Obstetric Neuropathy in Diabetic Patients: The "Double Hit Hypothesis".

The two-hit model has been proposed to explain the effects of diabetes on mothers who are already in a putative subclinical damaged state and then undergo neuronal damage during the delivery process. However, the anatomical and pathophysiological mechanisms are not well understood. Our overarching hypothesis in this review paper is that pregnant women who are diabetic have a damaged peripheral nervous system, constituting the "first hit" hypothesis. The delivery process itself-the "second hit"-can produce neurological damage to the mother. Women with diabetes mellitus (DM) are at risk for neurological damage during both hits, but the cumulative effects of both "hits" pose a greater risk of neurological damage and pathophysiological changes during delivery. In our analysis, we introduce the different steps of our concept paper. Subsequently, we describe each of the topics. First, we outline the mechanisms by which diabetes acts as a detrimental variable in neuropathy by focusing on the most common form of diabetic neuropathy, diabetic distal symmetrical polyneuropathy, also known as distal sensorimotor neuropathy. The possible role of macrosomia in causing diabetic neuropathy and obstetric neurological injury is discussed. Second, we describe how vaginal delivery can cause various obstetrical neurological syndromes and pathophysiological changes. Third, we highlight the risk of obstetric neuropathy and discuss anatomical sites at which lesions may occur, including lesions during delivery. Fourth, we characterize the pathophysiological pathways involved in the causation of diabetic neuropathy. Finally, we highlight diabetic damage to sensory vs. motor nerves, including how hyperglycemia causes different types of damage depending on the location of nerve cell bodies.

Instant clot forming and antibacterial wound dressings: Achieving hemostasis in trauma injuries with S-nitroso-N-acetylpenicillamine-tranexamic acid-propolis formulation.

Wound infection and excessive blood loss are the two major challenges associated with trauma injuries that account for 10% of annual deaths in the United States. Nitric oxide (NO) is a gasotransmitter cell signaling molecule that plays a crucial role in the natural wound healing process due to its antibacterial, anti-inflammatory, cell proliferation, and tissue remodeling abilities. Tranexamic acid (TXA), a prothrombotic agent, has been used topically and systemically to control blood loss in reported cases of epistaxis and combat-related trauma injuries. Its properties could be incorporated in wound dressings to induce immediate clot formation, which is a key factor in controlling excessive blood loss. This study introduces a novel, instant clot-forming NO-releasing dressing, and fabricated using a strategic bi-layer configuration. The layer adjacent to the wound was designed with TXA suspended on a resinous bed of propolis, which is a natural bioadhesive possessing antibacterial and anti-inflammatory properties. The base layer, located furthest away from the wound, has an NO donor, S-nitroso-N-acetylpenicillamine (SNAP), embedded in a polymeric bed of Carbosil®, a copolymer of polycarbonate urethane and silicone. Propolis was integrated with a uniform layer of TXA in variable concentrations: 2.5, 5.0, and 7.5 vol % of propolis. This design of the TXA-SNAP-propolis (T-SP) wound dressing allows TXA to form a more stable clot by preventing the lysis of fibrin. The lactate dehydrogenase-based platelet adhesion assay showed an increase in fibrin activation with 7.5% T-SP as compared with control within the first 15 min of its application. A scanning electron microscope (SEM) confirmed the presence of a dense fibrin network stabilizing the clot for fabricated dressing. The antibacterial activity of NO and propolis resulted in a 98.9 ± 1% and 99.4 ± 1% reduction in the colony-forming unit of Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii, respectively, which puts forward the fabricated dressing as an emergency first aid for traumatic injuries, preventing excessive blood loss and soil-borne infections.

SOARinG to New Heights Through a Structured Medical Student Research Program.

Introduction: Since the US Medical Licensing Examination (USMLE) Step 1 became Pass/Fall in 2022, medical students competing for residency spots must distinguish themselves with alternative criteria. Research experiences and output offer valuable skill development and objective metrics to support competitive residency applications. Objective: We describe the methodological development of a structured program to support, enhance, and track medical student research efforts at the University of South Carolina School of Medicine Greenville, explain the implementation of the program, and summarize initial program outcomes. Methods: The Student Opportunities for Academic Achievement Through Research in Greenville (SOARinG) Program was established to serve as a centralized hub for rising second year medical student research. The program matched medical students with mentored research projects scheduled during the summer following first-year coursework. The program included a required weekly seminar series on research basics and current biomedical literature. SOARinG culminated with a student research symposium for which students submitted abstracts and presented a poster or a talk. Quantitative and qualitative program outcomes of student and mentor satisfaction with the program were measured through surveys. Results and Discussion: The program was successfully implemented in summers 2021 and 2022. Most students (80-95%) in each class engaged in mentored summer research projects. Students reported overall satisfaction with research projects and mentor support. Overall, 69% of students rated their overall research experience in the program as extremely good or very good. Each student submitted an abstract and presented at the program's symposium or alternate research venue. Overall, 97% of research mentors reported that students were adequately prepared for summer research and suggested that students would benefit from additional skills-specific research training. Conclusion: The SOARinG Program provided a formalized process for tracking and showcasing medical student research and allowed for increased student participation in research. Additionally, each participating student produced objective research output, thus enhancing future residency applications.

Reduction in Foreign Body Response and Improved Antimicrobial Efficacy via Silicone-Oil-Infused Nitric-Oxide-Releasing Medical-Grade Cannulas.

Foreign body response and infection are two universal complications that occur with indwelling medical devices. In response, researchers have developed different antimicrobial and antifouling surface strategies to minimize bacterial colonization and fibrous encapsulation. In this study, the nitric oxide (NO) donor S-nitroso-N-acetylpenicillamine (SNAP) and silicone oil were impregnated into silicone rubber cannulas (SR-SNAP-Si) using a solvent swelling method to improve the antimicrobial properties and decrease the foreign body response. The fabricated SR-SNAP-Si cannulas demonstrated a stable, prolonged NO release, exhibited minimal SNAP leaching, and maintained sliding angles < 15° for 21 days. SR-SNAP-Si cannulas displayed enhanced antimicrobial efficacy against Staphylococcus aureus in a 7-day biofilm bioreactor study, reducing the viability of adhered bacteria by 99.2 ± 0.2% compared to unmodified cannulas while remaining noncytotoxic toward human fibroblast cells. Finally, SR-SNAP-Si cannulas were evaluated for the first time in a 14- and 21-day subcutaneous mouse model, showing significantly enhanced biocompatibility compared to control cannulas by reducing the thickness of fibrous encapsulation by 60.9 ± 6.1 and a 60.8 ± 10.5% reduction in cell density around the implant site after 3 weeks. Thus, this work demonstrates that antifouling, NO-releasing surfaces can improve the lifetime and safety of indwelling medical devices.

Electrospun Bioabsorbable Fibers Containing S-Nitrosoglutathione for Tissue Engineering Applications.

Blended and coaxial fibers comprising polycaprolactone and gelatin, containing the endogenous nitric oxide (NO) donor S-nitrosoglutathione (GSNO), were electrospun. Both types of fibers had their NO release profiles tested under physiological conditions to examine their potential applications as biomedical scaffolds. The coaxial fibers exhibited a prolonged and consistent release of NO over the course of 4 d from the core-encapsulated GSNO, while the blended fibers had a large initial release and leaching of GSNO that was exhausted over a shorter period of time. Bacterial testing of both fiber scaffolds was conducted over a 24 h period against Staphylococcus aureus (S. aureus) and demonstrated a 3-log reduction in bacterial viability. In addition, no cytotoxic response was reported when the material was tested on mouse fibroblast cells in vitro. These fibrous matrices were also shown to support cell growth, attachment, and overall activity of fibroblasts when exposed to NO, especially when GSNO was encapsulated within coaxial fibers. From an application point of view, these NO-releasing fibers offer great potential in tissue engineering and biomedical applications because of the crucial role of NO in regulating a variety of biological processes in humans such as angiogenesis, tissue remodeling, and eliminating foreign pathogens.

Antibacterial 3D bone scaffolds for tissue engineering application.

Open bone fractures are not only difficult to heal but also are at a high risk of infections. Annual cases of fractures which result from osteoporosis amount to approximately 9 million. Endogenously released nitric oxide (NO) has been shown to play a role in osteogenic differentiation in addition to eradicating infection against a wide variety of pathogens. In the current work, antimicrobial NO releasing 3D bone scaffolds were fabricated using S-nitroso-N-acetyl-penicillamine (SNAP) as the NO donor. During fabrication, nano-hydroxyapatite (nHA) was added to each of the scaffolds in the concentration range of 10-50 wt % in nHA-starch-alginate and nHA-starch-chitosan scaffolds. The mechanical strength of the scaffolds increased proportionally to the concentration of nHA and 50 wt % nHA-starch-alginate possessed the highest load bearing capacity of 203.95 ± 0.3 N. The NO flux of the 50 wt % nHA-starch-alginate scaffolds was found to be 0.50 ± 0.06 × 10-10 mol/min/mg initially which reduced to 0.23 ± 0.02 × 10-10 over a 24 h period under physiological conditions. As a result, a 99.76% ± 0.33% reduction in a gram-positive bacterium, Staphylococcus aureus and a 99.80% ± 0.62% reduction in the adhered viable colonies of gram-negative bacterium, Pseudomonas aeruginosa were observed, which is a significant stride in the field of antibacterial natural polymers. The surface morphology and pore size were observed to be appropriate for the potential bone cell growth. The material showed no toxic response toward mouse fibroblast cells. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1068-1078, 2019.