Upsala journal of medical sciences
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During the past 20 years, since I started as a postdoc, the world of genetics and genomics has changed dramatically. My main research goal throughout my career has been to understand human disease genetics, and I have developed comparative genomics and comparative genetics to generate resources and tools for understanding human disease. ⋯ Through comparative genetics, I have developed the dog as a model for human disease, characterising the genome itself and determining a list of germ-line loci and somatic mutations causing complex diseases and cancer in the dog. Pulling all these findings and resources together opens new doors for understanding genome evolution, the genetics of complex traits and cancer in man and his best friend.
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Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. ⋯ In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.
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Background. No study has examined the effect of low serum uric acid (SUA) concentrations on mortality in hypertrophic cardiomyopathy (HCM) patients. The aim of the present study was to assess the relations between both low and high SUA concentrations and the risk of mortality across the full range of SUA concentrations in a retrospective cohort of HCM patients. ⋯ The corresponding HRs in the highest SUA group (≥450 µmol/L) were 2.73 (95% CI 1.42-5.23, p = 0.003) and 4.14 (95% CI 1.70-10.13, p = 0.002), respectively. Conclusions. Both low and high SUA concentrations were significantly associated with increased risk of all-cause mortality and HCM-related mortality, which supported a U-shaped association between SUA concentrations and mortality in HCM patients.
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Background: Mortality is high among elderly patients with traumatic brain injury (TBI). Recent data suggest that early surgical intervention and aggressive rehabilitation may reduce mortality rates even in elderly patients. Our aim was therefore to study the Rapid Emergency Triage and Treatment System-Adult (RETTS-A) triage of patients with isolated TBI and examine the differences in acute management according to age. ⋯ LOS was significantly higher in elderly patients (median 9 days compared with 3 days for younger patients, p < 0.001). Finally, age, triage priority, and AIS score were independent risk factors for mortality. Conclusion: Elderly patients with isolated TBI are managed differently than younger patients, which could be due to an under-triage of elderly patients by RETTS-A.
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Background: Human seminal prostasomes are intrinsically heterogeneous extracellular vesicles (EVs) whose composition is, additionally, influenced by different physiological conditions. Aiming at the molecular properties of the prostasomal surface exemplified by glycan compositions as a possible distinction factor, we applied lectin-affinity chromatography (LAC) as a new tool for their separation. Since glycans, generally, exhibit various biological activities, introduction of glyco-parameters as reference could upgrade standardization of EVs isolated by different methods and intended for use in biomedicine. ⋯ Additional populations having distinct profiles of total glycoproteins and which can be tracked down by ALP activity were enriched on the Con A column. WGA-separated populations were similar in sPro-N and sPro-O, whereas Con A-separated ones were strikingly different. Conclusions: Membrane-associated gamma-glutamyl transferase and alkaline phosphatase in the context of Con A- and WGA-reactive glycans mark seminal prostasomes populations from normozoospermic and oligozoospermic men.