Identifying Isoononin and Candidissiol as Rho-associated protein kinase 1 (ROCK1) inhibitors: a combined virtual screening and MD simulation approach.

Rho-associated protein kinase 1 (ROCK1) is a member of the AGC family which plays crucial roles in inflammatory diseases and cancer progression. Elevated expression of ROCK1 has been reported in multiple cancer types, and thus it has emerged as a potential drug target for cancer therapeutics. In this study, we performed a structure-based virtual screening of the natural compounds taken from the IMPPAT database to find some potential molecules as inhibitors of ROCK1. For the first step, we selected the compounds based on the Lipinski rule of five, and then we filtered them based on their ADMET properties and PAINS value. After this, other parameters like binding affinities, docking score, biological properties and selectivity were calculated to find appropriate hits against ROCK1. Finally, we identified two natural compounds, Isoononin and Candidissiol, with appreciable binding affinity and selectivity towards ROCK1. Furthermore, all-atom molecular dynamics simulations were carried out on ROCK1 with the elucidated compounds, which suggested stability throughout the simulated trajectories of 100 ns. Taken together, Isoononin and Candidissiol could be considered as potential inhibitors of ROCK1 for developing anticancer therapeutics.Communicated by Ramaswamy H. Sarma.

Evaluation and treatment approaches for neurological post-acute sequelae of COVID-19: A consensus statement and scoping review from the global COVID-19 neuro research coalition.

Post-acute neurological sequelae of COVID-19 affect millions of people worldwide, yet little data is available to guide treatment strategies for the most common symptoms. We conducted a scoping review of PubMed/Medline from 1/1/2020-4/1/2023 to identify studies addressing diagnosis and treatment of the most common post-acute neurological sequelae of COVID-19 including: cognitive impairment, sleep disorders, headache, dizziness/lightheadedness, fatigue, weakness, numbness/pain, anxiety, depression and post-traumatic stress disorder. Utilizing the available literature and international disease-specific society guidelines, we constructed symptom-based differential diagnoses, evaluation and management paradigms. This pragmatic, evidence-based consensus document may serve as a guide for a holistic approach to post-COVID neurological care and will complement future clinical trials by outlining best practices in the evaluation and treatment of post-acute neurological signs/symptoms.

Cervical spine ligamentum flavum gaps: MR characterisation and implications for interlaminar epidural injection therapy.

BACKGROUND: Cervical epidural steroid injections are commonly performed to manage pain from cervical spine disease. Cadaveric studies have demonstrated incomplete ligamentum flavum fusion in the central interlaminar region with resultant midline gaps. We performed an MR-based characterization of cervical ligamentum flavum midline gaps to improve understanding of their prevalence and guide interventionalists in procedural planning. METHODS: Fifty patients were retrospectively reviewed following institutional review board approval. Axial T2-weighted spinecho sequences were used to evaluate ligamentum flavum integrity at the interlaminar spaces of C5-C6, C6-C7 and C7-T1. Interlaminar spaces were further subdivided into superior, middle, and inferior portions, yielding 150 interlaminar regions characterized from C5 to T1. Subsequently, a novel categorization of gap morphology was performed, highlighting gap morphology (anterior, posterior, full, or no gap). RESULTS: Full gaps of the ligamentum flavum, with direct epidural space exposure, were observed with variable prevalence at all three levels evaluated. The highest incidence of full ligamentum flavum gaps were observed at C7-T1, occurring in 71.4% of patients at both its middle and inferior portions. The inferior aspect of C5-C6 demonstrated the lowest observed rates of full ligamentum flavum gap (2%). CONCLUSIONS: Ligamentum flavum gaps occur in the lower cervical spine at high rates, with the highest prevalence of full thickness ligamentum flavum gaps at C7-T1. Interventionists must be aware of these important normal variants and evaluate preprocedural MRI to plan interventions.

Comparison of bare metal stents versus drug-eluting stents on clinical decision making in patients with previous percutaneous coronary intervention admitted for suspected acute coronary syndrome.

To determine whether the decreased rate of restenosis observed with drug-eluting stents (DES) has changed the treatment of patients with recurrent symptoms after stent placement, we compared patients hospitalized with presumed cardiac symptoms within 1 year after placement of either a DES or a bare metal stent (BMS). In this retrospective, single-center study, cases were identified from consecutive patients who received a DES from March 2003 to July 2004 or a BMS from August 2001 to June 2002. No differences were noted in the rate of hospitalization, hospitalization for presumed cardiac symptoms, use of coronary angiography in patients hospitalized for presumed cardiac symptoms, or average interval to hospitalization. In contrast, restenosis and the need for additional revascularization procedures were higher in the BMS group. The primary indication for additional revascularization was restenosis in the BMS group and progression of coronary artery disease in the DES group. In the DES group, the need for revascularization was significantly higher in patients with multi- versus single-vessel coronary artery disease (26% vs 7%, p < 0.05). In conclusion, the rate of hospitalization and use of coronary angiography in patients with recurrent symptoms were similar in patients who received a BMS or DES, despite the decreased rates of restenosis and additional revascularization procedures observed with DESs.

An overview of treatment strategies for cancer pain with a focus on interventional strategies and techniques.

SUMMARY As the incidence of cancer increases, considerations for pain treatments become more important and varied. While traditional views on pain therapy are successful in treating the majority of cancer-related pain, a continuum has developed to include interventional strategies in addition to pharmacologic management. Further improvements in understanding anatomy in the context of imaging and pathophysiology of cancer-pain syndromes direct our current interventional pain management options. We discuss the current interventional treatment options regularly used in the cancer-pain population.

Obesity and arterial compliance alterations.

Obesity is associated with increased cardiovascular disease (CVD) risk, especially when excess body fat is distributed preferentially within the abdominal region. Obese subjects usually have increased arterial stiffness compared with non-obese subjects of similar age. The factors associated with increased arterial stiffness in obesity include endothelial dysfunction (decreased nitric oxide bioavailability), impaired smooth muscle cell function, insulin resistance, as well as elevated cholesterol and C-peptide levels. Furthermore, visceral fat, the adipose tissue-related renin-angiotensin-aldosterone system and hyperleptinaemia contribute to the obesity-associated impaired arterial compliance. Weight loss improves CVD risk factors and arterial compliance. Because increased arterial stiffness is a marker of CVD risk these findings support the concept that the presence of obesity has vascular implications.