Postpartum Glucose Monitoring in Pregnant Women with Gestational Diabetes Mellitus: A Dual Center Experience.

Objective: Gestational diabetes mellitus (GDM) is known to be a predisposing factor in the development of type 2 diabetes mellitus in affected mothers and their offspring. Current guidelines recommend a two-hour postpartum glucose tolerance test (OGTT) in patients with a history of GDM. However, compliance rates for ordering and completion has been reported as suboptimal.

Circadian-Dependent Intermittent Fasting Influences Ischemic Tolerance and Dendritic Spine Remodeling.

Background: Preconditioning by intermittent fasting is linked to improved cognition and motor function, and enhanced recovery after stroke. Although the duration of fasting was shown to elicit different levels of neuroprotection after ischemic stroke, the impact of time of fasting with respect to the circadian cycles remains unexplored.

Methods: Cohorts of mice were subjected to a daily 16-hour fast, either during the dark phase (active-phase intermittent fasting) or the light phase (inactive-phase intermittent fasting) or were fed ad libitum.

Loss of Epitranscriptomic Modification N-Methyladenosine (mA) Reader YTHDF1 Exacerbates Ischemic Brain Injury in a Sexually Dimorphic Manner.

N-Methyladenosine (mA) is a neuronal-enriched, reversible post-transcriptional modification that regulates RNA metabolism. The mA-modified RNAs recruit various mA-binding proteins that act as readers. Differential mA methylation patterns are implicated in ischemic brain damage, yet the precise role of mA readers in propagating post-stroke mA signaling remains unclear.

Path Towards Biopsy-Free Diagnosis of Celiac Disease in Pediatric Patients.

Background: Laboratory testing for celiac disease in pediatric patients integrates serology, genetic susceptibility and duodenal biopsy examination. The 2023 American College of Gastroenterology guidelines recommend a biopsy-free approach in pediatric patients utilizing tissue transglutaminase antibody titers >10 times upper limit of normal and subsequent endomysial antibody seropositivity as sufficient for diagnosis. The objective of this study is to assess the diagnostic accuracy of biopsy-free approach at our pediatric hospital.

Validation of a whole blood machine learning strategy for distinguishing between bacterial and viral infection in a pediatric hospital setting.

Similar symptoms between viral and bacterial diseases often make diagnosis difficult. This study assessed the clinical performance of the newly cleared whole-blood Bacterial versus Viral Score assay in our pediatric cohort to the previously validated serum assay and emergency department physician diagnosis. This assay shows excellent agreement (R = 0.

Cystic fibrosis-related diabetes screening at a large pediatric center.

Objective: Cystic Fibrosis Foundation guidelines recommend annual diabetes screening by oral glucose tolerance test (OGTT) in pediatric patients with cystic fibrosis (CF) starting at the age of 10 years. Adherence to these guidelines proves to be challenging, and the nationwide screening rates are still considered suboptimal. The aim of this study was to assess and improve the screening rates at our large pediatric center.

ChatGPT-Exploring Its Role in Clinical Chemistry.

Objective: To evaluate the utility of artificial intelligence-powered language models (ChatGPT 3.5 and GPT-4) compared to trainees and clinical chemists in responding to common laboratory questions in the broad area of Clinical Chemistry.

Methods: 35 questions from real-life case scenarios, clinical consultations, and clinical chemistry testing questions were used to evaluate ChatGPT 3.

Best Practices for Effective Management of Point of Care Testing.

With the recent COVID-19 pandemic, point-of-care testing has gained tremendous attention, particularly in acute care settings. The point-of-care testing landscape is rapidly expanding and being contemplated for any crucial test with a central laboratory turnaround time >25% of the clinical decision time. A typical point-of-care testing program within a large hospital system encompasses a multitude of operators utilizing a wide range of devices across multiple testing sites.

SARS-CoV-2 Antibody Titers and Severity of Multisystem Inflammatory Syndrome in Children.

Objective: Multisystem inflammatory syndrome in children (MIS-C) is a rare yet serious pathological consequence of SARS-CoV-2 infection which is reported 4-12 weeks after the onset of COVID-19 in children and adolescents. The most common hyper-inflammatory conditions mimicking the clinical presentation of MIS-C include Kawasaki disease and toxic shock syndrome. The surveillance criteria of MIS-C were recently revised by US Center for Disease Control and Prevention to improve diagnostic precision.

Validation of a multi-analyte immunoassay for distinguishing bacterial vs. viral infections in a pediatric cohort.

Background: Clinical presentation of viral and bacterial infections or co-infections overlaps significantly. Pathogen identification is the gold standard for appropriate treatment. Recently, FDA cleared a multivariate index test called MeMed-BV that distinguishes viral and bacterial infections based on the differential expression of 3 host proteins.

Post-stroke depression: epigenetic and epitranscriptomic modifications and their interplay with gut microbiota.

Epigenetic and epitranscriptomic modifications that regulate physiological processes of an organism at the DNA and RNA levels, respectively, are novel therapeutic candidates for various neurological diseases. Gut microbiota and its metabolites are known to modulate DNA methylation and histone modifications (epigenetics), as well as RNA methylation especially N6-methyladenosine (epitranscriptomics). As gut microbiota as well as these modifications are highly dynamic across the lifespan of an organism, they are implicated in the pathogenesis of stroke and depression.

Immunomodulatory role of glycoRNAs in the brain.

Glycosylation of lipids and proteins significantly increases the molecular diversity in the brain. Membrane-localized glycoconjugates facilitate critical neuro-immune interactions. Therefore, glycodysregulation is increasingly recognized as a novel hallmark of various acute and chronic neurological diseases.

CDR1as regulates α-synuclein-mediated ischemic brain damage by controlling miR-7 availability.

Transient focal ischemia decreased microRNA-7 (miR-7) levels, leading to derepression of its major target α-synuclein (α-Syn) that promotes secondary brain damage. Circular RNA CDR1as is known to regulate miR-7 abundance and function. Hence, we currently evaluated its functional significance after focal ischemia.

Cerebroprotective Role of -Methyladenosine Demethylase FTO (Fat Mass and Obesity-Associated Protein) After Experimental Stroke.

Background: FTO (fat mass and obesity-associated protein) demethylates -methyladenosine (mA), which is a critical epitranscriptomic regulator of neuronal function. We previously reported that ischemic stroke induces mA hypermethylation with a simultaneous decrease in FTO expression in neurons. Currently, we evaluated the functional significance of restoring FTO with an adeno-associated virus 9, and thus reducing mA methylation in poststroke brain damage.

MMP-12 knockdown prevents secondary brain damage after ischemic stroke in mice.

We previously reported that increased expression of matrix metalloproteinase-12 (MMP-12) mediates blood-brain barrier disruption via tight junction protein degradation after focal cerebral ischemia in rats. Currently, we evaluated whether MMP-12 knockdown protects the post-stroke mouse brain and promotes better functional recovery. Adult male mice were injected with negative siRNA or MMP-12 siRNA (intravenous) at 5 min of reperfusion following 1 h transient middle cerebral artery occlusion.

An Antioxidant and Anti-ER Stress Combo Therapy Decreases Inflammation, Secondary Brain Damage and Promotes Neurological Recovery following Traumatic Brain Injury in Mice.

The complex pathophysiology of post-traumatic brain damage might need a polypharmacological strategy with a combination of drugs that target multiple, synergistic mechanisms. We currently tested a combination of apocynin (curtails formation of reactive oxygen species), tert-butylhydroquinone (promotes disposal of reactive oxygen species), and salubrinal (prevents endoplasmic reticulum stress) following a moderate traumatic brain injury (TBI) induced by controlled cortical impact in adult mice. Adult mice of both sexes treated with the above tri-combo showed alleviated motor and cognitive deficits, attenuated secondary lesion volume, and decreased oxidative DNA damage.

Epigenetic mechanisms and potential therapeutic targets in stroke.

Accumulating evidence indicates a central role for epigenetic modifications in the progression of stroke pathology. These epigenetic mechanisms are involved in complex and dynamic processes that modulate post-stroke gene expression, cellular injury response, motor function, and cognitive ability. Despite decades of research, stroke continues to be classified as a leading cause of death and disability worldwide with limited clinical interventions.

Dysregulation of the Epitranscriptomic Mark mA in Ischemic Stroke.

Methylation of adenosine at N1 position yields N-methyladenosine (mA), which is an epitranscriptomic modification that regulates mRNA metabolism. Recent studies showed that altered mA methylation promotes acute and chronic neurological diseases. We currently evaluated the effect of focal ischemia on cerebral mA methylome and its machinery.

High-Dose Vitamin C Prevents Secondary Brain Damage After Stroke via Epigenetic Reprogramming of Neuroprotective Genes.

Vitamin C has recently been identified as an epigenetic regulator by activating ten-eleven translocases (TETs), enzymes involved in generating DNA hydroxymethylcytosine (5hmC). Currently, we investigated whether high-dose vitamin C promotes neuroprotection through epigenetic modulation of 5hmC, if there are sex-specific differences in outcome, and the therapeutic potential of vitamin C in stroke-related comorbidities in adult mice. Post-stroke treatment with ascorbate (reduced form), but not dehydroascorbate (oxidized form), increased TET3 activity and 5hmC levels and reduced infarct following focal ischemia.

MicroRNA miR-7 Is Essential for Post-stroke Functional Recovery.

Transient focal ischemia induces a sustained downregulation of miR-7 leading to derepression of its target α-synuclein (α-Syn), which promotes neuronal death. We previously showed that treatment with miR-7 mimic prevents α-Syn induction and protects brain after stroke in rodents irrespective of age and sex. To further decipher the role of miR-7, we currently studied infarction and motor function in miR-7 double knockout mice (lack both miR-7a and miR-7b) subjected to focal ischemia.

Tenascin-C induction exacerbates post-stroke brain damage.

The role of tenascin-C (TNC) in ischemic stroke pathology is not known despite its prognostic association with cerebrovascular diseases. Here, we investigated the effect of TNC knockdown on post-stroke brain damage and its putative mechanism of action in adult mice of both sexes. Male and female C57BL/6 mice were subjected to transient middle cerebral artery occlusion and injected (i.

Noncoding RNA crosstalk in brain health and diseases.

The mammalian brain expresses several classes of noncoding RNAs (ncRNAs), including long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). These ncRNAs play vital roles in regulating cellular processes by RNA/protein scaffolding, sponging and epigenetic modifications during the pathophysiological conditions, thereby controlling transcription and translation. Some of these functions are the result of crosstalk between ncRNAs to form a competitive endogenous RNA network.

Epitranscriptomic Modifications Modulate Normal and Pathological Functions in CNS.

RNA is more than just a combination of four genetically encoded nucleobases as it carries extra information in the form of epitranscriptomic modifications. Diverse chemical groups attach covalently to RNA to enhance the plasticity of cellular transcriptome. The reversible and dynamic nature of epitranscriptomic modifications allows RNAs to achieve rapid and context-specific gene regulation.

Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke Functional Outcome.

Background And Purpose: Stroke induces the expression of several long noncoding RNAs in the brain. However, their functional significance in poststroke outcome is poorly understood. We recently observed that a brain-specific long noncoding RNA called Fos downstream transcript (FosDT) is induced rapidly in the rodent brain following focal ischemia.