High precision newborn screening for mucopolysaccharidosis type I by enzymatic activity followed by endogenous, non-reducing end glycosaminoglycan analysis.

Measurement of enzymatic activity in newborn dried blood spots (DBS) is the preferred first-tier method in newborn screening (NBS) for mucopolysaccharidosis (MPS) disorders. However, false positives are observed due mainly to the presence of pseudodeficiencies. Our previous publications on glycosaminoglycan (GAG) biomarker levels in dried blood spots (DBS) for mucopolysaccharidoses demonstrated that second-tier GAG biomarker analysis can dramatically reduce the false positive rate in NBS.

Reducing uncertainties of climate projections on solar energy resources in Brazil.

The share of solar power in Brazil's electrical grid has rapidly increased, relieving GHG emissions and diversifying energy sources for greater energy security. Besides that, solar resource is susceptible to climate change, adding uncertainty to electrical grid resilience. This study uses satellite and reanalysis data to evaluate the performance of CMIP6 models in replicating and predicting surface solar irradiance (SSR) in Brazil.

Mentoring up: How mentorship training influences mentee intent to change behavior.

Introduction: The purpose of this study was to evaluate data from different implementations of the curriculum, designed by the Center for the Improvement of Mentored Experiences in Research. The study investigated the relationship between participants' self-reported change in mentoring competence and the behaviors they intended to implement post-training.

Methods: The data set included 401 respondents who consented to participate after 59 training events hosted by 34 institutions between 2015 and 2022.

Integrating worthiness with leader identity development for college students.

While leader identity development (LID) and meaning making are interwoven and essential for student development, little research has explicitly explored their intersection. In this article, we briefly summarize the work of two research projects that explored the intersection of LID and meaning making, including a review of the findings that "worthiness" is a central component of the LID process among college students. Next, we propose an Input-Process-Worthiness-Outcome model for LID that highlights the centrality of worthiness, conceptualizing inputs as developmental experiences; processes as meaning making, and outcomes as personal development.

Association between electrodiagnosis and neuromuscular ultrasound in the diagnosis and assessment of severity of carpal tunnel syndrome.

Background: Neuromuscular ultrasound plays an increasing role in diagnosing carpal tunnel syndrome (CTS). There are limited data supporting the correlation between the electrodiagnostic studies and ultrasound measurements in CTS.

Objective: To assess the association between different electrodiagnostic severities and ultrasound measurements of the median nerve in CTS.

Newborn Screening for Krabbe Disease: Status Quo and Recommendations for Improvements.

Krabbe disease (KD) is part of newborn screening (NBS) in 11 states with at least one additional state preparing to screen. In July 2021, KD was re-nominated for addition to the federal Recommended Uniform Screening Panel (RUSP) in the USA with a two-tiered strategy based on psychosine (PSY) as the determinant if an NBS result is positive or negative after a first-tier test revealed decreased galactocerebrosidase activity. Nine states currently screening for KD include PSY analysis in their screening strategy.

ScreenPlus: A comprehensive, multi-disorder newborn screening program.

The increasing availability of novel therapies highlights the importance of screening newborns for rare genetic disorders so that they may benefit from early therapy, when it is most likely to be effective. Pilot newborn screening (NBS) studies are a way to gather objective evidence about the feasibility and utility of screening, the accuracy of screening assays, and the incidence of disease. They are also an optimal way to evaluate the complex ethical, legal and social implications (ELSI) that accompany NBS expansion for disorders.

VUS: Variant of uncertain significance or very unclear situation?

The advancements in population screening, including newborn screening, enables the identification of disease-causing variants and timely initiation of treatment. However, screening may also identify mild variants, non-disease variants, and variants of uncertain significance (VUS). The identification of a VUS poses a challenge in terms of diagnostic uncertainty and confusion.

Harmonization of Newborn Screening Results for Pompe Disease and Mucopolysaccharidosis Type I.

In newborn screening, false-negative results can be disastrous, leading to disability and death, while false-positive results contribute to parental anxiety and unnecessary follow-ups. Cutoffs are set conservatively to prevent missed cases for Pompe and MPS I, resulting in increased falsepositive results and lower positive predictive values. Harmonization has been proposed as a way to minimize false-negative and false-positive results and correct for method differences, so we harmonized enzyme activities for Pompe and MPS I across laboratories and testing methods (Tandem Mass Spectrometry (MS/MS) or Digital Microfluidics (DMF)).

When is the best time to screen and evaluate for treatable genetic disorders?: A lifespan perspective.

This paper focuses on the question of, "When is the best time to identify an individual at risk for a treatable genetic condition?" In this review, we describe a framework for considering the optimal timing for pursuing genetic and genomic screening for treatable genetic conditions incorporating a lifespan approach. Utilizing the concept of a carousel that represents the four broad time periods when critical decisions might be made around genetic diagnoses during a person's lifetime, we describe genetic testing during the prenatal period, the newborn period, childhood, and adulthood. For each of these periods, we describe the objectives of genetic testing, the current status of screening or testing, the near-term vision for the future of genomic testing, the advantages and disadvantages of each approach, and the feasibility and ethical considerations of testing and treating.

Moving away from one disease at a time: Screening, trial design, and regulatory implications of novel platform technologies.

Most rare diseases are caused by single-gene mutations, and as such, lend themselves to a host of new gene-targeted therapies and technologies including antisense oligonucleotides, phosphomorpholinos, small interfering RNAs, and a variety of gene delivery and gene editing systems. Early successes are encouraging, however, given the substantial number of distinct rare diseases, the ability to scale these successes will be unsustainable without new development efficiencies. Herein, we discuss the need for genomic newborn screening to match pace with the growing development of targeted therapeutics and ability to rapidly develop individualized therapies for rare variants.

Liquid Chromatography-Tandem Mass Spectrometry in Newborn Screening Laboratories.

Tandem mass spectrometry (MS/MS) is the most universal platform currently available for the analysis of enzymatic activities and biomarkers in dried blood spots (DBS) for applications in newborn screening (NBS). Among the MS/MS applications in NBS, the most common is flow-injection analysis (FIA-) MS/MS, where the sample is introduced as a bolus injection into the mass spectrometer without the prior fractionation of analytes. Liquid chromatography combined with MS/MS (LC-MS/MS) has been employed for second-tier tests to reduce the false-positive rate associated with several nonspecific screening markers, beginning two decades ago.

The Big Picture in Better Understanding the Equine Foot.

The multiple topics summarized in this article and discussed in detail in this issue of VCNA are comprehensive and in-depth, exploring concepts and clinical experiences for state-of-the-art care of the equine foot. The research on the equine foot will translate to the clinical setting and with this the compassionate care of the horse.

Evaluation of Individualized Cefepime Dosing Strategy Using Population Pharmacokinetics.

The use of population pharmacokinetics (PK) to optimize cefepime dosing could be an effective strategy, given the increasing prevalence of resistant gram-negative organisms. The objective of this study is to retrospectively compare dosing using a PK approach (intervention) vs traditional dosing (control) for cefepime in patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP). Adult hospitalized patients with HAP or VAP receiving cefepime for ≥72 hours were screened first from August 2018 to January 2019 to be included in the intervention group, then screened during the preintervention period from August 2017 to July 2018 for the control group.

The future of newborn screening for lysosomal disorders.

The goal of newborn screening is to enhance the outcome of individuals with serious, treatable disorders through early, pre-symptomatic detection. The lysosomal storage disorders (LSDs) comprise a group of more than 50 diseases with a combined frequency of approximately 1:7000. With the availability of existing and new enzyme replacement therapies, small molecule treatments and gene therapies, there is increasing interest in screening newborns for LSDs with the goal of reducing disease-related morbidity and mortality through early detection.

Low Psychosine in Krabbe Disease with Onset in Late Infancy: A Case Report.

Krabbe disease (KD) is a rare inherited neurodegenerative disorder caused by a deficiency in galactocerebrosidase enzyme activity, which can present in early infancy, requiring an urgent referral for hematopoietic stem cell transplantation, or later in life. Newborn screening (NBS) for KD requires identification and risk-stratification of patients based on laboratory values to predict disease onset in early infancy or later in life. The biomarker psychosine plays a key role in NBS algorithms to ascertain probability of early-onset disease.

A Novel Approach to Improve Newborn Screening for Congenital Hypothyroidism by Integrating Covariate-Adjusted Results of Different Tests into CLIR Customized Interpretive Tools.

Newborn screening for congenital hypothyroidism remains challenging decades after broad implementation worldwide. Testing protocols are not uniform in terms of targets (TSH and/or T4) and protocols (parallel vs. sequential testing; one or two specimen collection times), and specificity (with or without collection of a second specimen) is overall poor.

Consensus recommendations for the classification and long-term follow up of infants who screen positive for Krabbe Disease.

Objective: To provide updated evidence and consensus-based recommendations for the classification of individuals who screen positive for Krabbe Disease (KD) and recommendations for long-term follow-up for those who are at risk for late onset Krabbe Disease (LOKD).

Methods: KD experts (KD NBS Council) met between July 2017 and June 2020 to develop consensus-based classification and follow-up recommendations. The resulting newly proposed recommendations were assessed in a historical cohort of 47 newborns from New York State who were originally classified at moderate or high risk for LOKD.

MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines.

Background: Among boys with X-Linked adrenoleukodystrophy, a subset will develop childhood cerebral adrenoleukodystrophy (CCALD). CCALD is typically lethal without hematopoietic stem cell transplant before or soon after symptom onset. We sought to establish evidence-based guidelines detailing the neuroimaging surveillance of boys with neurologically asymptomatic adrenoleukodystrophy.