Analyses of mitochondrial metabolism in diseases: a review on C magnetic resonance tracers.

Metabolic diseases such as obesity, type 2 diabetes, and cardiovascular diseases have become a global health concern due to their widespread prevalence and profound impact on life expectancy, healthcare expenditures, and the overall economy. Devising effective treatment strategies and management plans for these diseases requires an in-depth understanding of the pathophysiology of the metabolic abnormalities associated with each disease. Mitochondrial dysfunction is intricately linked to a wide range of metabolic abnormalities and is considered an important biomarker for diseases.

Novel piperazine-based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety.

mRNA-based protein replacement therapy has received much attention as a novel intervention in clinical disease treatment. Lipid nanoparticles (LNPs) are widely used for their therapeutic potential to efficiently deliver mRNA. However, clinical translation has been hampered by the immunogenicity of LNPs that may aggravate underlying disease states.

Partial N-acetyl glutamate synthase deficiency presenting as postpartum hyperammonemia: Diagnosis and subsequent pregnancy management.

N-acetyl glutamate synthase (NAGS) deficiency (OMIM #: 237310) is a rare urea cycle disorder that usually presents early in life with hyperammonemia. NAGS catalyzes the synthesis of N-acetyl glutamate (NAG) which functions as an activator of the carbamoyl phosphate synthetase-1 mediated conversion of ammonia to carbamoyl phosphate. The absence of NAG results in a proximal urea cycle disorder which can result in severe neurologic sequelae secondary to hyperammonemia and even death.

Ursodeoxycholic Acid Decreases Incidence of Primary Biliary Cholangitis and Biliary Complications After Liver Transplantation.

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"If I wasn't a girl": Experiences of adolescent girls with heavy menstrual bleeding and inherited bleeding disorders.

Background: Heavy menstrual bleeding (HMB) is a presenting symptom of an inherited bleeding disorder (BD) and results in hospitalizations, limitations of daily activities, and a reduction in quality of life. Adult women with BD report a sense of stigma, difficulties understanding their bleeding, and challenges with diagnostic labels. The experiences of adolescents with HMB and BD are unknown despite advances in medical management through the rapidly growing network of young women's hematology programs.

Diagnosis of "cribriform" prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations.

Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs.

Membrane-destabilizing ionizable lipid empowered imaging-guided siRNA delivery and cancer treatment.

One of the imperative medical requirements for cancer treatment is how to establish an imaging-guided nanocarrier that combines therapeutic and imaging agents into one system. siRNA therapeutics have shown promising prospects in controlling life-threatening diseases. However, it is still challenging to develop siRNA formulations with excellent cellular entry capability, efficient endosomal escape, and simultaneous visualization.

Donor Characteristics and Recipient Outcomes After Heart Transplantation in Adult Congenital Heart Disease.

Background Patients with adult congenital heart disease (ACHD) experience long waitlist times for heart transplantation (HTx) while a large proportion of donor hearts are refused. The goal of this study was to inform optimal donor selection for patients with ACHD listed for HTx by examining the impact of donor characteristics on post-HTx outcomes. Methods and Results Using the Scientific Registry of Transplant Recipients, we conducted a retrospective analysis of patients aged ≥18 years listed for HTx in the United States between 2000 and 2016.

KRT-232 and navitoclax enhance trametinib's anti-Cancer activity in non-small cell lung cancer patient-derived xenografts with KRAS mutations.

Activating mutations of the KRAS gene are one of the major genomic alterations associated with tumorigenesis of non-small cell lung cancer (NSCLC). Thus far, treatment of KRAS-mutant NSCLC remains an unmet medical need. We determined the treatment responses of 13 KRAS mutant and 14 KRAS wild type NSCLC patient-derived xenografts (PDXs) to agents that target known NSCLC vulnerabilities: the MEK inhibitor trametinib, the MDM2 inhibitor KRT-232, and the BCL-X/BCL-2 inhibitor navitoclax.

Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group.

Glut1 deficiency syndrome (Glut1DS) is a brain energy failure syndrome caused by impaired glucose transport across brain tissue barriers. Glucose diffusion across tissue barriers is facilitated by a family of proteins including glucose transporter type 1 (Glut1). Patients are treated effectively with ketogenic diet therapies (KDT) that provide a supplemental fuel, namely ketone bodies, for brain energy metabolism.

Managing the Symptoms and Complications of Cholestasis.

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FRA1 contributes to MEK-ERK pathway-dependent PD-L1 upregulation by KRAS mutation in premalignant human bronchial epithelial cells.

Oncogenic KRAS mutations are frequently found in non-small cell lung carcinoma (NSCLC) and cause constitutive activation of the MEK-ERK pathway. Many cancer types have been shown to overexpress PD-L1 to escape immune surveillance. FRA1 is a MEK/ERK-dependent oncogenic transcription factor and a member of the AP-1 transcriptional factor superfamily.

No effect of triheptanoin on exercise performance in McArdle disease.

Objective: To study if treatment with triheptanoin, a 7-carbon triglyceride, improves exercise tolerance in patients with McArdle disease. McArdle patients have a complete block in glycogenolysis and glycogen-dependent expansion of tricarboxylic acid cycle (TCA), which may restrict fat oxidation. We hypothesized that triheptanoin metabolism generates substrates for the TCA, which potentially boosts fat oxidation and improves exercise tolerance in McArdle disease.

Acceleration of the formation of biofilms on contact lens surfaces in the presence of neutrophil-derived cellular debris is conserved across multiple genera.

Purpose: We have previously shown that invasive strains of exploit the robust neutrophil response to form biofilms on contact lens surfaces and invade the corneal epithelium. The present study investigated the ability of multiple bacterial genera, all commonly recovered during contact lens-related infectious events, to adhere to and form biofilms on contact lens surfaces in the presence of neutrophils.

Methods: Five reference strains from the American Type Culture Collection were used: and .

The opinions and practices of providers toward the sexual issues of cervical cancer patients undergoing treatment.

Objectives: Cervical cancer and its treatments impair women's sexual function. These complications may or may not be regarded when clinicians develop treatment plans. We aim to investigate the considerations of providers toward the sex life of cervical cancer patients.

Redox Regulation of Heart Regeneration: An Evolutionary Tradeoff.

Heart failure is a costly and deadly disease, affecting over 23 million patients worldwide, half of which die within 5 years of diagnosis. The pathophysiological basis of heart failure is the inability of the adult heart to regenerate lost or damaged myocardium. Although limited myocyte turnover does occur in the adult heart, it is insufficient for restoration of contractile function (Nadal-Ginard, 2001; Laflamme et al.

Neuroligin 1 modulates striatal glutamatergic neurotransmission in a pathway and NMDAR subunit-specific manner.

Together with its presynaptic partner Neurexin 1 (Nxn1), Neuroligin 1 (NL1) participates in synapse specification and synapse maintenance. We and others have shown that NL1 can also modulate glutamatergic synaptic function in the central nervous system of rodent models. These molecular/cellular changes can translate into altered animal behaviors that are thought to be analogous to symptomatology of neuropsychiatric disorders.

Living without insulin: the role of leptin signaling in the hypothalamus.

Since its discovery in 1922, insulin has been thought to be required for normal metabolic homeostasis and survival. However, this view would need to be revised as recent results from different laboratories have convincingly indicated that life without insulin is possible in rodent models. These data indicate that particular neuronal circuitries, which include hypothalamic leptin-responsive neurons, are empowered with the capability of permitting life in complete absence of insulin.