Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile.

Intellectual disability and autism in propionic acidemia: a biomarker-behavioral investigation implicating dysregulated mitochondrial biology.

Propionic acidemia (PA) is an autosomal recessive condition (OMIM #606054), wherein pathogenic variants in PCCA and PCCB impair the activity of propionyl-CoA carboxylase. PA is associated with neurodevelopmental disorders, including intellectual disability (ID) and autism spectrum disorder (ASD); however, the correlates and mechanisms of these outcomes remain unknown. Using data from a subset of participants with PA enrolled in a dedicated natural history study (n = 33), we explored associations between neurodevelopmental phenotypes and laboratory parameters.

Routine Use of a Standardized Mastectomy Diagram by Surgeons Improves Accuracy and Timeliness of the Final Pathological Report.

Background: Accurate and timely assessment of pathology specimens is critical for patient care and oncologic management. This study aimed to determine whether a standardized mastectomy diagram would facilitate communication among surgeons and pathologists and improve pathologic processing.

Methods: A prospective quality improvement study was conducted over a continuous 12-month period.

Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.

Methylmalonic Acidemia (MMA) is a heterogenous group of inborn errors of metabolism caused by a defect in the methylmalonyl-CoA mutase (MMUT) enzyme or the synthesis and transport of its cofactor, 5'-deoxy-adenosylcobalamin. It is characterized by life-threatening episodes of ketoacidosis, chronic kidney disease, and other multiorgan complications. Liver transplantation can improve patient stability and survival and thus provides clinical and biochemical benchmarks for the development of hepatocyte-targeted genomic therapies.

Surveillance testing for SARS-COV-2 infection in an asymptomatic athlete population: a prospective cohort study with 123 362 tests and 23 463 paired RT-PCR/antigen samples.

Objective: To assess the diagnostic accuracy of antigen compared with reverse transcriptase (RT)-PCR testing in an asymptomatic athlete screening programme and to monitor infection in college athletes.

Methods: Quidel Sofia-2 SARS-CoV-2 Antigen Tests were performed daily before sports participation for football, basketball, wrestling and water polo from 29 September 2020 to 28 February 2021. Paired RT-PCR and antigen tests were performed at least once a week.

Severity modeling of propionic acidemia using clinical and laboratory biomarkers.

Purpose: To conduct a proof-of-principle study to identify subtypes of propionic acidemia (PA) and associated biomarkers.

Methods: Data from a clinically diverse PA patient population ( https://clinicaltrials.gov/ct2/show/NCT02890342 ) were used to train and test machine learning models, identify PA-relevant biomarkers, and perform validation analysis using data from liver-transplanted participants.

1-C-propionate breath testing as a surrogate endpoint to assess efficacy of liver-directed therapies in methylmalonic acidemia (MMA).

Purpose: To develop a safe and noninvasive in vivo assay of hepatic propionate oxidative capacity.

Methods: A modified 1-C-propionate breath test was administered to 57 methylmalonic acidemia (MMA) subjects, including 19 transplant recipients, and 16 healthy volunteers. Isotopomer enrichment (CO/CO) was measured in exhaled breath after an enteral bolus of sodium-1-C-propionate, and normalized for CO production.

Oral Superabsorbent Hydrogel (Plenity) for Weight Management.

Objective: To describe the mechanism, clinical trial data, adverse effects, and potential role in therapy of an oral superabsorbent hydrogel (OSH) for weight management.

Data Sources: A literature search was completed using MEDLINE and Google Scholar using the following search terms: , and (September 1999 to July 2020). Abstracts and posters were identified from relevant scientific congress archives and published supplements.

Online monitoring of patient self-reported adverse events in early phase clinical trials: Views from patients, clinicians, and trial staff.

Background/aims: New classes of cancer drugs bring a range of unknown and undesirable adverse events. Adverse event monitoring is essential in phase I trials to assess toxicity and safety. In phase II, the focus is also on efficacy but robust data on adverse events continue to inform the safety and the adverse event profile.

Noninvasive monitoring of chronic kidney disease using pH and perfusion imaging.

Chronic Kidney Disease (CKD) is a cardinal feature of methylmalonic acidemia (MMA), a prototypic organic acidemia. Impaired growth, low activity, and protein restriction affect muscle mass and lower serum creatinine, which can delay diagnosis and management of renal disease. We have designed an alternative strategy for monitoring renal function based on administration of a pH sensitive MRI agent and assessed this in a mouse model.

Chronic kidney disease in propionic acidemia.

Purpose: Propionic acidemia (PA) is a severe metabolic disorder characterized by multiorgan pathology, including renal disease. The prevalence of chronic kidney disease (CKD) in PA patients and factors associated with CKD in PA are not known.

Methods: Thirty-one subjects diagnosed with PA underwent laboratory and clinical evaluations through a dedicated natural history study at the National Institutes of Health (ClinicalTrials.

FGF21 underlies a hormetic response to metabolic stress in methylmalonic acidemia.

Methylmalonic acidemia (MMA), an organic acidemia characterized by metabolic instability and multiorgan complications, is most frequently caused by mutations in methylmalonyl-CoA mutase (MUT). To define the metabolic adaptations in MMA in acute and chronic settings, we studied a mouse model generated by transgenic expression of Mut in the muscle. Mut-/-;TgINS-MCK-Mut mice accurately replicate the hepatorenal mitochondriopathy and growth failure seen in severely affected patients and were used to characterize the response to fasting.

Studying the differential efficacy of postsymptom antitoxin treatment in type A versus type B botulism using a rabbit spirometry model.

Botulinum neurotoxin (BoNT) serotypes A, B and E are responsible for most cases of human botulism. The only approved therapy for botulism is antitoxin treatment administered to patients after symptom onset. However, a recent meta-analysis of antitoxin efficacy in human botulism cases over the past century concluded that a statistically significant reduction in mortality is associated with the use of type E and type A antitoxin, but not with type B antitoxin.

Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model.

Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, , is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset.

A Novel Rabbit Spirometry Model of Type E Botulism and Its Use for the Evaluation of Postsymptom Antitoxin Efficacy.

Botulinum neurotoxins (BoNTs), the most poisonous substances known in nature, pose significant concern to health authorities. The only approved therapeutic for botulism is antitoxin. While administered to patients only after symptom onset, antitoxin efficacy is evaluated in animals mostly in relation to time postintoxication regardless of symptoms.

Optical Coherence Tomography Analysis of the Optic Nerve Head and Surrounding Structures in Long-Duration International Space Station Astronauts.

Importance: After long-duration spaceflight, morphological changes in the optic nerve head (ONH) and surrounding tissues have been reported.

Objective: To develop methods to quantify ONH and surrounding tissue changes using preflight and postflight optical coherence tomographic scans of the ONH region.

Design, Setting, And Participants: Two separate analyses were done on retrospective data, with the first comparing a preflight group with a control group, followed by preflight to postflight analysis.

Optical coherence tomography of the optic nerve head detects acute changes in intracranial pressure.

We aimed to determine if there are measurable objective changes in the optic nerve head (ONH) immediately after cerebrospinal fluid (CSF) drainage in a prospective case-series of five patients undergoing a clinically indicated lumbar puncture (LP) for diagnosis of idiopathic intracranial hypertension. A Cirrus high-definition optical coherence tomography machine (Carl Zeiss Meditec, Dublin, CA, USA) was used to acquire images in the lateral decubitus position. Optic disc cube and high-definition line raster scans centered on the ONH were obtained immediately before and after draining CSF, while the patient maintained the lateral decubitus position.

Intracranial arteriovenous malformation in a college football player and return-to-play considerations.

: The reported prevalence rates of arteriovenous malformations (AVMs) in the general population range from 0.001% to 0.50%.

Optic disc edema in an astronaut after repeat long-duration space flight.

Background: A number of ophthalmic findings including optic disc edema, globe flattening, and choroidal folds have been observed in several astronauts after long-duration space flights. The authors report the first astronaut with previously documented postflight ophthalmic abnormalities who developed new pathological changes after a repeat long-duration mission.

Methods: A case study of an astronaut with 2 long-duration (6 months) exposures to microgravity.

Robust audio-visual speech recognition under noisy audio-video conditions.

This paper presents the maximum weighted stream posterior (MWSP) model as a robust and efficient stream integration method for audio-visual speech recognition in environments, where the audio or video streams may be subjected to unknown and time-varying corruption. A significant advantage of MWSP is that it does not require any specific measurements of the signal in either stream to calculate appropriate stream weights during recognition, and as such it is modality-independent. This also means that MWSP complements and can be used alongside many of the other approaches that have been proposed in the literature for this problem.