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The Affordances for Motor Behavior of Schoolchildren (AMBS) is a standardized self-reporting tool comprising 73 questions, organized into seven sections aiming to assess affordances in children's regular contexts. This investigation aims to establish the reliability and validity of the results obtained from the AMBS in South Indian children. The AMBS reliability and construct validity were evaluated in 393 Indian families whose children were aged between 6 and 10 years old. The internal consistency of the AMBS was evaluated by retesting the tool in a subsample of 30 families following a 14-day interval between assessments (intraclass correlation coefficient), showing a reliability level of 0.933. The validity of the scale was evaluated using the confirmatory factor analysis. The model that was tested indicated a very good fit, and the structural model presented significant loading coefficients from the identified variables to the theoretically specified latent factors. Positively significant correlation values were found between factors: home and materials (r =0.78), home and school (r=0.55), and materials and school (r =0.77). Our findings suggest that AMBS is a reliable assessment tool and can evaluate the affordances provided to South Indian children. This information can be used to develop interventions to improve the physical activity levels of these children.

Abstract Branched chain amino acid (BCAA) catabolic impairments have been implicated in several diseases. Branched chain ketoacid dehydrogenase (BCKDH) controls the rate limiting step in BCAA degradation, the activity of which is inhibited by BCKDH kinase (BDK)-mediated phosphorylation. Screening efforts to discover BDK inhibitors led to identification of thiophene PF-07208254, which improved cardiometabolic endpoints in mice. Structure-activity relationship studies led to identification of a thiazole series of BDK inhibitors; however, these inhibitors did not improve metabolism in mice upon chronic administration. While the thiophenes demonstrated sustained branched chain ketoacid (BCKA) lowering and reduced BDK protein levels, the thiazoles increased BCKAs and BDK protein levels. Thiazoles increased BDK proximity to BCKDH-E2, whereas thiophenes reduced BDK proximity to BCKDH-E2, which may promote BDK degradation. Thus, we describe two BDK inhibitor series that possess differing attributes regarding BDK degradation or stabilization and provide a mechanistic understanding of the desirable features of an effective BDK inhibitor.

The Affordances for Motor Behavior of Schoolchildren (AMBS) is a standardized self-reporting tool comprising 73 questions, organized into seven sections aiming to assess affordances in children's regular contexts. This investigation aims to establish the reliability and validity of the results obtained from the AMBS in South Indian children. The AMBS reliability and construct validity were evaluated in 393 Indian families whose children were aged between 6 and 10 years old. The internal consistency of the AMBS was evaluated by retesting the tool in a subsample of 30 families following a 14-day interval between assessments (intraclass correlation coefficient), showing a reliability level of.933. The validity of the scale was evaluated using the confirmatory factor analysis. The model that was tested indicated a very good fit, and the structural model presented significant loading coefficients from the identified variables to the theoretically specified latent factors. Positively significant correlation values were found between factors: home and materials (r =.78), home and school (r =.55), and materials and school (r =.77). Our findings suggest that AMBS is a reliable assessment tool and can evaluate the affordances provided to South Indian children. This information can be used to develop interventions to improve the physical activity levels of these children. [ABSTRACT FROM AUTHOR]

Germ cell tumors (GCTs) are rare neoplasms which are seen in all age groups and both sexes. GCTs in the pediatric age group show considerable variation from their adult counterparts in relation to site, histological type, clinical and radiological features and response to treatment. Extragonadal gcts are much more common in the pediatric age group with the most common sites being sacrococcygeal region, head and neck, retroperitoneum and mediastinum. Unusual sites like the vagina and urinary bladder have also been reported. Therefore, the varied presentations and different treatment options should be considered.

Backbone N-methylation is common among peptide natural products and has a substantial impact on both the physical properties and the conformational states of cyclic peptides. However, the specific impact of N-methylation on passive membrane diffusion in cyclic peptides has not been investigated systematically. Here we report a method for the selective, on-resin N-methylation of cyclic peptides to generate compounds with drug-like membrane permeability and oral bioavailability. The selectivity and degree of N-methylation of the cyclic peptide was dependent on backbone stereochemistry, suggesting that conformation dictates the regiochemistry of the N-methylation reaction. The permeabilities of the N-methyl variants were corroborated by computational studies on a 1,024-member virtual library of N-methyl cyclic peptides. One of the most permeable compounds, a cyclic hexapeptide (molecular mass = 755 Da) with three N-methyl groups, showed an oral bioavailability of 28% in rat.

INTRODUCTION: Hashimoto’s thyroiditis (HT) is the most common cause of goitrous hypothyroidism in iodine sufficient areas. The diagnosis of HT is important because it progresses to hypothyroidism, and also, it is associated with thyroid lymphoma and papillary thyroid carcinoma. Apart from thyroid antibodies, assessment of thyroid function test (TFT) levels, ultrasonography (USG), and cytological analysis can help in early diagnosis and management of HT. AIMS AND OBJECTIVES OF THIS STUDY: To know the age incidence and clinical presentation of HT, its association with thyroid hormone levels and with thyroid antibodies and its correlation with the cytologic grade of HT. MATERIALS AND METHODS: Consecutive convenient method of sampling was adopted at the cytology clinic. Fine-needle aspiration cytology of patients presenting with thyroid enlargement was done using standard technique and aseptic precautions. RESULTS: Out of 875 cases of thyroid cytology, 134 cases were diagnosed as HT over a 4-year period. A strong female preponderance was observed. A significant proportion of them (103/134) presented in the first four decades of life. Majority of cases (60.63%) were hypothyroid, while 15.74% were hyperthyroid and 23.62% were euthyroid. Apart from thyroid enlargement, although a majority of patients presented with symptoms related to the thyroid, a significant number of patients (38.80%) were asymptomatic. Conclusions: A combined approach of cytological grading of HT along with USG, TFT levels, and thyroid antibodies can detect hypothyroid and subclinical hypothyroid or euthyroid state of HT and provide an appropriate guide to therapy.

Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver lipid accumulation and ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators of the AMP-Activated Protein Kinase (AMPK) have been proposed as a treatment for metabolic diseases; we show that the AMPK β1-biased activator PF-06409577 is capable of lowering hepatic and systemic lipid and cholesterol levels in both rodent and monkey preclinical models. PF-06409577 is able to inhibit de novo lipid and cholesterol synthesis pathways, and causes a reduction in hepatic lipids and mRNA expression of markers of hepatic fibrosis. These effects require AMPK activity in the hepatocytes. Treatment of hyperlipidemic rats or cynomolgus monkeys with PF-06409577 for 6 weeks resulted in a reduction in circulating cholesterol. Together these data suggest that activation of AMPK β1 complexes with PF-06409577 is capable of impacting multiple facets of liver disease and represents a promising strategy for the treatment of NAFLD and NASH in humans. Keywords: AMPK, NAFLD, Lipogenesis, ACC, Hyperlipidemia

Abstract\nHIGHLIGHTSStiffeners are frequently utilized in many engineering projects because they boost strength while adding only a small amount of weight to the overall structure. The environments that the stiffened composite constructions are typically exposed to are harsh, which can result in damage like interlayer delamination and debond at the plate-stiffener interface, which can cause catastrophic failure. As a result, it is necessary to examine these structures’ dynamic behavior in addition to their stability performance. The current study attempts to investigate the free vibration response of stiffened composite plates with plate-stiffener interfacial debonding under hygrothermal circumstances using a robust finite element (FE) model. The skin and stiffener flange are simulated in the current work using a 9-noded heterosis element to prevent the shear-locking issue. Additionally, to considerably enhance computational performance, the stiffener web is formulated as a 3-noded isoparametric beam element with the torsion correction factor. Additionally, a dummy node is created to represent the debond, and a fictitious spring is added to stop the nodes from interpenetrating one another. Three schemes of hygrothermally stable laminates (θ/(90- θ))s, (22.5/−67.5)s and (77.5/−12.5)s are considered to identify the stiffened plate configuration with improved free vibration characteristics. Further, extensive parametric analyses are conducted on the obtained stiffened plate with improved performance in a hygrothermal environment by considering debond at the skin-stiffener interface. The vibrational behavior of the debonded plate is shown to be significantly more affected by moisture than by temperature. Additionally, the debond has a more obvious impact on the vibration characteristics in the plate with a centrally attached stiffener than in the plate with an eccentricity attached stiffener. As a result, the established FE formulation is anticipated to be trustworthy and computationally effective while effectively analyzing the debonded stiffened panel’s free vibration behavior in a hygrothermal environment.Developed a simplified finite element model to incorporate the interfacial debonding between the plate and stiffener.The current model reduces the computational cost by partially modeling the T-stiffener with the beam element.Investigates free vibration behavior of hygrothermally stable stiffened composite panels in hygrothermal conditions.Extreme environmental conditions significantly reduce the panel’s natural frequency.Large stiffener depth debonded panel’s frequency drops considerably at higher moisture concentration.Developed a simplified finite element model to incorporate the interfacial debonding between the plate and stiffener.The current model reduces the computational cost by partially modeling the T-stiffener with the beam element.Investigates free vibration behavior of hygrothermally stable stiffened composite panels in hygrothermal conditions.Extreme environmental conditions significantly reduce the panel’s natural frequency.Large stiffener depth debonded panel’s frequency drops considerably at higher moisture concentration. [ABSTRACT FROM AUTHOR]

Myeloperoxidase (MPO) is a highly abundant protein within the neutrophil that is associated with lipoprotein oxidation, and increased plasma MPO levels are correlated with poor prognosis after myocardial infarct. Thus, MPO inhibitors have been developed for the treatment of heart failure and acute coronary syndrome in humans. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide PF-06282999 is a recently described selective small molecule mechanism-based inactivator of MPO. Here, utilizing PF-06282999, we investigated the role of MPO to regulate atherosclerotic lesion formation and composition in the Ldlr-/- mouse model of atherosclerosis. Though MPO inhibition did not affect lesion area in Ldlr-/- mice fed a Western diet, reduced necrotic core area was observed in aortic root sections after MPO inhibitor treatment. MPO inhibition did not alter macrophage content in and leukocyte homing to atherosclerotic plaques. To assess non-invasive monitoring of plaque inflammation, [18F]-Fluoro-deoxy-glucose (FDG) was administered to Ldlr-/- mice with established atherosclerosis that had been treated with clinically relevant doses of PF-06282999, and reduced FDG signal was observed in animals treated with a dose of PF-06282999 that corresponded with reduced necrotic core area. These data suggest that MPO inhibition does not alter atherosclerotic plaque area or leukocyte homing, but rather alters the inflammatory tone of atherosclerotic lesions; thus, MPO inhibition could have utility to promote atherosclerotic lesion stabilization and prevent atherosclerotic plaque rupture.