david ludwig

BACKGROUND: Evaluating effects of different macronutrient diets in randomized trials requires well defined infrastructure and rigorous methods to ensure intervention fidelity and adherence. METHODS: This controlled feeding study comprised two phases. During a Run-in phase (14-15 weeks), study participants (18-50 years, BMI, ≥27 kg/m2 ) consumed a very-low-carbohydrate (VLC) diet, with home delivery of prepared meals, at an energy level to promote 15 ± 3% weight loss...

BACKGROUND: This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). METHODS: Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke...

Complement-mediated diseases can be treated using systemic inhibitors. However, complement components are abundant in circulation, affecting systemic inhibitors' exposure and efficacy. Furthermore, because of complement's essential role in immunity, systemic treatments raise infection risk in patients. To address these challenges, we developed antibody fusion proteins combining the alternative-pathway complement inhibitor factor H (fH1-5 ) with an anti-C3d monoclonal antibody (C3d-mAb-2fH). Because C3d is deposited at sites of complement activity, this molecule localizes to tissue complement while minimizing circulating complement engagement...

All mobile organisms forage for resources, choosing how and when to search for new opportunities by comparing current returns with the average for the environment. In humans, nomadic lifestyles favouring exploration have been associated with genetic mutations implicated in attention deficit hyperactivity disorder (ADHD), inviting the hypothesis that this condition may impact foraging decisions in the general population. Here we tested this pre-registered hypothesis by examining how human participants collected resources in an online foraging task...

BACKGROUND AND OBJECTIVES: Histopathologic studies have identified immunoglobulin (Ig) deposition and complement activation as contributors of CNS tissue damage in multiple sclerosis (MS). Intrathecal IgM synthesis is associated with higher MS disease activity and severity, and IgM is the strongest complement-activating immunoglobulin. In this study, we investigated whether complement components (CCs) and complement activation products (CAPs) are increased in persons with MS, especially in those with an intrathecal IgM synthesis, and whether they are associated with disease severity and progression...

BACKGROUND AND AIMS: Perianal fistulizing Crohn's disease (CD-PAF) is an aggressive phenotype of Crohn's disease (CD) defined by frequent relapses and disabling symptoms. A novel consensus classification system was recently outlined by Geldof et al. that seeks to unify disease severity with patient-centered goals but has not yet been validated. We aimed to apply this to a real-world cohort and identify factors that predict transition between classes over time. METHODS: We identified all patients with CD-PAF and at least one baseline and one follow-up pelvic (pMRI)...

In Canada, the periodic circulation of West Nile Virus (WNV) is difficult to predict and, beyond climatic factors, appears to be related to the migratory movements of infected birds from the southern United States. This hypothesis has not yet been explored in a spatially distributed model. The main objective of this work was to develop a spatially explicit dynamic model for the transmission of WNV in Canada, that allows us to explore non-climate related hypotheses associated with WNV transmission. A Cellular Automata (CA) approach for multiple hosts (birds and humans) is used for a test region in eastern Ontario, Canada...

BACKGROUND: This study aimed to assess the association of sleep apnea syndrome (SAS) with methadone dose and timing of administration in patients receiving methadone maintenance treatment (MMT) for opioid use disorder (OUD). METHODS: This retrospective cross-sectional study was conducted on adult patients receiving MMT who had a nocturnal respiratory polygraphy between November 2015 and December 2021. Data on methadone treatment and polygraph recording, including the apnea-hypopnea index (AHI) were collected...

INTRODUCTION: A 2½ D point cloud registration method was developed to generate digital twins of different tissue shapes and resection cavities by applying a machine learning (ML) approach. This demonstrates the feasibility of quantifying soft tissue shifts. METHODS: An ML model was trained using simulated surface scan data obtained from tumor resections in a pig head cadaver model. It hereby uses 438 2½ D scans of the tissue surface. Tissue shift was induced by a temperature change from 7...

Behavioural and neuroimaging research has shown that older adults are less sensitive to financial losses compared to younger adults. Yet relatively less is known about age-related differences in social decisions and social reward processing. As part of a pilot study, we collected behavioural and functional magnetic resonance imaging (fMRI) data from 50 participants (Younger: N = 26, ages 18-34 years; Older: N = 24, ages 63-80 years) who completed three tasks in the scanner: an economic trust game as the investor with three partners (computer, stranger, friend) as the investee; a card-guessing task with monetary gains and losses shared with three partners (computer, stranger, friend); and an ultimatum game as responder to three anonymous proposers (computer, age-similar adults, age-dissimilar adults)...

PURPOSE: We evaluated additional mutations in RAS wild-type (WT) metastatic colorectal cancer (mCRC) as prognostic and predictive biomarkers for the efficacy of added panitumumab to a 5-fluorouracil plus folinic acid (FU/FA) maintenance as pre-specified analysis of the randomized PanaMa trial. PATIENTS AND METHODS: Mutations (MUT) were identified using targeted next-generation sequencing (NGS; Illumina Cancer Hotspot Panel v2) and IHC. RAS/BRAF V600E/PIK3CA/AKT1/ALK1/ERBB2/PTEN MUT and HER2/neu overexpressions were negatively hyperselected and correlated with median progression-free survival (PFS) and overall survival (OS) since start of maintenance treatment, and objective response rates (ORR)...

Mosquito-borne diseases pose ongoing global health concerns, demanding more cost-efficient methods to detect pathogens to support enhanced surveillance efforts. This study introduces an adapted TRIzol-based high-throughput RNA extraction protocol, tailored for the detection of California serogroup viruses in pooled mosquito samples in a rapid and cost-effective manner. This approach provided consistent RNA yields and sensitive viral detection relative to two commercial extraction kits (QIAGEN RNeasy Mini Kit and MACHEREY-NAGEL NucleoSpin RNA Plus Kit)...

OBJECTIVE: Characterize the distribution of healthcare utilization associated with pre-operative frailty in the year following evaluation by a surgeon. SUMMARY BACKGROUND DATA: Frailty is associated with increased morbidity, mortality, and costs for surgical patients. However, the total financial burden for frail patients beyond the index surgery and inpatient stay remains unknown. METHODS: Prospective cohort assembled from February 2016 to December 2020 within a multi-hospital integrated healthcare delivery and finance system (IDFS), from patients evaluated with the Risk Analysis Index (RAI) of frailty...

In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV-1 Envelope (Env) neutralization sensitivity to VRC01, as measured by 80% inhibitory concentration (IC80). Here, we performed a genotypic sieve analysis, a complementary approach to gaining insight into correlates of protection that assesses how PE varies with HIV-1 sequence features...

HYPOTHESIS: The middle ear (ME) epithelium transforms because of changed immunomodulation during infection. INTRODUCTION: The epithelial cells of the tympanic cavity represent the first line of defense in the context of otitis media. They can convert from a typical mucosal site into a respiratory epithelium and vice versa. Our goal is to depict the specific immune response of epithelial cells after infection at the molecular level. METHODS: The investigations were carried out on healthy and inflamed ME tissue, removed during surgical interventions in mouse and human models, and in a human in-vitro cell model in human ME epithelial cell line...

BACKGROUND: LDL-cholesterol (LDL-C) change with consumption of a low-carbohydrate diet (LCD) is highly variable. Identifying the source of this heterogeneity could guide clinical decision-making. OBJECTIVE: To evaluate LDL-C change in randomized controlled trials (RCTs) involving LCDs, with a focus on body mass index (BMI). DESIGN: Three electronic indexes (Pubmed, EBSCO, Scielo) were searched for studies between 1 January 2003 and 20 December 2022...

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. It is marked by extraordinary resistance to conventional therapies including chemotherapy and radiation, as well as to essentially all targeted therapies evaluated so far. More than 90% of PDAC cases harbor an activating KRAS mutation. As the most common KRAS variants in PDAC remain undruggable so far, it seemed promising to inhibit a downstream target in the MAPK pathway such as MEK1/2, but up to now preclinical and clinical evaluation of MEK inhibitors (MEKi ) failed due to inherent and acquired resistance mechanisms...

BACKGROUND: Whether physical activity could mitigate the adverse impacts of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) on incident cardiovascular disease (CVD) remains uncertain. OBJECTIVES: This study aimed to examine the independent and joint associations between SSB or ASB consumption and physical activity and risk of CVD, defined as fatal and nonfatal coronary artery disease and stroke, in adults from 2 United States-based prospective cohort studies...

BACKGROUND AND OBJECTIVES: Progression independent of relapse activity (PIRA) is a crucial determinant of overall disability accumulation in multiple sclerosis (MS). Accelerated brain atrophy has been shown in patients experiencing PIRA. In this study, we assessed the relation between PIRA and neurodegenerative processes reflected by (1) longitudinal spinal cord atrophy and (2) brain paramagnetic rim lesions (PRLs). Besides, the same relationship was investigated in progressive MS (PMS)...

OBJECTIVES: Relevant paravalvular leakage (PVL) due to prothesis dislodgement is a rare but potentially severe complication after transcatheter mitral valve implantation (TMVI). Due to the epicardial anchoring mechanism of the Tendyne® TMVI-system, repositioning of the valve stent may be possible by retensioning of the tether. This multicentre-study aimed to investigate the procedural and short-term safety as well as efficacy of retensioning-maneuvers. METHODS: From 2017 to 2021, N = 18 patients who underwent secondary tether-retensioning were identified...