Mitigating Factors in L4 and L5 Medial Branch Motor Stimulation During Radiofrequency Ablation.

PURPOSE OF REVIEW: Radiofrequency ablation (RFA) is a minimally invasive procedure for facet joint pain. The targets for the procedure are the medial branches of the dorsal spinal nerves which innervate the facet joints. Before RFA, patients undergo diagnostic meal branch blocks to ensure appropriate pain relief and confirm the utility of proceeding to RFA. The success of RFA relies heavily on procedural technique and accurate placement near the medial branch. RECENT FINDINGS: Motor testing is utilized in the lumbar region to assess the response of the multifidus and ensure proper placement of the RFA probe to prevent inadvertent damage to surrounding spinal anatomy. However, relying on motor responses in this area presents challenges given the frequency of lack of muscle twitching. Factors contributing to limited muscle twitch responses include muscle atrophy, excessive lordosis, facet arthropathy, local anesthetic use before ablation, and previous surgical neurotomy. These complexities highlight the challenges in ensuring precise motor stimulation during RFA. Despite these obstacles, accurate anatomical placement remains crucial. For RFA cases that prove challenging, relying on anatomical placement can be adequate to proceed with the procedure. Bridging knowledge gaps is vital for standardized practices and safer procedures. Further research is necessary to refine techniques, understand patient-specific factors, and enhance the efficacy of RFA in managing chronic lumbar facet joint pain.

Scavenging of Superoxide in Aprotic Solvents of Four Isoflavones That Mimic Superoxide Dismutase.

Isoflavones are plant-derived natural products commonly found in legumes that show a large spectrum of biomedical activities. A common antidiabetic remedy in traditional Chinese medicine, Astragalus trimestris L. contains the isoflavone formononetin (FMNT). Literature reports show that FMNT can increase insulin sensitivity and potentially target the peroxisome proliferator-activated receptor gamma, PPARγ, as a partial agonist. PPARγ is highly relevant for diabetes control and plays a major role in Type 2 diabetes mellitus development. In this study, we evaluate the biological role of FMNT, and three related isoflavones, genistein, daidzein and biochanin A, using several computational and experimental procedures. Our results reveal the FMNT X-ray crystal structure has strong intermolecular hydrogen bonding and stacking interactions which are useful for antioxidant action. Cyclovoltammetry rotating ring disk electrode (RRDE) measurements show that all four isoflavones behave in a similar manner when scavenging the superoxide radical. DFT calculations conclude that antioxidant activity is based on the familiar superoxide σ-scavenging mode involving hydrogen capture of ring-A H7(hydroxyl) as well as the π-π (polyphenol-superoxide) scavenging activity. These results suggest the possibility of their mimicking superoxide dismutase (SOD) action and help explain the ability of natural polyphenols to assist in lowering superoxide concentrations. The SOD metalloenzymes all dismutate O2•- to H2O2 plus O2 through metal ion redox chemistry whereas these polyphenolic compounds do so through suitable hydrogen bonding and stacking intermolecular interactions. Additionally, docking calculations suggest FMNT can be a partial agonist of the PPARγ domain. Overall, our work confirms the efficacy in combining multidisciplinary approaches to provide insight into the mechanism of action of small molecule polyphenol antioxidants. Our findings promote the further exploration of other natural products, including those known to be effective in traditional Chinese medicine for potential drug design in diabetes research.

X-ray Structure Determination, Antioxidant Voltammetry Studies of Butein and 2',4'-Dihydroxy-3,4-dimethoxychalcone. Computational Studies of 4 Structurally Related 2',4'-diOH Chalcones to Examine Their Antimalarial Activity by Binding to Falcipain-2.

Malaria is a huge global health burden with resistance to currently available medicines resulting in the search for newer antimalarial compounds from traditional medicinal plants in malaria-endemic regions. Previous studies on two chalcones, homobutein and 5-prenylbutein, present in E. abyssinica, have shown moderate antiplasmodial activity. Here, we describe results from experimental and computational investigations of four structurally related chalcones, butein, 2',4'-dihydroxy-3,4-dimethoxychalcone (DHDM), homobutein and 5-prenylbutein to elucidate possible molecular mechanisms by which these compounds clear malaria parasites. The crystal structures of butein and DHDM show that butein engages in more hydrogen bonding and consequently, more intermolecular interactions than DHDM. Rotating ring-disk electrode (RRDE) voltammetry results show that butein has a higher antioxidant activity towards the superoxide radical anion compared to DHDM. Computational docking experiments were conducted to examine the inhibitory potential of all four compounds on falcipain-2, a cysteine protease that is involved in the degradation of hemoglobin in plasmodium-infected red blood cells of the host. Overall, this work suggests butein as a better antimalarial compound due to its structural features which allow it to have greater intermolecular interactions, higher antioxidant activity and to create a covalent complex at the active site of falcipain-2.

A Decade of Studying Drivers of Disparities in End-of-Life Care for Black Americans: Using the NIMHD Framework for Health Disparities Research to Map the Path Ahead.

OBJECTIVE: The purpose of this paper is to provide a review of the existing literature on racial disparities in quality of palliative and end-of-life care and to demonstrate gaps in the exploration of underlying mechanisms that produce these disparities. BACKGROUND: Countless studies over several decades have revealed that our healthcare system in the United States consistently produces poorer quality end-of-life care for Black compared with White patients. Effective interventions to reduce these disparities are sparse and hindered by a limited understanding of the root causes of these disparities. METHODS: We searched PubMed, CINAHL and PsychInfo for research manuscripts that tested hypotheses about causal mechanisms for disparities in end-of-life care for Black patients. These studies were categorized by domains outlined in the National Institute of Minority Health and Health Disparities (NIMHD) framework, which are biological, behavioral, physical/built environment, sociocultural and health care systems domains. Within these domains, studies were further categorized as focusing on the individual, interpersonal, community or societal level of influence. RESULTS: The majority of the studies focused on the Healthcare System and Sociocultural domains. Within the Health Care System domain, studies were evenly distributed among the individual, interpersonal, and community level of influence, but less attention was paid to the societal level of influence. In the Sociocultural domain, most studies focused on the individual level of influence. Those focusing on the individual level of influence tended to be of poorer quality. CONCLUSIONS: The sociocultural environment, physical/built environment, behavioral and biological domains remain understudied areas of potential causal mechanisms for racial disparities in end-of-life care. In the Healthcare System domain, social influences including healthcare policy and law are understudied. In the sociocultural domain, the majority of the studies still focused on the individual level of influence, missing key areas of research in interpersonal discrimination and local and societal structural discrimination. Studies that focus on individual factors should be better screened to ensure that they are of high quality and avoid stigmatizing Black communities.