Acyclovir as a Novel Treatment for Severe Chronic Active Epstein-Barr Virus.

Epstein-Barr virus (EBV) is a widely infectious pathogen affecting most of the global population at some point in their life. While, typically, primary infections are subclinical, chronic persistence of the virus due to T-cell proliferation can cause severe complications. Acute hepatitis due to chronic active EBV (CAEBV) has rarely been documented. This case details a previously healthy 81-year-old woman who presented with complaints of diffuse abdominal pain, nausea, and vomiting. Her diagnostic workup demonstrated an EBV infection with worsening thrombocytopenia, transaminitis, and hepatocellular liver injury with acute ascites. Her hospitalization was resistant to the traditional supportive treatment of EBV, requiring intensive care management and unorthodox therapy. Although antivirals have demonstrated limited utility in the treatment of CAEBV, the severity of her illness and refractory hospital course necessitated the use of acyclovir. She made a complete recovery with no deficits. The case demonstrates the presentation of acute hepatitis and ascites as a result of CAEBV, the clinical sequelae, and acyclovir as a potential new treatment option.

A Case of Secondary Autoimmune Hemolytic Anemia Successfully Treated With Rituximab.

Secondary cold agglutinin autoimmune hemolytic anemia (AIHA) occurs most commonly due to infectious causes like Mycoplasma pneumonia and, more rarely, Epstein-Barr virus(EBV). Here we present a case of a 69-year-old female presenting with generalized weakness, who was found to have cold agglutinin hemolytic anemia. She unfortunately experienced some of the most severe complications of the disease including encephalopathy, hypoxia, and dry necrosis of peripheral extremities. Further investigation revealed an EBV infection, the rarest infectious cause of cold AIHA. She was started on steroids, the mainstay of treatment, but continued to worsen over the course of her extensive stay in the intensive care unit (ICU). Given the severity of the disease, the decision was made to use plasmapheresis and rituximab, the monoclonal antibody directed against CD20, as an experimental therapy. After adjunctive therapy was initiated, the patient began to clinically improve and ultimately made a full recovery. Rituximab is historically only effective in primary cold AIHA, but it appeared to elicit significant clinical improvement with our use in secondary cold AIHA. While there have been a handful of studies demonstrating its successful use in secondary cold AIHA, we propose that this medication be further studied to prevent the significant morbidity and mortality associated with the disease.

A Case With Twists and Turns: A Report of Vertebrobasilar Dolichoectasia.

Vertebrobasilar dolichoectasia (VBD) is a rare anatomical abnormality of the vertebral artery system, defined as irregular expansion, elongation, and tortuosity of vertebral arteries. Anomalies of the vertebrobasilar artery can have a wide variety of clinical presentations, ranging from simple headaches to debilitating strokes. We present the case of an atypical presentation of VBD which mimicked trigeminal neuralgia by compressing the trigeminal nerve. There are currently no guidelines concerning the management of VBD, nor is there evidence of a definitive cure. This case invoked discussions among the medical team as to whether management should be medically or surgically focused, as well as long-term outcomes for patients with VBD. The superiority of medical versus surgical treatment of this issue is still a debated topic. This patient trialed medical management with dexamethasone and carbamazepine with no improvement in symptoms. He then underwent surgical gamma knife treatment but even this invasive measure was unsuccessful at relieving his symptoms. We hope that by presenting this case, we can display how the therapies available for VBD are limited and often unsuccessful in relieving the disease burden in patients with VBD.

A Difficult Differential Diagnosis in New Neck Masses: Retropharyngeal Abscess or Malignancy?

Retropharyngeal abscesses (RPAs) are rare in the adult population and rarer without an inciting event or comorbidity such as recent oral surgery, neck infection, or pharyngeal trauma. The definitive treatment is incision and drainage of the abscess. Clinical researchers have recently questioned whether invasive surgical intervention is necessary and posed the question of what role antibiotics play in management. Sequelae of RPAs are severe and include rupture of the abscess, erosion of the carotid artery, thrombophlebitis, and most seriously, airway compromise. We present a case where an atypical presentation of an RPA caused a disagreement among specialists, and the debate of whether the described case represented an abscess or malignancy caused a delay in diagnosis and treatment for the patient. Only after invasive and emergent surgical intervention was a final diagnosis able to be made. This case demonstrates the need for more research and official guidance on the management of new neck masses to hasten diagnosis and prevent devastating outcomes.

Managing Opioid Withdrawal Symptoms During the Fentanyl Crisis: A Review.

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.

Lethal multiple pterygium syndrome, large cystic hygroma, and cleft palate: Rare and severe fetal presentations of RYR1- and NEB-related congenital myopathies.

Congenital myopathies are a genetically heterogeneous group of neuromuscular disorders that commonly present with congenital hypotonia and weakness but can also present broadly. The most severe presentation is neonatal with arthrogryposis and, rarely, fetal akinesia and pterygia, features also seen in lethal multiple pterygium syndrome (LMPS). We describe two fetuses with similar phenotype, including hydrops fetalis, large cystic hygromas, bilateral talipes, and fetal akinesia in the second trimester. Genetic diagnoses were made using exome sequencing. Both fetuses had a severe form of congenital myopathy. In the first fetus, we identified two novel compound heterozygous likely pathogenic variants consistent with autosomal recessive RYR1-related congenital myopathy (congenital myopathy 1B). In the second fetus, we identified two likely pathogenic variants, one of which is novel, likely in trans consistent with a diagnosis of autosomal recessive NEB-related congenital myopathy. Reaching a genetic diagnosis for these fetuses allowed the families to receive accurate genetic counseling for future pregnancies. These fetuses highlight the genetic and phenotypic heterogeneity of LMPS, and support a broad approach to genetic testing.

Prenatal findings in 11 cases with craniofacial microsomia using the Alberta Congenital Anomalies Surveillance System, 1997-2019.

Craniofacial microsomia (CFM) primarily includes specific head and neck anomalies that co-occur more frequently than expected. The anomalies are usually asymmetric and affect craniofacial features; however, there are frequently additional anomalies of variable severity. Published prenatal findings for CFM are limited. This study contributes 11 cases with CFM and their anomalies identified prenatally. Cases born between January 1, 1997 and December 31, 2019 with CFM were abstracted from the Alberta Congenital Anomalies Surveillance System, which is a population-based program ascertaining congenital anomalies for livebirths, stillbirths, and termination of pregnancies for fetal anomalies. There were 11 cases ascertained with prenatal findings including facial anomalies: one each with left cleft lip, right microtia, and bilateral microphthalmia. Two cases had vertebral anomalies. In addition, anomalies of the kidneys, brain, heart, and radial ray were identified. Six (55%) had a single umbilical artery, five (45%) were small for gestational age, and three (27%) were from a twin pregnancy that were discordant for anomalies. Four (36%) overlapped another proposed recurrent constellations of embryonic malformation condition. This study describes prenatal findings for 11 cases with CFM. Comparable to prior published cases, there were recurring anomalies on prenatal imaging, including anomalies of the brain, eye, heart, kidneys, and radial ray, which may aid in the prenatal diagnosis of CFM.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

Exploring Communication about Fall Risk and Prevention between Internal Medicine Residents and Geriatric Patients: A Needs Assessment.

OBJECTIVES: In the United States, falls are the leading cause of fatal and nonfatal injuries for geriatric patients. With a growing aging population, medical trainees must gain experience with geriatric assessments, including fall risk and prevention. To the authors' knowledge, no prior studies have explored who most often initiates fall discussions between Internal Medicine (IM) residents and geriatric (age 65 years and older) patients. Our objective was to determine who most often initiates fall discussions between IM residents and geriatric patients and the barriers to having these discussions. METHODS: This 2023 quantitative needs assessment used surveys distributed to ambulatory geriatric patients, IM residents, and attending physicians within an urban IM resident continuity clinic. We used the Stopping Elderly Accidents, Death & Injuries assessment from the Centers for Disease Control and Prevention to determine patient fall risk. RESULTS: Response rates were 46%, 51%, and 67% for patients, residents, and attendings, respectively. Of the 39 patients who were assessed, 51% were at risk of falling. Eighty-seven percent of patients have had a fall discussion with their residents, and 59% reported these were resident initiated; however, 75% of 28 residents reported initiating fall conversations rarely, and all 4 attendings said that they started these discussions most of the time while staffing patients with residents. Modifiable resident-identified barriers to discussing falls included forgetfulness and lack of knowledge regarding completing a fall risk assessment. CONCLUSIONS: Most patients have conversations about falling with their physicians, but discrepancies exist regarding who initiates them. Data from this study suggest that attendings may be instrumental in starting these conversations. Reminder systems and fall risk didactic curricula may increase resident-initiated fall discussions.

Publicly funded healthcare costs associated with orofacial clefts for children born in Alberta, Canada between 2002 and 2018.

BACKGROUND: Orofacial clefts (OFCs) include cleft palate (CP), cleft lip (CL), and cleft lip with cleft palate (CLP) and require multidisciplinary healthcare services. Alberta, Canada has a publicly funded, universal access healthcare system. This study determined publicly funded healthcare costs for children with an OFC and compared these costs to children without congenital anomalies. METHODS: This retrospective population-based cohort analysis used the Alberta Congenital Anomalies Surveillance System to identify children born between 2002 and 2018 with an isolated OFC. They were matched 1:1 to a reference cohort based on sex and year of birth. The study population included 1614 children, from birth to 17 years of age linked to administrative databases to estimate annual inpatient and outpatient costs. Average annual all-cause costs were compared using two-sample independent t tests. RESULTS: The mean total cleft-related costs per patient were highest for children with CLP ($74,138 CAD, standard deviation (SD) $43,447 CAD), followed by CP ($53,062 CAD, SD $74,366 CAD), and CL ($35,288 CAD, SD $49,720 CAD). The mean total all-cause costs per child were statistically significantly higher (p < .001) in children with an OFC ($56,305 CAD, SD $57,744 CAD) compared to children without a congenital anomaly ($18,600 CAD, SD $61,300 CAD). CONCLUSIONS: Despite public health strategies to mitigate risk factors, the trend for OFCs has remained stable in Alberta, Canada for over 20 years. The costs reported are useful to other jurisdictions for comparison, and to families, healthcare professionals, service planners, and policy makers.

Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age.

BACKGROUND: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. OBJECTIVE: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. STUDY DESIGN: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. RESULTS: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56-11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69-0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06-0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03-0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36-0.91; P=.019). CONCLUSION: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.

Importance of Low- and Moderate-Grade Adverse Events in Patients' Treatment Experience and Treatment Discontinuation: An Analysis of the E1912 Trial.

PURPOSE: Despite defined grades of 1 to 5 for adverse events (AEs) on the basis of Common Terminology Criteria for Adverse Events criteria, mild (G1) and moderate (G2) AEs are often not reported in phase III trials. This under-reporting may inhibit our ability to understand patient toxicity burden. We analyze the relationship between the grades of AEs experienced with patient side-effect bother and treatment discontinuation. METHODS: We analyzed a phase III Eastern Cooperative Oncology Group-American College of Radiology Imaging Network trial with comprehensive AE data. The Likert response Functional Assessment of Cancer Therapy-GP5 item, "I am bothered by side effects of treatment" was used to define side-effect bother. Bayesian mixed models were used to assess the impact of G1 and G2 AE counts on patient side-effect bother and treatment discontinuation. AEs were further analyzed on the basis of symptomatology (symptomatic or asymptomatic). The results are given as odds ratios (ORs) and 95% credible interval (CrI). RESULTS: Each additional G1 and G2 AEs experienced during a treatment cycle increased the odds of increased self-reported patient side-effect bother by 13% (95% CrI, 1.06 to 1.21) and 35% (95% CrI, 1.19 to 1.54), respectively. Furthermore, only AEs defined as symptomatic were associated with increased side-effect bother, with asymptomatic AEs showing no association regardless of grade. Count of G2 AEs increased the odds of treatment discontinuation by 59% (95% CrI, 1.32 to 1.95), with symptomatic G2 AEs showing a stronger association (OR, 1.75; 95% CrI, 1.28 to 2.39) relative to asymptomatic G2 AEs (OR, 1.45; 95% CrI, 1.12 to 1.89). CONCLUSION: Low- and moderate-grade AEs are related to increased odds of increased patient side-effect bother and treatment discontinuation, with symptomatic AEs demonstrating greater magnitude of association than asymptomatic. Our findings suggest that limiting AE capture to grade 3+ misses important contributors to treatment side-effect bother and discontinuation.

Maternal 15q11.2-q13.1 duplication syndrome-associated psychosis and mania: a new case and review of the literature.

Maternal 15q11.2-q13.1 duplication syndrome is associated with a variety of developmental and neuropsychiatric abnormalities. Although schizophrenia-like presentations have been reported, details pertaining to the nature of the corresponding psychotic symptoms and their response to treatment have only been described in a few cases, and no reviews summarizing the literature currently exist. As such, we describe a new case of 15q11.2-q13.1 duplication syndrome-associated schizoaffective disorder and also performed a systematic review of the literature. Our patient's presentation is somewhat unique as she experienced visual hallucinations in the absence of auditory hallucinations. This is also the first report to describe full symptomatic remission in response to relatively low-dose atypical antipsychotic therapy.

Characterization of the prenatal renal phenotype associated with 17q12, HNF1B, microdeletions.

OBJECTIVE: Recurrent deletions involving 17q12 are associated with a variety of clinical phenotypes, including congenital abnormalities of the kidney and urinary tract (CAKUT), maturity onset diabetes of the young, type 5, and neurodevelopmental disorders. Structural and/or functional renal disease is the most common phenotypic feature, although the prenatal renal phenotypes and the postnatal correlates have not been well characterized. METHOD: We reviewed pre- and postnatal medical records of 26 cases with prenatally or postnatally identified 17q12/HNF1B microdeletions (by chromosomal microarray or targeted gene sequencing), obtained through a multicenter collaboration. We specifically evaluated 17 of these cases (65%) with reported prenatal renal ultrasound findings. RESULTS: Heterogeneous prenatal renal phenotypes were noted, most commonly renal cysts (41%, n = 7/17) and echogenic kidneys (41%), although nonspecific dysplasia, enlarged kidneys, hydronephrosis, pelvic kidney with hydroureter, and lower urinary tract obstruction were also reported. Postnatally, most individuals developed renal cysts (73%, 11/15 live births), and there were no cases of end-stage renal disease during childhood or the follow-up period. CONCLUSION: Our findings demonstrate that copy number variant analysis to assess for 17q12 microdeletion should be considered for a variety of prenatally detected renal anomalies. It is important to distinguish 17q12 microdeletion from other etiologies of CAKUT as the prognosis for renal function and presence of associated findings are distinct and may influence pregnancy and postnatal management.

Exploring Models of Exposure to Primary Care Careers in Training: a Narrative Review.

Multiple models of clinical exposure to primary care exist within undergraduate medical education (UME) and graduate medical education (GME). In this narrative review, we explore the evidence behind these different models of exposure, their alignment with positive promoters of primary care careers, and the pros and cons of each. Without positive exposure to primary care during training, sustaining the future primary care work force becomes increasingly challenging. Here, we explore multiple models of clinical exposure in UME, including longitudinal integrated clerkships, primary care tracks, and primary care clerkships. Within GME, we will review the impact of primary care tracks, Area Health Education Centers, block scheduling models, and continuity clinic scheduling models. The goal of this narrative review is to allow educators to think broadly and intentionally about the array of models to develop positive primary care experiences and perceptions in training, ultimately sustaining the primary care workforce.

Patient Engagement and Provider Effectiveness of a Novel Sleep Telehealth Platform and Remote Monitoring Assessment in the US Military: Pilot Study Providing Evidence-Based Sleep Treatment Recommendations.

BACKGROUND: Sleep problems are common and costly in the US military. Yet, within the military health system, there is a gross shortage of trained specialist providers to address sleep problems. As a result, demand for sleep medicine care far exceeds the available supply. Telehealth including telemedicine, mobile health, and wearables represents promising approaches to increase access to high-quality and cost-effective care. OBJECTIVE: The purpose of this study was to evaluate patient engagement and provider perceived effectiveness of a novel sleep telehealth platform and remote monitoring assessment in the US military. The platform includes a desktop web portal, native mobile app, and integrated wearable sensors (ie, a commercial off-the-shelf sleep tracker [Fitbit]). The goal of the remote monitoring assessment was to provide evidence-based sleep treatment recommendations to patients and providers. METHODS: Patients with sleep problems were recruited from the Internal Medicine clinic at Walter Reed National Military Medical Center. Patients completed intensive remote monitoring assessments over 10 days (including a baseline intake questionnaire, daily sleep diaries, and 2 daily symptom surveys), and wore a Fitbit sleep tracker. Following the remote monitoring period, patients received assessment results and personalized sleep education in the mobile app. In parallel, providers received a provisional patient assessment report in an editable electronic document format. Patient engagement was assessed via behavioral adherence metrics that were determined a priori. Patients also completed a brief survey regarding ease of completion. Provider effectiveness was assessed via an anonymous survey. RESULTS: In total, 35 patients with sleep problems participated in the study. There were no dropouts. Results indicated a high level of engagement with the sleep telehealth platform, with all participants having completed the baseline remote assessment, reviewed their personalized sleep assessment report, and completed the satisfaction survey. Patients completed 95.1% of sleep diaries and 95.3% of symptom surveys over 10 days. Patients reported high levels of satisfaction with most aspects of the remote monitoring assessment. In total, 24 primary care providers also participated and completed the anonymous survey. The results indicate high levels of perceived effectiveness and identified important potential benefits from adopting a sleep telehealth approach throughout the US military health care system. CONCLUSIONS: Military patients with sleep problems and military primary care providers demonstrated high levels of engagement and satisfaction with a novel sleep telehealth platform and remote monitoring assessment. Sleep telehealth approaches represent a potential pathway to increase access to evidence-based sleep medicine care in the US military. Further evaluation is warranted.

HDL regulates TGFß-receptor lipid raft partitioning, restoring contractile features of cholesterol-loaded vascular smooth muscle cells.

Background: Cholesterol-loading of mouse aortic vascular smooth muscle cells (mVSMCs) downregulates miR-143/145, a master regulator of the contractile state downstream of TGFß signaling. In vitro, this results in transitioning from a contractile mVSMC to a macrophage-like state. This process likely occurs in vivo based on studies in mouse and human atherosclerotic plaques. Objectives: To test whether cholesterol-loading reduces VSMC TGFß signaling and if cholesterol efflux will restore signaling and the contractile state in vitro and in vivo. Methods: Human coronary artery (h)VSMCs were cholesterol-loaded, then treated with HDL (to promote cholesterol efflux). For in vivo studies, partial conditional deletion of Tgfßr2 in lineage-traced VSMC mice was induced. Mice wild-type for VSMC Tgfßr2 or partially deficient (Tgfßr2+/-) were made hypercholesterolemic to establish atherosclerosis. Mice were then treated with apoA1 (which forms HDL). Results: Cholesterol-loading of hVSMCs downregulated TGFß signaling and contractile gene expression; macrophage markers were induced. TGFß signaling positively regulated miR-143/145 expression, increasing Acta2 expression and suppressing KLF4. Cholesterol-loading localized TGFß receptors into lipid rafts, with consequent TGFß signaling downregulation. Notably, in cholesterol-loaded hVSMCs HDL particles displaced receptors from lipid rafts and increased TGFß signaling, resulting in enhanced miR-145 expression and decreased KLF4-dependent macrophage features. ApoA1 infusion into Tgfßr2+/- mice restored Acta2 expression and decreased macrophage-marker expression in plaque VSMCs, with evidence of increased TGFß signaling. Conclusions: Cholesterol suppresses TGFß signaling and the contractile state in hVSMC through partitioning of TGFß receptors into lipid rafts. These changes can be reversed by promotion of cholesterol efflux, consistent with evidence in vivo.

Scavenger receptor class B type I is required for efficient glucose uptake and metabolic homeostasis in adipocytes.

Obesity is a worldwide epidemic and places individuals at a higher risk for developing comorbidities that include cardiovascular disease and type 2 diabetes. Adipose tissue contains adipocytes that are responsible for lipid metabolism and reducing misdirected lipid storage. Adipocytes facilitate this process through insulin-mediated uptake of glucose and its subsequent metabolism into triglycerides for storage. During obesity, adipocytes become insulin resistant and have a reduced ability to mediate glucose import, thus resulting in whole-body metabolic dysfunction. Scavenger receptor class B type I (SR-BI) has been implicated in glucose uptake in skeletal muscle and adipocytes via its native ligands, apolipoprotein A-1 and high-density lipoproteins. Further, SR-BI translocation to the cell surface in adipocytes is sensitive to insulin stimulation. Using adipocytes differentiated from ear mesenchymal stem cells isolated from wild-type and SR-BI knockout (SR-BI -/- ) mice as our model system, we tested the hypothesis that SR-BI is required for insulin-mediated glucose uptake and regulation of energy balance in adipocytes. We demonstrated that loss of SR-BI in adipocytes resulted in inefficient glucose uptake regardless of cell surface expression levels of glucose transporter 4 compared to WT adipocytes. We also observed reduced glycolytic capacity, increased lipid biosynthesis, and dysregulated expression of lipid metabolism genes in SR-BI -/- adipocytes compared to WT adipocytes. These results partially support our hypothesis and suggest a novel role for SR-BI in glucose uptake and metabolic homeostasis in adipocytes.