Non-invasive pulse arrival time is associated with cardiac index in pediatric heart transplant patients with normal ejection fraction.

OBJECTIVE: Cardiac Index (CI) is a key physiologic parameter to ensure end organ perfusion in the pediatric intensive care unit (PICU). Determination of CI requires invasive cardiac measurements and is not routinely done at the PICU bedside. To date, there is no gold standard non-invasive means to determine CI. This study aims to use a novel non-invasive methodology, based on routine continuous physiologic data, called Pulse Arrival Time (PAT) as a surrogate for CI in patients with normal Ejection Fraction. Approach: Electrocardiogram (ECG) and photoplethysmogram (PPG) signals were collected from beside monitors at a sampling frequency of 250 samples per second. Continuous PAT, derived from the ECG and PPG waveforms was averaged per patient. Pearson's correlation coefficient was calculated between PAT and CI, PAT and heart rate (HR), and PAT and ejection fraction (EF). Main Results: Twenty patients underwent right heart cardiac catheterization. The mean age of patients was 11.7±5.4 years old, ranging from 11 months old to 19 years old, the median age was 13.4 years old. HR in this cohort was 93.8±17.0 beats per minute. The average EF was 54.4±9.6%. The average CI was 3.51±0.72 L/min/m2, with ranging from 2.6 to 4.77 L/min/m2. The average PAT was 0.31±0.12 seconds. Pearson correlation analysis showed a positive correlation between PAT and CI (0.57, p < 0.01). Pearson correlation between HR and CI, and correlation between EF and CI was 0.22 (p = 0.35) and 0.03 (p = 0.23) respectively. The correlation between PAT, when indexed by HR (i.e. PAT × HR), and CI minimally improved to 0.58 (p < 0.01). Significance: This pilot study demonstrates that PAT may serve as a valuable surrogate marker for CI at the bedside, as a non-invasive and continuous modality in the PICU. The use of PAT in clinical practice remains to be thoroughly investigated. .

Metacognitive bias resulting from trade-off between local and global motion signals.

Visual confidence generally depends on performance in targeted perceptual tasks. However, it remains unclear how factors unrelated to performance affect confidence. Given the hierarchical nature of visual processing, both local and global stimulus features can influence confidence, but their strengths of influence remain unknown. To address this question, we independently manipulated the local contrast signals and the global coherence signals in a multiple-aperture motion pattern. The drifting-Gabor elements were individually manipulated to give rise to a coherent global motion percept. In both dichotomous direction-discrimination task (Experiment 1) and analog direction-judgment task (Experiment 2), we found stimulus-dependent biases in metacognition despite matched perceptual performance. Specifically, participants systematically gave higher confidence ratings to an incoherent pattern with clear elements (i.e., strong local but weak global signals) than a coherent pattern with noisy elements (i.e., weak local but strong global signals). We did not find any systematic effects of local/global stimulus features on metacognitive sensitivity. Model comparisons show that variation in local/global signals in the stimulus should be considered a factor influencing confidence, even after controlling for the effects of performance. Our results suggest that the metacognitive system, when generating confidence for a perceptual task, puts more weights on local than global signals.

Repurposing a SARS-CoV-2 surveillance program for infectious respiratory diseases in a university setting.

Standard multiplex RT-qPCR diagnostic tests use nasopharyngeal swabs to simultaneously detect a variety of infections, but commercially available kits can be expensive and have limited throughput. Previously, we clinically validated a saliva-based RT-qPCR diagnostic test for SARS-CoV-2 to provide low-cost testing with high throughput and low turnaround time on a university campus. Here, we developed a respiratory diagnostic panel to detect SARS-CoV-2, influenza A and B within a single saliva sample. When compared to clinical results, our assay demonstrated 93.5% accuracy for influenza A samples (43/46 concordant results) with no effect on SARS-CoV-2 accuracy or limit of detection. In addition, our assay can detect simulated coinfections at varying virus concentrations generated from synthetic RNA controls. We also confirmed the stability of influenza A in saliva at room temperature for up to 5 days. The cost of the assay is lower than standard nasopharyngeal swab respiratory panel tests as saliva collection does not require specialized swabs or trained clinical personnel. By repurposing the lab infrastructure developed for the COVID-19 pandemic, our multiplex assay can be used to provide expanded access to respiratory disease diagnostics, especially for community, school, or university testing applications where saliva testing was effectively utilized during the COVID-19 pandemic.

Enhancing Lung Cancer Classification through Integration of Liquid Biopsy Multi-Omics Data with Machine Learning Techniques.

Early detection of lung cancer is crucial for patient survival and treatment. Recent advancements in next-generation sequencing (NGS) analysis enable cell-free DNA (cfDNA) liquid biopsy to detect changes, like chromosomal rearrangements, somatic mutations, and copy number variations (CNVs), in cancer. Machine learning (ML) analysis using cancer markers is a highly promising tool for identifying patterns and anomalies in cancers, making the development of ML-based analysis methods essential. We collected blood samples from 92 lung cancer patients and 80 healthy individuals to analyze the distinction between them. The detection of lung cancer markers Cyfra21 and carcinoembryonic antigen (CEA) in blood revealed significant differences between patients and controls. We performed machine learning analysis to obtain AUC values via Adaptive Boosting (AdaBoost), Multi-Layer Perceptron (MLP), and Logistic Regression (LR) using cancer markers, cfDNA concentrations, and CNV screening. Furthermore, combining the analysis of all multi-omics data for ML showed higher AUC values compared with analyzing each element separately, suggesting the potential for a highly accurate diagnosis of cancer. Overall, our results from ML analysis using multi-omics data obtained from blood demonstrate a remarkable ability of the model to distinguish between lung cancer and healthy individuals, highlighting the potential for a diagnostic model against lung cancer.

Improving CNV Detection Performance in Microarray Data Using a Machine Learning-Based Approach.

Copy number variation (CNV) is a primary source of structural variation in the human genome, leading to several disorders. Therefore, analyzing neonatal CNVs is crucial for managing CNV-related chromosomal disabilities. However, genomic waves can hinder accurate CNV analysis. To mitigate the influences of the waves, we adopted a machine learning approach and developed a new method that uses a modified log R ratio instead of the commonly used log R ratio. Validation results using samples with known CNVs demonstrated the superior performance of our method. We analyzed a total of 16,046 Korean newborn samples using the new method and identified CNVs related to 39 genetic disorders were identified in 342 cases. The most frequently detected CNV-related disorder was Joubert syndrome 4. The accuracy of our method was further confirmed by analyzing a subset of the detected results using NGS and comparing them with our results. The utilization of a genome-wide single nucleotide polymorphism array with wave offset was shown to be a powerful method for identifying CNVs in neonatal cases. The accurate screening and the ability to identify various disease susceptibilities offered by our new method could facilitate the identification of CNV-associated chromosomal disease etiologies.

An Isochroman Analog of CD3254 and Allyl-, Isochroman-Analogs of NEt-TMN Prove to Be More Potent Retinoid-X-Receptor (RXR) Selective Agonists Than Bexarotene.

Bexarotene is an FDA-approved drug for the treatment of cutaneous T-cell lymphoma (CTCL); however, its use provokes or disrupts other retinoid-X-receptor (RXR)-dependent nuclear receptor pathways and thereby incites side effects including hypothyroidism and raised triglycerides. Two novel bexarotene analogs, as well as three unique CD3254 analogs and thirteen novel NEt-TMN analogs, were synthesized and characterized for their ability to induce RXR agonism in comparison to bexarotene (1). Several analogs in all three groups possessed an isochroman ring substitution for the bexarotene aliphatic group. Analogs were modeled for RXR binding affinity, and EC50 as well as IC50 values were established for all analogs in a KMT2A-MLLT3 leukemia cell line. All analogs were assessed for liver-X-receptor (LXR) activity in an LXRE system to gauge the potential for the compounds to provoke raised triglycerides by increasing LXR activity, as well as to drive LXRE-mediated transcription of brain ApoE expression as a marker for potential therapeutic use in neurodegenerative disorders. Preliminary results suggest these compounds display a broad spectrum of off-target activities. However, many of the novel compounds were observed to be more potent than 1. While some RXR agonists cross-signal the retinoic acid receptor (RAR), many of the rexinoids in this work displayed reduced RAR activity. The isochroman group did not appear to substantially reduce RXR activity on its own. The results of this study reveal that modifying potent, selective rexinoids like bexarotene, CD3254, and NEt-TMN can provide rexinoids with increased RXR selectivity, decreased potential for cross-signaling, and improved anti-proliferative characteristics in leukemia models compared to 1.

Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go.

The introduction of immune checkpoint inhibitors (ICIs) represents a key shift in the management strategy for patients with hepatocellular carcinoma (HCC). However, there is a paucity of predictive biomarkers that facilitate the identification of patients that would respond to ICI therapy. Although several researchers have attempted to resolve the issue, the data is insufficient to alter daily clinical practice. The use of minimally invasive procedures to obtain patient-derived specimen, such as using blood-based samples, is increasingly preferred. Circulating tumor DNA (ctDNA) can be isolated from the blood of cancer patients, and liquid biopsies can provide sufficient material to enable ongoing monitoring of HCC. This is particularly significant for patients for whom surgery is not indicated, including those with advanced HCC. In this review, we summarize the current state of understanding of blood-based biomarkers for ICI-based therapy in advanced HCC, which is promising despite there is still a long way to go.

Simultaneous Sigmoid Volvulus and Small Bowel Obstruction: A Case Report.

Sigmoid volvulus and small bowel obstruction are typically thought to be separate clinical pathologies with distinct clinical features, diagnostic criteria, and treatment strategies. We present a rare case of simultaneous sigmoid volvulus and small bowel obstruction. To our knowledge, this is the first such case in literature and presented a unique set of challenges in regard to treatment and management. This case discusses a different approach to the surgical management of sigmoid volvulus and small bowel obstruction, which is markedly different from the expected and traditional surgical management of isolated sigmoid volvulus and small bowel obstruction.

Glucose Mediates Niche-Specific Repression of Staphylococcus aureus Toxic Shock Syndrome Toxin-1 through the Activity of CcpA in the Vaginal Environment.

Staphylococcus aureus chronically colonizes up to 30% of the human population on the skin or mucous membranes, including the nasal tract or vaginal canal. While colonization is often benign, this bacterium also has the capability to cause serious infections. Menstrual toxic shock syndrome (mTSS) is a serious toxinosis associated with improper use of tampons, which can induce an environment that is favorable to the production of the superantigen known as toxic shock syndrome toxin-1 (TSST-1). To better understand environmental signaling that influences TSST-1 production, we analyzed expression in the prototype mTSS strain S. aureus MN8. Using transcriptional and protein-based analysis in two niche-related media, we observed that TSST-1 expression was significantly higher in synthetic nasal medium (SNM) than in vaginally defined medium (VDM). One major divergence in medium composition was high glucose concentration in VDM. The glucose-dependent virulence regulator gene ccpA was deleted in MN8, and, compared with wild-type MN8, we observed increased TSST-1 expression in the ΔccpA mutant when grown in VDM, suggesting that TSST-1 is repressed by catabolite control protein A (CcpA) in the vaginal environment. We were able to relieve CcpA-mediated repression by modifying the glucose level in vaginal conditions, confirming that changes in nutritional conditions contribute to the overexpression of TSST-1 that can lead to mTSS. We also compared CcpA-mediated repression to other key regulators of tst, finding that CcpA regulation is dominant compared to other characterized regulatory mechanisms. This study underlines the importance of environmental signaling for S. aureus pathogenesis in the context of mTSS. IMPORTANCE Menstrual toxic shock syndrome (mTSS) is caused by strains of Staphylococcus aureus that overproduce a toxin known as toxic shock syndrome toxin-1 (TSST-1). This work studied how glucose levels in a model vaginal environment could influence the amount of TSST-1 that is produced by S. aureus. We found that high levels of glucose repress TSST-1 production, and this is done by a regulatory protein called catabolite control protein A (CcpA). The research also demonstrated that, compared with other regulatory proteins, the CcpA regulator appears to be the most important for maintaining low levels of TSST-1 in the vaginal environment, and this information helps to understand how changes in the vaginal environmental can lead to mTSS.

14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing.

Recent studies demonstrate that α cells contribute to glucose-stimulated insulin secretion (GSIS). Glucagon-like peptide-1 receptor (GLP-1R) agonists potently potentiate GSIS, making these drugs useful for diabetes treatment. However, the role of α and ß cell paracrine interactions in the effects of GLP-1R agonists is undefined. We previously found that increased ß cell GLP-1R signaling activates α cell GLP-1 expression. Here, we characterized the bidirectional paracrine cross-talk by which α and ß cells communicate to mediate the effects of the GLP-1R agonist, liraglutide. We find that the effect of liraglutide to enhance GSIS is blunted by α cell ablation in male mice. Furthermore, the effect of ß cell GLP-1R signaling to activate α cell GLP-1 is mediated by a secreted protein factor that is regulated by the signaling protein, 14-3-3-zeta, in mouse and human islets. These data refine our understanding of GLP-1 pharmacology and identify 14-3-3-zeta as a potential target to enhance α cell GLP-1 production.

The Impact of eConsults on Access to Specialty Care for the Uninsured in Rural Texas.

OBJECTIVE: This study evaluated the impact of eConsults on access to specialty care for uninsured patients in Central Texas. METHODS: eConsults for four specialties, cardiology, gastroenterology, rheumatology, and endocrinology, were implemented in a large, multi-site federally qualified health center. Data were collected on specialty care access and utilization for a one-year period before and after implementation of the new process. RESULTS: Prior to implementation, 23% of uninsured patients referred to the included specialties completed a visit with a specialist. After implementation, 62% received a specialty consultation either through an eConsult or with a face-to-face visit. Wait times for referrals improved from a median of 54 days to seven days. CONCLUSION: This project demonstrated that eConsults improve access and reduce wait times for specialty care for uninsured patients. Interventions such as this have the potential to reduce health inequalities by providing timely access to care for common specialty concerns.

Differences in Attitudes of Front-Line Clinicians, Healthcare Workers, and Non-Healthcare Workers Toward COVID-19 Safety Protocols.

Background The advent of the coronavirus disease 2019 (COVID-19) has generated varying opinions toward adhering to safety protocols among public health experts. With decreasing restrictions on public gatherings, lax protective behaviors, distortion of facts, and increasing availability of COVID-19 vaccines, response to public health guidelines vary greatly. Personal experiences with COVID-19, education, and work environment may influence decisions on safety recommendations and vaccination protocols among the public and healthcare professionals alike. To better understand how individuals process and make decisions regarding COVID-19 safety measures, this study investigated the attitudes among clinical and non-clinical healthcare workers and non-healthcare workers toward COVID-19 safety protocols. Methodology Cross-sectional data were collected from Florida residents using an online, 20-item anonymous questionnaire. Participants were recruited using the Florida Department of Health database for physician emails, social media, and snowball sampling strategies. The survey consisted of demographic items and questions regarding patient attitudes toward safety protocols for COVID-19 (e.g., likeliness to wear a mask in public despite state regulations being lifted, maintaining a distance of at least 6 feet between close friends and family, dining at restaurants/bars, gathering in groups larger than 10 people, getting a COVID-19 vaccine if one becomes available). Data were analyzed using one-way analysis of variance and chi-square test using SPSS version 27 (IBM Corp., Armonk, NY, USA). Results Of the 373 participants who completed the survey, 183 (49.1%) worked in the healthcare field, with 100 (28.6%) providing direct patient care. The rest (n = 190; 50.9%) reported that they do not work in the healthcare industry. Findings suggest that those working in healthcare with direct involvement in patient care were more likely to get the COVID-19 vaccine than those not working in healthcare. Additionally, those working in healthcare and providing direct patient care were more likely to think that masks were effective in reducing the spread of COVID-19 compared to those who worked in healthcare but did not provide direct patient care. Conclusions This study provides new insights into the attitudes of front-line clinicians, non-clinical healthcare workers, and the general population. Increasing health promotion efforts and debunking myths about COVID-19 may prove useful in mitigating the spread of the disease.

Single-Laboratory Validation Study of a Rapid TD-NMR Method for Quantitation of Total Fat in Sunflower Oil Powder.

BACKGROUND: A rapid total fat quantitation method for sunflower oil powder was developed using time-domain nuclear magnetic resonance (TD-NMR). Currently, industry has three major methods for the total fat quantitation: gravimetric analysis after ether extraction (AOAC Methods 933.05 and 989.05), gas chromatography with flame ionization detector (GC-FID; AOAC Method 996.06), and High-resolution NMR. The gravimetric analysis method takes a day using highly flammable solvents, and the GC-FID method takes two days requiring harsh chemicals for hydrolyzation, extraction, and methylation. The High-resolution NMR spectroscopy method requires simpler sample preparation and shorter analysis time compared to the other two methods. Often, the only required sample preparation step is to dissolve a sample in a solvent. The acquisition time depends on types of analyzing nuclei and sample. The vegetable oil analysis by 13C NMR takes about 4 h per sample. 1H NMR usually takes less time to analyze. In contrast, the TD-NMR relaxometry method takes only 1 h to prepare and analyze samples if the test is for total fat only. The acquisition time is 40 s per sample, and samples are analyzed "as is". A rapid analysis method in a quality control laboratory is very crucial for laboratory efficiency in releasing products. In this paper, a single-laboratory validation study is described for a rapid TD-NMR method to quantitate total fat in sunflower oil powder. OBJECTIVE: This validation work is to provide documented evidence for the method validity as well as the method performance. METHOD: The method used a Bruker minispec mq-20 NMR analyzer® with minispec plus® software. A Hahn echo pulse program was used in the method to collect spin echo signal to determine total fat content. RESULTS: The linearity/range result from 10 standards (0, 21, 42, 63, 83, 92, 100, 108, 117, and 125%) has coefficients of determination (R2) of 1.0000. The 100% level is 1.2 g-fat in 2.5 g sample, which is targeted fat content in a sunflower oil powder raw material. The method is specific for the quantitation of total fat in sunflower oil powder with no background interference from the matrix. The precision result of the 6 replicate samples at 100% level is 0.3% RSD. The accuracies measured from triplicate analysis of 80, 100, and 120% sample matrices are 100, 100, and 100% average recoveries, respectively. The ruggedness of the test method is 0.4% RSD of 12 analysis from 2 analysts (6 results from each analyst) on the different days. CONCLUSIONS: The test method is proven to be specific, linear, precise, accurate, rugged, and suitable for the intended use of quantitative analysis for total fat in sunflower oil powder. HIGHLIGHTS: Traditional methods of gravimetric or GC-FID for total fat analysis of raw materials require lengthy sample preparation and experiment time. Laboratory needs to spend a day to perform gravimetric analysis following ether extraction method and 2 days for the GC-FID method. In addition, these test methods use highly flammable and harsh chemicals that generate hazardous chemical wastes. These hazardous wastes are harmful to analysts and environments. In contrast, the TD-NMR method is safe, environmentally friendly, and fast. Therefore, TD-NMR is a preferred method for quality control laboratories.

GLP-1 receptor signaling increases PCSK1 and ß cell features in human α cells.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates glucose-stimulated insulin secretion. GLP-1 is classically produced by gut L cells; however, under certain circumstances α cells can express the prohormone convertase required for proglucagon processing to GLP-1, prohormone convertase 1/3 (PC1/3), and can produce GLP-1. However, the mechanisms through which this occurs are poorly defined. Understanding the mechanisms by which α cell PC1/3 expression can be activated may reveal new targets for diabetes treatment. Here, we demonstrate that the GLP-1 receptor (GLP-1R) agonist, liraglutide, increased α cell GLP-1 expression in a ß cell GLP-1R-dependent manner. We demonstrate that this effect of liraglutide was translationally relevant in human islets through application of a new scRNA-seq technology, DART-Seq. We found that the effect of liraglutide to increase α cell PC1/3 mRNA expression occurred in a subcluster of α cells and was associated with increased expression of other ß cell-like genes, which we confirmed by IHC. Finally, we found that the effect of liraglutide to increase bihormonal insulin+ glucagon+ cells was mediated by the ß cell GLP-1R in mice. Together, our data validate a high-sensitivity method for scRNA-seq in human islets and identify a potentially novel GLP-1-mediated pathway regulating human α cell function.

Trends in bariatric surgery in Texas: an analysis of a statewide administrative database 2013-2017.

BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) tracks 30-day outcomes of bariatric patients, but only at accredited centers. Presently, these cases are not broken down by state. Administrative databases can be used to answer some of the questions that are not asked by clinical databases and also to validate those databases. We proposed using the inpatient and outpatient administrative databases in Texas to examine both the numbers and trends of bariatric surgery in Texas over a 5-year period. METHODS: The Texas Inpatient Public Use Data File (IPUDF) and the Texas Outpatient Public Data File (OPUDF) were examined for the years 2013-2017. We searched for patients undergoing laparoscopic adjustable gastric banding (LAGB), sleeve gastrectomy (SG), laparoscopic Roux-en-Y gastric bypass (LRYGB) and duodenal switch. Robotic assisted cases were also examined. RESULTS: There were 105,199 bariatric cases performed in Texas from 2013 to 2017. There were 173 centers performing bariatric surgery. The most common operation performed was the sleeve gastrectomy at 73,663 case (70% of total). Gastric bypasses were second at 22,890 cases. During this time period, LAGB almost disappeared; dropping from 2090 cases in 2013 to 115 cases in 2017, with removal of 2097 LAGB in the study period in the OPUDF. During this time period, there was a lower growth rate of the number of SG in the IPUDF with a large increase in SG performed with outpatient status, while LRYGB remained relatively stable. CONCLUSION: Rates of bariatric surgery in Texas are increasing slowly. The dominant procedure is the SG with a trend towards being done under outpatient status. LAGB has been essentially phased out. There is an increase in SG being performed under 'outpatient' status.

Single-Laboratory Validation Study of a Proton NMR Method for the Determination of L-Arginine, L-Citrulline, and Taurine Contents in Dietary Supplements.

BACKGROUND: A quantitative NMR (qNMR) method can provide rapid analysis compared to chromatographic methods. Sample preparation steps are relatively simpler and run time is shorter. Rapid analysis methods for release tests in quality control laboratories are very important for laboratory efficiency. Here, we describe a single-laboratory validation study for a rapid qNMR analysis of L-arginine, L-citrulline, and taurine in powdered and tablet dietary supplement products. OBJECTIVES: This validation work is to provide documented evidence for the qNMR method validity as well as method performance. METHODS: The method used Bruker 400 MHz high-resolution proton NMR spectroscopy for simultaneous determination of L-arginine, L-citrulline, and taurine contents in dietary supplement product 1 (powder) and dietary supplement product 2 (tablet). The absolute NMR quantitation is based on a principle of universal proton response intensity correlation with the number of protons in each target analyte (amino acids) vs. that of a reference standard (maleic acid). RESULTS: The test method performance was validated with dietary supplement-1 (powder) and dietary supplement-2 (tablet). The linearity of the method was studied from about 360 mg/g to about 675 mg/g of L-arginine; from about 15 mg/g to about 30 mg/g of L-citrulline; and from about 20 mg/g to about 40 mg/g of taurine in dietary supplement-1, and from about 15 mg/g to about 30 mg/g of taurine in dietary supplement-2. The coefficients of determination (R2) are 1.0000 for L-arginine, 0.9967 for L-citrulline, and 0.9995 for taurine in dietary supplement-1 and 0.9903 for taurine in dietary supplement-2. The accuracies measured from the sample matrices are 102%, 101%, and 100% average recoveries for 80%, 100%, and 120% concentration levels of L-arginine, 105%, 105%, and 103% average recoveries for 80%, 100%, and 120% concentration level of L-citrulline, and 101%, 102%, and 100% average recoveries of taurine for 80%, 100%, 120% concentration levels in dietary supplement-1; and 95, 98%, and 93% average recoveries of taurine for 80%, 100%, 120% concentration levels in dietary supplement-2, respectively. The precisions (RSD) are 1% for L-arginine, 5% for L-citrulline, and 2% for taurine in dietary supplement -1, respectively; and 4% for taurine in dietary supplement-2. The ruggedness of the test method is within 2%, 4%, and 2% for L-arginine, L-citrulline, and taurine for dietary supplement -1, respectively, and within 4% for dietary supplement-2. The method is specific for the quantitation of each nutrient with no background interference from the matrix for the proton peaks of L-arginine, L-citrulline, taurine, and maleic acid (standard). CONCLUSIONS: The test method is proven to be specific, precise, accurate, rugged, and suitable for intended quantitative analysis of L-arginine, L-citrulline, and taurine in powdered and tablet finished products. HIGHLIGHTS: The simultaneous determination of all three nutrients of L-arginine, L-citrulline, and taurine using proton NMR provides rapid analysis for quality control release tests that is more efficient versus that of two HPLC methods. Previously, our laboratory was using one HPLC method to analyze L-arginine and L-citrulline while using a second HPLC method to analyze taurine. That approach required two HPLC instruments and two analysts for parallel analysis that takes 2 days using volatile and flammable solvents for extraction and chemical derivatization. This rapid NMR method can analyze the sample "as is" with results obtained in less than 4 h, and is efficient, safe, and environmentally friendly. The initial higher NMR instrument investment versus two HPLC instruments is rewarded with high returns for continued quality control tests.

The effects of diploid male production on honey bee colony evolution and survival.

The order Hymenoptera includes most of the eusocial species on the planet. Correlated is the fact that many of the social species within the order are haplodiploid and use complementary sex determination (CSD) to determine the sex of offspring. CSD is the mechanism by why single sex alleles within an organism result in male development (haploid) and mismatched sex alleles develop into females (diploids). Related to this is the production of diploid males: fertilized eggs with matched sex alleles which develop as male instead of female. Honey bees are no exception to this, and as their numbers continue to suffer globally and their genetic diversity lowers, the effects of diploid male production (DMP) may pose an increased risk to the survival of bee colonies. In the present study, we develop a model for diploid male production in a honey bee colony and show that with ample resources, this phenomena has little effect on a colony's health, but there is a limit to the sustainability of a colony suffering from diploid male production. We use our model to show that there were likely no great evolutionary pressures against CSD and DMP in wild honey bees as its effects on colony health in the wild would have been negligible but increased environmental hazards such as pesticides and monoculture crops increase the effects of DMP on colony health.

Are Concomitant Operations During Bariatric Surgery Safe? An Analysis of the MBSAQIP Database.

INTRODUCTION: The American College of Surgeons tracks 30-day outcomes using the Metabolic and Bariatric Surgery Accreditation Quality Initiative Program (MBSAQIP) database. We examined the short-term outcomes of patients that undergo bariatric surgery concomitantly with other operations such as hernia repairs and cholecystectomy to determine the safety of this practice. METHODS: The MBSAQIP Participant Use Data File for 2015-2017 was examined for differences in primary bariatric operations vs concomitant procedures (CP). We looked for concurrent CPT codes for laparoscopic cholecystectomy (LC) and hernia repairs (ventral, epigastric, incisional, and inguinal). p was significant at < 0.05. RESULTS: There were 464,674 cases, of which 15,614 had CP. For both LRYGB+LC and SG+LC, there were increased operative times and length of stay. There were statistically significant higher rates of readmission, reintervention, and reoperation for SG+LC vs SG alone, as well as for LRYGB+hernia and SG+hernia. There was a higher risk of death (p < 0.001) in LRYGB+hernia patients. Also, LRYGB+hernia patients had statistically significant increases in unplanned admission to the intensive care unit and pulmonary embolus. SG+hernia patients had a higher rate of ventilation > 48 h, unplanned admission to the ICU, pulmonary embolism, deep vein thrombosis, and readmission, reintervention, and reoperation. CONCLUSIONS: There is a statistically higher rate of complications with concomitant procedures in the MBSAQIP database. Length of stay and operative times are increased in concomitant operations as are readmissions, reinterventions, and reoperations. These findings would indicate that additional procedures at the time of bariatric surgery should be deferred if possible.

How many sleeve gastrectomies are done at nonaccredited centers in Texas?

BACKGROUND: The American College of Surgeons created the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) to improve the safety of surgery and track outcomes of patients undergoing metabolic and bariatric surgery. The MBSAQIP captures all surgical procedures performed at accredited centers (AC) but not all metabolic and bariatric surgery cases performed in the United States. Texas has a large statewide administrative database that tracks nearly all surgical procedures performed in the state and we proposed using this database to assess the number of sleeve gastrectomies (SG) and whether they were performed at an AC or not. OBJECTIVE: Our objective was to determine the percentage of SG that are performed in MBSAQIP ACs. SETTING: University surgical department, United States. METHODS: The Texas Inpatient and Outpatient Public Use Data Files (PUDF) for the year 2017 were examined. We used the Current Procedural Terminology and International Classification of Diseases version 10 codes for SG, 43775 and 0 DB64 Z3, respectively. We compared the PUDF facility list to a list of MBSAQIP ACs in Texas. RESULTS: There were 4549 SG performed in Texas in 2017 reported in the Outpatient PUDF. Of these, 80.8% of cases were performed at ACs. Of the 136 facilities in the outpatient PUDF performing SG, 58 were MBSAQIP accredited. In the Inpatient PUDF for 2017 there were 11,287 SG, of which 9829 (87%) were performed at ACs. Of 153 centers performing SG, 77 were MBSAQIP accredited. There was a higher percentage of adjustable band conversions to SG at non-ACs in the Outpatient PUDF than the Inpatient PUDF. CONCLUSION: The MBSAQIP database is missing almost 20% of outpatient SG performed in Texas and 13% of inpatient SG. Administrative databases can be used to externally validate the MBSAQIP.

Lactobacillus salivarius BP121 prevents cisplatin­induced acute kidney injury by inhibition of uremic toxins such as indoxyl sulfate and p­cresol sulfate via alleviating dysbiosis.

The gut microbiota is important for maintaining the integrity of the intestinal barrier, promoting immunological tolerance and carrying out metabolic activities that have not evolved in hosts. Intestinal dysbiosis is associated with chronic kidney disease and probiotic supplementation has been shown to be beneficial. However, it is not known whether gut microorganisms­specifically, lactic acid bacteria (LAB) can protect against acute kidney injury (AKI). To address this issue, the present study investigated the effects of Lactobacillus salivarius BP121, an intestinal LAB isolated from the feces of newborns, in a rat model of cisplatin­induced AKI and also in Caco­2 human intestinal epithelial cells. BP121 prevented cisplatin­induced AKI in rats, as demonstrated by decreases in inflammation and oxidative stress in kidney tissue and in serum levels of uremic toxins such as indoxyl sulfate (IS) and p­cresol sulfate (PCS). BP121 also reduced intestinal permeability, as determined using fluorescein isothiocyanate­dextran by immunohistochemical detection of tight junction (TJ) proteins such as zona occludens­1 and occludin. The abundance of Lactobacillus spp., which are beneficial intestinal flora, was increased by BP121; this was accompanied by an increase in the concentrations of short­chain fatty acids in feces. Additionally, H2O2­induced TJ protein damage was reduced in Caco­2 cells treated with BP121 culture supernatant, an effect that was reversed by the 5' AMP­activated protein kinase (AMPK) inhibitor Compound C and Toll­like receptor (TLR)4 inhibitor TLR4­IN­C34. In conclusion, this study demonstrated that L. salivarius BP121 protects against cisplatin­induced AKI by decreasing inflammation and oxidative stress and this renoprotective effect is partially mediated by modulating the gut environment and thereby suppressing IS and PCS production as well as by regulating AMPK and TLR4 dependent TJ assembly.