Application of Intralesion Ultrasound-Guided Laser Ablation for Plantar Foot Mass Involving Arteriovenous Fistula: A Case Report.

Penetrating and blunt trauma to the plantar aspect of the foot are common. Both penetrating and blunt trauma may be associated with an injury to the blood vessels, which may go undetected clinically. A minor puncture, blunt trauma and repeated blunt trauma can injure small arteries leading to an arteriovenous fistula (AVF). The arterial rupture leads to a system of veins creating a small AVF and appearing clinically as a blue colored, painful lesion. A case of such an injury is presented where the clinical examination, magnetic resonance arteriogram and point of service ultrasound with duplex imaging was used to diagnose the AVF. The AVF was treated in the clinic with a percutaneous ultrasound-guided laser procedure. The laser procedure was effective and there was minimal post procedural morbidity.

Use of Topical Timolol Maleate as Re-Epithelialization Agent for Treatment of Recalcitrant Wounds of Varying Etiologies.

Background: Chronic wounds remain a challenge for the clinician and healthcare system. It is therefore vital for additional therapies that target steps involved in wound recalcitrance. Recently, topical timolol has shown promising results for use in wound healing. Objective: The goal of this study was to assess timolol's effectiveness in healing wounds of varying etiologies. Methods: This multi-center series took place from 2016¬­2019 at the wound healing centers at the University of Miami Health System and the Veterans Affairs Northern California Healthcare. We identified all wound patients who received treatment with topical timolol maleate 0.5% for at least 4 weeks after failing previous treatments. Timolol drops at a dose of 1 drop per cm2 of wound area were instilled with dressing changes twice a day, once a day, every other day, or continuous application. Once they began the study, they stopped all concurrent therapies aside from standard of care. Healing outcomes were classified into 3 categories: healed, defined as complete re-epithelialization of the wound and closure, improved, defined as decreasing wound size area (WSA), and worsening, defined as increasing WSA. Results: We identified 39 patients, 32 males and 7 females that had a total of 55 chronic wounds of varying etiologies. Thirty-four of the wounds had completely healed, 15 wounds improved in WSA, 4 wounds were unchanged in WSA, and 2 wounds worsened in WSA. Conclusions: In line with our previous experience, we found topical timolol to be a safe, cost-effective, and efficacious treatment for recalcitrant wounds of varying etiologies.

A comparative evaluation of remaining dentin thickness following biomechanical preparation of teeth using different rotary file systems: An in vitro study.

Aim: The aim of the study is to compare and evaluate the remaining dentin thickness following biomechanical preparation of teeth using different rotary file systems. Materials and Methodology: Sixty noncarious mandibular premolar teeth were collected and decoronated at the level of cementoenamel junction with a diamond disc. All specimens were randomly divided into 5 experimental groups - ProTaper Next (Dentsply Mallifer), Mtwo (VDW, Antaeus, Munich, Germany), RaCe (FKG, La Chaux-de-Fonds, Switzerland), Hyflex electro-discharge machining (EDM) (Coltene-Whaledent, Allstetten, Switzerland), NeoNiTi (Neolix, France) and 1 control group of 10 teeth each. After mounting the samples on a modeling wax sheet, preoperative cone-beam computed tomography (CBCT) scans were taken. Biomechanical preparation of canals was done following the assigned protocol of manufacturers. Postoperative CBCT scans were taken and comparison was carried out with preoperative scans. Statistical Analysis Used: Difference among the groups was analyzed by post hoc Turkey and analysis of variance tests. A P < 0.05 was considered statistically significant for all tests. Results: A comparison of preinstrumentation and postinstrumentation CBCT images revealed ProTaper Next group to remove more dentin at 7 mm as opposed to other groups in mesiodistal direction. However, no statistical difference was evident between ProTaper Next, MTwo, Race, Hyflex EDM, NeoNiTi file systems at 3 mm, 5 mm, and 7 mm in buccolingual direction. A statistically nonsignificant difference was evident between MTwo, Race, Hyflex EDM, NeoNiTi file systems at 3 mm, 5 mm, and 7 mm in both mesiodistal and buccolingual direction. Conclusion: Race file system performed better and removed lesser dentin in both buccolingual and mesiodistal directions. More dentin was removed at the coronal in mesiodistal direction with the use of ProTaper Next, and significant difference was seen between Protaper Next group and other groups in the study.

Covishield India: demystifying myths through an early multicenter study.

OBJECTIVES: Nationwide COVID-19 vaccination was initiated in India on January 16, 2021, in a phased manner with vaccines including Covishield. This vaccine was indigenously prepared by Serum Institute of India in line with the Oxford-AstraZeneca ChAdOx1 vaccine developed at the University of Oxford. This is the first multicenter study to assess the safety of the indigenously prepared Covishield vaccine in India. STUDY DESIGN: Multicenter observational descriptive study. METHODS: This was a multicenter study carried out in northern and eastern India. Individuals who received the first dose of the Covishield vaccine were followed up for 7 days to check for any adverse effects or systemic effects post vaccination. The data were collected by the authors with a participant-administered questionnaire. The primary end point was the incidence of adverse or systemic effects within 7 days post vaccination. RESULTS: No serious adverse or systemic effects were noted in 7 days of follow-up. Nonserious systemic effects were seen in 42.0% of individuals post vaccination. Myalgia and/or fatigue was the most common effect of vaccination in 25.7%, followed by fever in 22.0% of individuals. In most individuals, the systemic effects started 6 to 12 hours post vaccination. There were no reports of fresh onset of systemic effects of any kind beyond 48 hours of vaccination. Women and older adults tolerated the vaccination better. CONCLUSIONS: The absence of serious adverse effects in our study will help allay fears around vaccine acceptance and give a boost to the vaccination campaign worldwide.

Repurposing Ophthalmologic Timolol for Dermatologic Use: Caveats and Historical Review of Adverse Events.

Ophthalmic timolol solution is increasingly being repurposed as a topical therapeutic for a variety of dermatologic diseases, including pyogenic granulomas, infantile hemangiomas, and chronic wounds. There are no published guidelines or protocols for use in these indications in adults, and the dermatologic community may not be familiar with adverse events that have been extensively documented relating to its ophthalmic use. We review the evidence available relating to adverse events to topical timolol use to evaluate its safety in dermatologic applications and to alert clinicians to screening and monitoring that is needed when repurposing this drug for dermatologic use. The majority of serious adverse events associated with ophthalmic timolol were reported in the first 7 years of use, between 1978 and 1985, of which most common were cardiovascular and respiratory events, but also included 32 deaths. The available evidence suggests that ophthalmic timolol safety profiling may have been incomplete prior to widespread use. Recent clinical trials for dermatologic indications have focused on documenting efficacy and have not had rigorous monitoring for potential adverse events. Topical timolol may be safe and effective for the treatment of various dermatologic conditions in patients whose medical histories have been carefully reviewed for evidence of pre-existing cardiac or pulmonary disease and are monitored for potential adverse events. Despite the wide use of timolol in ophthalmologic practice, safe dermatologic repurposing requires recognition of the potential for facilitated systemic absorption though the skin and appreciation of its history of adverse events.

Females, their estrogens, and seizures.

Estrogens are essential for normal brain functions. The effects of estrogens on seizures are contradictory. More studies are necessary to determine under which conditions the estrogens have proconvulsant effects and when the estrogens may have beneficial action in patients with epilepsy.

Beta-adrenergic antagonist for the healing of chronic diabetic foot ulcers: study protocol for a prospective, randomized, double-blinded, controlled and parallel-group study.

BACKGROUND: Diabetic foot ulcers (DFUs) are the most common cause of leg amputations and their management is extremely challenging. Despite many advances and expensive therapies, there has been little success in improving outcomes of DFUs. In prior work our laboratory has examined the effects of beta-adrenergic antagonists (ßAAs) on skin and skin-derived cells. We have shown that ßAAs enhance the rate of keratinocyte migration, promote angiogenesis, and hasten wound healing in scratch wounds in vitro, in animal wound models, and in anecdotally reported cases of chronic wounds that healed successfully after topical application of the ßAA timolol. Thus, we propose to test timolol directly on DFUs to determine if it improves healing above the current standard of care (SOC). This study will examine the efficacy and safety of topically applied beta-antagonist Timoptic-XE® (timolol maleate ophthalmic gel forming solution) in subjects with DFUs. METHODS/DESIGN: This is a phase two, randomized, double-blinded, controlled, and parallel-group clinical trial with two treatment arms, SOC plus topical Timoptic-XE® and SOC plus a non-biologically active gel (hydrogel, as placebo drug). Study subjects with a DFU will be selected from the Veterans Affairs Northern California Health Care System (VANCHCS). Study duration is up to 31 weeks, with three phases (screening phase for two weeks, active phase for up to 12 weeks, with an additional second consecutive confirmatory visit after 2 weeks, and follow-up phase comprising monthly visits for 4 months). Subjects will apply daily either the topical study drug or the placebo on the foot ulcer for 12 weeks or until healed, whichever comes first. Measurements of wound size and other data will be collected at baseline, followed by weekly visits for 12 weeks, and then a monthly follow-up period. DISCUSSION: This is a clinical translation study, moving the investigators' pre-clinical laboratory research into a translational study in which we will analyze clinical outcomes to assess for safety and estimate the efficacy of a topical beta-antagonist in healing of DFUs. The results from this trial may establish new treatment paradigms and safety profile for DFU treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03282981. Registered on June 14th, 2018.

Safety of light emitting diode-red light on human skin: Two randomized controlled trials.

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.

Preparation and characterization of biocomposite films of carrageenan/locust bean gum/montmorrillonite for transdermal delivery of curcumin.

Introduction: Skin can be used as a site for local and systemic drug administration. Diffusion of drugs through the skin has led to the development of different transdermal drug delivery systems. Curcumin is a wound healing and anti-inflammatory agent. Curcumin was incorporated into biocomposite films of carrageenan (κC)/locust bean gum (LBG)/ montmorillonite (MMT) prepared by a solvent casting method. Methods: Film-forming solutions were prepared by adding and 2.5% v/v of propylene glycol and MMT (30% w/w). The curcumin loaded polymer composite transdermal films were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) spectroscopy and X-ray diffraction (XRD) analysis. Mechanical properties in terms of tensile strength and extensibility were studied. Films were also evaluated for moisture content, moisture uptake, thickness, folding endurance, swelling ratio and water vapor transmission rate (WVTR). Results: κC and κC/L40 showed the highest percent cumulative release of 80.42±1.61% and 69.38±1.26% among all of the polymer composite transdermal films in 8 hours and 24 hours respectively. Conclusion: In vitro release profiles showed that increasing concentration of LBG and MMT sustained the release of the drug from the polymer composite transdermal films. Decreased percent cumulative release as the concentration of LBG and MMT increases in polymer composite transdermal film.

A single-blind, dose-escalation, phase I study of high-fluence light-emitting diode-red light on Caucasian non-Hispanic skin: study protocol for a randomized controlled trial.

BACKGROUND: Visible light (400 to 700 nm) is common in our environment, comprising 44% of total solar radiation and a large component of environmental light exposure. The effects of visible light on skin remain undefined. The red light portion of the visible spectrum (600 to 700 nm) may be used to treat skin diseases as a monotherapeutic modality or in combination with other agents. Light-emitting diode-red light (LED-RL) phototherapy may represent an important advance in light-based treatment modalities because it is non-invasive, inexpensive, portable, and easily combinable with other therapies. We previously determined the maximum tolerated dose (MTD) of high-fluence LED-RL (HF-LED-RL) in skin of color individuals to be 320 J/cm2. To the best of our knowledge, no clinical trials have been performed to determine the safety of higher doses of HF-LED-RL in Caucasian non-Hispanic individuals. The aim of this study is to investigate the safety of HF-LED-RL at doses of 480 and 640 J/cm2 in healthy Caucasian non-Hispanic individuals. METHODS: This is a single-blind, dose-escalation, randomized, controlled, phase I trial titled Safety Trial Assessing Red-light on Skin (STARS) 2. Healthy subjects will be randomly assigned to groups of five (three subjects randomly assigned to HF-LED-RL phototherapy and two subjects randomly assigned to mock therapy). Subjects in group 1 will receive HF-LED-RL or mock irradiation at the starting dose of 480 J/cm2, and the dose will be escalated in the subsequent group (group 2) to 640 J/cm2. The MTD is defined as the dose level below the dose at which two or more subjects (>20% of the cohort) experience a dose-limiting toxicity (DLT). After either the MTD is established or the study endpoint of 640 J/cm2 is achieved, additional HF-LED-RL phototherapy subjects and mock therapy subjects will be enrolled at that fluence (group 3) for a total number of up to 60 subjects. Each subject will receive a total of nine irradiation sessions, three times per week for three consecutive weeks. DISCUSSION: This follow-up study aims to provide important knowledge about safety and cutaneous effects of HF-LED-RL phototherapy of 480 and 640 J/cm2 in Caucasian non-Hispanic subjects. The importance of this clinical trial is that it may establish new treatment paradigms and a safety profile for LED-RL based on race and ethnicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03433222 . Registered on February 1, 2018 - Retrospectively registered. Protocol date and version: January 12, 2018; version 1.

Imidazo[1,2-a]pyridine Scaffold as Prospective Therapeutic Agents.

Imidazo[1,2-a]pyridine is one of the most potential bicyclic 5-6 heterocyclic rings that is recognized as a "drug prejudice" scaffold due to its broad range of applications in medicinal chemistry such as anticancer, antimycobacterial, antileishmanial, anticonvulsant, antimicrobial, antiviral, antidiabetic, proton pump inhibitor, insecticidal activities. This scaffold has also been represented in various marketed preparations such as zolimidine, zolpidem, alpidem. Therefore, several attempts were made to carry out the structural modifications of this scaffold to discover and develop novel therapeutic agents. This review provides a valuable insight into the research findings of wide range of derivatives of imidazo[1,2-a]pyridine scaffold leading to promising heterocyclic compounds which could be explored further for the synthesis of new derivatives as well as construction of potential drug-like chemical libraries for biological screening in search of new therapeutic agents.