Basic Science and Pathogenesis.

Background: The accumulation of abnormal tau protein in neurons and glia in the human brain is the defining feature of neurodegenerative diseases known as tauopathies. Progressive supranuclear palsy (PSP), the most common primary tauopathy, is typified by selective vulnerability of dopaminergic neurons and glia in the midbrain leading to an atypical parkinsonian movement disorder. To investigate candidate disease mechanisms underlying PSP, there is a critical need for model systems that more accurately recapitulate the cellular and molecular environment in the human brain.

Basic Science and Pathogenesis.

Background: Progressive supranuclear palsy (PSP) is the most common primary tauopathy, with a constellation of pathological features including 4R-tau positive neurofibrillary tangles and tufted astrocytes. Most PSP cases are sporadic and associated with common structural variation in the 17q21.31 MAPT locus as well as other loci, including EIF2AK3 which is critical for the integrated stress response (ISR).

Basic Science and Pathogenesis.

Background: Lateral entorhinal cortex (LEC), medial entorhinal cortex (MEC), and hippocampal area exhibit cell damage due to B-Amyloid depositions, intracellular tau aggregates, and neurofibrillay tangles. AD mouse models allow us to investigate how AD neurodegeneration affects specific brains circuits and resulting behaviors. Specifically, the PS1 and APP NL-G-F knock in (APP-KI) mouse models are relevant due to their genetic modifications, episodic memory impairment, early AD pathophysiology, and novelty designed for study.

Basic Science and Pathogenesis.

Background: The entorhinal cortex and hippocampus are loci of early vulnerability in AD. These areas are crucial for episodic memory processing for space and contexts. The majority of AD model mouse imaging and electrode studies utilize simple tasks such open field and linear track.

Clinical Manifestations.

Background: Impaired cognition is prevalent in older adults in the emergency department (ED), but many cases go unrecognized. The Ascertain Dementia 8 (AD8) is a validated, self-administered screening tool that can be used by patients and caregivers to assess for early cognitive changes associated with dementia. However, little is known regarding the degree of alignment between respondents in the ED setting.

Basic Science and Pathogenesis.

Background: Neurofibrillary tangles (NFTs), one of the hallmarks of Alzheimer's disease (AD), are composed of highly phosphorylated forms of the microtubule-associated protein tau. Phosphorylation results from the activity of several threonine/serine kinases, and increased expression of glycogen synthase kinase-3β (GSK-3β). These are involved in the formation of paired helical filament (PHF)-tau, which induces the formation of NFTs.

Clinical Manifestations.

Background: Subjective cognitive decline (SCD) is a preclinical stage of Alzheimer's disease (AD), with correlations to cerebral amyloid and tau and accelerated cognitive decline. Studies have also revealed an association between sleep fragmentation and such AD biomarkers and cognitive decline, suggesting that cognitive function should be monitored in individuals experiencing excessive sleepiness. It is unclear if and how sleep dysfunction relates to SCD apart from AD biomarkers, as well as symptoms related to SCD and sleep dysfunction, such as depression.

Clinical Manifestations.

Background: Clinically meaningful cognitive impairment has typically been defined as a single impaired test score, but this approach is prone to false-positive errors. Examining two test scores at a lower threshold (i.e.

Clinical Manifestations.

Background: Traumatic encephalopathy syndrome (TES) is the proposed clinical syndrome of chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repetitive head impacts in contact/collision sports. A core clinical feature of TES is cognitive impairment, particularly in memory and executive functions. Cognitive intraindividual variability (IIV) is the extent of variability in neuropsychological test performance (i.

Congress of Neurological Surgeons systematic review and evidence based guideline on neuropathology for WHO grade II diffuse glioma: update.

Unlabelled: QUESTIONS AND RECOMMENDATIONS FROM THE PRIOR VERSION OF THESE GUIDELINES WITHOUT CHANGE: TARGET POPULATION: Adult patients (age ≥ 18 years) who have suspected low-grade diffuse glioma.

Question: What are the optimal neuropathological techniques to diagnose low-grade diffuse glioma in the adult?

Recommendation: Level I Histopathological analysis of a representative surgical sample of the lesion should be used to provide the diagnosis of low-grade diffuse glioma. Level III Both frozen section and cytopathologic/smear evaluation should be used to aid the intra-operative assessment of low-grade diffuse glioma diagnosis.

System vaccinology analysis of predictors and mechanisms of antibody response durability to multiple vaccines in humans.

We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.

Genomic signatures of adaptation in native lizards exposed to human-introduced fire ants.

Understanding the process of genetic adaptation in response to human-mediated ecological change will help elucidate the eco-evolutionary impacts of human activity. In the 1930s red imported fire ants (Solenopsis invicta) were accidently introduced to the Southeastern USA, where today they are both venomous predators and toxic prey to native eastern fence lizards (Sceloporus undulatus). Here, we investigate potential lizard adaptation to invasive fire ants by generating whole-genome sequences from 420 lizards across three populations: one with long exposure to fire ants, and two unexposed populations.

Prospects of the Surgical Management of Colorectal Peritoneal Metastasis.

Background: Colorectal cancer (CRC) is a common malignancy with the propensity to metastasize. Common sites of metastasis include the liver, lung, and peritoneum with peritoneal metastases (PM) having the worst prognosis. Unfortunately, systemic chemotherapy is often less effective in the treatment of peritoneal metastases.

Gallstone Ileus as an Occult Cause of Small Bowel Obstruction and Subsequent Large Bowel Obstruction: A Report of a Rare Case.

Gallstone ileus, a rare cause of mechanical bowel obstruction, occurs due to the formation of a cholecystenteric fistula allowing gallstones to migrate into the gastrointestinal tract. The condition occurs mostly in elderly patients, particularly women, and carries a significant mortality risk due to delayed diagnosis. This case report discusses a 77-year-old female patient with a history of chronic medical conditions, who self-presented with periumbilical pain, nausea, and reduced bowel movements.

Neoadjuvant anti-PD1 immunotherapy for surgically accessible recurrent glioblastoma: clinical and molecular outcomes of a stage 2 single-arm expansion cohort.

Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).

Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction in the United States.

Background: The role of Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) is still unclear in patients with STEMI undergoing PCI in the current second-generation DES era.

Aims: This study aimed to evaluate the trends and outcomes of IVUS-guided PCI in patients with STEMI.

Methods: We used the National Inpatient Sample (NIS) database from 2016 to 2021.

The ADHD Assessment Quality Assurance Standard for Children and Teenagers (CAAQAS).

Around 5% of the children and teenagers worldwide are affected by Attention-Deficit/Hyperactivity Disorder [ADHD], making it a major public health concern. Recently, demand for assessments has substantially increased, putting strain on healthcare and waiting lists. There is concern that pressure to clear service bottlenecks is leading to variable quality and reliability of ADHD assessments in this population.

Cephalomedullary Nails for Isolated Subtrochanteric Femur Fractures: Age-Related Variations in Fracture Pattern and Perioperative Factors Do Not Affect Clinical and Radiographic Outcomes.

Introduction: There is scarce data in literature on the demographics, treatment, and outcomes of subtrochanteric femur fracture patients. This study evaluated the effect of age on injury details, perioperative and hospital parameters, and outcomes following subtrochanteric fracture fixation.

Methods: An IRB-approved review of a consecutive series of subtrochanteric femoral fractures was performed.

Variability in Notification of Positive Newborn Screening Results for Sickle Cell Trait Across the United States.

Universal in the United States (US) since 2006, newborn screening (NBS) programs for sickle cell disease (SCD) allow for early identification of the disease and, as an unintentional byproduct, identification of sickle cell trait (SCT). Unlike other carrier states, SCT is highly prevalent and is found in nearly 3 million Americans, which results in important reproductive implications. Currently, all NBS programs in the US are responsible for their own policies regarding SCT notification, and little is known about how SCT notification practices are performed and how these practices vary across NBS programs.

Current Approaches to Optimize Donor Heart for Transplantation.

Heart transplantation remains a critical therapy for patients with end-stage heart failure, offering incremental survival and improved quality of life. One of the key components behind the success of heart transplantation is the condition and preservation of the donor heart. In this review, we provide a comprehensive overview of ischemic reperfusion injury, risk factors associated with primary graft dysfunction, current use of various preservation solutions for organ procurement and recent advancements in donor heart procurement technologies.

Circadian Influences on Brain Lipid Metabolism and Neurodegenerative Diseases.

Circadian rhythms are intrinsic, 24 h cycles that regulate key physiological, mental, and behavioral processes, including sleep-wake cycles, hormone secretion, and metabolism. These rhythms are controlled by the brain's suprachiasmatic nucleus, which synchronizes with environmental signals, such as light and temperature, and consequently maintains alignment with the day-night cycle. Molecular feedback loops, driven by core circadian "clock genes", such as Clock, Bmal1, Per, and Cry, are essential for rhythmic gene expression; disruptions in these feedback loops are associated with various health issues.

Increased copeptin may reflect vasopressin-related metabolic changes after bariatric surgery.

Objective: Mechanisms underlying metabolic improvement following metabolic and bariatric surgery (MBS) may provide insight into novel therapies. Vasopressin improves body composition and protects against hypoglycemia. Associations of copeptin, a stable cleavage product of vasopressin, with BMI and insulin resistance suggest an adaptive increase in vasopressin to counteract metabolic disruption.