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  • 1.
    Axelsson, K. F.
    et al.
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden.
    Wallander, M.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Johansson, H.
    Institute for Health and Ageing, Catholic University of Australia, Melbourne, VIC, Australia.
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, M.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Hip fracture risk and safety with alendronate treatment in the oldest-old2017In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 6, p. 546-559Article in journal (Refereed)
    Abstract [en]

    Background. There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (80 years old), the population with the highest fracture risk, has not been studied.

    Objective. To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety.

    Methods. Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term.

    Results. The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI.

    Conclusion. In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients.

  • 2.
    Axelsson, Kristian F.
    et al.
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden.
    Nilsson, Anna G.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Wedel, Hans
    Department of Endocrinology, Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Swede.
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, Mattias
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Association between alendronate use and hip fracture risk in older patients using oral prednisolone2017In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 318, no 2, p. 146-155Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Oral glucocorticoid treatment increases fracture risk, and evidence is lacking regarding the efficacy of alendronate to protect against hip fracture in older patients using glucocorticoids.

    OBJECTIVE To investigate whether alendronate treatment in older patients using oral prednisolone is associated with decreased hip fracture risk and adverse effects.

    DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study using a national database (N = 433 195) of patients aged 65 years or older undergoing a health evaluation (baseline) at Swedish health care facilities; 1802 patients who were prescribed alendronate after at least 3 months of oral prednisolone treatment (>= 5mg/d) were identified. Propensity score matching was used to select 1802 patients without alendronate use from 6076 patients taking prednisolone with the same dose and treatment time criteria. Follow-up occurred between January 2008 and December 2014.

    EXPOSURES Alendronate vs no alendronate use; no patients had previously taken alendronate at the time of prednisolone initiation.

    MAIN OUTCOMES AND MEASURES The primary outcome was incident hip fracture.

    RESULTS Of the 3604 included patients, the mean age was 79.9 (SD, 7.5) years, and 2524 (70%) were women. After a median follow-up of 1.32 years (interquartile range, 0.57-2.34 years), there were 27 hip fractures in the alendronate group and 73 in the no-alendronate group, corresponding to incidence rates of 9.5 (95% CI, 6.5-13.9) and 27.2 (95% CI, 21.6-34.2) fractures per 1000 person-years, with an absolute rate difference of -17.6 (95% CI, -24.8 to -10.4). The use of alendronate was associated with a lower risk of hip fracture in a multivariable-adjusted Cox model (hazard ratio, 0.35; 95% CI, 0.22-0.54). Alendronate treatment was not associated with increased risk of mild upper gastrointestinal tract symptoms (alendronate vs no alendronate, 15.6 [95% CI, 11.6-21.0] vs 12.9 [95% CI, 9.3-18.0] per 1000 person-years; P=.40) or peptic ulcers (10.9 [95% CI, 7.7-15.5] vs 11.4 [95% CI, 8.0-16.2] per 1000 person-years; P=.86). There were no cases of incident drug-induced osteonecrosis and only 1 case of femoral shaft fracture in each group.

    CONCLUSIONS AND RELEVANCE Among older patients using medium to high doses of prednisolone, alendronate treatment was associated with a significantly lower risk of hip fracture over a median of 1.32 years. Although the findings are limited by the observational study design and the small number of events, these results support the use of alendronate in this patient group.

  • 3.
    Axelsson, Kristian F.
    et al.
    Department of Orthopaedic Surgery, Skaraborg Hospital, Skövde, Sweden.
    Werling, Malin
    Department of Gastrosurgical Research & Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Eliasson, Björn
    Department of Molecular and Clinical Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Szabo, Eva
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Näslund, Ingmar
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wedel, Hans
    Health Metrics, Sahlgrenska Academin, University of Gothenburg, Gothenburg, Sweden.
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, Mattias
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Fracture Risk After Gastric Bypass Surgery: A Retrospective Cohort Study2018In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 33, no 12, p. 2122-2131Article in journal (Refereed)
    Abstract [en]

    Gastric bypass surgery constitutes the most common and effective bariatric surgery to treat obesity. Gastric bypass leads to bone loss, but fracture risk following surgery has been insufficiently studied. Furthermore, the association between gastric bypass and fracture risk has not been studied in patients with diabetes, which is a risk factor for fracture and affected by surgery. In this retrospective cohort study using Swedish national databases, 38,971 obese patients undergoing gastric bypass were identified, 7758 with diabetes and 31,213 without. An equal amount of well-balanced controls were identified through multivariable 1:1 propensity score matching. The risk of fracture and fall injury was investigated using Cox proportional hazards and flexible parameter models. Fracture risk according to weight loss and degree of calcium and vitamin D supplementation 1-year postsurgery was investigated. During a median follow-up time of 3.1 (interquartile range [IQR], 1.7 to 4.6) years, gastric bypass was associated with increased risk of any fracture, in patients with and without diabetes using a multivariable Cox model (hazard ratio [HR] 1.26; 95% CI, 1.05 to 1.53; and HR 1.32; 95% CI, 1.18 to 1.47; respectively). Using flexible parameter models, the fracture risk appeared to increase with time. The risk of fall injury without fracture was also increased after gastric bypass. Larger weight loss or poor calcium and vitamin D supplementation after surgery were not associated with increased fracture risk. In conclusion, gastric bypass surgery is associated with an increased fracture risk, which appears to be increasing with time and not associated with degree of weight loss or calcium and vitamin D supplementation following surgery. An increased risk of fall injury was seen after surgery, which could contribute to the increased fracture risk.

  • 4.
    Axelsson, Kristian
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Molndal, Sweden.
    Lorentzon, Mattias
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Molndal, Sweden.
    Lundh, Dan
    Jönköping University, School of Health and Welfare, HHJ. Biomedical Platform.
    Johansson, Helena
    Australian Catholic Univ, Inst Hlth & Aging, Sydney, NSW, Australia.
    Moller, Michael
    Sahlgrens Univ Hosp, Molndal, Sweden.
    Implementation of Fracture Liaison Services in two Swedish hospitals was associated with reduced risk of recurrent clinical fractures in patients with osteoporotic fracture2019In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 34, no 1, p. 43-44Article in journal (Refereed)
  • 5.
    Hedelin, Hans
    et al.
    Department of Research and Development, Skaraborgs Sjukhus, Skövde, Sweden.
    Jonsson, Karin
    Department of Research and Development, Skaraborgs Sjukhus, Skövde, Sweden.
    Lundh, Dan
    Department of Research and Development, Skaraborgs Sjukhus, Skövde, Sweden.
    Pain associated with the chronic pelvic pain syndrome is strongly related to the ambient temperature2012In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 4, p. 279-283Article in journal (Refereed)
    Abstract [en]

    Objective. There are indications suggesting that the pain associated with the chronic pelvic pain syndrome (CPPS) may be related to cold. The purpose of the present study was to evaluate how the symptom intensity reported by the patient relates to the time of the year in a temperate climate, i.e. to the ambient temperature and to weather changes.

    Material and methods. Thirty-one patients, mean age 51 years (range 35-66 years), with CPPS for 17 +/- 10 years (3-42 years) were asked to complete a set of questionnaires including questions concerning how they experienced their symptom intensity during the different seasons using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) questionnaire.

    Results. The total NIH-CPSI score was 22.2 +/- 8.2. There was a highly marked relationship between season and pain intensity as reported by the informants: it was experienced to be three times more intense during the winter months. All subjects reported that a temperature drop was associated with deterioration.

    Conclusion. The strong relationship between the ambient temperature, a drop in temperature and the pain experienced by men with CPPS confirms the association between cold and symptom intensity in the Scandinavian countries, where the seasonal temperature variation spans a long range and the winters are long. The cause of this relationship is still to be established. Muscular spasm/stiffness is a possibility that remains to be explored.

  • 6.
    Karlsson, Sandra
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Olausson, Josefin
    Högskolan i Skövde, Institutionen för vård och natur.
    Lundh, Dan
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Sögård, Peter
    Högskolan i Skövde, Institutionen för vård och natur.
    Mandal, Abul
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Holmström, Kjell-Ove
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Stahel, Anette
    Högskolan i Skövde, Institutionen för vård och natur.
    Bengtsson, Jenny
    Högskolan i Skövde, Institutionen för vård och natur.
    Larsson, Dennis
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Vitamin D and prostate cancer: The role of membrane initiated signaling pathways in prostate cancer progression2010In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 121, no 1-2, p. 413-416Article in journal (Refereed)
    Abstract [en]

    1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been demonstrated to mediate both genomic and non-genomic responses in prostate cancer (CaP) cells. Here, we give an overview of membrane initiated 1,25(OH)2D3 signaling in prostate cancer cell progression. The presence of PDIA3 was investigated and homologous modeling of the putative PDIA3 receptor complex was conducted. Furthermore, the cellular distribution of nVDR was analyzed. We could show that both nVDR and PDIA3 are expressed in the prostate cancer cell lines investigated. The homologous modeling of PDIA3 showed that the receptor complex exists in a trimer formation, which suggests for allosteric activity. Our findings support previous reports and suggest that 1,25(OH)2D3 is an important therapeutic agent in inhibiting prostate cancer progression. Furthermore, our data show that 1,25(OH)2D3 regulate prostate cell biology via multiple pathways and targeting specific pathways for 1,25(OH)2D3 might provide more effective therapies compared to the vitamin D therapies currently clinically tested.

  • 7.
    Landegren, Nils
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, Sci Life Lab, SE-75185 Uppsala, Sweden..
    Sharon, Donald
    Stanford Univ, Dept Genet, Stanford, CA 94305 USA.;Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06511 USA..
    Shum, Anthony K.
    Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care, San Francisco, CA 94143 USA..
    Khan, Imran S.
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA..
    Fasano, Kayla J.
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA..
    Hallgren, Åsa
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, Sci Life Lab, SE-75185 Uppsala, Sweden..
    Kampf, Caroline
    Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
    Freyhult, Eva
    Uppsala Univ, Canc Pharmacol & Computat Med, Dept Med Sci Bioinformat Infrastruct Life Sci, Sci Life Lab, SE-75185 Uppsala, Sweden..
    Ardesjo-Lundgren, Brita
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, SE-75007 Uppsala, Sweden..
    Alimohammadi, Mohammad
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, Sci Life Lab, SE-75185 Uppsala, Sweden.;Uppsala Univ, Dept Med Sci, SE-75185 Uppsala, Sweden..
    Rathsman, Sandra
    Univ Orebro, Dept Lab Med Microbiol, SE-70185 Orebro, Sweden..
    Ludvigsson, Jonas F.
    Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17176 Stockholm, Sweden..
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Motrich, Ruben
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol, RA-5000 Cordoba, Argentina..
    Rivero, Virginia
    Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, Ctr Invest Bioquim Clin & Inmunol, RA-5000 Cordoba, Argentina..
    Fong, Lawrence
    Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94115 USA..
    Giwercman, Aleksander
    Lund Univ, Mol Reprod Res, Dept Clin Sci Malmo, SE-20502 Malmo, Sweden..
    Gustafsson, Jan
    Uppsala Univ, Dept Womens & Childrens Hlth, SE-75185 Uppsala, Sweden..
    Perheentupa, Jaakko
    Univ Helsinki, Hosp Children & Adolescents, Helsinki 00029, Finland..
    Husebye, Eystein S.
    Univ Bergen, Dept Clin Sci, N-5020 Bergen, Norway.;Haukeland Hosp, Dept Med, N-5020 Bergen, Norway..
    Anderson, Mark S.
    Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA..
    Snyder, Michael
    Stanford Univ, Dept Genet, Stanford, CA 94305 USA..
    Kampe, Olle
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, SE-17176 Stockholm, Sweden.;Uppsala Univ, Dept Med Sci, Sci Life Lab, SE-75185 Uppsala, Sweden..
    Transglutaminase 4 as a prostate autoantigen in male subfertility2015In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, no 292, article id 292ra101Article in journal (Refereed)
    Abstract [en]

    Autoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pubertal age and subsequent to prostate maturation. We assessed the animal model for APS1, the Aire-deficient mouse, and found spontaneous development of TGM4 autoantibodies specifically in males. Aire-deficient mice failed to present TGM4 in the thymus, consistent with a defect in central tolerance for TGM4. In the mouse, we further link TGM4 immunity with a destructive prostatitis and compromised secretion of TGM4. Collectively, our findings in APS1 patients and Aire-deficient mice reveal prostate autoimmunity as a major manifestation of APS1 with potential role in male subfertility.

  • 8.
    Levefelt, Christer
    et al.
    School of Humanities and Informatics, University of Skövde, Skövde, Sweden.
    Lundh, Dan
    School of Humanities and Informatics, University of Skövde, Skövde, Sweden.
    A fold-recognition approach to loop modeling2006In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 12, no 2, p. 125-139Article in journal (Refereed)
    Abstract [en]

    A novel approach is proposed for modeling loop regions in proteins. In this approach, a prerequisite sequence-structure alignment is examined for regions where the target sequence is not covered by the structural template. These regions, extended with a number of residues from adjacent stem regions, are submitted to fold recognition. The alignments produced by fold recognition are integrated into the initial alignment to create an alignment between the target sequence and several structures, where gaps in the main structural template are covered by local structural templates. This one-to-many (1:N) alignment is used to create a protein model by existing protein-modeling techniques. Several alternative approaches were evaluated using a set of ten proteins. One approach was selected and evaluated using another set of 31 proteins. The most promising result was for gap regions not located at the C-terminus or N-terminus of a protein, where the method produced an average RMSD 12% lower than the loop modeling provided with the program MODELLER. This improvement is shown to be statistically significant.

  • 9.
    Lundh, Dan
    et al.
    University of Skövde, Skövde, Sweden.
    Coleman, Scott
    Motion and Sports Lab, Baylor University Medical Center, Dallas, TX, United States.
    Riad, Jacques
    Orthopaedic Department, Skaraborg Hospital Skövde, Skövde, Sweden.
    Movement deviation and asymmetry assessment with three dimensional gait analysis of both upper- and lower extremity results in four different clinical relevant subgroups in unilateral cerebral palsy2014In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 29, no 4, p. 381-386Article in journal (Refereed)
    Abstract [en]

    Background: In unilateral cerebral palsy, movement pattern can be difficult to define and quantify. The aim was to assess the degree of deviation and asymmetry in upper and lower extremities during walking.

    Methods: Forty-seven patients, 45 Gross Motor Function Classification Scale (GMFCS) I and 2 patients GMFCS 11, mean age 17.1 years (range 13.1 to 24.0) and 15 matched controls were evaluated. Gait profile score (GPS) and arm posture score (APS) were calculated from three-dimensional gait analysis (GA). Asymmetry was the calculated difference in deviation between affected and unaffected sides.

    Findings: The GPS was significantly increased compared to the control group on the affected side (6.93 (2.08) versus 4.23 (1.11) degrees) and on the unaffected side (6.67 (2.14)). The APS was also significantly increased on the affected side (10.39 (5.01) versus 5.52 (1.71) degrees) and on the unaffected side (7.13 (2.23)). The lower extremity asymmetry increased (significantly) in comparison with the control group (7.89 (3.82) versus 3.90 (1.01)) and correspondingly in the upper extremity (9.75 (4.62) versus 5.72 (1.84)). The GPS was not different between affected and unaffected sides, however the APS was different (statistically significant).

    Interpretation: We calculated deviation and asymmetry of movement during walking in unilateral CP, identifying four important clinical groups: close to normal, deviations mainly in the leg, deviations mainly in the arm and those with deviation in the arm and leg. This method can be applied to any patient group, and aid in diagnosing, planning treatment, and prognosis.

  • 10.
    Lundh, Dan
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Hedelin, Hans
    Skaraborgs Sjukhus, Skövde , Sweden.
    Jonsson, Karin
    Kärnsjukhuset, Skövde , Sweden.
    Gifford, Mervyn
    Högskolan i Skövde, Institutionen för vård och natur.
    Larsson, Dennis
    Högskolan i Skövde, Institutionen för vård och natur.
    Assessing chronic pelvic pain syndrome patients: Blood plasma factors and cortisol saliva2013In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 47, no 6, p. 521-528Article in journal (Refereed)
    Abstract [en]

    Objective:

    The aim of this study was to identify changes in inflammatory molecules in the blood (plasma) of patients with chronic prostatitis/chronic pelvic syndrome (CP/CPPS) compared with controls. Altered levels indicate a systemic component by possible involvement of the prostate and/or the inner pelvic floor musculature.

    Material and methods:

    In 32 patients with CP/CPPS and 37 controls, blood plasma levels of testosterone, macrophage migration inhibitory factor (MIF), tumour necrosis factor-alpha (TNF-alpha), TNF-beta, interleukin-2 (IL-2) and IL-1 beta were measured by enzyme-linked immunosorbent assay. Cortisol in saliva samples was measured in the morning and late evening. All participants answered a questionnaire regarding their health profile.

    Results:

    Significantly higher levels of MIF (p = 0.012) were detected in patients. The testosterone level was, contrary to other studies, little lower in patients (p = 0.014; age adjusted). When controls with health issues and patients with a parallel disease were excluded, the MIF and TNF-alpha levels were higher in the patients (p = 0.007, p = 0.016, respectively) than in controls, and the testosterone was slightly lower in patients (p = 0.047).

    Conclusions:

    The findings show an immune response extending to the circulatory system, in which MIF makes a significant contribution to CP/CPPS. This study also indicates TNF-alpha as a circulatory component when excluding subjects with concomitant diseases. Both MIF and TNF-alpha have previously been highlighted for other diseases related to chronic pain and here also for CP/CPPS. These results provide further insights into the immunological basis of CP/CPPS.

  • 11.
    Lundh, Dan
    et al.
    Högskolan i Skövde, Institutionen för vård och natur.
    Hedelin, Hans
    Department of Research and Development, Skaraborgs Sjukhus, Skövde, Sweden.
    Larsson, Dennis
    Högskolan i Skövde, Institutionen för vård och natur.
    Chronic prostatitis/chronic pelvic pain syndrome: Interplay of inflammatory mediators, "Beyond the Abstract"2013Other (Other academic)
  • 12.
    Lundh, Dan
    et al.
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Larsson, Dennis
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Nahar, Noor
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Mandal, Abul
    Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Arsenic accumulation in plants - Outlining strategies for developing improved variety of crops for avoiding arsenic toxicity in foods2010In: Journal of biological systems, ISSN 0218-3390, Vol. 18, no 1, p. 223-241Article in journal (Refereed)
    Abstract [en]

    Contamination of food with arsenics is a potential health risk for both humans and animals in many regions of the world, especially in Asia. Arsenics can be accumulated in humans, animals and plants for a longer period and a long-term exposure of humans to arsenics results in severe damage of kidney, lever, heart etc. and many other vascular diseases. Arsenic contamination in human may also lead to development of cancer. In this paper we report our results on data mining approach (an in silico analysis based on searching of the existing genomic databases) for identification and characterization of genes that might be responsible for uptake, accumulation or metabolism of arsenics. For these in silico analyses we have involved the model plant Arabidopsis thaliana in our investigation. By employing a system biology model (a kinetic model) we have studied the molecular mechanisms of these processes in this plant. This model contains equations for uptake, metabolism and sequestration of different types of arsenic; As(V), As(III), MMAA and DMAA. The model was then implemented in the software XPP. The model was also validated against the data existing in the literatures. Based on the results of these in silico studies we have developed some strategies that can be used for reducing arsenic contents in different parts of the plant. Data mining experiments resulted in identification of two candidate genes (ACR2, arsenate reductase 2 and PCS1, phytochelatin synthase 1) that are involved either in uptake, transport or cellular localization of arsenic in A. thaliana. However, our system biology model revealed that by increasing the level of arsenate reductase together with an increased rate of arsenite sequestration in the vacuoles (by involving an arsenite efflux pump MRP1/2), it is possible to reduce the amount of arsenics in the shoots of A. thaliana to 11–12%.

  • 13.
    Riad, Jacques
    et al.
    Department of Orthopedics, Skaraborgs Hospital, Skövde, Sweden.
    Coleman, Scott
    Motion and Sports Lab, Baylor University Medical Center, Dallas, TX, United States.
    Lundh, Dan
    Högskolan Skövde, Skövde, Sweden.
    Brostrom, Eva
    Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden.
    Arm posture score and arm movement during walking: A comprehensive assessment in spastic hemiplegic cerebral palsy2011In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 33, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    Patients with hemiplegic cerebral palsy often have noticeably deviant arm posture and decreased arm movement. Here we develop a comprehensive assessment method for the upper extremity during walking. Arm posture score (APS), deviation of shoulder flexion/extension, shoulder abduction/adduction, elbow flexion/extension and wrist flexion/extension were calculated from three-dimensional gait analysis. The APS is the root mean square deviation from normal, similar to Baker's Gait Profile Score (GPS) [1]. The total range of motion (ROM) was defined as the difference between the maximum and minimum position in the gait cycle for each variable. The arm symmetry, arm posture index (API) was calculated by dividing the APS on the hemiplegic side by that on the non-involved side, and the range of motion index (ROMI) by dividing the ROM on the hemiplegic side by that on the non-involved side. Using the APS, two groups were defined. Group 1 had minor deviations, with an APS under 9.0 and a mean of 6.0(95% CI 5.0-7.0). Group 2 had more pronounced deviations, with an APS over 9.0 and a mean of 13.1 (CI 10.8-15.5) (p = 0.000). Total ROM was 60.6 in group 1 and 46.2 in group 2 (p = 0.031). API was 0.89 in group 1 and 1.70 in group 2 (p < 0.001). ROMI was 1.15 in group 1 and 0.69 in group 2 (p = 0.003). APS describes the amount of deviation, ROM provides additional information on movement pattern and the indices the symmetry. These comprehensive objective and dynamic measurements of upper extremity abnormality can be useful in following natural progression, evaluating treatment and making prognoses in several categories of patients. 

  • 14.
    Wallander, M.
    et al.
    Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
    Axelsson, K. F.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Center for Bone Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lundh, Dan
    School of Health and Education, University of Skövde, Skövde, Sweden.
    Lorentzon, M.
    Geriatric Medicine, Department of Internal Medicine and Clinical Nutrition, Center for Bone Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Patients with prostate cancer and androgen deprivation therapy have increased risk of fractures - a study from the fractures and fall injuries in the elderly cohort (FRAILCO)2019In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 30, no 1, p. 115-125Article in journal (Refereed)
    Abstract [en]

    Summary

    Osteoporosis is a common complication of androgen deprivation therapy (ADT). In this large Swedish cohort study consisting of a total of nearly 180,000 older men, we found that those with prostate cancer and ADT have a significantly increased risk of future osteoporotic fractures.

    Introduction

    Androgen deprivation therapy (ADT) in patients with prostate cancer is associated to increased risk of fractures. In this study, we investigated the relationship between ADT in patients with prostate cancer and the risk of incident fractures and non-skeletal fall injuries both compared to those without ADT and compared to patients without prostate cancer.

    Methods

    We included 179,744 men (79.17.9years (meanSD)) from the Swedish registry to which national directories were linked in order to study associations regarding fractures, fall injuries, morbidity, mortality and medications. We identified 159,662 men without prostate cancer, 6954 with prostate cancer and current ADT and 13,128 men with prostate cancer without ADT. During a follow-up of approximately 270,300 patient-years, we identified 10,916 incident fractures including 4860 hip fractures.

    Results

    In multivariable Cox regression analyses and compared to men without prostate cancer, those with prostate cancer and ADT had increased risk of any fracture (HR 95% CI 1.40 (1.28–1.53)), hip fracture (1.38 (1.20–1.58)) and MOF (1.44 (1.28–1.61)) but not of non-skeletal fall injury (1.01 (0.90–1.13)). Patients with prostate cancer without ADT did not have increased risk of any fracture (0.97 (0.90–1.05)), hip fracture (0.95 (0.84–1.07)), MOF (1.01 (0.92–1.12)) and had decreased risk of non-skeletal fall injury (0.84 (0.77–0.92)).

    Conclusions

    Patients with prostate cancer and ADT is a fragile patient group with substantially increased risk of osteoporotic fractures both compared to patients without prostate cancer and compared to those with prostate cancer without ADT. We believe that this must be taken in consideration in all patients with prostate cancer already at the initiation of ADT.

  • 15.
    Wallander, Marit
    et al.
    Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
    Axelsson, Kristian F.
    Geriatric Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Nilsson, Anna G.
    Geriatric Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Lundh, Dan
    School of Bioscience, University of Skövde, Skövde, Sweden.
    Lorentzon, Mattias
    Geriatric Medicine, Center for Bone Research at the Sahlgrenska Academy, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
    Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From The Fractures And Fall Injuries In The Elderly Cohort (Frailco)2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 3, p. 449-460Article in journal (Refereed)
    Abstract [en]

    Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 +/- 8.2 years [mean +/- SD], 58% women) from the Swedish registry "Senior Alert" and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication.

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