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Andrea Nicole Weber,1 Joshua Trebach,2 Marielle A Brenner,2 Mary Margaret Thomas,3 Nicholas L Bormann4 1Department of Psychiatry, University of Iowa, Iowa City, IA, USA; 2Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA; 3Hardin Library for the Health Sciences, University of Iowa, Iowa City, IA, USA; 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USACorrespondence: Andrea Nicole Weber, Department of Psychiatry, University of Iowa, 500 Newton Road, 1-308 MEB, Iowa City, IA, 52242, USA, Tel +1-319-335-6980, Fax +1-319-384-7467, Email andrea-n-weber@uiowa.eduAbstract: Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.Keywords: synthetic opioids, treatment, diagnosis, prevention, addiction medicine

An important aspect of how viruses spread and infect is the viral burst size, or the number of new viruses produced by each infected cell. Surprisingly, this value remains poorly characterized for influenza A virus (IAV), commonly known as the flu. In this study, we screened tens of thousands of cells using a microfluidic method called droplet quantitative PCR (dqPCR). The high-throughput capability of dqPCR enabled the measurement of a large population of infected cells producing progeny virus. By measuring the fully assembled and successfully released viruses from these infected cells, we discover that the viral burst sizes for both the seasonal H3N2 and the 2009 pandemic H1N1 strains vary significantly, with H3N2 ranging from 101 to 104 viruses per cell, and H1N1 ranging from 101 to 103 viruses per cell. Some infected cells produce average numbers of new viruses, while others generate extensive number of viruses. In fact, we find that only 10% of the single-cell infections are responsible for creating a significant portion of all the viruses. This small fraction produced approximately 60% of new viruses for H3N2 and 40% for H1N1. On average, each infected cell of the H3N2 flu strain produced 709 new viruses, whereas for H1N1, each infected cell produced 358 viruses. This novel method reveals insights into the flu virus and can lead to improved strategies for managing and preventing the spread of viruses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Nucleic acid amplification testing (NAAT) remains one of the most reliable methods for pathogen identification. However, conventional bulk NAATs may not be sufficiently fast or sensitive enough for the detection of clinically-relevant pathogens in point-of-care testing. Here, we have developed a digital droplet RT-LAMP (ddRT-LAMP) assay that rapidly and quantitatively detects the SARS-CoV-2 viral E gene in microfluidic drops. Droplet partitioning using ddRT-LAMP significantly accelerates detection times across a wide range of template concentrations compared to bulk RT-LAMP assays. We discover that a reduction in droplet diameter decreases assay times up to a certain size, upon which surface adsorption of the RT-LAMP polymerase reduces reaction efficiency. Optimization of drop size and polymerase concentration enables rapid, sensitive, and quantitative detection of the SARS-CoV-2 E gene in only 8 min. These results highlight the potential of ddRT-LAMP assays as an excellent platform for quantitative point-of-care testing., Competing Interests: David A. Weitz is an editor‐in‐chief, and Fangfu Ye an associate editor of Smart Medicine. They were not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Author(s). Smart Medicine published by Wiley‐VCH GmbH on behalf of Wenzhou Institute, University of Chinese Academy of Sciences.)

Importance: The rate of maternal mortality in the United States is 2-fold to 3-fold greater than that in other high-income countries. While many national initiatives have been developed to combat maternal mortality, these efforts often fail to include mental illness., Objective: To highlight the underrecognized contribution of mental illness to maternal mortality, which is nearly double that of postpartum hemorrhage., Evidence Review: A topic outline was developed to include challenges in measuring perinatal mental conditions and mortality rates; contributions of social determinants of health to mental conditions and mortality; perinatal psychiatric disorder characterization; mechanisms by which maternal mental illness increases mortality, specifically, suicide and addictive disorders; access limitations and care "deserts"; prenatal stress and its impact on reproductive outcomes; increasing clinician expertise through cross-disciplinary education; intervention sites and models; and asserting that mental health is fundamental to maternal health. Publications in the last 3 years were prioritized, particularly those relating to policy. References were selected through consensus. Sources were PubMed, Ovid, direct data published on government websites, and health policy sources such as the Policy Center for Maternal Mental Health., Findings: Priority was given to recent sources. Citations from 2022-2023 numbered 26; within the last 5 years, 14; and historical references, 15. Recommendations to address each topic area serve as concluding statements for each section. To mitigate the contributions of mental illness to the maternal mortality risk, a coordinated effort is required across professional and governmental organizations., Conclusions and Relevance: Concrete programmatic and policy changes are needed to reduce perinatal stress and address trauma, standardize the collection of social determinant of health data among perinatal patients, increase access to reproductive psychiatry curricula among prescribers, reduce perinatal mental health and obstetrical deserts, institute paid parental leave, and support seamless integration of perinatal and behavioral health care. Moreover, instead of focusing on a relatively minor portion of the contributors to health that current medical practice targets, fortifying the social foundation strengthens the prospects for the health of families for our current and future generations.

Competing Interests: The authors have no conflicts of interest to declare.

With recent advancements in cancer therapy, especially immunotherapy, overall survival of many cancers has increased and patient toxicity has been reduced. However, many complications of traditional cancer therapy are still prevalent and complications of novel therapies are just beginning to appear. The neuroradiologist may be the first to visualize signs of these complications on imaging. This article describes the notable imaging findings of several unique and characteristic complications of CNS cancer therapy, including toxicities of chemotherapies, immunotherapies, and radiotherapy. Complications of chemotherapeutic agents covered include methotrexate-induced and disseminated necrotizing leukoencephalopathy, and chemotherapy-induced myelopathy. Immunotherapy complications included are Tacrolimus-related Optic Neuropathy, Rituximab and Immune reconstitution inflammatory syndrome-associated Progressive Multifocal Leukoencephalopathy, Bevacizumab-associated late radiation-induced neurotoxicity, and Ipilimumab-induced hypophysitis. Lastly, radiation-induced neurotoxicities are covered, including myelopathy, radiation necrosis, cerebral atrophy, leukoencephalopathy, optic neuropathy, mineralizing microangiopathy, stroke-like migraine attacks, osteonecrosis, and vasculopathies. Neuroradiologists will increasingly encounter patients who have undergone treatment with more than 1 therapeutic modality, resulting in overlapping findings as well. Recognition of the common complications of these therapies on imaging is critical to minimizing the effects of these potential short- and long-term complications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recurrent and severe infections occurred in children with Down Syndrome (DS) due to immunological parameter defects have been reported. The aim of the study is to evaluate the importance of using T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) as molecular markers for immunological investigation of children with DS. The study included 40 non-disjunction trisomy 21 confirmed DS children, and 25 healthy controls. Peripheral blood (PB) was analyzed for lymphocyte subpopulations by flow cytometry, serum immunoglobulin levels, and TREC and KREC copy numbers using quantitative real-time PCR. DS patients showed significantly lower absolute counts of PB T lymphocytes, T helper lymphocytes, T cytotoxic lymphocytes, B lymphocytes, and Natural killer cells, and lower serum IgA, IgG, and IgM levels compared to healthy controls. Copy number of TREC and KREC showed no significant differences between DS patients and healthy controls. There is a significant positive correlation between TREC copy number with a percentage and absolute count of helper T lymphocytes in patients. Also, the KREC copy number was significantly negatively correlated with the age of patients. These findings suggest that copy numbers of TREC and KREC could be useful as molecular markers for immunological evaluation of patients with DS., (© 2023. Springer Nature Limited.)

Abstract: Szivak, TK, Thomas, MM, Pietrzak, RH, Nguyen, DR, Ryan, DM, and Mazure, CM. Obesity Risk Among West Point Graduates Later in Life. J Strength Cond Res 37(6): 1284-1291, 2023-The purpose of this investigation was to evaluate sex differences in health and fitness outcomes among United States Military Academy (USMA) graduates (class years 1980-2011). Subjects ( n = 701 men, 641 women, age: 45.7 ± 9.3 years) were surveyed as a part of a larger investigation on risk and resiliency factors among USMA graduates. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) short form and calculation of weekly metabolic equivalents (METs). Overweight and obesity status were assessed by body mass index (BMI). Significance for the study was set at p ≤ 0.05. Obesity rates for men (30.1%) were significantly higher than for women (16.6%). Men reported significantly higher ( p = 0.01) vigorous METs·wk -1 (1,214.6 ± 1,171.6) than women (1,046.8 ± 1,133.2) despite significantly higher ( p = 0.00) BMI values (28.75 ± 4.53 kg·m -2 ) than women (25.90 ± 5.48 kg·m -2 ). Women were 89% more likely to have ever been on a diet and reported higher (15.2%) Army Body Composition Program enrollment rates than men (6.3%). Obesity rates among men reflect trends seen in the broader military, Veteran, and U.S. adult populations, whereas obesity rates among women were lower. Men may be at a greater risk for obesity later in life despite higher self-reported physical activity; however, lean body mass and self-report bias should be considered. Because lifetime obesity may be influenced by factors other than physical activity, health initiatives should use a comprehensive approach early in the career of military officers., (Copyright © 2023 National Strength and Conditioning Association.)

Background and Aims: COVID-19 has disrupted the patient workflow in all healthcare settings. Procedures such as bronchoscopy and spirometry require additional pre-procedure screening for SARS-CoV-2. However, there is uncertainty regarding the utility of this universal pre-procedure screening. The State of Qatar has a robust contact tracing system in place in the form of the mobile application 'Ehteraz.' This study assesses the utility of various pre-procedural screening measures in asymptomatic patients and generate recommendations for any potential improvement in the workflow., Methods: This is a cross-sectional study of asymptomatic patients who had SARS-CoV-2 RT-PCR screening performed before bronchoscopy or lung function testing scheduled on an elective basis. Descriptive statistics were used to summarize and determine the sample characteristics. The rate of the positive PCR test result was subsequently calculated., Results: Two patients (0.34%) tested positive for COVID-19 on their pre-procedural screen. Four patients (0.68%) had an inconclusive result., Conclusion: The positivity rate of SARS-CoV-2 RT-PCR is extremely low in asymptomatic individuals screened before bronchoscopy and spirometry. The authors recommend pre-procedural symptom and electronic application-based contact screening instead of universal pre-procedural SARS-CoV-2 RT-PCR for screening asymptomatic individuals., Competing Interests: The authors declare no competing interests.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Mutations in the filaggrin (FLG) gene has been reported to be an indicator of poor prognosis of atopic dermatitis (AD). It has been reported that there is a considerable variation in the mutations detected in the FLG gene in different ethnicities., Aim: To detect the presence of mutations in the FLG gene in pediatric subjects with atopic dermatitis (AD) and to compare the detected mutations with those already reported from different ethnicities., Materials and Methods: Genomic DNA extracted using standard procedure from peripheral venous blood of 30 patient and 15 control samples. Sequence analysis of the FLG gene carried out and detected changes was then cross referenced with those mutations already reported to check for novelty of detected changes., Results: Amino acid changes were detected in 28 of the patient samples and in none of the control samples indicating that changes in the FLG gene were more common in the patient group than the control group (Fishers exact test, P < 0.0001). The most commonly reported mutations R501X and 2282del4 were not detected. Only 5 of the detected 22 amino acid changes H2507Q, L2481S, K2444E, E2398Q, and S2366T have been previously reported and are not clinically significant; however, in one patient a stop codon was detected (S2366STOP). P2238N, R2239W, and V2243L detected in 70% of the samples and S2231E detected in 67% of the patient samples have not been reported so far and their clinical significance is yet to be analyzed., Conclusion: Analyses of mutations already reported showed that the changes detected from this study are novel to Indian traits. While this adds on to the minimal data available from the Indian subcontinent further analyses has to be carried out to analyze the pathogenicity of these detected changes on larger samples sizes., Aim: To detect the presence of mutations in the FLG gene in pediatric subjects with atopic dermatitis (AD) and to compare the detected mutations with those already reported from different ethnicities., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

Background and Purpose: Automated volumetric analysis of structural MR imaging allows quantitative assessment of brain atrophy in neurodegenerative disorders. We compared the brain segmentation performance of the AI-Rad Companion brain MR imaging software against an in-house FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline., Materials and Methods: T1-weighted images of 45 participants with de novo memory symptoms were selected from the OASIS-4 database and analyzed through the AI-Rad Companion brain MR imaging tool and the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. Correlation, agreement, and consistency between the 2 tools were compared among the absolute, normalized, and standardized volumes. Final reports generated by each tool were used to compare the rates of detection of abnormality and the compatibility of radiologic impressions made using each tool, compared with the clinical diagnoses., Results: We observed strong correlation, moderate consistency, and poor agreement between absolute volumes of the main cortical lobes and subcortical structures measured by the AI-Rad Companion brain MR imaging tool compared with FreeSurfer. The strength of the correlations increased after normalizing the measurements to the total intracranial volume. Standardized measurements differed significantly between the 2 tools, likely owing to differences in the normative data sets used to calibrate each tool. When considering the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline as a reference standard, the AI-Rad Companion brain MR imaging tool had a specificity of 90.6%-100% and a sensitivity of 64.3%-100% in detecting volumetric abnormalities. There was no difference between the rate of compatibility of radiologic and clinical impressions when using the 2 tools., Conclusions: The AI-Rad Companion brain MR imaging tool reliably detects atrophy in cortical and subcortical regions implicated in the differential diagnosis of dementia., (© 2023 by American Journal of Neuroradiology.)

The coronavirus disease 2019 (COVID-19) pandemic affected millions of people worldwide resulting in a substantial number of hospitalizations. Venous thromboembolism including pulmonary embolism is a known complication of COVID-19 pneumonia although its incidence in such patients is unclear. In this multicenter retrospective cohort study, we looked at the incidence of pulmonary embolism in COVID-19 patients and its associations with various risk factors including demographics, comorbidities, inflammatory markers and coagulation profiles. We analyzed data from 193 patients of mixed ethnicity with a mean age of 51, mostly South Asians (62%) and Arabs (29%). Diabetes and hypertension were the most prevalent comorbidities accounting for 46% (N = 88) and 36% (N = 71) respectively. Critical COVID-19 illness was diagnosed in 67% of patients. The frequency of COVID-19 related pulmonary embolism was 21.8% (N = 42). We found no association of pulmonary embolism with demographic, comorbid or inflammatory variables. Only a raised D-Dimer was found to be associated with pulmonary embolism. Having a pulmonary embolism had no impact on the length of stay, critical illness, or mortality. Receiving steroids or being on standard thromboprophylaxis or weight/D-Dimer adjusted thromboprophylaxis also had no impact on the frequency of pulmonary embolism. Nine incidents of major bleeding were recorded independent of therapeutic anticoagulation. Patients admitted to the hospital for COVID-19 pneumonia had a relatively high incidence of pulmonary embolism. D-dimer was the only associated laboratory parameter associated with pulmonary embolism. However, further research is needed to evaluate its predictive and prognostic utility, particularly in an older population., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

US physicians in multiple specialties who order or conduct radiological procedures lack formal radiation science education and thus sometimes order procedures of limited benefit or fail to order what is necessary. To this end, a multidisciplinary expert group proposed an introductory broad-based radiation science educational program for US medical schools. Suggested preclinical elements of the curriculum include foundational education on ionizing and nonionizing radiation (eg, definitions, dose metrics, and risk measures) and short- and long-term radiation-related health effects as well as introduction to radiology, radiation therapy, and radiation protection concepts. Recommended clinical elements of the curriculum would impart knowledge and practical experience in radiology, fluoroscopically guided procedures, nuclear medicine, radiation oncology, and identification of patient subgroups requiring special considerations when selecting specific ionizing or nonionizing diagnostic or therapeutic radiation procedures. Critical components of the clinical program would also include educational material and direct experience with patient-centered communication on benefits of, risks of, and shared decision making about ionizing and nonionizing radiation procedures and on health effects and safety requirements for environmental and occupational exposure to ionizing and nonionizing radiation. Overarching is the introduction to evidence-based guidelines for procedures that maximize clinical benefit while limiting unnecessary risk. The content would be further developed, directed, and integrated within the curriculum by local faculties and would address multiple standard elements of the Liaison Committee on Medical Education and Core Entrustable Professional Activities for Entering Residency of the Association of American Medical Colleges., (Published by Elsevier Inc.)

Gold nanoclusters (AuNCs) are an intensely pursued class of fluorophores with excellent biocompatibility, high water solubility, and ease of further conjugation. However, their low quantum yield limits their applications, such as ultra-sensitive chemical or molecular sensing. To address this problem, various strategies have been adopted for augmenting their fluorescence intensity. Herein, we report a facile and scalable approach for the fluorescence enhancement of bovine serum albumin (BSA) capped AuNCs (BSA-AuNCs) using periodic, close-packed polystyrene colloidal photonic crystals (CPCs). The slow photon effect at the bandgap edges is utilized for the increased light-matter interactions and thereby enhancing the fluorescence intensity of the BSA-AuNCs. Compared to the planar polystyrene control sample, the CPC film yielded a 14-fold enhancement in fluorescence intensity. Further, we demonstrated the as-prepared BSA-AuNCs-CPC as a solid-state platform for the highly sensitive and selective fluorescence turn-off detection of creatinine at nanomolar level., (© 2022 Wiley-VCH GmbH.)

Background: Arginase deficiency is considered a masquerader of diplegic cerebral palsy. The rarity of hyperammonemic crisis and the slowly progressive course has made it a unique entity among the urea cycle defects., Objectives: The aim of our study is to describe the varied phenotypic spectrum of children with arginase deficiency., Methodology: This retrospective study included children and adolescents aged <18 years with a biochemical or genetic diagnosis of arginase deficiency from May 2011 to May 2022. Data were collected from the hospital's electronic database. The clinical presentation, laboratory parameters at baseline and during metabolic decompensation, neuroimaging, electroencephalography findings, and molecular studies were analyzed., Results: About 11 children from nine families with biochemically or genetically proven arginase deficiency were analyzed. The male: female ratio was 2.7:1. Consanguineous parentage was observed in all children. The median age at presentation was 36 months (Range: 5 months-18 years). All children with onset of symptoms in early childhood had a predominant delay in motor milestones of varying severity. Metabolic decompensation with encephalopathy occurred in all except two children (n = 9, 81.8%). Pyramidal signs were present in all patients and additional extrapyramidal signs in two children. Positive family history was present in four probands. Seizures occurred in all children. Epilepsy with electrical status in slow wave sleep and West syndrome was noted in three children. All children had elevated ammonia and arginine at the time of metabolic crisis. The spectrum of neuroimaging findings includes periventricular, subcortical, and deep white matter signal changes and diffusion restriction. The mean duration of follow-up was 38.6 ± 34.08 months. All patients were managed with an arginine-restricted diet and sodium benzoate with or without ornithine supplementation., Conclusion: Spastic diparesis, recurrent encephalopathy, presence of family history, and elevated serum arginine levels must alert the clinician to suspect arginase deficiency. Atypical presentations in our cohort include frequent metabolic crises and epileptic encephalopathy. Early identification and management will ensure a better neurodevelopmental outcome., Competing Interests: There are no conflicts of interest, (Copyright: © 2022 Annals of Indian Academy of Neurology.)

Objective: The aim of this study is to evaluate high-risk pregnant females' offspring as regard the presence of any medical condition, hereditary disorder, or major anomaly as well as to document parental sociodemographic characteristics and compliance with follow-up schedules of fetal medicine and clinical genetic clinics., Study Design: This prospective 2-year cohort study of neonates and infants reported the referral indications, investigations, and diagnoses obtained through prenatal and postnatal examinations. It also reported their parental follow-up vigilance., Results: Of the 811 infants of high risk females referred 460 (56.7%) came for assessment. Mean parental consanguinity and endogamy were 67 and 71.3%, respectively. All pregnant mothers underwent first-trimester biochemical testing (plasma protein-A, α-fetoprotein [AFP], human chorionic gonadotropin [hCG]) and serial ultrasound examinations. Seventy mothers needed second-trimester biochemical testing (AFP, hCG, and estriol). Sixty-two mothers underwent amniocentesis where G-banding karyotype, fluorescence in situ hybridization and targeted molecular testing for the specific gene mutation of single gene disorders were conducted according to suspected disorders. High quality fetal ultrasound was performed when brain malformations were suspected, while 16 fetuses required brain MRI examination. Mean age of newborns at first examination was 26.5 days. They were grouped according to the maternal indication for referral. Upon examination, 18 neonates had confirmed congenital malformations/genetic disorders. Five of them were diagnosed prenatally. In four other fetuses with single gene disorder, the molecular diagnosis of their affected siblings was not established prior to this pregnancy; thus, prenatal diagnosis was not possible. The remaining nine cases were diagnosed postnatally., Conclusion: Parental consanguinity and endogamy were increased among high-risk pregnancies. Public awareness about potential adverse effects of consanguineous marriages and the importance of genetic testing are imperative. A structured multidisciplinary team of specialists in fetal medicine, clinical genetics, and neonatology provides good genetic services. Expansion and financial support of these services are urgently required., Key Points: · A multidisciplinary team provides good genetic services in high-risk pregnancies.. · Parental consanguinity and endogamy are increased among high-risk pregnancies.. · Increased public awareness about genetic testing importance and financial support are imperative.., Competing Interests: None declared., (Thieme. All rights reserved.)

Drop-based microfluidics has revolutionized single-cell studies and can be applied toward analyzing tens of thousands to millions of single cells and their products contained within picoliter-sized drops. Drop-based microfluidics can shed insight into single-cell virology, enabling higher-resolution analysis of cellular and viral heterogeneity during viral infection. In this work, individual A549, MDCK, and siat7e cells were infected with influenza A virus (IAV) and encapsulated into 100-μm-size drops. Initial studies of uninfected cells encapsulated in drops demonstrated high cell viability and drop stability. Cell viability of uninfected cells in the drops remained above 75%, and the average drop radii changed by less than 3% following cell encapsulation and incubation over 24 h. Infection parameters were analyzed over 24 h from individually infected cells in drops. The number of IAV viral genomes and infectious viruses released from A549 and MDCK cells in drops was not significantly different from bulk infection as measured by reverse transcriptase quantitative PCR (RT-qPCR) and plaque assay. The application of drop-based microfluidics in this work expands the capacity to propagate IAV viruses and perform high-throughput analyses of individually infected cells. IMPORTANCE Drop-based microfluidics is a cutting-edge tool in single-cell research. Here, we used drop-based microfluidics to encapsulate thousands of individual cells infected with influenza A virus within picoliter-sized drops. Drop stability, cell loading, and cell viability were quantified from three different cell lines that support influenza A virus propagation. Similar levels of viral progeny as determined by RT-qPCR and plaque assay were observed from encapsulated cells in drops compared to bulk culture. This approach enables the ability to propagate influenza A virus from encapsulated cells, allowing for future high-throughput analysis of single host cell interactions in isolated microenvironments over the course of the viral life cycle.

Background: Most centers in developing countries prefer chelation therapy with D-penicillamine for the management of Wilson's disease (WD) because of its easy availability and affordability. Neurological worsening following treatment with D-penicillamine is not uncommon. However, there is a paucity of Indian data on the incidence of neurological worsening in children and adolescents with WD following chelation therapy. Our study objectives were to identify the prevalence of neurological worsening in children and adolescents with WD following chelation with D-penicillamine therapy and to describe the management options and outcomes in these patients., Materials and Methods: In this retrospective chart review, children and adolescents with an established diagnosis of WD from 2010 to 2020 were identified from the hospital electronic database. Among these patients, data of children and adolescents with neurological worsening following D-penicillamine therapy were extracted and analyzed., Results: Neurological worsening was observed in 27/122 (22.1%) children and adolescents with WD on chelation therapy with D-penicillamine. Fifteen patients with neurological worsening following D-penicillamine therapy were managed with zinc monotherapy. Four patients were managed with a combination therapy of zinc and trientine. Five patients were treated with trientine monotherapy. Re-challenging with D-penicillamine at a lower dose followed by a slow dose escalation was attempted in three patients. Gradual clinical and functional status improvement was observed in 24 cases while one patient succumbed to pneumonia., Conclusion: Children and adolescents with WD who had neurological worsening on D-penicillamine therapy may be managed with trientine. Zinc monotherapy with copper restricted diet was also found to be effective in non-affordable patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Annals of Indian Academy of Neurology.)

The aim of this study is to screen for variants in NPHS1 and NPHS2, in a cohort of Egyptian children with steroid-resistant nephrotic syndrome (SRNS)/focal segmental glomerulosclerosis (FSGS) and compare the prevalence of such variants among other ethnic groups. The study included 25 patients: 21 children diagnosed clinically as steroid-resistant nephrotic syndrome and confirmed as FSGS by renal biopsy and four patients diagnosed as congenital nephrotic syndrome with FSGS. Mutational analysis revealed nine NPHS2 and NPHS1 variants in 13/25 patients with a pathogenic variant detection rate of 52%. NPHS2 variants were found in 8 patients (32%) while five patients from four unrelated families (20%) harbored variants in NPHS1 gene. Six variants were not described before including a likely founder NPHS2 variant in our population, c.596dupA (p.Asn199LysfsTer14). In conclusion, we reported the largest series of patients with SRNS/FSGS from Egypt and identified many novel NPHS1 and NPHS2 variants expanding their mutational spectrum. Further studies on a larger number of patients could provide new insights into the pathogenic mechanisms of SRNS/FSGS which might help in patient's management and prognosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective To evaluate the chromosomal microarray (CMA) yield among children who presented with global developmental delay/intellectual disability (GDD/ID) with/without co-occurring conditions. Methods: The pathogenic copy number variation (pCNVs) findings on CMA of all children who presented with unexplained GDD/ID were categorized based on the clinical features. The karyotype results were compared with CMA. Results: The overall pCNV yield in children presenting with GDD/ID with or without comorbid conditions constituted 20.9%. Among the 17 pCNVs, 13 were losses and four were gains. Cardiac defect was the only co-morbidity in our study that demonstrated statistically significant prediction for pCNV (odds ratio 6.13, p value- 0.031). Six children who were karyotyped prior to CMA testing showed a structural abnormality. Conclusions: In our study, 20.9% of children with GDD/ID showed pCNVs on CMA. Cardiac defect alongside GDD/ID, emerged as the single strongest phenotype associated with pCNVs. CMA also provided vital information in previously karyotyped patients.

Urbanization introduces the threat of increased epidemic disease transmission resulting from crowding on mass transit. The coronavirus disease 2019 (COVID-19) pandemic, which has directly led to over 600,000 deaths in the US as of July 2021, triggered mass social distancing policies to be enacted as a key deterrent of widespread infections. Social distancing can be challenging in confined spaces required for transportation such as mass transit systems. Little is published regarding the degree to which mass transit system adoption effects impacted the rise of the COVID-19 pandemic in urban centers. Taking an ecological approach where areal data are the unit of observation, this national-scale study aims to measure the association between the adoption of mass transit and COVID-19 spread through confirmed cases in US metropolitan areas. National survey-based transit adoption measures are entered in negative binomial regression models to evaluate differences between areas. The model results demonstrate that mass transit adoption in US metropolitan areas was associated with the magnitude of outbreaks. Higher incidence of COVID-19 early in the pandemic was associated with survey results conveying higher transit use. Increasing weekly bus transit usage in metropolitan statistical areas by one scaled unit was associated with a 1.38 [95% CI: (1.25, 1.90)] times increase in incidence rate of COVID-19; a one scaled unit increase in weekly train transit usage was associated with an increase in incidence rate of 1.54 [95% CI: (1.42, 2.07)] times. These conclusions should inform early action practices in urban centers with busy transit systems in the event of future infectious disease outbreaks. Deeper understanding of these observed associations may also benefit modeling efforts by allowing researchers to include mathematical adjustments or better explain caveats to results when communicating with decision makers and the public in the crucial early stages of an epidemic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Since the first steps of creating the Alliance of Medical Student Educators in Radiology (AMSER) curriculum 20 years ago, dramatic advances in medical imaging, patient care, and medical education have occurred necessitating an update of this valuable resource. The 2020 update of the AMSER curriculum aims to address as many of these changes while providing a succinct resource that will hopefully remain useful for years to come. The updated AMSER curriculum document is freely available for download via the AMSER website at https://www.aur.org/en/affinity-groups/amser/curriculum., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Green thermoplastic starch (TPS) nanocomposite films aided by cellulose nanofibers (CNFs) from Chrysopogon zizanioides roots were developed and characterized. When compared to other lignocellulosic fibers, Chrysopogon zizanioides roots revealed exceptionally high cellulose content (~48%). CNFs were separated using an environmentally friendly acid isolation technique that included three stages: (i) alkali treatment; (ii) bleaching; and (iii) mild acid hydrolysis using oxalic acid in an autoclave. Following that, green nanocomposite films were made from potato starch using the solution casting process, by which we used glycerol (30 wt%) to make thermoplastic starch. Then, cellulose nanofibers in different concentrations (0, 1, 2, 3, 4 wt%) were added to the thermoplastic starch matrix. The isolated CNFs had diameters in the range of 17-27 nm. Besides, these nanostructures presented a very high crystallinity index (~65%), thereby enhanced the thermal stability. TPS/CNF green nanocomposites containing 3 wt% CNFs had exceptional tensile strength (~161%), tensile modulus (~167%), thermal stability, and crystallinity. As a result, nanocomposite films made of starch and cellulose nanofibers (3 wt%) extracted from Chrysopogon zizanioides roots would be alternatives for sustainable packaging. It can be concluded that Chrysopogon zizanioides roots have high potential for polymer industry., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The purpose of this study was to examine factors associated with psychological resilience in a nationally representative sample of West Point graduates. Aims: The aims of this study were to (a) employ a dimensional approach to operationalizing psychological resilience in a trauma-exposed population that had been highly trained and educated in persisting in the face of stress, was previously unstudied, and in which we could examine correlates of resilience, (b) identify key psychosocial factors, character traits, health variables, military experiences, and coping strategies as potential correlates of psychological resilience; and (c) examine whether reported gender moderated any of these associations in this population. Methods: A nationally representative sample of 1342 West Point graduates after gender integration from classes 1980 to 2011 were surveyed. Psychological resilience was operationalized using a discrepancy-based approach in which a measure of composite psychological distress (current posttraumatic stress disorder, generalized anxiety and depression symptoms) was regressed on measures of cumulative trauma burden. A multivariable linear regression model was then employed to identify factors that were independently associated with psychological resilience scores. Results: Purpose in life (29.8% of relative variance explained [RVE]), fewer perceived negative experiences in the military (20.6% RVE), social support (9.6% RVE), and grit (9.5% RVE) were the strongest correlates of psychological resilience scores for both women and men. Time in service was positively associated with resilience in women only. Conclusion: This study identifies key correlates of psychological resilience in West Point graduates, individuals who are highly trained to persevere in the face of stress and then were trauma-exposed. Most of these factors are modifiable and can be targeted in stress prevention and treatment interventions, especially for high-stress professions such as the military, frontline health care providers, and first responders., Competing Interests: Declaration of Conflicting Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The author Southwick wishes to declare he receives royalties for one of the cited references: Resilience: The science of mastering life’s greatest challenges. The authors Thomas, Pietrzak, Nguyen, Ryan, and Mazure report no financial affiliation or other relationship relevant to the subject of this manuscript., (© The Author(s) 2021.)

Competing Interests: There are no conflicts of interest.

The lacrimal drainage system (LDS) pathology is frequently encountered in the ophthalmology setting but is rarely discussed in the radiology literature. This is even truer for adult LDS lesions despite increase utilization of computed tomography and magnetic resonance in imaging for diagnosis of LDS pathology. The purpose of this image rich review is to highlight common adult LDS pathologies and introduce the radiologist to rare disease entities affecting this pathology rich anatomical region with emphasis on imaging findings, clinical presentation, and differential generation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Desbuquois dysplasia type 1 (DBQD1) is a very rare skeletal dysplasia characterized by growth retardation, short stature, distinct hand features, and a characteristic radiological monkey wrench appearance at the proximal femur. We report on 2unrelated Egyptian patients having the characteristic features of DBQD1 with different expressivity. Patient 1 presented at the age of 45 days with respiratory distress, short limbs, faltering growth, and distinctive facies while patient 2 presented at 5 years of age with short stature and hypospadias. The 2 patients shared radiological features suggestive of DBQD1. Whole-exome sequencing revealed a homozygous frameshift mutation in the CANT1 gene (NM&#95;001159772.1:c.277&#95;278delCT; p.Leu93ValfsTer89) in patient 1 and a homozygous missense mutation (NM&#95;138793.4:c.898C>T; p.Arg300Cys) in patient 2. Phenotypic variability and variable expressivity of DBQD was evident in our patients. Hypoplastic scrotum and hypospadias were additional unreported associated findings, thus expanding the phenotypic spectrum of the disorder. We reviewed the main features of skeletal dysplasias exhibiting similar radiological manifestations for differential diagnosis. We suggest that the variable severity in both patients could be due to the nature of the CANT1 gene mutations which necessitates the molecular study of more cases for phenotype-genotype correlations., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

The Accreditation Council for Graduate Medical Education is currently in the process of specialty-by-specialty revision of the Milestones. As a result, the Neuroradiology Milestones 2.0 Workgroup was created to refine a system of competency-based assessments for fellow educational growth and development. Strengths of the new Milestones include decreased complexity and uniformity within a subcompetency as it relates to a specific educational development trajectory. The Supplemental Guide serves to decrease clutter in the Milestones 2.0 document and provides a more practical resource for guidance. This article serves to review the history of the Neuroradiology Milestones, followed by a summary of the timeline of events and discussions of the workgroup for development of Neuroradiology Milestones 2.0 and a synopsis of major changes. The plan is for the updated Neuroradiology Milestones to take effect in 2021 or 2022 based on public commentary., (© 2021 by American Journal of Neuroradiology.)

At least 14 distinctive PEX genes function in the biogenesis of peroxisomes. Biallelic alterations in the peroxisomal biogenesis factor 12 (PEX12) gene lead to Zellweger syndrome spectrum (ZSS) with variable clinical expressivity ranging from early lethality to mildly affected with long-term survival. Herein, we define 20 patients derived from 14 unrelated Egyptian families, 19 of which show a homozygous PEX12 in-frame (c.1047&#95;1049del p.(Gln349del)) deletion. This founder mutation, reported rarely outside of Egypt, was associated with a uniformly severe phenotype. Patients showed developmental delay in early life followed by motor and mental regression, progressive hypotonia, unsteadiness, and lack of speech. Seventeen patients had sparse hair or partial alopecia, a striking feature that was not noted previously in PEX12. Neonatal cholestasis was manifested in 2 siblings. Neurodiagnostics showed consistent cerebellar atrophy and variable white matter demyelination, axonal neuropathy in about half, and cardiomyopathy in 10% of patients. A single patient with a compound heterozygous PEX12 mutation exhibited milder features with late childhood onset with gait disturbance and learning disability. Thus, the PEX12 relatively common founder mutation accounts for the majority of PEX12-related disease in Egypt and delineates a uniform clinical and radiographic phenotype.