Design and characterization of a dynamic vibrational culture system

To engineer a functional vocal fold tissue, the mechanical environment of the native tissue needs to be emulated in vitro. We have created a dynamic culture system capable of generating vibratory stimulations at human phonation frequencies. The novel device is composed of a function generator, a power amplifier, an enclosed loudspeaker and a circumferentially‐anchored silicone membrane. The vibration signals are translated to the membrane aerodynamically by the oscillating air pressure underneath. The vibration profiles detected on the membrane were symmetrical relative to the centre of the membrane as well as the resting position over the range of frequencies (60–300 Hz) and amplitudes tested (1–30 µm). The oscillatory motion of the membrane gave rise to two orthogonal, in‐plane strain components that are similar in magnitude (0.47%) and are strong functions of membrane thickness. Neonatal foreskin fibroblasts (NFFs) attached to the membrane were subjected to a 1 h vibration at 60, 110 and 300 Hz, with the displacement at the centre of the membrane varying in the range 1–30 µm, followed by a 6 h rest. These regimens did not cause morphological changes to the cells. An increase in cell proliferation was detected when NFFs were driven into oscillation at 110 Hz with a normal displacement of 30 µm. qPCR results showed that the expression of genes encoding some extracellular matrix proteins was altered in response to changes in vibratory frequency and amplitude. The dynamic culture device provides a potentially useful in vitro platform for evaluating cellular responses to vibration. Copyright © 2011 John Wiley & Sons, Ltd.     

Evidence for a role for Galphai1 in mediating weak agonist-induced platelet aggregation in human platelets: reduced Galphai1 expression and defective Gi signaling in the platelets of a patient with a chronic bleeding disorder

We have examined platelet functional responses and characterized a novel signaling defect in the platelets of a patient suffering from a chronic bleeding disorder. Platelet aggregation responses stimulated by weak agonists such as adenosine diphosphate (ADP) and adrenaline were severely impaired. In comparison, both aggregation and dense granule secretion were normal following activation with high doses of collagen, thrombin, or phorbol-12 myristate-13 acetate (PMA). ADP, thrombin, or thromboxane A2 (TxA2) signaling through their respective Gq-coupled receptors was normal as assessed by measuring either mobilization of intracellular calcium, diacylglycerol (DAG) generation, or pleckstrin phosphorylation. In comparison, Gi-mediated signaling induced by either thrombin, ADP, or adrenaline, examined by suppression of forskolin-stimulated rise in cyclic AMP (cAMP) was impaired, indicating dysfunctional Galphai signaling. Immunoblot analysis of platelet membranes with specific antiserum against different Galpha subunits indicated normal levels of Galphai2,Galphai3,Galphaz, and Galphaq in patient platelets. However, the Galphai1level was reduced to 25% of that found in normal platelets. Analysis of platelet cDNA and gDNA revealed no abnormality in either the Galphai1 or Galphai2 gene sequences. Our studies implicate the minor expressed Galphai subtype Galphai1 as having an important role in regulating signaling pathways associated with the activation of alphaIIbbeta3 and subsequent platelet aggregation by weak agonists.     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.     

Is Robotic Revisional Bariatric Surgery Justified? An MBSAQIP Analysis

Background

The laparoscopic approach is utilized in greater than 90% of bariatric surgeries. With the growing prevalence of robotic-assisted surgery in bariatrics, there has been limited consensus on the superiority of either laparoscopic or robotic approaches, especially in revisional procedures (conversion from sleeve gastrectomy (SG) to Roux-en-Y gastric bypass (RYGB)).

Methods

A retrospective analysis was performed of the MBSAQIP PUF database of patients who underwent conversion from SG to RYGB procedures in either laparoscopic or robotic-assisted approaches. The groups underwent 2:1 propensity matching and primary outcomes included post-conversion days until discharge (POD), conversion operation length, total and major morbidity, 30-day readmission, 30-day reoperation, 30-day reintervention, and 30-day mortality after conversion.

Results

After 2:1 propensity score matching, 3411 patients (2274 laparoscopic vs 1137 robotic) were included in the study. Intraoperatively, no significant difference was found in total morbidity (6.5% lap vs 5.9% robotic) or major morbidity (1.9% lap vs 1.7% robotic); however, the operative times were significantly longer robotically (126 min vs 164 min). Post-operatively, no significant differences were found in discharge day (1.8 lap vs 1.8 robotic), 30-day readmission (7.6% lap vs 8.6% robotic), reoperation rate (2.9% lap vs 3.7% robotic), additional intervention rate (2.5% lap vs 3.3% robotic), or 30-day mortality (0.1% vs 0.1%).

Conclusion

There is no significant difference in perioperative or intraoperative outcomes between laparoscopic and robotic-assisted SG to RYGB conversion procedures other than a longer operative time in the robotic approach, suggesting increased efficiency with the laparoscopic approach.

Graphical abstract

     

Therapist Self-Report of Fidelity to Core Elements of Family Therapy for Adolescent Behavior Problems: Psychometrics of a Pragmatic Quality Indicator Tool

Therapist-report measures of evidence-based interventions have enormous potential utility as quality indicators in routine care; yet, few such tools have shown strong psychometric properties. This study describes reliability and validity characteristics of a therapist-report measure of family therapy techniques for treating adolescent conduct and substance use problems: Inventory of Therapy Techniques for Core Elements of Family Therapy (ITT-CEFT). Study participants included 31 staff therapists treating 68 adolescent clients in eight community-based mental health and substance use clinics. Therapists submitted ITT-CEFT checklists and companion audio recordings for 189 sessions. The ITT-CEFT contains 13 techniques identified as core elements of three manualized family therapy models that are empirically supported for the target group. Therapists also reported on their use of three motivational interventions, and independent observers coded the submitted recordings. ITT-CEFT factor validity was shown via confirmatory factor analyses of the tool’s theoretical structure. Derived modules were: Family Engagement (four items; Cronbach’s α?=?.72); Relational Orientation (five items; α?=?.74); and Interactional Change (four items; α?=?.66). Concurrent validity analyses showed fair-to-excellent therapist reliability compared to observer ratings (ICCs range .64–.75); they showed moderate therapist accuracy compared to observer mean scores, reflecting a tendency to overestimate delivery of the techniques. Discriminant validity analyses showed tool differentiation from motivational interventions. Results offer provisional evidence for the feasibility of using the therapist-report ITT-CEFT to anchor quality procedures for family therapy interventions in real-world settings.

Trial Registration: The parent clinical trial is registered at www.ClinicalTrials.gov, ID: NCT03342872 (registration date: 11.10.17).

     

Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour

Aims:  Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene ( HMOX-1 ) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients.
Methods and results:  Tumour and corresponding healthy tissue DNA of 44 patients who underwent surgical resection of GIST were analysed by polymerase chain reaction, capillary electrophoresis and DNA sequencing. GTn polymorphism was classified into short (S) and long (L) allele. There was no difference detected in GTn genotype between tumour and healthy tissue DNA. Short GTn allele (SGTn) was significantly associated with metastatic disease, higher tumour recurrence rates and high risk GIST (consensus criteria 2001). Furthermore, SGTn allele carriers had significantly shorter disease-free and overall survival (log rank test, P  < 0.0001). On multivariate Cox regression analysis, GTn polymorphism was identified as an independent prognostic factor for survival ( P  = 0.001).
Conclusions:  HMOX-1 promoter GTn polymorphism is a potential prognostic marker and may help to allocate patients to different risk groups, customized therapy and follow-up. Haeme oxygenase-1 could represent an important candidate gene in the pathogenesis and growth of GIST.     

The Maxi Stabil 3: validation of an aneroid device according to a modified British Hypertension Society protocol

BACKGROUND: Measuring blood pressure with mercury-independent alternatives is rapidly gaining attention. Mercury will be phased out of clinical use as a result of environmental, health and safety concerns and it is of vital importance that any alternative to mercury has to be of a recognized standard. We assessed the accuracy of the Maxi Stabil 3 aneroid device in an adult population according to a modified British Hypertension Society protocol (with the low systolic category changed from less than 90 mmHg to less than 100 mmHg). POPULATION: Eighty-five subjects were recruited from among staff and patients at Guy's and St Thomas' Hospitals, London, UK. METHODS: The aneroid device was connected in parallel to two mercury sphygmomanometers. Nine sequential same-arm measurements were taken from each subject by two trained observers, alternating between mercury sphygmomanometry and the aneroid device. Simultaneous mercury readings were also recorded for additional analysis. RESULTS: The device achieved an A grade for both systolic and diastolic pressures and fulfilled the requirements of the Association for the Advancement of Medical Instrumentation. The mean and standard deviation for systolic and diastolic pressures respectively were -0.6 (4.6) mmHg and -1.3 (3.5) mmHg in sequential analysis, and -1.3 (2.2) mmHg and -1.9 (2.7) mmHg in simultaneous analysis. CONCLUSION: The Maxi Stabil aneroid device can be recommended for use in an adult population.