Acute exposure to electronic cigarette components alters mRNA expression of pre-osteoblasts.

The use of traditional nicotine delivery products such as tobacco has long been linked to detrimental health effects. However, little work to date has focused on the emerging market of aerosolized nicotine delivery known as electronic nicotine delivery systems (ENDS) or electronic cigarettes, and their potential for new effects on human health. Challenges studying these devices include heterogeneity in the formulation of the common components of most available ENDS, including nicotine and a carrier (commonly composed of propylene glycol and vegetable glycerin, or PG/VG). In the present study, we report on experiments interrogating the effects of major identified components in e-cigarettes. Specifically, the potential concomitant effects of nicotine and common carrier ingredients in commercial "vape" products are explored in vitro to inform the potential health effects on the craniofacial skeleton through novel vectors as compared to traditional tobacco products. MC3T3-E1 murine pre-osteoblast cells were cultured in vitro with clinically relevant liquid concentrations of nicotine, propylene glycol (PG), vegetable glycerin (VG), Nicotine+PG/VG, and the vape liquid of a commercial product (Juul). Cells were treated acutely for 24 h and RNA-Seq was utilized to determine segregating alteration in mRNA signaling. Influential gene targets identified with sparse partial least squares discriminant analysis (sPLS-DA) implemented in mixOmics were assessed using the PANTHER Classification system for molecular functions, biological processes, cellular components, and pathways of effect. Additional endpoint functional analyses were used to confirm cell cycle changes. The initial excitatory concentration (EC50) studied defined a target concentration of carrier PG/VG liquid that altered the cell cycle of the calvarial cells. Initial sPLS-DA analysis demonstrated the segregation of nicotine and non-nicotine exposures utilized in our in vitro modeling. Pathway analysis suggests a strong influence of nicotine exposures on cellular processes including metabolic processes and response to stimuli including autophagic flux. Further interrogation of the individual treatment conditions demonstrated segregation by treatment modality (Control, Nicotine, Carrier (PG+VG), Nicotine+PG/VG) along three dimensions best characterized by: latent variable 1 (PLSDA-1) showing strong segregation based on nicotine influence on cellular processes associated with cellular adhesion to collagen, osteoblast differentiation, and calcium binding and metabolism; latent variable 2 (PLSDA-2) showing strong segregation of influence based on PG+VG and Control influence on cell migration, survival, and cycle regulation; and latent variable 3 (PLSDA-3) showing strong segregation based on Nicotine and Control exposure influence on cell activity and growth and developmental processes. Further, gene co-expression network analysis implicates targets of the major pathway genes associated with bone growth and development, particularly craniofacial (FGF, Notch, TGFß, WNT) and analysis of active subnetwork pathways found these additionally overrepresented in the Juul exposure relative to Nicotine+PG/VG. Finally, experimentation confirmed alterations in cell count, and increased evidence of cell stress (markers of autophagy), but no alteration in apoptosis. These data suggest concomitant treatment with Nicotine+PG/VG drives alterations in pre-osteoblast cell cycle signaling, specifically transcriptomic targets related to cell cycle and potentially cell stress. Although we suspected cell stress and well as cytotoxic effects of Nicotine+PG/VG, no great influence on apoptotic factors was observed. Further RNA-Seq analysis allowed for the direct interrogation of molecular targets of major pathways involved in bone and craniofacial development, each demonstrating segregation (altered signaling) due to e-cigarette-type exposure. These data have implications directed toward ENDS formulation as synergistic effects of Nicotine+PG/VG are evidenced here. Thus, future research will continue to interrogate how varied formulation of Nicotine+PG/VG affects overall cell functions in multiple vital systems.

Examining the Influence of a General Surgery Resident's Transplant Experience on Their Pursuit of Transplant Surgery Fellowship.

BACKGROUND: Transplant surgery has historically been a less desirable fellowship among general surgery graduates. Limited work has been done to understand factors associated with residents' interest in transplantation. Using a multi-institutional cohort, we examined how the resident experience on transplant surgery may influence their decision to pursue transplant fellowship. METHODS: Individual demographics, program characteristics, and transplant-specific case logs were collected for graduates from 2010 to 2020 at 20 general surgery residency programs within the US Resident OPerative Experience (ROPE) Consortium. Residents who pursued transplant surgery fellowship were compared to those who went directly into practice or pursued a non-transplant fellowship. RESULTS: Among 1342 general surgery graduates, 52 (3.9%) pursued abdominal transplant fellowship. These residents completed more transplant (22 vs. 9), liver (14 vs. 9), pancreas (15 vs. 11), and vascular access operations (38 vs. 30) compared to residents who did not pursue transplant fellowship (all p < 0.05). Multivariable logistic regression found that residents underrepresented in medicine were three times more likely (95% CI 1.54-6.58, p < 0.01) and residents at a program co-located with a transplant fellowship six times more likely (95% CI 1.95-18.18, p < 0.01) to pursue transplant fellowship. Additionally, a resident's increasing total transplant operative volume was associated with an increased likelihood of pursuing a transplant fellowship (OR = 1.12, 95% CI 1.09-1.14, p < 0.01). CONCLUSION: The findings from this multi-institutional study demonstrate that increased exposure to transplant operations and interaction within a transplant training program is associated with a resident's pursuit of transplant surgery fellowship. Efforts to increase operative exposure, case participation, and mentorship may optimize the resident experience and promote the transplant surgery pipeline.

Variation in dentist participation between dental medicaid managed care organizations.

OBJECTIVES: Dentists' Medicaid participation is a critical factor affecting dental care access for Medicaid beneficiaries. An important gap in existing literature is the variation in participation across Medicaid dental Managed Care Organizations (MCOs) in states with more than one. This study examined the variation in participation overall and in predictors of dentist participation between two MCOs in Iowa's Dental Medicaid program. METHODS: Data were obtained from a survey of Iowa private practice dentists (n = 1256). Responding general dentists (n = 497) were included in the final analytic sample. Univariate, bivariate, and multivariable logistic regression analyses were conducted to examine demographic and practice characteristics associated with dentist participation (acceptance of new Medicaid patients) between MCOs and by age category. RESULTS: Among respondents, the proportions accepting new adults with Medicaid were 26% (MCO 1) and 7% (MCO 2); for children, they were 40% (MCO 1) and 11% (MCO 2). For adults, dentists who were too busy (MCO1) and solo practice dentists (MCO2) were positively significantly associated with the acceptance of new patients. For children, group and rural practice dentists, as well as dentists who worked <32 h/week were positively significantly associated with acceptance of new patients with MCO1. CONCLUSIONS: There was considerable variation in dentist-reported acceptance of new adult and child Medicaid patients, and in the factors affecting acceptance of new patients between MCOs in Iowa dental Medicaid. Future studies of Medicaid participation should consider variations by MCO in states with more than one dental MCO so as not to miss important factors affecting Medicaid participation.

Placental TLR recognition of salivary and subgingival microbiota is associated with pregnancy complications.

BACKGROUND: Pre-term birth, the leading cause of neonatal mortality, has been associated with maternal periodontal disease and the presence of oral pathogens in the placenta. However, the mechanisms that underpin this link are not known. This investigation aimed to identify the origins of placental microbiota and to interrogate the association between parturition complications and immune recognition of placental microbial motifs. Video Abstract METHODS: Saliva, plaque, serum, and placenta were collected during 130 full-term (FT), pre-term (PT), or pre-term complicated by pre-eclampsia (PTPE) deliveries and subjected to whole-genome shotgun sequencing. Real-time quantitative PCR was used to measure toll-like receptors (TLR) 1-10 expression in placental samples. Source tracking was employed to trace the origins of the placental microbiota. RESULTS: We discovered 10,007 functionally annotated genes representing 420 taxa in the placenta that could not be attributed to contamination. Placental microbial composition was the biggest discriminator of pregnancy complications, outweighing hypertension, BMI, smoking, and maternal age. A machine-learning algorithm trained on this microbial dataset predicted PTPE and PT with error rates of 4.05% and 8.6% (taxonomy) and 6.21% and 7.38% (function). Logistic regression revealed 32% higher odds of parturition complication (95% CI 2.8%, 81%) for every IQR increase in the Shannon diversity index after adjusting for maternal smoking status, maternal age, and gravida. We also discovered distinct expression patterns of TLRs that detect RNA- and DNA-containing antigens in the three groups, with significant upregulation of TLR9, and concomitant downregulation of TLR7 in PTPE and PT groups, and dense correlation networks between microbial genes and these TLRs. 70-82% of placental microbiota were traced to serum and thence to the salivary and subgingival microbiomes. The oral and serum microbiomes of PTPE and PT groups displayed significant enrichment of genes encoding iron transport, exosome, adhesion, quorum sensing, lipopolysaccharide, biofilm, and steroid degradation. CONCLUSIONS: Within the limits of cross-sectional analysis, we find evidence to suggest that oral bacteria might translocate to the placenta via serum and trigger immune signaling pathways capable of inducing placental vascular pathology. This might explain, in part, the higher incidence of obstetric syndromes in women with periodontal disease.

DCD liver transplant in patients with a MELD over 35.

Introduction: Donation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35. Methods: We analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching. Results: In the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively). Discussion: In highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

True coincidence summing correction for a BEGe detector in close geometry measurements.

The true coincidence summing correction factor for a Broad Energy Germanium detector has been calculated at far and close geometry set-up using radioactive γ-ray sources. The correction factors were calculated using both experimental and analytical methods. Geant4 simulation was done to calculate the full-energy peak and total efficiencies of the detector. Standard, as well as fabricated mono-energetic γ-ray sources, were used for the γ-ray efficiency measurements. The simulated efficiencies of mono-energetic γ-ray sources were matched to the experimental γ-ray efficiencies by optimizing the detector parameters. The same parameters were used to obtain the full-energy peak and total efficiencies for γ-rays of current interest. Analytical and experimental correction factors were found to agree well with each other. The coincidence summing effect is found to be significant for source-to-detector distances less than 5 cm.

COVID-19 associated oral and oropharyngeal microbiome: Systematic review and meta-analysis.

Three years into the coronavirus disease 2019 (COVID-19) pandemic, there are still growing concerns with the emergence of different variants, unknown long- and short-term effects of the virus, and potential biological mechanisms underlying etiopathogenesis and increased risk for morbidity and mortality. The role of the microbiome in human physiology and the initiation and progression of several oral and systemic diseases have been actively studied in the past decade. With the proof of viral transmission, carriage, and a potential role in etiopathogenesis, saliva and the oral environment have been a focus of COVID-19 research beyond diagnostic purposes. The oral environment hosts diverse microbial communities and contributes to human oral and systemic health. Several investigations have identified disruptions in the oral microbiome in COVID-19 patients. However, all these studies are cross-sectional in nature and present heterogeneity in study design, techniques, and analysis. Therefore, in this undertaking, we (a) systematically reviewed the current literature associating COVID-19 with changes in the microbiome; (b) performed a re-analysis of publicly available data as a means to standardize the analysis, and (c) reported alterations in the microbial characteristics in COVID-19 patients compared to negative controls. Overall, we identified that COVID-19 is associated with oral microbial dysbiosis with significant reduction in diversity. However, alterations in specific bacterial members differed across the study. Re-analysis from our pipeline shed light on Neisseria as the potential key microbial member associated with COVID-19.

iPHoP: An integrated machine learning framework to maximize host prediction for metagenome-derived viruses of archaea and bacteria.

The extraordinary diversity of viruses infecting bacteria and archaea is now primarily studied through metagenomics. While metagenomes enable high-throughput exploration of the viral sequence space, metagenome-derived sequences lack key information compared to isolated viruses, in particular host association. Different computational approaches are available to predict the host(s) of uncultivated viruses based on their genome sequences, but thus far individual approaches are limited either in precision or in recall, i.e., for a number of viruses they yield erroneous predictions or no prediction at all. Here, we describe iPHoP, a two-step framework that integrates multiple methods to reliably predict host taxonomy at the genus rank for a broad range of viruses infecting bacteria and archaea, while retaining a low false discovery rate. Based on a large dataset of metagenome-derived virus genomes from the IMG/VR database, we illustrate how iPHoP can provide extensive host prediction and guide further characterization of uncultivated viruses.

Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation.

The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings.

A novel screening method for free non-standard amino acids in human plasma samples using AccQ·Tag reagents and LC-MS/MS.

There are at least 500 naturally occurring amino acids, of which only 20 standard proteinogenic amino acids are used universally across all organisms in the synthesis of peptides and proteins. Non-standard amino acids can be incorporated into proteins or are intermediates and products of metabolic pathways. While the analysis of standard amino acids is well-defined, the analysis of non-standard amino acids can be challenging due to the wide range of physicochemical properties, and the lack of both reference standards and information in curated databases to aid compound identification. It has been shown that the use of an AccQ·Tag™ derivatization kit along with LC-MS/MS is an attractive option for the analysis of free standard amino acids in complex samples because it is fast, sensitive, reproducible, and selective. It has been demonstrated that the most abundant quantitative transition for MS/MS analysis of 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) derivatized amino acids corresponds to the fragmentation of the molecule at the 6-aminoquinoline carbonyl group producing a common m/z 171 fragment ion and occurs at similar mass spectrometry collision energy and cone voltages. In this study, the unique properties of AQC derivatized amino acids producing high intensity common fragment ions, along with chromatographic separation of amino acids under generic chromatography conditions, were used to develop a novel screening method for the detection of trace levels of non-standard amino acids in complex matrices. Structural elucidation was carried out by comparing the MS/MS fragment ion mass spectra generated with in silico predicted fragmentation spectra to enable a putative identification, which was confirmed using an appropriate analytical standard. This workflow was applied to screen human plasma samples for bioactive thiol-group modified cysteine amino acids and S-allylmercaptocysteine (SAMC), S-allylcysteine sulfoxide (SACS or alliin) and S-propenylcysteine (S1PC) are reported for the first time to be present in human plasma samples after the administration of garlic supplements.

Robotic training for medical students: feasibility of a pilot simulation curriculum.

While robotic procedures are growing rapidly, medical students have a limited role in robotic surgeries. Curricula are needed to enhance engagement. We examined feasibility of augmenting Intuitive Surgical (IS) robotic training for medical students. As a pilot, 18 senior students accepted an invitation to a simulation course with a daVinci robot trainer. Course teaching objectives included introducing robotic features, functionalities, and roles. A 1-h online module from the IS learning platform and a 4-h in-person session comprised the course. The in-person session included an overview of the robot by an IS trainer (1.5 h), skills practice at console (1.5 h), and a simulation exercise focused on the bedside assist role (1 h). Feasibility included assessing implementation and acceptability using a post-session survey and focus group (FG). Survey responses were compiled. FG transcripts were analyzed using inductive thematic analysis techniques. Fourteen students participated. Implementation was successful as interested students signed up and completed each of the course components. Regarding acceptability, students reported the training valuable and recommended it as preparation for robotic cases during core clerkships and sub-internships. In addition, FGs revealed 4 themes: (1) perceived expectations of students in the OR; (2) OR vs. outside-OR learning; (3) simulation of stress; and (4) opportunities to improve the simulation component. To increase preparation for the robotic OR and shift robotic training earlier in the surgical education continuum, educators should consider hands-on simulation for medical students. We demonstrate feasibility although logistics may limit scalability for large numbers of students.

Effect of Saccharomyces cerevisiae Fortified with Selenium on the Hematological and Some Biochemical Traits of Local Iraqi Goat.

Selenium (Se) is a mineral that is often used as a dietary supplement. Its deficiency has been associated with fertility disorders, as well as imbalances and inhibition of the immune system. This study aimed to estimate the role of organic selenium and Saccharomyces cerevisiae in improving kids' status, health, and physiological conditions. In total, 10 goat kids at seven days were used, with an average started life body weight (b.wt.) of 4±0.2 kg, and they were divided into two groups. Group 1 (G1) was treated with Se-fortified yeast (Saccharomyces cerevisiae+Se) with a dose (30 mg/kg) of body weight. On the other hand, group 2 (G2) was the control group and left untreated. The treatment was started from 7 days of age until three months of age. The kids were administered orally daily for three months of the experiment. The jugular vein was used to draw blood samples within 90 days of the experiment to measure RBC, Hb, PCV, and WBC. Blood serum was separated using a centrifuge to estimate ALT, AST, total protein, Albumin, and Globulin concentrations. The results revealed that Hb, PCV, and Globulin were increased significantly in the G1 (P≤0.05), compared to the control group. Moreover, AST was improved, compared to the control group. These results showed that using yeast fortified with organic Se has improved hematological and biochemical parameters' concentration.

Assessment of Surgeon Performance of Advanced Open Surgical Skills Using a Microskills-Based Novel Curriculum.

Importance: The increase in minimally invasive surgical procedures has eroded exposure of general surgery residents to open operations. High-fidelity simulation, together with deliberate instruction, is needed for advanced open surgical skill (AOSS) development. Objective: To collect validity evidence for AOSS tools to support a shared model for instruction. Design, Setting, and Participants: This prospective cohort study included postresidency surgeons (PRSs) and second-year general surgery residents (R2s) at a single academic medical center who completed simulated tasks taught within the AOSS curriculum between June 1 and October 31, 2021. Exposures: The AOSS curriculum includes 6 fine-suture and needle handling tasks, including deep suture tying (with and without needles) and continuous suturing using the pitch-and-catch and push-push-pull techniques (both superficial and deep). Teaching and assessment are based on specific microskills using a 3-dimensional printed iliac fossa model. Main Outcomes and Measures: The PRS group was timed and scored (5-point Likert scale) on 10 repetitions of each task. Six months after receiving instruction on the AOSS tasks, the R2 group was similarly timed and scored. Results: The PRS group included 14 surgeons (11 male [79%]; 8 [57%] attending surgeons) who completed the simulation; the R2 group, 9 surgeons (5 female [55%]) who completed the simulation. Score and time variability were greater for the R2s compared with the PRSs for all tasks. The R2s scored lower and took longer on (1) deep pitch-and-catch suturing (69% of maximum points for a mean [SD] of 142.0 [31.7] seconds vs 77% for a mean [SD] of 95.9 [29.4] seconds) and deep push-push-pull suturing (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 85% for a mean [SD] of 141.4 [29.1] seconds) relative to the corresponding superficial tasks; (2) suture tying with a needle vs suture tying without a needle (74% of maximum points for a mean [SD] of 64.6 [19.8] seconds vs 90% for a mean [SD] of 54.4 [15.6] seconds); and (3) the deep push-push-pull vs pitch-and-catch techniques (63% of maximum points for a mean [SD] of 284.0 [72.9] seconds vs 69% of maximum points for a mean [SD] of 142.0 [31.7] seconds). For the PRS group, time was negatively associated with score for the 3 hardest tasks: superficial push-push-pull (ρ = 0.60; P = .02), deep pitch-and-catch (ρ = 0.73; P = .003), and deep push-push-pull (ρ = 0.81; P < .001). For the R2 group, time was negatively associated with score for the 2 easiest tasks: suture tying without a needle (ρ = 0.78; P = .01) and superficial pitch-and-catch (ρ = 0.79; P = .01). Conclusions and Relevance: The findings of this cohort study offer validity evidence for a novel AOSS curriculum; reveal differential difficulty of tasks that can be attributed to specific microskills; and suggest that position on the surgical learning curve may dictate the association between competency and speed. Together these findings suggest specific, actionable opportunities to guide instruction of AOSS, including which microskills to focus on, when individual rehearsal vs guided instruction is more appropriate, and when to focus on speed.

Site-specific characteristics of bone and progenitor cells in control and ovariectomized rats.

One-third of postmenopausal women experience at least one osteoporotic bone fracture in their lifetime that occurs spontaneously or from low-impact events. However, osteoporosis-associated jaw bone fractures are extremely rare. It was also observed that jaw bone marrow stem cells (BMSCs) have a higher capacity to form mineralized tissues than limb BMSCs. At present, the underlying causes and mechanisms of variations between jaw bone and limb bone during postmenopause are largely unknown. Thus, the objective of the current study was to examine the site-specific effects of estrogen deficiency using comprehensive analysis of bone quantity and quality, and its association with characterization of cellular components of bone. Nine rats (female, 6 months old) for each bilateral sham and ovariectomy (OVX) surgery were obtained and maintained for 2 months after surgery. A hemi-mandible and a femur from each rat were characterized for parameters of volume, mineral density, cortical and trabecular morphology, and static and dynamic mechanical analysis. Another set of 5 rats (female, 9 months old) was obtained for assays of BMSCs. Following cytometry to identify BMSCs, bioassays for proliferation, and osteogenic, adipogenic, chondrogenic differentiation, and cell mitochondrial stress tests were performed. In addition, mRNA expression of BMSCs was analyzed. OVX decreased bone quantity and quality (mineral content, morphology, and energy dissipation) of femur while those of mandible were not influenced. Cellular assays demonstrated that mandible BMSCs showed greater differentiation than femur BMSCs. Gene ontology pathway analysis indicated that the mandibular BMSCs showed most significant differential expression of genes in the regulatory pathways of osteoblast differentiation, SMAD signaling, cartilage development, and glucose transmembrane transporter activity. These findings suggested that active mandibular BMSCs maintain bone formation and mineralization by balancing the rapid bone resorption caused by estrogen deficiency. These characteristics likely help reduce the risk of osteoporotic fracture in postmenopausal jawbone.

Nodular Regenerative Hyperplasia After Liver Transplant; It's All in the Presentation.

There is a paucity of data on nodular regenerative hyperplasia after liver transplant. We aim to define the clinical disease trajectory and identify predictors of outcome for this rare diagnosis. This is a retrospective review of postulated risk factors and outcome in patients with nodular regenerative hyperplasia. Patients were classified as having a late presentation if nodular regenerative hyperplasia was diagnosed > 48 months from transplant, and symptomatic if portal hypertensive symptoms were present. Forty-nine of 3,711 (1.3%) adult recipients developed nodular regenerative hyperplasia, and mortality was 32.7% with an average follow up of 84.6 months. The MELD-Na 6 months after diagnosis did not change significantly. Patients with symptomatic portal hypertension at the time of diagnosis had a significantly higher risk of mortality (51.8%) compared to patients with liver test abnormalities alone (10.5%). 44.9% of patients had no previously postulated risk factor. Anastomotic vascular complications do not appear to be the etiology in most patients. The results suggest the vast majority of patients presenting with liver test abnormalities alone have stable disease and excellent long term survival, in contrast to the 56.3% mortality seen in patients that present more than 48 months after LT with symptomatic portal hypertension at diagnosis.

Procurement of Deceased Donor Parathyroid Glands With the Aid of Near-infrared Autofluorescence Imaging.

Parathyroid allotransplantation is a burgeoning treatment for severe hypoparathyroidism. Deceased donor parathyroid gland (PTG) procurement can be technically challenging due to lack of normal intraoperative landmarks and exposure constraints in the neck of organ donors. In this study, we assessed standard 4-gland exposure in situ and en bloc surgical techniques for PTG procurement and ex vivo near-infrared autofluorescence (NIRAF) imaging for identification of PTGs during organ recovery. Methods: Research tissue consent was obtained from organ donors or donor families for PTG procurement. All donors were normocalcemic, brain-dead, solid organ donors between 18 and 65 y of age. PTGs were procured initially using a standard 4-gland exposure technique in situ and subsequently using a novel en bloc resection technique after systemic organ preservation flushing. Parathyroid tissue was stored at 4 °C in the University of Wisconsin solution up to 48 h post-procurement. Fluoptics Fluobeam NIRAF camera and Image J software were utilized for quantification of NIRAF signal. Results: Thirty-one brain-dead deceased donor PTG procurements were performed by abdominal transplant surgeons. In the initial 8 deceased donors, a mean of 1.75 glands (±1.48 glands SD) per donor were recovered using the 4-gland in situ technique. Implementation of combined en bloc resection with ex vivo NIRAF imaging in 23 consecutive donors yielded a mean of 3.60 glands (±0.4 SD) recovered per donor (P < 0.0001). Quantification of NIRAF integrated density signal demonstrated >1-fold log difference in PTG (2.13 × 105 pixels) versus surrounding anterior neck structures (1.9 × 104 pixels; P < 0.0001). PTGs maintain distinct NIRAF signal from the time of recovery (1.88 × 105 pixels) up to 48 h post-procurement (1.55 × 105 pixels) in organ preservation cold storage (P = 0.34). Conclusions: The use of an en bloc surgical technique with ex vivo NIRAF imaging significantly enhances the identification and recovery of PTG from deceased donors.

Biome-microbiome interactions in peri-implantitis: A pilot investigation.

BACKGROUND: Dental implants replace missing teeth in at least 100 million people, yet over one million implants fail every year due to peri-implantitis, a bacterially induced inflammatory disease. Our ability to treat peri-implantitis is hampered by a paucity of information on host-microbiome interactions that underlie the disease. Here, we present the first open-ended characterization of transcriptional events at the mucosal-microbial interface in the peri-implant crevice. METHODS: We simultaneously sequenced microbial and human mRNA from five pairs of healthy and diseased implants from the same patient and used graph theoretics to examine correlations between microbial and host gene expression in the peri-implant crevice. RESULTS: We identified a transcriptionally active peri-implant microbiome surrounding healthy implants. Microbial genes encoding phenylalanine, tyrosine, and tryptophan biosynthesis, cysteine, methionine, arginine, proline, and histidine metabolism correlated to human genes encoding cell development, metabolism, morphogenesis, adhesion, gap junctions, cell-cell signaling, and immunoinflammatory pathways, suggesting a role for commensals in protecting epithelial integrity. In disease, we found 4- to 200-fold upregulation in microbial genes encoding biofilm thickness, heme transport and utilization, and Gram-negative cell membrane synthesis. These genes correlated with mucosal zinc finger proteins, apoptosis, membrane transport, inflammation, and cell-cell communication. CONCLUSIONS: Within the limitations of a small sample size, our data suggest that microbial dysbiosis in the peri-implant sulcus might promote abandonment of host-bacterial transactions that dictate health and instead drive a move towards chronic programming of a non-healing wound.