Arsenic speciation analysis in human urine for long term epidemiological studies: The Multi-Ethnic Study of Atherosclerosis (MESA).

Arsenic is a ubiquitous toxic metalloid causing serious health problems. Speciation analysis of arsenic in human urine provides valuable insights for large-scale epidemiological studies and informs on sources of exposure as well as human metabolism. The Multi-Ethnic Study of Atherosclerosis (MESA) is a valuable cohort for assessing chronic low-moderate arsenic exposure and health effects in an ethnically diverse US population. We present a state-of-the-art arsenic speciation analysis methodology and its application to 7677 MESA spot urine samples based on high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry. This method is fast, robust and detects a total of 11 individual As species at method detection limits of 0.02-0.03 µg arsenic/L urine for each individual species. Our analytical approach features excellent mean method accuracy (98%) and precision (5%) for the main arsenic species in urine (arsenobetaine, methylarsonic acid, dimethylarsinic acid, and total inorganic As); intra- (3-6%) and inter-day coefficients of variability (5-6%); column recovery (96 ± 7%); and spike recovery (97 ± 6%). The main arsenic species were detectable in ≥95% of urine samples due to the implementation of an oxidation step. Each individual minor arsenic species was detectable in ≤25% of all urines, although at least one of them was detected in almost half the participants. We identified two minor urinary arsenic species as dimethylarsinoylacetic acid and dimethylarsinoylpropionic acid, potential metabolites of seafood-related arsenicals. We observed differences in individual As species excretion by race/ethnicity, with Asian-American participants featuring 3-4 times higher concentrations compared to other participants. We also found differences by site, body mass index, smoking status, rice intake, and water arsenic levels, potentially indicating different exposures or related to individual bio-metabolism. The proposed approach is suitable for epidemiological studies and the collected data will constitute the base for future research on potential health effects of chronic low-level arsenic exposure.

Efficacy of locoregional analgesic techniques after laparotomy for gynecologic cancer: a systematic review.

OBJECTIVE: To determine which locoregional techniques are effective in managing post-operative pain in major open oncologic gynecologic surgery in terms of pain scores and opioid consumption when epidural analgesia is not a feasible option. METHODS: A systematic review of the literature, based on the Preferred Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, was conducted. The ROB-2 assessment was used to assess bias. The primary outcomes were opioid consumption and post-operative pain scores. Secondary outcomes included post-operative markers such as time to mobilization and bowel movement. RESULTS: A total of nine studies (n=714) were included in the analysis. Eight studies had a low risk of bias. Five different forms of locoregional analgesia were described. Eight studies compared with placebo and one study compared rectus sheath block with epidural analgesia. Three of the five studies investigating transversus abdominis plane (TAP) blocks showed an improvement in pain scores and opioid consumption when compared with the placebo group. One study investigating rectus sheath blocks and another investigating paravertebral blocks demonstrated significantly less opioid consumption and improved pain scores at certain time points. The studies investigating continuous wound infiltration and superior hypogastric plexus block found no significant effect. No adverse effects of locoregional anesthesia were found. CONCLUSION: Our study showed that TAP blocks, rectus sheath blocks, and paravertebral blocks may decrease opioid consumption and improve pain scores in patients undergoing open abdominal surgery for gynecologic cancer. Additionally, these techniques might serve as a viable alternative for patients with contraindications to epidural analgesia.

Reporting Bias in the Form of Positive Spin Is Highly Prevalent in Abstracts of Systematic Reviews on Primary Repair of the Anterior Cruciate Ligament.

PURPOSE: To analyze reporting bias in the form of spin present in systematic reviews and meta-analyses on the topic of primary anterior cruciate ligament (ACL) repair. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed throughout this study. Peer-reviewed systematic reviews were collected from 3 databases (PubMed, Scopus, and SPORTDiscus), and their abstracts were assessed for the 15 most common types of spin. Articles were excluded if they were not published in English, had no evidence, were retracted, were published without an abstract, did not have full text available, or included cadaveric or nonhuman subjects. Full text quality was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews Version 2). Fisher exact tests were used to examine associations between the different types of spin and other study characteristics such as AMSTAR 2 confidence rating, study design, and level of evidence. RESULTS: Spin was present in the abstracts of 13 of 15 articles (86.7%). There were significant associations between PRISMA adherence and lower incidences of spin types 3, 6, and 8 (P = .029 for each). A critically low AMSTAR 2 confidence rating was significantly associated with an increased incidence of spin type 9 (P = .01), and a higher AMSTAR 2 score was significantly associated with decreased spin type 4 and type 5 (P = .039 and P = .048, respectively). A more recent year of publication was correlated with a lower incidence of spin type 14 (P = .044). CONCLUSIONS: Spin is present in most systematic reviews and meta-analyses regarding primary repair of the ACL, with two-thirds of abstracts spinning evidence in favor of ACL repair. Standardized guidelines including the PRISMA guidelines and the AMSTAR 2 assessment tool were negatively correlated with spin. More recently published articles were found to contain significantly less spin, as were articles published in journals with higher Clarivate Impact Factors and Scopus CiteScores. LEVEL OF EVIDENCE: Level V, systematic review of Level III through V studies.

Shoulder arthroplasty for inflammatory arthritis is associated with higher rates of medical and surgical complications: a nationwide matched cohort analysis from 2016-2020.

BACKGROUND: Inflammatory arthritis (IA) represents a less common indication for anatomic and reverse total shoulder arthroplasty (TSA) than osteoarthritis (OA). The safety and efficacy of anatomic and reverse TSA in this population has not been as well studied compared to OA. We analyzed the differences in outcomes between IA and OA patients undergoing TSA. METHODS: Patients who underwent primary anatomic total shoulder arthroplasty (aTSA) and reverse total shoulder arthroplasty (rTSA) from 2016-2020 were identified in the Premier Healthcare Database. Inflammatory arthritis (IA) patients were identified using International Classification of Diseases, Tenth Revision, diagnosis codes and compared to osteoarthritis controls. Patients were matched in a 1:8 fashion by age (±3 years), sex, race, and presence of pertinent comorbidities. Patient demographics, hospital factors, and patient comorbidities were compared. Multivariate regression was performed following matching to account for any residual confounding and 90-day complications were compared between the 2 cohorts. Descriptive statistics and regression analysis were employed with significance set at P < .05. RESULTS: Prior to matching, 5685 IA cases and 93,539 OA controls were identified. Patients with IA were more likely to be female, have prolonged length of stay and increased total costs (P < .0001). After matching and multivariate analysis, 4082 IA cases and 32,656 controls remained. IA patients were at increased risk of deep wound infection (OR 3.14, 95% CI 1.38-7.16, P = .006), implant loosening (OR 4.11, 95% CI 1.17-14.40, P = .027), and mechanical complications (OR 6.34, 95% CI 1.05-38.20, P = .044), as well as a decreased risk of postoperative stiffness (OR 0.36, 95% CI 0.16-0.83, P = .002). Medically, IA patients were at increased risk of PE (OR 2.97, 95% CI 1.52-5.77, P = .001) and acute blood loss anemia (OR 1.27, 95% CI 1.12-1.44, P < .0001). DISCUSSION AND CONCLUSION: Inflammatory arthritis represents a distinctly morbid risk profile compared to osteoarthritis patients with multiple increased surgical and postoperative medical complications in patients undergoing aTSA and rTSA. Surgeons should consider these potential complications and employ a multidisciplinary approach in preoperative risk stratification of IA undergoing shoulder replacement.

Effect of body mass index on complications following total shoulder arthroplasty: a population-wide analysis.

BACKGROUND: Evidence regarding the effect of body mass index (BMI) on complications following anatomic shoulder arthroplasty (aTSA) and reverse shoulder arthroplasty (rTSA) remains controversial. This high-powered study examines the effect of BMI on surgical and medical complications following aTSA and rTSA. METHODS: This retrospective cohort study was conducted using the Premier Healthcare Database to query all adult patients who underwent primary, elective TSA (aTSA, rTSA) from 2016 to 2020. Patients eligible for inclusion were identified using International Classification of Diseases -10 and CPT codes for primary TSA. Patients were stratified into 3 subgroups based on BMI (BMI <30 kg/m2, BMI 30-35 kg/m2, BMI >35 kg/m2). The primary endpoints assessed were 90-day risks of postoperative complications, revisions, and readmissions among the 3 BMI groups undergoing primary TSA. RESULTS: A total of 32,645 patients were analyzed; 10,951 patients underwent aTSA and 21,694 patients underwent rTSA. Patient populations for aTSA and rTSA differed significantly across all BMI categories in terms of age, sex, cost of care, and insurance status. After multivariate regression analysis, there was no increased risk of surgical complications in the aTSA and rTSA cohorts with BMI 30-35 kg/m2 and BMI >35 kg/m2. In the aTSA cohort, rates of acute respiratory failure (adjusted Odds Ratio [aOR] 2.65) was all significantly higher in the BMI >35 kg/m2 group. As for rTSA cohort, acute respiratory failure (aOR 1.67) and acute renal failure (aOR 1.53) were significantly higher in the BMI >35 kg/m2 group. CONCLUSION: While we found no increased risk of immediate postoperative surgical risks, patients with a BMI >35 kg/m2 demonstrated greater risk of medical complications after rTSA. Given this trend, providers should exercise caution in patient selection for TSA and counsel obese patients as to these increased risks. Future studies should aim to provide a more comprehensive picture of the effect of BMI on functional outcomes after TSA.

Feasibility of a Video Otoscope for Diagnosis of Otologic Pathology in the Pediatric Emergency Department.

OBJECTIVES: Performing pediatric otoscopy can be difficult secondary to patient compliance, which potentiates misdiagnosis and inaccurate treatment of acute otitis media. This study used a convenience sample to assess the feasibility of using a video otoscope for the examination of tympanic membranes in children presenting to a pediatric emergency department. METHODS: We obtained otoscopic videos using the JEDMED Horus + HD Video Otoscope. Participants were randomized to video or standard otoscopy, and a physician completed their bilateral ear examinations. In the video group, physicians reviewed otoscope videos with the patient's caregiver. The caregiver and physician completed separate surveys using a 5-point Likert Scale regarding perceptions of the otoscopic examination. A second physician reviewed each otoscopic video. RESULTS: We enrolled 213 participants in 2 groups (standard otoscopy, n = 94; video otoscopy, n = 119). We used Wilcoxon rank sum, Fisher exact test, and descriptive statistics to compare results across groups. For physicians, there were no statistically significant differences between groups with ease of device use, quality of otoscopic view, or diagnosis. There was moderate agreement between physician video otoscopic view satisfaction and slight agreement between physician video otologic diagnosis. Estimates of length of time to complete the ear examinations were longer more often for the video otoscope compared with standard for both caregivers (OR, 2.00; 95% confidence interval, 1.10-3.70; P = 0.02) and physicians (OR, 3.08; 95% confidence interval, 1.67-5.78; P < 0.01). There were no statistically significant differences between video and standard otoscopy with regard to caregiver perception of comfort, cooperation, satisfaction, or diagnosis understanding. CONCLUSIONS: Caregivers perceive that video otoscopy and standard otoscopy are comparable in comfort, cooperation, examination satisfaction, and diagnosis understanding. Physicians made a wider range of more subtle diagnoses with the video otoscope. However, examination length of time may limit the JEDMED Horus + HD Video Otoscope's feasibility in a busy pediatric emergency department.

Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a).

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) are relatively common disorders, posing a significant health burden due to increased risk of atherosclerotic cardiovascular disease (ASCVD). Development of electronic health record-based strategies with a linkage to the genetic test results has increased awareness, detection, and control of heritable lipid disorders. This review attempts to critically examine available data to provide a summary of the current evidence for lipoprotein apheresis in FH and elevated lipoprotein(a) (Lp(a)). REVIEW FINDINGS: Availability and indications for lipoprotein apheresis vary across the globe. On average, greater than 60% of atherogenic apoB-containing lipoproteins are immediately reduced following a single procedure, translating in substantial reduction of incident ASCVD events, and preventing accelerated vascular aging. Simultaneous lipid-lowering therapy targeting low-density lipoprotein (LDL) and Lp(a) enhances the efficacy of lipoprotein apheresis. Lipoprotein apheresis alters the proteomics of the lipoprotein particles, including reduction in the concentration of the oxidized-LDL and Lp(a) particles, and proinflammatory apoE bound to HDL particles and remnant lipoproteins. Other effects attributed to lipoprotein apheresis include improvement in blood rheology, endothelial function, microvascular flow, myocardial perfusion, reduction in circulating inflammatory markers. Development of lipoprotein apheresis registries provides data on benefits, challenges, and barriers to inform pertinent healthcare policies. Lipoprotein apheresis is a safe and effective procedure for lowering cholesterol in patients with combined and isolated FH and elevated Lp(a). It reduces the burden of ASCVD and improves long-term prognosis. A team approach is required by the patient, medical staff, and healthcare provider to initiate and maintain a lipoprotein apheresis program.

Postcesarean Analgesia With Epidural Morphine After Epidural 2-Chloroprocaine: A Randomized Noninferiority Trial.

BACKGROUND: Previous studies have suggested that administration of epidural 3% 2-chloroprocaine (CP) before epidural morphine results in decreased analgesic efficacy of epidural morphine. We sought to determine whether these observations were a result of antagonism or a window period between the conclusion of surgical anesthesia for cesarean delivery and the peak onset time of epidural morphine, and whether a method to preserve the analgesic efficacy of epidural morphine exists. METHODS: Term parturients scheduled for nonemergent, unscheduled cesarean delivery with preexisting labor epidural catheters were recruited for this exploratory, randomized, single-blinded, noninferiority trial. Subjects were randomized to initial dosing to a T4 dermatome surgical anesthetic level with either 3% CP or 2% lidocaine with 1:200,000 epinephrine and sodium bicarbonate (LEB). Subsequent redosing for both groups was performed with LEB at regular intervals. Epidural morphine 3 mg was administered to both groups after delivery. Assessing the difference between the 2 groups in total opioid use for the first 24 hours after epidural morphine administration was the primary objective. The noninferiority margin of 10 oral milligram morphine equivalents was prespecified based on previous noninferiority studies. Secondary end points included time from epidural morphine administration to first rescue opioid request, numerical pain scores, nausea/vomiting, and pruritus. RESULTS: Data were analyzed for 40 parturients, 20 in each group. The median 24-hour opioid consumption for the CP group was 0 (Q1 = 0 and Q3 = 15.6) oral milligram morphine equivalents compared to 15 (6.3-22.5) for the LEB group. The median difference was -7.5, with a 95% confidence interval -15 to 0. Noninferiority was concluded, as the confidence interval was less than the predetermined noninferiority margin of 10 oral milligram morphine equivalents. There was no treatment effect on time to first opioid request and no statistically significant differences in pain scores or nausea, vomiting, or pruritus at all time points (4, 8, 12, and 24 hours after epidural morphine administration). CONCLUSION: While designed as an exploratory study, initial epidural dosing with 3% CP and beginning subsequent redosing with LEB within 30 minutes of the initial CP bolus provided noninferior postcesarean analgesia with epidural morphine compared to initial epidural dosing and redosing with LEB. Previous observations of decreased analgesic efficacy of epidural morphine after epidural CP were likely due to a window period that may be mitigated by redosing with lidocaine; however, larger studies are necessary to confirm these findings.

Ecofriendly chromatographic estimation of spasmolytic pharmaceutical mixture along with official toxic impurity, 3,5-dichloroaniline: Complete green profile appraisal.

Nowadays, Green Analytical Chemistry is widely applied to provide various analytical methods with eco-friendly procedures employing the least toxic, harmful reagents on humans and the environment without affecting the efficacy of the determination. Accordingly, two eco-friendly, accurate, and reliable high-performance thin-layer chromatography-densitometry and high-performance liquid chromatographic methods were established for the determination and separation of two antispasmodic drugs, namely phloroglucinol and trimethylphloroglucinol in their pure, combined dosage form along with phloroglucinol toxic impurity, 3,5-dichloroaniline. For high-performance thin-layer chromatography-densitometry, efficient separation was developed via utilizing the stationary phase of high-performance thin-layer chromatography silica gel 60 F254 plates and developing a system comprising of ethyl acetate-butanol-ammonia in the ratio of 8.0:2.0:0.2, by volume and scanning of the developed bands at 210.0 nm. The subsequent method is isocratic high-performance liquid chromatography with diode array detection in which separation was successively attained using XTerra RP-C18 (250 × 4.6 mm, 5 µm) column as stationary phase and methanol-10.0 mM phosphate buffer, pH 3.7 ± 0.1 as mobile phase in the ratio of 75.0:25.0, v/v at flow rate 1.0 ml/min and scanning at 220.0 nm. The developed liquid chromatography methods were validated according to the International Council for Harmonization guidelines, and all results acknowledged their efficacy. Additionally, the proposed methods worked well for assessing the cited drugs in binary combined commercially available pharmaceutical formulation. The greenness profile of the present methods was assessed and estimated using various assessment tools, namely; Green Analytical Procedure Index, analytical eco-scale method, National Environmental Method Index in addition to Analytical GREEnness tool to evaluate the greenness of the provided methods with a statistical comparison between them to assess the more green ones.

Green micelle and complex inclusion enhance synchronous spectrofluorimetric quantification of a novel analgesic combination: Tramadol and celecoxib in tablet dosage form and spiked human plasma.

This work offers for the first time an optimized, highly sensitive, simple, and accurate synchronized spectrofluorimetric technique for the simultaneous measurement of tramadol and celecoxib in powder form, their combined multimodal tablet, and finally spiked human plasma samples. Tramadol and celecoxib were recently released as a new drug combination to alleviate intense, sudden pain when other pain medications had failed. The technique entailed taking measurements of the fluorescence amplitudes of the synchronized spectra at Δλ = 100 nm. Excitation was made at 220 nm and 264 nm, whereas the emission points were 282 nm and 368 nm for tramadol and celecoxib, respectively. This technique offers linearity of 40-400 ng/ml and 100-2000 ng/ml for tramadol and celecoxib, respectively. Complex formation between the cited medications with the surfactant sodium dodecyl sulphate enhanced the fluorescence intensity and other control parameters. Tramadol and celecoxib were both determined in spiked human plasma using the current technique with marked percentage recoveries of 98.63 ± 6.30% and 99.32 ± 6.67%, respectively. Last, the research was extended to check the greenness profile of the finally optimized method and the results revealed excellent eco-friendliness. Three greenness assessment tools were used including Eco-scale, the Green Analytical Procedure Index tool, and the AGREE calculator. Sustainable development, economic feasibility, and environmental soundness were all considered throughout the development of the present technique. The approach was validated in accordance with the requirements provided by the International Council for Harmonization.

Greenness-by-design approach for developing novel UV spectrophotometric methodologies resolving a quaternary overlapping mixture.

Greenness-by-design (GbD) is an approach that integrates green chemistry principles into the method development stage of analytical processes, aiming to reduce their environmental impact. In this work, we applied GbD to a novel univariate double divisor corrected amplitude (DDCA) method that can resolve a quaternary pharmaceutical mixture in a fixed-dose polypill product. We also used a genetic algorithm as a chemometric modeling technique to select the informative variables for the analysis of the overlapping mixture. This resulted in more accurate and efficient predictive models. We used a computational approach to study the effect of solvents on the spectral resolution of the mixture and to minimize the spectral interferences caused by the solvent, thus achieving spectral resolution with minimal analytical effort and ecological footprint. The validated methods showed wide linear concentration ranges for the four components (1-30 µg/mL for losartan, 2.5-30 µg/mL for atorvastatin and aspirin, and 2.5-35 µg/mL for atenolol) and achieved high scores on the hexagon and spider charts, demonstrating their eco-friendliness.

Genomic Analysis of Vascular Invasion in HCC Reveals Molecular Drivers and Predictive Biomarkers.

BACKGROUND AND AIMS: Vascular invasion (VI) is a critical risk factor for HCC recurrence and poor survival. The molecular drivers of vascular invasion in HCC are open for investigation. Deciphering the molecular landscape of invasive HCC will help identify therapeutic targets and noninvasive biomarkers. APPROACH AND RESULTS: To this end, we undertook this study to evaluate the genomic, transcriptomic, and proteomic profile of tumors with VI using the multiplatform cancer genome atlas (The Cancer Genome Atlas; TCGA) data (n = 373). In the TCGA Liver Hepatocellular Carcinoma cohort, macrovascular invasion was present in 5% (n = 17) of tumors and microvascular invasion in 25% (n = 94) of tumors. Functional pathway analysis revealed that the MYC oncogene was a common upstream regulator of the mRNA, miRNA, and proteomic changes in VI. We performed comparative proteomic analyses of invasive human HCC and MYC-driven murine HCC and identified fibronectin to be a proteomic biomarker of invasive HCC (mouse fibronectin 1 [Fn1], P = 1.7 × 10-11 ; human FN1, P = 1.5 × 10-4 ) conserved across the two species. Mechanistically, we show that FN1 promotes the migratory and invasive phenotype of HCC cancer cells. We demonstrate tissue overexpression of fibronectin in human HCC using a large independent cohort of human HCC tissue microarray (n = 153; P < 0.001). Lastly, we showed that plasma fibronectin levels were significantly elevated in patients with HCC (n = 35; mean = 307.7 µg/mL; SEM = 35.9) when compared to cirrhosis (n = 10; mean = 41.8 µg/mL; SEM = 13.3; P < 0.0001). CONCLUSIONS: Our study evaluates the molecular landscape of tumors with VI, identifying distinct transcriptional, epigenetic, and proteomic changes driven by the MYC oncogene. We show that MYC up-regulates fibronectin expression, which promotes HCC invasiveness. In addition, we identify fibronectin to be a promising noninvasive proteomic biomarker of VI in HCC.

Synchronous Spectrofluorimetry Coupled with Third-Order Derivative Signal Processing for the Simultaneous Quantitation of Telmisartan and Chlorthalidone Drug Combination in Human Plasma.

This study is the first to develop and optimize a method for the simultaneous determination of chlorthalidone (CLT) and telmisartan (TEL) in, human plasma samples as well as in their newly released pharmaceutical tablet form, (Telmikind-CT 40®). The method is based on measuring fluorescence intensity, employing synchronous fluorescence mode coupled to third-order derivative signal processing, 0.5% w/v cetyl trimethyl ammonium bromide was used as cationic surfactant to enhance the fluorescence signal intensity and improve method sensitivity. The third-order derivative synchronous spectra of CLT and TEL are well separated with two zero-crossing points which allowed for the determination of CLT and TEL at 362 nm and 351 nm, respectively. Different experimental parameters were carefully investigated and optimized, calibration curves were constructed over concentration ranges of 20-1200 ng.mL-1 and 5-800 ng.mL-1 for CLT and TEL respectively. The developed method is simple and rapid, analytical parameters were validated according to ICH guidelines and high sensitivity was achieved as represented by limits of detection (LOD) of 4.69 and 1.58 ng.mL-1 for CLT and TEL respectively.

Fecal adrenal hormone patterns during ovulatory and non-ovulatory reproductive cycles in female veiled chameleons (Chamaeleo calyptratus).

The relationship between the reproductive (hypothalamic-pituitary-gonadal; HPG) and adrenal (hypothalamic-pituitary-adrenal; HPA) hormone axes is complex and can vary depending on the species and environmental factors affecting an individual. In an effort to understand this relationship in female veiled chameleons (Chamaeleo calyptratus), the patterns of fecal metabolites of corticosterone (C), estradiol (E), testosterone (T), and progesterone (P) were analyzed by enzyme immunoassay (EIA) during ovulatory (OC; eggs laid) and non-ovulatory cycles (NOC; no eggs laid). Glucocorticoid (GC) metabolites in the fecal extracts were characterized by HPLC and corticosterone EIA performance was assessed by parallelism, accuracy and precision tests. The results indicated that the assay chosen reliably measured the hormone metabolites present in the fecal extracts. Regular, cyclical hormone metabolite patterns consisting of an E peak followed by peaks of T, P and C in close succession were observed during both ovulatory and non-ovulatory cycles; relative levels of P and C, however, were higher during ovulatory cycles. Corticosterone metabolite levels, in particular, increased throughout vitellogenesis and peaked in late vitellogenesis (in non-ovulatory cycles) or around the time of ovulation, and remained elevated throughout the gravid period, falling just prior to oviposition. The results provide evidence of variation in glucocorticoid production throughout different stages of the reproductive cycle, including a role in the ovulatory process; the physiology, however, remains unclear.

Simultaneous determination of citalopram and tadalafil by the second derivative synchronous fluorescence method in biological fluids; application of Box-Behnken optimization design.

This is the first study focusing solely on that determination of tadalafil in the presence of citalopram as an antidepressant drug. The determination in biological fluids of a co-administered antidepressant drug and a sexual stimulation drug is a very critical and important step for psychotic and ischaemic heart disease patients, especially in cases of emergency and this requires therapeutic drug monitoring. A sensitive, efficient and rapid assay was selected satisfactorily and applied for simultaneous determination of citalopram and tadalafil either in their pure forms, in tablet dosage forms or in spiked human plasma. There was a large overlap for both drugs, forming the broad band found in conventional fluorescence spectra and their related synchronous fluorescence intensity. Therefore, the development of a highly sensitive second derivative synchronous fluorescence method was demonstrated that removed this overlap. The proposed method depended on measuring the amplitudes of the second derivative of synchronous fluorescence intensity at suitable wavelengths of 301 nm and 367 nm for citalopram and tadalafil at Δλ = 60 nm, respectively. Box-Behnken design as a response surface methodology was used to fit models and create an optimization process encompassing a set of factors and resulting in an optimum response value specifically designed for this method. Under optimum conditions, the linear dynamic ranges for citalopram and tadalafil estimation were 20-900 and 5-400 ng ml-1 with detection limits of 5.40 and 1.43 ng ml-1 , respectively.

Maintenance of Certification Pediatrics: Pediatric Emergency Medicine (PEM): The New Part 3 Maintenance of Certification Assessment Option.

ABSTRACT: Starting in 2022, the American Board of Pediatrics will launch the Maintenance of Certification Assessment for Pediatrics: Pediatric Emergency Medicine (MOCA-Peds: PEM) longitudinal assessment, which will provide an at-home alternative to the point-in-time examination. This longitudinal assessment will help engage PEM physicians participating in continuing certification in a more flexible and continuous lifelong, self-directed learning process while still providing a summative assessment of their knowledge. This commentary provides background information on MOCA-Peds and an introduction to MOCA-Peds: PEM and how it gives the PEM physician another option to participate in continuing certification.

Using the electronic health record for genomics research.

PURPOSE OF REVIEW: Although primarily designed for medical documentation and billing purposes, the electronic health record (EHR) has significant potential for translational research. In this article, we provide an overview of the use of the EHR for genomics research with a focus on heritable lipid disorders. RECENT FINDINGS: Linking the EHR to genomic data enables repurposing of vast phenotype data for genomic discovery. EHR data can be used to study the genetic basis of common and rare disorders, identify subphenotypes of diseases, assess pathogenicity of novel genomic variants, investigate pleiotropy, and rapidly assemble cohorts for genomic medicine clinical trials. EHR-based discovery can inform clinical practice; examples include use of polygenic risk scores for assessing disease risk and use of phenotype data to interpret rare variants. Despite limitations such as missing data, variable use of standards and poor interoperablility between disparate systems, the EHR is a powerful resource for genomic research. SUMMARY: When linked to genomic data, the EHR can be leveraged for genomic discovery, which in turn can inform clinical care, exemplifying the virtuous cycle of a learning healthcare system.

Ghrelin-induced multi-organ damage in mice fed obesogenic diet.

OBJECTIVE AND DESIGN: Ghrelin has a key role in modulating energy metabolism and weight gain. The present study aimed at studying the potential role of ghrelin in the development and/or exacerbation of organ damage in a mouse model of diet-induced obesity. OBJECTIVE AND DESIGN: Adult mice were fed one of two diets for 20 weeks: standard high carbohydrate (HC) or high-fat high-sugar (HFHS). Starting week 17, the animals were given regular intraperitoneal ghrelin (160 µg/kg) or saline injections Abdominal fat, serum creatinine, and glucose levels, as well as kidney, liver and heart weight and pathology were assessed. RESULTS: Ghrelin-injected mice showed significant organ damage, which was more exacerbated in HFHS-fed animals. While the HFHS diet was associated with significant liver damage, ghrelin administration did not reverse it. Interestingly, ghrelin administration induced moderate kidney damage and significantly affected the heart by increasing perivascular and myocardium fibrosis, steatosis as well as inflammation. Moreover, serum creatinine levels were higher in the animal group injected with ghrelin. CONCLUSION: Ghrelin administration was associated with increased functional and structural organ damage, regardless of diet. The present study provides novel evidence of multi-organ physiologic alterations secondary to ghrelin administration.

Targeted Sequencing Study to Uncover Shared Genetic Susceptibility Between Peripheral Artery Disease and Coronary Heart Disease-Brief Report.

Objective- It is unclear to what extent genetic susceptibility variants are shared between peripheral artery disease (PAD) and coronary heart disease (CHD), both manifestations of atherosclerotic vascular disease. We investigated whether common and low-frequency/rare variants in loci associated with CHD are also associated with PAD. Approach and Results- Targeted sequencing of 41 genomic regions associated with CHD in genome-wide association studies was performed in 1749 PAD cases (65±11 years, 61% men) and 1855 controls (60±11 years, 56% men) of European ancestry. PAD cases had a resting/postexercise ankle-brachial index ≤0.9, or history of lower extremity revascularization; controls had no history of PAD. We tested the association of common (defined as minor allele frequency ≥5%) variants with PAD assuming an additive genetic model with adjustment for age and sex. To identify low-frequency/rare variants (minor allele frequency <5%) associated with PAD, we conducted gene-level analyses using sequence kernel association test and permutation test. After Bonferroni correction, we found common variants in SH2B3, ABO, and ZEB2 to be associated with PAD ( P<4.5×10-5). At the gene level, the strongest associations were for LPL and SH2B3. Conclusions- Targeted sequencing of 41 genomic regions associated with CHD revealed several common variants/genes to be associated with PAD, highlighting the basis of shared genetic susceptibility between CHD and PAD.

Association of Genetic Risk of Obesity with Postoperative Complications Using Mendelian Randomization.

BACKGROUND: The extent to which obesity and genetics determine postoperative complications is incompletely understood. METHODS: We performed a retrospective study using two population cohorts with electronic health record (EHR) data. The first included 736,726 adults with body mass index (BMI) recorded between 1990 and 2017 at Vanderbilt University Medical Center. The second cohort consisted of 65,174 individuals from 12 institutions contributing EHR and genome-wide genotyping data to the Electronic Medical Records and Genomics (eMERGE) Network. Pairwise logistic regression analyses were used to measure the association of BMI categories with postoperative complications derived from International Classification of Disease-9 codes, including postoperative infection, incisional hernia, and intestinal obstruction. A genetic risk score was constructed from 97 obesity-risk single-nucleotide polymorphisms for a Mendelian randomization study to determine the association of genetic risk of obesity on postoperative complications. Logistic regression analyses were adjusted for sex, age, site, and race/principal components. RESULTS: Individuals with overweight or obese BMI (≥25 kg/m2) had increased risk of incisional hernia (odds ratio [OR] 1.7-5.5, p < 3.1 × 10-20), and people with obesity (BMI ≥ 30 kg/m2) had increased risk of postoperative infection (OR 1.2-2.3, p < 2.5 × 10-5). In the eMERGE cohort, genetically predicted BMI was associated with incisional hernia (OR 2.1 [95% CI 1.8-2.5], p = 1.4 × 10-6) and postoperative infection (OR 1.6 [95% CI 1.4-1.9], p = 3.1 × 10-6). Association findings were similar after limitation of the cohorts to those who underwent abdominal procedures. CONCLUSIONS: Clinical and Mendelian randomization studies suggest that obesity, as measured by BMI, is associated with the development of postoperative incisional hernia and infection.