The artificial pancreas: two alternative approaches to achieve a fully closed-loop system with optimal glucose control.

INTRODUCTION: Diabetes mellitus type 1 is a chronic disease that implies mandatory external insulin delivery. The patients must monitor their blood glucose levels and administer appropriate insulin boluses to keep their blood glucose within the desired range. It requires a lot of time and endeavour, and many patients struggle with suboptimal glucose control despite all their efforts. MATERIALS AND METHODS: This narrative review combines existing knowledge with new discoveries from animal experiments. DISCUSSION: In the last decade, artificial pancreas (AP) devices have been developed to improve glucose control and relieve patients of the constant burden of managing their disease. However, a feasible and fully automated AP is yet to be developed. The main challenges preventing the development of a true, subcutaneous (SC) AP system are the slow dynamics of SC glucose sensing and particularly the delay in effect on glucose levels after SC insulin infusions. We have previously published studies on using the intraperitoneal space for an AP; however, we further propose a novel and potentially disruptive way to utilize the vasodilative properties of glucagon in SC AP systems. CONCLUSION: This narrative review presents two lesser-explored viable solutions for AP systems and discusses the potential for improvement toward a fully automated system: A) using the intraperitoneal approach for more rapid insulin absorption, and B) besides using glucagon to treat and prevent hypoglycemia, also administering micro-boluses of glucagon to increase the local SC blood flow, thereby accelerating SC insulin absorption and SC glucose sensor site dynamics.

Risk Factors for Equine Gastric Glandular Disease: A Case-Control Study in a Finnish Referral Hospital Population.

BACKGROUND: Equine gastric glandular disease (EGGD) is a term used to classify erosive and ulcerative diseases of the glandular mucosa of the equine stomach. Epidemiologic studies of risk factors for EGGD have not been reported. OBJECTIVE: To determine risk factors for EGGD. ANIMALS: Cases (n = 83) had endoscopic evidence of EGGD; controls (n = 34) included healthy horses and horses with equine squamous gastric disease (ESGD) without EGGD. METHODS: Retrospective case-control study. The data were analyzed by multivariable logistic regression modeling. Analysis was performed on the full dataset. An additional analysis compared horses with glandular lesions (n = 43) against healthy horses (n = 22). RESULTS: On first analysis, Warmblood breed (OR = 13.9, 95% CI 2.2-90.9, P = .005) and an increasing number of caretakers (OR = 7.3, 95% CI 0.98-55.6, P = .053) were associated with an increased risk of EGGD. On analysis of the subset of data, Warmblood breed (OR = 28.6, 95% CI 2.96-250.0, P = .004) and increasing number of riders (OR = 12.99, 95% CI 0.94-166.7, P = .056) were risk factors. The presence of sand in the colon appeared to have a protective effect against EGGD (OR = 0.195, 95% CI 0.04-1.0, P = .051 for sand versus not having sand). CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that Warmbloods are predisposed to EGGD and multiple handlers/riders might increase the risk of EGGD. Identification of risk factors allows speculation on potential pathophysiological mechanisms of EGGD.

Variation in the hyphal growth rate and the virulence of two genotypes of the crayfish plague organism Aphanomyces astaci.

Crayfish plague, a devastating disease of freshwater crayfish, is caused by an oomycete organism, Aphanomyces astaci. Currently five genotypes of A. astaci are known, but variable features between the strains or genotypes have not been studied extensively. This study analysed 28 isolates of the As genotype and 25 isolates of the Ps1 genotype and reveals that the radial growth rate is significantly (P < 0.001) different between these two genotypes, although highly variable inside the genotype As. Two Ps1 genotype isolates and two As genotype isolates with different radial growth rates were tested in an infection trial. Clear differences were detected in the development of mortality in the test groups. The representatives of the Ps1 genotype caused total mortality within a short time span. The As genotype isolates were much less virulent. The slow-growing As isolate showed higher virulence than the As isolate with a high growth capacity. Although slow growth could be one survival strategy of the pathogen, several other mechanisms are involved in the pathogenicity and warrant further studies.

Aleutian mink disease virus in free-ranging mustelids in Finland - a cross-sectional epidemiological and phylogenetic study.

Aleutian mink disease virus (AMDV) can cause severe immune-complex-mediated disease in American mink. AMDV has also been detected in several other mustelid species with potential negative impact on their health and population. A molecular and cross-sectional epidemiological study was conducted to obtain data on the prevalence, distribution, transmission and diversity of AMDV strains in Finnish free-ranging mustelids and risk factors associated with infection. The presence of anti-AMDV antibodies and/or AMDV DNA was tested from 308 samples representing eight mustelid species and 17 administrative regions. Positive samples were detected across Finland, and in 54 % (31/57) of feral American mink, 27 % (7/26) of European badgers and 7 % (1/14) of European polecats. Samples from Eurasian otters, European pine martens, least weasels, stoat and wolverine were negative. Major risk factors for infection were the species American mink with 335 and badger with 74 times higher odds than other species, and the years 2006-2009 with five times higher odds than the years 2010-2014. No clustering according to species, geographical origin or year was evident in phylogeny, except for four divergent sequences from Estonian badgers that formed a separate phylogroup distinct from other AMDV strains. This study showed that AMDV was prevalent in certain species of Finnish free-ranging mustelids and widely distributed across Finland. Furthermore, the free-ranging mustelids carried both strains similar to those found in farmed mink, but also distinct strains that may represent novel amdoparvoviruses.

Leukocyte telomere length and its relation to food and nutrient intake in an elderly population.

BACKGROUND/OBJECTIVES: Shorter leukocyte telomere length (LTL) is associated with several chronic diseases, but only a few studies have assessed the association between dietary factors and LTL. Our objective was to study the association between fats, fruits, vegetables and LTL in a cross-sectional study design. We hypothesized that intakes of fruits and vegetables would be positively associated with LTL and that intakes of fats, and especially saturated fatty acids (SFAs), would be negatively associated with LTL. SUBJECTS/METHODS: LTL was measured by quantitative real-time polymerase chain reaction in 1942 men and women aged 57-70 years from the Helsinki Birth Cohort Study. We assessed the whole diet by a validated semiquantitative 128-item food-frequency questionnaire. RESULTS: In general, there were only a few significant results. However, total fat and SFA intake (P=0.04 and 0.01, respectively) were inversely associated with LTL in men adjusting for age and energy intake. In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits (P=0.05). We found no association between LTL and body mass index, waist-hip ratio, smoking, physical activity or educational attainment. CONCLUSIONS: In this cross-sectional study of elderly men and women, there were only a few statistically significant effects of diet, but in general they support the hypothesis that fat and vegetable intakes were associated with LTL.

Validation of the Finnish national dairy disease register--data transfer from cow health cards to the disease register.

Information on diseases of dairy cows in Finland is entered into the national disease register. Before the data from such types of secondary database are used, the quality of the data needs to be validated. In this study, 7,324 veterinary records for culled cows were compared against records in the national disease register in the period 2002 to 2008. Evaluation of the national disease register data was done by calculating completeness and correctness values. Completeness is the proportion of events that were physically recorded in the secondary database, and correctness is the proportion of correctly recorded events of all recorded events. The use of both correctness and completeness is important when describing the accuracy of secondary data. The completeness and correctness values for the Finnish national dairy disease register were 83 and 92%, respectively. We found that 39% of all unmatched diagnostic events were unreported by the artificial insemination technician who transferred the data from cow cards to the register. Logistic regression models showed that diagnostic events for cows born into the herd had twice the odds of being transferred compared with events for purchased cows. Diagnostic events for reproductive diseases had higher odds of being transferred to the register compared with all other disease groups, and the odds for transfer of the diagnostic event decreased as the age increased. We also found that if the diagnostic event was the last diagnostic event on the cow card, then its odds of being transferred to the disease register were significantly lowered. Although the Finnish national dairy disease register has good completeness and excellent correctness values, different disease groups, age groups, origin of the cow, and timing of the diagnostic event affect how well diagnostic events are transferred to the Finnish national dairy register.

Up regulation of cathepsin K expression in articular chondrocytes in a transgenic mouse model for osteoarthritis.

OBJECTIVES: To study the expression of cysteine proteinases, particularly cathepsin K, and their extracellular inhibitor cystatin C in articular cartilage of transgenic Del1 mice which harbour a short deletion mutation in a type II collagen transgene and are predisposed to early onset osteoarthritis. METHODS: Northern analysis was used to measure mRNA levels of cathepsins B, H, K, L, and S, and cystatin C in total RNA extracted from knee joints of Del1 mice, using their non-transgenic litter mates as controls. Immunohistochemistry and morphometry was used to study the distribution of cathepsin K and cystatin C in the knee joints. RESULTS: Up regulation of cathepsin K mRNA expression was seen in the knee joints of transgenic Del1 mice at the onset of cartilage degeneration. Cathepsin K was found near sites of matrix destruction in articular chondrocytes, particularly in clusters of proliferating cells, and in calcified cartilaginous matrix. In intact articular cartilage of control animals, cathepsin K was only seen in a small number of chondrocytes. Upon aging, control animals also developed osteoarthritis, which was accompanied by increased cathepsin K expression. Cystatin C was mostly localised in and around chondrocytes located in calcified cartilage, with no obvious association with the onset of cartilage degeneration. CONCLUSION: The temporospatial distribution of cathepsin K in osteoarthritic cartilage suggests a role for this enzyme in the pathogenesis of osteoarthritis. Because cathepsin K can digest cartilage matrix components it may contribute to the development of osteoarthritic lesions. These data may provide new clues for the development of treatments aimed at preventing cartilage degeneration.

Differential expression patterns of matrix metalloproteinases and their inhibitors during development of osteoarthritis in a transgenic mouse model.

OBJECTIVE: To characterise the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during degeneration of articular cartilage in a transgenic Del1 mouse model for osteoarthritis. METHODS: Northern analysis was used to measure mRNA levels of MMP-2, -3, -8, -9, -13, and -14, and TIMP-1, -2, and -3 in total RNA extracted from knee joints of transgenic Del1 mice, harbouring a 15 amino acid deletion in the triple helical domain of the alpha1(II) collagen chain, using their non-transgenic littermates as controls. Immunohistochemistry was used to study the presence of cleavage products (neoepitopes) of type II collagen, and the distribution of MMP-13 and TIMP-1 in degenerating cartilage. RESULTS: Each of the MMP and TIMP mRNAs analysed exhibited distinct expression patterns during development and osteoarthritic degeneration of the knee joint. The most striking change was up regulation of MMP-13 mRNA expression in the knee joints of Del1 mice at the onset of cartilage degeneration. However, the strongest immunostaining for MMP-13 and its inhibitor TIMP-1 was not seen in the degenerating articular cartilage but in synovial tissue, deep calcified cartilage, and subchondral bone. The localisation of type II collagen neoepitopes in chondrocytes and their pericellular matrix followed a similar pattern; they were not seen in cartilage fibrillations, but in adjacent unaffected cartilage. CONCLUSION: The primary localisation of MMP-13 and TIMP-1 in hyperplastic synovial tissue, subchondral bone, and calcified cartilage suggests that up regulation of MMP-13 expression during early degeneration of articular cartilage is a secondary response to cartilage erosion. This interpretation is supported by the distribution of type II collagen neoepitopes. Synovial production of MMP-13 may be related to removal of tissue debris released from articular cartilage. In the deep calcified cartilage and adjacent subchondral bone, MMP-13 probably participates in tissue remodelling.