Molecular testing in newborn screening: VUS burden among true positives and secondary reproductive limitations via expanded carrier screening panels.

PURPOSE: Expanded carrier screening (ECS) gene panels have several limitations, including variable content, current knowledge of disease-causing variants, and differing reporting policies. This study evaluated if the disease-associated variants identified in affected neonates who screened positive by California newborn screening (NBS) for an inherited metabolic disorder (IMD) by tandem mass spectrometry (MS/MS) would likely be reported by ECS gene panels. METHODS: Retrospective review of neonates referred by the California Department of Public Health for a positive NBS by multianalyte MS/MS from January 1, 2020 through June 30, 2021. RESULTS: One hundred thirty-six neonates screened positive for ≥1 NBS MS/MS indication. Nineteen neonates (14%) were ultimately diagnosed with an IMD, all of whom had abnormal biochemical testing. Eighteen of the 19 underwent molecular testing; 10 (56%) neonates had ≥1 variants of uncertain significance, 9 of whom were of non-White ancestry. ECS panels would have been negative for 56% (20/36) of parents with an affected neonate, 85% (17/20) of whom were of non-White ancestry. CONCLUSION: The number of variants of uncertain significance identified in this cohort highlights the need for more diversified variant databases. Due in part to the lack of diversity in currently sequenced populations, genomic sequencing cannot replace biochemical testing for the diagnosis of an IMD.

Drains in Breast Reduction: How Good is the Recommendation Not to Use Them?

A clinical practice guideline (CPG) recommended not to use drains in breast reduction. This CPG was based on 3 randomized controlled trials (RCTs). The objective of this review was to double-check the methodological quality of the three RCTs. These RCTs were critically appraised using a) the Users' guide to RCT assessment for methodological quality, b) the CONSORT guideline for reporting quality, and c) the Cochrane risk of bias tool 2 (RoB 2) for risk of bias. Weaknesses were identified in all assessments for the three RCTs. Items with the poorest adherence in the User's guide to RCT included: "Were patients stratified?", "Was follow-up complete?", and "Were all clinically important outcomes considered?". The overall adherence to the CONSORT Reporting Checklist across all studies was moderate with 40.0%, 62.1% and 48.3% adherence. All 3 RCTs had a similar low to moderate risk of bias, with no areas with a high risk of bias. None of the studies took into consideration a single critical outcome (such as major hematoma) and the outcome's minimally important difference as the basis for the sample size and power calculation of the study. All three RCTs additionally lacked clear reporting of treatment effect sizes or precision of estimates. Our re-examination of the evidence questions the recommendation of the CPG. We believe that the recommendation should have been "we remain uncertain whether drains in breast reduction have a salutary effect". As such, we recommend that a methodologically robust RCTs be conducted to answer this question.

A comparison of skin grafts versus local flaps for facial skin cancer from the patient perspective: protocol for a feasibility study.

BRIEF ABSTRACT: This is a protocol to assess feasibility of conducting a prospective cohort study comparing local flaps versus skin grafts for surgical excision of skin cancer from the face. INTRODUCTION: Skin cancer is the most common malignancy worldwide and the face is one of the most common locations of occurrence. Surgical excision is the most popular treatment for small lesions of the face. Defects can be reconstructed using local flaps or skin grafts. There is a paucity of literature evaluating outcomes after skin cancer surgery from the patient's perspective using valid measurement tools. The purpose of this study is to assess the feasibility of conducting a prospective observational cohort study. The primary outcomes include recruitment rates, eligibility rate, compliance of intervention and rate of completion of the primary outcome (FACE-Q scales) at 3 months. Secondary outcomes include examining patient characteristic and FACE-Q score differences between local flaps to skin grafts and adverse events. METHODS AND ANALYSIS: This study is a prospective cohort study consisting of an anticipated 30 patients aged ≥18 years. The study population will consist of a consecutive sample of non-melanoma facial skin cancer patients undergoing a skin graft or local flap. Patients will be followed and evaluated with the FACE-Q questionnaire at 2 weeks, 3 months, 6 months and 1 year post-operation. The following criteria will determine success: patients who meet eligibility criteria >70%; recruitment rate >70%; compliance with intervention >90%; rate of completion of full-scale prospective study primary outcome (FACE-Q at 3 months) >80%; retention rate at 6-month follow-up visit >70%. DISCUSSION: The findings of this study will be used to guide the sample size calculation for a future, large-scale prospective study.Trial registration: ClinicalTrials.gov (NCT04842279).

Your mileage may vary: impact of data input method for a deep learning bone age app's predictions.

OBJECTIVE: The purpose of this study was to evaluate agreement in predictions made by a bone age prediction application ("app") among three data input methods. METHODS: The 16Bit Bone Age app is a browser-based deep learning application for predicting bone age on pediatric hand radiographs; recommended data input methods are direct image file upload or smartphone-capture of image. We collected 50 hand radiographs, split equally among 5 bone age groups. Three observers used the 16Bit Bone Age app to assess these images using 3 different data input methods: (1) direct image upload, (2) smartphone photo of image in radiology reading room, and (3) smartphone photo of image in a clinic. RESULTS: Interobserver agreement was excellent for direct upload (ICC = 1.00) and for photos in reading room (ICC = 0.96) and good for photos in clinic (ICC = 0.82), respectively. Intraobserver agreement for the entire test set across the 3 data input methods was variable with ICCs of 0.95, 0.96, and 0.57 for the 3 observers, respectively. DISCUSSION: Our findings indicate that different data input methods can result in discordant bone age predictions from the 16Bit Bone Age app. Further study is needed to determine the impact of data input methods, such as smartphone image capture, on deep learning app performance and accuracy.

Comparison of emergency pediatric breast ultrasound interpretations and management recommendations between pediatric radiologists and breast imaging radiologists.

PURPOSE: Pediatric patients with breast-related symptoms often initially present to the emergency department for evaluation. While pediatric radiologists are accustomed to evaluating acute infectious and traumatic etiologies, they may be less familiar with breast-specific findings. This study compares management recommendations of pediatric breast ultrasounds performed in the emergency setting between pediatric and breast imaging radiologists. METHODS: This retrospective cohort study reviewed data from all pediatric breast ultrasounds performed in the emergency setting from a single academic institution from 1/1/14 to 12/31/19. During the study period, 12 pediatric radiologists with experience ranging from 1 to 33 years interpreted pediatric breast ultrasounds. Three breast imaging radiologists (with 3, 8, and 25 years of experience) retrospectively reviewed each case and recorded whether further management was recommended. Differences in recommendations were compared using Fisher's exact test. Cohen's kappa was used to assess agreement between subspecialty radiologists. RESULTS: This study included 75 pediatric patients, with mean age 13 ± 5.6 years and malignancy rate of 1.3% (1/75). Pediatric radiologists and the most experienced breast imaging radiologist had moderate agreement in management recommendations (k = 0.54). There was no significant difference in recommendations for further management between pediatric radiologists (22/75 [29.3%]) and the most experienced breast imaging radiologist (15/75 [20.0%]), p = 0.26. CONCLUSION: Recommendations for pediatric breast complaints in the emergency setting are comparable between subspecialties.

Relationships Between Punch Impact Force and Upper- and Lower-Body Muscular Strength and Power in Highly Trained Amateur Boxers.

ABSTRACT: Dunn, EC, Humberstone, CE, Franchini, E, Iredale, KF, and Blazevich, AJ. Relationships between punch impact force and upper- and lower-body muscular strength and power in highly trained amateur boxers. J Strength Cond Res 36(4): 1019-1025, 2022-This study examined the relationship between upper- and lower-body strength and power characteristics and punch performance in 28 highly trained male amateur boxers. Punch performance was assessed with a custom-built punch integrator using a 3-minute maximal effort punch test that contained straight- and bent-arm punches from the lead and rear hands. Peak punch force and force-time variables including impulse and rate of force development (RFD; calculated to various points) were assessed. Force, power, and RFD of the upper and lower body were assessed with countermovement bench throw, isometric bench push, countermovement jump (CMJ), and isometric midthigh pull (IMTP) tests. Correlation and regression analyses revealed significant (p < 0.05) relationships between peak punch force and forces measured in CMJ and IMTP tests. In addition, peak punch force was moderately and significantly correlated to body mass, but RFD in the lower body was not. Moreover, no meaningful relationships between punch performance characteristics and any upper-body strength or power parameter were identified. The results of this study show that lower-body strength but not RFD had a moderate to strong positive and significant correlation to peak punch force production. Although upper-body strength and power are expected to be important in boxing, they did not discriminate between boxers who punched with higher or lower peak force nor were they correlated to peak punch force. Training that improves lower-body strength without increasing total body mass (to maintain weight category) may positively influence punch capacity in highly trained amateur boxers.

Single Cell RNA Sequencing of Human Milk-Derived Cells Reveals Sub-Populations of Mammary Epithelial Cells with Molecular Signatures of Progenitor and Mature States: a Novel, Non-invasive Framework for Investigating Human Lactation Physiology.

Cells in human milk are an untapped source, as potential "liquid breast biopsies", of material for investigating lactation physiology in a non-invasive manner. We used single cell RNA sequencing (scRNA-seq) to identify milk-derived mammary epithelial cells (MECs) and their transcriptional signatures in women with diet-controlled gestational diabetes (GDM) with normal lactation. Methodology is described for coordinating milk collections with single cell capture and library preparation via cryopreservation, in addition to scRNA-seq data processing and analyses of MEC transcriptional signatures. We comprehensively characterized 3740 cells from milk samples from two mothers at two weeks postpartum. Most cells (>90%) were luminal MECs (luMECs) expressing lactalbumin alpha and casein beta and positive for keratin 8 and keratin 18. Few cells were keratin 14+ basal MECs and a small immune cell population was present (<10%). Analysis of differential gene expression among clusters identified six potentially distinct luMEC subpopulation signatures, suggesting the potential for subtle functional differences among luMECs, and included one cluster that was positive for both progenitor markers and mature milk transcripts. No expression of pluripotency markers POU class 5 homeobox 1 (POU5F1, encoding OCT4) SRY-box transcription factor 2 (SOX2) or nanog homeobox (NANOG), was observed. These observations were supported by flow cytometric analysis of MECs from mature milk samples from three women with diet-controlled GDM (2-8 mo postpartum), indicating a negligible basal/stem cell population (epithelial cell adhesion molecule (EPCAM)-/integrin subunit alpha 6 (CD49f)+, 0.07%) and a small progenitor population (EPCAM+/CD49f+, 1.1%). We provide a computational framework for others and future studies, as well as report the first milk-derived cells to be analyzed by scRNA-seq. We discuss the clinical potential and current limitations of using milk-derived cells as material for characterizing human mammary physiology.

Supine versus prone positioning for ultrasound evaluation of postnatal urinary tract dilation in children.

BACKGROUND: Ultrasound (US) is used in the initial evaluation and surveillance of urinary tract dilation in children. Urinary tract dilation is diagnosed in 1-2% of all pregnancies during routine prenatal sonography with technological advances in US imaging. Urinary tract dilation classification systems, including the 2014 multidisciplinary consensus, assess anterior-posterior renal pelvic diameter and calyceal dilation. There is no consensus regarding optimal patient positioning - supine versus prone - during US assessment of urinary tract dilation. OBJECTIVE: We performed this study to determine whether there is a significant difference in the measurement of the anterior-posterior renal pelvic diameter, presence of calyceal dilation, or resulting urinary tract dilation consensus score obtained between supine and prone positions. MATERIALS AND METHODS: Two raters retrospectively reviewed renal bladder US exams of children with urinary tract dilation of one or both kidneys. We included technically adequate US examinations of orthotopic kidneys that were imaged in both supine and prone positions; we excluded children with renal anomalies or prior surgery. Anterior-posterior renal pelvic diameter measurements as well as central and peripheral calyceal dilation were documented in both supine and prone positions. A postnatal urinary tract dilation consensus score was assigned to each kidney based only on these features. RESULTS: Urinary tract dilation in either the supine or prone position was performed in 146 kidneys (69 right, 77 left) in 89 children. Median age was 0.26 years (interquartile ratio [IQR] 0.08-0.61 years). Female-to-male ratio was 1:3 (21/89). The interclass correlations of the anterior-posterior renal pelvic diameter were 0.88 and 0.87 in the supine and prone positions, respectively, without significant differences (P=0.1). When comparing all kidneys together, the mean anterior-posterior renal pelvic diameter was 7.1 mm (95% confidence interval [CI] 6.4-7.8) in supine and 7.9 (95% CI 7.1-8.7) in prone, with a mean difference between the measurements of 0.83 mm (95% CI 0.3-1.4; P=0.16). Central calyceal and peripheral calyceal dilation were more commonly found in the prone position versus the supine position in both kidneys. Central calyceal dilation was observed in 15 cases in the prone but not in the supine position. In one kidney, it was seen only in the supine but not in the prone position. Overall the urinary tract dilation score differed between positions in 10.3% (15/146) of cases, most of them (14/15) with a higher score in prone compared to the supine position. CONCLUSION: Scanning in prone position tends to more frequently show calyceal dilation and a greater size of the anterior-posterior renal pelvic diameter, resulting in higher urinary tract dilation classification scores, with almost perfect interobserver agreement.

Pregnancy and parental leave among plastic surgery residents in Canada: a nationwide survey of attitudes and experiences.

SUMMARY: Small surgical residency programs like plastic surgery can be challenging environments to accommodate parental leave. This study aimed to report the experiences, attitudes and perceived support of Canadian plastic surgery residents, recent graduates and staff surgeons with respect to pregnancy and parenting during training. Residents and staff surgeons were invited via email to participate in an online survey. The results presented here explore experiences of pregnancy and parental leave of current plastic surgery residents and staff surgeons. Residents' and staff surgeons' perceptions of program director support, policies, negative comments and the impact of parental leave on the workload of others were also explored. Although the findings suggest that there may be improvements in the support of program directors, there continues to be a negative attitude in surgical culture toward pregnancy during residency. The perceived confusion of respondents with respect to programspecific policies emphasizes the need for open conversations and standardization of parental leave.

Reliability and Usefulness of Time-Motion and Physiological Responses in Simulated Judo Matches.

Franchini, E, Dunn, E, and Takito, MY. Reliability and usefulness of time-motion and physiological responses in simulated judo matches. J Strength Cond Res 34(9): 2557-2564, 2020-Match simulations have been used to investigate different interventions in judo. However, no study has assessed the reliability of actions performed and the physiological responses to the match and its usefulness. Thus, 2 studies were conducted to verify the reliability of time-motion and physiological responses to judo matches. In the first study, 25 judo athletes performed one 5-minute judo match simulation twice, 1 week apart, and had their heart rate and blood lactate measured. In the second, 12 judo athletes performed one 5-minute judo simulation 4 times, 72 hours apart, and had their primary actions and match temporal structure analyzed. Comparisons between conditions, reliability (using intraclass correlation coefficient, ICC), typical error (TE), smallest worthwhile change (SWC), and minimal detectable change were determined. The main findings indicated that: (a) there were no differences between matches for any variable; (b) ICCs were significant (except for blood lactate before matches in both studies) with 6 variables presenting large (number of attacks plus defensive actions, number of scoring actions, efficiency, number of sutemi-waza, time per combat sequence, and time per interval phase time), and the remaining 15 variables presenting very large reliability; (c) TE was higher than SWC for all variables when small differences were considered. Moderate changes in peak blood lactate and the change in blood lactate (in both studies), and time in tachi-waza could be properly detected; however, only large changes could be detected for all other variables, suggesting that investigations using match simulation as an outcome variable may only detect large changes.

The Reporting Quality of Randomized Controlled Trial Abstracts in Plastic Surgery.

BACKGROUND: When evaluating randomized controlled trials (RCTs), clinicians will often refer to the abstract for an initial assessment of the results and to determine whether a full-text review is warranted. OBJECTIVES: This project aims to assess the reporting quality of RCT abstracts published within the top 5 plastic surgery journals utilizing the Consolidated Standards of Reporting Trials (CONSORT) for abstracts checklist. METHODS: A computerized database search of OVID MEDLINE was performed. All primary RCTs published within the top 5 plastic surgery journals (by 2016 International Scientific Indexing impact factor) from 2011 to 2018 were included. Two reviewers, blinded to journal and author, independently and in duplicate, scored abstracts employing the 16-item CONSORT for abstracts checklist. RESULTS: This review identified 126 RCTs that satisfied the inclusion criteria. Included studies were distributed across 5 journals: Plastic and Reconstructive Surgery (n = 83), JAMA Facial Plastic Surgery (n = 8), Aesthetic Surgery Journal (n = 33), Journal of Reconstructive Microsurgery (n = 2), and the Journal of Hand Surgery-European Volume (n = 0). Mean overall item adherence across all abstracts was 7 (SD ± 2). The most poorly reported items were "trial registration," "method of randomization," and "source of trial funding" and appeared in 4%, 2.4%, and 0% of abstracts, respectively. CONCLUSIONS: There is limited adherence to the CONSORT for abstracts checklist among RCT abstracts published within the top 5 plastic surgery journals. Given the reliance of clinicians on abstract reporting, omitting essential trial details can lead to an inaccurate interpretation of trial results and improper application in clinical practice. Active endorsement of the CONSORT for abstracts checklist is required to improve the quality of RCT abstract reporting.

Comparative efficacy of valnoctamide and sec-butylpropylacetamide (SPD) in terminating nerve agent-induced seizures in pediatric rats.

OBJECTIVES: Children and adults are likely to be among the casualties in a civilian nerve agent exposure. This study evaluated the efficacy of valnoctamide (racemic-VCD), sec-butylpropylacetamide (racemic-SPD), and phenobarbital for stopping nerve agent seizures in both immature and adult rats. METHODS: Female and male postnatal day (PND) 21, 28, and 70 (adult) rats, previously implanted with electroencephalography (EEG) electrodes were exposed to seizure-inducing doses of the nerve agents sarin or VX and EEG was recorded continuously. Five minutes after seizure onset, animals were treated with SPD, VCD, or phenobarbital. The up-down method was used over successive animals to determine the anticonvulsant median effective dose (ED50 ) of the drugs. RESULTS: SPD-ED50 values in the VX model were the following: PND21, 53 mg/kg (male) and 48 mg/kg (female); PND28, 108 mg/kg (male) and 43 mg/kg (female); and PND70, 101 mg/kg (male) and 40 mg/kg (female). SPD-ED50 values in the sarin model were the following: PND21, 44 mg/kg (male) and 28 mg/kg (female); PND28, 79 mg/kg (male) and 34 mg/kg (female); and PND70, 53 mg/kg (male) and 53 mg/kg (female). VCD-ED50 values in the VX model were the following: PND21, 34 mg/kg (male) and 43 mg/kg (female); PND28, 165 mg/kg (male) and 59 mg/kg (female); and PND70, 87 mg/kg (male) and 91 mg/kg (female). VCD-ED50 values in the sarin model were the following: PND21, 45 mg/kg (male), 48 mg/kg (female); PND28, 152 mg/kg (male) 79 mg/kg (female); and PND70, 97 mg/kg (male) 79 mg/kg (female). Phenobarbital-ED50 values in the VX model were the following: PND21, 43 mg/kg (male) and 18 mg/kg (female); PND28, 48 mg/kg (male) and 97 mg/kg (female). Phenobarbital-ED50 values in the sarin model were the following: PND21, 32 mg/kg (male) and 32 mg/kg (female); PND28, 58 mg/kg (male) and 97 mg/kg (female); and PND70, 65 mg/kg (female). SIGNIFICANCE: SPD and VCD demonstrated anticonvulsant activity in both immature and adult rats in the sarin- and VX-induced status epilepticus models. Phenobarbital was effective in immature rats, whereas in adult rats, higher doses were required that were accompanied by toxicity. Overall, significantly less drug was required to stop seizures in PND21 animals than in the older animals, and overall, males required higher amounts of drug than females.

Anatomy of Classic Bladder Exstrophy: MRI Findings and Surgical Correlation.

PURPOSE OF REVIEW: The exstrophy-epispadias complex (EEC) represents a group of congenitally acquired malformations involving the musculoskeletal, gastrointestinal, and genitourinary systems. Classic bladder exstrophy (CBE) is the most common and best studied entity within the EEC. In this review, imaging features of CBE anatomy will be presented with surgical correlation. RECENT FINDINGS: Magnetic resonance imaging (MRI) has emerged as a useful modality for pre- and postnatal assessment of the abdominal wall, pelvic floor, and gastrointestinal and genitourinary systems of children with CBE. The authors' experience supports use of preoperative MRI, in conjunction with navigational software, as a method for identifying complex CBE anatomy. Imaging facilitates surgical approach and improves visualization of complex anatomy, potentially helping to avoid complications. Continued investigation of imaging guidance in CBE repair is needed as surgical techniques improve.

Novel Anatomical Observations of the Prostate, Prostatic Vasculature and Penile Vasculature in Classic Bladder Exstrophy Using Magnetic Resonance Imaging.

PURPOSE: We used magnetic resonance imaging to define the innate pelvic neurovascular course and prostatic anatomy in infants with classic bladder exstrophy before the pelvis was altered by surgery. MATERIALS AND METHODS: Pelvic magnetic resonance imaging was performed in male infants with classic bladder exstrophy and compared to a group of age matched controls. Data collected included prostatic dimensions as well as course of the prostatic artery, periprostatic vessels and pudendal neurovasculature. RESULTS: The prostate was larger in the transverse (p <0.001) and anteroposterior (p <0.001) dimensions in patients with classic bladder exstrophy compared to those with normal prostates but was smaller in the craniocaudal dimension (p <0.001). This finding resulted in a larger calculated prostate volume in patients with classic bladder exstrophy compared to controls (p = 0.015). The pelvic vasculature and prostatic artery followed a similar course in patients with classic bladder exstrophy and controls. Relative to each other, the lateral to medial course of the prostatic arteries in males with classic bladder exstrophy was less pronounced than in normal males. A similar externally rotated pattern was seen when both sides of the pudendal vasculature were compared in males with classic bladder exstrophy. CONCLUSIONS: The prostate in infants with classic bladder exstrophy has a consistent configuration and dimensions that differ from those in normal infants. When both sides are compared, the periprostatic vasculature and penile sensory neurovascular bundles are externally rotated in infants with classic bladder exstrophy. However, these components course along the same landmarks as in normal patients.

Novel Observations of Female Genital Anatomy in Classic Bladder Exstrophy Using 3-Dimensional Magnetic Resonance Imaging Reconstruction.

PURPOSE: Understanding the distinct female anatomy in classic bladder exstrophy is crucial for optimal reconstructive and functional outcomes. We present novel quantitative anatomical data in females with classic bladder exstrophy before primary closure. MATERIALS AND METHODS: 3-Dimensional reconstruction was performed in patients undergoing pelvic magnetic resonance imaging, and pelvic anatomy was characterized, including measurements of the vagina, cervix and erectile bodies. RESULTS: We examined magnetic resonance imaging of 5 females (mean age 5.5 months) with classic bladder exstrophy and 4 age matched controls (mean age 5.8 months). Mean distance between the anal verge and vaginal introitus was greater in patients with classic bladder exstrophy (2.43 cm) than in controls (1.62 cm). Mean total vaginal length in patients with classic bladder exstrophy was half that of controls (1.64 cm vs 3.39 cm). All 4 controls had posterior facing cervical ora, while 4 of 5 females with exstrophy had anterior facing cervical ora located in the anterior vaginal wall. Lateral deviation of the cervical ora was also seen in all 5 patients with classic bladder exstrophy but in only 1 control. Clitoral body length was comparable in both groups (26.2 mm and 28.0 mm). However, the anterior cavernosa-to-posterior (pelvic rami associated) cavernosa ratio was much greater in patients with classic bladder exstrophy (6.4) compared to controls (2.5). CONCLUSIONS: This study uncovers the uniquely novel finding that contrary to their male counterparts, females with classic bladder exstrophy have the majority of the clitoral body anterior to the pelvic attachment. This discovery has surgical and embryological implications.

Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication.

Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34 000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research.

Novel Contrast-Enhanced Ultrasound Evaluation in Neonatal Hypoxic Ischemic Injury: Clinical Application and Future Directions.

Sensitive, specific, and safe bedside evaluation of brain perfusion is key to the early diagnosis, treatment, and improved survival of neonates with hypoxic ischemic injury. Contrast-enhanced ultrasound (US) imaging is a novel imaging technique in which intravenously injected gas-filled microbubbles generate enhanced US echoes from an acoustic impedance mismatch. This article describes contrast-enhanced US imaging in 2 neonates with hypoxic ischemic injury and future directions on developing quantitative contrast-enhanced US techniques for improved characterization of perfusion abnormalities. The importance of studying the temporal evolution of brain perfusion in neonatal hypoxic ischemic injury is also highlighted.

Chemometric brand differentiation of commercial spices using direct analysis in real time mass spectrometry.

RATIONALE: Commercial spices represent an emerging class of fuels for improvised explosives. Being able to classify such spices not only by type but also by brand would represent an important step in developing methods to analytically investigate these explosive compositions. Therefore, a combined ambient mass spectrometric/chemometric approach was developed to quickly and accurately classify commercial spices by brand. METHODS: Direct analysis in real time mass spectrometry (DART-MS) was used to generate mass spectra for samples of black pepper, cayenne pepper, and turmeric, along with four different brands of cinnamon, all dissolved in methanol. Unsupervised learning techniques showed that the cinnamon samples clustered according to brand. Then, we used supervised machine learning algorithms to build chemometric models with a known training set and classified the brands of an unknown testing set of cinnamon samples. RESULTS: Ten independent runs of five-fold cross-validation showed that the training set error for the best-performing models (i.e., the linear discriminant and neural network models) was lower than 2%. The false-positive percentages for these models were 3% or lower, and the false-negative percentages were lower than 10%. In particular, the linear discriminant model perfectly classified the testing set with 0% error. Repeated iterations of training and testing gave similar results, demonstrating the reproducibility of these models. CONCLUSIONS: Chemometric models were able to classify the DART mass spectra of commercial cinnamon samples according to brand, with high specificity and low classification error. This method could easily be generalized to other classes of spices, and it could be applied to authenticating questioned commercial samples of spices or to examining evidence from improvised explosives.