About seller
Dose-dependent life-threatening doxorubicin-induced cardiotoxicity (DIC) is a major clinical challenge that needs to be addressed. Here, we developed an integrated multiscale and translational quantitative systems toxicology and pharmacokinetic-toxicodynamic (QST-PK/TD) model for optimization of doxorubicin dosing regimens for early monitoring and minimization of DIC. A QST model was established by exposing human cardiomyocytes, AC16 cells, to doxorubicin over a time course, and measuring the dynamics of intracellular signaling proteins, AC16 cell viability and released biomarkers of cardiomyocyte injury such as the B-type natriuretic peptide (BNP). Experiments were scaled up to a three-dimensional and dynamic (3DD) cell culture system to evaluate DIC under various dosing regimens. The PK determinants of doxorubicin influencing DIC were identified in vitro and then translated to the in vivo setting through hybrid physiologically based PK (PBPK)/TD models using preclinical- and clinical-level data extracted from literature. The developed cellular-level QST model captured well the observed dynamics of intracellular proteins, AC16 cell viability and BNP kinetics. In the 3DD setting, dose fractionation of doxorubicin displayed a significant reduction in cardiotoxicity compared to single intravenous doses with equal exposure, implying doxorubicin peak concentrations as the PK determinant for DIC. The in vivo hybrid PBPK/TD models captured well doxorubicin PK and DIC. Peak doxorubicin concentrations correlated well with acute DIC for dose-fractionated regimens, while maximum 48-h moving average concentrations correlated with DIC for dose-fractionated and long-term infusion regimens in vivo. The developed multiscale and translational QST-PK/TD modeling platform may serve as an in silico tool for assessment of early toxicity and/or efficacy of developmental drugs in vitro. We review the recent literature regarding college student experiences with and attitudes toward telemental health (TMH). We examine their perspectives of the advantages and drawbacks to this form of mental healthcare and their willingness to engage in TMH. College students view TMH as convenient, accessible, easy to use, and helpful. TMH helps to overcome the barrier of stigma associated with seeking mental health treatment. Despite positive reviews, many students find a lack of customization or connection to the provider to be drawbacks to some forms of TMH. Willingness to engage in TMH varies based on prior experience with mental health treatment, ethnicity, and severity of symptoms. The recent literature highlights the potential for TMH to play a key role in mental health services for college students. It also highlights some of its shortcomings, which are indicative of the continued need for in-person services. Future studies should continue to track college student perspectives toward and utilization of TMH.College students view TMH as convenient, accessible, easy to use, and helpful. TMH helps to overcome the barrier of stigma associated with seeking mental health treatment. Despite positive reviews, many students find a lack of customization or connection to the provider to be drawbacks to some forms of TMH. Clozapine N-oxide AChR agonist Willingness to engage in TMH varies based on prior experience with mental health treatment, ethnicity, and severity of symptoms. The recent literature highlights the potential for TMH to play a key role in mental health services for college students. It also highlights some of its shortcomings, which are indicative of the continued need for in-person services. Future studies should continue to track college student perspectives toward and utilization of TMH.Light energy causes damage to Photosystem I (PSI) and Photosystem II (PSII). The majority of the previous photoinhibition studies have been conducted with PSII, which shows much larger photoinhibition than PSI; therefore, relatively little is known about the mechanism of PSI photoinhibition so far. A previous report showed that the photoinhibition action spectrum measured with PSI activity of isolated thylakoid is similar to the absorption spectrum of chlorophyll. However, it is known that the extent of PSI photoinhibition is much smaller in vivo compared to in vitro. It is also possible that the different extent of PSII photoinhibition, caused by different spectral light qualities, can affect the photoinhibition of PSI in vivo because PSI receives electrons from PSII. In the present research, to study the effect of light quality and the effect of the extent of PSII photoinhibition on the PSI photoinhibition in vivo, intact leaves were photoinhibited under four different light qualities. The rate coefficient of PSI photoinhibition was significantly higher in blue and red light compared to white light. The rate of PSI photoinhibition at the same photon-exposure was the largest in blue and red light and followed by white and green light. These results support the notion that light absorption by chlorophyll is responsible for the PSI photoinhibition, even in intact leaves. The variation among light colors in the relationships between the extent of photoinhibition of PSII and that of PSI indicate that PSI and PSII are independently photoinhibited with different mechanisms in the early stage of in vivo photoinhibition.Loss of function mutations in STAT3 (STAT3-LOF; autosomal dominant hyper-IgE (Job's) syndrome) are associated with a variety of musculoskeletal manifestations, including scoliosis, osteoporosis, and minimal trauma fractures. This retrospective magnetic resonance (MR) imaging study sought to characterize an unusual pattern of cervical spine degeneration among a cohort of STAT3-LOF patients. Cervical spine MR images of the STAT3-LOF cohort (n = 38) were assessed for a variety of degenerative changes and compared to age-matched groups of controls (n = 42) without known immune or musculoskeletal abnormalities. A unique pattern of premature cervical spine degeneration was identified among the STAT3-LOF cohort which included straightening and eventual reversal of the normal cervical lordosis, mainly due to multi-level spondylolisthesis, as well as early development of spinal canal narrowing, cord compression, and myelomalacia. Cervical spine degeneration in the STAT3-LOF cohort was significantly worse than controls in both the 30-45 and 45 + age groups.