Potential targets and traditional Chinese medicine treatment strategy of cough after SARS-CoV-2 infection.

The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) Omicron variants BA.5.2 and BF.7 have become the main epidemic strains in China since the quarantine policy was lifted in 7th December 2022. Cough is one of the main symptoms induced by SARS-CoV-2 infection. SARS-CoV-2 infection-associated cough injuries the lung and upper respiratory tract, while the infected people cough out virus and liquid which forms virus-containing aerosols, a medium for quickly spreading. Furthermore, cough is one of primary sequelae of discharged patients in corona virus disease 2019 (COVID-19). By now, there are no efficacious drugs for treatment of upper respiratory tract infection associated cough induced by omicron. Traditional Chinese medicine (TCM) has a long history on treating cough. By reviewing the mechanisms of the occurrence of cough after SARS-CoV-2 infection, potential therapeutic targets and cough suppressant herbs with significant efficacy in clinical and basic research, we provide a reference for the treatment of cough after SARS-Cov-2 infection and a basis for the majority of infected patients to select appropriate herbs for cough relief under guidance of physicians.Copyright © 2023 Editorial Office of Chinese Traditional and Herbal Drugs. All rights reserved.

Year 2022 in review - Chronic pain.

This article presents a selection of interesting basic research, clinical studies, new recommendations, new definitions of pain, a new type of nociplastic pain, and a completely new type of post-covid headache. Only foreign and relevant sources are discussed.Copyright © 2022, Czech Medical Association J.E. Purkyne. All rights reserved.

Emerging topics on basic research in hypertension: interorgan communication and the need for interresearcher collaboration.

The pathogenesis of hypertension is multifactorial and highly complex. Basic research plays critical roles in elucidating the complex pathogenesis of hypertension and developing its treatment. This review covers recent topics in basic research related to hypertension in the following six parts: brain/autonomic nervous system, kidney, vascular system, potential treatments, extracellular vesicles, and gut microbiota. The brain receives afferent nerve inputs from peripheral organs, including the heart, kidneys, and adipose tissue, and humoral inputs from circulating factors such as proinflammatory cytokines and leptin, which are involved in the regulation of central sympathetic outflow. In the kidneys, changes in Wnt/ß-catenin signaling have been reported in several hypertensive models. New findings on the renin-angiotensin-aldosterone system in the kidneys have also been reported. Sirtuin 6, which participates in various cellular functions, including DNA repair, has been shown to have protective effects on the vascular system. Skin water conservation, mediated by skin vasoconstriction and the accumulation of osmolytes such as sodium, has been found to contribute to hypertension. Studies of rivaroxaban and sodium-glucose cotransporter-2 inhibitors as drug repositioning candidates have been performed. Extracellular vesicles have been shown to be involved in novel diagnostic approaches and treatments for hypertension as well as other diseases. In gut microbiota studies, interactions between microbiota and antihypertensive drugs and potential pathophysiology linking microbiota and COVID-19 have been reported. It can be seen that inter-organ communication has received particular attention from these recent research topics. To truly understand the pathogenesis of hypertension and to develop treatments for conquering hypertension, interresearcher communication and collaboration should be further facilitated. This mini-review focuses on recent topics on basic research in hypertension from the several points of view. The recent topics indicate that inter-organ communication has received particular attention. Interresearcher communication and collaboration should also be further facilitated to truly understand the complex pathogenesis of hypertension and to develop the treatments.

Management and Scheduling of Spine Surgery in a Level 1 Trauma Center in the Setting of the COVID-19 Pandemic: Feasibility and Considerations for Reimplementation of Elective Spine Surgery.

Introduction: Determination of what constitutes necessary surgery in the setting of acute hospital resource strain during the COVID-19 pandemic is an unprecedented challenge for healthcare systems. Over the past two years during the COVID-19 pandemic, there have been many changes in reviews of medically necessary spine surgery. There continues to be no clear guidelines on recommendations and further discussion is necessary to continue to provide appropriate and high-level care during future pandemics. Significance: This review critically appraises and evaluates current barriers to medically necessary spine surgery during the COVID-19 pandemic and evaluates future decision making to maintain spine surgery during future pandemics or limitations in medical care. Results: Multiple studies included in this review have shown that while various orthopaedic surgeries may be considered elective, medically necessary spine surgery will need to continue during settings of limited medical care. This review discussed multiple methods and recommendations to limit transmission of virus from patients to providers and providers to patients. Conclusion: Continued medically necessary spine surgery in the setting of the COVID-19 pandemic and future pandemics should continue while limiting risk of transmission to continue providing high-level medical care and allowing hospitals to maintain financial responsibility.

Potential therapeutic role of antimicrobial peptides against SARS-CoV-2 evidenced by computational analyses of peptide-protein interactions

Introduction: The pandemic of coronavirus disease 2019 (COVID-19) poses critical challenges for the public health, research, and medical communities worldwide. While vaccines were made available at record speed, there remains the need to develop effective therapeutic agents. Therefore, we evaluated the potential pharmaceutical role of naturally occurring antimicrobial peptides (AMPs) against SARS-CoV-2 by studying their peptide-protein interactions through computational analyses. Material(s) and Method(s): Antimicrobial peptides from the antimicrobial peptide database (APD3) were considered and shortlisted based on stringent physicochemical properties. Promising AMPs were subjected to 3D structure predictions by ab initio modeling, and the peptide best models were selected based on their higher confidence score (C-score). Schrodinger Maestro's protein preparation wizard was used to prepare and optimize the modelled peptides' structure. The spike protein of SARS-CoV-2 and peptide-protein docking were evaluated using the Piper module. Additionally, protein-protein non-bonding interactions were assessed. Furthermore, the stability of the top complex was subjected to explicit molecular dynamics. The study was funded by Malaysian Fundamental Research Grant Scheme [[ref no. FRGS/1/2020/SKK0/UNIKL/02/1]. Result(s) and Conclusion(s): Of the shortlisted thirty AMPs, five potential peptides that efficiently bound to the spike protein were identified based on the lowest Piper energy scores - HD-5, Rat NP-4, Kalata B8, HFIAP-3, and Circulin D. These potential AMPs were further analysed by molecular dynamic simulations to verify the stability of the docked complexes, and HD-5 was observed to have robust interaction with the spike protein. Thus, the findings of the computational analyses highlight the antiviral potential of AMPs in inhibiting host cell entry of SARS-CoV-2 and could serve as anti-SARS-CoV-2 therapeutic candidates, and further future in vitro and in vivo experimental studies are warranted.

Building Capacity for Congenital Heart Patient- Centered Outcomes Research in Under-Represented Minorities

Background: In congenital heart disease, racial and ethnic disparities impact mortality, especially among Blacks and Hispanics in Texas and surrounding regions, however meaningful engagement in ACHD, especially interventional patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) has been limited by socioeconomic, cultural, and geographic factors. We employed a patient-driven peer-to-peer approach to recruit and engage racial minority ACHD patients and family members with the capacity to act as equal research partners to identify, participate in, develop, lead, and disseminate transcatheter intervention PCOR and CER. Method(s): In addition to the study team, four expert PCORI funded-consultants provided strategies and training on stakeholder recruitment and engagement for targeting minorities and underserved communities. The following strategies were employed: 1) engaging through faithbased organizations like churches, synagogues, and mosques 2) working with Houston Methodist Primary Care Providers (PCP) group to identify ACHD patients 3) recruiting through the project's Online Portal and participants' Video Blogs to appeal to stakeholders 4) using social media for mainstream outreach. Result(s): Eighteen total ACHD collaborative members were successfully recruited. Six ACHD patient advocates were recruited as Steering Committee Members (SCM) of the stakeholder collaborative (STK), however, two SCMs resigned from their positions due to family reasons and time commitments. One member was replaced by previously interviewed candidates and another was promoted from our lay STKs. Other applicants remain involved in a non-decision maker capacity as in-waiting STK members. Social media outreach and our online portal proved to be the most efficient recruitment and engagement strategies. On average, we received three new candidate applications after every social media post. Eleven stakeholders were recruited through social media. One stakeholder was recruited through the PCP network. Two churches promoted our flier in their newsletter but we did not receive any applications. Onsite recruiting from faith-based organizations was not feasible due to the ongoing global health crisis from COVID- 19. Discussion(s): Addressing racial disparities in congenital heart and interventional cardiology is challenging and requires a patient-centered approach to research. Despite the COVID-19 pandemic, we successfully built an 18-member ACHD patient collaborative of underrepresented minorities, employing a peer-to-peer strategy through a multi-faceted approach. Social media was the most successful approach especially in the absence of in-person gatherings, however, despite financial compensation for involvement, attrition due to personal reasons occurred. Current efforts are directed toward training the ACHD patient collaborative in basic research methods to serve as equal partners in patient-centered outcomes and comparative effectiveness research.

Understanding mental stress and skin aging connection among dermatologists and psychologists through real world evidence

Preaging is an emerging concept in China whereby young women are looking for skin aging solutions. Among the intrinsic and extrinsic causes of skin aging, mental stress was highlighted as a possible cause of preaging in young women. The COVID-19 pandemic has further impacted the mental well-being of the younger generation, with 44% of Asian women aged 18 to 34 under poor mental well-being based on WHO-5. While 76.5% of dermatologists agreed that there is a strong connection between stress and skin aging, there is limited evidence on the pathophysiology. The aim of this research is to explore how clinicians understand the impact of stress and the biologic pathways connecting stress and skin aging. A quantitative survey with 60 dermatologists and 60 psychologists from China and Japan was conducted to assess the link between stress and skin aging. Overall, 69.2% of both health care professionals agree that psychological stress has a significant link to skin aging. Three meta-themes were perceived by clinician as possible pathways connecting psychological stress and skin aging, including stress hormone, inflammation, and overactive immune system. While all health care professionals have heard of inflammaging, only 52% are very familiar with the concept. Both groups agree that unresolved acute inflammatory response can accelerate skin aging. Surprisingly, a significant difference was observed in that psychologists believe more strongly than dermatologists that chronic low-grade inflammation accelerates skin aging. This study highlights the need for further fundamental research, which could help clinicians provide appropriate recommendations for patients under psychological stress.

Mesenchymal Stem/Stromal Cells: ENDOGENOUS NON-TUMORIGENIC PLURIPOTENT MUSE CELLS;BASIC RESEARCH AND CLINICAL TRIALS

Background & Aim: Multilineage-differentiating stress enduring (Muse) cells, collectable as pluripotent surface marker SSEA-3-positive, are naturally existing non-tumorigenic pluripotent stem cells that distribute in the bone marrow, peripheral blood, connective tissue of every organ, and exhibit triploblastic differentiation and self-renewability at a single cell level. They are also contained in cultured MSCs and fibroblasts as several percent, and are expandable to a clinical scale. Circulating Muse cells, both endogenous and intravenously injected exogenous cells, selectively home to damaged tissue by sensing sphingosine-1-phosphate (S1P), one of the general alert signals produced by the damaged tissue, and then spontaneously differentiate into multiple tissue-constituent cells to replace damaged/ apoptotic cells. In this manner, they repair tissues. In addition, they have a specific immunomodulatory system, represented by HLA-G expression, allowing allogenic-Muse cells to directly administrate to patients without HLA-matching or long-term immunosuppressant (Figure Presented) treatment, and to remain in the host tissue as differentiated functional cells for more than half a year, as shown by animal models. Methods, Results & Conclusion: For these characteristics, intravenous drip is the main route of treatment and do not require surgery for their administration, nor do they require gene introduction or cytokine treatment to be rendered pluripotency and/or differentiation. Currently, clinical trials using intravenously administered donor- Muse cells have been conducted for myocardial infarction, stroke, epidermolysis bullosa, spinal cord injury, perinatal hypoxic ischemic encephalopathy, amyotrophic lateral sclerosis and COVID19-ARDS, all by intravenous drip of donor-derived Muse cell formula, CL2020, without HLA-matching or immunosuppressant treatment. The result of randomized, double-blind, placebo-controlled clinical trial in stroke patients confirmed safety and efficacy of Muse cell-based product for up to 52 weeks (1 year). Muse cells may safely provide beneficial effects compatible with the ‘body’s natural repair systems’ by a simple cost- effective strategy;collection, expansion and intravenous drip.

Delivering digital learning packages to address allied health professionals skill gaps in research

Keywords: Digital learning;Research hospital;Digital research Purpose: Higher levels of research activity within healthcare contexts is associated with improved organizational efficiency;staff and patient satisfaction;reduced staff turnover and mortality rates (Harding et al., 2017). COVID-19 has increased demand for digital infrastructure to support clinical work and enable high quality data driven research. Electronic patient records require new digital skills, whilst established research skill packages need transformed delivery. This project aimed to build individual AHP's knowledge of basic research concepts and skills, to promote confidence in the early stages of research in a digital environment. Online packages enable participation that is flexibly managed within their own clinical schedules, addressing one of the barriers identifies to undertaking research. 1. To develop a practical guide using electronic training resources to support research amongst AHP clinicians 2. To provide a sustainable resource across a Research Hospital Methods: The RCC tool is a cross-sectional survey of research capacity and culture (RCC) was completed by 170 AHPs (OT, PT, SALT, Dietetics)2. This captured research experience and skill and identified knowledge gaps and barriers to undertaking research. The top 10 items identified were mapped to trust research strategy, and topics shared with the trust Learning Academy to match 10 topics to digital formats. Results: The first 5 short learning packages have been completed using a multi-dimensional approach to ensure engagement and widespread appeal. These include short animations, podcasts, mini-clips supported by the digital team at GOSH Learning Academy, piloting novel formats for future education packages, and helping build research capacity within Physiotherapy and allied disciplines. Conclusion(s): These ‘bite-sized’ digital learning resources will be widely accessible and both engaging and appealing to clinicians and easier to access within their own time. Although time and clinical commitment are reported to be barriers towards enhancing learning skills in research, these novel packages are designed to tackle this. Impact: – Online learning packages may promote research capacity building for individuals. –Content delivered in a variety of digital formats is accessible to a wider, more diverse audience in part addressing research inequalities across Physiotherapy and AHPs. –Online learning packages can be shared more widely to benefit a wider audience. Funding acknowledgements: Great Ormond Street Capacity Building scheme funded by GOSHCC and the BRC.

Research ready: Strategies for successful implementation of research in clinical settings

Through our experience implementing pragmatic studies, the Louisiana Public Health Institute recognized clinic support staff as unique stakeholders in clinicbased research whose role in study implementation is often overlooked. Our project, Research Ready, aimed to find innovative ways to engage staff in the design and implementation of research studies. Specifically, the project team designed, piloted, and disseminated materials to improve clinic staff capacity to partner in research. During this pandemic, reliance on clinical staff for study adherence is critical. COVID-related research has been rapidly implemented, which relies upon having well-prepared staff to handle the rapid implementation of new protocols. The team developed and piloted two tools for improving staff engagement in research activities: a training for clinic support staff and a guide for researchers. The staff training was developed to inform clinic staff, such as medical assistants and nurses, about basic research principles and considerations for supporting the implementation of research in a clinical setting. The training is available in three formats: e-learning, facilitated session, and self-guided workbook. The researcher guide was created to share insights and best practices for engaging and partnering with clinic staff to successfully implement pragmatic research. Both resources are available on Louisiana Public Health Institute's website. The Research Ready resources were informed by interviews conducted with clinic support staff and researchers (including principal investigators, study managers, and clinical research coordinators) who had implemented studies in outpatient settings. Clinic staff from a variety of settings were interviewed, including Federally Qualified Health Centers, private healthcare systems, and academic medical centers. Research staff were either affiliated with academic institutions or clinical research firms. Major themes identified in the key-informant interviews include (1) clinic staff play key roles in implementing research: they are gatekeepers of clinic workflow and brokers of patient trust;(2) clinic staff lack knowledge about research and the research process, which is a barrier to implementing studies in clinic settings;(3) communication and relationship-building are important facilitators for researchers seeking to work with clinical staff;(4) clinic staff prioritize the care and wellbeing of their patients, which can be both a barrier and a facilitator of clinic-based research. The training was piloted in three sites with a total of 52 participants. Participants were surveyed after completing the training. Survey results showed that participants thought the training was easy to understand and increased their knowledge about research. Results also showed that participants felt the information from their training was applicable to their jobs. As more research is conducted in clinic settings, researchers and clinic staff will benefit from best practices to assure a mutual understanding of research objectives and processes. Identifying strategies for successful implementation of research in clinical settings will enhance the conduct of pragmatic research and allow it to equitably reach patients in diverse outpatient care settings. Using the Research Ready materials, researchers can ensure that clinic staff have adequate understanding of research principles and that staff concerns about time and competing priorities are addressed and accounted for in study workflows.

[Rapid establishment of traditional Chinese medicine prevention and treatment of 2019-nCoV based on clinical experience and molecular docking].

The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.