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Varying the hydrophobic core composition of polymeric nanoparticles affects NLRP3 inflammasome activation
No full textUnderstanding the interactions of nanoparticle carriers with innate immune cells is crucial for informing the design and efficacy of future nano-immunotherapies. An intriguing aspect of their interaction with the immune system has recently emerged, i.e., their ability to activate the NLRP3 inflammasome, a key component of the innate immune response. While the effect of the surface properties of nanoparticles has been extensively investigated in the context of nanoparticle-immune cell interactions, the influence of core composition remains largely unexplored, particularly regarding its impact on inflammasome activation. To shed light on these interactions, we developed a library of supramolecular polymer nanoparticles (SNPs) with different core compositions, varying their hydrophobic quotient by virtue of the side chain length and the repeating units in the polymer construct. The impact of modulating SNP core hydrophobic properties was investigated in macrophages by evaluating their cellular internalization, cytokine release, lysosomal rupture-calcium signaling, calcium flux-mitochondrial ROS production and their ability to activate the NLRP3 inflammasome, providing mechanistic insights into inflammasome activation. We established a direct correlation between increasing the side chain length of the polymer construct, thereby increasing the core hydrophobicity of SNPs and enhanced NLRP3 complex formation, as indicated by ASC speck imaging analysis and the elevated 1L-1β expression. Furthermore, the results demonstrated that the inflammasome signaling cascades and kinetics varied based on the SNP\u27s hydrophobic side chain length and repeating units. Specifically, the nanoparticle with the longest alkyl side chain effectuated NLRP3 activation preferentially through the mitochondrial damage pathway. In vivo evaluation of SNPs in C57BL/6 mice confirmed elevated proinflammatory cytokines, notably with the SNP having the longest C12-alkyl side chain. This confirms that the higher core hydrophobicity composition of the SNP results in inflammasome activation in vivo. In summary, this study established SNP core composition as a novel nanoparticle-associated molecular pattern (NAMP) responsible for NLRP3 inflammasome activation, shedding light on intricate cellular pathways for informed nanoparticle design in immunotherapy and vaccine applications
Givosiran for the Treatment of Pediatric Acute Intermittent Porphyria
No full textAcute intermittent porphyria (AIP) causes neurovisceral symptoms and organ toxicity resulting in acute and chronic health conditions. Treatment has traditionally involved avoiding triggers and utilizing carbohydrates and hemin infusions for acute attacks. Givosiran, an FDA-approved small interfering RNA, has shown benefit in adults in reducing attacks. However, its usage in pediatrics is extremely limited. We present a pediatric patient with AIP, requiring frequent hemin infusions for severe attacks, which have a resolution of her disease state and symptoms with the initiation of givosiran therapy
Is Phenobarbital an Effective Treatment for Alcohol Withdrawal Syndrome?
No full textBackground: Alcohol use disorder is associated with a variety of complications, including alcohol withdrawal syndrome (AWS), which may occur in those who decrease or stop alcohol consumption suddenly. AWS is associated with a range of signs and symptoms, which are most commonly treated with GABAergic medications.
Clinical question: Is phenobarbital an effective treatment for AWS?
Evidence review: Studies retrieved included two prospective, randomized, double-blind studies and three systematic reviews. These studies provided estimates of the effectiveness and safety of phenobarbital for treatment of AWS.
Conclusions: Based on the available literature, phenobarbital is reasonable to consider for treatment of AWS. Clinicians must consider the individual patient, clinical situation, and comorbidities when selecting a medication for treatment of AWS.
Keywords: GABA; alcohol; alcohol use disorder; alcohol withdrawal syndrome; benzodiazepines; phenobarbital
Correction to: Consensus guidance for monitoring individuals with islet autoantibody‑positive pre‑stage 3 type 1 diabetes
No full textThe Development and Testing of an Instrument to Measure Perceptions of Body Art Among Nurse Educators and Nursing Students
Get PDFhttps://scholarlycommons.libraryinfo.bhs.org/nurs_presentations2024/1023/thumbnail.jp
A Mindful Moment: Using Mindfulness to Combat Burnout
Get PDFhttps://scholarlycommons.libraryinfo.bhs.org/nurs_presentations2024/1010/thumbnail.jp
Evaluating the Perceived Value of Holistic Certification Among Nurses Using the PVCT-12 Tool
Get PDFhttps://scholarlycommons.libraryinfo.bhs.org/nurs_presentations2024/1024/thumbnail.jp
Recommended Guidelines for Screening for Underlying Malignancy in Extramammary Paget\u27s Disease Based on Anatomic Subtype
No full textIntroduction: Extramammary Paget\u27s disease (EMPD) may be associated with an underlying internal adenocarcinoma, referred to as secondary EMPD. Differences in this association by EMPD anatomic subtype and implications for screening are not fully understood.
Objective: Define the rates of secondary EMPD and types of associated adenocarcinomas by EMPD anatomic subtype and propose a screening algorithm for underlying adenocarcinoma.
Methods: Systematic literature review of EMPD (January 1990- November 2022). One hundred twenty-two studies met the inclusion criteria. A multidisciplinary expert panel reviewed the recommendation statements on adenocarcinoma screening.
Results: Perianal EMPD was associated with a high rate of underlying adenocarcinoma (25%, primarily colorectal) compared with penoscrotal and vulvar EMPD (6% each, primarily of genitourinary origin). Thorough screening in perianal EMPD includes a colonoscopy, urine cytology, and computed tomography (CT) of the chest, abdomen and pelvis. Cost-conscious screening tests in low-risk penoscrotal disease include urine cytology, heme-occult test, and prostate-specific antigen test (especially if under 70 years of age). For low-risk vulvar EMPD, urine cytology and mammography are recommended. EMPD with high-risk features may warrant more sensitive organ-specific testing.
Limitations: Selection bias; retrospective data without systematic follow-up.
Conclusions: Screening for underlying adenocarcinoma in EMPD should be guided by anatomic location.
Keywords: Extramammary Paget’s disease; adenocarcinoma; cancer screening; secondary EMPD
The Impact of COVID on Early Intervention Parenting Support for Mothers in Recovery from Substance Use Disorder
No full textCOVID-19 adversely impacted parents with substance use disorders (SUDs) as evidenced by increased overdoses. This study used a qualitative approach to examine COVID\u27s impact on experiences and perceptions of a parenting program designed for mothers in recovery from SUDs, Mothering from the Inside Out (MIO), implemented through Early Intervention (EI) home-visiting services. Four EI programs participated in training and implementation of MIO. Subjects included 10 eligible EI providers trained in August 2019 or August 2021 and 11 mothers in recovery from SUDs. More mothers completed MIO during the pandemic compared to before. We conducted inductive thematic analysis of exit interviews and field notes, along with interpretation of process measures of intervention implementation. Initially, the switch to telehealth negatively impacted the provider-parent relationship but made engagement logistically easier for some mothers. Parent and provider participants reported the need for additional psychosocial support due to increased stressors, as well as ways that MIO helped them cope during the pandemic. COVID made EI enrollment of families more difficult in general; however once enrolled, telehealth improved retention in MIO, meeting a critical need during the pandemic.
Keywords: COVID; Home-visiting; Parenting; Substance use disorders; Telehealth
Validity of Computer-interpreted Normal and Otherwise Normal ECG in Emergency Department Triage Patients
No full textIntroduction: Chest pain is the second most common chief complaint for patients undergoing evaluation in emergency departments (ED) in the United States. The American Heart Association recommends immediate physician interpretation of all electrocardiograms (ECG) performed for adults with chest pain within 10 minutes to evaluate for the finding of ST-elevation myocardial infarction (STEMI). The ECG machines provide computerized interpretation of each ECG, potentially obviating the need for immediate physician analysis; however, the reliability of computer-interpreted findings of normal or otherwise normal ECG to rule out STEMI requiring immediate intervention in the ED is unknown.
Methods: We performed a prospective cohort analysis of 2,275 ECGs performed in triage in the adult ED of a single academic medical center, comparing the computerized interpretations of normal and otherwise normal ECGs to those of attending cardiologists. ECGs were obtained with a GE MAC 5500 machine and interpreted using Marquette 12SL.
Results: In our study population, a triage ECG with a computerized interpretation of normal or otherwise normal ECG had a negative predictive value of 100% for STEMI (one-sided, lower 97.5% confidence interval 99.6%). None of the studied patients with these ECG interpretations had a final diagnosis of STEMI, acute coronary syndrome, or other diagnosis requiring emergent cardiac catheterization.
Conclusion: In our study population, ECG machine interpretations of normal or otherwise normal ECG excluded findings of STEMI. The ECGs with these computerized interpretations could safely wait for physician interpretation until the time of patient evaluation without delaying an acute STEMI diagnosis