Publications by authors named "Michael Busch"

Background: Osteochondritis dissecans (OCD) of the knee is a focal idiopathic alteration of subchondral bone and/or its precursor with risk for instability and disruption of adjacent cartilage. Treatment options focused on preventing premature osteoarthritis vary depending on multiple patient and lesion characteristics, including lesion mobility.

Purpose: To differentiate lesion mobility before arthroscopy using a multivariable model that includes patient demographic characteristics and physical examination findings.

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Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies.

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  • - Glucose-6-phosphate dehydrogenase (G6PD) deficiency, affecting 500 million people, impairs red blood cell antioxidant functions, raising the risk of hemolysis during oxidative stress, particularly during exercise.
  • - A study using mice with a specific G6PD variant showed that, despite lower enzyme activity, these mice had better exercise performance and improved heart function post-exercise compared to normal mice.
  • - Analysis revealed enhanced mitochondrial function and changes in energy metabolism and protein turnover, indicating that G6PD-deficient individuals might have a metabolic advantage during exercise, challenging existing beliefs about hemolytic risks.
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Increasing global life expectancy motivates investigations of molecular mechanisms of aging and age-related diseases. This study examines age-associated changes in red blood cells (RBCs), the most numerous host cell in humans. Four cohorts, including healthy individuals and patients with sickle cell disease, were analyzed to define age-dependent changes in RBC metabolism.

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Background: General vaccination rates have been falling globally despite unequivocal health benefits. Noncompliance can result from access barriers and/or hesitant attitudes. Few studies have investigated the prevalence and determinants of noncompliance with COVID-19 vaccination in blood donors.

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  • - COVID-19 convalescent plasma (CCP) may be beneficial for immunocompromised patients, but the FDA's current threshold for qualifying plasma based on antibody levels might be too low.
  • - A study evaluated antibody levels in blood donors with different infection and vaccination histories, revealing that those with hybrid immunity (infection followed by vaccination) had higher antibody levels and better neutralizing capabilities.
  • - The research suggests establishing new test-based criteria for qualifying CCP, highlighting that plasma with high antibody levels could effectively neutralize various COVID-19 variants for several months after infection or vaccination.
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  • Hepatitis B core antibody (anti-HBc) screening is used in blood establishments worldwide to help prevent the transmission of hepatitis B virus (HBV), especially from donors with occult HBV infection (OBI).
  • A survey conducted revealed varied practices in HBV screening across 30 responses from 25 countries, with some establishments screening all donations for anti-HBc and HBV DNA, while others had different approaches, leading to inconsistencies in donor deferral strategies.
  • The findings highlight the need for improved confirmation of anti-HBc results to minimize unnecessary donor deferrals while balancing the risk of transmission from anti-HBc negative OBI donors, particularly in high-endemic regions where sensitive HBV DNA testing is crucial.
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Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening.

Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP).

Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users.

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  • Cardiometabolic diseases can worsen COVID-19 outcomes, and this study aimed to see if variability in related health indicators affects hospitalizations and long-term symptoms (PCC) in generally healthy individuals.
  • The study involved 3,344 blood donors whose health data was analyzed over several years and found that higher variability in body mass index (BMI) was linked to increased hospitalization and PCC risk, while blood pressure and cholesterol variability did not show a significant relationship.
  • The findings suggest that maintaining consistent BMI could be important for reducing COVID-19 severity and associated long-term effects.
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Formox, a highly energy-intensive process, currently serves as the primary source of formaldehyde (HCHO), for which there is a crucial and steadily growing chemical demand. The alternative electrochemical production of HCHO from C1 carbon sources such as CO and CO is still in its early stages, with even the few identified cases lacking mechanistic rationalization. In this study, we demonstrate that cobalt phthalocyanine (CoPc) immobilized on multiwalled carbon nanotubes (MW-CNTs) constitutes an excellent electrocatalytic system for producing HCHO with productivity through the direct reduction of CO, the two-electron reduction product of CO.

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In response to the 2015 Zika virus (ZIKV) epidemic that occurred in Brazil, numerous commercial serological assays have been developed for clinical and research applications. Diagnosis of recent infection in pregnant women remains challenging. Having standardized, comparative studies of ZIKV tests is important for implementing optimal diagnostic testing and disease surveillance.

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  • Blood donations have played a critical role in advancing public health understanding, especially highlighted during the SARS-CoV-2 pandemic, which showed the potential for blood services to contribute to public health surveillance and research.
  • The International Society of Blood Transfusion (ISBT) created a Public Health Research Toolkit to support blood services and researchers in expanding their involvement in public health initiatives.
  • This toolkit offers resources and templates for blood services to leverage donor data, engage in research studies, and establish biobanks, ultimately aiming to enhance recognition and funding for public health contributions.
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Background: Monitoring genotypes of HIV infections in blood donors may provide insights into infection trends in the general population.

Methods: HIV RNA was extracted from plasma samples of blood donors confirmed as HIV positive by blood screening nucleic acid and antibody tests. HIV genome target regions were amplified using nested real time-polymerase chain reaction followed by next-generation sequencing.

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  • Long COVID is a complex condition affecting about 12% of COVID-19 survivors, with various symptoms and no widely accepted definition, pushing researchers to study its immune profile.
  • A survey of over 33,000 blood donors revealed that higher levels of anti-nucleocapsid antibodies are linked to an increased risk of long COVID, while higher anti-spike IgG levels can reduce that risk.
  • The study identified four clinical subphenotypes—ranging from neurological to multi-systemic symptoms—suggesting that different immune responses may contribute to varied long COVID experiences.
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  • * A study involving 142,599 blood donors established a new, lower threshold for detecting past infections using the Ortho VITROS Anti-SARS-CoV-2 Total-N Antibody assay, which boosted detection sensitivity while keeping specificity above 98%.
  • * The updated test showed a high sensitivity of 98.1% for unvaccinated individuals and 95.6% for those who were vaccinated, though sensitivity was influenced by factors like the virus variant, donor age,
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Mature red blood cells (RBCs) lack mitochondria and thus exclusively rely on glycolysis to generate adenosine triphosphate (ATP) during aging in vivo or storage in blood banks. Here, we leveraged 13,029 volunteers from the Recipient Epidemiology and Donor Evaluation Study to identify associations between end-of-storage levels of glycolytic metabolites and donor age, sex, and ancestry-specific genetic polymorphisms in regions encoding phosphofructokinase 1, platelet (detected in mature RBCs); hexokinase 1 (HK1); and ADP-ribosyl cyclase 1 and 2 (CD38/BST1). Gene-metabolite associations were validated in fresh and stored RBCs from 525 Diversity Outbred mice and via multi-omics characterization of 1,929 samples from 643 human RBC units during storage.

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  • - The Asanté HIV-1 Rapid Recency assay identified HIV infection about 18 days later than traditional nucleic acid tests, indicating a delay in detection.
  • - It showed performance comparable to 19 other rapid HIV antibody tests already in use.
  • - If approved by regulators, this assay could be integrated into national HIV testing systems, allowing for the collection of HIV recency information during regular screenings without needing extra tests.
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Unlabelled: Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. Here, we leveraged a diversity outbred mouse population to map the genetic drivers of fresh/stored RBC metabolism and extravascular hemolysis upon storage and transfusion in 350 mice. We identify the ferrireductase Steap3 as a critical regulator of a ferroptosis-like process of lipid peroxidation.

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Objectives: To compare the clinical, radiographic, and patient-reported outcomes of nonoperative and operative treatment of adolescents with comminuted "Z-type" midshaft clavicle fractures.

Design: Prospective observational cohort.

Setting: Eight tertiary care pediatric centers.

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Background: Shortening of midshaft clavicle fractures has been described as a critical fracture characteristic to guide treatment. The degree to which shortening may change in the initial weeks following injury has not been well studied. The purpose of this study was to evaluate the change in shortening of adolescent clavicle fractures in the first 2 weeks following injury.

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  • Traditional methods for analyzing SARS-CoV-2 seroprevalence often underestimate antibody presence in vaccinated individuals, particularly in detecting anti-nucleocapsid responses.
  • A study compared four different immunoassays using a new method that focuses on increases in anti-N antibody levels, revealing significantly better sensitivity than conventional approaches.
  • Results showed that while the conventional approach fell short of regulatory standards for sensitivity, the new ratio-based method allowed all tested immunoassays to meet the necessary criteria, enhancing reliability in assessing seroprevalence.
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  • Nucleic acid-amplification testing (NAT) is a method used to check blood donations for harmful viruses to keep people safe.
  • In 2019, a global survey showed that countries mostly followed government rules for testing blood for viruses like HIV and hepatitis.
  • The results indicated a trend towards using individual samples for testing instead of larger pools to improve safety in blood donations.
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Recent large-scale multiomics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor.

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Serial blood and mucosal samples were characterized for 102 participants enrolled a median of 7.0 days after coronavirus disease 2019 diagnosis. Mucosal RNA was detectable for a median of 31.

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