teemi: An open-source literate programming approach for iterative design-build-test-learn cycles in bioengineering.

Synthetic biology dictates the data-driven engineering of biocatalysis, cellular functions, and organism behavior. Integral to synthetic biology is the aspiration to efficiently find, access, interoperate, and reuse high-quality data on genotype-phenotype relationships of native and engineered biosystems under FAIR principles, and from this facilitate forward-engineering strategies. However, biology is complex at the regulatory level, and noisy at the operational level, thus necessitating systematic and diligent data handling at all levels of the design, build, and test phases in order to maximize learning in the iterative design-build-test-learn engineering cycle. To enable user-friendly simulation, organization, and guidance for the engineering of biosystems, we have developed an open-source python-based computer-aided design and analysis platform operating under a literate programming user-interface hosted on Github. The platform is called teemi and is fully compliant with FAIR principles. In this study we apply teemi for i) designing and simulating bioengineering, ii) integrating and analyzing multivariate datasets, and iii) machine-learning for predictive engineering of metabolic pathway designs for production of a key precursor to medicinal alkaloids in yeast. The teemi platform is publicly available at PyPi and GitHub.

Emergency treatment of pelvic ring injuries: state of the art.

High energy pelvic injuries sustain significant mortality rates, due to acute exsanguination and severe associated injuries. Managing the hemodynamically unstable trauma patient with a bleeding pelvic fracture still forms a major challenge in acute trauma care. Various approaches have been applied through the last decades. At present the concept of Damage Control Resuscitation (DCR) is universally accepted and applied in major trauma centers internationally. DCR combines hemostatic blood transfusions to restore blood volume and physiologic stability, reduced crystalloid fluid administration, permissive hypotension, and immediate hemorrhage control by operative or angiographic means. Different detailed algorithms and orders of hemostatic procedures exist, without clear consensus or guidelines, depending on local traditions and institutional setups. Fracture reduction and immediate stabilization with a binder constitute the basis for angiography and embolization (AE) or pelvic packing (PP) in the hemodynamically unstable patient. AE is time consuming and may not be available 24/7, whereas PP offers a quick and technically easy procedure well suited for the patient in extremis. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has also been described as a valuable adjunct in hemostatic non-responders, but merely constitute a bridge to surgical or angiographic hemostasis and its definitive role in DCR is not yet clearly established. A swift algorithmic approach to the hemodynamically unstable pelvic injury patient is required to achieve optimum results. The present paper summarizes the available literature on the acute management of the bleeding pelvic trauma patient, with emphasis on initial assessment and damage control resuscitation including surgical and angiographic hemostatic procedures. Furthermore, initial treatment of open fractures and associated injuries to the nervous and genitourinary system is outlined.

Functional outcomes and health-related quality of life after reconstruction of segmental bone loss in femur and tibia using the induced membrane technique.

INTRODUCTION: The induced membrane technique (IMT), frequently called Masquelet technique, is an operative, two-staged technique for treatment of segmental bone loss. Previous studies mainly focused on radiological outcome parameters and complication rates, while functional outcomes and health-related quality of life after the IMT were sparsely reported. MATERIALS AND METHODS: Retrospective study containing of a chart review as well as a clinical and radiological follow-up examination of all patients treated with the IMT at a single institution. The clinical outcomes were evaluated using the Lower Extremity Functional Scale (LEFS), the Short-Form-36 (SF-36) and the visual analog scale (VAS) for pain. The radiographic evaluation contained of standard anteroposterior and lateral, as well as hip-knee-ankle (HKA) radiographs. RESULTS: Seventeen patients were included in the study. All had suffered high-energy trauma and sustained additional injuries. Ten bone defects were localized in the femur and seven in the tibia. Ten patients underwent additional operative procedures after IMT stage 2, among them three patients who contracted a postoperative deep infection. The median LEFS was 59 (15-80), and the SF-36 physical component summary (PCS) and mental component summary (MCS) were 41.3 (24.0-56.1) and 56.3 (13.5-66.2), respectively. The median length of the bone defect was 9 (3-15) cm. In 11 patients, union was obtained directly after IMT stage 2. Bone resorption was observed in two patients. At follow-up, 16 of the 17 bone defects had healed. The median follow-up was 59 months (13-177). CONCLUSION: Our results show a high occurrence of complications after IMT stage 2 in segmental bone defects of femur and tibia requiring additional operative procedures. However, fair functional outcomes as well as a good union rate were observed at follow-up.

A cost-effectiveness analysis of reverse total shoulder arthroplasty compared with locking plates in the management of displaced proximal humerus fractures in the elderly: the DelPhi trial.

AIM: To evaluate the cost-effectiveness of surgical treatment with reverse total shoulder arthroplasty (RTSA) compared with open reduction and internal fixation (ORIF) with a locking plate for patients 65-85 years old with a displaced proximal humerus fracture. METHODS: A cost-utility analysis was conducted alongside a multicenter randomized controlled trial, taking a health care perspective. A total of 124 patients with displaced proximal humerus fractures were randomized to treatment with RTSA (n = 64) or ORIF (n = 60) during a 2-year period. The outcome measure was quality-adjusted life years derived from the generic questionnaire 15D in an intention to treat population. The results were expressed as incremental cost-effectiveness ratios, and a probabilistic sensitivity analysis was performed to account for uncertainty in the analysis. RESULTS: At 2 years, 104 patients were eligible for analyses. The mean quality-adjusted life year was 1.24 (95% confidence interval: 1.21-1.28) in the RTSA group and 1.26 (95% confidence interval: 1.22-1.30) in the ORIF group. The mean cost in the RTSA group (€36.755 [€17,654-€55,855]) was higher than that in the ORIF group (€31.953 [€16,226-€47,279]). Using incremental cost-effectiveness ratio, ORIF was the dominant treatment. When using a probabilistic sensitivity analysis with 1000 replications, the plots were centered around origo. This indicates that there is no significant difference in cost or effect. CONCLUSION: In the cost-utility analysis of treatment of displaced proximal humeral fractures, there were no differences between RTSA and ORIF.

Outcome after nonoperative treatment of stable Lisfranc injuries. A prospective cohort study.

BACKGROUND: The aim of this study was to evaluate the outcome after nondisplaced and stable Lisfranc injuries. METHODS: 26 patients with injuries to the Lisfranc joint complex detected on CT scans, but without displacement were tested to be stable using a fluoroscopic stress test. The patients were immobilized in a non-weightbearing short leg cast for 6 weeks. The final follow-up was 55 (IQR 53-60) months after injury. RESULTS: All the Lisfranc injuries were confirmed to be stable on follow-up weightbearing radiographs at a minimum of 3 months after injury. Median American Foot and Ankle Society (AOFAS) midfoot score at 1-year follow-up was 89 (IQR 84-97) and at final follow-up 100 (IQR 90-100); The AOFAS score continued to improve after 1-year (P=.005). The median visual analog scale (VAS) for pain was 0 (IQR 0-0) at the final follow-up. One patient had radiological signs of osteoarthritis at 1-year follow-up. CONCLUSION: Stable Lisfranc injuries treated nonoperatively had an excellent outcome in this study with a median follow-up of 55 months. The AOFAS score continued to improve after 1 year.

External validity in a multicenter randomized clinical trial of proximal humeral fractures: the DelPhi trial.

BACKGROUND: Randomized controlled trials (RCT) are regarded as the gold standard for effect evaluation in clinical interventions. However, RCTs may not produce relevant results to all patient groups. We aimed to assess the external validity of a multicenter RCT (DelPhi trial). METHODS: The DelPhi RCT investigated whether elderly patients with displaced proximal humeral fractures (PHFs) receiving reversed total shoulder prosthetic replacement (RTSA) gained better functional outcomes compared to open reduction and internal fixation (ORIF) using an proximal humerus locking plate (PHILOS). Eligible patients were between 65 and 85 years old with severely displaced 11-B2 or 11-C2 fractures (AO/OTA-classification, 2007). We compared baseline and follow-up data of patients for two of the seven hospitals that were included in the DelPhi trial (n = 54) with non-included patients (n = 69). Comparisons were made based on reviewing medical records regarding demographic, health and fracture parameters. RESULTS: Forty-four percent of the eligible patients were included in the DelPhi trial. Comparing included and non-included patients indicated higher incidences of serious heart disease (P = 0.044) and a tendency toward higher tobacco intake (P = 0.067) in non-included patients. Furthermore, non-included patients were older (P = 0.040) and had higher ASA classification (P < 0.001) and were in more need for resident aid (in-home assistance) (P = 0.022) than included patients. The cause of PHF was more frequently related to fall indoors in non-included vs. included patients (P = 0.018) and non-included patients were more prone to other concomitant fractures (P = 0.004). Having concomitant fractures was associated with osteoporosis (P = 0.014). We observed no significant differences in rates of complications or deaths between included and non-included patients within 3 months after treatment. In descending order, non-included patients were treated conservatively, with PHILOS, RTSA, anatomic hemi-prothesis or an alternative type of ORIF. RTSA was the preferred treatment choice for C2-type fractures (P < 0.001). CONCLUSIONS: Results from the DelPhi RCT may not directly apply to older PHFs patients with lower health status or concomitant fractures. LEVEL OF EVIDENCE: Level 4.

Differential inflammasome activation predisposes to acute-on-chronic liver failure in human and experimental cirrhosis with and without previous decompensation.

OBJECTIVE: Systemic inflammation predisposes acutely decompensated (AD) cirrhosis to the development of acute-on-chronic liver failure (ACLF). Supportive treatment can improve AD patients, becoming recompensated. Little is known about the outcome of patients recompensated after AD. We hypothesise that different inflammasome activation is involved in ACLF development in compensated and recompensated patients. DESIGN: 249 patients with cirrhosis, divided into compensated and recompensated (previous AD), were followed prospectively for fatal ACLF development. Two external cohorts (n=327) (recompensation, AD and ACLF) were included. Inflammasome-driving interleukins (ILs), IL-1α (caspase-4/11-dependent) and IL-1ß (caspase-1-dependent), were measured. In rats, bile duct ligation-induced cirrhosis and lipopolysaccharide exposition were used to induce AD and subsequent recompensation. IL-1α and IL-1ß levels and upstream/downstream gene expression were measured. RESULTS: Patients developing ACLF showed higher baseline levels of ILs. Recompensated patients and patients with detectable ILs had higher rates of ACLF development than compensated patients. Baseline CLIF-C (European Foundation for the study of chronic liver failure consortium) AD, albumin and IL-1α were independent predictors of ACLF development in compensated and CLIF-C AD and IL-1ß in recompensated patients. Compensated rats showed higher IL-1α gene expression and recompensated rats higher IL-1ß levels with higher hepatic gene expression. Higher IL-1ß detection rates in recompensated patients developing ACLF and higher IL-1α and IL-1ß detection rates in patients with ACLF were confirmed in the two external cohorts. CONCLUSION: Previous AD is an important risk factor for fatal ACLF development and possibly linked with inflammasome activation. Animal models confirmed the results showing a link between ACLF development and IL-1α in compensated cirrhosis and IL-1ß in recompensated cirrhosis.

Stable glenoid component of reverse total shoulder arthroplasty at 2 years as measured with model-based radiostereometric analysis (RSA).

Background and purpose - Reverse total shoulder arthroplasty (TSA) is used for treating cuff arthropathy, displaced proximal humeral fractures (PHF), and in revision shoulder surgery, despite sparse evidence on long-term results. We assessed stability of the glenoid component in reverse TSA, using model-based RSA.Patients and methods - 20 patients (mean age 76 years, 17 female), operated on with reverse TSA at Oslo University Hospital, in 2015-2017 were included. Indications for surgeries were PHFs, malunion, cuff arthropathy, and chronic shoulder dislocation. RSA markers were placed in the scapular neck, the coracoid, and the acromion. RSA radiographs were conducted postoperatively, at 3 months, 1 year, and 2 years. RSA analysis was performed using RSAcore with Reversed Engineering (RE) modality, with clinical precision < 0.25 mm for all translations (x, y, z) and < 0.7° for rotations (x, z). Scapular "notching" was assessed in conventional radiographs.Results - 1 patient was excluded due to revision surgery. More than half of the patients displayed measurable migration at 2 years: 6 patients with linear translations below 1 mm and 8 patients who showed rotational migration. Except for one outlier, the measured rotations were below 2°. The migration pattern suggested implant stability at 2 years. 10 patients showed radiolographic signs of "notching", and the mean Oxford Shoulder Score (OSS) at 2 years was 29 points (15-36 points).Interpretation - Stability analysis of the glenoid component of reversed total shoulder arthroplasty using reversed engineering (RE) model-based RSA indicated component stability at 2 years.

Trochanteric stabilizing plate in the treatment of trochanteric fractures: a scoping review.

Background and purpose - The trochanteric stabilizing plate (TSP) may be used as an adjunct to a sliding hip screw (SHS) in the treatment of trochanteric fractures to increase construct stability. We performed a scoping review of the literature to clarify when and how the TSP may be useful.Methods - A systematic search was performed in 5 databases and followed by a backwards-and-forwards citation search of the identified papers. 24 studies were included.Results - 6 biomechanical studies and 18 clinical studies were included in the review. The studies presented mainly low-level evidence. All studies were on unstable trochanteric fractures or fracture models. Due to the heterogeneity of methods and reporting, we were not able to perform a meta-analysis. In the biomechanical trials, the TSP appeared to increase stability compared with SHS alone, up to a level comparable with intramedullary nails (IMNs). We identified 1,091 clinical cases in the literature where a TSP had been used. There were 82 (8%) reoperations. The rate of complications and reoperations for SHS plus TSP was similar to previous reports on SHS alone and IMN. It was not possible to conclude whether the TSP gave better clinical results, when compared with either SHS alone or with IMN.Interpretation - The heterogeneity of methods and reporting precluded any clear recommendations on when to use the TSP, or if it should be used at all.

Postprandial Nutrient Handling and Gastrointestinal Hormone Secretion After Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy.

BACKGROUND & AIMS: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) induce substantial weight loss and improve glycemic control in patients with type 2 diabetes, but it is not clear whether these occur via the same mechanisms. We compared absorption rates of glucose and protein, as well as profiles of gastro-entero-pancreatic hormones, in patients who had undergone SG or RYGB vs controls. METHODS: We performed a cross-sectional study of 12 patients who had undergone sleeve gastrectomy, 12 patients who had undergone RYGB, and 12 individuals who had undergone neither surgery (controls), all in Denmark. Study participants were matched for body mass index, age, sex, and postoperative weight loss, and all had stable weights. They received continuous infusions of stable isotopes of glucose, glycerol, phenylalanine, tyrosine, and urea before and during a mixed meal containing labeled glucose and intrinsically phenylalanine-labeled caseinate. Blood samples were collected for 6 hours, at 10- to 60-minute intervals, and analyzed. RESULTS: The systemic appearance of ingested glucose was faster after RYGB and SG vs controls; the peak glucose appearance rate was 64% higher after RYGB, and 23% higher after SG (both P < .05); the peak phenylalanine appearance rate from ingested casein was 118% higher after RYGB (P < .01), but similar between patients who had undergone SG and controls. Larger, but more transient increases in levels of plasma glucose and amino acids were accompanied by higher secretion of insulin, glucagon-like peptide 1, peptide YY, and cholecystokinin after RYGB, whereas levels of ghrelin were lower after SG, compared with RYGB and controls. Total 6-hour oral recovery of ingested glucose and protein was comparable among groups. CONCLUSIONS: Postprandial glucose and protein absorption and gastro-entero-pancreatic hormone secretions differ after SG and RYGB. RYGB was characterized by accelerated absorption of glucose and amino acids, whereas protein metabolism after SG did not differ significantly from controls, suggesting that different mechanisms explain improved glycemic control and weight loss after these surgical procedures. ClinicalTrials.gov ID NCT03046186.

Bilio-enteric flow and plasma concentrations of bile acids after gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: Bile acids in plasma are elevated after bariatric surgery and may contribute to metabolic improvements, but underlying changes in bile flow are poorly understood. We assessed bilio-enteric flow of bile and plasma bile concentrations in individuals with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with matched non-surgical controls (CON). SUBJECTS/METHODS: Fifteen RYGB, 10 SG and 15 CON underwent 99Tc-mebrofenin cholescintigraphy combined with intake of a high-fat 111In-DTPA-labelled meal and frequent blood sampling. A 75Se-HCAT test was used to assess bile acid retention. RESULTS: After RYGB, gallbladder filling was decreased (p = 0.045 versus CON), basal flow of bile into the small intestine increased (p = 0.005), bile acid retention augmented (p = 0.021) and basal bile acid plasma concentrations elevated (p = 0.009). During the meal, foods passed unimpeded through the gastric pouch resulting in almost instant postprandial mixing of bile and foods, but the postprandial rise in plasma bile acids was brief and associated with decreased overall release of fibroblast growth factor-19 (FGF-19) compared with CON (p = 0.033). After SG, bile flow and retention were largely unaltered (p > 0.05 versus CON), but gastric emptying was accelerated (p < 0.001) causing earlier mixture of bile and foods also in this group. Neither basal nor postprandial bile acid concentrations differed between SG and CON. CONCLUSIONS: Bilio-enteric bile flow is markedly altered after RYGB resulting in changes in plasma concentrations of bile acids and FGF-19, whereas bile flow and plasma concentrations are largely unaltered after SG.

Cardiodynamic state is associated with systemic inflammation and fatal acute-on-chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by high short-term mortality and systemic inflammation (SI). Recently, different cardiodynamic states were shown to independently predict outcomes in cirrhosis. The relationship between cardiodynamic states, SI, and portal hypertension and their impact on ACLF development remains unclear. The aim of this study was therefore to evaluate the interplay of cardiodynamic state and SI on fatal ACLF development in cirrhosis. RESULTS: At inclusion, hemodynamic measures including cardiac index (CI) and hepatic venous pressure gradient of 208 patients were measured. Patients were followed prospectively for fatal ACLF development (primary endpoint). SI was assessed by proinflammatory markers such as interleukins (ILs) 6 and 8 and soluble IL-33 receptor (sIL-33R). Patients were divided according to CI (<3.2; 3.2-4.2; >4.2 L/min/m2 ) in hypo- (n = 84), normo- (n = 69) and hyperdynamic group (n = 55). After a median follow-up of 3 years, the highest risk of fatal ACLF was seen in hyperdynamic (35%) and hypodynamic patients (25%) compared with normodynamic (14%) (P = .011). Hyperdynamic patients showed the highest rate of SI. The detectable level of IL-6 was an independent predictor of fatal ACLF development. CONCLUSIONS: Cirrhotic patients with hyperdynamic and hypodynamic circulation have a higher risk of fatal ACLF. Therefore, the cardiodynamic state is strongly associated with SI, which is an independent predictor of development of fatal ACLF.

Biomechanical comparison of tension band wiring and plate fixation with locking screws in transverse olecranon fractures.

BACKGROUND: Tension band wiring (TBW) is the standard method for treating transverse olecranon fractures, but high rates of complications and reoperations have been reported. Plate fixation (PF) with locking screws has been introduced as an alternative method that may retain the fracture reduction better with a higher load to failure. METHODS: Twenty paired cadaveric elbows were used. All soft tissues except for the triceps tendon were removed. A standardized transverse fracture was created, and each pair was allocated randomly to TBW or PF with locking screws. The triceps tendon was mounted to the materials testing machine with the elbow in 90° of flexion. Construct stiffness was compared 3 times. Then, the elbows underwent a chair lift-off test by loading the triceps tendon to 300 N for 500 cycles. Finally, a load-to-failure test was performed, and failure mechanism was recorded. RESULTS: The construct stiffness of PF was higher in the first of 3 measurements. No difference was observed in the cyclic test or in load to failure. Hardware failure was the failure mechanism in 8 of 10 TBW constructs, and all failures occurred directly under the twists of the metal wire. Hardware failure was the cause of failure in only 1 elbow in the PF group (P < .01). CONCLUSION: There was no difference in fracture displacement following fixation with TBW and PF with locking screws in transverse olecranon fractures. However, assessment of the mode of hardware failure identified the metal cerclage twist as the weakest link in the TBW construct.

Results after introduction of a hip fracture care pathway: comparison with usual care.

Background and purpose - We established a care pathway for hip fracture patients, a "Hip Fracture Unit" (HFU), aiming to provide better in-hospital care and thus improve outcome. We compared the results after introduction of the HFU with a historical control group.Patients and methods - The HFU consisted of a series of measures within the orthopedic ward, such as reducing preoperative waiting time, increased use of nerve blocks, early mobilization, and osteoporosis treatment. 276 patients admitted from May 2014 to May 2015 constituted the HFU group and 167 patients admitted from September 2009 to January 2012 constituted the historical control group. Patients were followed prospectively up to 12 months post fracture.Results - Mean preoperative waiting time was 24 hours in the HFU group and 29 hours in the control group (p = 0.003). 123 patients (47%) in the HFU were started on anti-osteoporosis treatment while in hospital. "Short Physical Performance Battery" score (SPPB) was mean 5.5 in the HFU group and 3.8 in the control group at 4 months (p < 0.001), and 5.7 vs. 3.6 at 12 months (p < 0.001). The mortality rate at 4 months was 15% in both groups. No statistically significant differences were found in readmissions, complications, new nursing home admissions, in Barthel ADL index or a mental capacity test at the follow-ups.

Randomized trial comparing suture button with single 3.5 mm syndesmotic screw for ankle syndesmosis injury: similar results at 2 years.

Background and purpose - Better outcomes are reported for suture button (SB) compared with syndesmotic screws (SS) in patients treated for an acute ankle syndesmotic injury. One reason could be that screws are more rigid than an SB. A single tricortical 3.5 mm syndesmotic screw (TS) is the most dynamic screw option. Our hypothesis is that 1 SB and 1 TS provide similar results. Therefore, in randomized controlled trial, we compared the results between SB and TS for syndesmotic stabilization in patients with acute syndesmosis injury. Patients and methods - 113 patients with acute syndesmotic injury were randomized to SB (n = 55) or TS (n = 58). The American Orthopedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Score was the primary outcome measure. Secondary outcome measures included Manchester Oxford Foot Questionnaire (MOXFQ), Olerud-Molander Ankle score (OMA), visual analogue scale (VAS), EuroQol- 5D (EQ-5D), radiologic results, range of motion, complications, and reoperations (no implants were routinely removed). CT scans of both ankles were obtained after surgery, and after 1 and 2 years. Results - The 2-year follow-up rate was 84%. At 2 years, median AOFAS score was 97 in both groups (IQR SB 87-100, IQR TS 90-100, p = 0.7), median MOXFQ index was 5 in the SB group and 3 in the TS group (IQR 0-18 vs. 0-8, p = 0.2), and median OMA score was 90 in the SB group and 100 in the TS group (IQR 75-100 vs. 83-100, p = 0.2). The syndesmotic reduction was similar 2 years after surgery; 19/55 patients in the SB group and 13/58 in the TS group had a difference in anterior syndesmotic width ≥ 2 mm (p = 0.3). 0 patients in the SB group and 5 patients in the TS group had complete tibiofibular synostosis (p = 0.03). At 2 years, 10 TS were broken. Complications and reoperations were similar between the groups. Interpretation - We found no clinically relevant differences regarding outcome scores between the groups. TS is an inexpensive alternative to SB.

Lisfranc injuries: Incidence, mechanisms of injury and predictors of instability.

BACKGROUND: In Lisfranc injuries the stability of the tarsometatarsal joints guides the treatment of the injury. Determining the stability, especially in the subtle Lisfranc injuries, can be challenging. The purpose of this study was to identify incidence, mechanisms of injury and predictors for instability in Lisfranc injuries. METHODS: Eighty-four Lisfranc injuries presenting at Oslo University Hospital between September 2014 and August 2015 were included. The diagnosis was based on radiologically verified injuries to the tarsometatarsal joints. Associations between radiographic findings and stability were examined. RESULTS: The incidence of Lisfranc injuries was 14/100,000 person-years, and only 31% were high-energy injuries. The incidence of unstable injuries was 6/100,000 person-years, and these were more common in women than men (P = 0.016). Intraarticular fractures in the two lateral tarsometatarsal joints increased the risk of instability (P = 0.007). The height of the second tarsometatarsal joint was less in the unstable injuries than in the stable injuries (P = 0.036). CONCLUSION: The incidence of Lisfranc injuries in the present study is higher than previously published. The most common mechanism of injury is low-energy trauma. Intraarticular fractures in the two lateral tarsometatarsal joints, female gender and shorter second tarsometatarsal joint height increase the risk of an unstable injury. LEVEL OF EVIDENCE: Level III, cross-sectional study.

Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity.

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2 (range of 47.9-69.0)] and 10 men without obesity [BMI of 24.6 kg/m2 (range of 21.7-26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipid P = 0.046; GMETwater P = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion. NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.

Indocyanine green retention test in cirrhosis and portal hypertension: Accuracy and relation to severity of disease.

BACKGROUND AND AIMS: Patients with cirrhosis and portal hypertension often develop complications relating to hepatic excretory dysfunction. The standard measurement of the hepatic excretion is the constant infusion indocyanine green clearance (ICGCI ) technique. The ICG 15-min retention test (ICG-r15) is faster, more patient friendly, and cheaper. The aims were to compare the ICG-r15 test with the standard method, to assess relations to patient characteristics and survival, and to assess the ICG-r15 level in healthy control subjects. METHODS: This study included 68 patients with cirrhosis and portal hypertension (Child class A/B/C:17/37/14). All patients underwent a full liver vein catheterization and hemodynamic evaluation with determination of ICG-r15 and ICGCI as the reference in a subset of 38 patients. Sixteen healthy control subjects were included for compiling a reference interval. RESULTS: The ICG-r15 was increased in the cirrhotic patients with increasing values in parallel with liver dysfunction (15/41/58%) in Child class A/B/C compared with 7% in the controls (P < 0.001). ICG-r15 correlated highly significantly with the ICGCI (r = -0.96, P < 0.0001) and in a multivariate regression analysis with hepatic venous pressure gradient, markers of liver dysfunction and hyperdynamic circulation (P < 0.05-0.005). In the control group, normal reference values ranged from 0% to 13%. In addition, ICG-r15 was significantly related to mortality in the patient group (P = 0.02). CONCLUSIONS: Indocyanine green-r15 reflects portal hypertension, the degree of hepatic failure, and survival and may replace the standard ICGCI . A more elaborated reference interval needs to be compiled, and the prognostic value of ICG-r15 should be validated.

Gastrointestinal motility, gut hormone secretion, and energy intake after oral loads of free fatty acid or triglyceride in older and middle-aged men.

In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ±â€¯3.4 (mean ±â€¯SD) years) and 10 middle-aged (age 43.1 ±â€¯8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p < 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p < 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p < 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.

D-VASim: an interactive virtual laboratory environment for the simulation and analysis of genetic circuits.

Simulation and behavioral analysis of genetic circuits is a standard approach of functional verification prior to their physical implementation. Many software tools have been developed to perform in silico analysis for this purpose, but none of them allow users to interact with the model during runtime. The runtime interaction gives the user a feeling of being in the lab performing a real world experiment. In this work, we present a user-friendly software tool named D-VASim (Dynamic Virtual Analyzer and Simulator), which provides a virtual laboratory environment to simulate and analyze the behavior of genetic logic circuit models represented in an SBML (Systems Biology Markup Language). Hence, SBML models developed in other software environments can be analyzed and simulated in D-VASim. D-VASim offers deterministic as well as stochastic simulation; and differs from other software tools by being able to extract and validate the Boolean logic from the SBML model. D-VASim is also capable of analyzing the threshold value and propagation delay of a genetic circuit model. AVAILABILITY AND IMPLEMENTATION: D-VASim is available for Windows and Mac OS and can be downloaded from bda.compute.dtu.dk/downloads/. CONTACT: haba@dtu.dk, jama@dtu.dk.