Effect of altered production and storage of dopamine on development and behavior in C. elegans.

Introduction: The nematode, Caenorhabditis elegans (C. elegans), is an advantageous model for studying developmental toxicology due to its well-defined developmental stages and homology to humans. It has been established that across species, dopaminergic neurons are highly vulnerable to neurotoxicant exposure, resulting in developmental neuronal dysfunction and age-induced degeneration. C. elegans, with genetic perturbations in dopamine system proteins, can provide insight into the mechanisms of dopaminergic neurotoxicants. In this study, we present a comprehensive analysis on the effect of gene mutations in dopamine-related proteins on body size, development, and behavior in C. elegans. Methods: We studied C. elegans that lack the ability to sequester dopamine (OK411) and that overproduce dopamine (UA57) and a novel strain (MBIA) generated by the genetic crossing of OK411 and UA57, which both lack the ability to sequester dopamine into vesicles and, additionally, endogenously overproduce dopamine. The MBIA strain was generated to address the hypothesis that an endogenous increase in the production of dopamine can rescue deficits caused by a lack of vesicular dopamine sequestration. These strains were analyzed for body size, developmental stage, reproduction, egg laying, motor behaviors, and neuronal health utilizing multiple methods. Results: Our results further implicate proper dopamine synthesis and sequestration in the regulation of C. elegans body size, development through larval stages into gravid adulthood, and motor functioning. Furthermore, our analyses demonstrate that body size in terms of length is distinct from the developmental stage as fully developed gravid adult C. elegans with disruptions in the dopamine system have decreased body lengths. Thus, body size should not be used as a proxy for the developmental stage when designing experiments. Discussion: Our results provide additional evidence that the dopamine system impacts the development, growth, and reproduction in C. elegans. Furthermore, our data suggest that endogenously increasing the production of dopamine mitigates deficits in C. elegans lacking the ability to package dopamine into synaptic vesicles. The novel strain, MBIA, and novel analyses of development and reproduction presented here can be utilized in developmental neurotoxicity experiments.

Behavioural and neurodevelopmental characteristics of SYNGAP1.

BACKGROUND: SYNGAP1 variants are associated with varying degrees of intellectual disability (ID), developmental delay (DD), epilepsy, autism, and behavioural difficulties. These features may also be observed in other monogenic conditions. There is a need to systematically compare the characteristics of SYNGAP1 with other monogenic causes of ID and DD to identify features unique to the SYNAGP1 phenotype. We aimed to contrast the neurodevelopmental and behavioural phenotype of children with SYNGAP1-related ID (SYNGAP1-ID) to children with other monogenic conditions and a matched degree of ID. METHODS: Participants were identified from the IMAGINE-ID study, a UK-based, national cohort study of neuropsychiatric risk in children with ID of known genetic origin. Thirteen children with SYNGAP1 variants (age 4-16 years; 85% female) were matched (2:1) with 26 controls with other monogenic causes of ID for chronological and mental age, sex, socio-economic deprivation, adaptive behaviour, and physical health difficulties. Caregivers completed the Development and Wellbeing Assessment (DAWBA) and physical health questionnaires. RESULTS: Our results demonstrate that seizures affected children with SYNGAP1-ID (84.6%) more frequently than the ID-comparison group (7.6%; p = < 0.001). Fine-motor development was disproportionally impaired in SYNGAP1-ID, with 92.3% of children experiencing difficulties compared to 50% of ID-comparisons(p = 0.03). Gross motor and social development did not differ between the two groups. Children with SYNGAP1-ID were more likely to be non-verbal (61.5%) than ID-comparisons (23.1%; p = 0.01). Those children able to speak, spoke their first words at the same age as the ID-comparison group (mean = 3.25 years), yet achieved lower language competency (p = 0.04). Children with SYNGAP1-ID compared to the ID-comparison group were not more likely to meet criteria for autism (SYNGAP1-ID = 46.2%; ID-comparison = 30.7%; p = .35), attention-deficit hyperactivity disorder (15.4%;15.4%; p = 1), generalised anxiety (7.7%;15.4%; p = .49) or oppositional defiant disorder (7.7%;0%; p = .15). CONCLUSION: For the first time, we demonstrate that SYNGAP1-ID is associated with fine motor and language difficulties beyond those experienced by children with other genetic causes of DD and ID. Targeted occupational and speech and language therapies should be incorporated early into SYNGAP1-ID management.

Gastrointestinal toxicities of proteasome inhibitor therapy.

PURPOSE: Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib. METHODS: We conducted a retrospective study of cancer patients treated with PIs at a tertiary care cancer center to investigate the clinical characteristics of PI-related gastrointestinal adverse events. RESULTS: Our sample comprised 973 patients with PI exposure and stool studies ordered between January 2017 and December 2022. Of these, 193 patients (20%) had PI-related gastrointestinal toxicity based on clinical symptoms and stool study results. The most common symptom was diarrhea, present in 169 (88% of those with gastrointestinal toxicity). Twenty-two (11%) required hospitalization, and 71 (37%) developed recurrence of symptoms. Compared to bortezomib or carfilzomib, ixazomib had a longer interval from PI initiation to the onset of gastrointestinal symptoms (313 days vs 58 days vs 89 days, p = 0.002) and a significantly lower percentage of diarrhea-predominant presentation of gastrointestinal toxicity (71% vs 96% vs 91%, p = 0.048). CONCLUSION: While PI-related gastrointestinal toxicities have various presentations and courses based on different regimens, the vast majority of patients presented with milder disease behavior. Despite a considerably high rate of hospitalization and recurrence after treatment necessitating optimization of clinical management, our cohort demonstrates favorable outcomes without long-term consequences.

Mental health disparities of sexual minority refugees and asylum seekers: Provider perspectives on trauma exposure, symptom presentation, and treatment approach.

Refugees and asylum seekers who identify as sexual minorities and/or who have been persecuted for same-sex acts maneuver through multiple oppressive systems at all stages of migration. Sexual minority refugees and asylum seekers (SM RAS) report experiencing a greater number of persecutory experiences and worse mental health symptoms than refugees and asylum seekers persecuted for reasons other than their sexual orientation (non-SM RAS). SM RAS are growing in numbers, report a need and desire for mental health treatment, and are often referred to therapy during the asylum process. However, little research has been conducted on the treatment needs of SM RAS in therapy or the strategies therapists use to address these needs. This study sought to identify these factors through qualitative interviews with providers at a specialty refugee mental health clinic (N = 11), who had experience treating both SM RAS and non-SM RAS. Interviews were transcribed and coded for themes of similarities and differences between SM RAS and non-SM RAS observed during treatment and factors that could be leveraged to reduce mental health disparities between SM RAS and non-SM RAS. Clinicians reported that compared to the non-SM RAS, SM RAS reported greater childhood trauma exposure, increased isolation, decreased support, identity-related shame, difficulty trusting others, and continued discrimination due to their SM identitiy. Suggested adaptations included reducing isolation, preparing for ongoing identity-based challenges, creating safe spaces to express SM identity, and a slower treatment pace. Providers reported benefits and drawbacks to centering the client's SM identity in treatment and encouraging community involvement for SM RAS, and noted additional training in cultural awareness would be beneficial. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

MYC Family Amplification Dictates Sensitivity to BET Bromodomain Protein Inhibitor Mivebresib (ABBV075) in Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) accounts for nearly 15% of all lung cancers. Although patients respond to first-line therapy readily, rapid relapse is inevitable, with few treatment options in the second-line setting. Here, we describe SCLC cell lines harboring amplification of MYC and MYCN but not MYCL1 or non-amplified MYC cell lines exhibit superior sensitivity to treatment with the pan-BET bromodomain protein inhibitor mivebresib (ABBV075). Silencing MYC and MYCN partially rescued SCLC cell lines harboring these respective amplifications from the antiproliferative effects of mivebresib. Further characterization of genome-wide binding of MYC, MYCN, and MYCL1 uncovered unique enhancer and epigenetic preferences. Implications: Our study suggests that chromatin landscapes can establish cell states with unique gene expression programs, conveying sensitivity to epigenetic inhibitors such as mivebresib.

Experiences of Motivational Interviewing in Virtual Health-care Visits for Adults With Type 2 Diabetes Mellitus: A Qualitative Analysis.

OBJECTIVES: The purpose of this qualitative study is to identify barriers minimizing the effectiveness of motivational interviewing during virtual clinic encounters for individuals with type 2 diabetes based on the capability, opportunity, motivation, and behaviour (COM-B) model. METHODS: One-on-one semistructured interviews were conducted from March to June 2023, with 17 adults with type 2 diabetes (64.7% female; median age 69 years [range 47 to 83 years]) followed at St. Michael's Hospital (Toronto, Canada). Themes from transcribed interviews were identified through descriptive analysis using a grounded theory approach. RESULTS: The following main themes were identified: 1) face-to-face appointments strengthen provider-patient rapport and collaboration; 2) virtual encounters reduce patient accountability and hinder health-seeking behaviour; and 3) individuals with physical disabilities and/or low technological proficiency experience decreased provider accessibility. Protective factors that can mitigate these negative impacts include establishing rapport during in-person appointments before transitioning to virtual appointments and incorporating a video component during virtual encounters. CONCLUSIONS: Several barriers of virtual appointments currently limit the effectiveness of motivational interviewing for individuals with type 2 diabetes and make it difficult to provide person-centred care, especially by phone. However, there are protective factors that help to maintain healthy lifestyle behaviours, even after transitioning to virtual settings, and are areas for optimization moving forward.

Nontraumatic orbital hematoma secondary to labor and childbirth: a case report and review of the literature.

PURPOSE: Non-traumatic orbital hemorrhage without underlying vascular malformations or predisposing conditions is uncommon, and particularly rare in the context of maternal labor. This study combines a novel case report and retrospective review to analyze reported cases and propose insights. METHODS: This study is both a unique case report and literature review examining PubMed publications with articles traced back to original sources through citations for inclusion. Analysis included clinical presentation, visual examination, hematoma characteristics, neuroimaging, management strategies, and outcomes. RESULTS: We present a 37-year-old multigravida woman at 40 weeks gestation who developed acute right-sided proptosis, diplopia, retrobulbar pain, and periorbital edema during the second stage of labor. Computed tomography (CT) revealed a subperiosteal hemorrhage, with subsequent magnetic resonance imaging (MRI) excluding vascular anomalies. Symptoms resolved within two months. Only 14 cases of maternal orbital hematoma associated with labor have been reported. The average age was 28 with 42% (6/14) being primigravid. Including our case, forty percent (6/15) developed symptoms during the second stage of labor, 40% (6/15) immediately postpartum, and 20% (3/15) over 24 hours postpartum. Overall, 33% (5/15) had potentially contributing conditions including coagulopathies, delivery complications, or vascular malformations. Unilateral orbital hemorrhage occurred in 87% (13/15). Surgical intervention was necessary in 13% (2/15). Most (87%, 13/15) underwent observation or medical management with full recovery of symptoms. CONCLUSIONS: Non-traumatic orbital hematomas associated with maternal labor are rare and likely related to increased valsalva during delivery and heightened blood volume in pregnancy. Neuro-imaging and systemic workup are recommended to assess for vascular anomalies or underlying coagulopathies. The overall prognosis is favorable with most having full recovery.

Thio-2 Inhibits Key Signaling Pathways Required for the Development and Progression of Castration-resistant Prostate Cancer.

Therapies that abrogate persistent androgen receptor (AR) signaling in castration-resistant prostate cancer (CRPC) remain an unmet clinical need. The N-terminal domain of the AR that drives transcriptional activity in CRPC remains a challenging therapeutic target. Herein we demonstrate that BCL-2-associated athanogene-1 (BAG-1) mRNA is highly expressed and associates with signaling pathways, including AR signaling, that are implicated in the development and progression of CRPC. In addition, interrogation of geometric and physiochemical properties of the BAG domain of BAG-1 isoforms identifies it to be a tractable but challenging drug target. Furthermore, through BAG-1 isoform mouse knockout studies, we confirm that BAG-1 isoforms regulate hormone physiology and that therapies targeting the BAG domain will be associated with limited "on-target" toxicity. Importantly, the postulated inhibitor of BAG-1 isoforms, Thio-2, suppressed AR signaling and other important pathways implicated in the development and progression of CRPC to reduce the growth of treatment-resistant prostate cancer cell lines and patient-derived models. However, the mechanism by which Thio-2 elicits the observed phenotype needs further elucidation as the genomic abrogation of BAG-1 isoforms was unable to recapitulate the Thio-2-mediated phenotype. Overall, these data support the interrogation of related compounds with improved drug-like properties as a novel therapeutic approach in CRPC, and further highlight the clinical potential of treatments that block persistent AR signaling which are currently undergoing clinical evaluation in CRPC.

Detecting Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder Using Multimodal Time-Frequency Analysis with Machine Learning Using the Electroretinogram from Two Flash Strengths.

PURPOSE: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are conditions that similarly alter cognitive functioning ability and challenge the social interaction, attention, and communication skills of affected individuals. Yet these are distinct neurological conditions that can exhibit diverse characteristics which require different management strategies. It is desirable to develop tools to assist with early distinction so that appropriate early interventions and support may be tailored to an individual's specific requirements. The current diagnostic procedures for ASD and ADHD require a multidisciplinary approach and can be lengthy. This study investigated the potential of electroretinogram (ERG), an eye test measuring retinal responses to light, for rapid screening of ASD and ADHD. METHODS: Previous studies identified differences in ERG amplitude between ASD and ADHD, but this study explored time-frequency analysis (TFS) to capture dynamic changes in the signal. ERG data from 286 subjects (146 control, 94 ASD, 46 ADHD) was analyzed using two TFS techniques. RESULTS: Key features were selected, and machine learning models were trained to classify individuals based on their ERG response. The best model achieved 70% overall accuracy in distinguishing control, ASD, and ADHD groups. CONCLUSION: The ERG to the stronger flash strength provided better separation and the high frequency dynamics (80-300 Hz) were more informative features than lower frequency components. To further improve classification a greater number of different flash strengths may be required along with a discrimination comparison to participants who meet both ASD and ADHD classifications and carry both diagnoses.

Increased chromatin accessibility mediated by nuclear factor I drives transition to androgen receptor splice variant dependence in castration-resistant prostate cancer.

Androgen receptor (AR) splice variants, of which ARv7 is the most common, are increased in prostate cancer (PC) that develops resistance to androgen signaling inhibitor drugs, but the extent to which these variants drive AR activity, and whether they have novel functions or dependencies, remain to be determined. We generated a subline of VCaP PC cells (VCaP16) that is resistant to the AR inhibitor enzalutamide (ENZ) and found that AR activity was independent of the full-length AR (ARfl), despite its continued high-level expression, and was instead driven by ARv7. The ARv7 cistrome and transcriptome in VCaP16 cells mirrored that of the ARfl in VCaP cells, although ARv7 chromatin binding was weaker, and strong ARv7 binding sites correlated with higher affinity ARfl binding sites across multiple models and clinical samples. Notably, although ARv7 expression in VCaP cells increased rapidly in response to ENZ, there was a long lag before it gained chromatin binding and transcriptional activity. This lag was associated with an increase in chromatin accessibility, with the AR and nuclear factor I (NFI) motifs being most enriched at these more accessible sites. Moreover, the transcriptional effects of combined NFIB and NFIX knockdown versus ARv7 knockdown were highly correlated. These findings indicate that ARv7 can drive the AR program, but that its activity is dependent on adaptations that increase chromatin accessibility to enhance its intrinsically weak chromatin binding.

A Pilot Nonrandomized Controlled Trial Examining the Use of Artificial Tears on the Radioactivity of Tears After Radioactive Iodine Treatment for Thyroid Cancer.

Background: Nasolacrimal duct obstruction (NLDO) is an adverse effect of high dose radioactive iodine (RAI) therapy for thyroid carcinoma. There are currently no established preventive measures. This study assesses whether preservative free artificial tears (PFATs) can decrease the 131I sodium iodide (131I) activity in the tears of patients following RAI therapy for thyroid carcinoma, and potentially serve as a preventive measure for RAI-associated NLDO. Methods: This non-randomized prospective pilot clinical trial recruited contact-lens wearing patients undergoing RAI therapy for thyroid cancer to self-administer PFATs into the right eye for four days starting on the day of RAI ingestion. Left eyes were the controls. While wearing contacts, patients self-administered PFATs per the following-Day 1: every 15 minutes for 2 hours, then every 30 minutes until bedtime, day 2: every hour for at least 12 hours, day 3: four times a day, and day 4: two times a day. Contact lenses were changed daily, and all lenses were collected one week later. Levels of 131I activity were measured by a well counter, decay-corrected, and converted to units of becquerel. Statistical analyses were performed to compare the 131I activities of the experimental and control eyes. Results: Sixteen eyes of eight patients treated with an average of 145.7 mCi (range 108-159) of 131I for papillary thyroid cancer were included. On day 1, artificial tears decreased the geometric mean 131I activity by 26% in the experimental eyes (p = 0.008). Artificial tears also decreased the geometric mean area under the curve over four days by 23% (p = 0.002). Conclusions: 131I is present in the tears following RAI therapy for thyroid carcinoma. Frequent PFATs starting on the day of RAI ingestion may decrease the level of 131I in the tears. This finding could have implications for lowering the risk of NLDO. Future multi-center clinical trials are needed to determine whether the use of artificial tears after RAI therapy may decrease the risk of NLDO. Clinical Trial Registration: NCT04327999.

Pediatric neuroimaging findings and clinical presentations of COVID-19: A systematic review.

OBJECTIVES: Symptoms from SARS-CoV-2 infection can involve multiple organ systems. Several reviews discussed the neurologic involvement and neuroimaging findings in adults but research on children is lacking. This study aimed to analyze the incidence of neurologic involvement in patients diagnosed with pediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) or multisystem inflammatory syndrome in children (MIS-C); and also to summarize current literature on possible neuroimaging findings in SARS-CoV-2 infected children. METHODS: A literature search in six electronic databases was performed to retrieve case series, cohort studies, and cross-sectional studies on neurologic involvement in COVID-19 patients younger than 21 years of age published between December 2019 to September 2023, including COVID-19 patients. RESULTS: A total of 2224 patients with MIS-C from 10 cohorts and cross-sectional studies suggested that neurologic involvement in these subsets ranges from 8.5% to 32.1%. Symptoms included acute encephalitis, seizures, stroke, cranial nerve palsy, nausea/vomiting, and intracranial hypertension. Neuroradiology findings of 114 children from 50 case reports included splenial or acute disseminated encephalomyelitis (ADEM)-like lesions, cytotoxic brain edema, autoimmune demyelinating diseases, ischemic stroke and arteritis, venous thrombosis, intracranial hemorrhage, meningitis, posterior reversible encephalopathy syndrome, anti-N-methyl-D-aspartate receptor autoimmune encephalitis, acute hemorrhagic leukoencephalitis, hydrocephalus, olfactory bulb atrophy, cerebellitis, and acute necrotizing encephalitis. CONCLUSION: Radiologic findings of SARS-CoV-2 infection in the pediatric population are diverse. Neuroimaging studies should be considered in critically ill patients to rule out neurologic involvement and facilitate early interventions.

Effect of altered production and storage of dopamine on development and behavior in C. elegans.

The nematode, Caenorhabditis elegans, is an advantageous model for studying developmental toxicology due to its homology to humans and well-defined developmental stages. Similarly to humans, C. elegans utilize dopamine as a neurotransmitter to regulate motor behavior. We have previously reported behavioral deficits in a genetic model of C. elegans (OK411) that lack the neurotransmitter transporter necessary for packaging dopamine into synaptic vesicles. Anecdotally, we observed these C. elegans appeared to have a smaller body size, which is supported by prior studies that observed a larger body size in C. elegans that lack the enzyme that catalyzes dopamine synthesis, suggesting a complex regulatory system in which dopamine mediates body size in C. elegans. However, the question of whether body size abnormalities apparent in C. elegans with disruptions to their dopamine system are developmental or purely based on body size remains unanswered. Here, we present data characterizing the effect of gene mutations in dopamine-related proteins on body size, development, and behavior. We analyzed C. elegans that lack the ability to sequester dopamine (OK411), that overproduce dopamine (UA57), and a novel strain (MBIA) generated through crossing OK411 and UA57, which lacks the ability to sequester dopamine into vesicles and additionally endogenously overproduces dopamine. This novel strain was generated to address the hypothesis that an endogenous increase in production of dopamine can rescue deficits caused by a lack of vesicular dopamine sequestration. Compared to wild type, OK411 have shorter body lengths and behavioral deficits in early life stages. In contrast, the MBIA strain have similar body lengths to wild-type by early adulthood and display similar behavior to wild-type by early adulthood. Our data suggests that endogenously increasing the production of dopamine is able to mitigate deficits in C. elegans lacking the ability to package dopamine into synaptic vesicles. These results provide evidence that the dopamine system impacts development, growth, and reproduction in C. elegans.

Chemical Tools to Image the Activity of PAR-Cleaving Proteases.

Protease-activated receptors (PARs) comprise a family of four G protein-coupled receptors (GPCRs) that have broad functions in health and disease. Unlike most GPCRs, PARs are uniquely activated by proteolytic cleavage of their extracellular N termini. To fully understand PAR activation and function in vivo, it is critical to also study the proteases that activate them. As proteases are heavily regulated at the post-translational level, measures of total protease abundance have limited utility. Measures of protease activity are instead required to inform their function. This review will introduce several classes of chemical probes that have been developed to measure the activation of PAR-cleaving proteases. Their strengths, weaknesses, and applications will be discussed, especially as applied to image protease activity at the whole organism, tissue, and cellular level.

Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer.

Immunotherapies have yet to demonstrate significant efficacy in the treatment of hormone receptor-positive (HR+) breast cancer. Given that endocrine therapy (ET) is the primary approach for treating HR+ breast cancer, we investigated the effects of ET on the tumor immune microenvironment (TME) in HR+ breast cancer. Spatial proteomics of primary HR+ breast cancer samples obtained at baseline and after ET from patients enrolled in a neoadjuvant clinical trial (NCT02764541) indicated that ET upregulated ß2-microglobulin and influenced the TME in a manner that promotes enhanced immunogenicity. To gain a deeper understanding of the underlying mechanisms, the intrinsic effects of ET on cancer cells were explored, which revealed that ET plays a crucial role in facilitating the chromatin binding of RelA, a key component of the NF-κB complex. Consequently, heightened NF-κB signaling enhanced the response to interferon-gamma, leading to the upregulation of ß2-microglobulin and other antigen presentation-related genes. Further, modulation of NF-κB signaling using a SMAC mimetic in conjunction with ET augmented T-cell migration and enhanced MHC-I-specific T-cell-mediated cytotoxicity. Remarkably, the combination of ET and SMAC mimetics, which also blocks prosurvival effects of NF-κB signaling through the degradation of inhibitors of apoptosis proteins, elicited tumor regression through cell autonomous mechanisms, providing additional support for their combined use in HR+ breast cancer. SIGNIFICANCE: Adding SMAC mimetics to endocrine therapy enhances tumor regression in a cell autonomous manner while increasing tumor immunogenicity, indicating that this combination could be an effective treatment for HR+ patients with breast cancer.

Pneumatic computers for embedded control of microfluidics.

Alternative computing approaches that interface readily with physical systems are well suited for embedded control of those systems. We demonstrate finite state machines implemented as pneumatic circuits of microfluidic valves and use these controllers to direct microfluidic liquid handling procedures on the same chip. These monolithic integrated systems require only power to be supplied externally, in the form of a vacuum source. User input can be provided directly to the chip by covering pneumatic ports with a finger. State machines with up to four bits of state memory are demonstrated, and next-state combinational logic can be fully reprogrammed by changing the hole-punch pattern on a membrane in the chip. These pneumatic computers demonstrate a framework for the embedded control of physical systems and open a path to stand-alone lab-on-a-chip devices capable of highly complex functionality.

The Impact of CFTR Modulator Triple Therapy on Type 2 Inflammatory Response in Patients with Cystic Fibrosis.

Background Treatment of cystic fibrosis (CF) has been revolutionized by the use of cystic fibrosis transmembrane conductance regulator (CFTR) protein modulators such as elexacaftor/tezacaftor/ivacaftor (ETI) triple therapy. Prior studies support a role for type 2 (T2) inflammation in many people with CF (PwCF) and CF-asthma overlap syndrome (CFAOS) is considered a separate clinical entity. It is unknown whether initiation of ETI therapy impacts T2 inflammation in PwCF. We hypothesized that ETI initiation decreases T2 inflammation in PwCF. Methods A single center retrospective chart review was conducted for adult PwCF. As markers of T2 inflammation, absolute eosinophil count (AEC) and total immunoglobulin E (IgE) data were collected longitudinally 12 months prior to ETI therapy initiation and 12 months following therapy initiation. Multivariable analyses adjusted for the age, gender, CFTR mutation, disease severity, inhaled steroid use, and microbiological colonization. Results There was a statistically significant reduction (20.10%, p < 0.001) in 12-month mean IgE following ETI initiation; this change remained statistically significant in the multivariate model. The longitudinal analysis demonstrated no change in AEC following therapy initiation. Conclusion This study shows reduction in IgE but no change in AEC after ETI therapy initiation. We think that the lack of influence on AEC argues against an impact on previously established T2 inflammation and that the reduction in IgE is likely related to antigen load reduction post ETI. Further studies are warranted to determine the underlying mechanism of ETI impact on T2 inflammation and possible role for asthma immunomodulator therapy post ETI initiation in CFAOS.