Publications by authors named "Fleming M"
Background: Variants in the mitochondrial genome (mtDNA) cause a diverse collection of mitochondrial diseases and have extensive phenotypic overlap with Mendelian diseases encoded on the nuclear genome. The mtDNA is often not specifically evaluated in patients with suspected Mendelian disease, resulting in overlooked diagnostic variants.
Methods: Using dedicated pipelines to address the technical challenges posed by the mtDNA - circular genome, variant heteroplasmy, and nuclear misalignment - single nucleotide variants, small indels, and large mtDNA deletions were called from exome and genome sequencing data, in addition to RNA-sequencing when available.
Background: Socioeconomic inequality in infant mortality in the UK is rising. This study aims to identify contributory maternal and pregnancy factors that can explain the known association between area deprivation and infant mortality.
Methods: A cohort study was conducted using Clinical Practice Research Datalink (CPRD) primary care data between 2004 and 2019 linked to the Index of Multiple Deprivation (IMD), and infant mortality from the Office for National Statistics death data.
Article Synopsis
- The study evaluated the sustainability of 26 Whole Person Care pilots in California that integrated medical and social services for Medicaid enrollees.
- Key factors affecting sustainability included the program's adaptability, funding structures, and collaborative leadership with managed care plans.
- Many pilots struggled with sustainability due to challenges posed by system and policy changes when transitioning services into Medicaid benefits, especially in rural areas.
Protein lipoylation, a vital lysine post-translational modification, plays a crucial role in the function of key mitochondrial tricarboxylic acid cycle enzymatic complexes. In eukaryotes, lipoyl post-translational modification synthesis occurs exclusively through de novo pathways, relying on lipoyl synthesis/transfer enzymes, dependent upon mitochondrial fatty acid and Fe-S cluster biosynthesis. Dysregulation in any of these pathways leads to diminished cellular lipoylation.
View Article and Find Full Text PDFBackground: Metabolic and bariatric surgery is a safe and effective treatment strategy for severe childhood obesity, affecting 10% of US adolescents.
Objectives: This prospective observational study addresses knowledge gaps related to changes in weight, cardiometabolic risk, and weight-related quality of life (WRQOL) in adolescents 10 years after laparoscopic adjustable gastric band (LAGB) insertion.
Setting: Five Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) US centers.
Objectives: We identify the association between high- and low-intensity case management services on hospital and emergency department (ED) use among CommunityConnect patients.
Background: Social needs case management services vary in intensity, including the modality, workforce specialization, and maximum caseload. CommunityConnect is a social needs case management program implemented by Contra Costa Health, a county safety-net health system in California's San Francisco Bay Area.
Introduction: Metabolic syndrome (MetS) continues to impact the health-related quality of life (HRQoL) of patients despite various available therapeutic interventions. There is a dearth of information on how patient-centered factors holistically predict HRQoL to provide more insights on addressing MetS.
Objectives: To predict the HRQoL of patients with MetS in the Southern states, using the predisposing, enabling, and need factors.
Objective: This study investigated the association between patient treatment capacity rates and the percentage of racial/ethnic minorities at the county level.
Design: Ecological study at the county level.
Exposure: The percentages of racial/ethnic minorities and the people living in poverty in 3,140 counties serve as the main exposure and confounder variables.
Cancers develop resistance to inhibitors of oncogenes mainly due to target-centric mechanisms such as mutations and splicing. While inhibitors or antagonists force targets to unnatural conformation contributing to protein instability and resistance, activating tumor suppressors may maintain the protein in an agonistic conformation to elicit sustainable growth inhibition. Due to the lack of tumor suppressor agonists, this hypothesis and the mechanisms underlying resistance are not understood.
View Article and Find Full Text PDFArticle Synopsis
- The study examines the relationship between the physical traits (morphology) of neuromas and the symptoms they cause, aiming to create a classification system to help understand their clinical implications.
- A total of 45 neuroma specimens from 27 patients were analyzed, revealing that atypical neuromas were linked to higher pain levels and were more common in patients with conditions like diabetes and peripheral vascular disease.
- The proposed classification system shows strong reliability and may help surgeons and researchers improve their understanding of neuroma development and its connections to patient health factors, though further research is needed in this area.
Importance: Housing deposits and tenancy supports have become new Medicaid benefits in multiple states; however, evidence on impacts from these specific housing interventions is limited.
Objective: To evaluate the association of rental housing deposits and health care use among Medicaid beneficiaries receiving social needs case management as part of a Whole-Person Care (Medicaid 1115 waiver) pilot program in California.
Design, Setting, And Participants: This cohort study compared changes in health care use among a group of adults who received a housing deposit between October 2018 and December 2021 along with case management vs a matched comparison group who received case management only in Contra Costa County, California, a large county in the San Francisco Bay Area.
Article Synopsis
- Rare genetic diseases like Type 5 Long QT Syndrome (LQT5) are often underdiagnosed due to limited studies in referral populations, leading to skewed insights into these conditions.
- A new method was developed to identify undiagnosed LQT5 carriers in a broader population, leading to the discovery of 22 additional individuals sharing a specific genetic variant linked to LQT5.
- The analysis revealed that both referred and non-referred carriers have a prolonged QT interval, and a specific polygenic score can predict QT prolongation among those with the variant, enhancing the understanding of LQT5's impact.
Importance: Institutions have adopted protocol-driven standardized hip fracture programs (SHFPs). However, concerns persist regarding bias in adherence to guideline-concordant care leading to disparities in implementing high-quality care for patients recovering from surgery for hip fracture.
Objective: To assess disparities in the implementation of guideline-concordant care for patients after hip fracture surgery in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Targeted Hip Fracture (THF) Database.
Article Synopsis
- - The SPOTLIGHT study aimed to improve representation of African American (AA) patients in prostate cancer clinical trials, finding that 17% of enrolled patients were AA, which is above the typical rate of 8.5% in oncology trials.
- - Using a novel diagnostic tool, F-flotufolastat, the study evaluated its effectiveness in detecting prostate cancer in AA patients, recording a 93% detection rate which varied with prostate-specific antigen levels.
- - Although the overall detection rate for AA patients was slightly higher in those with intact prostates, both AA and non-AA patients had similar performance after prostate surgery, with verified detection rates at 64% and positive predictive values at 68% for AA patients
: : To provide contemporary data on cancer mortality rates within the context of incidence in the population with intellectual disabilities. : : Scotland's 2011 Census was used to identify adults with intellectual disabilities and controls with records linked to the Scottish Cancer Registry and death certificate data (March 2011-December 2019). The control cohort without intellectual disabilities and/or autism were used for indirect standardisation and calculation of crude incident rates/crude mortality rates, and age-sex standardised incident rate ratios/standardised mortality ratios (SIR/SMR), with 95% CIs.
View Article and Find Full Text PDFThe NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.
View Article and Find Full Text PDFBackground: Nine in every thousand children born in the United Kingdom have congenital heart disease, and 250,000 adults are living with the condition. This study aims to investigate the associations between congenital heart disease and educational outcomes among school-aged children in Scotland.
Methods: Routine health and education databases were linked to produce a cohort of all singleton children born in Scotland and attending a local authority run primary, secondary, or special school in Scotland at some point between 2009 and 2013.
Article Synopsis
- X-linked sideroblastic anemia (XLSA) and X-linked protoporphyria (XLPP) are rare genetic diseases caused by mutations affecting the enzyme ALAS2, crucial for heme production, with XLSA resulting from loss-of-function and XLPP from gain-of-function mutations.
- Researchers created knockin mouse models using CRISPR-CAS9 to study these diseases along with a model for congenital sideroblastic anemia (CSA) linked to SLC25A38 mutations, allowing for in-depth examination of disease characteristics and responses to dietary vitamin B6.
- The study revealed varying sensitivities to pyridoxine deficiency across models, highlighting a unique lethal interaction between certain sideroblastic anemias and vitamin
Background: One factor for the poor health outcomes among adult people with metabolic syndrome (MetS) is poor utilization of disease management resources, which may be attributable to prior experience with pharmacists (PEwP) and perceptions of disease management resource utilization (PMU). Therefore, understanding patients' experience could be critical to improving their perceptions and promoting health outcomes.
Objectives: The study explored the influence of PEwP and PMU on the health-related quality of life (HRQoL) of people with MetS.
Background: In the United States, Black men are at highest risk for being diagnosed with and dying from prostate cancer. Given this disparity, we examined relevant data to establish clinical prostate-specific antigen (PSA) screening guidelines for Black men in the United States.
Methods: A comprehensive literature search identified 1848 unique publications for screening.