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.

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.

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.].

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.

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.

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.

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.

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.

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.

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.

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.

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.

Psidium guajava L. leaf extract inhibits adipocyte differentiation and improves insulin sensitivity in 3T3-L1 cells.

BACKGROUND/OBJECTIVES: Psidium guajava L. (guava) leaves have been shown to exhibit hypoglycemic and antidiabetic effects in rodents. This study investigated the effects of guava leaf extract on adipogenesis, glucose uptake, and lipolysis of adipocytes to examine whether the antidiabetic properties are mediated through direct effects on adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with 25, 50, 100 µg/mL of methanol extract from guava leaf extract (GLE) or 0.1% dimethyl sulfoxide as a control. Lipid accumulation was evaluated with Oil Red O Staining and AdipoRed assay. Immunoblotting was performed to measure the expression of adipogenic transcription factors, fatty acid synthase (FAS), and AMP-activated protein kinase (AMPK). Glucose uptake under basal or insulin-stimulated condition was measured using a glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose. Lipolysis from fully differentiated adipocytes was measured by free fatty acids release into the culture medium in the presence or absence of epinephrine. RESULTS: Oil Red O staining and AdipoRed assay have shown that GLE treatment reduced lipid accumulation during adipocyte differentiation. Mitotic clonal expansion, an early essential event for adipocyte differentiation, was inhibited by GLE treatment. GLE inhibited the expression of transcription factors involved in adipocyte differentiation, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP-1c). FAS expression was also decreased while the phosphorylation of AMPK was increased by GLE treatment. In addition, GLE increased insulin-induced glucose uptake into adipocytes. In lipid-filled mature adipocytes, GLE enhanced epinephrine-induced lipolysis but reduced basal lipolysis dose-dependently. CONCLUSIONS: The results show that GLE inhibits adipogenesis and improves adipocyte function by reducing basal lipolysis and increasing insulin-stimulated glucose uptake in adipocytes, which can be partly associated with antidiabetic effects of guava leaves.

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.

SOD1 oligomers in amyotrophic lateral sclerosis.

Identifying nonnative, trimeric forms of SOD1 trimers as the toxic species, rather than large aggregates revolutionizes our understanding of ALS pathophysiology. Large protein aggregates, what was previously thought as the central cause of neurodegeneration, play protective role and are not responsible for neuronal death. SOD1 trimers are implicated at the molecular, cellular, and organismal level. Understanding the formation of the nonnative trimer and its role in the cell, leading to cell death, holds the key to developing a new standard of therapeutics for ALS and for other neurodegenerative diseases. This review highlights recent advances of knowledge for the role of SOD1 oligomers in ALS.

Mapeamento anatômico das anomalias vasculares dos lábios / Anatomical mapping of vascular anomalies of the lips

Introdução: O lábio é a região do corpo mais frequentemente acometida por anomalias vasculares (AV). A correta determinação da etiologia da lesão é determinante à escolha do tratamento do paciente e à correta condução do caso. O objetivo deste estudo é correlacionar o posicionamento anatômico e as características das lesões com o diagnóstico etiológico das AVs dos lábios, a fim de promover uma ferramenta que auxilie na prática clínica. Métodos: Análise retrospectiva de 150 pacientes com AV dos lábios, avaliados entre 1999 e 2017. O diagnóstico etiológico foi baseado na classificação de ISSVA 2014. Análise clínica e fotográfica foi realizada para avaliar o padrão anatômico de envolvimento e mapear as lesões. Resultados: Hemangioma infantil apresentou acometimento de apenas um lábio, em menor extensão e situado mais centralmente, com raro envolvimento de comissura oral. Malformações venosas e venolinfáticas (MVs) e malformações arteriovenosas (MAVs) envolveram o lábio superior predominantemente, situadas mais lateralmente e acarretando significativa deformidade. Contudo, MAVs apresentaram mais frequente extensão além dos limites do vermelhão. Os pacientes com malformações capilares (MCs) sofriam de acometimento integral do lábio inferior. Todos os casos de malformações linfáticas exclusivas (MLs) envolveram o lábio superior inteiro, com grande distorção. Conclusão: A apresentação inicial das AVs muitas vezes consiste em pequenas alterações, desafiadoras ao diagnóstico assertivo. Padrões específicos de acometimentos foram observados para cada diagnóstico etiológico estudado. O mapeamento pode ser utilizado como ferramenta auxiliar diagnóstica e contribuir para melhor intervenção nos pacientes com anomalias vasculares labiais.

Introduction: The lip is the body region more often affected by vascular anomalies (VAs). Identifying the appropriate etiology of the lesion is significantly important when determining the treatment of choice for the patient. This study aimed to determine the association between the anatomical positioning and the characteristics of the lesions and the etiological diagnosis of VAs of the lips to identify the appropriate tool to be used in clinical practice. Methods: A retrospective analysis was performed in 150 patients with VA of the lips evaluated between 1999 and 2017. The etiological diagnosis was based on the International Society for the Study of Vascular Anomalies 2014 classification. Clinical and photographic analysis was performed to assess the anatomical pattern of involvement and map the lesions. Results: An infantile hemangioma was observed to a lesser extent in only one lip and was situated more centrally, with rare involvement of the labial commissure. Venous and venous-lymphatic malformations and arteriovenous malformations (AVMs) involving the upper lip were predominantly located more laterally and caused significant deformity. However, AVMs more often extended beyond the limits of the vermilion. Capillary malformations were observed in the entire lower lip in some patients. Simple lymphatic malformations were observed in the entire upper lip with significant distortion in some patients. Conclusion: The initial presentation of VAs often comprises minimal changes; hence, establishing an assertive diagnosis is considered difficult. Specific patterns of involvement were observed for each etiological diagnosis studied. Anatomical mapping can be used as an auxiliary diagnostic tool and can possibly identify an appropriate clinical intervention in patients with VAs of the lip.

Parvalbumin-Positive Neuron Loss and Amyloid-ß Deposits in the Frontal Cortex of Alzheimer's Disease-Related Mice.

Alzheimer's disease (AD) has several hallmark features including amyloid-ß (Aß) plaque deposits and neuronal loss. Here, we characterized Aß plaque aggregation and parvalbumin-positive (PV) GABAergic neurons in 6-9-month-old 5xFAD mice harboring mutations associated with familial AD. We used immunofluorescence staining to compare three regions in the frontal cortex-prelimbic (PrL), cingulate (Cg, including Cg1 and Cg2), and secondary motor (M2) cortices-along with primary somatosensory (S1) cortex. We quantified the density of Aß plaques, which showed significant laminar and regional vulnerability. There were more plaques of larger sizes in deep layers compared to superficial layers. Total plaque burden was higher in frontal regions compared to S1. We also found layer- and region-specific differences across genotype in the density of PV interneurons. PV neuron density was lower in 5xFAD mice than wild-type, particularly in deep layers of frontal regions, with Cg (-50%) and M2 (-39%) exhibiting the largest reduction. Using in vivo two-photon imaging, we longitudinally visualized the loss of frontal cortical PV neurons across four weeks in the AD mouse model. Overall, these results provide information about Aß deposits and PV neuron density in a widely used mouse model for AD, implicating deep layers of frontal cortical regions as being especially vulnerable.

Armed Conflict in Central America and Immigrant Health in the United States.

BACKGROUND: While many researchers document the immediate and localized health effects of armed conflicts on combatants are well documented in the literature, less is known about the effects of armed conflict on individuals who have subsequently migrated elsewhere. Objective: This study aims to estimate associations between pre-migration armed conflict in Central America and post-migration health in the United States. METHODS: We created a new dataset that combines information on armed conflicts in Central America and immigrant health in the United States. We used ordered probit regressions to estimate age-adjusted associations between pre-migration armed conflict and post-migration health. FINDINGS: The study sample of Central American immigrants included 15,563 females and 16,236 males between the ages 15 and 69. The mean age was 37.2 years (standard deviation, 11.6 years) for females and 35.5 years (standard deviation, 11.2 years) for males. After adjusting for age, pre-migration armed conflict was associated with a 8.6 percentage point decrease in excellent health for females (95% confidence interval, 6.0 to 11.1), and a 7.3 percentage point decrease for males (95% confidence interval, 4.0 to 10.7). Each decade of pre-migration armed conflict was associated a 2.9-percentage point decrease in excellent health for females (95% confidence interval, 2.0 to 3.8) and a 1.6-percentage point decrease for males (95% confidence interval, 0.6 to 2.6). For those individuals exposed to armed conflict, each decade since the most recent armed conflict was associated with a 1.5 percentage point increase in excellent health for females (95% confidence interval, 0.4 to 2.5). For males, the average marginal effect of decades since last conflict was not statistically significant (95% confidence interval, -0.001 to 0.002). CONCLUSIONS: Pre-migration armed conflict in Central America is associated with decreases in excellent post-migration health in the United States. The effects of armed conflict are cumulative and fade over time for females.