Microbiota-Dependent Fiber Responses: A Proof-of-Concept Study on Short-chain Fatty Acid Production in Prevotella- and Bacteroides-Dominated Healthy Individuals.

Background: Dietary fiber supports metabolic health via microbial fermentation, producing short-chain fatty acids (SCFAs). However, metabolic responses to fiber vary between individuals, potentially due to differences in gut microbiota composition. The Prevotella-to-Bacteroides (P/B) ratio has emerged as a potential biomarker for fiber responsiveness.

On the analysis of functional PET (fPET)-FDG: Baseline mischaracterization can introduce artifactual metabolic (de)activations.

Functional Positron Emission Tomography (fPET) with (bolus plus) constant infusion of [F]-fluorodeoxyglucose (FDG), known as fPET-FDG, is a recently introduced technique in human neuroimaging, enabling the detection of dynamic glucose metabolism changes within a single scan. However, the statistical analysis of fPET-FDG data remains challenging because its signal and noise characteristics differ from both classic bolus-administration FDG PET and from functional Magnetic Resonance Imaging (fMRI), which together compose the primary sources of inspiration for analytical methods used by fPET-FDG researchers. In this study, we present an investigation of how inaccuracies in modeling baseline FDG uptake can introduce artifactual patterns to detrended time-activity curve (TAC) residuals, potentially introducing spurious (de)activations to general linear model (GLM) analyses.

Determination of the Epitopes of Alpha-Glucosidase Anti-Drug Antibodies in Pompe Disease Patient Plasma Samples.

Pompe disease is a rare autosomal-recessive neuromuscular disorder caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to the pathological accumulation of glycogen and impaired autophagy. Enzyme replacement therapy (ERT) with recombinant human alpha-glucosidase (rhGAA) has been available since 2006, but may lead to the formation of anti-drug antibodies (ADAs) against the recombinant human enzyme, which, in turn, may adversely affect the response to ERT. Knowledge of the antigenic determinants of rhGAA involved in interaction with ADAs may facilitate the development of strategies to attenuate the anti-drug immune response in patients.

Breastfeeding in Preterm Infants Is Not Compromised by Early Discharge and Home Nasogastric Tube Feeding up to 3 Months Postmenstrual Age: A Prospective Cohort Study.

: Breastmilk offers numerous benefits for the health and development of preterm infants, while prolonged hospitalization may impair neurodevelopment. At our institution, the implementation of enhanced family-centered care (FCC) has enabled earlier discharge of preterm infants. This study aimed to assess the impact of early discharge on breastfeeding and breastmilk provision.

Gut microbiota and circadian disruption in humans: Is there a rationale for metabolic disorders?

Circadian disruption, arising from behaviors such as shift work and sleep deprivation, is increasingly prevalent and associated with metabolic disorders, including obesity, type 2 diabetes, and cardiovascular disease. The gut microbiome plays a crucial role in metabolic homeostasis by producing metabolites - such as short-chain fatty acids, secondary bile acids, and microbial-associated molecular patterns - that influence nutrient absorption, immune responses, and host metabolism in alignment with circadian rhythms. This review explores how circadian disruptors influence the human gut microbiome, focusing on changes in microbial composition, diversity, and functionality, and their implications for metabolic health.

Hydration Meets Regulation: Insights into Bicarbonate Mineral Water and Acid-Base Balance.

Acid-base balance is critical to human health and can be significantly influenced by dietary choices. The Western diet, characterized by high meat and cheese consumption, induces excess acidity, highlighting the need for strategies to mitigate this. Recent studies have focused on bicarbonate-rich mineral water as a viable solution.

Primary endpoint acceptance and its association with benefit ratings and market access in German health technology assessments: a retrospective cohort study.

Background: In Germany, the Health Technology Assessment process, governed by the Federal Joint Committee (G-BA), evaluates relative efficacy and safety of newly European Medicines Agency (EMA)-approved drugs against the standard of care using patient-relevant endpoints. This study aimed to investigate the impact of the acceptance of the primary endpoint on the likelihood of an additional benefit and patient access in assessments that fulfilled criteria for study design and comparator for both authorities.

Methods: We examined whether the acceptance of the primary endpoint by G-BA resulted in a higher likelihood of a positive benefit rating and a reduced risk of market withdrawal by pharmaceutical companies of drugs that underwent a benefit assessment between 2011 and 2023, in which an RCT with an adequate comparator according to G-BA served as evidence base.

Effect of a saffron extract on sleep quality in adults with moderate insomnia: A decentralized, randomized, double-blind, placebo-controlled trial.

Aim: Natural interventions for sleep disturbances, such as saffron extract, are gaining scientific and clinical interest. This 3-arm, randomized, double-blind, placebo-controlled trial examined the effect of a standardized saffron extract (Safr'Inside™) on sleep, stress, and other associated psychological outcomes in 165 adults reporting moderate insomnia.

Methods: Participants received 30 mg, 20 mg saffron extract, or placebo for 4 weeks.

Multimicronutrient and omega-3 fatty acid supplementation reduces low-grade inflammation in older participants: An exploratory study.

Aging is associated with chronic low-grade inflammation, while the status of anti-inflammatory (INFLA) micronutrients such as long-chain omega-3 fatty acids (n-3 PUFA), vitamin D, folate, and cobalamin is often low in older people. We hypothesized that n-3 PUFA and certain micronutrients reduce low-grade inflammation in older participants. To test this hypothesis the aim of this randomised, double-blinded, 12-week intervention study involving 112 healthy and physically active older participants (75.

Phenotyping extracellular vesicles and their serotonin transporter cargo in major depressive disorder.

With their ability to cross the blood-brain barrier, transport and regulate the release of various signaling molecules, extracellular vesicles (EVs) constitute a novel avenue to study intercellular communication in various pathologies, including psychiatric disorders. We studied 34 major depressive disorder (MDD) patients and 57 healthy controls and characterized EVs isolated from plasma using digital holographic tomography (DHT) and nanoparticle tracking analysis (NTA). EVs detected in DHT were markedly smaller and less variable in size in MDD patients.

Disease-Modifying, Neuroprotective Effect of N-Acetyl-l-Leucine in Adult and Pediatric Patients With Niemann-Pick Disease Type C.

Background And Objectives: N-acetyl-l-leucine (NALL) has been established to improve the neurologic manifestations of Niemann-Pick disease type C (NPC) after 12 weeks in a placebo-controlled trial. In the open-label extension phase (EP) follow-up, data were obtained after 12 and 18 months to evaluate the long-term effects of NALL for NPC.

Methods: This is an ongoing, multinational, multicenter EP.

A large-scale multimodal investigation of the interplay between the serotonergic system and emotion processing.

Considering the complexity of serotonergic influence on emotions, we conducted a comprehensive investigation of the interplay between emotion processing and the serotonergic system using simultaneous functional and molecular neuroimaging during pharmacological challenge while disentangling the effects of serotonin transporter (SERT) binding, genotype, and diagnosis of major depressive disorder (MDD). Herein, 153 subjects (44 with MDD) performed a facial emotion processing task during functional magnetic resonance imaging (fMRI) before and after an acute intravenous application of 8 mg citalopram or placebo. Patients with MDD were assessed again after at least three months of antidepressant treatment.

Deciphering DST-associated disorders: biallelic variants affecting DST-b cause a congenital myopathy.

Dystonin (DST) encodes three major isoforms, DST-a, DST-b, and DST-e. Biallelic pathogenic variants in DST have previously been associated with two allelic monogenic disorders: Hereditary Sensory and Autonomic Neuropathy type VI (caused by a loss of DST-a) and Epidermolysis bullosa simplex 3 (caused by a loss of DST-e). We investigated patients diagnosed with congenital myopathy using exome or genome sequencing.

In vivo serotonin 1A receptor distribution in treatment-resistant depression.

Major depressive disorder (MDD) ranks among the leading causes of disability worldwide. An additional burden arises from treatment-resistance, defined by a lack of response to two or more adequate pharmacotherapeutic treatment trials. Unlike in MDD, where the serotonin 1A receptor subtype (5-HT) has commonly been used to study pathophysiological alterations, treatment-resistant depression (TRD) subjects represent a less investigated cohort.

Connecting the dots: approaching a standardized nomenclature for molecular connectivity in positron emission tomography.

Positron emission tomography (PET)-based connectivity analysis provides a molecular perspective that complements fMRI-derived functional connectivity. However, lack of standardized terminology and diverse methodologies in PET connectivity studies has resulted in inconsistencies, complicating the interpretation and comparison of results across studies. A standardized nomenclature is thus needed to reduce ambiguity, enhance reproducibility, and facilitate interpretability across radiotracers, imaging modalities and studies.

Adaptation of a commercially available module for the production of alpha-[C]methyl-L-tryptophan ([C]AMT) for human use.

The complex radiosynthesis of alpha-[C]methyl-L-tryptophan ([C]AMT) involves harsh chemicals and conditions, posing challenges for its implementation on commercially available synthesis modules. This study describes the adaptation of the GE TRACERlab FX2 C module for [C]AMT production using both a half-manual approach and a semi-automated method incorporating a 16-way valve system. [C]AMT was synthesized with decay-corrected radiochemical yields of 13 ± 7.

Calanus Oil and Lifestyle Interventions Improve Glucose Homeostasis in Obese Subjects with Insulin Resistance.

Obesity increases the risk for insulin resistance (IR) and type-2 diabetes. Lifestyle interventions (LI) and dietary supplementation can help mitigate IR. We investigated the effect of calanus oil (CO) supplementation, combined with LI, on glucose homeostasis in obese subjects.

Simplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion.

Assessment of an antidepressant's occupancy at the serotonin transporter (SERT) in vivo using PET scans represents a demanding procedure. We evaluated novel approaches for SERT quantification to simplify the occupancy calculation. [C]DASB PET/MRI scans with bolus plus constant infusion were performed twice in 47 healthy controls and 31 patients with major depressive disorder with intravenous application of 8 mg citalopram or saline solution (randomized, cross-over, double-blind).

Optimal filtering strategies for task-specific functional PET imaging.

Functional Positron Emission Tomography (fPET) is an effective tool for studying dynamic processes in glucose metabolism and neurotransmitter action, providing insights into brain function and disease progression. However, optimizing signal processing to extract stimulation-specific information remains challenging. This study systematically evaluates state-of-the-art filtering techniques for fPET imaging.

Impact of MEK Inhibition on Childhood RASopathy-Associated Hypertrophic Cardiomyopathy.

There is an unmet medical need to treat patients with severe hypertrophic cardiomyopathy leading to heart failure and death in children carrying pathogenic activating variants in the RAS/mitogen-activated protein kinase pathway. A retrospective analysis of 61 patients provides evidence for decreased mortality and morbidity with improved cardiac status in patients with RASopathy with severe hypertrophic cardiomyopathy receiving mitogen-activated protein kinase kinase inhibition (n = 30) vs those with standard-of-care treatment (n = 31). Side effects were not life threatening and were manageable.

Standardized low-resolution brain electromagnetic tomography does not improve EEG Alzheimer's disease assessment.

Quantitative EEG has been shown to reflect neurodegenerative processes in Alzheimer's disease (AD) and may provide non-invasive and widely available biomarkers to enhance the objectivization of disease assessment. To address EEG's major drawback - its low spatial resolution - many studies have employed 3D source localization. However, none have investigated whether this complex mapping into 3D space actually adds value over standard surface derivation.

Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease: A Phase II Randomized Trial (CIPER Study).

Background: Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' health and quality of life, and substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) to 50 (aspirin, statins, and vorapaxar).

Objectives: This randomized, placebo-controlled, double-blinded crossover interventional trial aims to measure the effect of L-citrulline and tetrahydrobiopterin (HBip) on walking distance in patients with PAD, stratified by plasma levels of asymmetric dimethyl L-arginine (ADMA), the endogenous inhibitor of endothelial nitric oxide (NO) synthase.

Long-Term Dynamics of CSF and Serum Neurofilament Light Chain in Adult Patients With 5q Spinal Muscular Atrophy Treated With Nusinersen.

Background And Objectives: The availability of disease-modifying therapies for 5q-associated spinal muscular atrophy (SMA) has heightened the need to identify suitable biomarkers. This study investigates neurofilament light chain (NfL) concentrations during long-term nusinersen treatment in adult SMA.

Methods: In a retrospective study of prospectively collected data, NfL concentrations in the CSF (cNfL) and serum (sNfL) were measured in patients with SMA from 8 German centers and in neurologic controls using a single-molecule array (Simoa) assay.

Serum chitotriosidase-1 (CHIT1) as candidate biomarker for mitochondriopathies.

Background: Neuromuscular diseases (NMDs) and mitochondriopathies are rare and heterogeneous disorders. Diagnosis is often difficult and delayed, partly due to the lack of reliable biomarkers. Chitotriosidase (CHIT1) as a candidate marker for lysosomal storage diseases is elevated in Niemann pick disease type C as a prototype of this group of diseases.