Tissue-specific modulation of NADH consumption as an anti-aging intervention in Drosophila.

Aging is characterized by extensive metabolic dysregulation. Redox coenzyme nicotinamide adenine dinucleotide (NAD) can exist in oxidized (NAD) or reduced (NADH) states, which together form a key NADH/NAD redox pair. Total levels of NAD decline with age in a tissue-specific manner, thereby playing a significant role in the aging process.

Adaptive laboratory evolution recruits the promiscuity of succinate semialdehyde dehydrogenase to repair different metabolic deficiencies.

Promiscuous enzymes often serve as the starting point for the evolution of novel functions. Yet, the extent to which the promiscuity of an individual enzyme can be harnessed several times independently for different purposes during evolution is poorly reported. Here, we present a case study illustrating how NAD(P)-dependent succinate semialdehyde dehydrogenase of Escherichia coli (Sad) is independently recruited through various evolutionary mechanisms for distinct metabolic demands, in particular vitamin biosynthesis and central carbon metabolism.

A model-informed clinical trial simulation tool with a graphical user interface for Duchenne muscular dystrophy.

Quantitative model-based clinical trial simulation tools play a critical role in informing study designs through simulation before actual execution. These tools help drug developers explore various trial scenarios in silico to select a clinical trial design to detect therapeutic effects more efficiently, therefore reducing time, expense, and participants' burden. To increase the usability of the tools, user-friendly and interactive platforms should be developed to navigate various simulation scenarios.

GIP Receptor Antagonism Eliminates Paradoxical Growth Hormone Secretion in Some Patients With Acromegaly.

Context: About 30% of patients with active acromegaly experience paradoxically increased growth hormone (GH) secretion during the diagnostic oral glucose tolerance test (OGTT). Endogenous glucose-dependent insulinotropic polypeptide (GIP) is implicated in this paradoxical secretion.

Objective: We used the GIP receptor (GIPR) antagonist GIP(3-30)NH2 to test the hypothesis that GIP mediates this paradoxical response when GIPR is abundantly expressed in somatotropinomas.

Semaglutide treatment of hypothalamic obesity - a real-life data study.

Purpose: Patients with tumors involving the hypothalamic region are at high risk of developing morbid obesity due to disturbances in the appetite regulative nuclei in hypothalamus. We evaluated the effect of the Glucagon-like peptide 1 (GLP-1) analogue semaglutide in patients with hypothalamic obesity.

Methods: We recorded weight changes from real-time data before and after treatment with semaglutide in patients with hypothalamic obesity from our outpatient clinic at the Department of Endocrinology at Rigshospitalet, from September 2020 to November 2023.

Type 1 diabetes prevention clinical trial simulator: Case reports of model-informed drug development tool.

Clinical trials seeking to delay or prevent the onset of type 1 diabetes (T1D) face a series of pragmatic challenges. Despite more than 100 years since the discovery of insulin, teplizumab remains the only FDA-approved therapy to delay progression from Stage 2 to Stage 3 T1D. To increase the efficiency of clinical trials seeking this goal, our project sought to inform T1D clinical trial designs by developing a disease progression model-based clinical trial simulation tool.

Acromegaly management in the Nordic countries: A Delphi consensus survey.

Objective: Acromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist.

Can the DEX/CRH test or markers of oxidative stress distinguish work-related stress from major depressive disorder and normal controls?

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC).

Long-term pituitary function and functional and patient-reported outcomes in severe acquired brain injury.

Objective: Assessment of posttraumatic hypothalamic-pituitary dysfunctions is expected to be the most relevant assessment to offer patients with severe intracranial affection. In this study, we aim to investigate the prevalence of hypopituitarism in patients with severe acquired traumatic brain injury (TBI) compared with nontraumatic brain injury (NTBI) and to relate pituitary insufficiency to functional and patient-reported outcomes.

Design: This is a prospective study.

Changes in acromegaly comorbidities, treatment, and outcome over three decades: a nationwide cohort study.

Objective: To study the time-dependent changes in disease features of Danish patients with acromegaly, including treatment modalities, biochemical outcome, and comorbidities, with a particular focus on cancer and mortality.

Methods: Pertinent acromegaly-related variables were collected from 739 patients diagnosed since 1990. Data are presented across three decades (1990-1999, 2000-2009, and 2010-2021) based on the year of diagnosis or treatment initiation.

Imaging Neuropeptide Release from Clock and Motor Neurons.

Electrophysiological studies of synaptic function do not robustly report release of neuropeptides and neurotrophins. These limitations have been overcome with the presynaptic expression of optical release reporters based on green fluorescent protein and fluorogen-activating protein. Here we describe how to image neuropeptide release in at the neuromuscular junction and in the adult brain.

GFP and FAP Imaging of Neuropeptide Release in .

Genetics in have revealed the role of neuropeptides in development and behavior. However, determining when and where neuropeptides are released has been challenging. Furthermore, the cell biology underlying neuropeptide release has largely been unexplored.

Tracing clinically-relevant antimicrobial resistances in Acinetobacter baumannii-calcoaceticus complex across diverse environments: A study spanning clinical, livestock, and wastewater treatment settings.

Acinetobacter baumannii has become a prominent nosocomial pathogen, primarily owing to its remarkable ability to rapidly acquire resistance to a wide range of antimicrobial agents and its ability to persist in diverse environments. However, there is a lack of data on the molecular epidemiology and its potential implications for public health of A. baumannii strains exhibiting clinically significant resistances that originate from non-clinical environments.

Determination of cortisol cut-off limits and steroid dynamics in the ACTH stimulation test: a comparative analysis using Roche Elecsys Cortisol II immunoassay and LC-MS/MS.

Purpose: Measurement of cortisol concentrations is method dependent. The study aimed to establish assay-specific cut-off limits for cortisol after adrenocorticotropic hormone (ACTH) stimulation, comparing Roche Elecsys Cortisol II immunoassay to liquid chromatography-mass spectrometry (LC-MS/MS), and to assess the impact of patient characteristics, estrogen containing oral contraceptives as well as relation to other adrenocortical steroid hormone dynamics.

Methods: One hundred healthy participants underwent a 250 μg ACTH-test, with plasma samples analyzed using ElecsysCortI, ElecsysCortII, and LC-MS/MS.

TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16).

Background: TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors.

Patients And Methods: We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy.

Dual-release hydrocortisone improves body composition and the glucometabolic profile in patients with secondary adrenal insufficiency.

Purpose: Studies have suggested improved metabolic profiles in patients with adrenal insufficiency treated with dual-release hydrocortisone (DR-HC) compared with conventional hydrocortisone (C-HC). This study investigates the effect of DR-HC compared with C-HC treatment on five health variables: diurnal salivary cortisol/cortisone, body composition, bone health, glucose metabolism, lipids, and blood pressure.

Methods: Prospective study of 27 participants (24 men) with secondary adrenal insufficiency with measurements during stable C-HC and 16 weeks after treatment switch to DR-HC.

Outlook for 615 Small Intestinal Neuroendocrine Tumor Patients: Recurrence Risk after Surgery and Disease-Specific Survival in Advanced Disease.

Background: Small intestinal neuroendocrine tumors (siNET) are one of the most common neuroendocrine neoplasms. Radical surgery is the only curative treatment.

Method: We utilized a single-center study including consecutive patients diagnosed from 2000 to 2020 and followed them until death or the end of study.

Recurrence-Free Survival and Disease-Specific Survival in Patients with Pancreatic Neuroendocrine Neoplasms: A Single-Center Retrospective Study of 413 Patients.

Introduction: The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial.

Aim: To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3).

Method: A single-center retrospective study including consecutive patients over a 20-year period.

Exploring the impact of CYP2D6 and UGT2B7 gene-drug interactions, and CYP-mediated DDI on oxycodone and oxymorphone pharmacokinetics using physiologically-based pharmacokinetic modeling and simulation.

Oxycodone is one of the most commonly used opioids to treat moderate to severe pain. It is metabolized mainly by CYP3A4 and CYP2D6, while only a small fraction of the dose is excreted unchanged into the urine. Oxymorphone, the metabolite primarily formed by CYP2D6, has a 40- to 60-fold higher mu-opioid receptor affinity than the parent compound.

Circadian Vesicle Capture and Phase-Delayed Activity Maximize Synaptic Neuropeptide Release by Clock Neurons.

Unlabelled: sLNv clock neurons release the neuropeptide PDF to control circadian rhythms. Strikingly, PDF content in sLNv terminals is rhythmic with late night synaptic accumulation occurring in preparation for exocytosis from dense-core vesicles (DCVs) hours later at midmorning. The timing of this rhythm has been puzzling because (a) DCV exocytosis occurs hours after elevations in resting membrane potential (RMP) and Ca levels in the soma, which have traditionally been considered surrogates for activity and peptidergic transmission, and (b) the mechanism for the daily surge in synaptic neuropeptide content is unknown.

Risks of suboptimal and excessive thyroid hormone replacement across ages.

Background: Hypothyroidism is prevalent at all ages and represents a non-communicable disease with preventable consequences.

Method: Narrative review.

Review: In children and adolescents, the most devastating consequences of undertreatment with levothyroxine (LT4) are poor growth and development.

Treatment of esophageal leakages with the Microtech-VAC-Stent: a monocentric early experience of three cases.

Background: Endoscopic approaches in the treatment of transmural esophageal defects, either after esophageal resection or due to perforation, have demonstrated convincing feasibility. Surgical options are limited and associated with high morbidity and mortality rates. Currently, internal endoscopic drainage with pigtail stents, self-expanding metal stent (SEMS), or endoscopic vacuum therapy (EVT) are options for first-line treatment.