Comprehensive assessment of gastric emptying with a stable isotope breath test

Background The [¹³C]‐Spirulina platensis gastric emptying breath test (GEBT) with five samples is accurate relative to scintigraphy. This study was primarily designed to further validate this GEBT using a slightly different process for incorporating [¹³C] in Spirulina and to evaluate the utility of additional samples for assessing early gastric emptying. Methods After a 223 kcal, test meal labeled with ^99mTc and [¹³C]‐S. platensis, scintigraphic images, and five breath samples (45, 90, 120, 180, and 240 min, GEBT5) were collected in 14 controls (Part A). In Part B, nine breath samples were collected at 15, 30, 45, 60, 90, 120, 150, 180, and 240 min (GEBT9) in 30 subjects (15 controls, 15 dyspepsia). Using correlation between [¹³C] breath excretion and scintigraphic emptying, lag time (t₁₀, time for 10% emptying), emptying at 30 min (GE₃₀), and half time (t₅₀) were estimated for GEBT5 (Parts A and B) and GEBT9 (Part B). Key Results Half time values for scintigraphy, GEBT5, and GEBT9 were highly concordant. t₁₀ by GEBT9 (90%CI, 6–15 min) was more strongly correlated [CCC 0.80 (95% CI, 0.63–0.90)] with scintigraphy (90% CI, 5–12 min), than GEBT5 [10–19 min, CCC 0.73 (95% CI, 0.54–0.85)]. The correlation between estimated values (GEBT9) and linearly interpolated values (GEBT5) was closer at 60 [CCC 0.95 (95% CI, 0.91–0.97)] than 30 min [CCC 0.81 (95% CI, 0.71–0.89)]. Conclusions & Inferences The [¹³C]‐S. platensis GEBT can accurately measure GE. While 5‐ and 9‐samples are equally accurate for measuring t₅₀, GEBT9 provides a more comprehensive assessment of early GE (t₁₀ and GE₃₀).     

Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms

Background Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin‐treated diabetes. Methods On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire. Key Results We included 115 patients with insulin‐treated diabetes (median age 53, range 21–69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P < 0.0001). Eighty‐three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P < 0.001) and nausea/vomiting (r = 0.30; P < 0.001). Conclusions & Inferences A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.     

Derivation of a Composite Measure of Embedded Symptom Validity Indices

Assessment of effort on cognitive testing has become a suggested standard in both forensic and clinical neuropsychological assessment. Both stand-alone and empirically derived embedded measures have been developed, however guidelines for combining several measures are not always available. This study used logistic regression analysis to derive a multivariable composite to detect suboptimal effort using scores extracted from commonly administered neuropsychological tests. A model predicting suboptimal effort, as defined by performance on the Medical Symptom Validity Test, was created with 124 participants using variables from the California Verbal Learning test 2nd edition, Rey Complex Figure Test and the Wechsler Memory Scale 3rd edition. The model reliably predicted suboptimal effort (χ^2?=?44.37, p?<?.001) with excellent discrimination (AUC?=?.84).     

The Minimum Clinically Important Difference in the Repeatable Battery for the Assessment of Neuropsychological Status

Objective: There is no established minimum clinically important difference (MCID) for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) index and total scale scores. This study aimed to estimate the MCID for the RBANS index scores and total scale score. Method: Participants included 1,856 ethnic Chinese, older adults. Distribution- and anchor-based methods were used to estimate values for the MCID. Distribution-based estimates were calculated as the standard error of measurement (SEM) and .5 standard deviations (SD). For anchor-based estimates, we compared RBANS scores between the clinical dementia rating (CDR) scale no dementia and very mild dementia groups and between the clinical assessment of dementia (CAD) cognitively normal and mild cognitive impairment groups using regression models adjusting for demographic characteristics. Results: Estimates from the CDR anchor were 7.79, 8.63, 10.74, 9.74, 5.61, and 3.77 for the total scale score, language, immediate memory, delayed memory, visuospatial/constructional, and the attention index, respectively. Estimates from the distribution-based methods were similar to the estimates based on the CDR, except for the language and attention indexes. Estimates from the CAD anchor were larger. Conclusions: We estimated the MCID for the total scale score, language, immediate memory, delayed memory, visuospatial/constructional, and attention indexes of the RBANS as 8, 9, 10, 10, 6, and 4 points, respectively. These estimates are best suited to discriminate between patient groups, for example, in a clinical trial setting. Further research is needed using longitudinal data to assess their applicability to assess within patient differences.     

Neurotoxic effects of iron overload under high glucose concentration

Iron overload can lead to cytotoxicity, and it is a risk factor for diabetic peripheral neuropathy. However, the underlying mechanism remains unclear. We conjectured that iron overload-induced neurotoxicity might be associated with oxidative stress and the NF-E2-related factor 2 （Nrf2）/ARE signaling pathway. As an in vitro cellular model of diabetic peripheral neuropathy, PC12 cells ex- posed to high glucose concentration were used in this study. PC12 cells were cultured with ferric ammonium citrate at different concentrations to create iron overload. PC12 cells cultured in ferric ammonium citrate under high glucose concentration had significantly low cell viability, a high rate of apoptosis, and elevated reactive oxygen species and malondialdehyde levels. These changes were dependent on ferric ammonium citrate concentration. Nrf2 mRNA and protein expression in the ferric ammonium citrate groups were inhibited markedly in a dose-dependent manner. All changes could be inhibited by addition of deferoxamine. These results indicate that iron overload aggravates oxidative stress injury in neural cells under high glucose concentration and that the Nrf2/ARE sigfnaling pathway might play an important role in this process.     

Deep brain stimulation affects conditioned and unconditioned anxiety in different brain areas

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) has proven to be an effective treatment for therapy refractory obsessive–compulsive disorder. Clinical observations show that anxiety symptoms decrease rapidly following DBS. As in clinical studies different regions are targeted, it is of principal interest to understand which brain area is responsible for the anxiolytic effect and whether high-frequency stimulation of different areas differentially affect unconditioned (innate) and conditioned (learned) anxiety. In this study, we examined the effect of stimulation in five brain areas in rats (NAc core and shell, bed nucleus of the stria terminalis (BNST), internal capsule (IC) and the ventral medial caudate nucleus (CAU)). The elevated plus maze was used to test the effect of stimulation on unconditioned anxiety, the Vogel conflict test for conditioned anxiety, and an activity test for general locomotor behaviour. We found different anxiolytic effects of stimulation in the five target areas. Stimulation of the CAU decreased both conditioned and unconditioned anxiety, while stimulation of the IC uniquely reduced conditioned anxiety. Remarkably, neither the accumbens nor the BNST stimulation affected conditioned or unconditioned anxiety. Locomotor activity increased with NAc core stimulation but decreased with the BNST. These findings suggest that (1) DBS may have a differential effect on unconditioned and conditioned anxiety depending on the stimulation area, and that (2) stimulation of the IC exclusively reduces conditioned anxiety. This suggests that the anxiolytic effects of DBS seen in OCD patients may not be induced by stimulation of the NAc, but rather by the IC.     

Multiaxial mechanical properties and constitutive modeling of human adipose tissue: A basis for preoperative simulations in plastic and reconstructive surgery

A preoperative simulation of soft tissue deformations during plastic and reconstructive surgery is desirable to support the surgeon’s planning and to improve surgical outcomes. The current development of constitutive adipose tissue models, for the implementation in multilayer computational frameworks for the simulation of human soft tissue deformations, has proved difficult because knowledge of the required mechanical parameters of fat tissue is limited. Therefore, for the first time, human abdominal adipose tissues were mechanically investigated by biaxial tensile and triaxial shear tests. The results of this study suggest that human abdominal adipose tissues under quasi-static and dynamic multiaxial loadings can be characterized as a nonlinear, anisotropic and viscoelastic soft biological material. The nonlinear and anisotropic features are consequences of the material’s collagenous microstructure. The aligned collagenous septa observed in histological investigations causes the anisotropy of the tissue. A hyperelastic model used in this study was appropriate to represent the quasi-static multiaxial mechanical behavior of fat tissue. The constitutive parameters are intended to serve as a basis for soft tissue simulations using the finite element method, which is an apparent method for obtaining promising results in the field of plastic and reconstructive surgery.