Synthesis and Inhibitory Activity of Machaeridiol-Based Novel Anti-MRSA and Anti-VRE Compounds and Their Profiling for Cancer-Related Signaling Pathways.

Three unique 5,6-seco-hexahydrodibenzopyrans (seco-HHDBP) machaeridiols A-C, reported previously from Machaerium Pers., have displayed potent activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium, and E. faecalis (VRE). In order to enrich the pipeline of natural product-derived antimicrobial compounds, a series of novel machaeridiol-based analogs (1-17) were prepared by coupling stemofuran, pinosylvin, and resveratrol legends with monoterpene units R-(-)-α-phellandrene, (-)-p-mentha-2,8-diene-1-ol, and geraniol, and their inhibitory activities were profiled against MRSA ATCC 1708, VRE ATCC 700221, and cancer signaling pathways. Compounds 5 and 11 showed strong in vitro activities with MIC values of 2.5 µg/mL and 1.25 µg/mL against MRSA, respectively, and 2.50 µg/mL against VRE, while geranyl analog 14 was found to be moderately active (MIC 5 µg/mL). The reduction of the double bonds of the monoterpene unit of compound 5 resulted in 17, which had the same antibacterial potency (MIC 1.25 µg/mL and 2.50 µg/mL) as its parent, 5. Furthermore, a combination study between seco-HHDBP 17 and HHDBP machaeriol C displayed a synergistic effect with a fractional inhibitory concentrations (FIC) value of 0.5 against MRSA, showing a four-fold decrease in the MIC values of both 17 and machaeriol C, while no such effect was observed between vancomycin and 17. Compounds 11 and 17 were further tested in vivo against nosocomial MRSA at a single intranasal dose of 30 mg/kg in a murine model, and both compounds were not efficacious under these conditions. Finally, compounds 1-17 were profiled against a panel of luciferase genes that assessed the activity of complex cancer-related signaling pathways (i.e., transcription factors) using T98G glioblastoma multiforme cells. Among the compounds tested, the geranyl-substituted analog 14 exhibited strong inhibition against several signaling pathways, notably Smad, Myc, and Notch, with IC50 values of 2.17 µM, 1.86 µM, and 2.15 µM, respectively. In contrast, the anti-MRSA actives 5 and 17 were found to be inactive (IC50 > 20 µM) across the panel of these cancer-signaling pathways.

Radio Frequency Heating of Washable Conductive Textiles for Bacteria and Virus Inactivation.

The ongoing COVID-19 pandemic has increased the use of single-use medical fabrics such as surgical masks, respirators, and other personal protective equipment (PPE), which have faced worldwide supply chain shortages. Reusable PPE is desirable in light of such shortages; however, the use of reusable PPE is largely restricted by the difficulty of rapid sterilization. In this work, we demonstrate successful bacterial and viral inactivation through remote and rapid radio frequency (RF) heating of conductive textiles. The RF heating behavior of conductive polymer-coated fabrics was measured for several different fabrics and coating compositions. Next, to determine the robustness and repeatability of this heating response, we investigated the textile's RF heating response after multiple detergent washes. Finally, we show a rapid reduction of bacteria and virus by RF heating our conductive fabric. 99.9% of methicillin-resistant Staphylococcus aureus (MRSA) was removed from our conductive fabrics after only 10 min of RF heating; human cytomegalovirus (HCMV) was completely sterilized after 5 min of RF heating. These results demonstrate that RF heating conductive polymer-coated fabrics offer new opportunities for applications of conductive textiles in the medical and/or electronic fields.

Therapists' experiences of remotely deliveredcognitive-behavioural and graded-exerciseinterventions to lessen the impact of fatigue ininflammatory rheumatic diseases: A qualitativeevaluation

Background/AimsThere is evidence for non-pharmacological interventions to supportpatients to self-manage fatigue, however implementation in clinicalpractice is a challenge. LIFT (Lessening the Impact of Fatigue ininflammatory rheumatic diseases: a randomised Trial) is a multi-centrethree-arm randomised trial using a remotely delivered cognitivebehavioural approach (CBA) or personalized exercise programme(PEP) interventions, in addition to usual care, compared to normal carealone. Interventions were delivered to patients by rheumatology healthprofessionals using a manual, after training. The aim of this nestedqualitative evaluation was to understand their perspectives ofdelivering the interventions. MethodsA subgroup of rheumatology healthcare professionals who haddelivered the CBA and PEP interventions took part in semi-structuredtelephone interviews to explore their experiences of training anddelivery, the challenges and benefits of learning new skills, and thebarriers and facilitators to supporting patients remotely (mainly bytelephone) using the LIFT manual.ResultsA total of 17 rheumatology healthcare professionals (13 women, 4 men)from the CBA (n = 9) and PEP (n = 8) arms contributed. SB conducted aninductive thematic analysis of the data set. ED, CA, AW and KL revieweda sub-set of transcripts. Five main themes were identified: The benefitsof informative, structured training: Rheumatology healthcare professionals reflected how training, including role-play, helped them topractice their skills, even though this could feel uncomfortable. Thoseallocated shorter four-hour training sessions would have liked more timeto practice. Many felt anxious before meeting patients for the first timebut liked the manual to refer to.Getting into the swing of it: Practice gave rheumatology healthcareprofessionals the confidence to tailor content to individual patients'requirements. Clinical supervision in the PEP and CBA arm supportedrheumatology healthcare professionals to query their own practice, gain valuable feedback, and request assistance where needed.Benefits of telephone delivery: The initial face-to-face session enabledrheumatology healthcare professionals to build rapport with patients.Thereafter, patients seemed engaged and valued the opportunity toaddress their fatigue and challenge their own beliefs via the telephone.Some patients not ready to change: Rheumatology healthcareprofessionals struggled to work collaboratively with a minority ofpatients who were not willing to make changes, lacked motivation tocomplete tasks or stopped engaging with the intervention.LIFT developing clinical skills: Rheumatology healthcare professionalswere confident that they were doing the 'right thing' for patients withfatigue and gained professional satisfaction seeing patients' fatigueimprove. Many felt that the skills they acquired and their experiencesof remote delivery were helping them to respond to the current COVID-19 related changes in service provision.ConclusionFindings support the value of skills training for rheumatology healthprofessionals to deliver fatigue management interventions remotely.These insights can inform service provision and clinical practice.