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Current Opinion in Lipidology Jun 2024Newborn screening is one of the most successful public health programs of the last century and offers unparalleled access to universal screening for a variety of... (Review)
Review
PURPOSE OF REVIEW
Newborn screening is one of the most successful public health programs of the last century and offers unparalleled access to universal screening for a variety of metabolic and other disorders. Interest in development of newborn screening for lipid disorders has intensified in recent years. Screening newborns for lipid disorders has important implications for the health of the newborn as well as their relatives, and in the case of more common lipid disorders like familial hypercholesterolemia, could have important public health implications.
RECENT FINDINGS
Recent studies have demonstrated feasibility of measuring biomarkers for heterozygous familial hypercholesterolemia from newborn screening dried blood spot specimens. Another lipid disorder, cerebrotendinous xanthomatosis, is currently amenable to newborn screening utilizing currently available assays. New research in next-generation sequencing as a primary screen in newborns will also identify both common and rare lipid disorders in newborns.
SUMMARY
Historically, newborn screening for lipid disorders was not done for many reasons, but new research has developed testing methods that may successfully identify common and rare lipid disorders. This will impact the health of the newborn but could also impact family members and public health.
Topics: Humans; Neonatal Screening; Infant, Newborn; Biomarkers
PubMed: 38408035
DOI: 10.1097/MOL.0000000000000928 -
Annals of Clinical and Translational... Aug 2023Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory...
OBJECTIVE
Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis.
METHODS
At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene.
RESULTS
In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified.
INTERPRETATION
This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.
Topics: Infant; Humans; Male; Infant, Newborn; Female; Muscular Dystrophy, Duchenne; Neonatal Screening; Pilot Projects; Genetic Testing; High-Throughput Nucleotide Sequencing
PubMed: 37350320
DOI: 10.1002/acn3.51829 -
Bioanalysis Sep 2023A sensitive and selective method for the determination of PF-07059013 in dried blood collected by Mitra™ tips was developed and qualified from 50 to 50,000 ng/ml.... (Review)
Review
A sensitive and selective method for the determination of PF-07059013 in dried blood collected by Mitra™ tips was developed and qualified from 50 to 50,000 ng/ml. PF-07059013 is isolated from 10 μl of human dried blood by extraction with methanol and analyzed by HPLC-MS/MS. In addition to routine validation elements, impact of hematocrit and Mitra tip's lot-to-lot variation on assay accuracy were evaluated. The qualified method was used in one clinical study with excellent performance. Correlation coefficient between blood concentrations obtained from liquid-incurred blood samples and dried-incurred blood samples is 0.95. NCT04323124 (ClinicalTrials.gov).
Topics: Humans; Tandem Mass Spectrometry; Dried Blood Spot Testing; Specimen Handling; Chromatography, High Pressure Liquid; Hematocrit
PubMed: 37584365
DOI: 10.4155/bio-2023-0066 -
Journal of Separation Science Aug 2023Dried blood spot samples are simple to prepare and transport, enabling safe and accessible diagnostics, both locally and globally. We review dried blood spot samples for... (Review)
Review
Dried blood spot samples are simple to prepare and transport, enabling safe and accessible diagnostics, both locally and globally. We review dried blood spot samples for clinical analysis, focusing on liquid chromatography-mass spectrometry as a versatile measurement tool for these samples. Dried blood spot samples can provide information for, for example, metabolomics, xenobiotic analysis, and proteomics. Targeted analyses of small molecules are the main application of dried blood spot samples and liquid chromatography-mass spectrometry, but emerging applications include untargeted metabolomics and proteomics. Applications are highly varied, including analyses related to newborn screening, diagnostics and monitoring of disease progression and treatment effects of virtually any disease, as well as studies into the physiology and effects of diet, exercise, xenobiotics, and doping. A range of dried blood spot products and methods are available, and applied liquid chromatography-mass spectrometry instrumentation is varied with regard to liquid chromatography column formats and selectivity. In addition, novel approaches such as on-paper sample preparation (e.g., selective trapping of analytes with paper-immobilized antibodies) are described. We focus on research papers published in the last 5 years.
Topics: Infant, Newborn; Humans; Tandem Mass Spectrometry; Dried Blood Spot Testing; Chemistry, Clinical; Chromatography, Liquid; Specimen Handling
PubMed: 37269205
DOI: 10.1002/jssc.202300210 -
Journal of Pharmacological and... 2023Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development....
INTRODUCTION
Pharmacokinetic/pharmacodynamic modelling has emerged as a valuable technique for understanding drug exposure and response relationships in drug development. Pharmacokinetic data are often obtained by taking multiple blood samples, which may disturb physiological parameters and complicate study designs. Wearable automatic blood sampling systems can improve this limitation by collecting dried blood samples at programmable time points without disrupting cardiovascular parameters. It is the objective of this study to evaluate the bioanalysis of DBS in comparison to conventional blood sampling techniques and to optimize the recovery of various compounds spiked into canine blood dried on filter paper tape.
METHODS
Incubated blood samples from Beagle dogs were spiked with 16 different compounds and half of the whole blood sample was centrifuged to obtain plasma. After the dried blood sample drops were dried, liquid chromatography-mass spectrometry methods were used to analyze the samples. The study explored different anticoagulants, sample preparation methods and technical approaches to best determine the compound concentrations in dried blood samples.
RESULTS
With the two anticoagulants tested and using the optimized sample preparation methods and technical approaches we employed, the bioanalysis of dried blood samples can provide equivalent results to conventional blood sampling techniques.
DISCUSSION
Automated blood sampling systems have the potential to provide increased numbers of blood samples, providing substantially more Pharmacokinetic data within safety pharmacology studies without disrupting physiological parameters. They can provide a viable alternative to traditional methods of obtaining blood for various other types of studies or analyses.
Topics: Animals; Dogs; Tandem Mass Spectrometry; Chromatography, Liquid; Blood Specimen Collection; Plasma; Anticoagulants
PubMed: 37482323
DOI: 10.1016/j.vascn.2023.107296 -
Scientific Reports Dec 2023Future lunar exploration will be based on in-situ resource utilization (ISRU) techniques. The most abundant raw material on the Moon is lunar regolith, which, however,...
Future lunar exploration will be based on in-situ resource utilization (ISRU) techniques. The most abundant raw material on the Moon is lunar regolith, which, however, is very scarce on Earth, making the study of simulants a necessity. The objective of this study is to characterize and investigate the sintering behavior of EAC-1A lunar regolith simulant. The characterization of the simulant included the determination of the phase assemblage, characteristic temperatures determination and water content analysis. The results are discussed in the context of sintering experiments of EAC-1A simulant, which showed that the material can be sintered to a relative density close to 90%, but only within a very narrow range of temperatures (20-30 °C). Sintering experiments were performed for sieved and unsieved, as well as for dried and non-dried specimens of EAC-1A. In addition, an analysis of the densification and mechanical properties of the sintered specimens was done. The sintering experiments at different temperatures showed that the finest fraction of sieved simulant can reach a higher maximum sintering temperature, and consequently a higher densification and biaxial strength. The non-dried powder exhibited higher densification and biaxial strength after sintering compared to the dried specimen. This difference was explained with a higher green density of the non-dried powder during pressing, rather than due to an actual influence on the sintering mechanism. Nevertheless, drying the powder prior to sintering is important to avoid the overestimation of the strength of specimens to be fabricated on the Moon.
PubMed: 38155314
DOI: 10.1038/s41598-023-50391-y -
Clinical Biochemistry Jul 2023Dried blood spot (DBS) sampling is a minimally invasive method for specimen collection with potential multifaceted uses, particularly for serosurveillance of previous...
INTRODUCTION
Dried blood spot (DBS) sampling is a minimally invasive method for specimen collection with potential multifaceted uses, particularly for serosurveillance of previous SARS-CoV-2 infection. In this study, we assessed DBS as a potential specimen type for assessing IgG and total (including IgG and IgM) antibodies to SARS-CoV-2 in vaccinated and naturally infected patients.
METHODS
Six candidate buffers were assessed for eluting blood from DBS cards. The study utilized one hundred and five paired plasma specimens and DBS specimens from prospectively collected SARS-CoV-2 vaccinated individuals, remnants from those with PCR confirmed SARS-CoV-2 infections, or remnants from those without history of infection or vaccination. All specimens were tested with the Siemens SARS-CoV-2 total assay (COV2T) or IgG assay (sCOVG).
RESULTS
The lowest backgrounds were observed with water and PBS, and water was used for elution. Relative to plasma samples, DBS samples had a positive percent agreement (PPA) of 94.4% (95% CI: 94.9-100%) for COV2T and 79.2 (68.4-87.0) for sCOVG using the manufacturer's cutoff. The NPA was 100 % (87.1-100.0 and 85.13-100) for both assays. Dilution studies revealed 100% (95% CI: 90.8-100%) qualitative agreement between specimen types on the COV2T assay and 98.0% (88.0-99.9%) with the sCOVG using study defined cutoffs.
CONCLUSION
DBS specimens demonstrated high PPA and NPA relative to plasma for SARS-CoV-2 serological testing. Our data support feasibility of DBS sampling for SARS-CoV-2 serological testing.
Topics: Humans; COVID-19; SARS-CoV-2; COVID-19 Testing; Specimen Handling; Antibodies, Viral; Immunoglobulin M; Immunoglobulin G; Dried Blood Spot Testing
PubMed: 34990593
DOI: 10.1016/j.clinbiochem.2021.12.012 -
Journal of Exposure Science &... Sep 2023Pediatric thyroid diseases have been increasing in recent years. Environmental risk factors such as exposures to chemical contaminants may play a role but are largely...
BACKGROUND
Pediatric thyroid diseases have been increasing in recent years. Environmental risk factors such as exposures to chemical contaminants may play a role but are largely unexplored. Archived neonatal dried blood spots (DBS) offer an innovative approach to investigate environmental exposures and effects.
OBJECTIVE
In this pilot study, we applied a new method for quantifying per- and polyfluoroalkyl substances (PFAS) to 18 archived DBS from babies born in California from 1985-2018 and acquired thyroid hormone measurements from newborn screening tests. Leveraging these novel data, we evaluated (1) changes in the concentrations of eight PFAS over time and (2) the relationship between PFAS concentrations, thyroid hormone concentrations, and neonatal characteristics to inform future research.
METHODS
PFAS concentrations in DBS were measured using ultra-high-performance liquid chromatography-mass spectrometry. Summary statistics and non-parametric Wilcoxon rank-sum and Kruskal-Wallis tests were used to evaluate temporal changes in PFAS concentrations and relationships between PFAS concentrations, thyroid hormone concentrations, and neonatal characteristics.
RESULTS
The concentration and detection frequencies of several PFAS (PFOA, PFOS, and PFOSA) declined over the assessment period. We observed that the timing of specimen collection in hours after birth was related to thyroid hormone but not PFAS concentrations, and that thyroid hormones were related to some PFAS concentrations (PFOA and PFOS).
IMPACT STATEMENT
This pilot study examines the relationship between concentrations of eight per- and polyfluoroalkyl substances (PFAS), thyroid hormone levels, and neonatal characteristics in newborn dried blood spots (DBS) collected over a period of 33 years. To our knowledge, 6 of the 22 PFAS we attempted to measure have not been quantified previously in neonatal DBS, and this is the first study to examine both PFAS and thyroid hormone concentrations using DBS. This research demonstrates the feasibility of using newborn DBS for quantifying PFAS exposures in population-based studies, highlights methodological considerations in the use of thyroid hormone data for future studies using newborn DBS, and indicates potential relationships between PFAS concentrations and thyroid hormones for follow-up in future research.
Topics: Infant, Newborn; Humans; Child; Pilot Projects; Environmental Pollutants; Thyroid Hormones; Environmental Exposure; Fluorocarbons; Alkanesulfonic Acids
PubMed: 37730931
DOI: 10.1038/s41370-023-00603-4 -
Journal of Microscopy Sep 2023Soft X-ray tomography (SXT) is an imaging technique to visualise whole cells without fixation, staining, and sectioning. For SXT imaging, cells are cryopreserved and...
Soft X-ray tomography (SXT) is an imaging technique to visualise whole cells without fixation, staining, and sectioning. For SXT imaging, cells are cryopreserved and imaged at cryogenic conditions. Such 'near-to-native' state imaging is in high demand and initiated the development of the laboratory table-top SXT microscope. As many laboratories do not have access to cryogenic equipment, we asked ourselves whether SXT imaging is feasible on dry specimens. This paper shows how the dehydration of cells can be used as an alternative sample preparation to obtain ultrastructure information. We compare different dehydration processes on mouse embryonic fibroblasts in terms of ultrastructural preservation and shrinkage. Based on this analysis, we chose critical point (CPD) dried cells for SXT imaging. In comparison to cryopreserved and air-dried cells, CPD dehydrated cells show high structural integrity although with about 3-7 times higher X-ray absorption for cellular organelles. As the difference in X-ray absorption values between organelles is preserved, 3D anatomy of CPD-dried cells can be segmented and analysed, demonstrating the applicability of CPD-dried sample preparation for SXT imaging. LAY DESCRIPTION: Soft X-ray tomography (SXT) is an imaging technique that allows to see the internal structures of cells without the need for special treatments like fixation or staining. Typically, SXT imaging involves freezing and imaging cells at very low temperatures. However, since many labs lack the necessary equipment, we explored whether SXT imaging could be done on dry samples instead. We compared different dehydration methods and found that critical point drying (CPD) was the most promising for SXT imaging. CPD-dried cells showed high structural integrity, although they absorbed more X-rays than hydrated cells, demonstrating that CPD-dried sample preparation is a viable alternative for SXT imaging.
Topics: Animals; Mice; Dehydration; Imaging, Three-Dimensional; Fibroblasts; Tomography, X-Ray; Microscopy
PubMed: 37433616
DOI: 10.1111/jmi.13214 -
Clinical Chemistry and Laboratory... Jan 2024The collection of capillary blood microsamples via finger-prick has several advantages over traditional blood collection. It is considered convenient and more... (Review)
Review
The collection of capillary blood microsamples via finger-prick has several advantages over traditional blood collection. It is considered convenient and more patient-centric, enabling collection of the sample by the patient at her/his home with subsequent analysis in the lab following postal shipment. Determination of the diabetes biomarker HbA in self-collected microsamples to remotely monitor diabetes patients seems to be a very promising option which could eventually lead to better treatment adaptations and disease control. This is especially convenient/relevant for patients living in areas where venipuncture is impractical, or to support virtual consultations using telemedicine. Over the years, a substantial numbers of reports on HbA and microsampling have been published. However, the heterogeneity of the applied study designs and data evaluation is remarkable. This review provides a general and critical overview of these papers, along with specific points of attention that should be dealt with when aiming at implementing microsampling for reliable HbA determination. We focus on the used (dried) blood microsampling techniques, collection conditions, stability of the microsamples, sample extraction, analytical methods, method validation, correlation studies with conventional venous blood samples and patient satisfaction. Lastly, the possibility of using liquid instead of dried blood microsamples is discussed. Liquid blood microsampling is expected to have similar advantages as dried blood microsampling and several studies suggest it to be a suitable approach to collect samples remotely for subsequent HbA analysis in the lab.
Topics: Humans; Female; Blood Specimen Collection; Dried Blood Spot Testing; Phlebotomy; Diabetes Mellitus
PubMed: 37419657
DOI: 10.1515/cclm-2023-0228