The Mature Minor Doctrine and COVID Vaccination in Connecticut

The mature minor doctrine is an exception to the common law rule of parental informed consent for a child’s medical decisions. The mature minor doctrine is applicable as either doctrine or statute in some states, but not all. Connecticut currently upholds the common law view for a minor child’s medical decision-making authority. Consequently, one prominent topic of discussion in recent years deals with the Covid-19 pandemic and the public policy discussions over nation-wide vaccination efforts. Many minors, children legally under the age of eighteen, are looking to make their own medical decisions when dealing with vaccination for the Coronavirus. By expanding the parameters of the mature minor doctrine, and implementing it into Connecticut statute, mature minors can be given the autonomy to acquire, or resist, vaccination despite their parent’s wishes. Although there has been a history of case law favoring parental authority over children, psychologists and legal scholars have brought to light new studies demonstrating adolescent development and capacity with understanding medical treatment. Furthermore, other northeastern U.S. states have gradually started to recognize mature minors in the context of vaccinations. As with any new introduction of a rule to a particular state, Connecticut legislation and courts must weigh the benefits, as well as the potential drawbacks that the mature minor doctrine may bring to light. Overall, the mature minor doctrine is a complicated doctrine, and it includes many different competing interests. However, if applied correctly, the doctrine can help competent and capable minors to make their own informed medical decisions in the state of Connecticut

Sex Differences in the Inflammatory Profile in the Brain of Young and Aged Mice

Neurodegenerative diseases are a leading cause of death worldwide with no cures identified. Thus, there is a critical need for preventative measures and treatments as the number of patients is expected to increase. Many neurodegenerative diseases have sex-biased prevalence, indicating a need to examine sex differences when investigating prevention and treatment strategies. Inflammation is a key contributor to many neurodegenerative diseases and is a promising target for prevention since inflammation increases with age, which is known as inflammaging. Here, we analyzed the protein expression levels of cytokines, chemokines, and inflammasome signaling proteins in the cortex of young and aged male and female mice. Our results show an increase in caspase-1, interleukin (IL)-1β, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and ASC specks in females compared to males. Additionally, there was an increase in IL-1α, VEGF-A, CCL3, CXCL1, CCL4, CCL17, and CCL22 in aging females and an increase in IL-8, IL-17a, IL-7, LT-α, and CCL22 in aging males. IL-12/IL-23p40, CCL13, and IL-10 were increased in females compared to males but not with age. These results indicate that there are sex differences in cortical inflammaging and provide potential targets to attenuate inflammation to prevent the development of neurodegenerative disease

Methods to Study Inflammasome Activation in the Central Nervous System: Immunoblotting and Immunohistochemistry

The inflammasome is a multiprotein complex that is responsible for mounting an innate immune response through the activation of caspase-1 and the cleavage of interleukin-1β. This multiprotein complex plays an important role in a variety of central nervous system (CNS) diseases and conditions such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and traumatic brain injury, among others. Here we describe methodological procedures to carry out immunoblotting and immunohistochemical techniques used to study inflammasome signaling in CNS tissues (brain and spinal cord)

Age-Dependent Microglial Response to Systemic Infection

Inflammation is part of the aging process, and the inflammatory innate immune response is more exacerbated in older individuals when compared to younger individuals. Similarly, there is a difference in the response to systemic infection that varies with age. In a recent article by Hoogland et al., the authors studied the microglial response to systemic infection in young (2 months) and middle-aged mice (13-14 months) that were challenged with live to investigate whether the pro- and anti-inflammatory responses mounted by microglia after systemic infection varies with age. Here, we comment on this study and its implications on how inflammation in the brain varies with age

Age-Dependent Microglial Response to Systemic Infection

Inflammation is part of the aging process, and the inflammatory innate immune response is more exacerbated in older individuals when compared to younger individuals. Similarly, there is a difference in the response to systemic infection that varies with age. In a recent article by Hoogland et al., the authors studied the microglial response to systemic infection in young (2 months) and middle-aged mice (13–14 months) that were challenged with live Escherichia coli to investigate whether the pro- and anti-inflammatory responses mounted by microglia after systemic infection varies with age. Here, we comment on this study and its implications on how inflammation in the brain varies with age

ASC, IL-18 and Galectin-3 as Biomarkers of Non-Alcoholic Steatohepatitis: A Proof of Concept Study

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is growing in prevalence. Symptoms of NASH become apparent when the disease has progressed significantly. Thus, there is a need to identify biomarkers of NASH in order to detect the disease earlier and to monitor disease severity. The inflammasome has been shown to play a role in liver diseases. Here, we performed a proof of concept study of biomarker analyses (cut-off points, positive and negative predictive values, receiver operating characteristic (ROC) curves, and likelihood ratios) on the serum of patients with NASH and healthy controls on apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, Galectin-3 (Gal-3), and C-reactive protein (CRP). ASC, IL-18, and Gal-3 were elevated in the serum of NASH patients when compared to controls. The area under the curve (AUC) for ASC was the highest (0.7317) with an accuracy of 68%, followed by IL-18 (0.7036) with an accuracy of 66% and Gal-3 (0.6891) with an accuracy of 61%. Moreover, we then fit a stepwise multivariate logistic regression model using ASC, IL-18, and Gal-3 to determine the probability of patients having a NASH diagnosis, which resulted in an AUC of 0.71 and an accuracy of 79%, indicating that combining these biomarkers increases their diagnostic potential for NASH. These results indicate that ASC, IL-18, and Gal-3 are reliable biomarkers of NASH and that combining these analytes increases the biomarker potential of these proteins

The Role of Non-canonical and Canonical Inflammasomes in Inflammaging

Neurodegenerative diseases currently affect millions of people worldwide and continues to increase in the expanding elderly population. Neurodegenerative diseases usually involve cognitive decline and are among the top causes of death. Thus, there is a critical need for the development of treatments and preventive strategies for neurodegenerative diseases. One of the risk factors of neurodegeneration is inflammaging, a low level of chronic inflammation due to old age. We have previously shown that the inflammasome contributes to inflammaging in the central nervous system (CNS). The inflammasome is a multiprotein complex of the innate immune response consisting of a sensor protein, apoptosis speck-like protein containing a CARD (ASC), and caspase-1. Our lab has developed a humanized monoclonal antibody against ASC (anti-ASC). Here, we analyzed cortical lysates from young (3 months old), aged (18 months old), and aged anti-ASC treated mice for the expression of canonical and non-canonical inflammasome proteins. We show that the protein levels of NLRP1, ASC, caspase-1, and caspase-8 were elevated in the cortex of aged mice, and that anti-ASC decreased the expression of these proteins, consistent with lower levels of the pro-inflammatory cytokine interleukin (IL)-1 beta. Additionally, we show that these proteins form a novel NLRP1-caspase-8 non-canonical inflammasome comprised of NLRP1, caspase-8 and ASC. Moreover, these inflammasome proteins were present in neurons in young and aged mice. Together, these results indicate that a novel NLRP1-caspase-8 non-canonical inflammasome is present in the cortex of mice and that anti-ASC is a potential therapeutic to decrease inflammasome-mediated inflammaging in the CNS

Inflammasome Proteins as Inflammatory Biomarkers of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) can result in severe vision loss and blurriness in the older population. The early and intermediate stages of AMD typically start without noticeable symptoms and can only be detected with a comprehensive eye exam. Because of the quiet onset of the disease, it is necessary to identify potential biomarkers to aid in the diagnosis, staging, and association with disease onset. Inflammasome signaling proteins are prominent biomarkers in the central nervous system, and the inflammasome has been shown to play a role in the innate inflammatory response in aging and AMD. Serum from healthy controls and AMD patients were analyzed for the protein levels of Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18 and C-reactive protein (CRP) to determine cutoff points, positive and negative predictive values, and receiver operator characteristic curves, as well as univariate and multivariate linear and logistic regression models. ASC, IL-18, and CRP were elevated in the serum of AMD patients when compared to healthy controls. The area under the curve (AUC) for ASC was 0.98 with a cutoff point of 365.6 pg/mL, whereas IL-18 had an AUC of 0.73 and a cutoff point of 242.4 pg/mL, and the AUC for CRP was 0.67 with a cutoff point of 8,684,152 pg/mL. Levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted of 0.1906, indicating that 19% of IL-18 could be explained by ASC protein levels in serum. Moreover, a logistic regression model for the diagnosis of AMD consists of ASC and having a diagnosis of hypertension, indicating that these two factors (elevated levels of ASC and a diagnosis of hypertension [HTN]) are associated with the diagnosis of AMD. ASC, IL-18, and CRP are elevated in patients with AMD, and the protein levels of IL-18 are partially the result of ASC protein expression. Moreover, elevated protein levels of ASC in serum and a diagnosis of HTN increase the odds of patients having a diagnosis of AMD. Biomarkers of AMD may be used to monitor disease risk, response to treatment and disease progression

Electrically Elicited Muscle Torque: Comparison Between 2500-Hz Burst-Modulated Alternating Current and Monophasic Pulsed Current.

*STUDY DESIGN: Single-blind, block-randomization crossover design. * OBJECTIVE: To compare the knee extensor muscle torque production elicited with 2500-Hz burst-modulated alternating current (BMAC) and with a monophasic pulsed current (MPC) at the maximum tolerated stimulation intensity. * BACKGROUND: Neuromuscular electrical stimulation (NMES) is often used for strengthening the quadriceps following knee surgery. Strength gains are dependent on muscle torque production, which is primarily limited by discomfort. Burst-modulated alternating current stimulation is a clinically popular waveform for NMES. Prior research has established that MPC with a relatively long pulse duration is effective for high muscle torque production. *METHODS: Participants in this study were 20 adults with no history of knee injury. A crossover design was used to randomize the order in which each participant\u27s dominant or nondominant lower extremity received NMES and the waveform (MPC or BMAC) this limb received. Stimulation intensity was incrementally increased until participants reached their maximum tolerance. The torque produced was converted to a percentage of each participant\u27s maximum volitional isometric contraction of the respective limb. * RESULTS: A general linear model for a 2-treat-ment, 2-period crossover design was utilized to analyze the results. The mean ± SD electrically induced percent maximum volitional isometric contraction at maximal participant tolerance was 49.5% ± 19.6% for MPC and 29.8% ± 12.4% for BMAC. This difference was statistically significant (P = .002) after accounting for treatment order and limb, which had no effect on torque production. *CONCLUSION: Neuromuscular stimulation using MPC may be more efficacious than using BMAC to achieve a high torque output in patients with quadriceps weakness