Publications by authors named "Neil Kelly"

Article Synopsis
  • Sleep deprivation is linked to significant health risks, including an increased likelihood of influenza, particularly following acute sleep deprivation events (ASDEs) identified in a large population study.
  • The study used data from Fitbit users to analyze sleep patterns and health outcomes, revealing a correlation between political/non-political events and instances of decreased sleep.
  • Genetic factors related to sleep duration were found to influence both the severity of sleep deprivation and the risk of subsequent health issues, emphasizing the need for awareness of health impacts during major national events.
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Background Only a few studies have examined the impact of the coronavirus disease 2019 pandemic on spine ambulatory surgeries and changes in trends. Therefore, we investigated trends during the pre-pandemic period and three pandemic stages in patients undergoing lumbar decompression procedures in the ambulatory surgery (AMS) setting. Methodology A total of 2,670 adult patients undergoing one- or two-level lumbar decompression surgery were retrospectively reviewed.

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  • The study explores how hypoxia affects blood vessel behavior in pulmonary arterial hypertension (PAH) through a genetic and epigenetic mechanism involving HIF-2α.
  • HIF-2α enhances the expression of certain genes and long noncoding RNAs that contribute to increased vascular dysfunction, creating a feedback loop that further boosts HIF-2α activity.
  • A specific genetic variant (rs73184087) is linked to an increased risk of PAH; interventions that either inhibit this pathway or reduce HIF-2α levels showed protective effects against the disease in animal models.
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Background: Polypharmacy, commonly defined as taking ≥5 medications, is an undesirable state associated with lower quality of life. Strategies to prevent polypharmacy may be an important priority for patients. We sought to examine the association of healthy lifestyle, a modifiable risk factor, with incident polypharmacy.

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Background: Left heart disease is the most common cause of pulmonary hypertension (PH) and is frequently accompanied by increases in pulmonary vascular resistance. However, the distinction between phenotypes of PH due to left heart disease with a normal or elevated pulmonary vascular resistance-isolated postcapillary PH (IpcPH) and combined pre- and postcapillary PH (CpcPH), respectively-has been incompletely defined using unbiased methods.

Methods And Results: Patients with extremes of IpcPH versus CpcPH were identified from a single-center record of those who underwent right heart catheterization.

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Purpose: There are reports that performing lateral lumbar interbody fusion (LLIF) in a prone, single position (single-prone LLIF) can be done safely in the prone position because the retroperitoneal organs reflect anteriorly with gravity. However, only a few study has investigated the safety of single-prone LLIF and retroperitoneal organ positioning in the prone position. We aimed to investigate the positioning of retroperitoneal organs in the prone position and evaluate the safety of single-prone LLIF surgery.

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Background Pulmonary arterial hypertension (PAH) is a complex, fatal disease where disease severity has been associated with the single nucleotide polymorphism (SNP) rs2856830, located near the human leukocyte antigen DPA1 (HLA-DPA1) gene. We aimed to define the genetic architecture of functional variants associated with PAH disease severity by identifying allele-specific binding transcription factors and downstream targets that control endothelial pathophenotypes and PAH. Methods and Results Electrophoretic mobility shift assays of oligonucleotides containing SNP rs2856830 and 8 SNPs in linkage disequilibrium revealed functional SNPs via allele-imbalanced binding to human pulmonary arterial endothelial cell nuclear proteins.

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Study Design: A retrospective observational study.

Objective: The objective of this study was to investigate the factors associated with the conversion of patient status from ambulatory surgery (AMS) to observation service (OS) (<48 h) or inpatient (>48 h).

Summary Of Background Data: AMS is becoming increasingly common in the United States because it is associated with a similar quality of care compared with inpatient surgery, significant costs reduction, and patients' desire to recuperate at home.

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Pulmonary arterial hypertension (PAH) features pathogenic and abnormal endothelial cells (ECs), and one potential origin is clonal selection. We studied the role of p53 and toll-like receptor 3 (TLR3) in clonal expansion and pulmonary hypertension (PH) via regulation of bone morphogenetic protein (BMPR2) signaling. ECs of PAH patients had reduced p53 expression.

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Background/objectives: People with obesity (PWO) face an increased risk of severe outcomes from COVID-19, including hospitalisation, ICU admission and death. Obesity has been seen to impair immune memory following vaccination against influenza, hepatitis B, tetanus, and rabies. Little is known regarding immune memory in PWO following COVID-19 adenovirus vector vaccination.

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Pulmonary arterial hypertension (PAH) is an enigmatic and deadly vascular disease with no known cure. Recent years have seen rapid advances in our understanding of the molecular underpinnings of PAH, with an expanding knowledge of the molecular, cellular, and systems-level drivers of disease that are being translated into novel therapeutic modalities. Simultaneous advances in clinical technology have led to a growing list of tools with potential application to diagnosis and phenotyping.

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Background: Healthy lifestyle is associated with reduced all-cause mortality, but it is not known whether this association persists for individuals with high medication burden. We examined the association between healthy lifestyle behaviors and all-cause mortality across different degrees of polypharmacy.

Methods: This was a secondary analysis of 20,417 adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study.

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Utilizing publicly available ribonucleic acid sequencing data, we identified as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity.

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Rationale: Impaired myocardial relaxation is an intractable feature of several heart failure (HF) causes. In human HF, detyrosinated microtubules stiffen cardiomyocytes and impair relaxation. Yet the identity of detyrosinating enzymes have remained ambiguous, hindering mechanistic study and therapeutic development.

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Detyrosinated microtubules provide mechanical resistance that can impede the motion of contracting cardiomyocytes. However, the functional effects of microtubule detyrosination in heart failure or in human hearts have not previously been studied. Here, we utilize mass spectrometry and single-myocyte mechanical assays to characterize changes to the cardiomyocyte cytoskeleton and their functional consequences in human heart failure.

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Article Synopsis
  • Aging muscle atrophy is influenced by neurodegenerative changes like motor unit remodeling, but the details and effects are unclear, especially across different aging populations.* -
  • The study examines the relationship between myofiber type grouping, NMJ stability, and the effects of age and Parkinson's disease on muscle recruitment during tasks, finding that PD leads to excessive motor unit remodeling.* -
  • Resistance training shows potential benefits for stabilizing NMJ and improving motor unit efficiency in older adults and those with Parkinson's, suggesting a therapeutic avenue for age-related muscle decline.*
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BACKGROUND Pathologic alterations in resting-state brain activity patterns exist among individuals with Parkinson's disease (PD). Since physical exercise alters resting-state brain activity in non-PD populations and improves PD symptoms, we assessed the acute effect of exercise on resting-state brain activity in exercise-trained individuals with PD. MATERIAL AND METHODS Resting-state functional magnetic resonance imaging (fMRI) was collected twice for 17 PD participants at the conclusion of an exercise intervention.

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Purpose: The myriad consequences of age-related muscle atrophy include reduced muscular strength, power, and mobility; increased risk of falls, disability, and metabolic disease; and compromised immune function. At its root, aging muscle atrophy results from a loss of myofibers and atrophy of the remaining type II myofibers. The purpose of this trial (NCT02442479) was to titrate the dose of resistance training (RT) in older adults in an effort to maximize muscle regrowth and gains in muscle function.

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  • The study investigates myofiber type grouping in older adults compared to younger adults, focusing on how age affects muscle fiber characteristics and organization.* -
  • Biopsy results show older individuals have significantly larger and more grouped type I myofibers, which also exhibit distinct features such as increased myonuclei but reduced capillary supply compared to ungrouped fibers.* -
  • Findings suggest that the process of muscle fiber conversion during age-related changes may not be fully completed, as grouped fibers still show characteristics of type II fibers.*
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Chronic obstructive pulmonary disease (COPD) is caused by a complex interaction of environmental exposures, most commonly cigarette smoke, and genetic factors. Chronic cigarette smoke exposure in the mouse is a commonly used animal model of COPD. We aimed to expand our knowledge about the variable susceptibility of inbred strains to this model and test for genetic variants associated with this trait.

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Rationale: Macrophage elastase (matrix metalloproteinase [MMP]-12) is a potent protease that contributes to the lung destruction that accompanies cigarette smoking; it simultaneously inhibits lung tumor angiogenesis and metastasis by catalyzing the formation of antiangiogenic peptides. Recent studies have revealed novel nonproteolytic functions of MMP12, including antimicrobial activity through a peptide within its C-terminal domain (CTD).

Objectives: To determine whether the MMP12 CTD contributes to its antitumor activity in lung cancer.

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Rationale: Genetic association studies in chronic obstructive pulmonary disease have primarily tested for association with common variants, the results of which explain only a portion of disease heritability. Because rare variation is also likely to contribute to susceptibility, we used whole-genome sequencing of subjects with clinically extreme phenotypes to identify genomic regions enriched for rare variation contributing to chronic obstructive pulmonary disease susceptibility.

Objectives: To identify regions of rare genetic variation contributing to emphysema with severe airflow obstruction.

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Pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (PH-HFpEF; World Health Organization Group II) secondary to left ventricular (LV) diastolic dysfunction is the most frequent cause of PH. It is an increasingly recognized clinical complication of the metabolic syndrome. To date, no effective treatment has been identified, and no genetically modifiable mouse model is available for advancing our understanding for PH-HFpEF.

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