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Neurodevelopmental proteasomopathies represent a distinctive category of neurodevelopmental disorders (NDD) characterized by genetic variations within the 26S proteasome, a protein complex governing eukaryotic cellular protein homeostasis. In our comprehensive study, we identified 23 unique variants in PSMC5 , which encodes the AAA-ATPase proteasome subunit PSMC5/Rpt6, causing syndromic NDD in 38 unrelated individuals. Overexpression of PSMC5 variants altered human hippocampal neuron morphology, while PSMC5 knockdown led to impaired reversal learning in flies and loss of excitatory synapses in rat hippocampal neurons. PSMC5 loss-of-function resulted in abnormal protein aggregation, profoundly impacting innate immune signaling, mitophagy rates, and lipid metabolism in affected individuals. Importantly, targeting key components of the integrated stress response, such as PKR and GCN2 kinases, ameliorated immune dysregulations in cells from affected individuals. These findings significantly advance our understanding of the molecular mechanisms underlying neurodevelopmental proteasomopathies, provide links to research in neurodegenerative diseases, and open up potential therapeutic avenues.

Background: Depression is a highly prevalent disease affecting more than 350 million people and has recently been associated with low-grade chronic inflammation. The role of diet in the development of a pro-inflammatory state was demonstrated in a recent study that found a high Empirical Dietary Inflammatory Index (EDII) score was associated with increased concentrations of circulating plasma inflammatory markers. It is becoming increasingly clear that diet and depression are linked, but the relationship itself has not been determined with absolute certainty. Pharmacologic and device assisted therapies are considered our most advanced treatments for major depressive disorder, though numerous studies suggest that they are not sufficient. Exploring the relationship of a pro-inflammatory diet and depressive symptoms is crucial for a holistic, evidenced-based approach to treating depression., Methods: Our study investigated this association using the EDII to evaluate the inflammatory potential of diet and Patient Health Questionnaire-9 (PHQ-9) to score depression among healthcare personnel. Results from 631 participants were collected for analysis using REDCap software., Results: High PHQ-9 scores and high EDII scores were significantly correlated (F = 18.32, p < 0.0001) even when accounting for gender, psychiatric diagnosis, physical exercise, and spiritual exercise., Conclusions: Our findings suggest that anti-inflammatory diets can play a key role in the treatment of depression., (© 2022. The Author(s).)

Background: Many infants in the neonatal intensive care unit (NICU) have genetic disorders or birth defects. The demand for genetic services is often complicated by a shortage of genetic providers., Problem: Our hospital experienced a significant reduction in genetic workforce, leading to insufficient genetic services to meet demand., Methods: The Plan-Do-Study-Act method of quality improvement was used to assess available resources, select an intervention plan, and collect patient outcome and provider satisfaction data., Intervention: An asynchronous telehealth model was deployed for clinical genetics consultations in our NICU utilizing a remote clinical geneticist., Results: The pilot study included 111 asynchronous telehealth consultations; 21% received a genetic diagnosis before discharge. Diagnoses were primarily chromosomal and single gene disorders. Referring NICU providers reported high satisfaction., Conclusion: Asynchronous telehealth for clinical genetics is a feasible and successful alternative to an on-site clinical geneticist and should be considered in areas with a genetic workforce shortage., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

As demand for genetic services grows, innovative genetic counseling service delivery models (SDMs) are needed. However, there is limited research on the barriers and needs of genetic counselors (GCs) interested in implementing new SDMs into their practice. In fall 2017, the National Society of Genetic Counselors (NSGC) Access and Service Delivery Committee's SDM Subcommittee sent an online survey to the NSGC membership regarding the use of SDMs, which aimed to update the understanding of current SDM use and how this has changed over time. The survey included several questions with open-response components assessing the need for new SDMs and barriers to implementation. Inductive thematic analysis was used to identify common themes. Among 517 usable responses (16% response rate), more than half (54.4%) of respondents indicated their current SDM was inadequate to address the patient need in their area. Nearly two-thirds (64.8%) indicated they were in the process of or planning to make changes to their SDM, although 40.6% did not have a specific timeline. Three major themes related to expanding access, reimbursement for services, and lack of support were identified from responses to questions about implementation of additional SDMs. Access included subthemes of geographic and physical location limitations, addressing long wait times, and the need to expand services. Reimbursement for services included issues with billing, genetic counselor licensure, and limitations due to the need for physician involvement in billing. The lack of support was evident with issues related to understaffing; difficulty gaining support at the administrative, institutional, or physician level; time constraints; and funding concerns. This study shows that GCs need education, tools, and resources to overcome barriers in implementing new or adapting current SDMs, and there is a need for policy change, including new billing and coverage models., (© 2020 National Society of Genetic Counselors.)

In 2010, the National Society of Genetic Counselors (NSGC) membership was surveyed about their use of genetic counseling service delivery models (SDMs) including in-person, telephone, telegenetics, and group genetic counseling. Since that time, the demand for genetic counseling services has increased in the United States (US). We hypothesized that the use of various SDMs has increased to help address the growing demand. To assess for changes in SDM use and interest in implementing innovative SDMs, the NSGC SDM subcommittee sent an electronic survey to the NSGC membership (N = 3,616), which was open from August 2017 to December 2017. Descriptive statistics and chi-square analysis were used to compare and identify differences in SDM utilization between 2010 and 2017. There were 590 total responses (16.3% response rate) with 517 usable responses, representing multiple genetic counseling specialties. Compared to 2010, significantly fewer respondents indicated they 'always' provide services in-person in 2017 (p < .04, df = 4), with 92.6% of respondents reporting 'always' or 'often' utilizing in-person SDM in 2017. Telephone genetic counseling was reported by 12.5% as a model used always or often, compared to 8% in 2010; however, the shift toward or away from telephone genetic counseling since 2010 was not statistically significant (p = .27, df = 4). The number of respondents using telegenetics always or often increased from 2.3% in 2010 to 6.7% in 2017, and more respondents report using telegenetics at an increased frequency (p < .01, df = 4). In contrast, those reporting use of a group genetic counseling SDM always or often decreased from 3.0% to 1.4%, though there was not a significant shift toward or away the frequency of respondents using group genetic counseling (p = .21, df = 4). Almost all respondents (93%) were interested in implementing an additional and/or different SDM; however, many (74%) identified barriers to implementation. There was an increase in those reporting use of 3 or 4 SDMs in practice since 2010 (p < .02). Genetic counselors may be attempting to compensate for longer wait times by implementing additional SDMs to improve access for patients. There is strong interest in learning about and implementing innovative SDMs to improve access and efficiency. However, resources need to be developed to help genetic counselors identify and overcome implementation barriers to achieve these goals., (© 2020 National Society of Genetic Counselors.)

A 36-year-old Mexican female with a slowly growing foot mass was referred to orthopedic surgery clinic for further evaluation. Foot magnetic resonance imaging revealed an infiltrative soft tissue mass along the dorsal aspect of the fourth metatarsal. T2-weighted images revealed multiple central low-signal "dots" surrounded by areas of bright signal intensity, known as the "dot-in-circle" sign, which is highly specific for mycetoma. Surgical biopsy confirmed the diagnosis of bacterial mycetoma in this patient. Mycetoma can lead to progressive deformity and loss of function, as well as possible limb amputation in the case of delayed diagnosis or misdiagnosis. The "dot-in-circle" sign on magnetic resonance imaging can assist in rendering a final diagnosis and distinguish mycetoma from other etiologies of a soft tissue mass, such as a sarcoma or benign soft tissue lesions., (© 2020 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Objective: To analyze the impact of pelvic computed tomography (CT) technique optimization on estimated dose and subjective and objective image quality., Materials and Methods: An institutional review board (IRB)-approved retrospective records review was performed with waived informed consent. Five CT scanners (various manufacturers/models) were standardized to match the lowest dose profile on campus via subjective assessment of clinical images by experienced musculoskeletal radiologists. The lowest dose profile had previously been established through image assessment by experienced musculoskeletal radiologists after a department-wide radiation dose reduction initiative. A consecutive series of 60 pre- and 59 post-optimization bony pelvis CTs were analyzed by two residents, who obtained signal-to-noise ratio for femoral cortex and marrow, gluteus medius muscle, and subcutaneous and visceral fat in a standardized fashion. Two blinded attending radiologists ranked image quality from poor to excellent., Results: Pre- and post-optimization subjects exhibited no difference in gender, age, or BMI (p > 0.2). Mean CT dose index (CTDIvol) and dose-length product (DLP) decreased by approximately 45%, from 39± 14 to 18± 12 mGy (p < 0.0001) and 1,227± 469 to 546± 384 mGy-cm (p < 0.0001). Lower body mass index (BMI) was associated with a larger dose reduction and higher BMI with higher DLP regardless of pre- or post-optimization examination. Inter-observer agreement was 0.64-0.92 for SNR measurements. Cortex SNR increased significantly for both observers (p < 0.02). Although qualitative image quality significantly decreased for one observer (p < 0.01), adequate mean quality (3.3 out of 5) was maintained for both observers., Conclusion: Subjective and objective image quality for pelvic CT examination remains adequate, despite a substantially reduced radiation dose.

Chronic pelvic pain syndrome is commonly caused by nerve injury, inflammation, or entrapment. Owing to the complex anatomy and branching patterns of pelvic nerves, pelvic neuropathies are often difficult to illustrate and diagnose. High-resolution 3-T magnetic resonance neurography is a promising technique for the evaluation of peripheral neuropathy. In this article, the authors discuss the normal anatomy of major pelvic nerves, technical considerations of high-resolution imaging, and normal and abnormal imaging appearances with relevant case examples., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Accurate diagnosis and prompt therapy of musculoskeletal infections are important prognostic factors. In most cases, clinical history, examination and laboratory findings help one make the diagnosis, and routine magnetic resonance imaging (MRI) is useful to identify the extent of the disease process. However, in many situations, a routine MRI may not be specific enough especially if the patient cannot receive contrast intravenously, thereby delaying the appropriate treatment. Diffusion-weighted imaging (DWI) can help in many such situations by providing additional information, accurate characterization and defining the extent of the disease, so that prompt treatment can be initiated. In this article, we illustrate the imaging findings of the spectrum of musculoskeletal infections, emphasizing the role of DWI in this domain., Key Points: • Abscess in background cellulitis is detected on DWI. • Infectious tenosynovitis shows diffusion restriction as compared to mechanical tenosynovitis. • Pyomyositis with abscess can be differentiated from diabetic myonecrosis on DWI. • Intraosseous abscess is bright on DWI versus devitalized tissue, sequestrum and air. • DWI can be used to differentiate spine infection from simple Modic changes.

Background and Purpose: The number of centers currently performing 3D fat-suppressed isotropic imaging is limited. If the angular orientations of the major lumbosacral plexus nerves on 3D isotropic MR neurography could be determined, similar planes could be prescribed during acquisition of 2D or 3D nonisotropic techniques for optimal depiction of various nerves. Our aim was to determine oblique sagittal and coronal angular measurements for longitudinal depiction of lumbosacral plexus nerves. Interobserver and intraobserver performance and mean calibers of sciatic and femoral nerves were also determined., Materials and Methods: A consecutive series of lumbosacral plexus MR neurography examinations with 3D nerve-selective imaging performed during a 10-month period on a 3T scanner were evaluated. Two observers performed reconstructions and angular measurements. Sciatic and femoral nerve diameters were measured. Descriptive statistics and intraclass correlation coefficient correlations were used., Results: There were 52 subjects, 11 men and 41 women. Mean sagittal thecal sac angles for coronal demonstration of lumbosacral plexus nerve roots from L1 to S1 for 2 independent observers measured 13.58° ± 2.87° and 13.61° ± 2.18°. Mean sagittal femoral nerve angles were 27.78° ± 4.81° and 28.94° ± 4.49°, and mean sagittal sciatic nerve angles were -10.7° ± 3.75° and -11.82° ± 2.87°. Coronal angular measurements of the femoral and sciatic nerves were similar. The intraclass correlation coefficient was moderate (0.582-0.671) for interobserver performance. For intraobserver performance among various angular measurements, the intraclass correlation coefficient was moderate to good (0.586-0.788). Femoral nerve caliber on MR imaging was almost half that of the sciatic nerve. Mean right femoral nerve thickness was 4.52 ± 1.11 mm and 4.85 ± 0.64 mm for the 2 observers, and mean left femoral nerve thickness was 4.48 ± 0.97 mm and 4.94 ± 0.57 mm. Mean right sciatic nerve thickness was 9.71 ± 1.76 mm and 9.94 ± 0.83 mm, and mean left sciatic nerve thickness was 10.03 ± 1.71 mm and 9.98 ± 0.99 mm., Conclusions: Angular lumbosacral plexus measurements aid in the prescription of different planes on MR imaging for the optimal longitudinal demonstration of nerves., (© 2016 by American Journal of Neuroradiology.)

Objective: To assess the clinical spectrum of postdiarrheal hemolytic uremic syndrome (D(+)HUS) hospitalizations and sought predictors of in-hospital death to help identify children at risk of poor outcomes., Study Design: We assessed clinical variables collected through population-based surveillance of D(+)HUS in children <18 years old hospitalized in 10 states during 1997-2012 as predictors of in-hospital death by using tree modeling., Results: We identified 770 cases. Of children with information available, 56.5% (430 of 761) required dialysis, 92.6% (698 of 754) required a transfusion, and 2.9% (22 of 770) died; few had a persistent dialysis requirement (52 [7.3%] of 716) at discharge. The tree model partitioned children into 5 groups on the basis of 3 predictors (highest leukocyte count and lowest hematocrit value during the 7 days before to 3 days after the diagnosis of hemolytic uremic syndrome, and presence of respiratory tract infection [RTI] within 3 weeks before diagnosis). Patients with greater leukocyte or hematocrit values or a recent RTI had a greater probability of in-hospital death. The largest group identified (n = 533) had none of these factors and had the lowest odds of death. Many children with RTI had recent antibiotic treatment for nondiarrheal indications., Conclusion: Most children with D(+)HUS have good hospitalization outcomes. Our findings support previous reports of increased leukocyte count and hematocrit as predictors of death. Recent RTI could be an additional predictor, or a marker of other factors such as antibiotic exposure, that may warrant further study., (Published by Elsevier Inc.)

During 2003-2009, we identified 544 cases of Cronobacter spp. infection from 6 US states. The highest percentage of invasive infections occurred among children <5 years of age; urine isolates predominated among adults. Rates of invasive infections among infants approximate earlier estimates. Overall incidence of 0.66 cases/100,000 population was higher than anticipated.

The onset of parental behavior has profound and enduring effects on behavior and neurobiology across a variety of species. In some cases, mere exposure to a foster neonate (and a subsequent parental response) can have similar effects. In the present experiment, we exposed adult male and female prairie voles (Microtus ochrogaster) to two foster pups for 20 min and quantified cell proliferation in the dentate gyrus of the hippocampus (DG), medial amygdala (MeA) and cortical amygdala (CorA). Prairie voles are highly social rodents that typically display biparental care and spontaneous parental care when exposed to foster pups. Comparisons were made between the animals that responded parentally or non-parentally towards the pups, as well as control conditions. Cell proliferation was assessed using injections of 5-bromo-2'-deoxyuridine (BrdU) and immunocytochemical localization of this marker. The phenotype of the cells was determined using double label immunofluoresence for BrdU and TuJ1 (a neuronal marker). An increase in cell proliferation in the DG was seen in animals exposed to pups. However, animals that responded non-parentally had a greater number of BrdU labeled cells in the DG compared to those that responded parentally. The majority of BrdU labeled cells co-expressed TuJ1 across all groups. These results demonstrate that exposure to a foster pup and the behavioral reaction to it (parental or non-parental) are associated with site-specific changes in cell proliferation.

African Americans tend to enter the health care system at the chronic stage of illness. Delayed knowledge results in increased morbidity (Lee & Estes, 1994). An understanding of factors surrounding decreased participation in formal health care is important for dispensers of healing as well as for African Americans who are themselves affected. One purpose of this study is to describe elements of an Africentric model and its potential for affecting nursing education and nursing practice. The objective for this research is to show how the Africentric model promotes change based on education.