Background: Alzheimer’s disease (AD) is the fifth leading cause of death for Americans older than 65. Though fluctuations have been noticed over the past two decades, the mortality of Alzheimer’s patients increased considerably during the COVID-19 pandemic. This study aims to explore the temporal trends in AD-associated mortality (ADAM) and disparities in these trends, and we aim to discern changes to these trends during the COVID-19 pandemic. Methods: The CDC WONDER Multiple Cause-of-Death Public Use Records from 1999 to 2022 were used to extract population data on deaths related to AD and stratify them based on age, biological sex, race, ethnicity, place of death, census region, and state. ICD-10 codes G30.0, G30.1, G30.8, and G30.9 were used to identify AD-related mortality. Statistical analysis was performed using the Joinpoint Regression Program version 5.0.2. Results: We confirmed an increase in mortality rate in all races, sexes, places of death, age groups above 65, and states/census regions. Interestingly, the age-adjusted mortality rate (AAMR) of AD was consistently higher in females compared to males. Non-Hispanic whites had the highest AD mortality by race and ethnicity. At the intersection of race and biological sex, White females had the highest AAMR with AD. Lastly, we noted an increase in AD mortality at hospice facilities as compared to other places of death. Conclusions: Our findings demonstrate that the number of deaths due to AD was exacerbated by the recent pandemic and that White females were disproportionately affected. The disparities relating to ADAM uncovered in this study may assist healthcare administrators and policymakers in their decisions. Additionally, the findings might help initiate larger studies focusing on these disparities to explore novel risk/prognostic factors for AD.

Glioblastoma aggressively invades surrounding tissue by expressing matrix metalloproteinase-2 (MMP-2). Therefore, effective inhibition of MMP-2 is a desirable target for treatment. In some reports, the chlorotoxin (Ctx) polypeptide produced by the scorpion Leiurus quinquestriatus, interacts with human MMP-2 to inhibit tumor invasion without affecting surrounding tissue. We employed three molecular docking methodologies followed by molecular dynamics simulations to find consensus binding and calculate the binding energy of these peptide ligands to MMP-2. In addition to the Ctx itself, four C-terminal fragments were chosen to study their binding to MMP-2. The molecular docking platforms HPEPDOCK, HADDOCK, and AlphaFold2 created peptide – protein poses for each candidate binding to MMP-2. These poses underwent 500 ns molecular dynamics simulations. Peptide binding on MMP-2 and final binding energies were calculated using the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method. Configurational entropy and root-mean square deviation analyses showed stable peptide – protein complexes. Ctx and its peptide fragments frequently bound to regions on MMP-2 other than the catalytic site. All docking methods shared consensus on large negative binding energies, indicating favorable interaction between Ctx and its analogs with MMP-2. While Ctx and its fragments bind to MMP-2, there is no consensus on which region of MMP-2 they are bound to or which peptide binds strongest. Neither Ctx nor its fragments inhibited MMP-2 enzymatic activity, however, glioblastoma cellular migration was inhibited. Interactions with the non-catalytic regions of MMP-2 suggest allosteric binding to MMP-2. Inhibition of cellular migration without inhibition of MMP-2 activity warrants further study into the possible targets of Ctx expressed in glioblastoma.

Glioblastoma aggressively invades surrounding tissue by expressing matrix metalloproteinase-2 (MMP-2). Therefore, effective inhibition of MMP-2 is a desirable target for treatment. In some reports, the chlorotoxin (Ctx) polypeptide produced by the scorpion Leiurus quinquestriatus, interacts with human MMP-2 to inhibit tumor invasion without affecting surrounding tissue. We employed three molecular docking methodologies followed by molecular dynamics simulations to find consensus binding and calculate the binding energy of these peptide ligands to MMP-2. In addition to the Ctx itself, four C-terminal fragments were chosen to study their binding to MMP-2. The molecular docking platforms HPEPDOCK, HADDOCK, and AlphaFold2 created peptide – protein poses for each candidate binding to MMP-2. These poses underwent 500 ns molecular dynamics simulations. Peptide binding on MMP-2 and final binding energies were calculated using the Molecular Mechanics Poisson-Boltzmann Surface Area method. Configurational entropy and root-mean square deviation analyses showed stable peptide – protein complexes. Ctx and its peptide fragments frequently bound to regions on MMP-2 other than the catalytic site. All docking methods shared consensus on large negative binding energies, indicating favorable interaction between Ctx and its analogs with MMP-2. While Ctx and its fragments bind to MMP-2, there is no consensus on which region of MMP-2 they are bound to or which peptide binds strongest. Neither Ctx nor its fragments inhibited MMP-2 enzymatic activity, however, glioblastoma cellular migration was inhibited. Interactions with the non-catalytic regions of MMP-2 suggest allosteric binding to MMP-2. Inhibition of cellular migration without inhibition of MMP-2 activity warrants further study into the possible targets of Ctx expressed in glioblastoma.

Objective: Ischemic strokes are the leading cause of neurological morbidity and mortality, and atrial fibrillation (AF) substantially increases risk. Thyrotoxicosis is associated with cardiovascular complications, including arrhythmias and hypercoagulability, yet its impact on stroke outcomes remains poorly defined. This study evaluates whether thyrotoxicosis impacts outcomes among patients with middle cerebral artery (MCA) ischemic strokes and AF to inform risk stratification and management.Methods: This retrospective cohort study utilized data from the National Inpatient Sample (NIS) database (2016 to 2022). Adult hospitalizations with primary diagnoses of MCA ischemic stroke and AF were identified using ICD-10-CM codes, and the exposure was thyrotoxicosis. Outcomes included in-hospital mortality, length of stay (LOS), and total hospital charges.Results: Among 83,255 hospitalizations for MCA ischemic stroke with AF, 230 (0.28%) had thyrotoxicosis. Thyrotoxicosis was not significantly associated with increased mortality (odds ratio 1.43, 95% CI: 0.55 to 3.76; p = 0.46). However, thyrotoxicosis was associated with a shorter LOS (mean difference –3.1 days; 95% CI: –5.7 to –0.5; p = 0.018) and lower hospital charges (mean difference -$52,426; 95% CI: –97,206 to –7,646; p = 0.022).Discussion: Although thyrotoxicosis promotes arrhythmogenic and prothrombotic states, it may not independently worsen the clinical course of ischemic stroke in patients with AF. These findings highlight the importance of demographic factors and clinical comorbidities and management in stroke outcomes and resource utilization. These findings may inform targeted, equitable strategies to optimize stroke care and reduce disparities. Further studies incorporating stroke severity and thyroid-specific factors are needed to clarify underlying mechanisms.

Background: Acute respiratory failure (ARF) is a common cause of hospitalization and is associated with substantial morbidity. For critically ill patients, neurological complications such as cerebral edema may worsen outcomes, but the impact among adults hospitalized with ARF has not been well established. Clarifying this association may guide clinical judgement. This study aims to assess whether cerebral edema is associated with differences in in-hospital mortality, length of stay (LOS), and total hospital charges among adults hospitalized with ARF. Methods: This retrospective cohort study used data from the National Inpatient Sample database from 2016 to 2022 for adults ≥18 hospitalized with ARF, comparing outcomes of in-hospital mortality, hospitalization length, and total hospital charges between patients with and without cerebral edema. Results: Cerebral edema made up 252,510 (2.4%) of the 10,463,481 hospitalizations for ARF. Increasing age had higher odds of mortality (OR per year: 1.02, 95% CI: 1.02 to 1.02, p < 0.001). Cerebral edema was associated with increased odds of in-hospital mortality compared with no cerebral edema (OR: 3.36, 95% CI: 3.26–3.46, p < 0.001). Admissions with cerebral edema also had longer hospital length of stay (LOS ratio: 1.16, 95% CI: 1.14 to 1.18, p < 0.001) and higher total hospital charges (Charges ratio: 1.45, 95% CI: 1.43 to 1.48, p < 0.001). Conclusions: Cerebral edema is an important marker of illness severity and poor prognosis in ARF. Future studies should further evaluate strategies for early identification, risk stratification, and targeted management to improve outcomes and reduce resource utilization.

Medical students are exposed to human suffering more frequently and intensely than before they began their training, but they are often not sufficiently ed