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.

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.

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.

Probing periodontal microbial dark matter using metataxonomics and metagenomics.

Our view of the periodontal microbial community has been shaped by a century or more of cultivation-based and microscopic investigations. While these studies firmly established the infection-mediated etiology of periodontal diseases, it was apparent from the very early days that periodontal microbiology suffered from what Staley and Konopka described as the "great plate count anomaly", in that these culturable bacteria were only a minor part of what was visible under the microscope. For nearly a century, much effort has been devoted to finding the right tools to investigate this uncultivated majority, also known as "microbial dark matter". The discovery that DNA was an effective tool to "see" microbial dark matter was a significant breakthrough in environmental microbiology, and oral microbiologists were among the earliest to capitalize on these advances. By identifying the order in which nucleotides are arranged in a stretch of DNA (DNA sequencing) and creating a repository of these sequences, sequence databases were created. Computational tools that used probability-driven analysis of these sequences enabled the discovery of new and unsuspected species and ascribed novel functions to these species. This review will trace the development of DNA sequencing as a quantitative, open-ended, comprehensive approach to characterize microbial communities in their native environments, and explore how this technology has shifted traditional dogmas on how the oral microbiome promotes health and its role in disease causation and perpetuation.

Outcomes of arterial bypass preceding resection of retroperitoneal masses involving major vessels.

BACKGROUND: Current surgical management of retroperitoneal masses involving major vessels now includes complete en bloc resection with in situ venous, arterial, or combined reconstruction. No studies have investigated preresection arterial bypass for continuous lower extremity perfusion during definitive resection. Here, we characterize and compare the outcomes of surgery for retroperitoneal masses with major vascular involvement by a two-stage approach (femoral-femoral bypass preceding resection) and the traditional one-stage approach (consecutive resection and in situ vascular reconstruction). MATERIALS AND METHODS: We retrospectively reviewed patients who underwent resection of retroperitoneal masses and reconstruction of major arterial or venous structures from 2004 to 2016. Outcomes were compared with unpaired t-tests, chi-squared tests, and Kaplan-Meier analysis. RESULTS: Eight patients underwent a two-stage procedure, and seven underwent a one-stage procedure for retroperitoneal masses with vascular involvement. Mean (±SD) oncologic resection time (443 ± 215 versus 648 ± 128 min, P = 0.047) and postoperative ICU stay (0.9 ± 1.3 versus 4.4 ± 2.9 d, P = 0.018) were significantly shorter for the two-stage approach. CONCLUSIONS: To our knowledge, this is the first report of a two-stage approach for resection of retroperitoneal masses with major vessel involvement. Femoral-femoral arterial bypass before definitive resection could be a viable option for improving intraoperative vascular control and decreasing perioperative complications in these complex procedures.

Site-level risk predictors of peri-implantitis: A retrospective analysis.

AIM: The goal of the present investigation was to identify site-level factors that might allow prognostication of individual implants in partially dentate patients with multiple non-splinted restorations. METHODS: We analysed clinical and radiographic characteristics of 222 non-splinted single implants in function for at least 5 years in 86 partially dentate individuals at the time of functional loading and at follow-up, with the outcome variable being peri-implantitis. Principal component analysis identified factors contributing to greatest variability and linear discriminant analysis coupled with Random Forest Classifier used to identify risk predictors. RESULTS: After controlling for patient-level factors, the following characteristics were associated with significantly increased risk for peri-implantitis: Periodontal disease on adjoining teeth at the time of restoration (Odds Ratio (OR): 8.0), implant placement at a depth of 6 mm or more in relation to the CEJ of adjacent tooth (OR: 8.5), asymmetric prosthesis (OR: 4.3), history of tooth loss due to periodontitis (OR: 2.4) and a mean baseline plaque index of 1.6 or more (OR: 7.9). CONCLUSIONS: Our findings suggest that a system that incorporates both subject level and implant-level factors is required to effectively prognosticate the success of individual implants.

Physical and balance performance following exercise induced muscle damage in male soccer players.

[Purpose] The present study aimed to determine the changes in physical and balance performance following exercise-induced muscle damage using a sport-specific protocol. [Subjects and Methods] Fifteen collegiate soccer players were asked to perform a sport-specific sprint protocol to induce muscle damage. The markers of muscle damage (soreness, range of motion, limb girth, muscle strength, creatine kinase and lactate dehydrogenase), physical performance (speed, agility and power) and balance (static and dynamic balance) were assessed at baseline and 24, 48 and 72 hours following the sprint protocol. [Results] All variables, including the markers of muscle damage, physical performance and balance showed a significant difference when assessed at the 4 time points. [Conclusion] The study demonstrated that both the physical and balance performance were affected following repeated sprint protocol in soccer players. It is recommended the balance performance of an athlete be continually assessed following exercise-induced muscle damage so as to determine the appropriate return to sport decision thereby, minimizing the risk of further injury.

Granulysin expression increases with increasing clinical severity of psoriasis.

BACKGROUND: Psoriasis is an erythematosquamous dermatosis, which has strong expression of antimicrobial peptides (AMPs), imparting a high resistance to lesional skin infection. Granulysin is a proinflammatory AMP that has been found in some infection-resistant dermatoses. AIM: To assess granulysin expression in psoriasis. METHODS: Immunohistochemical expression of granulysin was assessed in lesional skin biopsies taken from 30 patients with psoriasis and 10 normal skin specimens from healthy controls (HCs) matched for age, gender and skin site. Granulysin expression was found to be high in 11 patients (36.7%), moderate in 10 (33.3%) and low in 9 (30%). A highly significant (P = 0.001) difference in granulysin expression between patients with psoriasis and HCs was found. There were also significant differences in granulysin expression between patients with low Psoriasis Area and Severity Index (PASI) (≤ 10) and those with high PASI (> 10) (P = 0.001), and between patients with early-onset (< 40 years of age) and those with late-onset (> 40 years of age) disease (P < 0.04). There was a significant (P = 0.001) positive correlation between granulysin expression and PASI (r = 0.84) and a significant (P = 0.02) negative correlation with age of onset (r = -0.38). Patients with psoriasis hadhigh granulysin expression, which increased with increased clinical severity of the disease. CONCLUSIONS: These findings suggest a role for granulysin in psoriasis pathogenesis, and may explain the triggering effect of skin infection in psoriasis. If the pathogenic role of granulysin is substantiated by further studies, granulysin may be a potential target for immunomodulatory therapy for psoriasis.

Interactions between Trichinella spiralis infection and induced colitis in mice.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation afflicting any part of the bowel wall as a result of a deregulated and inappropriate immune response. In recent years, experimental and clinical evidence has demonstrated that infection with parasitic worms could protect hosts from IBD. The aims of this study were to determine if the underlying mechanism of the host immune regulation inherent to Trichinella spiralis infection involves Foxp3-expressing regulatory T cells, and to gain insight about time-related interactions between intestinal nematode infection and induced colitis using an experimental model for ulcerative colitis. Mice were experimentally subjected to acetic acid-induced colitis, which was either preceded or followed by T. spiralis infection. Assessment of colitis was done by histopathological examination of the colon and determination of pentraxin 3 levels. Immunohistochemistry was done for demonstration of Foxp3-expressing regulatory T cells in colonic tissues. It was evident that T. spiralis infection ameliorated the severe inflammation induced by acetic acid, evidenced by amelioration of histopathological changes and diminution of pentraxin 3 levels. The amelioration was more pronounced when T. spiralis infection preceded the induction of colitis. Regarding the immunohistochemical staining of regulatory T cells, T. spiralis infection induced recruitment of Foxp3-expressing regulatory T cells to areas of inflammation. In conclusion, T. spiralis regulatory mechanism can improve inflammation of the colon through the 'inflammatory-regulatory' axis. Finally, it would be of great importance to apply these results to the development of new therapeutic approaches for the treatment of ulcerative colitis.

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.

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.

The Mohs histotechnician: a review of training and practice within 29 centres in the UK.

BACKGROUND: Although various assessments pertaining to the surgical aspect of Mohs micrographic surgery (MMS) have been performed, the pivotal role played by the MMS histotechnician (MH) has not previously been addressed in the UK. AIM: To undertake a review of the training and practice of MHs in all centres performing MMS within the National Health Service (NHS) in the UK. METHODS: NHS dermatology departments performing MMS in the UK were identified and contacted by telephone between November 2011 and January 2012. MMS practice data pertaining to the role of the MH in tissue processing was collected by speaking directly to a histotechnician in each department. RESULTS: In total, 29 centres were identified. The number of MHs at each centre varied from 1 to 13 (median 3). All MHs had undergraduate degrees in biomedical science. Most (85%) MHs worked full-time under the directorate of their local pathology department. In 19 centres (66%), the Mohs surgeon reviewed the slides, and in the remaining 10 centres (34%), a consultant histopathologist reviewed the slides, either alone or in partnership with the Mohs surgeon. There was significant variation in tissue handling and processing techniques across the centres. All centres used MMS to treat primarily high-risk basal cell carcinomas, with over half (55%) also treating squamous cell carcinomas. MHs from all centres had learned about the specifics of MMS tissue processing 'on the job', with a minority having received formal training by attending a larger MMS centre or an MMS course. CONCLUSIONS: Significant variation in MMS tissue-processing techniques exists across the UK. A standard of practice should perhaps be considered, as this has risk-management, quality-control and possible medicolegal implications.

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.

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.

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.

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.

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.