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Background/Objectives: Although COVID-19 has been linked to worse outcomes in patients with neurological disorders, its impact on those with essential tremor (ET) remains unclear. To investigate clinical outcomes of ET patients with and without COVID-19 three and a half years post-pandemic. Methods: 1074 ET patients were evaluated in this retrospective study in the Montefiore Health System from January 2016 to July 2023. Comparisons between ET patients with and without a positive SARS-CoV-2 polymerase chain reaction test were made. Outcomes included post-index date major adverse cardiovascular events (MACEs), new-onset sleep disturbances, fatigue, dyspnea, first-time fall, new-onset anxiety, new-onset depression, headache, new-onset imbalance, new-onset mild cognitive impairment, and all-cause mortality, adjusted hazard ratios (aHR) adjusting for covariates were calculated. Results: ET patients with COVID-19 had higher prevalence of pre-existing type-2 diabetes, depression, and anxiety compared to ET patients without COVID-19. COVID-19 was significantly associated with higher risk of MACEs, (aHR = 2.39 [1.49, 3.82]), new-onset sleep disturbance, (aHR = 2.12 [1.44, 3.13]), fatigue, (aHR = 1.83 [1.27, 2.65]), dyspnea, (aHR = 1.98 [1.40, 2.80]), first-time fall, (aHR = 4.76 [2.24, 10.14]), new-onset anxiety, (aHR = 3.66 [2.02, 6.64]), and new-onset depression, (aHR = 2.38 [1.20, 4.70]). COVID-19 was not associated with all-cause mortality. Conclusions: In patients with ET, COVID-19 significantly increases the risk of several long-term adverse health outcomes, but not mortality.

Objectives Patients with pre‐existing Parkinson's disease (PD) face higher risks of severe acute COVID‐19 outcomes than matched controls, but long‐term post‐COVID‐19 outcomes remain largely unknown. This study investigated clinical outcomes up to 3.5 years post‐infection in a Bronx inner‐city PD population. Methods This retrospective study evaluated 3512 patients with PD in the Montefiore Health System (January 2016–July 2023), which serves a large diverse population and was an epicenter of the early COVID‐19 pandemic and subsequent infection surges. Comparisons were made with PD patients without a positive SARS‐CoV‐2 test (defined by polymerase chain reaction test). Outcomes were post‐index date all‐cause mortality, major adverse cardiovascular events (MACE), altered mental status, fatigue, dyspnea, headache, psychosis, dementia, depression, anxiety, dysphagia, falls, and orthostatic hypotension. Changes in Levodopa prescriptions were also tabulated. Adjusted hazard ratios (aHR) were computed accounting for competing risks. Results PD patients with COVID‐19 had similar demographics but a higher prevalence of pre‐existing comorbidities compared to PD patients without COVID‐19. PD patients with COVID‐19 had greater risk of mortality (aHR = 1.58 [95% CI: 1.03, 2.41]), MACE (aHR = 1.57 [1.19, 2.07]), dyspnea, fatigue, and fall compared to PD patients without COVID‐19. Levodopa dose adjustment was higher post‐infection in the COVID‐19 cohort. Conclusions Among PD patients, COVID‐19 was associated with a higher risk of adverse long‐term outcomes. PD patients who survive COVID‐19 may benefit from heightened clinical awareness and close follow‐up. Findings highlight the need to improve post‐COVID care for PD patients to mitigate disease progression and maintain quality of life.

Aggregation of mutant Huntingtin protein (mHtt) leads to neuronal cell death and human disease. We investigated the effect of inclusion formation on yeast cells. Previous work indicates that mHtt protein moves both in and out of inclusions, potentially undergoing refolding in the inclusion. However, the sustained influx of unfolded protein into an inclusion leads to a dramatic change from a phase-separated body to an irregular, less soluble form at a threshold inclusion size. Altered morphology was associated with a prion-like seeding that accelerated inclusion growth despite loss of soluble cytoplasmic protein. The structural change abolished exchange of material between the inclusion and the cytosol and resulted in early cell death. Affected cells continued to divide occasionally, giving rise to daughters with a similar phenotype. Most newly born cells were able to reverse the prion-like aggregation, restoring both soluble cytoplasmic protein and a normal inclusion structure.Competing Interest StatementThe authors have declared no competing interest.