Personalized Lifestyle Intervention and Functional Evaluation Health Outcomes SurvEy: Presentation of the LIFEHOUSE Study Using N-of-One Tent–Umbrella–Bucket Design

The working definition of health is often the simple absence of diagnosed disease. This common standard is limiting given that changes in functional health status represent early warning signs of impending health declines. Longitudinal assessment of functional health status may foster prevention of disease occurrence and modify disease progression. The LIFEHOUSE (Lifestyle Intervention and Functional Evaluation-Health Outcomes SurvEy) longitudinal research project explores the impact of personalized lifestyle medicine approaches on functional health determinants. Utilizing an adaptive tent–umbrella–bucket design, the LIFEHOUSE study follows the functional health outcomes of adult participants recruited from a self-insured employee population. Participants were each allocated to the tent of an all-inclusive N-of-one case series. After assessing medical history, nutritional physical exam, baseline functional status (utilizing validated tools to measure metabolic, physical, cognitive, emotional and behavioral functional capacity), serum biomarkers, and genomic and microbiome markers, participants were assigned to applicable umbrellas and buckets. Personalized health programs were developed and implemented using systems biology formalism and functional medicine clinical approaches. The comprehensive database (currently 369 analyzable participants) will yield novel interdisciplinary big-health data and facilitate topological analyses focusing on the interactome among each participant’s genomics, microbiome, diet, lifestyle and environment.

Detection and Functional Evaluation of the P2X7 Receptor in hiPSC Derived Neurons and Microglia-Like Cells

A large body of evidence suggests the involvement of the ATP-gated purinergic receptor P2X7 (P2X7R) in neurodegenerative diseases, including Alzheimer’s disease. While it is well-described to be present and functional on microglia cells contributing to inflammatory responses, some reports suggest a neuronal expression of the receptor as well. Here, we present experimental results showing P2X7 receptors to be expressed on human hiPSC-derived microglia-like cells, hiPSC-derived neuronal progenitors and hiPSC-derived matured neuronal cells. By applying cell surface protein detection assays, we show that P2X7R is not localized on the cell membrane, despite being detected in neuronal cells and thus may not be available for directly mediating neurotoxicity. On hiPSC-derived microglia-like cells, a clear membranous expression was detected. Additionally, we have not observed differences in P2X7R functions between control and familial Alzheimer’s disease patient-derived neuronal cells. Functional assays employing a P2X7R antagonist JNJ 47965567 confirm these findings by showing P2X7R-dependent modulation of microglia-like cells viability upon treatment with P2X7R agonists ATP and BzATP, while the same effect was absent from neuronal cells. Since the majority of P2X7R research was done on rodent models, our work on human hiPSC-derived cells presents a valuable contribution to the field, extending the work on animal models to the human cellular system and toward clinical translation.

Three-dimensional Alignment of the Upper Extremity in the Standing Neutral Position in Healthy Subjects

Background: Though alignment of the spine and lower extremities in the standing neutral position has been evaluated, a few studies evaluating the alignment of the upper extremities have also been made. This study assessed the normal alignment of the upper extremities in the standing neutral position and clarified the three-dimensional angular rotations of the upper extremity joints.Methods: Computed tomography (CT) images of 158 upper extremities from 79 healthy volunteers were prospectively acquired in the standing neutral position using an upright CT scanner. Three-dimensional coordinate systems of the thorax, scapula, humerus, and forearm were designated, and three-dimensional angular rotations of the scapulothoracic, glenohumeral, and elbow joints were calculated.Results: The mean angle of the scapulothoracic joint was 8.5° ± 5.9° of upward rotation, 28.7° ± 5.9° of internal rotation, and 7.9° ± 5.2° of anterior inclination. The mean angle of the glenohumeral joint was 4.4° ± 5.9° of abduction, 9.4° ± 12.3° of internal rotation, and 0.3° ± 4.4° of extension. The mean angle of the elbow joint was 9.6° ± 3.7° of valgus, 88.8° ± 14.3° of pronation, and 15.4° ± 4.2° of flexion. Correlations in angular rotation values were found, and interactions for keeping the upper extremities in a neutral position were observed.Conclusions: This study clarified the three-dimensional angular rotation of upper extremity joints in the standing neutral position using an upright CT scanner. Our results may provide important insights for the functional evaluation of upper extremity alignment.

Coronary Flow Velocity Reserve Using Dobutamine Test for Noninvasive Functional Assessment of Myocardial Bridging

Background: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. Purpose: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. Methods: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27–74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10–40 μg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. Results: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967–1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001–0.534; p = 0.019; OR: 1.147; 95% CI: 1.042–1.263; p = 0.005; respectively). Conclusions: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

Isokinetic and functional shoulder outcomes after arthroscopic capsulolabral stabilization

Introduction Shoulder stability is secured by dynamic and static stabilizers. Rotator cuff is responsible for dynamic stabilization. In cases of shoulder instability their activity is disturbed. Capsulolabral repair restores mainly static stabilization. This surgery treatment technique of shoulder instability was first described by Bankart in 1923. His idea, with further modifications, is commonly used up to this day. Evaluation of muscle shoulder recovery after stabilization should be one of the important criteria to allow patient to return to sport and work. However, not much isokinetic assessment after capsulolabral repair was described. The aim of this study were the following: the comparative assessment of the shoulder rotatory strength in patients following arthroscopic capsulolabral repair of unilateral anterior traumatic instability and clinical assessment with comparison of pre and post-operative results. Material and methods Forty-five patients, 14 women and 31 men, with an average follow-up of 4.4 years were tested bilaterally for internal and external rotation strength at four angular velocities. ASES and UCLA tests were collected before and after surgery. Results The values of peak moment and muscle power parameters were slightly lower for an operated shoulder in comparison to a healthy shoulder for the external rotation. Total work parameter in external rotation was significantly lower for the operated shoulder in comparison to the non-operated side. The internal/external muscle group balance was lower for the operated shoulder in comparison to reference values in the women group. Furthermore, both ASES and UCLA scores were significantly higher after operation. Conclusions After arthroscopic capsulolabral shoulder stabilization, slight differences in isokinetic evaluation, especially in external shoulder rotation, occur. It affects rotators muscle balance. In functional evaluation significant improvement in shoulder function occurs.

Evaluation of Macular Function after Vitrectomy in Diabetic Macular Edema

Purpose: To document the effects of successful vitrectomy on retinal function and anatomy in diabetic patients. Methods: Three-port pars plana vitrectomy with detachment of posterior vitrous face was performed in 30 eyes of 25 patients with diabetic macular oedema DME (11 male, 14 Female).For each patients, visual acuity (VA) examination, measurement of retinal thickness using optical coherence tomography (OCT), full field electro-retinogram (ERG) and multifocal eletroretinogram (MF-ERG) were performed before and 1week,1month and 3months after vitrectomy. Results: Mean postoperative visual acuity was significantly improved (P<0.05); mean retinal thickness was significantly (P=0.001 ) decreased after 3monthes of surgery (from 450±150 into 220±50 micron ) .b-wave amplitudes of all cone and rod responses of ERG were significantly decreased in all vitrectomized eyes after 1 week. At one month, rod response was still unimproved but improved after 3months. Reduction in foveal Function as well as in para-foveal areas detected in the MF-ERG within 1st month. Then, mean P1 wave amplitude of MF-ERG of central ring increased and mean P1 wave implicit time decreased. These changes of MF-ERG parameters observed 3 months after vitrectomy. Conclusion: Multifocal electroretinogram can be useful to provide objective criteria for functional evaluation before and after vitrectomy in diabetic oedema.