Application of three-dimensional printed biomodels in endoscopic spinal surgery.

Background: Three-dimensional printing (3DP) is increasingly used to individualise surgery and may be an effective tool for representing patient anatomy. Current literature on patient-specific anatomical models (biomodels) for minimally invasive spinal surgery is a limited number of case series and cohort studies. However, studies investigating 3DP in other specialties have reported multiple benefits. Methods: This prospective study considered a series of patients (n=33) undergoing elective endoscopic spinal surgery, including combinations of microdiscectomy (n=27), foraminotomy (n=7), and laminectomy (n=3). These surgeries were conducted at vertebral levels ranging from L2/3 to L5/S1. The surgeon then recorded the impact on preoperational planning, intraoperative decision-making and accelerating the learning curve with a qualitative questionnaire. Results: There were benefits to planning in 54.5% of cases (n=18), improved intraoperative decision-making in 60.6% of cases (n=20). These benefits were reported more frequently earlier in the cases, with improvements to learning reported in 60% of the first five cases and not in subsequent cases. The surgeon commented that the biomodels were more useful on. Conclusions: The rates of preoperative and intraoperative benefits are consistent with existing studies, and the early benefit to the learning curve may be suitable for applications to surgical training. Additional research is required to determine the practicality of biomodels and their impact on patient outcomes for endoscopic spinal surgery.

Cigarette smoke stimulates clonal expansion of Jak2V617F and Tet2-/- cells.

Introduction: Somatic mutations in myeloid growth factor pathway genes, such as JAK2, and genes involved in epigenetic regulation, such as TET2, in hematopoietic stem cells (HSCs) leads to clonal hematopoiesis of indeterminate potential (CHIP) which presents a risk factor for hematologic malignancy and cardiovascular disease. Smoking behavior has been repeatedly associated with the occurrence of CHIP but whether smoking is an environmental inflammatory stressor in promoting clonal expansion has not been investigated. Methods: We performed in vivo smoke exposures in both wildtype (WT) mice and transplanted mice carrying Jak2V617F mutant and Tet2 knockout (Tet-/-) cells to determine the impact of cigarette smoke (CS) in the HSC compartment as well as favoring mutant cell expansion. Results: WT mice exposed to smoke displayed increased oxidative stress in long-term HSCs and suppression of the hematopoietic stem and progenitor compartment but smoke exposure did not translate to impaired hematopoietic reconstitution in primary bone marrow transplants. Gene expression analysis of hematopoietic cells in the bone marrow identified an imbalance between Th17 and Treg immune cells suggesting a local inflammatory environment. We also observed enhanced survival of Jak2V617F cells exposed to CS in vivo and cigarette smoke extract (CSE) in vitro. WT bone marrow hematopoietic cells from WT/Jak2V617F chimeric mice exposed to CS demonstrated an increase in neutrophil abundance and distinct overexpression of bone marrow stromal antigen 2 (Bst2) and retinoic acid early transcript 1 (Raet1) targets. Bst2 and Raet1 are indicative of increased interferon signaling and cellular stress including oxidative stress and DNA damage, respectively. In chimeric mice containing both WT and Tet2-/- cells, we observed an increased percentage of circulating mutant cells in peripheral blood post-cigarette smoke exposure when compared to pre-exposure levels while this difference was absent in air-exposed controls. Conclusion: Altogether, these findings demonstrate that CS results in an inflamed bone marrow environment that provides a selection pressure for existing CHIP mutations such as Jak2V617F and Tet2 loss-of-function.

Definitive treatment choice among Black immigrants with prostate cancer: Analysis of patient surveys distributed at a single safety-net institution.

BACKGROUND: Large-scale prostate cancer (PCa) database reviews have found a consistent discrepancy in the mortality rate in Black patients compared to their White counterparts. Furthermore, differences in PCa treatment and outcomes among Black men of different ethnic origins have also been identified. Due to the heterogeneity of PCa-impacted communities and the unclear impact of patient immigration status on treatment outcomes, we sought to determine the demographic factors associated with treatment choice for definitive treatment of PCa in our single institution's patient population of Black immigrants. METHODS: We distributed surveys to all patients in the Kings County Hospital Center urologic oncology clinic from February 2019 to February 2020 and collected relevant health information via EMR. The survey collected demographic information regarding age, education, health insurance, employment status, socioeconomic status, country of birth, and years living in the United States (US). RESULTS: Out of the 253 patients surveyed, the majority of patients surveyed were Black and foreign born. There were no significant differences in demographic data between US-born and foreign-born patients except number of years living in the United States. In the intermediate risk group, patients living in the United States for <10 years chose surgery significantly more often than US-born patients (90.9% vs. 50.0%, p = 0.036). On multivariate analysis, patients that chose surgery were more likely to be older when diagnosed (odds ratio [OR] = 1.21) and less likely to be born in the United States than in African or Caribbean countries (OR = 0.054). CONCLUSIONS: In our study of a majority-Black population, we found that patients born in the United States were less likely than their foreign counterparts to opt for surgery, as previous studies have shown. The choice of definitive treatment modality for Black men with intermediate risk PCa was found to be influenced by age at diagnosis and immigration status.

Osseous Loading by a Volume-Reduced Tongue During Muscle Contractions.

PURPOSE: To investigate how tongue volume reduction affects loads on surrounding bone surfaces produced by neuromuscular stimulation of the tongue. MATERIALS AND METHODS: Of each pair of same-gender minipig siblings, 1 received tongue reduction and 1 underwent sham surgery. Either immediately (acute, 6 pairs) or 1 month (chronic, 5 pairs) after surgery, bone surface and/or suture strains and pressures were recorded from the following locations when the hypoglossal nerve trunk, hypoglossal nerve medial branch, hypoglossal nerve lateral branch, genioglossus, and styloglossus (SG) were electrically stimulated: 1) three rosette strain gauges on the premaxillary palatal surface (premaxilla [PM]) and lingual surfaces of the mandibular alveolus at anterior (mandibular incisor [MI]) and posterior (mandibular molar [MM]) locations; 2) two single-element strain gauges over the palatal surface of the premaxillary-maxillary suture and the lingual surface of the mandibular symphysis; and 3) two pressure transducers on the palatal surface of the maxilla (palatal process) and the lingual surface of the mandibular alveolus (mandibular corpus). RESULTS: Compared with the sham animals in the acute study, reduction animals showed significantly decreased PM and MI strains, as well as palatal process pressure. With muscle contractions, mandibular symphysis and MM strains were enhanced significantly with a more dorsal orientation. In the chronic study, reduction animals showed decreased PM and increased MM strains. On comparison of chronic versus acute studies, PM, MI, and MM strains under SG stimulation were significantly smaller whereas MM strain was significantly larger under hypoglossal nerve trunk, hypoglossal nerve lateral branch, and SG stimulations. CONCLUSIONS: Muscle contractions from a volume-reduced tongue produce lower and higher loads in the anterior and posterior mouth, respectively. However, although the effects on reducing loads in the anterior mouth are persisting over time, compensatory load enhancement in the posterior mouth diminishes owing to surgical healing.

Enhanced activity and stability of organophosphorus hydrolase via interaction with an amphiphilic polymer.

A simple approach to enhancing the activity and stability of organophosphorus hydrolase (OPH) is developed based on interactions between the hydrophobic poly(propylene oxide) (PPO) block of amphiphilic Pluronics and the enzyme. This strategy provides an efficient route to new formulations for decontaminating organophosphate neurotoxins.

Cardiovascular-related proteins identified in human plasma by the HUPO Plasma Proteome Project pilot phase.

Proteomic profiling of accessible bodily fluids, such as plasma, has the potential to accelerate biomarker/biosignature development for human diseases. The HUPO Plasma Proteome Project pilot phase examined human plasma with distinct proteomic approaches across multiple laboratories worldwide. Through this effort, we confidently identified 3020 proteins, each requiring a minimum of two high-scoring MS/MS spectra. A critical step subsequent to protein identification is functional annotation, in particular with regard to organ systems and disease. Performing exhaustive literature searches, we have manually annotated a subset of these 3020 proteins that have cardiovascular-related functions on the basis of an existing body of published information. These cardiovascular-related proteins can be organized into eight groups: markers of inflammation and/or cardiovascular disease, vascular and coagulation, signaling, growth and differentiation, cytoskeletal, transcription factors, channels/receptors and heart failure and remodeling. In addition, analysis of the peptide per protein ratio for MS/MS identification reveals group-specific trends. These findings serve as a resource to interrogate the functions of plasma proteins, and moreover, the list of cardiovascular-related proteins in plasma constitutes a baseline proteomic blueprint for the future development of biosignatures for diseases such as myocardial ischemia and atherosclerosis.

Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals.

The proinflammatory effects of particulate pollutants, including diesel exhaust particles (DEP), are related to their content of redox cycling chemicals and their ability to generate oxidative stress in the respiratory tract. An antioxidant defense pathway, which involves phase II enzyme expression, protects against the pro-oxidative and proinflammatory effects of DEP. The expression of enzymes, including heme oxygenase-1 (HO-1) and GST, is dependent on the activity of a genetic antioxidant response element in their promoters. In this study we investigated the mechanism by which redox cycling organic chemicals, prepared from DEP, induce phase II enzyme expression as a protective response. We demonstrate that aromatic and polar DEP fractions, which are enriched in polycyclic aromatic hydrocarbons and quinones, respectively, induce the expression of HO-1, GST, and other phase II enzymes in macrophages and epithelial cells. We show that HO-1 expression is mediated through accumulation of the bZIP transcription factor, Nrf2, in the nucleus, and that Nrf2 gene targeting significantly weakens this response. Nrf2 accumulation and subsequent activation of the antioxidant response element is regulated by the proteasomal degradation of Nrf2. This pathway is sensitive to pro-oxidative and electrophilic DEP chemicals and is also activated by ambient ultrafine particles. We propose that Nrf2-mediated phase II enzyme expression protects against the proinflammatory effects of particulate pollutants in the setting of allergic inflammation and asthma.