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Sleeping pattern and activities of daily living modulate protein expression in AMD.

ABSTRACT: Degeneration of macular photoreceptors is a prominent characteristic of age-related macular degeneration (AMD) which leads to devastating and irreversible vision loss in the elderly population. In this exploratory study, the contribution of environmental factors on the progression of AMD pathology by probing the expression of candidate proteins was analyzed. Four hundred and sixty four participants were recruited in the study comprising of AMD (n = 277) and controls (n = 187). Genetics related data was analyzed to demonstrate the activities of daily living (ADL) by using regression analysis and statistical modeling, including contrast estimate, multinomial regression analysis in AMD progression. Regression analysis revealed contribution of smoking, alcohol, and sleeping hours on AMD by altered expression of IER-3, HTRA1, B3GALTL, LIPC and TIMP3 as compared to normal levels. Contrast estimate supports the gender polarization phenomenon in AMD by significant decreased expression of SLC16A8 and LIPC in control population which was found to be unaltered in AMD patients. The smoking, food habits and duration of night sleeping hours also contributed in AMD progression as evident from multinomial regression analysis. Predicted model (prediction estimate = 86.7%) also indicated the crucial role of night sleeping hours along with the decreased expression of TIMP-3, IER3 and SLC16A8. Results revealed an unambiguous role of environmental factors in AMD progression mediated by various regulatory proteins which might result in intermittent AMD phenotypes and possibly influence the outcome of anti-VEGF treatment.

SUBMITTER: Sharma K

PROVIDER: S-EPMC8168906 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Percutaneous osseointegrated (OI) implants for direct skeletal attachment of upper extremity prosthetics represent an alternative to traditional socket suspension that may yield improved patient function and satisfaction. This is especially true in high-level, transhumeral amputees where prosthetic fitting is challenging and abandonment rates remain high. However, maintaining mechanical integrity of the bone-implant interface is crucial for safe clinical introduction of this technology. The collection of population data on the transhumeral loading environment will aid in the design of compliance and overload protection devices that mitigate the risk of periprosthetic fracture. We collected marker-based upper extremity kinematic data from non-amputee volunteers during advanced activities of daily living (AADLs) that applied dynamic loading to the humerus. Inverse dynamic analysis was applied to calculate the axial force, bending and torsional moments at three virtual amputation levels representing 25, 50, and 75% residual humeral length. The influences of amputation level, elbow flexion constraint, gender and anthropometric scaling were assessed. Results indicate that the proximal (25%) amputation level experienced significantly higher axial forces and bending moments across all subjects when compared to distal amputation levels (p?0.030). Constraining elbow flexion had a limited influence on peak transhumeral loads. Male subjects experienced higher axial forces during all evaluated activities (p?0.023). Peak axial force for all activities occurred during jumping jacks (174.5N). Peak bending (57.6Nm) and torsional (57.2Nm) moments occurred during jumping jacks and rapid internal humeral rotation, respectively. Calculated loads fall within the range of implant fixation failure loads reported in cadaveric investigations of humeral stem fixation; indicating that periprosthetic fracture may occur during non-contact AADLs. These kinematic data, collected over a range of AADLs, will aid in the development of overload protection devices and appropriate post-operative rehabilitation protocols that balance return to an active lifestyle with patient safety.

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Sleeping pattern and activities of daily living modulate protein expression in AMD.

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