The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks.

Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO3 or water (H2O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSChigh/SSClow ratio of FSChighCD11bc + cells, decreased in the spleen following NaHCO3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO3-induced immunomodulation. Artificial neural networks accurately classified NaHCO3 and H2O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO3-induced immunomodulatory changes to the spleen, emphasizing NaHCO3's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.

Mandible Reconstruction in a Rural Population: Comparison of Radial Forearm and Free Fibula Flap Outcomes.

Comparison of microsurgical reconstructive options after mandible resection is limited in the literature. Fibula free flaps (FFFs) can be costly and have timing limitations, but dental restoration can be performed, with varied reported rates of completion. The radial forearm free flap (RFFF) with mandible plating may be an alternative in select populations. The purpose of this study was to determine if the RFFF has similar outcomes to the FFF for mandible reconstruction in a rural population. A retrospective review of patients who underwent mandibulectomy from 2017 to 2021 at a single tertiary-care academic institution was performed. Those with FFF or RFFF reconstruction were included. Mandible defects were classified using the Jewer-Boyd H-C-L system. Sixty-eight patients were included with 53 undergoing FFF and 15 undergoing RFFF. Immediate reconstruction was significantly more common with RFFF than FFF (100% versus 64.2%; P =0.01). Lateral mandible defects were most common among both groups (52.9% FFF versus 73.3% RFFF; P =0.04). Osseous defect length was similar (9.5 cm FFF versus 7.7 cm RFFF; P =0.07), but soft tissue defect size was significantly larger in the RFFF group (28.6 cm 2 versus 15.3 cm 2 ; P =0.01). Complication rates (47.1% FFF versus 46.7% RFFF; P =0.98) and disease-free status at last follow-up (96.2% FFF versus 80.0% RFFF; P =0.06) were similar. Dental restoration occurred in 21.3% of patients undergoing FFF. Patients undergoing RFFF or FFF reconstruction after mandibulectomy had similar surgical and disease outcomes, with a low rate of completed dental restoration after FFF. Our findings suggest RFFF is a reasonable alternative to FFF for mandible reconstruction in select patients.

The Impact of Prior Breast Augmentation on Breast Reconstruction after Mastectomy.

The risk of women developing breast cancer after augmentation mammaplasty may be lower than the general population, with minimal current literature on breast reconstruction in this population. We sought to evaluate the impact of previous augmentation on postmastectomy breast reconstruction. Methods: Retrospective review of patients who underwent mastectomies from 2017 to 2021 at our institution was performed. Analysis included frequencies and percentages, descriptive statistics, chi-square analysis, and Fisher exact test. Results: Four hundred seventy patients were included, with average body mass index of 29.1 kg/m2, 96% identifying as White, and an average age at diagnosis of 59.3 years. Twenty (4.2%) patients had a prior breast augmentation. Reconstruction was performed in 80% of the previously augmented patients compared to 49.9% of nonaugmented patients (P = 0.01). Reconstruction was alloplastic in 100% of augmented and 88.7% of nonaugmented patients (P = 0.15). All reconstructed augmented patients underwent immediate reconstruction compared with 90.5% of nonaugmented patients (P = 0.37), and two-stage reconstruction was most common (75.0% versus 63.5%; P = 0.42). Of the previously augmented patients, 87.5% increased implant volume, 75% underwent same implant plane reconstruction, and 68.75% underwent same implant-type reconstruction as their augmentation. Conclusions: Previously augmented patients were more likely to undergo reconstruction after mastectomy at our institution. All reconstructed augmented patients underwent alloplastic reconstruction, with most performed immediately in staged fashion. Most patients favored silicone implants and maintained the same implant type and plane of reconstruction, with increased implant volume. Larger studies are required to further investigate these trends.

Effect of polyester-based artificial tendons on movement biomechanics: A preliminary in vivo study.

Artificial tendons may be valuable clinical devices for replacing damaged or missing biological tendons. In this preliminary study, we quantified the effect of polyester-suture-based artificial tendons on movement biomechanics. New Zealand White rabbits underwent surgical replacement of either the Achilles (n = 2) or tibialis cranialis (TC, n = 2) biological tendons with artificial tendons. Once pre-surgery and weekly from 2 to 6 weeks post-surgery, we quantified hindlimb kinematics and ground contact pressures during the stance phase of hopping gait. Post-surgical movement biomechanics were either consistent or improved over time in both groups. However, the Achilles group had greater overall biomechanical and muscle deficits than the TC group. In the TC group, at 6 weeks post-surgery, foot angles were about 10° greater than those in healthy controls during the first 30 % of stance. At 6 weeks post-surgery, the Achilles group exhibited lesser (i.e., more dorsiflexed) ankle angles (minimum angle = 31.5 ± 9.4°) and vertical ground reaction forces (37.4 ± 2.6 %BW) during stance than those in healthy controls (65.0 ± 11.2° and 50.2 ± 8.3 %BW, respectively). Future studies are needed to quantify long-term biomechanical function with artificial tendons, the effect of artificial tendons on muscle function and structure, and the effect of formal rehabilitation.

The Impact of Travel Distance and Income on Breast Reconstruction after Mastectomy in a Rural Population.

Factors that influence breast reconstruction after mastectomy have been previously examined in national databases. The purpose of this study was to determine the impact of patient travel distance and income on breast reconstruction after mastectomy in a rural population. Methods: Retrospective review of mastectomy patients from 2017 to 2021 was performed from our prospectively enrolled tumor registry. Analysis included frequencies and percentages, descriptive statistics, χ 2 analysis, independent sample t tests, and multivariable analysis. Results: In total, 462 patients were included. Median BMI was 27.6 kg/m2, 96.1% of patients were White, and median age at diagnosis was 60.0 years. Reconstruction rate was 52.6%, and median length of follow-up was 24.6 months. No significant difference was found in the distance traveled by patients who underwent reconstruction (16.6 versus 16.7 miles; P = 0.94). Rates of reconstruction in patients who traveled 0-10 miles, 11-30 miles, and over 30 miles did not differ significantly (P = 0.16). Median household income was significantly different in reconstructed and nonreconstructed patients ($55,316.00 versus $51,629.00; P = 0.047). Rates of reconstruction were significantly higher in patients with median household income greater than $65,000 (P = 0.024). This difference was not significant on multivariable analysis. Conclusions: Travel distance did not significantly impact reconstruction rates after mastectomy, while household income did on univariable analysis. Studies at an institutional or regional level remain valuable, especially in populations that may not be accurately represented in larger database studies. Our findings highlight the importance of patient education, resource allocation, and multidisciplinary approach to breast cancer care, especially in the rural setting.

Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus.

Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood-brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus.

Feasibility of Implanting a Foot-Ankle Endoprosthesis within Skin in a Rabbit Model of Transtibial Amputation.

Prosthetic limbs that are completely implanted within skin (i.e., endoprostheses) could permit direct, physical muscle-prosthesis attachment to restore more natural sensorimotor function to people with amputation. The objective of our study was to test, in a rabbit model, the feasibility of replacing the lost foot after hindlimb transtibial amputation by implanting a novel rigid foot-ankle endoprosthesis that is fully covered with skin. We first conducted a pilot, non-survival surgery in two rabbits to determine the maximum size of the skin flap that could be made from the biological foot-ankle. The skin flap size was used to determine the dimensions of the endoprosthesis foot segment. Rigid foot-ankle endoprosthesis prototypes were successfully implanted in three rabbits. The skin incisions healed over a period of approximately 1 month after surgery, with extensive fur regrowth by the pre-defined study endpoint of approximately 2 months post surgery. Upon gross inspection, the skin surrounding the endoprosthesis appeared normal, but a substantial subdermal fibrous capsule had formed around the endoprosthesis. Histology indicated that the structure and thickness of the skin layers (epidermis and dermis) were similar between the operated and non-operated limbs. A layer of subdermal connective tissue representing the fibrous capsule surrounded the endoprosthesis. In the operated limb of one rabbit, the subdermal connective tissue layer was approximately twice as thick as the skin on the medial (skin = 0.43 mm, subdermal = 0.84 mm), ventral (skin = 0.80 mm, subdermal = 1.47 mm), and lateral (skin = 0.76 mm, subdermal = 1.42 mm) aspects of the endoprosthesis. Our results successfully demonstrated the feasibility of implanting a fully skin-covered rigid foot-ankle endoprosthesis to replace the lost tibia-foot segment of the lower limb. Concerns include the fibrotic capsule which could limit the range of motion of jointed endoprostheses. Future studies include testing of endoprosthetics, as well as materials and pharmacologic agents that may suppress fibrous encapsulation.

Fully Implanted Prostheses for Musculoskeletal Limb Reconstruction After Amputation: An In Vivo Feasibility Study.

Previous prostheses for replacing a missing limb following amputation must be worn externally on the body. This limits the extent to which prostheses could physically interface with biological tissues, such as muscles, to enhance functional recovery. The objectives of our study were to (1) test the feasibility of implanting a limb prosthesis, or endoprosthesis, entirely within living skin at the distal end of a residual limb, and (2) identify effective surgical and post-surgical care approaches for implanting endoprostheses in a rabbit model of hindlimb amputation. We iteratively designed, fabricated, and implanted unjointed endoprosthesis prototypes in six New Zealand White rabbits following amputation. In the first three rabbits, the skin failed to heal due to ishemia and dehiscence along the sutured incision. The skin of the final three subsequent rabbits successfully healed over the endoprotheses. Factors that contributed to successful outcomes included modifying the surgical incision to preserve vasculature; increasing the radii size on the endoprostheses to reduce skin stress; collecting radiographs pre-surgery to match the bone pin size to the medullary canal size; and ensuring post-operative bandage integrity. These results will support future work to test jointed endoprostheses that can be attached to muscles.

Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis.

PURPOSE: The extracellular matrix (ECM) labyrinthine network secreted by mesenchymal stem cells (MSCs) provides a microenvironment that enhances cell adherence, proliferation, viability, and differentiation. The potential of graphene-based nanomaterials to mimic a tissue-specific ECM has been recognized in designing bone tissue engineering scaffolds. In this study, we investigated the expression of specific ECM proteins when human fat-derived adult MSCs adhered and underwent osteogenic differentiation in the presence of functionalized graphene nanoparticles. METHODS: Graphene nanoparticles with 6-10% oxygen content were prepared and characterized by XPS, FTIR, AFM and Raman spectroscopy. Calcein-am and crystal violet staining were performed to evaluate viability and proliferation of human fat-derived MSCs on graphene nanoparticles. Alizarin red staining and quantitation were used to determine the effect of graphene nanoparticles on osteogenic differentiation. Finally, immunofluorescence assays were used to investigate the expression of ECM proteins during cell adhesion and osteogenic differentiation. RESULTS: Our data show that in the presence of graphene, MSCs express specific integrin heterodimers and exhibit a distinct pattern of the corresponding bone-specific ECM proteins, primarily fibronectin, collagen I and vitronectin. Furthermore, MSCs undergo osteogenic differentiation spontaneously without any chemical induction, suggesting that the physicochemical properties of graphene nanoparticles might trigger the expression of bone-specific ECM. CONCLUSION: Understanding the cell-graphene interactions resulting in an osteogenic niche for MSCs will significantly improve the application of graphene nanoparticles in bone repair and regeneration.