Modeling the temporal dynamics of master regulators and CtrA proteolysis in Caulobacter crescentus cell cycle.

The cell cycle of Caulobacter crescentus involves the polar morphogenesis and an asymmetric cell division driven by precise interactions and regulations of proteins, which makes Caulobacter an ideal model organism for investigating bacterial cell development and differentiation. The abundance of molecular data accumulated on Caulobacter motivates system biologists to analyze the complex regulatory network of cell cycle via quantitative modeling. In this paper, We propose a comprehensive model to accurately characterize the underlying mechanisms of cell cycle regulation based on the study of: a) chromosome replication and methylation; b) interactive pathways of five master regulatory proteins including DnaA, GcrA, CcrM, CtrA, and SciP, as well as novel consideration of their corresponding mRNAs; c) cell cycle-dependent proteolysis of CtrA through hierarchical protease complexes. The temporal dynamics of our simulation results are able to closely replicate an extensive set of experimental observations and capture the main phenotype of seven mutant strains of Caulobacter crescentus. Collectively, the proposed model can be used to predict phenotypes of other mutant cases, especially for nonviable strains which are hard to cultivate and observe. Moreover, the module of cyclic proteolysis is an efficient tool to study the metabolism of proteins with similar mechanisms.

Novel combination approaches to locoregional and systemic therapy in the management of primary and metastatic liver tumors.

Several pathways and mutations must develop or be in place for the onset of cancer. Therefore, therapies should ideally target as many of these pathways as possible to improve outcomes. Combining several agents has proven to be more effective than the use of monotherapy in the treatment of renal cell carcinoma, hepatocellular carcinoma, and other cancers. Combination therapy can also include locoregional therapies such as ablation and embolization with systemic agents for synergistic effects. This review article discusses the current literature and clinical trials covering these multifactorial combination therapies in primary and metastatic liver tumors.

Atherogenic Indices as a Predictor of Aortic Calcification in Prostate Cancer Patients Assessed Using 18F-Sodium Fluoride PET/CT.

A major pathophysiological cause of cardiovascular disease is vascular plaque calcification. Fluorine 18−Sodium Fluoride (18F-NaF) PET/CT can be used as a sensitive imaging modality for detection of vascular calcification. The aim of this study was to find a non-invasive, cost-efficient, and readily available metric for predicting vascular calcification severity. This retrospective study was performed on 36 participants who underwent 18F-NaF fused PET/CT scans. The mean standard uptake values (SUVs) were calculated from manually sectioned axial sections over the aortic arch and thoracic aorta. Correlation analyses were performed between SUVs and calculated atherogenic indices (AIs). Castelli's Risk Index I (r = 0.63, p < 0.0001), Castelli's Risk Index II (r = 0.64, p < 0.0001), Atherogenic Coefficient (r = 0.63, p < 0.0001), Atherogenic Index of Plasma (r = 0.51, p = 0.00152), and standalone high-density lipoprotein (HDL) cholesterol (r = −0.53, p = 0.000786) were associated with aortic calcification. AIs show strong association with aortic arch and thoracic aorta calcifications. AIs are better predictors of vascular calcification compared to standalone lipid metrics, with the exception of HDL cholesterol. Clinical application of AIs provides a holistic metric beneficial for enhancing screening and treatment protocols.

Tackling Health Inequities: A Unique, Asynchronous Course Designed Through Peer-to-Peer Methods.

OBJECTIVES: This study investigates the efficacy and feasibility of an asynchronous, peer-to-peer health disparities enrichment course on postbaccalaureate prehealth students' knowledge, behaviors, and reaction to course materials. INTRODUCTION: Growing awareness of social inequities has prompted educators of prehealth and medical students to explore student education by addressing systemic healthcare issues. This cross-sectional study assessed reactions, learning, and self-reported behavior changes in students after taking the course "Social Determinants, Disparities, and Preparing for the Future of Healthcare" (SDDH). METHODS: The curriculum was designed by prehealth postbaccalaureate students for their peers. Course goals were to educate participants on social determinants of health and to build cultural and structural competence in their roles as future healthcare professionals. SDDH is an asynchronous, noncredit-bearing, 5-h online course with 10 modules covering various topics. The Kirkpatrick Model was used to assess the effectiveness of the curriculum, alongside qualitative and quantitative analyses of student performance. RESULTS: Out of the 102 active students in the prehealth program that accepted the invitation to join, 29 students successfully completed the course (rate of completion = 28%). On average, students expressed positive reactions and attitudes toward the course and experienced an observable increase in knowledge assessment scores upon curriculum completion (P-value = .0002). Students' self-reported observations demonstrated sustained behavioral change 3 months after course completion. CONCLUSION: It is critical to educate prehealth students on health disparities, structural, and cultural competence. A course such as SDDH may help prehealth students build effective communication skills for advocacy and develop an empathetic, patient-centered approach earlier on in their career pursuit. Some barriers to students completing the entire course include its length, uncredited status, and voluntary self-enrollment.

Uncovering the System Vulnerability and Criticality of Human Brain Under Dynamical Neuropathological Events in Alzheimer's Disease.

BACKGROUND: Despite the striking efforts in investigating neurobiological factors behind the acquisition of amyloid-ß (A), protein tau (T), and neurodegeneration ([N]) biomarkers, the mechanistic pathways of how AT[N] biomarkers spreading throughout the brain remain elusive. OBJECTIVE: To disentangle the massive heterogeneities in Alzheimer's disease (AD) progressions and identify vulnerable/critical brain regions to AD pathology. METHODS: In this work, we characterized the interaction of AT[N] biomarkers and their propagation across brain networks using a novel bistable reaction-diffusion model, which allows us to establish a new systems biology underpinning of AD progression. We applied our model to large-scale longitudinal neuroimages from the ADNI database and studied the systematic vulnerability and criticality of brains. RESULTS: Our model yields long term prediction that is statistically significant linear correlated with temporal imaging data, produces clinically consistent risk prediction, and captures the Braak-like spreading pattern of AT[N] biomarkers in AD development. CONCLUSIONS: Our major findings include (i) tau is a stronger indicator of regional risk compared to amyloid, (ii) temporal lobe exhibits higher vulnerability to AD-related pathologies, (iii) proposed critical brain regions outperform hub nodes in transmitting disease factors across the brain, and (iv) comparing the spread of neuropathological burdens caused by amyloid-ß and tau diffusions, disruption of metabolic balance is the most determinant factor contributing to the initiation and progression of AD.

Peyronie's Disease: An Outcomes-Based Guide to Non-Surgical and Novel Treatment Modalities.

The clinical landscape of Peyronie's disease is everchanging. There has been growing interest in non-invasive therapeutic options that could assist patients with achieving a meaningful reduction in penile curvature without surgical intervention. These therapies are wide-ranging in terms of their mechanisms of action, efficacies, and short- and long-term safety profiles. Recently, an abundance of outcomes literature on longstanding and novel non-surgical treatment modalities has been published. For sexual medicine providers hoping to offer patients the most up-to-date and evidence-based treatments for the management of Peyronie's disease, it can be challenging to gain a thorough understanding of this body of literature. In this clinical management review, the workup and current theories on the pathophysiology of Peyronie's disease are reviewed, and the most recent outcomes data on the currently available non-surgical treatment modalities are presented. With an accurate understanding of the current landscape of Peyronie's disease treatment, sexual health providers will be able to better evaluate and engage in evidence-based shared decision-making with their patients.

Is urgent surgical management necessary for priapism in pediatric patients with hematologic conditions?

INTRODUCTION: Acute priapism is usually considered a medical emergency that warrants prompt urologic evaluation and treatment. Efforts have been made to determine the optimal management strategy for pediatric priapism. OBJECTIVE: The aim of this study is to assess differences in conservative, minimally-invasive, and operative management of acute priapism in the pediatric population. STUDY DESIGN: A retrospective study of pediatric patients with acute priapism from 2015 to 2021 at a single tertiary care children's hospital was conducted. Conservative, minimally-invasive, and operative approaches for the priapism episodes during these hospital encounters were analyzed. RESULTS: Thirty-nine patients were identified with a total of 61 cases of acute pediatric priapism were evaluated in the study period. Eight-three percent of patients were African-Americans, and 72% of patients had a history of sickle cell disease. Oxygen therapy (P = 0.001) and hydration with intravenous fluids (P = 0.00318) were more commonly utilized for hematologic-associated cases compared to other etiologies. For priapism episodes of hematologic etiology, 18 (40.0%) and 18 (40.0%) patients received phenylephrine injection and aspiration/irrigation (e.g., minimally-invasive therapy), respectively, while for the other causes of priapism, three (18.8%) and four (25.0%) received phenylephrine injection and aspiration/irrigation (e.g., minimally-invasive), respectively. Conservative and minimally-invasive treatment resulted in complete resolution of priapism in 27 (60%) and 16 (35.5%) patients with hematologic-associated priapism while 12 (75%) and 1 (6.3%) patients with other etiologies had resolution of priapism with conservative and minimally-invasive treatment, respectively. One patient received shunting in the hematologic group while two patients received shunting in the non-hematologic group (P = 0.1031). DISCUSSION: Hematologic disorders are the most common causes of priapism in children and adolescents. An overwhelming majority of priapism events in the pediatric population can be managed with conservative therapies including oxygenation and intravenous hydration as well as minimally-invasive procedures such as corporal aspiration, irrigation and/or injections. The utilization of corporal shunting, anesthesia, and hospital resources is infrequently necessary for pediatric priapism episodes. CONCLUSION: While urgent surgical management is often performed in the adult population, a minimally-invasive management strategy can be implemented in the pediatric population where an extended period of conservative management that avoids operative management and general anesthesia is effective.