereegranskat)abstract Objectives: This cross-sectional questionnaire study was carried out at 4 open-pit mines in Finland, Norway, Russia and Sweden as part of the MineHealth project. The aim has been to compare the prevalence of musculoskeletal symptoms between drivers of mining vehicles and non-drivers. Material and Methods: The mine workers were asked whether they had suffered from any musculoskeletal symptoms during the previous 12 months in specified body regions, and to grade the severity of these symptoms during the past month. They were also asked about their daily driving of mining vehicles. Results: The questionnaire was completed by 1323 workers (757 vehicle drivers) and the reported prevalence and severity of symptoms were highest for the lower back, followed by pain in the neck, shoulder and upper back. Drivers in the Nordic mines reported fewer symptoms than non-drivers, while for Russian mine workers the results were the opposite of that. The daily driving of mining vehicles had no significant association with the risk of symptoms. Female drivers indicated a higher prevalence of symptoms as compared to male drivers. Conclusions: The study provided only weak support for the hypothesis that drivers of vehicles reported a higher prevalence of musculoskeletal symptoms than non-vehicle drivers. There were marked differences in the prevalence of symptoms among workers in various enterprises, even though the nature of the job tasks was similar.
9.	Bäckström, Torbjörn, 1948-, et al. (författare) Pathogenesis in menstrual cycle-linked CNS disorders. 2003 Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 1007, s. 42-53 Forskningsöversikt (övrigt vetenskapligt/konstnärligt)
10.	Cutts, Briony, 1976, et al. (författare) Nf1 deficiency cooperates with oncogenic K-RAS to induce acute myeloid leukemia in mice. 2009 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:17, s. 3629-32 Tidskriftsartikel (refereegranskat)abstract Hyperactive RAS signaling is caused by mutations in RAS genes or a deficiency of the neurofibromatosis gene (NF1) and is common in myeloid malignancies. In mice, expression of oncogenic K-RAS or inactivation of Nf1 in hematopoietic cells results in myeloproliferative disorders (MPDs) that do not progress to acute myeloid leukemia (AML). Because NF1 is a RAS-GTPase-activating protein it has been proposed that NF1 deficiency is functionally equivalent to an oncogenic RAS. It is not clear, however, whether Nf1 deficiency would be redundant in K-RAS-induced MPD development or whether the 2 mutations would cooperate in leukemogenesis. Here, we show that the simultaneous inactivation of Nf1 and expression of K-RAS(G12D) in mouse hematopoietic cells results in AML that was fatal in primary mice within 4 weeks and transplantable to sublethally irradiated secondary recipients. The data point to a strong cooperation between Nf1 deficiency and oncogenic K-RAS.
11.	Einbeigi, Zakaria, 1962, et al. (författare) Occurrence of both breast and ovarian cancer in a woman is a marker for the BRCA gene mutations: a population-based study from western Sweden. 2007 Ingår i: Familial cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 6:1, s. 35-41 Tidskriftsartikel (refereegranskat)abstract AIM: This study aimed to analyze whether the occurrence of both breast and ovarian cancer in a woman serves as a marker for BRCA gene mutations. MATERIAL AND METHODS: This population-based study included 256 women in western Sweden who developed both invasive breast and ovarian tumors between 1958 and 1999. Archival paraffin tissue blocks of their tumors were retrieved for DNA-extraction to analyze the founder mutation, BRCA1 c.3171_3175dup (c.3171ins5), which is most common in this geographic area and four other common Scandinavian BRCA1 gene mutations and one BRCA2 mutation. Together, account these mutations for approximately 75% of the BRCA1/2 gene mutations in the clinical unit. RESULTS: Ninteen percent (95% confidence interval (CI) 14-24%) of the women carried one of the analyzed BRCA1 gene mutations but none of the women were positive for the analyzed BRCA2 mutation. One-third of the women with both tumors before age 60 were mutation carriers. BRCA1 c.3171_3175dup (c.3171ins5) constituted 84% of all identified mutations. Although the majority of breast cancers were invasive ductal and atypical medullary types, a variety of other breast malignancies were seen among mutation carriers. Serous ovarian carcinomas predominated among ovarian tumors. A variety of other ovarian tumors, including three granulosa-theca cell tumors, were also observed among mutation carriers. CONCLUSIONS: The occurrence of both breast and ovarian cancer in a woman is associated with a high likelihood of a constitutional BRCA1 mutation. These women and their families might therefore be considered for mutation screening after appropriate genetic counselling.
12.	Eliasson, Ann-Christin, 1950-, et al. (författare) Mini-MACS : development of the Manual Ability Classification System for children younger than 4 years of age with signs of cerebral palsy 2017 Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 59:1, s. 72-78 Tidskriftsartikel (refereegranskat)abstract AIM: To develop the Mini-Manual Ability Classification System (Mini-MACS) and to evaluate the extent to which its ratings are valid and reliable when children younger than 4 years are rated by their parents and therapists.METHOD: The Mini-MACS was created by making adjustments to the MACS. The development involved a pilot project, consensus discussions within an expert group, and the creation of a test version of the Mini-MACS that was evaluated for content validity and interrater reliability. A convenience sample of 61 children with signs of cerebral palsy aged 12 to 51 months (mean age 30.2mo [SD 10.1]) were classified by one parent and two occupational therapists across a total of 64 assessments. Agreement between the parents' and therapists' ratings was evaluated using the intraclass correlation coefficient (ICC) and the percentage of agreement.RESULTS: The first sentence of the five levels in the MACS was kept, but other descriptions within the Mini-MACS were adjusted to be more relevant for the younger age group. The ICC between parents and therapists was 0.90 (95% confidence interval [CI] 0.79-0.92), and for the two therapists it was 0.97 (95% CI 0.78-0.92). Most parents and therapists found the descriptions in the Mini-MACS suitable and easy to understand.INTERPRETATION: The Mini-MACS seems applicable for children from 1 to 4 years of age.
13.	Ericsson, Pernilla, et al. (författare) Reliability testing of two ergonomic risk assessment tools 2012 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract INTRODUCTIONQuick Exposure Check (QEC¹) and Rapid Upper Limb Assessment (RULA²) are two ergonomic risk assessment tools that have been designed to be useful for ergonomists assessing musculoskeletal risk factors in upper extremities at workplaces.AIMThe aim was to describe the variation between and within ergonomists assessments using QEC and RULA, and to compare the two tools regarding within-observer agreement.SUBJECTS & METHODSTwenty ergonomists observed five different work tasks twice with three weeks in between, watching video clips. They made ergonomic risk assessments using both QEC and RULA.The observed work tasks were: Window replacement, nailing a wooden pallet, toilet cleaning, instrumentation in an operating theatre, and sorting post.For the statistical analyses, percent agreement and kappa value was used.RESULTSThere was a variation in assessments between the ergonomists in all positions and movements both when using QEC and RULA, except from assessing armposition when observing window replacement using QEC, where all ergonomists assessed the same position (figure 1).The ergonomists had higher percent agreement between observation one and two using QEC compared with RULA (table 1).CONCLUSIONThere was a variation when assessing positions and movements in different worktasks both between ergonomists and within the same ergonomist using both QEC and RULA. However the agreement between two observations within observers was higher for QEC.
14.	Eriksson, Hans-G., et al. (författare) Sickness absence and self-reported health a population-based study of 43,600 individuals in central Sweden 2008 Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 8, s. 426- Tidskriftsartikel (refereegranskat)abstract BACKGROUNDSickness absence is very high in Sweden. The reasons for this phenomenon are not well known. The aim of this study was to investigate the association between degree of self-reported sickness absence and health. The hypothesis was that individuals with long-term sickness absence would report more symptoms and lower self-rated health. Another hypothesis was that women are more likely to self-rate psychiatric diagnoses compared to men, who are more likely to self-rate musculoskeletal diagnoses.METHODSThe data was obtained with a postal survey questionnaire answered by 43,589 individuals, a Swedish random population sample of men and women aged 18-84 years. The response rate was 65%. This study included 19,826 individuals aged 18-64 years old and still at work. They were divided into four groups, based on the number of reported days of sickness absence during the past year.RESULTSApproximately 40% of the individuals at work mentioned that they had been absent due to illness sometime during the past year. Of those who had been absent 90 days or more, two thirds were women. There was a significant difference between the groups in self-rated health (p < 0.05). Every fifth woman (19.4%) and every fourth man (25.9%) in the group with a sickness absence of more than 89 days rated their health as poor or very poor, but a large proportion, 43.5% of the women and 31.6% of the men, rated their health as good. Long-term illnesses and complaints differed between the groups. The correlations between the groups and illness were mostly significant (p < 0.01). Two thirds of the subjects had both psychiatric and musculoskeletal symptoms. There was a significant difference among them, as men more often had musculoskeletal diagnoses. One third had only psychiatric or musculoskeletal symptoms and in those groups there were no significant diagnosis differences between the sexes.CONCLUSIONIndividuals with long-term sickness absence reported more symptoms and lower self-rated health than did those who had not been absent at all, and than those who had been ill 1-28 days. Men and women sick-listed 29 days or more generally reported more illness and complaints. No sex differences among psychiatric and musculoskeletal diagnoses were found, but when reported both psychiatric and musculoskeletal symptoms the musculoskeletal diagnoses were significant among men.
15.	Ghalebani, Leila, et al. (författare) pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-beta peptide 2012 Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 421:3, s. 554-560 Tidskriftsartikel (refereegranskat)abstract Metal ions like Cu(II) and Zn(II) are accumulated in Alzheimer's disease amyloid plaques. The amyloid-beta (A beta) peptide involved in the disease interacts with these metal ions at neutral pH via ligands provided by the N-terminal histidines and the N-terminus. The present study uses high-resolution NMR spectroscopy to monitor the residue-specific interactions of Cu(II) and Zn(II) with N-15- and C-13,N-15-labeled A beta(1-40) peptides at varying pH levels. At pH 7.4 both ions bind to the specific ligands, competing with one another. At pH 5.5 Cu(II) retains its specific histidine ligands, while Zn(II) seems to lack residue-specific interactions. The low pH mimics acidosis which is linked to inflammatory processes in vivo. The results suggest that the cell toxic effects of redox active Cu(II) binding to AD may be reversed by the protective activity of non-redox active Zn(II) binding to the same major binding site under non-acidic conditions. Under acidic conditions, the protective effect of Zn(II) may be decreased or changed, since Zn(II) is less able to compete with Cu(II) for the specific binding site on the AD peptide under these conditions.
16.	Ghalebani, Leila, et al. (författare) pH dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid β peptide Annan publikation (övrigt vetenskapligt/konstnärligt)
17.	Gotcheva, Nadezhda, et al. (författare) Managing safety culture in design activities: evidence from the Nordic nuclear power domain 2014 Ingår i: 7th international conference of WOS.net (Workingonsafety.net), Glasgow, Scotland, UK, Sept 30-Oct 3, 2014. Konferensbidrag (refereegranskat)abstract The importance of safe and functional design is growing with the new nuclear builds across the globe. The existing literature on design emphasises the typical tensions of design activity but pays little attention to their relation to safety. The functional requirements can be met in many different ways, some safer than others. This conceptual paper aims at understanding how designers as humans affect safety in the nuclear industry. Rather than merely evaluating the quality of the design outcome, we argue for the need to study design processes from organizational perspective as they pose a variety of nuclear safety implications. We carried out a follow up study and content analysis of interview data with designers in the Nordic nuclear domain to shed more light on the specific cultural features, assumptions and norms that guide designers’ work processes. These cultural assumptions seem to be well in line with the six safety culture criteria of the DISC model. Managing the overall design project and understanding the big picture is seen as one of the main issues as the networked aspects of the design work are gradually acknowledged. This paper provides new insights on managing overall system safety and thus safety culture in design, suggesting that organizational culture can be systematically affected by management and organizational solutions.
18.	Gotchevaa, Nadezhda, et al. (författare) Cultural features of design and shared learning for safety: A Nordic nuclear industry perspective 2016 Ingår i: Safety Science. - : Elsevier BV. - 0925-7535 .- 1879-1042. ; 81, s. 90-98 Tidskriftsartikel (refereegranskat)abstract Safe and functional nuclear industry design is a topic of growing interest due to new builds and modernization projects in the operating nuclear power plants. Provided that good design of components and systems is critical for safe operation of the plants, understanding what influences the process of learning for safety in design activities is of utmost importance. The existing literature emphasizes tensions of design activity but pays insufficient attention to the culture of design and its relation to safety and learning. This paper aims at identifying cultural features of design organizations, such as shared conceptions, assumptions, norms, beliefs, and exploring their influence on the process of shared learning for safety. Case studies were carried out in Finland and Sweden to generate insights on cultural characteristics of design in the nuclear domain. The paper indicates the importance of requirements as a media for sharing knowledge and learning in nuclear industry design projects. As the networked aspects of the design work are gradually acknowledged, the need to learn how to systematically manage the requirements and understand the big picture of the overall design project are highlighted.
19.	Jussila, Kirsi, et al. (författare) Thermal comfort sustained by cold protective clothing in Arctic open-pit mining : a thermal manikin and questionnaire study 2017 Ingår i: Industrial Health. - : National Institute of Occupational Safety and Health. - 0019-8366 .- 1880-8026. ; 55:6, s. 537-548 Tidskriftsartikel (refereegranskat)abstract Workers in the Arctic open-pit mines are exposed to harsh weather conditions. Employers are required to provide protective clothing for workers. This can be the outer layer, but sometimes also inner or middle layers are provided. This study aimed to determine how the Arctic open-pit miners protect themselves against cold and the sufficiency, and the selection criteria of the garments. Workers' cold experiences and the clothing in four Arctic open-pit mines in Finland, Sweden, Norway and Russia were evaluated by a questionnaire (n=1323). Basic thermal insulation (Icl) of the reported clothing was estimated (ISO 9920). The Icl of clothing from the mines were also measured by thermal manikin (standing/walking) in 0.3 and 4.0 m/s wind. The questionnaire showed that the Icl of the selected clothing was on average 1.2 and 1.5 clo in mild (-5 to +5°C) and dry cold (-20 to -10°C) conditions, respectively. The Icl of the clothing measured by thermal manikin was 1.9w2.3 clo. The results show that the Arctic open-pit miners' selected their clothing based on occupational (time outdoors), environmental (temperature, wind, moisture) and individual factors (cold sensitivity, general health). However, the selected clothing was not sufficient to prevent cooling completely at ambient temperatures below -10°C.
20.	Kecklund, Göran, et al. (författare) Sleepiness and the risk of car crash : a case-control study 2012 Ingår i: Journal of Sleep Research. - Hoboken, NJ : Wiley-Blackwell. - 0962-1105 .- 1365-2869. ; 21, s. 307-307 Tidskriftsartikel (refereegranskat)
21.	Kecklund, Göran, et al. (författare) Sleepiness and the risk of car crash : a case control study 2011 Rapport (övrigt vetenskapligt/konstnärligt)abstract Driver sleepiness is believed to be a strong contributing factor to road traffic crashes. Acute sleepiness risk factors, such as driving during early morning hours or having insufficient sleep, was observed in 15% to 25% of the car crash injuries in New Zealand. Most studies are observational and describe the information about the crashes, whereas controlled studies are rare. One exception is the study by Connor et al. (2002), which used a case-control design and compared 571 car drivers involved in crashes (in which at least one driver was admitted to hospital or killed - "cases") with 588 representative drivers (controls) recruited while driving on public roads. The results showed a strong association between indicators of acute sleepiness and the risk of an injury crash, whereas measures of chronic sleepiness showed no association with injury risk. The aim of the present study was to carry out a similar study in Sweden and examine the relationship between acute and chronic sleepiness characteristics, including disturbed sleep and other factors that may contribute to driver sleepiness, with the risk of crashes in which the driver was admitted to hospital.
22.	Kovatcheva-Datchary, Petia, et al. (författare) Simplified Intestinal Microbiota to Study Microbe-Diet-Host Interactions in a Mouse Model 2019 Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 26:13 Tidskriftsartikel (refereegranskat)abstract The gut microbiota can modulate human metabolism through interactions with macronutrients. However, microbiota-diet-host interactions are difficult to study because bacteria interact in complex food webs in concert with the host, and many of the bacteria are not yet characterized. To reduce the complexity, we colonize mice with a simplified intestinal microbiota (SIM) composed of ten sequenced strains isolated from the human gut with complementing pathways to metabolize dietary fibers. We feed the SIM mice one of three diets (chow [fiber rich], high-fat/high-sucrose, or zero-fat/high-sucrose diets [both low in fiber]) and investigate (1) how dietary fiber, saturated fat, and sucrose affect the abundance and transcriptome of the SIM community, (2) the effect of microbe-diet interactions on circulating metabolites, and (3) how microbiota-diet interactions affect host metabolism. Our SIM model can be used in future studies to help clarify how microbiota-diet interactions contribute to metabolic diseases.
23.	Lendel, Christofer, et al. (författare) Detergent-like interaction of Congo red with the amyloid beta peptide 2010 Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 49:7, s. 1358-1360 Tidskriftsartikel (refereegranskat)abstract Accumulating evidence links prefibrillar oligomeric species of the amyloid beta peptide (Abeta) to cellular toxicity in Alzheimer's disease, potentially via disruption of biological membranes. Congo red (CR) affects protein aggregation. It is known to self-associate into micelle-like assemblies but still reduces the toxicity of Abeta aggregates in cell cultures and model organisms. We show here that CR interacts with Abeta(1-40) in a manner similar to that of anionic detergents. Although CR promotes beta sheet formation and peptide aggregation, it may also solubilize toxic protein species, making them less harmful to critical cellular components and thereby reducing amyloid toxicity.
24.	Lind, Jacob, et al. (författare) Jakt på papperslösa gör oss till en polisstat 2016 Ingår i: Svenska Dagbladet. - : Svenska Dagbladet. - 1101-2412. ; :2016-10-04 Tidskriftsartikel (populärvet., debatt m.m.)abstract Regeringen föreslår nio åtgärder för att hitta och utvisa papperslösa. Det kommer att slå hårt och främst gå ut över redan svaga och jagade människor. Vi uppmanar därför regeringen att ta tillbaka åtgärderna, skriver 43 forskare.
25.	Lindegård, A., et al. (författare) Can biofeedback training in combination with ergonomic information reduce pain among young adult computer users with neck and upper extremity symptoms? : A randomized controlled intervention study 2024 Ingår i: Applied Ergonomics. - : Elsevier. - 0003-6870 .- 1872-9126. ; 114 Tidskriftsartikel (refereegranskat)abstract The aim of this randomized controlled study was to explore if an intervention with biofeedback training in combination with ergonomic discussions, could improve working technique and work postures, and reduce pain intensity and perceived exertion in young adult computer users with ongoing neck and upper extremity symptoms. 39 participants were divided into an intervention group and a control group. The intervention consisted of 4 sessions during a three-month period. Working technique, working postures, rated perceived exertion, pain intensity, and duration of computer use were measured at baseline and follow ups after 6 and 12 months. The intervention did not significantly improve working technique and working postures, nor reduce pain intensity and perceived exertion in the intervention group compared to the control group. However, there was a statistically significant reduction in reported pain intensity in the neck/shoulder for the whole group. Also, there was a trend that time spent with computer work without breaks was more reduced in the intervention group than in the control group.
26.	Lindgren, Joel, et al. (författare) N-terminal engineering of amyloid-β-binding Affibody molecules yields improved chemical synthesis and higher binding affinity 2010 Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2319-2329 Tidskriftsartikel (refereegranskat)abstract The aggregation of amyloid-beta (A beta) peptides is believed to be a major factor in the onset and progression of Alzheimer's disease Molecules binding with high affinity and selectivity to A beta-peptides are important tools for investigating the aggregation process An A beta-binding Affibody molecule, Z(A beta 3), has earlier been selected by phage display and shown to bind A beta(1-40) with nanomolar affinity and to inhibit A beta-peptide aggregation In this study, we create truncated functional versions of the Z(A beta 3) Affibody molecule better suited for chemical synthesis production Engineered Affibody molecules of different length were produced by solid phase peptide synthesis and allowed to form covalently linked homodimers by S-S-bridges The N-terminally truncated Affibody molecules Z(A beta 3)(12-58), Z(A beta 3)(15-58), and Z(A beta 3)(18-58) were produced in considerably higher synthetic yield than the corresponding full-length molecule Z(A beta 3)(1-58) Circular dichroism spectroscopy and surface plasmon resonance-based biosensor analysis showed that the shortest Affibody molecule, Z(A beta 3)(18-58), exhibited complete loss of binding to the A beta(1-40)-peptide, while the Z(A beta 3)(12-58) and Z(A beta 3)(15-58) Affibody molecules both displayed approximately one order of magnitude higher binding affinity to the A beta(1-40)-peptide compared to the full-length Affibody molecule Nuclear magnetic resonance spectroscopy showed that the structure of A beta(1-40) in complex with the truncated Affibody dimers is very similar to the previously published solution structure of the A beta(1-40)-peptide in complex with the full-length Z(A beta 3) Affibody molecule This indicates that the N-terminally truncated Affibody molecules Z(A beta 3)(12-58) and Z(A beta 3)(15-58) are highly promising for further engineering and future use as binding agents to monomeric A beta(1-40)
27.	Lindgren, Stig-Åke, 1950, et al. (författare) Coverage-dependent frequency for Li-atom vibrations on Cu(111) 1996 Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 54:15, s. 10912 - 10916 Tidskriftsartikel (refereegranskat)abstract Electron-energy-loss spectra recorded for monolayer amounts of Li adsorbed on Cu(111) show a loss peak associated with Li vibrations perpendicular to the substrate. The loss energy shifts from 38 meV at low coverage to 43 meV at 0.3 ML and remains constant for coverages between 0.3 and 0.5 ML. The loss intensity passes a maximum at a Li coverage of 0.15 ML and gradually decreases such that it is difficult to resolve a loss peak at coverages above 0.5 ML. The high loss energy indicates that the adatom resides on the surfaces rather than in substitutional sites. The frequency shift is much too large to be explained by dipole-dipole interactions. The above results are obtained with the evaporation source loaded with the natural Li isotope mixture (92.6% 7Li, 7.4% 6Li). Measurements with 6Li show that the increase of the vibration frequency with increasing coverage is not an isotope effect.
28.	Lindkvist, Anna, et al. (författare) Hypoxia mediated up-regulation of telomerase activity in neuroblastoma cell lines Annan publikation (övrigt vetenskapligt/konstnärligt)
29.	Liu, Meng, 1976, et al. (författare) Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer 2010 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476 Tidskriftsartikel (refereegranskat)abstract RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
30.	Luigi, Macchi, et al. (författare) Improving design processes in the nuclear domain–Insights on organisational challenges from safety culture and resilience engineering perspectives 2014 Ingår i: NKS (Nordic Nuclear Safety Research) Article Series. ; NKS-301 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Design flaws have been contributing to major industrial accidents. However, design activities are understudied in human and organisational factors studies. In the nuclear power domain, both pre-operational design and design of modifications depend on a network of organizations, and aim at developing solutions which meet different criteria. Nuclear power companies often outsource the design work to organisations, which might not be hitherto familiar with the safety requirements of nuclear industry. The final phase of SADE project focused on testing and evaluating the results of the first two phases through in depth analysis of case studies conducted in Finland and Sweden. The study aimed at providing insights on the inter-organizational challenges related to design activities, which could potentially affect safety of the Nordic nuclear power plants. In 2013 we carried out 14 semi-structured interviews with representatives of power plant organisations, design organisations and regulators. Interviews of the Finnish case studies were complemented by one group interview each. The study indicated that design-related challenges in the nuclear domain are mainly inter-organizational. This implies that safety management and safety culture approaches should take better into account the inter-organisational nature of work processes. For some of the challenges (e.g. coordination) many coping practices exist throughout the network, whereas for others (e.g. shared understanding) just a few were mentioned. This signifies that design organisations have learned the consequences of insufficient coordination in previous projects, while reaching a shared understanding proves to be challenging. The design process involves both rational and creative approaches to deal with real-life problems. In nuclear industry, designers face the need to balance between fulfilling requirements and doing an extensive amount of paperwork, and creating new, safe and functional solutions. To better manage safety culture in design activities in a networked context, nuclear power companies and design supply chains need to reach a shared understanding on achieving this balance. Finally, the study provides a set of recommendations to support and improve the design process and to help anticipate emerging risks in the nuclear industry.
31.	Lyu, Yezhe, 1987-, et al. (författare) Recycling of worn out brake pads impact on tribology and environment 2020 Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1 Tidskriftsartikel (refereegranskat)abstract Disc brake systems are widely used on commercial vehicles for braking. The brake pads are usually replaced by new ones before being totally worn out. Current methods to deal with the replaced brake pads include landfill and combustion, resulting in a huge waste of resources and increase of CO2 footprint. From a sustainable point of view, this study aims to evaluate the feasibility of recycling replaced brake pads by addressing a protocol recycling procedure. The results show that the recycled brake pads yield similar friction, wear and airborne particle emission to virgin brake pads. A streamlined life cycle assessment is conducted to compare the environmental impacts between producing virgin brake pads and recycling replaced brake pads. Energy consumption and CO2 footprint of the recycled brake pads are 36% and 34% less than virgin brake pads, indicating that recycling could be a promising method of handling replaced brake pads.
32.	Löfgren, Kajsa, et al. (författare) Antiprion properties of prion protein-derived cell-penetrating peptides 2008 Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 22:7, s. 2177-2184 Tidskriftsartikel (refereegranskat)abstract In prion diseases, the cellular prion protein (PrPC) becomes misfolded into the pathogenic scrapie isoform (PrPSc) responsible for prion infectivity. We show here that peptides derived from the prion protein N terminus have potent antiprion effects. These peptides are composed of a hydrophobic sequence followed by a basic segment. They are known to have cell-penetrating ability like regular cell-penetrating peptides (CPPs), short peptides that can penetrate cellular membranes. Healthy (GT1–1) and scrapie-infected (ScGT1–1) mouse neuronal hypothalamic cells were treated with various CPPs, including the prion protein-derived CPPs. Lysates were analyzed for altered protein levels of PrPC or PrPSc. Treatment with the prion protein-derived CPPs mouse mPrP1–28 or bovine bPrP1–30 significantly reduced PrPSc levels in prion-infected cells but had no effect on PrPC levels in noninfected cells. Further, presence of prion protein-derived CPPs significantly prolonged the time before infection was manifested when infecting GT1–1 cells with scrapie. Treatment with other CPPs (penetratin, transportan-10, or poly-L-arginine) or prion protein-derived peptides lacking CPP function (mPrP23–28, mPrP19–30, or mPrP23–50) had no effect on PrPSc levels. The results suggest a mechanism by which the signal sequence guides the prion protein-derived CPP into a cellular compartment, where the basic segment binds specifically to PrPSc and disables formation of prions.—Löfgren, K., Wahlström, A., Lundberg, P., Langel, U., Gräslund, A., and Bedecs, K. Antiprion properties of prion protein-derived cell-penetrating peptides.
33.	Löfman, Owe, 1945-, et al. (författare) Women with low-energy fracture should be investigated for osteoporosis 2007 Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 78:6, s. 813-821 Tidskriftsartikel (refereegranskat)abstract Introduction: Treatment of osteoporosis is becoming more effective, but methods to identify patients who are most suitable for investigation and treatment are still being debated. Should any type of fracture have higher priority for investigation of osteoporosis than any other? Is the number of previous fractures useful information? Material and methods: We investigated 303 consecutive women patients between 55 and 75 years of age who had a newly diagnosed low-energy fracture. They answered a questionnaire on previous fractures which also dealt with risk factors. Bone mineral density (BMD) was measured at the hip, lumbar spine, and forearm. Results: The distribution of fracture location was: distal forearm 56%, proximal humerus 12%, vertebra 18%, and hip 13%, all with similar age. Half of the subjects had had at least one previous fracture before the index fracture, 19% had had two previous fractures, and 6% had had three or more previous fractures. Patients with vertebral or hip fracture had lower BMD and had had more previous fractures than patients with forearm or humerus fractures. There was an inverse correlation between number of fractures and BMD. Osteoporosis was present in one-third of patients with forearm fracture, in one-half of those with hip or humerus fracture, and in two-thirds of those with vertebral fracture. Interpretation: Vertebral fractures were the strongest marker of low BMD and forearm fractures the weakest. The number of previous fractures is helpful information for finding the most osteoporotic patient in terms of severity. Investigation of osteoporosis therefore seems warranted in every woman between the ages of 55 and 75 with a recent low-energy fracture, with highest priority being given to those with vertebral, hip, or multiple fractures. Copyright© Taylor & Francis 2007. all rights reserved.
34.	Ma, Jijie, et al. (författare) A Comparison of Airborne Particles Generated from Disk Brake Contacts : Induction Versus Frictional Heating 2020 Ingår i: Tribology letters. - : SPRINGER/PLENUM PUBLISHERS. - 1023-8883 .- 1573-2711. ; 68:1 Tidskriftsartikel (refereegranskat)abstract Volatile emissions of vehicle brakes relate to the high temperature of the brake friction pair. However, as a passive parameter of braking applications, temperature is usually studied together with other parameters such as sliding speed and load. Heating tests that increase the friction pair temperature with an induction heater instead of friction are proposed in this study to imitate the rise in temperature in friction tests. Non-friction airborne particles produced solely by the high temperature in heating tests were studied in comparison with friction tests. The results confirmed the existence of non-friction airborne particles and they can represent about 4.5% of the total airborne particles in friction tests. The high-temperature behaviour as well as the composition of the non-friction airborne particles is also presented.
35.	Ma, Jijie, et al. (författare) ECO DESIGN OF BRAKE PADS WITH RECYCLED FRICTION MATERIALS 2019 Konferensbidrag (refereegranskat)
36.	Narratives of Motherhood and Mothering in Fiction and Life Writing 2023 Samlingsverk (redaktörskap) (refereegranskat)abstract This open access volume offers original essays on how motherhood and mothering are represented in contemporary fiction and life writing across several national contexts. Providing a broad range of perspectives in terms of geopolitical places, thematic concerns, and theoretical and interdisciplinary approaches, it demonstrates the significance of literary narratives for understanding and critiquing motherhood and mothering as social phenomena and subjective experiences. The chapters contextualize motherhood and mothering in terms of their particular national and cultural location and analyze narratives about mothers who are firmly placed in one national context, as well as those who are in “in-between” positions due to migrant experiences. The contributions foreground and link together the themes central to the volume: embodied experience and maternal embodiment; notions of what is “normal” or natural (or not) about motherhood; maternal health and illness; mother-daughter relations; maternality and memory; and the (im)possibilities of giving voice to the mother. They raise questions about how motherhood and mothering are marked by absence and/or presence, as well as by profound ambivalences.
37.	Norman, Mikael, et al. (författare) The Swedish Neonatal Quality Register - contents, completeness and validity 2019 Ingår i: Acta Paediatrica. - : WILEY. - 0803-5253 .- 1651-2227. ; 108:8, s. 1411-1418 Tidskriftsartikel (refereegranskat)abstract Aim: To describe the Swedish Neonatal Quality Register (SNQ) and to determine its completeness and agreement with other registers.Methods: SNQ collects data for infants admitted to neonatal units during the first four postnatal weeks. Completeness and registers' agreement were determined cross-linking SNQ data with Swedish population registers (the Inpatient, Medical Birth and Cause of Death Registers) for a study period of five years.Results: In total, 84 712 infants were hospitalised. A total of 52 806 infants occurred in both SNQ and the population registers; 28 692 were only found in the population registers, and 3214 infants were only found in SNQ. Between gestational weeks 24-34, completeness of SNQ was 98-99%. Below and above these gestational ages, completeness was lower. Infants missing in SNQ were term or near-term in 99% of the cases, and their diagnoses indicated conditions managed in maternity units, or re-admissions for acute infections, managed in paediatric units. For most diagnoses, the agreement between SNQ and population registers was high, but some (bronchopulmonary dysplasia and grade of hypoxic-ischaemic encephalopathy) were often missing in the population registers.Conclusion: SNQ completeness and agreement against other registers, especially for preterm infants, is excellent. SNQ is a valid tool for benchmarking, quality improvement and research.
38.	Olofsson, Ulf, 1962-, et al. (författare) Laser Cladding Treatment for Refurbishing Disc Brake Rotors : Environmental and Tribological Analysis 2021 Ingår i: Tribology letters. - New York : Springer Nature. - 1023-8883 .- 1573-2711. ; 69:2 Tidskriftsartikel (refereegranskat)abstract In this study, grey cast iron disc brake rotors are refurbished by adding a surface layer through laser cladding. Current methods to deal with replaced rotors mainly include remelting, with a minority fraction disposed in landfill. Both approaches result in a huge waste of resources and an increase in CO2 footprint. From a sustainable point of view, this study aims to evaluate the feasibility of refurbishing brake rotors by a combined environmental and tribological performance approach. A streamlined life cycle assessment is conducted to compare the environmental impacts between producing virgin grey cast iron brake rotors and refurbishing replaced brake rotors by laser cladding. It turns out that the energy consumption and CO2 footprint of the laser cladding refurbished brake rotors are 80% and 90% less than the virgin brake rotors. The results show that the refurbished brake rotor yields higher friction compared to the original cast iron utilizing the same pad material. The wear and particle emissions of the disc brake contact are in this study higher for the laser-cladded one compared to the original cast iron one.
39.	Perez-Karlsson, Åsa, 1970- (författare) Meeting the other and oneself : experience and learning in international, upper secondary sojourns 2014 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The aim of the study was to investigate into and characterise students’ experiences of learning from their having taken part in an international upper secondary exchange in an intercultural context. Focusing on educational and intercultural dimensions, the thesis contributes knowledge of the implications of increasing internationalization and student mobility in education. The study builds on audio-recorded qualitative, in-depth interviews with Swedes and Chileans who respectively sojourned in Chile and Sweden as upper secondary students. The analysis of the narratives draws on theories regarding qualification, socialization and subjectification - the three educational functions or processes identified by Biesta (2010) - and learning from experiences, particularly experiences of disjuncture leading to feelings of disturbed harmony and experiences from encounters and engagement with others (Jarvis, 2009; Biesta, 2010; Hansen, 2011). As extracurricular activities with 'recreational' elements, upper secondary sojourns are often not taken into account by students' educational institutions. However, the results from this study show that sojourners experience transformative changes and extensive learning related to qualification, socialization and (particularly) subjectification. Furthermore, they perceive the as different, more holistic and complete than learning in other contexts. When leaving the familiarity and comfort in the home environment and engaging with the relative unfamiliarity of everyday activities in an international, intercultural the sojourners commonly confront perceived limitations and cross both physical (geographical) and conceptual boundaries. Such confrontations and crossing often lead to experiences of disjuncture and disturbed harmony. The complex processes of resolving difficulties, understanding and meaning making are sources to learning that infuse a sojourn with potential to foster learning as a 'bildungsreise’. There are notable potentials for transformations of sojourners' views of both the other and themselves, involving increases in self-confidence, personal growth, connectedness and feelings of being qualified, capable and empowered, which promote synergistic developments in all three educational functions. Notably, the homestay, communicative situations and interpersonal interactions provide such situations of potent learning opportunities that boost personal growth. In sojourners' engagement and interest in the other, and willingness to consider other perspectives and modify one’s own there are apparent potentials for further developments of an intercultural and cosmopolitan attitude and outlook. A major conclusion, based on the presented evidence, is that even short stays (potentially less costly than longer stays) provide extensive learning rooted in social and subjective transformations (in addition to their value for qualification per se) that may have benefits extending well beyond upper secondary school years. Furthermore, they may also have prolonged benefits for wider society through the enhanced understanding of others and other perspectives. Thus, they appear to have high educational value beyond recreational pleasure.
40.	Prytz, Ingela, et al. (författare) Fed-batch production of recombinant beta-galactosidase using the universal stress promoters uspA and uspB in high cell density cultivations. 2003 Ingår i: Biotechnology and bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 83:5, s. 595-603 Tidskriftsartikel (refereegranskat)abstract A high-level production system using the universal stress promoters uspA and uspB in a fed-batch cultivation based on minimal medium was designed. In development it was shown that a standard industrial fed-batch protocol could not be used for this purpose since it failed to induce the levels of product as compared to the basal level. Instead, a batch protocol followed by a low constant feed of glucose was shown to give full induction. The levels of the product protein, beta-galactosidase, corresponded to approximately 25% of the total protein. Higher levels were found using the uspA than uspB vectors where uspA showed considerably higher basal level. The data indicate that the sigma(70) regulated promoter, uspA, although affected by the alarmone guanosine tetraphosphate, ppGpp, worked partly in a similar manner to constitutive promoters. An industrial high cell density fed-batch cultivation on the basis of the suggested fed-batch protocol and the uspA promoter gave a final beta-galatosidase concentration of 7 g/L and a final cell concentration of 65 g/L. The heterogeneity in production of the individual cell was measured by fluorescence microscopy. The data show that there is a process time independent heterogeneity in production, which is suggested to be caused by heterogeneity in the substrate uptake rate of the individual cell.
41.	Richman, Michal, et al. (författare) In Vitro and Mechanistic Studies of an Antiamyloidogenic Self-Assembled Cyclic D,L-alpha-Peptide Architecture 2013 Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:9, s. 3474-3484 Tidskriftsartikel (refereegranskat)abstract Misfolding of the A beta protein and its subsequent aggregation into toxic oligomers are related to Alzheimer's disease. Although peptides of various sequences can self-assemble into amyloid structures, these structures share common three-dimensional features that may promote their cross-reaction. Given the significant similarities between amyloids and the architecture of self-assembled cyclic D,L-alpha-peptide, we hypothesized that the latter may bind and stabilize a nontoxic form of A beta thereby preventing its aggregation into toxic forms. By screening a focused library of six-residue cyclic D,L-alpha-peptides and optimizing the activity of a lead peptide, we found one cyclic D,L-alpha-peptide (CP-2) that interacts strongly with A beta and inhibits its aggregation. In transmission electron microscopy, optimized thioflavin T and cell survival assays, CP-2 inhibits the formation of A beta aggregates, entirely disassembles preformed aggregated and fibrillar A beta, and protects rat pheochromocytoma PC12 cells from A beta toxicity, without inducing any toxicity by itself. Using various immunoassays, circular dichroism spectroscopy, photoinduced cross-linking of unmodified proteins (PICUP) combined with SDS/PAGE, and NMR, we probed the mechanisms underlying CP-2's antiamyloidogenic activity. NMR spectroscopy indicates that CP-2 interacts with A beta through its self-assembled conformation and induces weak secondary structure in A beta. Upon coincubation, CP-2 changes the aggregation pathway of A beta and alters its oligomer distribution by stabilizing small oligomers (1-3 mers). Our results support studies suggesting that toxic early oligomeric states of A beta may be composed of antiparallel beta-peptide structures and that the interaction of A beta with CP-2 promotes formation of more benign parallel beta-structures. Further studies will show whether these kinds of abiotic cyclic D,L-alpha-peptides are also beneficial as an intervention in related in vivo models.
42.	Rohlin, Anna, et al. (författare) A mutation in POLE predisposing to a multi-tumour phenotype 2014 Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 45:1, s. 77-81 Tidskriftsartikel (refereegranskat)abstract Somatic mutations in the POLE gene encoding the catalytic subunit of DNA polymerase epsilon have been found in sporadic colorectal cancers (CRCs) and are most likely of importance in tumour development and/or progression. Recently, families with dominantly inherited colorectal adenomas and colorectal cancer were shown to have a causative heterozygous germline mutation in the proofreading exonuclease domain of POLE. The highly penetrant mutation was associated with predisposition to CRC only and no extra-colonic tumours were observed. We have identified a mutation in a large family in which the carriers not only developed CRC, they also demonstrate a highly penetrant predisposition to extra-intestinal tumours such as ovarian, endometrial and brain tumours. The mutation, NM_006231.2:c.1089C>A, p.Asn363Lys, also located in the proofreading exonuclease domain is directly involved in DNA binding. Theoretical prediction of the amino acid substitution suggests a profound effect of the substrate binding capability and a more severe impairment of the catalytic activity compared to the previously reported germline mutation. A possible genotype to phenotype correlation for deleterious mutations in POLE might exist that needs to be considered in the follow-up of mutation carriers.
43.	Sahamkhadam, Nasrin, et al. (författare) Testing the assumptions in the process of cultural competence in the delivery of healthcare services using empirical data, focusing on cultural awareness 2023 Ingår i: Journal of Transcultural Nursing. - : SAGE PUBLICATIONS INC. - 1043-6596 .- 1552-7832. Tidskriftsartikel (refereegranskat)abstract Introduction: Encounters with children of foreign origin call for school nurses' cultural competence during the health visits. This study aimed to investigate the statistical associations between the cultural constructs described by the Process of Cultural Competence in the Delivery of Healthcare Services (PCCDHS) model and whether school nurses' cultural encounters, cultural knowledge, and cultural skill could statistically predict their cultural awareness. Methodology: Spearman correlation and hierarchical regression analyses were conducted using cross-sectional secondary data from 816 Swedish school nurses. The cultural constructs in the theoretical description of the PCCDHS model guided the selection and sorting of the items on cultural competence. Results: The constructs of cultural knowledge, cultural skill, cultural encounters, and cultural awareness were positively correlated with each other. However, becoming culturally aware was not statistically predicted by included cultural constructs (R-2 = 13.4, p = .06). Discussion: Despite the interrelations between the investigated cultural constructs of the PCCDHS model, understanding cultural awareness development requires further empirical testing.
44.	Sjögren, Anna-Karin, 1980, et al. (författare) GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer 2007 Ingår i: J Clin Invest. - 0021-9738. ; 117:5, s. 1294-304 Tidskriftsartikel (refereegranskat)abstract Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
45.	Stjernbrandt, Albin, et al. (författare) Neurosensory and vascular symptoms and clinical findings in the hands of Arctic open-pit miners in Sweden and Norway : a descriptive study 2023 Ingår i: International Journal of Circumpolar Health. - : Taylor & Francis. - 1239-9736 .- 2242-3982. ; 82:1 Tidskriftsartikel (refereegranskat)abstract This cross-sectional study aimed to describe exposure to cold climate and hand-arm vibration (HAV) as well as neurosensory and vascular symptoms and clinical findings among open-pit Arctic miners. It was based on data from questionnaires and physical examinations, including 177 men and 75 women from two open-pit mines in Sweden and Norway (response rate 54%). Working outdoors or in an unheated building or machine for at least two hours per day was reported by 44% and HAV exposure of the same duration by 10%. Neurosensory symptoms (e.g. reduced perception of touch) in the hands were reported by 47% and Raynaud’s phenomenon by 14%. In brief conclusion, the study showed that Arctic miners were commonly exposed to both cold temperatures and HAV. They also reported a broad range of neurosensory and vascular symptoms in their hands and had abnormal clinical findings related to the symptoms. The results emphasise the need for additional preventive measures in this occupational setting.
46.	Stjernbrandt, Albin, et al. (författare) Raynaud's phenomenon in the feet of Arctic open-pit miners 2024 Ingår i: International Journal of Circumpolar Health. - : Taylor & Francis. - 1239-9736 .- 2242-3982. ; 83:1 Tidskriftsartikel (refereegranskat)abstract The literature on Raynaud's phenomenon (RP) in the feet is scarce, especially in the occupational setting. The primary aim of our study was to investigate the occurrence of RP in the feet of miners. As part of the MineHealth project, written surveys and clinical examinations were completed by 260 Arctic open-pit miners working in northern Sweden and Norway (participation rate 53.6%). Data on RP were collected using standardised colour charts and questionnaire items. Clinical examination included assessing the perception of vibration and pain in both feet. There were eight women and three men who reported RP in the feet. Four also had RP in their hands but none acknowledged any first-degree relatives with the condition. Nine reported exposure to foot-transmitted vibration and one to hand-arm vibration. Seven showed signs of neurosensory injury in the feet. To conclude, the occurrence of RP in the feet of miners was 4.4%. Most cases with RP in the feet did not report the condition in the hands and were exposed to vibration transmitted directly to the feet. There were no reports of a hereditary component. Most cases with RP in the feet also had clinical findings suggestive of peripheral neuropathy in the feet.
47.	Strålin, Kristoffer, et al. (författare) Mortality in hospitalized COVID-19 patients was associated with the COVID-19 admission rate during the first year of the pandemic in Sweden 2022 Ingår i: Infectious Diseases. - : Taylor & Francis Ltd. - 2374-4235 .- 2374-4243. ; 54:2, s. 145-151 Tidskriftsartikel (refereegranskat)abstract Introduction Studies from the first pandemic wave found associations between COVID-19 hospital load and mortality. Here, we aimed to study if mortality of hospitalized COVID-19 patients was associated with the COVID-19 admission rate during a full year of the pandemic in Sweden. Method Observational review of all patients admitted to hospital with COVID-19 in Sweden between March 2020 and February 2021 (n = 42,017). Primary outcome was 60-day all-cause mortality related to number of COVID-19 hospital admissions per month/100,000 inhabitants. Poisson regression was used to estimate the relative risk for death by month of admission, adjusting for pre-existing factors. Results The overall mortality was 17.4%. Excluding March 2020, mortality was clearly correlated to the number of COVID-19 admissions per month (coefficient of correlation rho=.96; p<.0001). After adjustment for pre-existing factors, the correlation remained significant (rho=.75, p=.02). Patients admitted in December (high admission rate and high mortality) had more comorbidities and longer hospital stays, and patients treated in intensive care units (ICU) had longer pre-ICU hospital stays and worse respiratory status on ICU admission than those admitted in July to September (low admission rate and low mortality). Conclusion Mortality in hospitalized COVID-19 patients was clearly associated with the COVID-19 admission rate. Admission of healthier patients between pandemic waves and delayed ICU care during wave peaks could contribute to this pattern. The study supports measures to flatten-the-curve to reduce the number of COVID-19 patients admitted to hospital.
48.	Strålin, Kristoffer, et al. (författare) Mortality trends among hospitalised COVID-19 patients in Sweden : A nationwide observational cohort study 2021 Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 4 Tidskriftsartikel (refereegranskat)abstract Background: It is important to know if mortality among hospitalised COVID-19 patients has changed as the pandemic has progressed. The aim of this study was to describe the dynamics over time of mortality among patients hospitalised for COVID-19 in Sweden, using nationwide data compiled by the Swedish National Board of Health and Welfare. Methods: Observational cohort study where all patients hospitalised in Sweden between March 1 and September 30, 2020, with SARS-CoV-2 RNA positivity 14 days before to 5 days after admission and a discharge code for COVID-19 were included. Outcome was 60-day all-cause mortality. Patients were categorised according to month of hospital admission. Poisson regression was used to estimate the relative risk of death by month of admission, adjusting for, age, sex, comorbidities, care dependency, country of birth, healthcare region, and Simplified Acute Physiology, version 3 (patients in intensive care units; ICU). Findings: A total of 17,140 patients were included, of which 2943 died within 60 days of admission. The overall 60-day mortality was thus 17.2% (95% CI, 16.6%-17.7%), and it decreased from 24.7% (95% CI, 23.0%-26.5%) in March to 10.4% (95% CI, 8.9%-12.1%) post-wave (July-September). Adjusted relative risk (RR) of death was 0.46 (95% CI, 0.39-0.54) post-wave, using March as reference. Corresponding RR for patients not admitted to ICU and those admitted to ICU were 0.49 (95% CI, 0.42-0.59) and 0.49 (95% CI, 0.33-0.72), respectively. The proportion of patients admitted to ICU decreased from 19.4% (95% CI, 17.9%-21.1%) in the March cohort to 8.9% (95% CI, 7.5%-10.6%) post-wave. Interpretation: There was a gradual decline in mortality during the spring of 2020 in Swedish hospitalised COVID-19 patients, independent of baseline patient characteristics. Future research is needed to explain the reasons for this decline. The changing COVID-19 mortality should be taken into account when management and results of studies from the first pandemic wave are evaluated. (C) 2021 The Authors. Published by Elsevier Ltd.
49.	Wahlström, Annika, 1975, et al. (författare) Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease. 2008 Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:4, s. 1357-65 Tidskriftsartikel (refereegranskat)abstract Hyperactive signaling through the RAS proteins is involved in the pathogenesis of many forms of cancer. The RAS proteins and many other intracellular signaling proteins are either farnesylated or geranylgeranylated at a carboxyl-terminal cysteine. That isoprenylcysteine is then carboxyl methylated by isoprenylcysteine carboxyl methyltransferase (ICMT). We previously showed that inactivation of Icmt mislocalizes the RAS proteins away from the plasma membrane and blocks RAS transformation of mouse fibroblasts, suggesting that ICMT could be a therapeutic target. However, nothing is known about the impact of inhibiting ICMT on the development of malignancies in vivo. In the current study, we tested the hypothesis that inactivation of Icmt would inhibit the development or progression of a K-RAS-induced myeloproliferative disease in mice. We found that inactivating Icmt reduced splenomegaly, the number of immature myeloid cells in peripheral blood, and tissue infiltration by myeloid cells. Moreover, in the absence of Icmt, the ability of K-RAS-expressing hematopoietic cells to form colonies in methylcellulose without exogenous growth factors was reduced dramatically. Finally, inactivating Icmt reduced lung tumor development and myeloproliferation phenotypes in a mouse model of K-RAS-induced cancer. We conclude that inactivation of Icmt ameliorates phenotypes of K-RAS-induced malignancies in vivo.
50.	Wahlström, Anna, 1982- (författare) NMR studies on interactions between the amyloid β peptide and selected molecules 2011 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Alzheimer’s disease is an incurable neurodegenerative disorder linked to the amyloid β (Aβ) peptide, a 38-43 residue peptide. The detailed molecular disease mechanism(s) is (are) unknown, but oligomeric Aβ structures are proposed to be involved. In common for the papers in this thesis is interactions; interactions between Aβ(1-40) and selected molecules and metal ions. The purpose has been to find out more about the structural states that Aβ can adopt, in particular the β-sheet state, which probably is linked to the oligomeric structures. The methods used have been nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence spectroscopy using Thioflavin T (ThT). Upon addition of SDS/LiDS detergent or Congo red (CR) to Aβ(1-40), the initial random coil/PII-helix state was transformed into β-sheet and, in the case of detergent, a final α-helical state. In contrast to SDS/LiDS and CR, the dimeric Affibody molecule locks monomeric Aβ(1-40) in a β-hairpin state. It was found that by truncating the flexible N-terminal end of the Affibody molecule its affinity to Aβ was improved. The aggregation of Aβ(1-40) was further studied in the presence of a β-cyclodextrin dimer by a kinetic assay using ThT. Although having a weak dissociation constant in the millimolar range, the β-cyclodextrin dimer modified the aggregation pathways of Aβ. Finally Aβ(1-40) was studied in presence of Cu2+ and Zn2+ at physiological and low pH. Cu2+ was observed to maintain its specific binding to Aβ when decreasing the pH to 5.5 while Zn2+ behaved differently. This could be of importance in the Alzheimer’s disease brain in which the environment can become acidic due to inflammation. In conclusion the results show that Aβ(1-40) is very sensitive to its environment, responding by adopting different conformations and aggregating in aqueous solutions. The β-sheet state is induced by varying molecules with different properties, properties that govern the final Aβ state.

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