A scoping review of graphene-based biomaterials for in vivo bone tissue engineering.

The growing demand for more efficient materials for medical applications brought together two previously distinct fields: medicine and engineering. Regenerative medicine has evolved with the engineering contributions to improve materials and devices for medical use. In this regard, graphene is one of the most promising materials for bone tissue engineering and its potential for bone repair has been studied by several research groups. The aim of this study is to conduct a scoping review including articles published in the last 12 years (from 2010 to 2022) that have used graphene and its derivatives (graphene oxide and reduced graphene) in preclinical studies for bone tissue regeneration, searching in PubMed/MEDLINE, Embase, Web of Science, Cochrane Central, and clinicaltrials.gov (to confirm no study has started with clinical trial). Boolean searches were performed using the defined key words "bone" and "graphene", and manuscript abstracts were uploaded to Rayyan, a web-tool for systematic and scoping reviews. This scoping review was conducted based on Joanna Briggs Institute Manual for Scoping Reviews and the report follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Extension for Scoping Reviews (PRISMA-ScR) statement. After the search protocol and application of the inclusion criteria, 77 studies were selected and evaluated by five blinded researchers. Most of the selected studies used composite materials associated with graphene and its derivatives to natural and synthetic polymers, bioglass, and others. Although a variety of graphene materials were analyzed in these studies, they all concluded that graphene, its derivatives, and its composites improve bone repair processes by increasing osteoconductivity, osteoinductivity, new bone formation, and angiogenesis. Thus, this systematic review opens up new opportunities for the development of novel strategies for bone tissue engineering with graphene.

Atypical Warfarin-Induced Calciphylaxis Outside a Typical Presentation of End-Stage Renal Disease on Hemodialysis.

We present a case report highlighting a 47-year-old woman who developed warfarin-induced calciphylaxis. She initially developed bilateral leg wounds secondary to restraint straps from helicopter transportation to a higher level of care for treatment of critical aortic stenosis. She was started on warfarin following surgical implantation of a mechanical aortic valve. After her wounds failed to heal, a punch biopsy of the wounds demonstrated ulceration, altered vasculature, and soft tissue calcification. The pathology confirmed the clinical concern for calciphylaxis, which is most often diagnosed in patients with a history of end-stage renal disease on hemodialysis. However, our patient did not demonstrate evidence of renal disease prior to the onset of calciphylaxis. Her wounds began to heal after treatment with sodium thiosulfate and changing her anticoagulation from warfarin to rivaroxaban.

Scurvy Presenting as Blood Loss Anemia in the United States.

INTRODUCTION: Scurvy is a deadly disease caused by a lack of vitamin C in the diet. Although frequently considered a disease from the past, it still occurs in modern-day society, including in developed countries. CASE REPORT: We report a case of an 18-year-old male who was admitted with bleeding into his legs, prolonged prothrombin time and partial thromboplastin time, and anemia requiring a blood transfusion. His history included congenital deafness and a restrictive eating pattern primarily consisting of fast food. He was deficient in folic acid, vitamin K, and vitamin C. Scurvy best explained the bleeding, and he improved with vitamin supplementation. DISCUSSION: Scurvy is a collagen production disorder that can cause bleeding on the skin and mucous membranes. Although rare in industrialized nations, scurvy is typically the result of a restrictive diet or malnutrition. Those who are at a particularly high risk are the elderly, alcohol abusers, and those with eating disorders. CONCLUSIONS: Scurvy is easily treatable but can be missed; therefore, a high level of suspicion should be present in patients at risk for malnutrition. Those diagnosed with scurvy should be screened for concomitant nutritional deficiencies.

Case Report of COVID-19 mRNA Vaccine-Associated Myocarditis.

INTRODUCTION: We present a case report highlighting a single patient out of 3 who developed myocarditis within days after receiving Pfizer and Moderna COVID-19 mRNA vaccines. CASE PRESENTATION: A 19-year-old male was admitted to our hospitalist service with substernal chest pain that was sharp, constant, and varied with position. He had received his second dose of the Pfizer-BioNTech COVID-19 vaccine (Pfizer vaccine) 2 days prior. Electrocardiogram was consistent with pericarditis. He had persistently elevated troponins and globally reduced systolic function by echocardiogram, which was consistent with myocarditis. He received colchicine, ibuprofen, and proton pump inhibitors with a resolution of symptoms. After 32 days, follow-up echocardiogram had returned to normal, and his symptoms had resolved completely. DISCUSSION: Given the onset of symptoms after the second dose of vaccine and our review of similar cases in the literature, it seems likely the patient's myopericarditis was caused by the vaccine. Rare complications of new vaccines given to millions of people are rapidly identified by the Vaccine Adverse Event Reporting System. CONCLUSIONS: The identification of myopericarditis as a complication of mRNA vaccines will need further study to understand the pathophysiology, incidence, and prevalence in specific age groups and biological sexes.

Therapeutic downregulation of neuronal PAS domain 2 (Npas2) promotes surgical skin wound healing.

Attempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgfß1, and α-smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.

In vitro assessment of Neuronal PAS domain 2 mitigating compounds for scarless wound healing.

Background: The core circadian gene Neuronal PAS domain 2 (NPAS2) is expressed in dermal fibroblasts and has been shown to play a critical role in regulating collagen synthesis during wound healing. We have performed high throughput drug screening to identify genes responsible for downregulation of Npas2 while maintaining cell viability. From this, five FDA-approved hit compounds were shown to suppress Npas2 expression in fibroblasts. In this study, we hypothesize that the therapeutic suppression of Npas2 by hit compounds will have two effects: (1) attenuated excessive collagen deposition and (2) accelerated dermal wound healing without hypertrophic scarring. Materials and methods: To test the effects of each hit compound (named Dwn1, 2, 3, 4, and 5), primary adult human dermal fibroblasts (HDFa) were treated with either 0, 0.1, 1, or 10 µM of a single hit compound. HDFa behaviors were assessed by picrosirius red staining and quantitative RT-PCR for in vitro collagen synthesis, cell viability assay, in vitro fibroblast-to-myofibroblast differentiation test, and cell migration assays. Results: Dwn1 and Dwn2 were found to significantly affect collagen synthesis and cell migration without any cytotoxicity. Dwn3, Dwn4, and Dwn5 did not affect collagen synthesis and were thereby eliminated from further consideration for their role in mitigation of gene expression or myofibroblast differentiation. Dwn1 also attenuated myofibroblast differentiation on HDFa. Conclusion: Dwn1 and Dwn2 may serve as possible therapeutic agents for future studies related to skin wound healing.

Case Report of Metronidazole-Induced Encephalopathy.

This report describes the case of an 83-year-old woman who was admitted to a hospitalist service with weakness and falls. She was transferred from an outside facility where she was treated with 3 courses of metronidazole for diagnosed Clostridium difficile colitis and presumed reoccurrences. Magnetic resonance imaging (MRI) demonstrated T2 enhancement of the dorsal pons and dentate nuclei consistent with metronidazole-induced encephalopathy. Her metronidazole was stopped and her symptoms resolved. This condition is rare, poorly understood, and causes reversible changes in the brain that are detectable through T2-weighted MRI. It will need ongoing study with current widespread use of metronidazole.