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Background and Purpose: CT imaging exposes patients to ionizing radiation. MR imaging is radiation free but previously has not been able to produce diagnostic-quality images of bone on a timeline suitable for clinical use. We developed automated motion correction and use deep learning to generate pseudo-CT images from MR images. We aim to evaluate whether motion-corrected pseudo-CT produces cranial images that have potential to be acceptable for clinical use., Materials and Methods: Patients younger than age 18 who underwent CT imaging of the head for either trauma or evaluation of cranial suture patency were recruited. Subjects underwent a 5-minute golden-angle stack-of-stars radial volumetric interpolated breath-hold MR image. Motion correction was applied to the MR imaging followed by a deep learning-based method to generate pseudo-CT images. CT and pseudo-CT images were evaluated and, based on indication for imaging, either presence of skull fracture or cranial suture patency was first recorded while viewing the MR imaging-based pseudo-CT and then recorded while viewing the clinical CT., Results: A total of 12 patients underwent CT and MR imaging to evaluate suture patency, and 60 patients underwent CT and MR imaging for evaluation of head trauma. For cranial suture patency, pseudo-CT had 100% specificity and 100% sensitivity for the identification of suture closure. For identification of skull fractures, pseudo-CT had 100% specificity and 90% sensitivity., Conclusions: Our early results show that automated motion-corrected and deep learning-generated pseudo-CT images of the pediatric skull have potential for clinical use and offer a high level of diagnostic accuracy when compared with standard CT scans., (© 2024 by American Journal of Neuroradiology.)

Background: Though traumatic digital amputations are common, outcomes data are scarce. The FRANCHISE study clarified functional outcomes after digital amputation, but little information is available regarding mental health outcomes. The aims of this study were to document patient-reported mental health outcomes after traumatic digital amputation, elucidate the relationship between mental health and functional outcomes, and determine which patient/injury attributes conferred risk of unfavorable mental health outcomes., Methods: This was a descriptive, retrospective study of 77 patients with history of single digit, non-thumb traumatic amputation. Eligible patients completed Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity, Pain Interference, Anger, Anxiety, and Depression computer adaptive tests, and a short questionnaire recorded handedness, demographics, and worker's compensation status., Results: Correlation across the 3 PROMIS mental health domains (Anger, Anxiety, Depression) was uniformly strong and statistically significant. Correlation between the PROMIS mental health and functional (Upper Extremity and Pain Interference) scores was statistically significant but much weaker. Multivariable analysis revealed younger age and a worker's compensation claim had independent statistically significant predictive value for worse PROMIS Anger, Anxiety, and Depression scores. Female sex was also found to independently predict PROMIS Anxiety., Conclusions: By identifying patients at increased risk for feelings of anger, anxiety, and depression after digital amputation, anticipatory counseling can be provided. Anger, anxiety, and depression are very likely to coexist in the same patient; when responding to a patient who exhibits 1 element of this triad, the surgeon should be aware that the other 2 elements are likely to be present, even if not obvious., Competing Interests: Disclosures: The authors declare that they have no conflict of interest and received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors., (© 2023 HMP Global. All Rights Reserved. Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of ePlasty or HMP Global, their employees, and affiliates.)

Objective: Several studies have compared perioperative parameters and early postoperative morphology between endoscope-assisted strip craniectomy with orthotic therapy (endoscopic repair) and cranial vault remodeling (open repair). To extend these results, the authors evaluated school-age anthropometric outcomes after these techniques across three institutions., Methods: School-aged children (age range 4-18 years) with previously corrected isolated sagittal craniosynostosis were enrolled. Upon inclusion, 3D photographs and patient-reported outcomes were obtained, and the cephalic index and head circumference z-scores were calculated. Analyses of covariance models controlling for baseline differences and a priori covariates were performed., Results: Eighty-one participants (median [range] age 7 [4-15] years) were included. The mean (95% CI) school-age cephalic index was significantly higher in the endoscopic cohort, though within the normal range for both groups (endoscopic 78% [77%-79%] vs open 76% [74%-77%], p = 0.027). The mean change in the cephalic index from preoperation to school age was significantly greater in the endoscopic group (9% [7%-11%] vs open 3% [1%-5%], p < 0.001). Compared to preoperative measurements, mean school-age head circumference z-scores decreased significantly more in the open cohort (-1.6 [-2.2 to -1.0] vs endoscopic -0.3 [-0.8 to -0.2], p = 0.002). Patient-reported levels of stigma were within the normal limits for both groups., Conclusions: Endoscopic and open repair techniques effectively normalize school-age anthropometric outcomes. However, endoscopic repair produces a clinically meaningful and significantly greater improvement in the school-age cephalic index, with maintenance of head growth. These findings demonstrate the importance of early referral by pediatricians and inform treatment decisions.

The purpose of this study was to quantify the stigma associated with digital amputation and examine factors associated with it. One hundred and sixty-four digital amputees completed the Neurological Quality of Life-Stigma questionnaire and a battery of Patient-Reported Outcome Measurement Information System instruments. Multivariable analysis examined factors associated with stigma experience. The mean observed stigma score of 47 (SD 8, range 36-64) was similar to the mean value of the normal population. Younger age, a worker's compensation claim and depression were each independently associated with a more severe experience of stigma after digital amputation. Socioeconomic variables, anatomical details and mechanism of injury were not independently associated with stigma. Digital amputation is not highly stigmatizing overall. Surgeons should consider referring at-risk patients to a mental health provider for support during the coping and adjustment process after amputation. Level of evidence: III.

Petrolatum is widely used in cosmetics, topical pharmaceuticals and also as a vehicle in dermal toxicity studies. New Zealand white rabbits treated with white petrolatum (vehicle control) in a 2-week dermal irritation study exhibited moderate to severe erythema starting on Day 7 that subsided towards the end of the study. Histological examination of abraded and non-abraded petrolatum-treated skin obtained at termination (Day 15) revealed mild acanthosis, hyperkeratosis, dermal edema with mixed inflammatory cells in the dermis. Macroscopic and microscopic features noted in rabbits were consistent with dermal irritation to petrolatum. Wistar-Han rats, CD1 mice, C57/Bl/6J mice and Göttingen minipigs treated topically with white petrolatum did not exhibit clinical or histologic evidence of dermal irritation. Therapeutic agents developed for topical application are generally tested in rabbits during some point in development. Interpretation of skin irritation data from a single species can impact risk assessment for humans and on product labeling., (Copyright © 2013 John Wiley & Sons, Ltd.)

Withdrawal from benzodiazepines in physically dependent rodents often requires that the drug be dislodged from its receptor with a competitive antagonist. Withdrawal Seizure-Prone (WSP) mice were selectively bred for their susceptibility to handling-induced withdrawal convulsions following chronic treatment with ethanol. Reflecting pleiotropic genetic influences, they also experience more severe withdrawal from other sedative-hypnotics including the benzodiazepine, diazepam. We used this susceptible genotype to test whether other benzodiazepine receptor (BZR) agonists also produce physical dependence following acute administration, comparing studies of spontaneous withdrawal with those where convulsions were precipitated by a BZR antagonist (flumazenil). Separate groups of mice were tested following a single injection of one of eight BZR agonists. Several doses of each drug were tested for spontaneous withdrawal, and a single dose of each drug was tested for precipitated withdrawal. Withdrawal convulsions were seen after all of the drugs by at least one method, suggesting that BZR agonists as a class elicit acute physical dependence in this susceptible genotype.

It is sometimes supposed that standardizing tests of mouse behavior will ensure similar results in different laboratories. We evaluated this supposition by conducting behavioral tests with identical apparatus and test protocols in independent laboratories. Eight genetic groups of mice, including equal numbers of males and females, were either bred locally or shipped from the supplier and then tested on six behaviors simultaneously in three laboratories (Albany, NY; Edmonton, AB; Portland, OR). The behaviors included locomotor activity in a small box, the elevated plus maze, accelerating rotarod, visible platform water escape, cocaine activation of locomotor activity, and ethanol preference in a two-bottle test. A preliminary report of this study presented a conventional analysis of conventional measures that revealed strong effects of both genotype and laboratory as well as noteworthy interactions between genotype and laboratory. We now report a more detailed analysis of additional measures and view the data for each test in different ways. Whether mice were shipped from a supplier or bred locally had negligible effects for almost every measure in the six tests, and sex differences were also absent or very small for most behaviors, whereas genetic effects were almost always large. For locomotor activity, cocaine activation, and elevated plus maze, the analysis demonstrated the strong dependence of genetic differences in behavior on the laboratory giving the tests. For ethanol preference and water escape learning, on the other hand, the three labs obtained essentially the same results for key indicators of behavior. Thus, it is clear that the strong dependence of results on the specific laboratory is itself dependent on the task in question. Our results suggest that there may be advantages of test standardization, but laboratory environments probably can never be made sufficiently similar to guarantee identical results on a wide range of tests in a wide range of labs. Interpretations of our results by colleagues in neuroscience as well as the mass media are reviewed. Pessimistic views, prevalent in the media but relatively uncommon among neuroscientists, of mouse behavioral tests as being highly unreliable are contradicted by our data. Despite the presence of noteworthy interactions between genotype and lab environment, most of the larger differences between inbred strains were replicated across the three labs. Strain differences of moderate effects size, on the other hand, often differed markedly among labs, especially those involving three 129-derived strains. Implications for behavioral screening of targeted and induced mutations in mice are discussed., (Copyright 2003 Wiley Periodicals, Inc.)

Background: Genetic factors are well known to play an important role in determining individual differences in the metabolism of ethanol (EtOH), and several specific polymorphic loci have been identified that significantly contribute to the variability of EtOH metabolism in humans. However, these variant genes are either alcohol or aldehyde dehydrogenases, and the identification of new gene products that contribute to variation in alcohol metabolism would be useful., Methods: To identify quantitative trait loci (QTLs), we correlated variation in polymorphic markers with blood EtOH concentration and the rate of EtOH metabolism (beta) in C57BL/6J and DBA/2J strains and in 25 of their recombinant inbred strains after 2 and 3 g/kg of EtOH intraperitoneally., Results: A QTL associated with beta values for both doses was definitively mapped to the proximal region of chromosome 17, syntenic with human chromosome 6q25-27. Seven to 12 chromosomal regions were provisionally identified for each phenotype; several were associated with 2 or more phenotypes. Each QTL suggests the location of a gene or genes affecting EtOH pharmacokinetics. Candidate genes suggested by these analyses included several whose gene products are known to be induced by EtOH (e.g., superoxide dismutase, glutathione transferase, and cytochrome P450 2E1), as well as several whose gene products have signaling functions likely to contribute to this induction., Conclusions: These studies provide evidence for the existence of genes affecting EtOH metabolism in multiple chromosomal regions. Future studies will be required to identify the chromosome 17 gene product. Use of other genetic populations, such as B6D2F2 crosses, will be required to determine which of the provisional loci represent true and which represent false-positive associations.

Through the genetic technique of selective breeding, a mouse line [Withdrawal Seizure Prone (WSP)] has been developed that expresses severe handling-induced convulsions (HIC) after cessation of chronic ethanol exposure. These mice also display rebound elevations in HIC after a single ethanol injection. In the current studies, we tested WSP mice in several paradigms. WSP mice were found to be marginally sensitive to the effects of acute doses of dizocilpine to reduce HIC. However, when tested during acute withdrawal from a single ethanol injection, WSP were more sensitive to this compound. Although N-methyl-D-aspartate significantly elevated HIC in naive WSP mice, it was more effective at low doses when given during acute withdrawal. Withdrawing mice were slightly more sensitive than naive mice to kainic acid. Pentylenetetrazole elevated HIC in naive and withdrawing mice; it was marginally more effective in naive mice. Diazepam inhibited HIC in both naive and withdrawing mice, and was slightly more effective during acute withdrawal. This pattern of results suggests that acute alcohol withdrawal is accompanied by altered sensitivity to convulsants and anticonvulsants. These changes include enhanced sensitivity in at least two excitatory amino acid-gated ion channel binding sites.

Using the techniques of selective breeding, mouse lines have been developed that express severe (Withdrawal Seizure Prone: WSP) or mild (Withdrawal Seizure Resistant: WSR) handling induced convulsions after cessation of chronic ethanol exposure. These lines differ at least ten-fold in severity of withdrawal after identical ethanol treatment. One feature of the genetic model is that other traits which distinguish these lines are presumably influenced by those genes determining ethanol withdrawal severity. WSP and WSR mice do not differ markedly in the metabolism of ethanol. In addition to handling induced convulsions, they also differ in other withdrawal signs: for example, WSP mice show more pronounced tremor. WSP and WSR mice do not differ in sensitivity to ethanol's hypothermic, anesthetic, or locomotor stimulant effects, nor in the magnitude of tolerance development to these responses. This suggests that sensitivity, tolerance and dependence are distinct genetic entities. WSP mice also display more severe withdrawal from diazepam, phenobarbital, and nitrous oxide than WSR mice, suggesting that some genes generally predispose mice to withdrawal from depressants. WSP mice display withdrawal handling induced convulsions after a single dose of ethanol, pentobarbital, or diazepam. The effective dose for producing drug seizures is not markedly different between WSP and WSR mice for a number of compounds with varied mechanisms of action. However, WSP mice are more sensitive than WSR mice to the effects of acute doses of convulsants to elevate handling induced convulsions. WSP mice have more binding sites in hippocampus for the N-methyl-D-aspartate antagonist MK 801. Binding of this ligand is increased during ethanol dependence in both mouse lines.(ABSTRACT TRUNCATED AT 250 WORDS)