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Article Summary: Introduction: Breast implants are under recent scrutiny owing to concerns about their potential for inducing immunological diseases, namely breast implant-associated anaplastic large cell lymphoma and breast implant illness. However, the impact of silicone on biologic systems remains unclear. Therefore, we performed a systematic literature review to evaluate the information available on silicone breast implants and their effect on one arm of the adaptive immune response—B lymphocytes and antibody formation. Methods: We conducted a systematic review in EMBASE/PUBMED in accordance with the PRISMA guidelines, with search entry terms requiring discussion of silicone and immunity. The initial review returned 1079 citations. Manual screening was performed to include studies that were specific to the humoral response after exposure to silicone. Secondary full text review was performed. The extracted data included animal models and findings pertinent to B cells/antibodies in response to breast implant silicones. Results: In total, 39 studies on B cells/antibodies and breast-implant-associated silicones were identified. Among them, 23 studies were in humans, 14 in animal models, and 2 were in vitro. Common themes included identification of antisilicone antibodies in women with breast implants, anticollagen antibodies, presence of activated B cells or immunoglobulin G in implant capsules, and sensitization of lymphocytes to silicone in vitro. Conclusion: Despite controversial findings in the literature, there is evidence that silicone breast implants activate B cells in the breast implant capsule and may have systemic effects on the production of autoantibodies and/or sensitization of B lymphocytes to silicone. Further research is needed on how breast implants impact other arms of the immune system to understand their long-term biological impact.

Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.

Background:. Capsular contracture is one of the most common reasons for reoperation after implant-based breast reconstruction. Prior investigations have suggested that biologic mesh may mitigate capsular contracture development. This study sought to compare capsular contracture rates between patients undergoing immediate implant-based breast reconstruction with biologic versus synthetic mesh. Methods:. A retrospective review was conducted of the senior author’s primary implant-based breast reconstructions between 2008 and 2023. Demographics and the incidence of clinically significant Baker grade III or IV capsular contractures were compared between biologic and synthetic mesh cohorts. Univariate and multivariate logistic regressions were then performed to assess potential risk factors for the development of capsular contracture. Results:. A total of 772 breasts underwent immediate reconstruction, of which 689 (89.2%) used biologic and 83 (10.8%) used synthetic mesh. Capsular contracture occurred in 15 (2.2%) biologic mesh breasts and three (3.6%) synthetic mesh breasts with no significant difference between the two groups (P = 0.430). Logistic regression showed that radiation was a borderline significant risk factor for developing capsular contracture, but the use of either biologic or synthetic mesh was not significant (P = 0.351). Conclusions:. Biologic and synthetic meshes function as effective tools in prosthetic breast reconstruction. Our long-term data suggest that the risk of capsular contracture with these devices is low, and there does not seem to be a difference between the two materials. However, there does need to be a shift in how capsular contracture is assessed and discussed in the reconstruction population.

Cerebrovasculature is critical in maintaining brain homeostasis; its dysregulation often leads to vascular cognitive impairment and dementia (VCID) during aging. VCID is the second most prevalent cause of dementia in the elderly, after Alzheimer’s disease (AD), with frequent cooccurrence of VCID and AD. While multiple factors are involved in the pathogenesis of AD and VCID, APOE4 increases the risk for both diseases. A major apolipoprotein E (apoE) receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in vascular mural cells (pericytes and smooth muscle cells). Here, we investigated how deficiency of vascular mural cell LRP1 affects the cerebrovascular system and cognitive performance using vascular mural cell–specific Lrp1-KO mice (smLrp1–/–) in a human APOE3 or APOE4 background. We found that spatial memory was impaired in the 13- to 16-month-old APOE4 smLrp1–/– mice but not in the APOE3 smLrp1–/– mice, compared with their respective littermate control mice. These disruptions in the APOE4 smLrp1–/– mice were accompanied with excess paravascular glial activation and reduced cerebrovascular collagen IV. In addition, blood-brain barrier (BBB) integrity was disrupted in the APOE4 smLrp1–/– mice. Together, our results suggest that vascular mural cell LRP1 modulates cerebrovasculature integrity and function in an APOE genotype–dependent manner.

The CD47/signal regulatory protein α (SIRPα) axis, which functions as an inhibitory phagocytosis checkpoint, also serves as a key mediator in cancer immune evasion. Many cancers, including colorectal cancer (CRC), exploit the expression of CD47 to escape phagocytic clearance and activate the innate immune system. Previous work has indicated that distinct paradigms of posttranslational modifications mediate the regulatory mechanisms of the CD47/SIRPα axis. In this issue of the JCI, Li et al. show that neddylation, a ubiquitin-like modification, inactivates Src homology region 2–containing protein tyrosine phosphatase 2 (SHP2), a downstream target of this pathway. They further show that inhibition of SHP2 sensitizes CRC cells to immunotherapies to which they were previously resistant. Collectively, the results underscore the need for cotargeting SHP2 and immune checkpoints (e.g., programmed death 1 [PD1]) in CRC and possibly other immunotherapy-resistant tumors.

Summary: The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013–2018), Phase 2 of the program (ERCC2, 2019–2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2’s current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Novel therapeutic strategies targeting glioblastoma (GBM) often fail in the clinic, partly because preclinical models in which hypotheses are being tested do not recapitulate human disease. To address this challenge, we took advantage of our previously developed spontaneous Qk/Trp53/Pten (QPP) triple-knockout model of human GBM, comparing the immune microenvironment of QPP mice with that of patient-derived tumors to determine whether this model provides opportunity for gaining insights into tumor physiopathology and preclinical evaluation of therapeutic agents. Immune profiling analyses and single-cell sequencing of implanted and spontaneous tumors from QPP mice and from patients with glioma revealed intratumoral immune components that were predominantly myeloid cells (e.g., monocytes, macrophages, and microglia), with minor populations of T, B, and NK cells. When comparing spontaneous and implanted mouse samples, we found more neutrophils and T and NK cells in the implanted model. Neutrophils and T and NK cells were increased in abundance in samples derived from human high-grade glioma compared with those derived from low-grade glioma. Overall, our data demonstrate that our implanted and spontaneous QPP models recapitulate the immunosuppressive myeloid-dominant nature of the tumor microenvironment of human gliomas. Our model provides a suitable tool for investigating the complex immune compartment of gliomas.

Introduction Based on the results showing that there are more alcoholics in the low-income bracket, case management (CM) for such cases was initiated in 2011. As a result, the treatment failure rate was identified between 43-44% based on the WHO criteria. Objectives We investigated the predictive factors for the treatment failure to maximize successful CM treatment. Methods Thirty-nine subjects from Sasang-gu and Saha-gu treated by four social workers using CM were included in this study. Failure was defined when the level of risk was maintained or increased as per the WHO criteria. The clinical characteristics of the subjects including their age and gender were collected. Results Typically, 17 (43.6%) subjects demonstrated treatment failure by the CM (TF). Compared with the subjects who were treated successfully (n=22; TS), TF maintained abstinence in shorter periods in terms of the longest abstinent period compared with TS while CM (28.24±.99 vs. 76.82±.27, p=.025). The higher population in TF did not make an effort to quit drinking compared with TS while CM (41.2% vs.13.6%, p=.051). Also, more TF stayed with their family members compared with TS (58.8% vs. 31.8%, p=.092). Conclusions The results showed that shorter abstinence periods and the absence of efforts initiated to quit drinking while CM, and living with family members were the predictive factors for failure in treating alcoholics by the CM. It is presumed that influencing patients to quit drinking and encouraging them to abstain for longer periods are crucial to attaining successful treatment. Disclosure No significant relationships.

Introduction Despite the fact that 95% of all

Background:. Scars can have significant morbidity and negatively impact psychological, functional, and cosmetic outcomes as well as the overall quality-of-life, especially among ethnic minorities. The objective of this study was to evaluate African American and White patients’ perception of their scars’ impact on symptoms, appearance, psychosocial health, career, and sexual well-being, using validated assessment tools. Method:. A total of 675 abdominoplasty and breast surgery patients from four providers completed the SCAR-Q, and Career/Sexual Well-Being scales via phone or email. A higher score on both assessments indicates a more positive patient perception. Results:. Of the 675 respondents, 77.0% were White, and 23.0% were African American. White patients scored significantly higher on the SCAR-Q (232 ± 79 versus 203 ± 116), appearance (66 ± 26 versus 55 ± 29), and Career/Sexual Well-Being (16 ± 2 versus 15 ± 5) scales than African American patients (P < 0.001, P < 0.001, P < 0.001, respectively). There was no significant correlation between duration after surgery and symptoms or appearance scores for African American patients (P = 0.11, P = 0.37). There was no significant correlation between patient age and SCAR-Q score or time after surgery and psychosocial scores. Conclusions:. African American patients are more likely to have lower perceptions of their scarring appearance, symptoms, psychosocial impact, career impact, and sexual well-being impact than White patients. Scar appearance and symptoms are less likely to improve over time for African American patients. This study highlights the need to address patient ethnicity when considering further follow-up, counseling, or other measures to enhance scar perception.

This study investigated the combined effects of cooking temperature and time on the meat and eating quality characteristics of the sous-vide chicken breast. For the control group, chicken breast samples were cooked in a convection oven until the internal temperature reached 71°C. Each sample for sous-vide cooking was vacuum packaged and then cooked under continuous thermocontrolled conditions in a water bath at 6 combinations of cooking temperature (60 and 70°C) and time (1, 2, and 3 h). Sous-vide cooked chicken meat at 60°C for 1 h (SV60-1h) showed lower cooking loss (6.58 vs. 26.5%, P

A new infra-red (IR) thermography system with high spatial resolution has been installed on KSTAR and is now mainly applied to measure the outer divertor heat load profile. The first measurement results of the outer divertor heat load profiles between ELMs have been applied to characterize the inter-ELMs outer divertor heat loads in KSTAR H-mode plasmas. In particular, the power decay length (λq) of the divertor heat load profile has been determined by fitting the profile to a convolution of an exponential decay and a Gaussian function. The analysis on the power decay length shows a good agreement with the recent multi-machine λq scaling, which predicts λq of the inter-ELMs divertor heat load to be ∼1 mm under the standard H-mode scenario in ITER. The divertor IR thermography system has also successfully measured the strike point splitting of the outer divertor heat flux during the application of resonant magnetic perturbation (RMP) fields. In addition, it has provided a clear evidence that the strike point splitting pattern depends on the RMP fields configuration.

Background:. As fat grafting in breast reconstruction evolves, questions of technique and outcomes persist. We compared 2 common fat processing techniques—decantation (DEC) versus closed wash and filtration (CWF)—with regard to outcomes and efficacy. Methods:. Chart review of a single surgeon experience with breast fat grafting was performed. Data extracted included demographics, technique, complications, graft volume, and revision rates. Secondarily, the timeline of complication profiles was analyzed. Lastly, subgroup analysis of radiated versus nonradiated breast outcomes was performed. Results:. One thousand one hundred fifty-eight fat grafting procedures were performed on 775 breasts (654 DEC, 504 CWF). Time-to-event analysis for all complications showed no difference between groups. Independent risk factors for fat necrosis included DEC technique, body mass index >30 kg/m2, and fat injection >75 mL. The majority of cases of fat necrosis, cyst/nodule formation, ultrasounds, and biopsies occurred more than 6 months after grafting. Average graft volume was lower in DEC compared with CWF breasts (50.6 versus 105.0 mL, P < 0.01), and more DEC breasts required repeat fat grafting procedures (39.9% versus 29.6%, P < 0.01). Radiated breasts received larger fat graft volume (89.9 versus 72.4 mL, P < 0.01) and required more fat graft procedures (average 1.62 versus 1.47, P < 0.01). Conclusions:. This study represents the largest series of breast reconstruction fat grafting to date. DEC harvest technique may be a risk factor for fat necrosis, which results in less fat injection and greater need for repeat procedures. Similarly, radiated breasts require larger graft volume and more repeat procedures.

High-performance research reactors require fuel that operates at high specific power to high fission density, but at relatively low temperatures. Research reactor fuels are designed for efficient heat rejection, and are composed of assemblies of thin-plates clad in aluminum alloy. The development of low-enriched fuels to replace high-enriched fuels for these reactors requires a substantially increased uranium density in the fuel to offset the decrease in enrichment. Very few fuel phases have been identified that have the required combination of very-high uranium density and stable fuel behavior at high burnup. UMo alloys represent the best known tradeoff in these properties. Testing of aluminum matrix U-Mo aluminum matrix dispersion fuel revealed a pattern of breakaway swelling behavior at intermediate burnup, related to the formation of a molybdenum stabilized high aluminum intermetallic phase that forms during irradiation. In the case of monolithic fuel, this issue was addressed by eliminating, as much as possible, the interfacial area between U-Mo and aluminum. Based on scoping irradiation test data, a fuel plate system composed of solid U-10Mo fuel meat, a zirconium diffusion barrier, and Al6061 cladding was selected for development. Developmental testing of this fuel system indicates that it meets core criteria for fuel qualification, including stable and predictable swelling behavior, mechanical integrity to high burnup, and geometric stability. In addition, the fuel exhibits robust behavior during power-cooling mismatch events under irradiation at high power.

Since 2001, a series of five irradiation test campaigns for atomized U-Mo dispersion fuel rods, KOMO-1, -2, -3, -4, and -5, has been conducted at HANARO (Korea) in order to develop high performance low enriched uranium dispersion fuel for research reactors. The KOMO irradiation tests provided valuable information on the irradiation behavior of U-Mo fuel that results from the distinct fuel design and irradiation conditions of the rod fuel for HANARO. Full size U-Mo dispersion fuel rods of 4–5 g-U/cm3 were irradiated at a maximum linear power of approximately 105 kW/m up to 85% of the initial U-235 depletion burnup without breakaway swelling or fuel cladding failure. Electron probe microanalyses of the irradiated samples showed localized distribution of the silicon that was added in the matrix during fuel fabrication and confirmed its beneficial effect on interaction layer growth during irradiation. The modifications of U-Mo fuel particles by the addition of a ternary alloying element (Ti or Zr), additional protective coatings (silicide or nitride), and the use of larger fuel particles resulted in significantly reduced interaction layers between fuel particles and Al.

We investigated the relationship between phosphorylation of alphaB-crystallin (αBC) and retinal apoptosis in type 2 diabetes. The retinas of male Otsuka Long–Evans Tokushima fatty (OLETF) rats at 24 and 35 weeks were used as an animal model for type 2 diabetes and sex- and age-matched Long–Evans Tokushima Otsuka (LETO) rats were used as controls. In the retinas of 35-week OLETF rats, the interaction between αBC and protein kinase C delta (PKC δ) among the PKC isozymes, αBC phosphorylation at Ser45 (S45p-αBC), TUNEL-positive apoptotic ganglion cells, several apoptotic signs, and co-localization of S45p-αBC and TUNEL significantly increased as compared with other groups while the αBC–Bax interaction greatly decreased. These changes were abolished by rottlerin treatment, a highly specific PKC δ inhibitor. These results suggest that PKC δ is involved in regulation of anti-apoptotic function of αBC in the retina of type 2 diabetes.

We examined the effect of triamcinolone acetonide (TA), a corticosteroid, on the relationship between vascular pathophysiology and vascular endothelial growth factor (VEGF) activation in the retina of a rat model of oxygen-induced retinopathy (OIR). OIR was induced by exposure of hyperoxia (80% oxygen) to Sprague–Dawley (SD) rats from P2 to P14 and then returned to normoxic conditions. TA was intravitreal-injected once into the right eye of OIR rats at P15. Effects of TA on vascular pathophysiology or changes of various genes in response to hypoxia and/or proinflammation under hypoxic retina were assessed by the Evans-blue method, fluorescein isothiocyanate-dextran (FITC-D) infusion, immunoblotting, and ELIZA. TA not only reduced retinal neovascularization and vascular leakage in the OIR-rat retina, but also blocked the induction of hypoxia-response proinflammatory genes before it negatively controlled VEGF activation. These findings suggest a potential that TA suppresses retinal neovascular pathophysiology via proinflammation-mediated activation of VEGF during hypoxia.

Over the last decades, the incidence of ultraviolet B (UVB)-related skin problems has been increasing. Damages induced by UVB radiation are related to mutations that occur as a result of direct DNA damage and/or the production of reactive oxygen species. We investigated the anti-oxidant effects of a Polygonum multiflorum thumb extract against skin damage induced by UVB irradiation. Female SKH-1 hairless mice were divided into three groups: control (N = 7), distilled water- (N = 10), and P. multiflorum extract-treated (PM, N = 10) groups. The PM (10 g) was extracted with 100 mL distilled water, cryo-dried and 9.8 g was obtained. The animals received a topical application of 500 µL distilled water or PM extract (1, 2, 4, 8, and 16%, w/v, dissolved in distilled water) for 30 min after UVB irradiation (wavelength 280-320 nm, 300 mJ/cm²; 3 min) of the dorsal kin for 14 days, and skin immunohistochemistry and Cu,Zn-superoxide dismutase (SOD1) activity were determined. SOD1 immunoreactivity, its protein levels and activities in the skin were significantly reduced by 70% in the distilled water-treated group after UVB irradiation compared to control. However, in the PM extract-treated groups, SOD1 immunoreactivity and its protein and activity levels increased in a dose-dependent manner (1-16%, w/v, PM extract) compared to the distilled water-treated group. SOD1 protein levels and activities in the groups treated with 8 and 16%, w/v, PM extract recovered to 80-90% of the control group levels after UVB. These results suggest that PM extract strongly inhibits the destruction of SOD1 by UV radiation and probably contains anti-skin photoaging agents.