Neurodegeneration in the cortical sulcus is a feature of chronic traumatic encephalopathy and associated with repetitive head impacts.

Neurodegeneration is a seminal feature of many neurological disorders. Chronic traumatic encephalopathy (CTE) is caused by repetitive head impacts (RHI) and is characterized by sulcal tau pathology. However, quantitative assessments of regional neurodegeneration in CTE have not been described.

Roles of Nucleic Acids in Protein Folding, Aggregation, and Disease.

The role of nucleic acids in protein folding and aggregation is an area of continued research, with relevance to understanding both basic biological processes and disease. In this review, we provide an overview of the trajectory of research on both nucleic acids as chaperones and their roles in several protein misfolding diseases. We highlight key questions that remain on the biophysical and biochemical specifics of how nucleic acids have large effects on multiple proteins' folding and aggregation behavior and how this pertains to multiple protein misfolding diseases.

An intein-based biosensor to measure protein stability in vivo.

Biosensors to measure protein stability in vivo are valuable tools for a variety of applications. Previous work has demonstrated that a tripartite design, whereby a protein of interest (POI) is inserted within a reporter, can link POI stability to reporter activity. Inteins are translated within other proteins and excised in a self-mediated protein splicing reaction.

Chronic RNA G-quadruplex Accumulation in Aging and Alzheimer's Disease.

Introduction: As the world population ages, new molecular targets in aging and Alzheimer's Disease (AD) are needed to combat the expected influx of new AD cases. Until now, the role of RNA structure in aging and neurodegeneration has largely remained unexplored.

Methods: In this study, we examined human hippocampal postmortem tissue for the formation of RNA G-quadruplexes (rG4s) in aging and AD.

Why are G-quadruplexes good at preventing protein aggregation?

Maintaining a healthy protein folding environment is essential for cellular function. Recently, we found that nucleic acids, G-quadruplexes in particular, are potent chaperones for preventing protein aggregation. With the aid of structure-function and NMR analyses of two G-quadruplex forming sequences, PARP-I and LTR-III, we uncovered several contributing factors that affect G-quadruplexes in preventing protein aggregation.

Three dimensional evaluation of cerebrovascular density and branching in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts (RHI) and characterized by perivascular accumulations of hyperphosphorylated tau protein (p-tau) at the depths of the cortical sulci. Studies of living athletes exposed to RHI, including concussive and nonconcussive impacts, have shown increased blood-brain barrier permeability, reduced cerebral blood flow, and alterations in vasoreactivity. Blood-brain barrier abnormalities have also been reported in individuals neuropathologically diagnosed with CTE.

Perifoveal exudative vascular anomalous complex and resembling lesions treated with intravitreal triamcinolone.

Purpose: To report the use of intravitreal triamcinolone to treat macular edema associated with isolated perifoveal exudative vascular anomalous complex (PVAC) and resembling lesion (PVAC-RL).

Methods: In this case series, three diabetic patients (3 eyes) with PVAC-RLs and one healthy patient (1 eye) with PVAC lesion associated with cystic spaces underwent three intravitreal injections of aflibercept before switching to one intravitreal triamcinolone injection in each patient.

Results: Macular edema improved from 297.

G-quadruplexes rescuing protein folding.

Maintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of . However, the roles of G4s in protein folding were not yet explored.

Hyperfractionated Cyclophosphamide and Dexamethasone Alone or in Combination with Daratumumab and/or Carfilzomib for the Treatment of Relapsed or Refractory Multiple Myeloma: A Single-Center Retrospective Analysis.

Background: Hyperfractionated cyclophosphamide and dexamethasone (HyperCd) alone, or with carfilzomib(K) and/or daratumumab(D), represents a potential treatment option when rapid disease control is needed for patients with aggressive presentations of relapsed/refractory multiple myeloma (RRMM).

Patients And Methods: This is a single-center, retrospective analysis of adult patients with RRMM who received HyperCd with or without K and/or D between May 1, 2016 and August 1, 2019 at the University of Texas MD Anderson Cancer Center. We here report treatment response and safety outcomes.

Retinal microvascular abnormalities, cotton wool-like lesions, and macular edema following COVID-19 in a patient previously vaccinated with AstraZeneca and idiopathic myopathy.

In this case study, the authors describe peculiar bilateral cotton wool-like retinal lesions associated with macular edema in a patient with COVID-19 who was vaccinated with a single dose of AstraZeneca one month earlier. This patient had no pulmonary or systemic cardiovascular complications from COVID-19, as reported in other papers that found retinal lesions. However, the patient was diagnosed with idiopathic myopathy when discovering the SARS-CoV-2 infection.

Emerging roles for G-quadruplexes in proteostasis.

How nucleic acids interact with proteins, and how they affect protein folding, aggregation, and misfolding is a still-evolving area of research. Considerable effort is now focusing on a particular structure of RNA and DNA, G-quadruplexes, and their role in protein homeostasis and disease. In this state-of-the-art review, we track recent reports on how G-quadruplexes influence protein aggregation, proteolysis, phase separation, and protein misfolding diseases, and pose currently unanswered questions in the advance of this scientific field.

Foldamers reveal and validate therapeutic targets associated with toxic α-synuclein self-assembly.

Parkinson's disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (αS) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of αS aggregation.

Analysis of a panel-based pharmacogenomics testing program among members of a commercial and Medicare client of a pharmacy benefits manager.

Although the field of pharmacogenomics (PGx) has existed for decades, use of pharmacogenomic information by providers to optimize medication therapy for patients has had relatively slow adoption. There are many factors that have contributed to the slow adoption of PGx testing, but it is partially due to a lack of coverage by payers. If PGx testing is covered by payers, frequently only testing of a specific gene is covered, rather than a panel of many genes.

A Medical Financial Partnership in a Pediatric Medical Home.

The Volunteer Income Tax Assistance (VITA) program is an underutilized free taxpreparation service that directly addresses poverty by maximizing tax refunds. A pediatric medical home (PMH) with an embedded VITA site provides an excellent opportunity for a medical-financial partnership. We sought to assess the knowledge, attitudes, and practices of caregivers of children who used a PMH after embedding a VITA site.

Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma.

Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy.

Experiences of implementing treatment manuals: Clinician, supervisor, and researcher reflections.

Introduction: Treatment manuals play an essential role in clinical trials that aim to determine the efficacy of an intervention. Yet, the idea of needing to adhere to a treatment manual may seem counterintuitive to many music therapy clinicians. The purpose of this article is to offer clinician, supervisor, and researcher perspectives on the process of developing and executing a manualized music therapy treatment protocol in a randomized controlled trial.

G-Quadruplexes act as sequence-dependent protein chaperones.

Maintaining proteome health is important for cell survival. Nucleic acids possess the ability to prevent protein aggregation more efficiently than traditional chaperone proteins. In this study, we explore the sequence specificity of the chaperone activity of nucleic acids.

Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma.

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel).

Chaperna: linking the ancient RNA and protein worlds.

As a mental framework for the transition of self-replicating biological forms, the RNA world concept stipulates a dual function of RNAs as genetic substance and catalyst. The chaperoning function is found intrinsic to ribozymes involved in protein synthesis and tRNA maturation, enriching the primordial RNA world with proteins of biological relevance. The ribozyme-resident protein folding activity, even before the advent of protein-based molecular chaperone, must have expedited the transition of the RNA world into the present protein theatre.