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1.
Proc Natl Acad Sci U S A ; 121(21): e2321584121, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38739793

ABSTRACT

We study the effect of Facebook and Instagram access on political beliefs, attitudes, and behavior by randomizing a subset of 19,857 Facebook users and 15,585 Instagram users to deactivate their accounts for 6 wk before the 2020 U.S. election. We report four key findings. First, both Facebook and Instagram deactivation reduced an index of political participation (driven mainly by reduced participation online). Second, Facebook deactivation had no significant effect on an index of knowledge, but secondary analyses suggest that it reduced knowledge of general news while possibly also decreasing belief in misinformation circulating online. Third, Facebook deactivation may have reduced self-reported net votes for Trump, though this effect does not meet our preregistered significance threshold. Finally, the effects of both Facebook and Instagram deactivation on affective and issue polarization, perceived legitimacy of the election, candidate favorability, and voter turnout were all precisely estimated and close to zero.


Subject(s)
Politics , Social Media , Humans , United States , Attitude , Male , Female
2.
JAMA Surg ; 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38506884

ABSTRACT

Importance: Delayed autotransplantation of cryopreserved parathyroid tissue (DACP) is the only surgical treatment for permanent postoperative hypoparathyroidism. Studies suggest that only a small minority of cryopreserved samples are ultimately autotransplanted with highly variable outcomes. For these reasons, many have questioned the economic utility of the process, although, to the authors' knowledge, this has never been formally studied. Objective: To report the clinical outcomes of parathyroid cryopreservation and DACP at a large academic institution and to determine the cost-effectiveness of this treatment. Design, Setting, and Participants: An institutional review board-approved, retrospective review of patients at a single institution who underwent DACP over a 17-year period was conducted with a median follow-up of 48.2 months. A forward-looking cost-utility analysis was then performed to determine the economic utility of cryopreservation/DACP vs usual care (monitoring and supplementation). Patients who had parathyroid tissue in cryopreserved storage between August 2005 to September 2022 at a single-center, academic, quaternary care center were identified. Exposure: Parathyroid cryopreservation and DACP. Main Outcomes and Measures: Graft functionality, clinical outcomes, and cost utility using a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY). Results: A total of 591 patients underwent cryopreservation. Of these, 10 patients (1.7%; mean [SD] age, 45.6 [17.9] years; 6 male [60%]) underwent DACP. A minority of autografts (2 [20%]) were subsequently fully functional, one-half (5 [50%]) were partially functional, and 3 (30%) were not functional. The cost-utility model estimated that at a large academic center over 10 years, the additional cost of 591 patients undergoing cryopreservation and 10 patients undergoing autotransplantation would be $618 791.64 (2022 dollars) and would add 8.75 QALYs, resulting in a cost per marginal QALY of $70 719.04, which is less than the common willingness-to-pay threshold of $100 000/QALY. Conclusions and Relevance: The reimplantation rate of cryopreserved tissue was low (<2%), but when implanted, autografts were at least partially functional 70% of the time. In the first-ever, to the authors' knowledge, formal cost analysis for this treatment, results of the current model suggest that cryopreservation and autotransplantation were cost-effective compared with the usual care for hypoparathyroidism at a large, academic institution. It is recommended that each surgical center consider whether the economic and logistical commitments necessary for cryopreservation are worthwhile for their individual needs.

3.
Am J Surg ; 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38519404

ABSTRACT

Pandemic-related distancing regulations gave medical educators at our college an opportunity to reimagine and expand our evidenced-based medicine curriculum to an asynchronous, virtual format. We share the experience of course directors, faculty, and students with our new surgical journal club format. Our goal was to support learners' critical appraisal skills of the surgical literature through active learning modalities such as visual abstract generation and audio-synopsis creation. We included surgeons whose practice locations and schedules may preclude participation. The curriculum was applied to our pre-existing community-based journal clubs. The asynchronous, virtual format allowed us to expand these journal clubs to include rural surgeons.

4.
J Psychiatr Res ; 170: 328-339, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38194850

ABSTRACT

Research has shown a link between depression risk and how gamers form relationships with their in-game figure of representation, called avatar. This is reinforced by literature supporting that a gamer's connection to their avatar may provide broader insight into their mental health. Therefore, it has been argued that if properly examined, the bond between a person and their avatar may reveal information about their current or potential struggles with depression offline. To examine whether the connection with an individuals' avatars may reveal their risk for depression, longitudinal data from 565 adults/adolescents (Mage = 29.3 years, SD = 10.6) were evaluated twice (six months apart). Participants completed the User-Avatar-Bond [UAB] scale and Depression Anxiety Stress Scale to measure avatar bond and depression risk. A series of tuned and untuned artificial intelligence [AI] classifiers analyzed their responses concurrently and prospectively. This allowed the examination of whether user-avatar bond can provide cross-sectional and predictive information about depression risk. Findings revealed that AI models can learn to accurately and automatically identify depression risk cases, based on gamers' reported UAB, age, and length of gaming involvement, both at present and six months later. In particular, random forests outperformed all other AIs, while avatar immersion was shown to be the strongest training predictor. Study outcomes demonstrate that UAB can be translated into accurate, concurrent, and future, depression risk predictions via trained AI classifiers. Assessment, prevention, and practice implications are discussed in the light of these results.


Subject(s)
Avatar , Depression , Adult , Adolescent , Humans , Artificial Intelligence , Cross-Sectional Studies , Machine Learning
5.
Med Phys ; 51(4): 2707-2720, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37956263

ABSTRACT

BACKGROUND: Contrastive learning, a successful form of representational learning, has shown promising results in pretraining deep learning (DL) models for downstream tasks. When working with limited annotation data, as in medical image segmentation tasks, learning domain-specific local representations can further improve the performance of DL models. PURPOSE: In this work, we extend the contrastive learning framework to utilize domain-specific contrast information from unlabeled Magnetic Resonance (MR) images to improve the performance of downstream MR image segmentation tasks in the presence of limited labeled data. METHODS: The contrast in MR images is controlled by underlying tissue properties (e.g., T1 or T2) and image acquisition parameters. We hypothesize that learning to discriminate local representations based on underlying tissue properties should improve subsequent segmentation tasks on MR images. We propose a novel constrained contrastive learning (CCL) strategy that uses tissue-specific information via a constraint map to define positive and negative local neighborhoods for contrastive learning, embedding this information in the representational space during pretraining. For a given MR contrast image, the proposed strategy uses local signal characteristics (constraint map) across a set of related multi-contrast MR images as a surrogate for underlying tissue information. We demonstrate the utility of the approach for downstream: (1) multi-organ segmentation tasks in T2-weighted images where a DL model learns T2 information with constraint maps from a set of 2D multi-echo T2-weighted images (n = 101) and (2) tumor segmentation tasks in multi-parametric images from the public brain tumor segmentation (BraTS) (n = 80) dataset where DL models learn T1 and T2 information from multi-parametric BraTS images. Performance is evaluated on downstream multi-label segmentation tasks with limited data in (1) T2-weighted images of the abdomen from an in-house Radial-T2 (Train/Test = 30/20), (2) public Cartesian-T2 (Train/Test = 6/12) dataset, and (3) multi-parametric MR images from the public brain tumor segmentation dataset (BraTS) (Train/Test = 40/50). The performance of the proposed CCL strategy is compared to state-of-the-art self-supervised contrastive learning techniques. In each task, a model is also trained using all available labeled data for supervised baseline performance. RESULTS: The proposed CCL strategy consistently yielded improved Dice scores, Precision, and Recall metrics, and reduced HD95 values across all segmentation tasks. We also observed performance comparable to the baseline with reduced annotation effort. The t-SNE visualization of features for T2-weighted images demonstrates its ability to embed T2 information in the representational space. On the BraTS dataset, we also observed that using an appropriate multi-contrast space to learn T1+T2, T1, or T2 information during pretraining further improved the performance of tumor segmentation tasks. CONCLUSIONS: Learning to embed tissue-specific information that controls MR image contrast with the proposed constrained contrastive learning improved the performance of DL models on subsequent segmentation tasks compared to conventional self-supervised contrastive learning techniques. The use of such domain-specific local representations could help understand, improve performance, and mitigate the scarcity of labeled data in MR image segmentation tasks.


Subject(s)
Brain Neoplasms , Humans , Benchmarking , Image Processing, Computer-Assisted
6.
Arthroscopy ; 40(4): 1300-1308, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37734446

ABSTRACT

PURPOSE: To perform a systematic review of randomized controlled trials comparing clinical outcomes of rotator cuff repair with and without patch augmentation. METHODS: A systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching PubMed, the Cochrane Library, and Embase to identify randomized controlled trials that directly compared outcomes between rotator cuff repair (RCR) with versus without patch augmentation. Patients were evaluated based on retear rate, histological outcomes, radiological outcomes, and patient-reported outcomes (Constant score; American Shoulder and Elbow Surgeons [ASES] score; University of California-Los Angeles shoulder scale; Simple Shoulder Test; EuroQol-visual analog scale; Disabilities of the Arm, Shoulder and Hand score; and PENN shoulder score questionnaire). RESULTS: Six studies (1 level I, 5 level II) met inclusion criteria, including 188 patients undergoing RCR alone (Control) and 193 patients undergoing RCR with patch augmentation (Patch). Patient age ranged from 56.0 to 68.0 years. The mean follow-up time ranged from 14.0 to 68.4 months. The average body mass index ranged from 24.4 to 29.4, and the overall percentage of males ranged from 32.5% to 82.3%. Three studies found significantly decreased retear rates with patch augmentation. The retear rate ranged from 34.0% to 65.4% in the Control group and 9.1% to 52.9% in the Patch group. One study found a significant difference for the Constant score favoring the Patch group. Two studies found a significant difference for the ASES score favoring the Patch group. One study found significantly better results with patch augmentation in terms of repaired tendon thickness and footprint coverage, based on magnetic resonance imaging. CONCLUSIONS: Patch augmentation of rotator cuff repairs may be associated with lower retear rates for large tears. There is limited evidence to suggest that patch augmentation is associated with improved patient-reported outcomes. LEVEL OF EVIDENCE: Level II, systematic review of level I and II studies.


Subject(s)
Rotator Cuff Injuries , Rotator Cuff , Humans , Arthroscopy/methods , Randomized Controlled Trials as Topic , Rotator Cuff/surgery , Rotator Cuff Injuries/surgery , Treatment Outcome
7.
Am J Surg ; 228: 146-150, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37805303

ABSTRACT

BACKGROUND: Previous studies demonstrate isthmus thyroid nodules are more likely to be malignant than lobar nodules. Additional data suggest that isthmus papillary thyroid cancers (PTCs) are more aggressive than lobar PTCs. We hypothesize that isthmus PTCs have a more unfavorable molecular profile. METHODS: The Cancer Genome Atlas (TCGA) database was queried to analyze clinical, mutation and gene expression data of isthmus PTCs compared to non-isthmus PTCs. RESULTS: We analyzed characteristics of 472 â€‹PTCs, including 19 isthmus PTCs. There were no significant differences between isthmus and non-isthmus PTC demographic and clinical variables or the frequency of RAS family, fusion driver, TERT, and tumor suppressor gene mutations. There was a trend towards increased BRAF mutations (68% vs 55%, p â€‹= â€‹0.28). A more aggressive gene expression profile was observed in isthmus PTC compared to lobar/multifocal PTC with differences in ERK score (19.4 vs 7.71, p â€‹< â€‹0.05) and TDS score (-0.58 vs 0.02, p â€‹< â€‹0.05). CONCLUSIONS: These results provide a possible molecular explanation for the more aggressive behavior reported in isthmus PTCs.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Transcriptome , Proto-Oncogene Proteins B-raf/genetics , Mutation
9.
Cureus ; 15(8): e43582, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37719562

ABSTRACT

Pyomyositis is a skeletal muscle infection mainly found in tropical regions. It commonly affects larger muscles, especially those of the hips. MRI tends to be the gold standard for diagnosis. Staphylococcus aureus remains the predominant causal organism in most cases of pyomyositis. Immunocompromised patients are more likely to be susceptible to this infection. In our case, an immunocompetent 27-year-old male in rural southwest Virginia was found to have a large abscess in his upper arm. Contrast-enhanced CT scan was acquired prior to drainage, leading to the diagnosis of pyomyositis. Empiric treatment with IV vancomycin 1 g q 24 hours and piperacillin/tazobactam 3.375 mg q 8 hours, prompt incision and drainage, and negative pressure wound VAC led to a complete resolution of the infection.

10.
Facial Plast Surg ; 39(5): 474-476, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37567564

ABSTRACT

Many facial plastic and reconstructive surgery providers are interested in incorporating clinical trials into their own practice. Clinical trials in facial plastics have made key contributions to current practices. Clinical trials range from investigating the safety and efficacy of Juvederm filler to reducing pain associated with injecting Juvederm. This article summarizes landmark clinical trials in facial plastic and reconstructive surgery and provides a framework for providers to get involved in clinical trials.


Subject(s)
Plastic Surgery Procedures , Surgery, Plastic , Humans , Face/surgery , Hyaluronic Acid , Clinical Trials as Topic
11.
Surgery ; 173(3): 659-664, 2023 03.
Article in English | MEDLINE | ID: mdl-37534706

ABSTRACT

BACKGROUND: Parathyroid hormone demonstrates a circadian rhythm in nondiseased patients, but it is unclear if this diurnal variation persists in the context of primary hyperparathyroidism. We anecdotally noticed that parathyroid hormone levels drawn early on the morning of parathyroid surgery (preincision parathyroid hormone), were of lower magnitude than values obtained at later times in the day. If present, a time-of-day based variation in parathyroid hormone could have important clinical implications on intraoperative surgical decision making. METHODS: We performed an Institutional Review Board-approved, retrospective chart review of patients undergoing parathyroidectomy for primary hyperparathyroidism between October 2019 and February 2022 at a quaternary care referral center. Demographic, laboratory, imaging, and operative parameters were extracted. Analysis was performed using mixed models for repeated measures with a first order autoregression correlation structure. Parathyroid hormone values were compared before and after hourly intervals between 6:00 A.M. and 12:00 P.M. RESULTS: Of 418 patients, the mean age was 61 years old, 80% of patients were female, and two-thirds had single-gland disease. A total of 933 parathyroid hormone levels were included in the analysis and median parathyroid hormone was 97.3 pg/mL. Parathyroid hormone levels were noted to be significantly lower if they were drawn before 7:00 A.M. This diurnal variation persisted in patients with single-gland and advanced hyperparathyroidism but was abrogated in multi-gland and low-baseline-parathyroid hormone disease. CONCLUSION: In patients with primary hyperparathyroidism, parathyroid hormone levels were significantly lower in the early morning hours, especially in patients with single-gland and high-baseline-parathyroid hormone hyperparathyroidism. This may have implications for intraoperative decision making when utilizing an early morning, preincision parathyroid hormone value.


Subject(s)
Hyperparathyroidism, Primary , Hypoparathyroidism , Humans , Female , Middle Aged , Male , Parathyroid Hormone , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/surgery , Retrospective Studies , Parathyroidectomy/methods
12.
Nature ; 620(7972): 137-144, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37500978

ABSTRACT

Many critics raise concerns about the prevalence of 'echo chambers' on social media and their potential role in increasing political polarization. However, the lack of available data and the challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem1,2. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from 'like-minded' sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes.


Subject(s)
Attitude , Politics , Social Media , Adult , Humans , Emotions , Language , United States , Disinformation
13.
MedEdPORTAL ; 19: 11327, 2023.
Article in English | MEDLINE | ID: mdl-37520013

ABSTRACT

Introduction: Physicians often care for patients who have experienced traumatic events including abuse, discrimination, and violence. Trauma-informed care (TIC) is a framework that recognizes the prevalence of trauma, promotes patient empowerment, and minimizes retraumatization. There are limited education curricula on how to apply TIC to acute care settings, with simulation-based training presenting a novel educational tool for this aim. Methods: Students participated in a didactic on TIC principles and its applications in acute care settings. Learners participated in three simulation cases where they performed physical exams and gathered history on patients with urgent medical needs related to intimate partner violence, transgender health, and health care discrimination. Debriefing followed each simulation. Results: Seventeen medical students participated across four sessions. The sessions were evaluated with pre- and postparticipation surveys, including Likert scales and free-response questions. After participation, individuals' self-assessed confidence improved across multiple domains, including identifying situations for trauma screenings, inquiring about trauma, and responding as a bystander. Learners also felt more familiar with TIC-specific history taking and physical exam skills. Finally, simulation was perceived as a beneficial educational tool. All findings were statistically significant (p ≤ .01). Discussion: Our simulation-based training enabled students to practice conversations and interventions related to trauma. This novel training represents a feasible and effective means for teaching TIC for acute care settings, including in the emergency department and in-patient settings. Development and evaluation were supported by the Society for Academic Emergency Medicine.


Subject(s)
Simulation Training , Students, Medical , Humans , Delivery of Health Care , Curriculum
14.
Science ; 381(6656): 398-404, 2023 07 28.
Article in English | MEDLINE | ID: mdl-37498999

ABSTRACT

We investigated the effects of Facebook's and Instagram's feed algorithms during the 2020 US election. We assigned a sample of consenting users to reverse-chronologically-ordered feeds instead of the default algorithms. Moving users out of algorithmic feeds substantially decreased the time they spent on the platforms and their activity. The chronological feed also affected exposure to content: The amount of political and untrustworthy content they saw increased on both platforms, the amount of content classified as uncivil or containing slur words they saw decreased on Facebook, and the amount of content from moderate friends and sources with ideologically mixed audiences they saw increased on Facebook. Despite these substantial changes in users' on-platform experience, the chronological feed did not significantly alter levels of issue polarization, affective polarization, political knowledge, or other key attitudes during the 3-month study period.


Subject(s)
Social Media , Humans , Attitude , Politics , Friends , Algorithms
15.
Science ; 381(6656): 392-398, 2023 07 28.
Article in English | MEDLINE | ID: mdl-37499003

ABSTRACT

Does Facebook enable ideological segregation in political news consumption? We analyzed exposure to news during the US 2020 election using aggregated data for 208 million US Facebook users. We compared the inventory of all political news that users could have seen in their feeds with the information that they saw (after algorithmic curation) and the information with which they engaged. We show that (i) ideological segregation is high and increases as we shift from potential exposure to actual exposure to engagement; (ii) there is an asymmetry between conservative and liberal audiences, with a substantial corner of the news ecosystem consumed exclusively by conservatives; and (iii) most misinformation, as identified by Meta's Third-Party Fact-Checking Program, exists within this homogeneously conservative corner, which has no equivalent on the liberal side. Sources favored by conservative audiences were more prevalent on Facebook's news ecosystem than those favored by liberals.


Subject(s)
Politics , Social Media , Humans , Communication , Ecosystem
16.
Science ; 381(6656): 404-408, 2023 07 28.
Article in English | MEDLINE | ID: mdl-37499012

ABSTRACT

We studied the effects of exposure to reshared content on Facebook during the 2020 US election by assigning a random set of consenting, US-based users to feeds that did not contain any reshares over a 3-month period. We find that removing reshared content substantially decreases the amount of political news, including content from untrustworthy sources, to which users are exposed; decreases overall clicks and reactions; and reduces partisan news clicks. Further, we observe that removing reshared content produces clear decreases in news knowledge within the sample, although there is some uncertainty about how this would generalize to all users. Contrary to expectations, the treatment does not significantly affect political polarization or any measure of individual-level political attitudes.


Subject(s)
Politics , Social Media , Humans , Attitude , Knowledge , Uncertainty
17.
Int J Emerg Med ; 16(1): 38, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37208640

ABSTRACT

A patient's current or previous experience of trauma may have an impact on their health and affect their ability to engage in health care. Every year, millions of patients who have experienced physically or emotionally traumatic experiences present to emergency departments (ED) for care. Often, the experience of being in the ED itself can exacerbate patient distress and invoke physiological dysregulation. The physiological reactions that lead to fight, flight, or freeze responses can make providing care to these patients complex and can even lead to harmful encounters for providers. There is a need to improve the care provided to the vast number of patients in the ED and create a safer environment for patients and healthcare workers. One solution to this complex challenge is understanding and integrating trauma-informed care (TIC) into emergency services. The federal Substance Abuse and Mental Health Service Administration's (SAMHSA) six guiding principles of TIC offer a universal precaution framework that ensures quality care for all patients, providers, and staff in EDs. While there is growing evidence that TIC quantitatively and qualitatively improves ED care, there is a lack of practical, emergency medicine-specific guidance on how to best operationalize TIC. In this article, using a case example, we outline how emergency medicine providers can integrate TIC into their practice.

18.
PLoS One ; 18(5): e0285707, 2023.
Article in English | MEDLINE | ID: mdl-37192201

ABSTRACT

Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, we generated a cancer-associated EpCAM mutant (EpCAM-L240A) that is retained in the cytosol compartment. Normal MCF-10A cells were transduced with H-Ras together with EpCAM wild-type (WT) or EpCAM-L240A. WT-EpCAM marginally effected invasion, proliferation, and soft agar growth. EpCAM-L240A, however, markedly altered cells and transformed to mesenchymal phenotype. Ras-EpCAM-L240A expression also promoted expression of EMT factors FRA1, ZEB1 with inflammatory cytokines IL-6, IL-8, and IL1. This altered morphology was reversed using MEK-specific inhibitors and to some extent JNK inhibition. Furthermore, these transformed cells were sensitized to apoptosis using paclitaxel and quercetin, but not other therapies. For the first time, we have demonstrated that EpCAM mutations can cooperate with H-Ras and promote EMT. Collectively, our results highlight future therapeutic opportunities in EpCAM and Ras mutated cancers.


Subject(s)
Epithelial-Mesenchymal Transition , Signal Transduction , Humans , Cell Line, Tumor , Cytosol/metabolism , Epithelial Cell Adhesion Molecule/genetics , Epithelial Cell Adhesion Molecule/metabolism , Epithelial-Mesenchymal Transition/genetics , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism
19.
Front Cell Neurosci ; 17: 1094503, 2023.
Article in English | MEDLINE | ID: mdl-37187609

ABSTRACT

Introduction: Huntington's disease (HD) is a neurodegenerative disease that primarily affects the striatum, a brain region that controls movement and some forms of cognition. Neuronal dysfunction and loss in HD is accompanied by increased astrocyte density and astrocyte pathology. Astrocytes are a heterogeneous population classified into multiple subtypes depending on the expression of different gene markers. Studying whether mutant Huntingtin (HTT) alters specific subtypes of astrocytes is necessary to understand their relative contribution to HD. Methods: Here, we studied whether astrocytes expressing two different markers; glial fibrillary acidic protein (GFAP), associated with astrocyte activation, and S100 calcium-binding protein B (S100B), a marker of matured astrocytes and inflammation, were differentially altered in HD. Results: First, we found three distinct populations in the striatum of WT and symptomatic zQ175 mice: GFAP+, S100B+, and dual GFAP+S100B+. The number of GFAP+ and S100B+ astrocytes throughout the striatum was increased in HD mice compared to WT, coinciding with an increase in HTT aggregation. Overlap between GFAP and S100B staining was expected, but dual GFAP+S100B+ astrocytes only accounted for less than 10% of all tested astrocytes and the number of GFAP+S100B+ astrocytes did not differ between WT and HD, suggesting that GFAP+ astrocytes and S100B+ astrocytes are distinct types of astrocytes. Interestingly, a spatial characterization of these astrocyte subtypes in HD mice showed that while S100B+ were homogeneously distributed throughout the striatum, GFAP+ preferentially accumulated in "patches" in the dorsomedial (dm) striatum, a region associated with goal-directed behaviors. In addition, GFAP+ astrocytes in the dm striatum of zQ175 mice showed increased clustering and association with white matter fascicles and were preferentially located in areas with low HTT aggregate load. Discussion: In summary, we showed that GFAP+ and S100B+ astrocyte subtypes are distinctly affected in HD and exist in distinct spatial arrangements that may offer new insights to the function of these specific astrocytes subtypes and their potential implications in HD pathology.

20.
Cureus ; 15(2): e35524, 2023 Feb.
Article in English | MEDLINE | ID: mdl-37007414

ABSTRACT

SARS-CoV2 is a well-recognized pathogen with a myriad of presenting symptoms. Well-documented pulmonary, neurological, gastrointestinal, and hematologic complications have occurred during the global COVID-19 pandemic. While gastrointestinal symptoms are the most commonly reported extrapulmonary symptom of COVID-19, the incidence of primary perforation has not been widely reported. In this case report, we describe a spontaneous small bowel perforation in a patient who was incidentally found to be COVID-19 positive. This peculiar case underlies the continued evolution of SARS-CoV2 understanding and potential unknown complications of the virus.

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