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Purpurogallin (PPG), an orange-red crystalline compound from nutgalls and oak bark, is an exemplar of numerous, ubiquitous natural colorants, biosynthesized through oxidative dimerization-decarboxylation of phenolic compounds. It possesses antioxidant, anticancer, and anti-inflammatory effects. Herein, a robust method is presented to allow students to expediently make this interesting compound that contains a tropolone ring, whose identity initiated a paradigm shift in the understanding of aromaticity. 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data ([superscript 1]H, [superscript 13]C-DEPT-Q, HSQC, HMBC) were used to identify which protons are connected to carbon atoms. Fourier transform infrared spectroscopy (FT-IR), mass spectrometry, and X-ray diffraction were used to provide complementary information. Importantly, sufficient historical detail is given to provide a useful narrative that highlights the shift from deductive and synthetic proof of structural identity to modern methods of structural elucidation. As a minor, but important, aspect of iron gall inks, PPG links the work of important western historical documents from Da Vinci's Vitruvian Man to the United States Declaration of Independence. In the experience of the authors, such a pedagogic approach enlivens students with practical exercises which place them within the historical arc and reasoning of notable scientists, adding a sense of scientific discovery.

The industrial solvent trichloroethylene (TCE) and its two major metabolites trichloroethanol (TCE-OH) and trichloroacetic acid (TCA) cause formic aciduria in male F344 rats. Prior treatment of male F344 rats with 1-aminobenzotriazole a cytochrome P450 inhibitor, followed by TCE (16mk/kg, po), completely prevented formic aciduria, but had no effect on formic acid excretion produced by TCA (8 or 16 mg/kg, po), suggesting TCA may be the proximate metabolite producing this response. Dow and Green reported an increase in the concentration of 5-methyltetrahydrofolate (5-MTHF) in the plasma of rats treated with TCE-OH, suggesting a block in the cycling of 5-MTHF to tetrahydrofolate (THF). This pathway is under the control of the vitamin B12-dependent methionine salvage pathway. We therefore treated rats with three daily doses of methylcobalamin (CH3Cbl) or hydroxocobalamin (OHCbl), a cofactor for methionine synthase, or L-methionine, followed by TCE (16 mg/kg) to determine if they could alleviate the formic aciduria. These pretreatments only partially reduced the excretion of formic acid in the urine. Although prior treatment with S-adenosyl-L-methionine had no effect on formic acid excretion. Consistent with these findings, the activity of methionine synthase in the liver of TCE-treated rats was not inhibited. Transcriptomic analysis of the liver-identified nine differential expressed genes, of note, was downregulation of Lmbrd1 involved in the conversion of vitamin B12 into CH3Cbl, a cofactor for methionine synthase. Our findings indicate that the formic aciduria produced by TCE-OH and TCA may be the result of a block in the recycling of 5-MTHF to THF, the effect on the methionine salvage pathway being a secondary response following acute exposure. [ABSTRACT FROM AUTHOR]

Commiphora africana (A. Rich.) Endl. (Burseraceae) is a medicinal plant widely used in Nigerian ethnomedicine. The in vitro cytotoxicity of the stem bark extract of C. africana and isolated cytotoxic compounds was investigated. Three resveratrol derivatives: (E)-resveratrol 3-O-rutinoside (1), 5-methoxy-(E)-resveratrol 3-O-rutinoside (2), and pinostilbene (3), together with 3-hydroxy-5-methoxybenzoic acid (4) were isolated from the methanol fraction of C. africana. Their structures were determined by extensive analysis of their HREIMS and NMR spectra. The cytotoxicity of the isolated compounds against four human carcinoma cells was determined using the MTT assay. Compound 1 displayed the highest antiproliferative effect on the cell lines, with IC50 values of 16.80, 21.74, 17.89, and 17.44 μM, against MCF7, A549, PC3, and HepG2 human cancer cell lines, respectively. In addition, compounds 1-3 showed low toxicity against normal human prostate cell line, with selectivity indices greater than five across the carcinoma cells, indicating that the compounds possess potential in the development of low-toxicity chemotherapeutic agents. These results support the traditional use of this plant in the treatment of cancer. [ABSTRACT FROM AUTHOR]

Osteoporosis and fragility fractures (FFs) are closely intertwined as the former is a common predisposing factor to the latter. This causal relationship is due to low bone density of osteoporosis and compromised bone microarchitecture, leading to structural failure, decreased ability to withstand applied stresses, and increased propensity to fracture. Osteoporosis can be idiopathic or due to a variety of secondary causes, and numerous treatment strategies are available. FFs are common injuries among the elderly and are caused by factors both intrinsic and extrinsic to the patient. The clinical and economic significances of osteoporosis and FFs are substantial, with considerable associated morbidity and mortality, and billions spent on healthcare expenditures in the US annually. Osteoporosis and FFs are two of the most important topics related to fracture liaison services (FLSs), and their understanding is integral to appreciating the benefits an FLS can provide for patients and providers. [ABSTRACT FROM AUTHOR]

Despite its classification as an atypical pneumonia, COVID-19 is a disease that is capable of inflicting damage beyond the respiratory system. The wide range of musculoskeletal complications secondary to acute COVID-19 are a significant source of morbidity in hospitalized patients. We present the case of a 23-year-old woman with severe COVID-19 who required intubation and had a prolonged hospital course that was complicated by partial-thickness necrosis of her fingers and heterotopic ossification of the distal thigh. We review current treatments for these orthopedic conditions in the setting of SARS-CoV-2 infection as well as highlight areas for future research. Additionally, we discuss the subacute musculoskeletal complications of COVID-19, which are among the most common long-term manifestations of the disease and are increasingly important for a growing number of COVID-19 survivors. [ABSTRACT FROM AUTHOR]

Introduction: Femoral neck fractures in the young patient require prompt anatomic reduction and stabilization to preserve the vascular supply to the femoral head and minimize future need for arthroplasty. Secondary to unique biomechanical and vascular considerations, these injuries are prone to nonunion. Case Report: A 29-year-old male with a chronic femoral neck fracture nonunion who experienced successful fracture healing and symptom resolution following Bone Marrow Aspirate Concentrate (BMAC) administration. Discussion: Femoral neck nonunion in young patients is a challenging problem with treatment strategies aimed at improving the biological and biomechanical fracture environment. While the use of both vascularized and nonvascularized bone grafting has shown promising results, they have high complication rates and substantial donor site morbidity. BMAC has demonstrated multiple uses throughout orthopedic surgery and may result in an improved fracture healing environment with minimal patient morbidity. Conclusion: The success of the BMAC procedure for this patient is promising and may be considered in similar patients, with or without revision internal fixation methods. [ABSTRACT FROM AUTHOR]

Orthopaedics as a field and a profession is fundamentally concerned with the treatment of musculoskeletal disease, in all of its many forms. Our collective understanding of the cellular mechanisms underlying musculoskeletal pathology resulting from injury continues to evolve, opening novel opportunities to develop orthobiologic treatments to improve care. It is a long path to move from an understanding of cellular pathology to development of successful clinical treatment, and this article proposes to discuss some of the challenges to achieving translational therapies in orthopaedics. The article will focus on challenges that clinicians will likely face in seeking to bring promising treatments forward to clinical practice and strategies for improving success in translational efforts., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist., Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections., Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers., Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder., Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence., Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections., Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin., Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

Fracture healing is a complex cascade of cellular and molecular processes. These processes require the appropriate cellular and molecular environment to ensure the restoration of skeletal stability and resolution of inflammation. In order for fracture healing to occur, the necessary building blocks for bone metabolism and synthesis must be supplied through proper nutrition. Pharmacologic therapies aimed at modulating the inflammatory response to fractures have the potential to interfere with the synthesis of molecules needed for the production of bone. Infection can interfere with, and even prevent normal fracture healing from occurring. Cellular and genetic treatment strategies are actively being developed to target deficiencies, and bridge gaps that can influence how fractures heal. Evolving technologies, including nutritional supplementation, pharmacotherapies, antibiotics, surgical techniques, as well as genetic and cellular therapies, have the potential to enhance, optimize, and even revolutionize the process of fracture healing., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Orthopaedic Trauma Association.)

The industrial solvent trichloroethylene (TCE) and its two major metabolites trichloroethanol (TCE-OH) and trichloroacetic acid (TCA) cause formic aciduria in male F344 rats. Prior treatment of male F344 rats with 1-aminobenzotriazole a cytochrome P450 inhibitor, followed by TCE (16mk/kg, po), completely prevented formic aciduria, but had no effect on formic acid excretion produced by TCA (8 or 16 mg/kg, po), suggesting TCA may be the proximate metabolite producing this response. Dow and Green reported an increase in the concentration of 5-methyltetrahydrofolate (5-MTHF) in the plasma of rats treated with TCE-OH, suggesting a block in the cycling of 5-MTHF to tetrahydrofolate (THF). This pathway is under the control of the vitamin B 12 -dependent methionine salvage pathway. We therefore treated rats with three daily doses of methylcobalamin (CH 3 Cbl) or hydroxocobalamin (OHCbl), a cofactor for methionine synthase, or L-methionine, followed by TCE (16 mg/kg) to determine if they could alleviate the formic aciduria. These pretreatments only partially reduced the excretion of formic acid in the urine. Although prior treatment with S-adenosyl-L-methionine had no effect on formic acid excretion. Consistent with these findings, the activity of methionine synthase in the liver of TCE-treated rats was not inhibited. Transcriptomic analysis of the liver-identified nine differential expressed genes, of note, was downregulation of Lmbrd1 involved in the conversion of vitamin B 12 into CH 3 Cbl, a cofactor for methionine synthase. Our findings indicate that the formic aciduria produced by TCE-OH and TCA may be the result of a block in the recycling of 5-MTHF to THF, the effect on the methionine salvage pathway being a secondary response following acute exposure., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)