Search

AbstractPrimary age-related tauopathy (PART) is a neurodegenerative tauopathy with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-β (Aβ) deposition in plaques. The pathogenesis of PART is unknown, but evidence suggests it is associated with genes that promote tau pathology as well as others that protect from Aβ toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n=647) using Braak neurofibrillary tangle stage as a quantitative trait adjusting for sex, age, genotyping platform, and principal components. We found significant associations with some candidate loci associated with AD and progressive supranuclear palsy, a primary tauopathy (SLC24A4, MS4A6A, HS3ST1, MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brain from tauopathies containing isoforms with four microtubule-binding domain repeats (4R) and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation revealed a direct and specific binding of JADE1 protein to tau containing four (4R) and no N-terminal inserts (0N4R) in post-mortem human PART brain tissue. Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a mediator of neurofibrillary degeneration.

The article discusses the challenges and resistance to implementing change in medical practices, emphasizing the slow pace of progress despite advances in research and technology. Topics discussed include the importance of evidence-based practices, the role of personal opinions in hindering progress, and strategies for encouraging acceptance of new methods among medical staff.

The article focuses on the evolution of ventilation practices in neonatal care, particularly regarding lung protection, including the decline of chronic lung disease (CLD) in higher post-menstrual age (PMA) cohorts and the utilization of non-invasive ventilation (NIV) modes to reduce CLD risk in smaller infants, emphasizing the importance of understanding the impact of ventilatory strategies on lung development and outcomes.

The article focuses on the administration of antenatal steroids (AS). Topics discussed include the first demonstration of the benefits to infants receiving AS in the late 1960s in experiments using sheep, effect of steroid when delivered prematurely, and trends revealed by investigations in Ontario about the administration of AS.

The article reflects on 35 years of Neonatal intensive care unit practice, emphasizing the evolution of techniques and philosophies. Topics include team-based care, outdated practices like chest physiotherapy, and advancements such as dexamethasone dosing protocols, highlighting the importance of adapting practices based on evolving evidence and knowledge in neonatology.

The article highlights the often overlooked collateral damage experienced by families of premature infants, discussing socioeconomic factors, parental stress, and long-term implications on children's outcomes. It emphasizes the need for a more comprehensive understanding of the challenges faced by families beyond the immediate NICU setting to enable informed decision-making and support allocation.

The article offers information on the importance of employee happiness and retention in the workplace, particularly in healthcare settings like the NICU. Topics include the impact of happy workers on efficiency, the value of human infrastructure in the workplace, and the challenges and dynamics of a multi-generational workforce, including Baby Boomers, Gen X, Gen Y (Millennials), and Gen Z.

The article discusses the use of inotropes in infants in the NICU, emphasizing the importance of considering the risks and benefits of each intervention. It highlights that while some interventions are relatively benign, others, such as inotropes, carry significant risks of morbidity and mortality. Premature infants treated with inotropes are at a higher risk of various morbidities, including IVH, ROP, NEC, and CLD, as well as increased mortality.

The article focuses on the evolving understanding of COVID-19's impact, emphasizing the misconceptions regarding its negligible threat to children and infants. Topics include the risks posed to children, the consequences of initial overconfidence in the low transmission from children, and emerging findings on COVID-19's effects on pregnancy, infants, and children, challenging earlier assumptions.

The article discuss the challenges and strategies for managing chronic lung disease (CLD) in premature infants. It emphasizes the importance of lung-protective ventilation techniques in preventing moderate to severe CLD in infants born at or after 25 weeks post-menstrual age (PMA). It further highlights the characteristics of CLD, including dysplastic changes in the lungs and airways that reduce their normal function.

The article focuses on the moral distress felt by NICU caregivers in the wake of advances in technology and treatment. Topics include the history of resuscitation practices and their effects on mortality rates, advances in mechanical ventilation and pulmonary outcomes, and the challenges of caring for increasingly premature infants.

The article focuses on the prevalence of alarm fatigue in neonatal care, drawing parallels with an aviation incident (LAPA 3142) to highlight the dangers of ignoring alarms. Topics discussed include challenges in Neonatal Intensive Care Unit (NICU) alarm management, especially regarding oxygen saturation alarms, proposed solutions such as adjusting alarm limits, and the importance of balancing patient safety with the risk of alarm fatigue.

The article focuses on the challenges and considerations in resuscitating infants at ≤23 weeks postmenstrual age (PMA), known as "nano-prems," highlighting the difficulties related to their immature skin, risk of infection, and the need for careful monitoring, especially regarding blood gases. Topics include the impact of electrode gel and fixation rings on the fragile skin of nano-prems, the importance of monitoring heart rate and PaCO2.

The article discusses a study on high-frequency jet ventilation (HFJV) and recruitment maneuvers in neonatal ventilation. It mentions that the study explores the use of recruitment maneuvers (RMs) to optimize lung recruitment and stability in neonates with chronic lung disease, particularly when using HFJV, and highlights the potential benefits of this approach. It provides insights into the author's clinical practice and principles in neonatal ventilation.

The article reflects on the evolution of artificial intelligence (AI) and its growing impact on various aspects of daily life. Topics include the historical development of AI from early diagnostic algorithms to its current applications, the potential of AI to enhance healthcare by providing unbiased information and evaluating evidence, and the future role of AI in improving safety and efficiency in fields such as automotive technology and medical diagnostics.

The article focuses on the evolving field of epigenetics, revealing how environmental factors can alter gene expression over time, potentially leading to unforeseen health risks. Topics include the impact of oxygen exposure in medical settings, the epigenetic effects of chemicals leaching from medical devices, and the long-term consequences of therapeutic interventions like steroids and blood transfusions on gene expression and health outcomes.

The article focuses on the efficacy of mechanical ventilation which is determined by the laws of physics related to gas flow. Topics include considered the resistance and compliance are most often referenced and considered the determinants and dynamics thereof are not necessarily understood or considered in and of themselves.

The article discusses the author's experience at The Neonatal Intensive Care Unit's (NICU) annual "Premie Picnic" and highlights the positive outcomes of premature infants as they grow. Topics include the importance of addressing parental distress and trauma, promoting attachment through kangaroo care, and enhancing family-centered care to provide comprehensive support for both infants and parents in the NICU.