Ablation of lysophosphatidic acid receptor 1 attenuates hypertrophic cardiomyopathy in a mouse model.

Myocardial fibrosis is a key pathologic feature of hypertrophic cardiomyopathy (HCM). However, the fibrotic pathways activated by HCM-causing sarcomere protein gene mutations are poorly defined. Because lysophosphatidic acid is a mediator of fibrosis in multiple organs and diseases, we tested the role of the lysophosphatidic acid pathway in HCM. Lysphosphatidic acid receptor 1 (LPAR1), a cell surface receptor, is required for lysophosphatidic acid mediation of fibrosis. We bred HCM mice carrying a pathogenic myosin heavy-chain variant (403+/-) with Lpar1-ablated mice to create mice carrying both genetic changes (403+/- LPAR1 -/-) and assessed development of cardiac hypertrophy and fibrosis. Compared with 403+/- LPAR1WT, 403+/- LPAR1 -/- mice developed significantly less hypertrophy and fibrosis. Single-nucleus RNA sequencing of left ventricular tissue demonstrated that Lpar1 was predominantly expressed by lymphatic endothelial cells (LECs) and cardiac fibroblasts. Lpar1 ablation reduced the population of LECs, confirmed by immunofluorescence staining of the LEC markers Lyve1 and Ccl21a and, by in situ hybridization, for Reln and Ccl21a. Lpar1 ablation also altered the distribution of fibroblast cell states. FB1 and FB2 fibroblasts decreased while FB0 and FB3 fibroblasts increased. Our findings indicate that Lpar1 is expressed predominantly by LECs and fibroblasts in the heart and is required for development of hypertrophy and fibrosis in an HCM mouse model. LPAR1 antagonism, including agents in clinical trials for other fibrotic diseases, may be beneficial for HCM.

Treatment of oral graft-versus-host disease with intraoral nbUVB phototherapy.

PURPOSE: There are limited treatment options available for hematopoietic stem-cell transplant patients (HSCT) with oral graft-versus-host disease (GVHD). Intraoral phototherapy is a novel, yet promising therapeutic regimen. RESEARCH QUESTION: To assess the safety and effectiveness of intraoral narrowband UVB (nbUVB) phototherapy in the treatment of oral GVHD. METHODS: This case series evaluated 10 patients with refractory oral GVHD, who were treated at Northwestern Memorial Hospital with nbUVB between July 2019 and October 2023. Primary outcomes were to evaluate the safety and efficacy of phototherapy. Efficacy was measured by objective improvement in symptom scores and subjective improvement in patient reported symptoms. Safety was determined by the withdrawal due to adverse events. Total nbUVB exposure, number of treatments, and change in systemic immunosuppressive medications were also examined. RESULTS: The study cohort comprised 10 patients who developed oral GVHD at a median of 9.5 months after HSCT. The total median dose of nbUVB was 36 J/cm2, and the median number of sessions was 55. All 10 patients demonstrated some degree of improvement in symptoms. Notably, there was a reduction in the number of patients who reported symptoms of oral pain (83%), bleeding (67%), xerostomia (50%), and oral sensitivity (78%) after initiating phototherapy. There was also a statistically significant decrease in the levels of pain, erythema, and edema (p ≤ 0.001, < 0.001, 0.01, respectively). Most patients tolerated phototherapy well, but 1 patient withdrew from treatment due to adverse effects. Seventy-five percent of patients who were on immunosuppressive medications were able to decrease or stop these medications. CONCLUSION: This case series suggests that nbUVB phototherapy is well tolerated and efficacious in patients with oral GVHD.

Evolution of Medical and Surgical Management of Carotid Disease - From Carotid Endarterectomy to Transfemoral Carotid Stenting to TCAR.

Patients with carotid stenosis can be broadly classified into two categories: symptomatic and asymptomatic. While there is little disagreement about surgical management of symptomatic carotid stenosis, the optimal management strategy for the patients with asymptomatic carotid disease has undergone significant evolution over past five decades. With increasing focus on role of plaque morphology on the etiology of symptoms, there has been an increased focus on optimizing the medical management targeted at plaque stabilization, especially for the patients with asymptomatic carotid disease, while reserving the most aggressive surgical treatment options for the patients with symptomatic carotid stenosis. This review summarizes the scientific evidence based on multiple large clinical studies showing how the modern-day management of carotid stenosis has evolved. Multiple, large randomized clinical trials have established carotid endarterectomy (CEA) as the treatment of choice for symptomatic patients with symptomatic, >50% stenosis of carotid artery or those who have asymptomatic high grade carotid stenosis. With the advancements in endovascular techniques, the technique of Trans Femoral Carotid Artery Stenting (TF-CAS) was popularized, but after multiple, large randomized controlled trials demonstrated superiority of CEA, the indications for TF-CAS as the initial operation of choice for carotid disease for all patients have been reduced. In the past five years, the introduction of the newer technique of Trans Carotid Artery Revascularization (TCAR) has shown promising results with significant reduction in the incidence of perioperative complications as compared to CEA and TF-CAS, however, there have been no randomized controlled trials comparing TCAR to either CEA or TF-CAS. Moreover, with the developments in the medical field with introduction of several new medications which have been demonstrated to successfully change the plaque morphology, there has been a renewed interest in exploring if the indications for surgical management for the asymptomatic carotid disease should be revisited.

The Influence of the Superficial Venous System on DIEP Flap Drainage in Breast Reconstruction.

BACKGROUND: Autologous tissue has become the gold standard in breast reconstruction. The use of a deep inferior epigastric perforator (DIEP) flap has the advantages of giving a natural appearance to the reconstructed breast and being associated with lower morbidity at the donor site when compared with the transverse rectus abdominis myocutaneous flap. Venous complications such as venous thrombosis and insufficiency remain the main causes of flap loss and surgical revisions. The aim of this study was to evaluate the influence of superficial venous drainage of the DIEP flap and the addition of a second venous anastomosis have on flap survival. METHODS: This was a retrospective cohort study collected from a prospective database maintained by our institution. Data was obtained from the medical records of female patients who underwent mastectomy and breast reconstruction with a DIEP flap between March 2010 and March 2017. We evaluated 137 DIEP patients with unilateral breast reconstructions. In 64 (46.7%) the deep venous system was chosen and 73 (53.3%) had an additional superficial vein anastomosed. RESULTS: Out of the 137 patients evaluated, there were 16 (11.67%) cases of revision, 14 (10.21%) were due to venous thrombosis. Twelve cases (8.75%) of flap loss were reported. Reoperation rate was lower in the dual venous drainage group when compared with the single venous drainage group (p = 0.005), as was the rate of flap loss (p = 0.006) and reoperation due to venous thrombosis (p = 0.002). Out of the 125 DIEP flaps, fat necrosis was clinically identified in 7 (5.1%) cases, and the rate was lower in the dual venous drainage system group (p = 0.01). CONCLUSION: Dual venous drainage of a DIEP flap appears to reduce the rates of venous thrombosis, reoperation, total flap loss, and fat necrosis.

Evaluation of Factors Associated with, and Outcomes for Patients with Nonhome Discharge Destinations Following Carotid Endarterectomy.

INTRODUCTION: Following a carotid endarterectomy (CEA) procedure, patients are discharged to their homes or other locations than home such as an acute care facility or skilled nursing facility based on their functional status and level of medical attention needed. Decision-making for discharge destination following a CEA to home or nonhome locations is important due to the differences in survival and postoperative complications. While primary outcomes such as mortality and occurrence of stroke following CEA have been extensively studied, there is a paucity of information characterizing outcomes of discharge destination and the factors associated. The purpose of this study was to explore the factors associated with discharge to nonhome destinations after CEA, and outcomes after discharge. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified patients who underwent CEA from 2011 to 2018. Patients were divided into two groups based on their discharge destination (home versus nonhome). Univariate and multivariate analysis were performed for preoperative and intraoperative factors associated with different discharge destinations. Postoperative complications associated with discharge to nonhome destinations were analyzed and mortality after discharge from hospital was compared between the 2 groups. RESULTS: A total of 25,094 patients met the criteria for inclusion in the study, of which 39% were females and 61% were males; median age was 71 years. Twenty four thousand one hundred twenty-five patients (93.13%) were discharged to home (Group I) and 1,779 (6.87%) were discharged to nonhome destinations (Group II). Following preoperative and intraoperative factors were associated with discharge to nonhome locations: older age, diabetes mellitus, functional independent status, transfer from other hospitals, symptomatic status, need for preoperative blood transfusions, severe ipsilateral carotid stenosis, elective CEA, need for intraoperative shunt and general anesthesia (all P< 0.05). Following postoperative complications had statistically significant association with discharge to nonhome destinations: postoperative blood transfusion, pneumonia, unplanned intubation, longer than 48 hours on ventilator, development of stroke, myocardial infarction, deep vein thrombosis, and sepsis (all P< 0.05). Mortality after discharge from hospital was 0.39% (n = 100). Mortality among those who were discharged to home was 0.29% vs. 1.63% for those who were discharged to nonhome locations (P< 0.05). CONCLUSIONS: Majority of the patients after CEA are discharged back to their homes. This study identifies the factors which predispose patients discharged to locations, other than home. Patients who are not discharged home have higher mortality as compared to those who are discharged to their homes.

A transgenic TCR directs the development of IL-4+ and PLZF+ innate CD4 T cells.

MHC class II-expressing thymocytes can efficiently mediate positive selection of CD4 T cells in mice. Thymocyte-selected CD4 (T-CD4) T cells have an innate-like phenotype similar to invariant NKT cells. To investigate the development and function of T-CD4 T cells in-depth, we cloned TCR genes from T-CD4 T cells and generated transgenic mice. Remarkably, positive selection of T-CD4 TCR transgenic (T3) thymocytes occurred more efficiently when MHC class II was expressed by thymocytes than by thymic epithelial cells. Similar to polyclonal T-CD4 T cells and also invariant NKT cells, T3 CD4 T cell development is controlled by signaling lymphocyte activation molecule/signaling lymphocyte activation molecule-associated protein signaling, and the cells expressed both IL-4 and promyelocytic leukemia zinc finger (PLZF). Surprisingly, the selected T3 CD4 T cells were heterogeneous in that only half expressed IL-4 and only half expressed PLZF. IL-4- and PLZF-expressing cells were first found at the double-positive cell stage. Thus, the expression of IL-4 and PLZF seems to be determined by an unidentified event that occurs postselection and is not solely dependent on TCR specificity or the selection process, per se. Taken together, our data show for the first time, to our knowledge, that the TCR specificity regulates but does not determine the development of innate CD4 T cells by thymocytes.

Unveiling the double-edged sword: SOD1 trimers possess tissue-selective toxicity and bind septin-7 in motor neuron-like cells.

Misfolded species of superoxide dismutase 1 (SOD1) are associated with increased death in amyotrophic lateral sclerosis (ALS) models compared to insoluble protein aggregates. The mechanism by which structurally independent SOD1 trimers cause cellular toxicity is unknown but may drive disease pathology. Here, we uncovered the SOD1 trimer interactome-a map of potential tissue-selective protein-binding partners in the brain, spinal cord, and skeletal muscle. We identified binding partners and key pathways associated with SOD1 trimers and found that trimers may affect normal cellular functions such as dendritic spine morphogenesis and synaptic function in the central nervous system and cellular metabolism in skeletal muscle. We discovered SOD1 trimer-selective enrichment of genes. We performed detailed computational and biochemical characterization of SOD1 trimer protein binding for septin-7. Our investigation highlights key proteins and pathways within distinct tissues, revealing a plausible intersection of genetic and pathophysiological mechanisms in ALS through interactions involving SOD1 trimers.

Clinicopathologic comparison of basal cell carcinoma among a diverse patient population in Los Angeles County.

Introduction: Basal cell carcinoma (BCC) is the most common malignancy in the United States. The majority of cases are identified in Non-Hispanic Whites (NHW) and are far less demonstrated in patients of colour (POC). However, the Hispanic population represents a large and growing proportion of the US population, and skin cancer diagnoses in Hispanics are rising. Thus, the goal of this study is to examine clinicopathologic differences between BCC in Hispanics versus NHW. Methods: A retrospective chart review of Hispanic and NHW patients with BCC at Los Angeles County + USC Medical Center from January 2018 to March 2020 was performed. In total, 101 BCC samples from the first 100 patients identified of Hispanic ancestry, as well as 50 BCC samples identified from the first 50 patients identifying as NHW, were included for analysis. Patient characteristics (age, sex, medical history, and ethnicity), as well as tumour characteristics (location, subtype, tumour depth, and perineural invasion), were collected. We used between subjects t-tests for continuous variables, and chi-square tests for categorical variables. Results: In total, 151 specimens were collected amongst 122 subjects (79 Hispanics and 43 NHW patients). Among NHW, the majority of patients (74.4%) were men, but among the Hispanic population, the majority (68.4%) were female (p < 0.001). Prior history of other skin cancer was more common among NHW (67.4%) than Hispanics (31.6%) (p=<0.001). The Hispanic population had a significantly higher proportion of head and neck tumours (p = 0.0004) but a lower proportion of extremity tumours (p = 0.001) compared to NHW. Pigmented BCC was significantly more common among Hispanic patients (p < 0.01). Finally, within the Hispanic group, there was a significant association between sex and histology (p = 0.004), with Hispanic men demonstrating more aggressive mix histology compared to Hispanic women. Discussion: Our study supports the notion that BCC disparities occur among POC compared to NHW. This includes variations in epidemiologic factors such as sex and past medical history, primary tumour location, and pathologic characteristics. Further research should be conducted to identify additional differences in skin cancer presentation in POC to reduce the gaps in skin cancer knowledge and care.

Pulmonary Overcirculation Requiring Surgical and Pulmonary Flow Restrictor Device Intervention in Critical Coarctation of the Aorta-A Case Series.

The use of prostaglandin infusion to maintain patency of the ductus arteriosus in patients with critical coarctation of the aorta (CoA) to support systemic circulation is the standard of care. However, pulmonary overcirculation resulting from a patent ductus arteriosus in patients with critical CoA is not well described in the literature. We report two cases of critical CoA that required invasive measures to control pulmonary blood flow before surgical repair of the CoA. Both patients had signs of decreased oxygen delivery, hyperlactatemia, and systemic to pulmonary flow via the ductus arteriosus. One patient required surgical pulmonary artery banding and the second patient underwent pulmonary flow restrictor device placement for the control of pulmonary blood flow. A rapid improvement in oxygen delivery and normalization of lactate levels were observed after control of pulmonary overcirculation. Both patients underwent successful surgical repair of the coarctation A and were discharged home.

Development of Therapeutic Alliance and Social Presence in a Digital Intervention for Pediatric Concussion: Qualitative Exploratory Study.

BACKGROUND: Despite the promising benefits of self-guided digital interventions for adolescents recovering from concussion, attrition rates for such interventions are high. Evidence suggests that adults can develop therapeutic alliance with self-guided digital interventions, which is in turn associated with intervention engagement. However, no research has examined whether adolescents develop therapeutic alliance with self-guided digital interventions and what factors are important to its development. Additionally, social presence-the extent to which digital encounters feel like they are occurring in person-may be another relevant factor to understanding the nature of the connection between adolescents and a self-guided digital intervention, though this has yet to be explored. OBJECTIVE: This qualitative study explored the extent to which adolescents recovering from concussion developed therapeutic alliance and social presence during their use of a self-guided digital mindfulness-based intervention. Additionally, this study aimed to determine factors important to adolescents' development of therapeutic alliance and social presence with the intervention. METHODS: Adolescents aged between 12 and 17.99 years who sustained a concussion were recruited from 2 sites: a pediatric emergency department up to 48 hours after a concussion and a tertiary care clinic over 1 month following a concussion to capture adolescents who had both acute and persisting symptoms after concussion. Participants (N=10) completed a 4-week mindfulness-based intervention delivered through a smartphone app. Within the app, participants listened to audio recordings of mindfulness guides (voice actors) narrating psychoeducation and mindfulness practices. At 4 weeks, participants completed questionnaires and a semistructured interview exploring their experience of therapeutic alliance and social presence with the mindfulness guides in the intervention. RESULTS: Themes identified within the qualitative results revealed that participants developed therapeutic alliance and social presence by "developing a genuine connection" with their mindfulness guides and "sensing real people." Particularly important to the development of therapeutic alliance and social presence were the mindfulness guides' "personal backgrounds and voices," such that participants felt more connected to the guides by knowing information about them and through the guides' calm tone of voice in audio recordings. Quantitative findings supported qualitative results; participants' average score for therapeutic alliance was far above the scale midpoint, while the mixed results for social presence measures aligned with qualitative findings that participants felt that the mindfulness guides seemed real but not quite as real as an in-person connection would. CONCLUSIONS: Our data suggest that adolescents can develop therapeutic alliance and social presence when using digital interventions with no direct human contact. Adolescents' development of therapeutic alliance and social presence with self-guided digital interventions can be bolstered by increasing human-like qualities (eg, real voices) within interventions. Maximizing therapeutic alliance and social presence may be a promising way to reduce attrition in self-guided digital interventions while providing accessible treatment.

Correction: Development of Therapeutic Alliance and Social Presence in a Digital Intervention for Pediatric Concussion: Qualitative Exploratory Study.

[This corrects the article DOI: 10.2196/49133.].

Acceptability, usability, and credibility of a mindfulness-based digital therapeutic for pediatric concussion: A mixed-method study.

Background: The ability to cope with concussion symptoms and manage stress is an important determinant of risk for prolonged symptoms. Objective: This open-label mixed-methods pilot study assessed the acceptability and credibility of a mindfulness-based intervention delivered through a digital therapeutic (DTx; therapeutic smartphone app) for pediatric concussion. Methods: Participants aged 12 to 18 years were recruited from an emergency department within 48 hours of a concussion (acute cohort) or from a tertiary care clinic at least 1-month post-concussion (persisting symptoms cohort). Participants completed a novel 4-week mindfulness-based intervention, for 10 to 15 minutes/day, at a minimum of 4 days/week. At 2 weeks, participants completed a credibility and expectancy questionnaire. At 4 weeks, participants completed questionnaires assessing satisfaction, usability and working alliance, as well as a semi-structured phone interview. Results: Ten participants completed the study outcomes (7 acute; 3 persisting symptoms). The intervention was perceived as credible (median/max possible = 6.50/9.00 [6.83,8.75]) and DTx was usable (median/max possible = 70.00/100.00 [55.00,82.50]). Participants rated their satisfaction with the DTx (median/max possible = 27.00/32.00 [24.50,29.50]) and the working alliance with the digital mindfulness guides (median/max possible = 3.92/5.00 [3.38-4.33]) as high. Four themes were identified from the qualitative data: (a) positive attributes; (b) negative attributes; (c) ideas for modifications; and (d) technical issues. Conclusion: Results show modifications to the DTx, instructions and mindfulness intervention, and potential ways to increase adherence by leveraging positive attributes. A randomized control trial will assess the effectiveness of the DTx MBI to decrease the risk of persisting symptoms and reduce the symptom burden following pediatric concussion.

Alopecia Areata After Initiation of Secukinumab Therapy for Plaque Psoriasis.

The development of psoriasis and alopecia areata (AA) is multifactorial. The interleukin-17 (IL-17) cytokine is believed to be associated with the pathophysiology of both diseases. This case report demonstrates a 64-year-old female patient who experienced a new onset of AA after the initiation of IL-17A inhibitor, secukinumab, for the treatment of her psoriasis. To our knowledge, there are only three case reports specifically discussing IL-17A inhibitors and AA. This case report highlights a potential rare but significant side effect of IL-17A inhibitors.

Navigating Intersectional Identities: Clinical Considerations for Working With LGBTQ Asian American Youth.

LGBTQ Asian American youth face unique challenges related to their marginalized identities. It is well documented that Asian Americans who need mental health treatment access care at lower rates than White populations.1 Although Asian cultural values are often cited as reasons for decreased help-seeking behavior, research suggests structural barriers including cost, lack of culturally tailored services, and lack of knowledge of available resources as greater contributors to these disparities.1 Asian Americans have also been subject to the "model minority" myth, the stereotype that the community is universally high achieving, rule following, and well adjusted. This false narrative contributes to negative mental health outcomes driven by racial discrimination and homogenizing the Asian American experience. This masks the diversity in mental health needs among Asian Americans. In addition, LGBTQ Asian Americans experience microaggressions, the perception of being "not queer enough," and racism from LGBTQ spaces that often primarily cater to a White population.2.

Enhanced Left Ventricular Recovery in Treatment of Mitral Regurgitation With Severe Left Ventricular Dysfunction.

A 73-year-old male patient presented with shortness of breath at rest resulting from new-onset severe primary mitral regurgitation with a flail posterior leaflet, left ventricular dysfunction, and cardiogenic shock. After initial stabilization in the intensive care unit, multiple treatment options were considered for this patient, all associated with significant mortality. Ultimately, operative mitral valve repair with Impella 5.5 placement was performed for postoperative hemodynamic support. Surgical repair provided elimination of mitral regurgitation. Impella support was maintained for 7 days to provide unloading of the left ventricle. After device removal, the patient had sustained left ventricular recovery with significantly improved ejection fraction. Full left ventricular support and unloading may decrease operative risk and promote left ventricular recovery in patients with severe mitral regurgitation and left ventricular dysfunction. This case emphasizes the value of ventricular unloading to facilitate the recovery of left ventricular function as a treatment option for patients with challenging cases of severe mitral regurgitation and left ventricular dysfunction.

Big versus small: The impact of aggregate size in disease.

Protein aggregation results in an array of different size soluble oligomers and larger insoluble fibrils. Insoluble fibrils were originally thought to cause neuronal cell deaths in neurodegenerative diseases due to their prevalence in tissue samples and disease models. Despite recent studies demonstrating the toxicity associated with soluble oligomers, many therapeutic strategies still focus on fibrils or consider all types of aggregates as one group. Oligomers and fibrils require different modeling and therapeutic strategies, targeting the toxic species is crucial for successful study and therapeutic development. Here, we review the role of different-size aggregates in disease, and how factors contributing to aggregation (mutations, metals, post-translational modifications, and lipid interactions) may promote oligomers opposed to fibrils. We review two different computational modeling strategies (molecular dynamics and kinetic modeling) and how they are used to model both oligomers and fibrils. Finally, we outline the current therapeutic strategies targeting aggregating proteins and their strengths and weaknesses for targeting oligomers versus fibrils. Altogether, we aim to highlight the importance of distinguishing the difference between oligomers and fibrils and determining which species is toxic when modeling and creating therapeutics for protein aggregation in disease.

A pilot randomized controlled trial of ketamine in Borderline Personality Disorder.

This study is the first randomized controlled trial to test the effects of ketamine in Borderline Personality Disorder (BPD). BPD remains undertreated in the community and no medication has FDA approval for this indication. People with BPD experience chronic mood disturbances with depressed mood, suicidal ideation, and severe social difficulties. In this double-blind, randomized controlled pilot study, we tested the effects of one infusion of ketamine (0.5 mg/kg, n = 10) or the psychoactive comparator drug midazolam (0.04 mg/kg, n = 12) in adults with BPD. Infusions were well tolerated in both groups. Dissociative symptoms during infusion were more intense with ketamine than midazolam (t(12.3) = 3.61, p = 0.01), but they resolved by 40 min after infusion in both groups. Post-infusion adverse events were at the expected low levels in both groups. For our primary outcome measure of suicidal ideation and our secondary outcome measure of depression, we found numerical reduction but not significant group or group x timepoint difference (p > 0.05). For our secondary outcome measures of anxiety and BPD symptoms, we did not observe group or group x timepoint differences. There was a group x timepoint effect for socio-occupational functioning (F(1,20.12) = 5.16, p = 0.03, at Day 14, ketamine group showed more improvement than midazolam group). An exploratory analysis revealed that improvement in socio-occupational functioning was correlated with improvement in depression in the ketamine group (r(8) = 0.65, p = 0.04) but not midazolam group (r(9) = 0.41, p = 0.216). This pilot study provides the first randomized controlled evidence of the effects of antidepressant-dosed ketamine in people with BPD. Our results provide reason for optimism that antidepressant-dosed ketamine will be well-tolerated in larger studies and may provide clinical benefit for mood symptoms and related impairments in people with BPD.

Childhood aggression, callous-unemotional traits and oxytocin genes.

Given the known behavior effects of oxytocin,and in particular its putative effect on trust, affiliation and anxiety, we hypothesized that oxytocin may be involved in the development and expression of callous-unemotional traits in children with aggressive antisocial behavior. We recruited 162 children between the ages of 6 and 16. The majority of subjects were Caucasian (84.0%) compared to African-Canadian (4.9%) and others (11.1%). The oxytocin and oxytocin receptor gene polymorphisms were genotyped and analyzed for possible association with child aggression in a case­control study design as well as with callous-unemotional traits in a within cases analysis. We did not have significant findings with our tested OXTR markers in the case­control analysis. We found the OXTR_rs237885 AA genotype carriers to score higher than AC or CC genotype carriers on the callous-unemotional traits. This result remained significant following correction for multiple testing. No other markers were found to be significant. However, the haplotype consisting of the OXTR_rs237885 A allele and OXTR_rs2268493 A allele was associated with significantly higher callous-unemotionals cores than other haplotypes. This is the first known study to show a significant association between callous unemotional traits in children and adolescents with extreme, persistent pervasive aggression and a polymorphism on the oxytocin receptor. Given the small sample size and the possibility of false positive effects, the need to replicate and verify these findings is required.

Motor neuron-derived induced pluripotent stem cells as a drug screening platform for amyotrophic lateral sclerosis.

The development of cell culture models that recapitulate the etiology and features of nervous system diseases is central to the discovery of new drugs and their translation onto therapies. Neuronal tissues are inaccessible due to skeletal constraints and the invasiveness of the procedure to obtain them. Thus, the emergence of induced pluripotent stem cell (iPSC) technology offers the opportunity to model different neuronal pathologies. Our focus centers on iPSCs derived from amyotrophic lateral sclerosis (ALS) patients, whose pathology remains in urgent need of new drugs and treatment. In this sense, we aim to revise the process to obtain motor neurons derived iPSCs (iPSC-MNs) from patients with ALS as a drug screening model, review current 3D-models and offer a perspective on bioinformatics as a powerful tool that can aid in the progress of finding new pharmacological treatments.

Comparison of Low-Energy and Medium-Energy Collimators for Thyroid Scintigraphy with 123I.

CE credit: For CE credit, you can access the test for this article, as well as additional JNMT CE tests, online at https://www.snmmilearningcenter.org Complete the test online no later than March 2025. Your online test will be scored immediately. You may make 3 attempts to pass the test and must answer 75% of the questions correctly to receive Continuing Education Hour (CEH) credit. Credit amounts can be found in the SNMMI Learning Center Activity. SNMMI members will have their CEH credit added to their VOICE transcript automatically; nonmembers will be able to print out a CE certificate upon successfully completing the test. The online test is free to SNMMI members; nonmembers must pay $15.00 by credit card when logging onto the website to take the test.123I thyroid scintigraphy can be performed with either a low-energy or a medium-energy (ME) collimator. The high-energy photon emissions from 123I cause septal penetration with scattered photons, which deteriorate image quality. The aim of this study was to evaluate the impact of collimator choice on 123I thyroid scintigraphy in clinical practice. Methods: Forty-seven patients who underwent thyroid planar scintigraphy with both a low-energy, high-resolution (LEHR) collimator and a ME collimator were prospectively recruited using the same imaging protocol. Image quality, collimator sensitivity, and estimation of thyroid size were assessed between LEHR and ME collimators and were compared with thyroid ultrasonography as the gold standard. Results: Images acquired with the ME collimator demonstrated reduced scattered background noise, improved thyroid-to-background contrast, and increased sensitivity in the thyroid gland compared with images acquired by the LEHR collimator. Manual measurement of the thyroid length is more accurate using the ME collimator. Automatic estimation of the thyroid area using the same thyroid threshold is larger in ME collimator images than in LEHR collimator images. Conclusion: Compared with the LEHR collimator, the ME collimator generates cleaner 123I thyroid scintigraphy images with less background noise and has higher collimator sensitivity for thyroid imaging. Different thyroid thresholds should be used to estimate the thyroid area and volume between low and ME collimators.