👤 Sameh Obeid

Toddler movement patterns challenge current accelerometer-based detection of physical activity (PA) and sedentary time (SED). The objectives of this study were to: (1) develop a novel machine learning (ML) model to detect toddlers' PA and SED; and (2) compare this ML model to existing cut-point methods to analyze toddlers' PA (independent sample cross-validation of existing methods). We recruited 111 toddlers (21 ± 7 months; 51% female) to two 1-hour semi-structured visits wearing a waist-worn ActiGraph wGT3X-BT accelerometer. Video recordings were manually annotated using a modified Children's Activity Rating Scale to determine a ground truth. We extracted 40 time and frequency domain features from raw accelerations and trained 4 gradient boosted tree ML models (distinguishing SED, total PA (TPA), light PA (LPA), moderate-to-vigorous PA (MVPA), and non-volitional movement (NVM)). Models were assessed using accuracy, F1 scores, and confusion matrices. For the validation of 11 existing methods, we calculated accuracy, F1, and mean absolute differences in TPA and MVPA estimation. ML models classifying NVM/SED/TPA and NVM/SED/LPA/MVPA reached 82% and 74% accuracy with mean absolute differences of 3.0 and 3.2 min/h, respectively. Independent sample cross-validation found accuracies from 33 to 74% and mean absolute differences from 7.6 to 18.6 min/h in TPA and 10.7 to 25.8 min/h in MVPA. We recommend the NVM/SED/TPA or NVM/SED/LPA/MVPA models' given alignment with toddler TPA guidelines and MVPA link to health outcomes, respectively. We additionally present an open-access interface for using these ML models that does not require coding knowledge. This presents a substantial step forward in the measurement of toddlers' physical activity. Show less

Atrial natriuretic peptide (ANP) and oxidized low-density lipoprotein (ox-LDL) play essential roles in the development and progression of vascular complications associated with type 2 diabetes mellitus (T2DM), and both are independently linked to cardiovascular diseases (CVD). However, the relationship between ANP and ox-LDL in patients with T2DM remains unclear as previous studies have primarily focused on circulating levels in various diseases. This study investigated the relationship between ANP and ox-LDL levels in obese individuals with T2DM. The cohort included 57 patients with T2DM (mean age 61.14 ± 9.99 years; HbA1c 8.66 ± 1.60%; BMI 35.15 ± 6.65 kg/m Show less

Glucagon-like peptide 1 (GLP-1R) and glucose-dependent insulinotropic polypeptide (GIPR) receptors are G-protein-coupled receptors involved in glucose homeostasis. Diabetogenic conditions decrease β-arrestin 2 (ARRB2) levels in human islets. In mouse β cells, ARRB2 dampens insulin secretion by partially uncoupling cyclic AMP (cAMP)/protein kinase A (PKA) signaling at physiological doses of GLP-1, whereas at pharmacological doses, the activation of extracellular signal-related kinase (ERK)/cAMP-responsive element-binding protein (CREB) requires ARRB2. In contrast, GIP-potentiated insulin secretion needs ARRB2 in mouse and human islets. The GIPR-ARRB2 axis is not involved in cAMP/PKA or ERK signaling but does mediate GIP-induced F-actin depolymerization. Finally, the dual GLP-1/GIP agonist tirzepatide does not require ARRB2 for the potentiation of insulin secretion. Thus, ARRB2 plays distinct roles in regulating GLP-1R and GIPR signaling, and we highlight (1) its role in the physiological context and the possible functional consequences of its decreased expression in pathological situations such as diabetes and (2) the importance of assessing the signaling pathways engaged by the agonists (biased/dual) for therapeutic purposes. Show less

Antileishmanial chemotherapy is currently limited due to severe toxic side effects and drug resistance. Hence, new antileishmanial compounds based on alternative approaches, mainly to avoid the emergence of drug resistance, are needed. The present work aims to decipher the mechanism of action of an antileishmanial drug candidate, named VP343, inhibiting intracellular Show less

Clinical and molecular data on the occurrence and frequency of inherited neuromuscular disorders (NMD) in the Lebanese population is scarce. This study aims to provide a retrospective overview of hereditary NMDs based on our clinical consultations in Lebanon. Clinical and molecular data of patients referred to a multi-disciplinary consultation for neuromuscular disorders over a 20-year period (1999-2019) was reviewed. A total of 506 patients were diagnosed with 62 different disorders encompassing 10 classes of NMDs. 103 variants in 49 genes were identified. In this cohort, 81.4% of patients were diagnosed with motor neuron diseases and muscular dystrophies, with almost half of these described with spinal muscular atrophy (SMA) (40.3% of patients). We estimate a high SMA incidence of 1 in 7,500 births in Lebanon. Duchenne and Becker muscular dystrophy were the second most frequently diagnosed NMDs (17% of patients). These disorders were associated with the highest number of variants (39) identified in this study. A highly heterogeneous presentation of Limb Girdle Muscular Dystrophy and Charcot-Marie-Tooth disease was notably identified. The least common disorders (5.5% of patients) involved congenital, metabolic, and mitochondrial myopathies, congenital myasthenic syndromes, and myotonic dystrophies. A review of the literature for selected NMDs in Lebanon is provided. Our study indicates a high prevalence and underreporting of heterogeneous forms of NMDs in Lebanon- a major challenge with many novel NMD treatments in the pipeline. This report calls for a regional NMD patient registry. Show less

1. In order to investigate the biological function of the human CLN3 gene that is defective in Batten disease, we created a yeast strain by PCR-targeted disruption of the yeast gene (YHC3), which is a homologue of the human CLN3 gene. 2. The phenotypic characterization revealed that the yhc3 delta mutants are more sensitive to combined heat and alkaline stress than the wild-type strains as determined by inhibition of cell proliferation. 3. This suggests that the yhc3 delta mutant is a good model to investigate the biological function of human CLN3 gene in mammalian cells and to understand the pathophysiology of juvenile Batten disease. Show less

The late infantile and juvenile variants of Batten disease are genetically distinct neurodegenerative disorders. Hallmarks of Batten disease include cognitive and motor decline, seizures and blindness due to retinitis pigmentosa. Recently, the CLN3 gene responsible for the juvenile variant has been cloned. Also, apoptosis was proven to be the mechanism by which neurons and photoreceptors die. This paper provides mechanistic support for the occurrence of apoptosis in this disease: There was marked upregulation of Bcl-2 in brain from the late infantile and juvenile types at the protein and RNA levels both by immunocytochemistry and by Northern blot analysis; there were also a 42% to 197% increase in brain ceramide determinations in brains from three patients with the juvenile type and three patients with the late infantile type. Double immunolabeling of brain sections for apoptosis and Bcl-2 supported a protective role for Bcl-2 in the juvenile form of Batten disease. These results raise the possibility that the intact CLN3 gene is normally antiapoptotic, and that it could be an upstream regulator of ceramide. Show less