Edge artificial intelligence wireless video capsule endoscopy.

Gastrointestinal (GI) tract diseases are responsible for substantial morbidity and mortality worldwide, including colorectal cancer, which has shown a rising incidence among adults younger than 50. Although this could be alleviated by regular screening, only a small percentage of those at risk are screened comprehensively, due to shortcomings in accuracy and patient acceptance. To address these challenges, we designed an artificial intelligence (AI)-empowered wireless video endoscopic capsule that surpasses the performance of the existing solutions by featuring, among others: (1) real-time image processing using onboard deep neural networks (DNN), (2) enhanced visualization of the mucous layer by deploying both white-light and narrow-band imaging, (3) on-the-go task modification and DNN update using over-the-air-programming and (4) bi-directional communication with patient's personal electronic devices to report important findings. We tested our solution in an in vivo setting, by administrating our endoscopic capsule to a pig under general anesthesia. All novel features, successfully implemented on a single platform, were validated. Our study lays the groundwork for clinically implementing a new generation of endoscopic capsules, which will significantly improve early diagnosis of upper and lower GI tract diseases.

The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement.

OBJECTIVES: The dolutegravir/valproic acid drug-drug interaction (DDI) is suggested to be caused by protein displacement. Here, we assess the underlying mechanism. METHODS: Participants in a randomized controlled trial investigating valproic acid as an HIV latency reversing agent were recruited in a predefined pharmacokinetic substudy if they were on once-daily 50 mg dolutegravir-containing combination ART (cART) for >12 months with a plasma HIV-RNA <50 copies/mL (trial registration: ClinicalTrials.gov NCT03525730). Participants were randomized to receive 30 mg/kg/day valproic acid orally (divided into two equal doses) for 14 days or not. Total and unbound dolutegravir concentrations were measured on day 0 (before intake of valproic acid and 6 h after intake of valproic acid) and on days 1, 7, 14 and 42. Intra- and inter-subject dolutegravir concentrations and geometric means (GMs) were evaluated. RESULTS: Six of 10 participants on dolutegravir were randomized to receive valproic acid. During 14 days of valproic acid treatment, the GM total dolutegravir concentration decreased sharply from 1.36 mg/L on day 0 to 0.85, 0.31 and 0.20 mg/L on days 0, 1, 7 and 14, respectively, while total dolutegravir concentrations in the controls remained comparable during the same period: 1.27-1.49 mg/L. We observed a parallel increase in unbound dolutegravir fractions ranging from 0.39% to 0.58% during valproic acid administration, compared with 0.25% to 0.28% without valproic acid. Unbound dolutegravir concentrations were above the established in vitro EC90 value for unbound dolutegravir in 85% of the tested samples. CONCLUSIONS: This study confirms protein displacement as the main mechanism for this DDI, although additional mechanisms might be involved too. If dolutegravir is taken with food, this DDI is probably not clinically relevant.

Strontium ion reinforced bioceramic scaffold for load bearing bone regeneration.

Bone defects in load bearing areas require bone reconstruction with strong biomaterial having mechanical characteristics like cortical bone. Bioceramics are biomaterials that support bone formation as well as provide adequate mechanical properties. A strontium substitution of the bioceramic is expected to further increase its bioactivity by enhancing osteogenesis and protect the bone from osteoclastic resorption. The study involves development, characterization and in vivo testing of a newly developed strontium substituted hydroxyapatite based bioceramic scaffold (SrHAB) with sufficient biomechanical properties. Optimal concentration of strontium ion required for enhanced osteogenic differentiation was identified by comparing three compositions of SrHAB scaffold; namely Sr10HAB, Sr30HAB and Sr50 HAB for their Alkaline phosphatase activity in vitro. The selected Sr10HAB scaffold demonstrated in vivo bone formation with osteogenic differentiation of stromal derived mesenchymal stem cells (MSC) from human and ovine sources in ectopic and ovine models. Thus, Sr10HAB scaffold has a potential for application in load bearing bone requirements of orthopaedics and dentistry.

Effect of plasmapheresis on the immune system in endotoxin-induced sepsis.

BACKGROUND: It has been proposed that plasmapheresis is most effective when applied early in Gram-negative sepsis. We therefore studied the effect of early plasmapheresis on immunity in experimental Escherichia coli endotoxin-induced sepsis. METHODS: 20 pigs received 30 microg/kg of E. coli endotoxin. 40 min later, half of the pigs were treated with plasmapheresis which lasted 4 h. The adhesion molecules, the oxidative burst, the number of neutrophils in blood and lungs, and cytokines were measured. RESULTS: Infusion of endotoxin was associated with activation of adhesion molecules increased oxidative burst, increased concentration of cytokine, and accumulation of granulocytes in lung tissue. Plasmapheresis reduced the oxidative burst, and there was a tendency towards a reduced accumulation of granulocytes in the lung. CONCLUSION: Though plasmapheresis was initiated early after the endotoxin infusion, it only temporarily attenuated a part of the activated cell-mediated immunity.

The impact of long-term haemofiltration (continuous veno-venous haemofiltration) on cell-mediated immunity during endotoxaemia.

BACKGROUND: Increased survival with high-volume continuous veno-venous haemofiltration (CVVH) has been demonstrated in critically ill patients. This may be the result of intensified blood purification or an effect on the immune system. We hypothesized that CVVH modifies the cell-mediated immunity. We investigated the effect of high-volume CVVH for 24 h on the cell-mediated immunity following endotoxin infusion. METHODS: Thirty pigs were divided into three groups. Ten pigs received 30 microg/kg of Escherichia coli endotoxin. These pigs were treated with CVVH (replacement 35 ml/kg/h) over the following 24 h. Ten pigs received the same bolus of endotoxin and ten pigs served as a control group. The adhesion molecules CD18, CD44 and CD62L and the ability to respond with an oxidative burst were measured. The number of neutrophils was counted in blood and lung tissue. The lymphoproliferative response and cytokines interleukin-6 and interleukin-10 were measured. RESULTS: The infusion of endotoxin was followed by initial granulocytopenia and, later, granulocytosis, activation of CD18 and CD62L, and increased oxidative burst. The cytokine level was increased. CVVH had no effect on the adhesion molecules or cytokine level and did not reduce the number of granulocytes in the lung significantly. CVVH, however, reduced the oxidative burst activity of neutrophils after 2 h of treatment. CONCLUSION: In the first few hours after endotoxaemia, high-volume CVVH reduced the oxidative burst activity of neutrophils. However, in the long term, CVVH was unable to modify the endotoxin-induced changes in cell-mediated immunity.

Growth differences of male and female Göttingen minipigs during ad libitum feeding: a pilot study.

Even though minipigs have been used in biomedical research for nearly half a century now, no specific nutrient requirements are available. For that reason a series of studies into the nutrient requirements of Göttingen minipigs were carried out. Firstly, a pilot study was carried out to determine the ad libitum feed intake (FI) during growth, as a reference for later feed restriction studies. Four male and four female minipigs were fed two types of diet, one standard pig diet (20.6% crude protein; 11.7% crude fat; 13.5 mJ/kg DM metabolizable energy) and one diet specially designed for minipigs (12.0% crude protein; 2.9% crude fat; 11.9 MJ/kg DM metabolizable energy). When fed ad libitum for 13 weeks, female Göttingen minipigs developed a significantly (P<0.05) higher body weight (BW) than males (27.4 vs 16.6 kg) on either diet. The large difference in growth between male and female Göttingen minipigs did not appear to be the result from differences in metabolizable energy intake. Metabolizable energy intake of male and female Göttingen minipigs could be predicted by ME=1877 kJxBW(0.61). Both male and female Göttingen minipigs became obese when fed ad libitum, defined by relative backfat thickness. Relative backfat thickness ranged from 5 to 13 cm/100 kg. Females had thicker relative backfat layers than males. Remarkably, no large changes in haematology and clinical chemistry occurred in ad libitum fed Göttingen minipigs as compared to reference values, and no abnormalities other than enlarged fat reserves were observed at necropsy. Apparently, Göttingen minipigs do not restrain FI voluntarily, and restricted feeding is therefore indicated to prevent obesity.

Non-invasive method for sampling and extraction of mouse DNA for PCR.

We adapted a non-invasive, fast, reliable and inexpensive procedure for the sampling and extraction of deoxyribonucleic acid (DNA) for genetic testing of mice. The procedure is based on a simple DNA extraction procedure used in the forensic genetic testing of humans. It involves mouth swabbing of the inner cheek using a cotton stick, followed by alkaline lysis of the harvested buccal epithelial cells. This procedure allows for repeated sampling and genetic testing of the individual mouse, and it is faster, simpler and, in our hands, more reliable than the currently used routine procedures for the sampling and extraction of mouse DNA. Current procedures all involve biopsy of a piece of the tail, ear or toe, followed by lengthy procedures to release and isolate the DNA.

Immune complex-associated thrombocytopenic purpura syndrome in sexually mature Göttingen minipigs.

Eleven cases of thrombocytopenic purpura (TP) in sexually mature male or female Göttingen minipigs occurred sporadically over 3 1/2 years in a closed breeding colony protected by strict barrier conditions. Typical clinical signs of TP, including extensive subcutaneous haemorrhages, were seen in all affected animals. Haematological abnormalities included marked thrombocytopenia and anaemia. A consistent histopathological finding was the presence of membranoproliferative lesions in the renal glomeruli. Immunohistochemically, glomerular deposits were positively labelled for complement factor C1q and often also for immunoglobulins. Bone marrow findings consisting of increased numbers of immature and apoptotic megakaryocytes were compatible with a state of increased platelet consumption. Based on the combined presence of thrombocytopenia and renal immune complexes, it is suggested that the syndrome was related to a type III hypersensitivity reaction. However, further studies are needed to verify this hypothesis.

Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study.

The objective of this study was to determine whether use of mupirocin nasal ointment for perioperative eradication of Staphylococcus aureus nasal carriage is effective in preventing the development of surgical site infections (SSIs). A randomized, double-blind, placebo-controlled design was used. Either mupirocin or placebo nasal ointment was applied twice daily to 614 assessable patients from the day of admission to the hospital until the day of surgery. A total of 315 and 299 patients were randomized to receive mupirocin and placebo, respectively. Eradication of nasal carriage was significantly more effective in the mupirocin group (eradication rate, 83.5% versus 27.8%). In the mupirocin group, the rate of endogenous S. aureus infections was 5 times lower than in the placebo group (0.3% and 1.7%, respectively; relative risk, 0.19; 95% confidence interval, 0.02-1.62). Mupirocin nasal ointment did not reduce the SSI rate (by S. aureus) or the duration of hospital stay.

Parameters of glucose and lipid metabolism in the male Göttingen minipig: influence of age, body weight, and breeding family.

The pig is useful as a model for human physiology and pathophysiology and could be an important supplement to the many available rodent models of diabetes mellitus. Due to their small size, Göttingen minipigs are especially suitable for long-term studies. The aim of the study reported here was to establish reference values for a range of glucose and lipid homeostasis parameters of interest that could be used to identify possible diabetes-prone male Göttingen minipig individuals, families, or age groups. Plasma samples from nonfed animals were analyzed for glucose, leptin, fructosamine, insulin, C-peptide, triglyceride, free fatty acids, and total cholesterol values. Breeding family had significant effects only on plasma triglyceride concentrations (P < 0.001). Plasma concentrations of glucose (P = 0.012), fructosamine (P < 0.001) and triglycerides (P < 0.001) increased significantly with age, whereas total cholesterol concentration decreased significantly (P = 0.001) with age. Age did not influence other parameters. In conclusion, glycemia and insulinemia increased with age and body weight, possibly indicating a small deterioration in insulin sensitivity with age. It is, therefore, hypothesized that older, compared to younger animals may be more useful in the development of a model of type-2 diabetes mellitus. Furthermore, on the basis of decrease in cholesterol concentration with age, animals fed ad libitum with possibly a high calorie diet might be even more useful in the development of a type-2 diabetes mellitus model.

Intragastric balloons in adolescents with morbid obesity.

OBJECTIVES: Morbid obesity inducing medical pathologies such as hypertension, hypercholesterolaemia or orthopaedic abnormalities is an increasing problem in adolescents. Intragastric balloons have been used, with a varying degree of success, in adults. METHODS: An intragastric silicone balloon was filled with 500-700 ml physiological serum in five adolescents (11-17 years old) with a morbid obesity (body mass index percentage (BMI %, calculated as a percentage of normal BMI for patient's sex and age, range 148-293%), and was left in place for six months. RESULTS: The balloons were well tolerated. A transient beneficial effect was noted, with a non-significant trend in decrease of the BMI % after 3 months (P = 0.07). However, 3 months later (6 months after the insertion), the BMI % in all five adolescents was significantly higher than before insertion of the balloon (P < 0.05). CONCLUSION: We observed a failure to lose weight with the help of an intragastric balloon in five selected adolescents. Since the beneficial effect of intragastric balloons in the five adolescents studied was only temporary, these balloons seem not to be indicated in adolescents with morbid obesity.

Lumbar spine bone mineral density in diabetic children with recent onset.

To detect early abnormalities in bone mineralization, the lumbar spine bone mineral density (BMD) of diabetic children with a diabetes onset of less than 5 years and treated with a similar insulin treatment scheme was measured at the level of the lumbar spine by dual-energy X-ray absorptiometry (DEXA), a most sensitive technique for detecting osteopenia in children. Fifteen male and 8 female children and adolescents (mean age +/- SD: 12.5+/-3.7 years), 1-5 years after the clinical onset of their diabetes, were studied. Measurements of the lumbar spine (L1-L4) BMD, expressed in gHA/cm2 and as a z-score for age, were performed with a commercial DEXA apparatus (Hologic QDR 1000 W, Hologic Inc., Waltham, USA). Calcium-phosphorus metabolism was studied by measuring the circulating levels of calcium, phosphorus, alkaline phosphatase, osteocalcin, 25-OH-vitamin D and parathyroid hormone and the urinary excretion of calcium and phosphorus. The mean BMD of the studied group was 0.75 (0.16) gHA/cm2 giving a mean z-score of -0.31+/-0.95. Only 1 of the patients had a BMD lower than -2 SD. No sex difference in BMD z-score existed. BMD SD was positively correlated with height SD (R = 0.56, p < 0.005), but not with the age of the patients, the duration of the disease, the degree of metabolic control or the studied parameters of the calcium-phosphorus metabolism. In conclusion, diabetic children have a normal lumbar spine BMD during the first years of the disease, when a good metabolic control and no abnormalities in the calcium-phosphorus metabolism are present. As in normal children, areal BMD by DEXA is highly dependent on the body height, necessitating corrections if abnormalities in skeletal growth or pubertal development exist.

Microbiological monitoring of laboratory pigs.

Purpose-bred minipigs, are often used as the non-rodent species in toxicology. Infections may interfere with animal experiments, and there are no scientific reasons why the non-rodent species should be of a lower microbiological quality than the rodent species. Therefore, a system for health monitoring of pigs was developed in order to raise the quality of laboratory pigs to the level of laboratory rodents. This system, which includes screening for several viruses, bacteria and ecto- and endoparasites, was used for monitoring minipigs from a barrier unit with the same standards applied to rodents units. In these pigs only rotaviruses are found, which was shown by both serological antibody detection and by detection of rotaviral antigen in faeces. In minipigs from another unit with far less hygienic protection rotaviruses were also found along with certain influenza- and coronaviruses, as well as Pasteurella spp. It is concluded, that it is possible to raise pigs of a microbiological quality comparable to the quality of rats and mice, and that advanced microbiological monitoring in pigs will reveal useful information.

Nutrition of (Göttingen) minipigs: facts, assumptions and mysteries.

Detailed guidelines are available concerning the nutrient requirements of pigs (National Research Council 1988). These nutrient requirements are based on ad libitum feeding and obtaining maximum growth, as they have originated from feeding schedules for slaughter pigs. Whether these nutrient guidelines for pigs can be applied to minipigs as well remains to be answered. Moreover, ad libitum feeding and maximum growth are not considered the optimum in scientific research. The German Society for Laboratory Animal Science has published guidelines for the composition of minipig diets, mainly based on empirical results (1993). Upon comparison of dietary guidelines for pigs and minipigs, differences can be found. At the moment it is unclear which of the two dietary guidelines guarantees that all minimum nutrient requirements of the minipig are met. Restricted feeding is often applied in studies using minipigs, in order to prevent obesity. As the two guidelines are based on ad libitum feeding, this raises the question whether restriction results in (marginal) nutrient deficiencies, which may interfere with experimental results.

The Göttingen minipig in pharmacology and toxicology.

Pigs traditionally are used in surgical and physiological research. Since the development of the Minnesota minipig in 1949 at the Hormel Institute (USA), miniature pigs have been introduced as a model in pharmacology and toxicology, because of scientific, economic and ethical reasons.