Selective antibacterial and antibiofilm activity of chlorinated hemicyanine against gram-positive bacteria.

Antibiotic-free therapies are highly needed due to the limited success of conventional approaches especially against biofilm related infections. In this direction, antimicrobial phototherapy, either in the form of antimicrobial photothermal therapy (aPTT) or antimicrobial photodynamic therapy (aPDT), have appeared to be highly promising candidates in recent years. These are local and promising approaches for antibiotic resistant bacterial infections and biofilms. Organic small photosensitizers (PSs) are extensively preferred in antimicrobial phototherapy applications as they offer a great opportunity to combine therapeutic action (aPTT, aPDT or both) with fluorescence imaging on a single molecule. In this study, the bactericidal effect of cationic chlorinated hemicyanine (Cl-Hem)-based type I PS, which can function as a dual aPDT/aPTT agent, was investigated on both planktonic cells and biofilms of different gram-positive (E. faecalis and S. epidermidis) and gram-negative bacteria (P. aeruginosa and K. pneumoniae) with and without 640 nm laser irradiation. Cl-Hem was shown to induce a selective phototheranostic activity against gram-positive bacteria (E. faecalis and S. epidermidis). Cl-Hem exhibited both dose and laser irradiation time dependent bactericidal effect on planktonic and biofilms of S. epidermidis. These results clearly showed that highly potent Cl-Hem can treat resistant microbial infections, while allowing fluorescence detection at the same time. High biofilm reduction observed with combined aPDT/aPTT action of Cl-Hem together with its non-cytotoxic nature points out that Cl-Hem is a promising PS for antibacterial and antibiofilm treatments.

Effectiveness of auditory distraction on the management of dental anxiety in patients undergoing tooth extraction at a tertiary care hospital in Islamabad.

OBJECTIVES: The study aimed to assess the effectiveness of anxiety reduction protocol using auditory distraction in alleviating dental anxiety among patients undergoing tooth extraction. MATERIALS AND METHODS: A randomized controlled trial was conducted at the Oral Surgery Department at Islamabad Dental Hospital from July to December 2022, involving 50 patients scheduled for tooth extraction. Participants were randomly divided into two groups: an interventional group, exposed to auditory distraction, and a noninterventional group, without exposure to auditory distraction before the dental extraction. Dental anxiety was measured using the modified dental anxiety scale (MDAS) questionnaire, which scores anxiety levels on a range from 5 (not anxious) to 25 (extremely anxious). Anxiety levels were assessed in the waiting room and just before extraction, and the results were compared across both groups to evaluate the effectiveness of auditory distraction in reducing dental anxiety. RESULTS: The sample size of 50 was randomly and equally allocated to the interventional and noninterventional groups. The study population consisted of 28 (56%) female and 22 (44%) male participants. No significant difference was observed between the anxiety scores of interventional and noninterventional groups at baseline. A significant reduction in anxiety scores was observed in the intervention group during postintervention assessment, while no significant difference was seen in the noninterventional group's anxiety scores. CONCLUSIONS: The study supports the efficacy of anxiety reduction protocol using auditory distraction as a practical tool for reducing dental anxiety among patients undergoing tooth extraction.

ALA/Ag2S/MnO2 Hybrid Nanoparticles for Near-Infrared Image-Guided Long-Wavelength Phototherapy of Breast Cancer.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) based on temperature increase and the formation of reactive oxygen species (ROS), respectively, is an exciting avenue to provide local and improved therapy of tumors with minimal off-site toxicity. 5-Aminolevulinic acid (ALA) is one of the most popular PDT pro-drugs, and its efficiency improves significantly when delivered to tumors with nanoparticles (NPs). But the tumor site's hypoxic environment is a handicap for the oxygen-consuming PDT process. In this work, highly stable, small, theranostic NPs composed of Ag2S quantum dots and MnO2, electrostatically loaded with ALA, were developed for enhanced PDT/PTT combination of tumors. MnO2 catalyzes endogenous H2O2 to O2 conversion and glutathione depletion, enhancing ROS generation and ALA-PDT efficiency. Ag2S quantum dots (AS QDs) conjugated with bovine serum albumin (BSA) support MnO2 formation and stabilization around Ag2S. AS-BSA-MnO2 provided a strong intracellular near-infrared (NIR) signal and increased the solution temperature by 15 °C upon laser irradiation at 808 nm (215 mW, 10 mg/mL), proving the hybrid NP as an optically trackable, long-wavelength PTT agent. In the in vitro studies, no significant cytotoxicity was observed in the absence of laser irradiation in healthy (C2C12) or breast cancer cell lines (SKBR3 and MDA-MB-231). The most effective phototoxicity was observed when AS-BSA-MnO2-ALA-treated cells were co-irradiated for 5 min with 640 nm (300 mW) and 808 nm (700 mW) due to enhanced ALA-PDT combined with PTT. The viability of cancer cells decreased to approximately 5-10% at 50 µg/mL [Ag], corresponding to 1.6 mM [ALA], whereas at the same concentration, individual PTT and PDT treatments decreased the viability to 55-35%, respectively. The late apoptotic death of the treated cells was mostly correlated with high ROS levels and lactate dehydrogenase. Overall, these hybrid NPs overcome tumor hypoxia, deliver ALA to tumor cells, and provide both NIR tracking and enhanced PDT + PTT combination therapy upon short, low-dose co-irradiation at long wavelengths. These agents that may be utilized for treating other cancer types are also highly suitable for in vivo investigations.

Technology-enhanced trauma training in low-resource settings: A scoping review and feasibility analysis of educational technologies.

BACKGROUND: Lack of training contributes to the burden of trauma-related mortality and morbidity in low- and lower-middle-income countries (LMICs). Educational technologies present a unique opportunity to enhance the quality of trauma training. Therefore, this study reviews current technologies used in trauma courses and evaluates their feasibility for LMICs. METHODS: We conducted a scoping review evaluating the learning outcomes of technology-enhanced training in general trauma assessment, team skills or any procedures covered in the 2020 Advanced Trauma Life Support® program. Based on the Technology-Enhanced Learning criteria, we created and applied a feasibility analysis tool to evaluate the technologies for use in LMICs. RESULTS: We screened 6471 articles and included 64. Thirty-four (45%) articles explored training in general trauma assessment, 28 (37%) in team skills, and 24 (32%) in procedures. The most common technologies were high-fidelity mannequins (60%), video-assisted debriefing (19%), and low-fidelity mannequins (13%). Despite their effectiveness, high-fidelity mannequins ranked poorly in production, maintenance, cost, and reusability categories, therefore being poorly suited for LMICs. Virtual simulation and digital courses had the best feasibility scores, but still represented a minority of articles in our review. CONCLUSION: To our knowledge, this is the first study to perform a feasibility analysis of trauma training technologies in the LMIC context. We identified that the majority of trauma courses in the literature use technologies which are less suitable for LMICs. Given the urgent need for pediatric trauma training, educators must use technologies that optimize learning outcomes and remain feasible for low-resource settings. LEVEL OF EVIDENCE: IV.

Development of a cysteine responsive chlorinated hemicyanine for image-guided dual phototherapy.

A cysteine (Cys) activatable chlorinated hemicyanine (Cl-Cys) was introduced as a tumour selective image-guided dual phototherapy agent. Cl-Cys exhibited a significant turn on response in its near-IR emission signal and activated its singlet oxygen generation as well as photothermal conversion potentials upon reacting with Cys. The laser irradiation of Cl-Cys induced significant cell death in cancer cells with high Cys level, while it stayed deactivated and non-emissive in a healthy cell line. A profound synergistic PDT/PTT effect was observed at high doses. Remarkably, Cl-Cys marks the first ever example of Cys-responsive small organic-based therapeutic agent and holds a great promise to develop new activity-based photosensitizers for dual phototherapy action.

Teaching Trauma in Resource-Limited Settings: A Scoping Review of Pediatric Trauma Courses.

PURPOSE: Injury remains an important cause of death and disability globally, with 95% of all childhood injury deaths occurring in low- and lower-middle-income countries (LMICs). Pediatric trauma training, tailored to the resources in LMICs, represents an opportunity to improve such outcomes. We explored the nature of course offerings in pediatric trauma in resource-limited settings. METHODS: Seven databases were interrogated up to June 12, 2020, to retrieve articles examining pediatric trauma training in LMICs, as defined by the World Bank, without language restrictions. Independent authors reviewed and selected abstracts based on set criteria. Data from included studies was extracted and analyzed. An adapted Critical Appraisal Skills Programme checklist designed for cohort studies was used to assess the risk of bias. RESULTS: After screening 3960 articles for eligibility, 16 were included for final analysis. Course delivery methods included didactic modules, simulations, clinical mentorship, small group discussion, audits, assessments, and feedback. Knowledge acquisition was primarily assessed through pre/post-tests, clinical skills assessments, and self-assessment questionnaires. Twelve studies detailed course content, nine of which were based on the WHO Emergency Triage, Assessment and Treatment model, which is not specific to trauma. The other three studies involved locally developed pediatric trauma-focused training courses, including airway management, head trauma and cervical spine management, thoracic and abdominal trauma, orthopedic trauma, burn and wound management, and shock. CONCLUSION: Despite being essential to decreasing pediatric trauma morbidity and mortality worldwide, educational programs in pediatric trauma are not a widespread reality in low-and-middle-income countries. The development of accessible and efficient pediatric trauma education programs is critical for improving pediatric trauma quality of care.

Determination of the Wavelength-Dependent Photothermal Conversion Efficiency of Photosensitizers for Photothermal Therapy: Application to Ag2S-Glutathione Quantum Dots.

Nanoparticles have become popular photosensitizers for photothermal therapy (PTT), as they can be targeted to specific cancer tissues and deliver a chemotherapeutic drug, providing a multimodal therapeutic approach. Photothermal conversion efficiency of nanoparticles is critical in the assessment of their therapeutic use in PTT. We describe an accurate calorimetric method for the determination of the photothermal conversion efficiency of nanoparticles in solution. A tightly focused laser beam was used to irradiate a cuvette containing a solution of silver sulfide-glutathione quantum dots (Ag2S-GSH QDs), and the maximum steady-state temperature rise was measured with an infrared camera. The data were analyzed using two different photothermal conversion efficiencies, the intrinsic and external conversion efficiencies, to relate the induced heating power of the nanoparticles to the absorbed and incident optical powers, respectively. Measurements with a tunable Ti3+:sapphire laser showed that the intrinsic photothermal conversion efficiency of Ag2S-GSH QDs exceeded 91% over the 720-810 nm wavelength range. The method was also used to analyze poly(acrylic acid)-coated superparamagnetic iron oxide nanoparticles (PAA/SPIONs), and the intrinsic photothermal conversion efficiency was determined to be 83.4% at 810 nm. This approach is useful for the evaluation of various potential nanoparticles for photothermal therapy applications.