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Metabolites Jan 2024Recent research has identified a unique population of 'Lean Mass Hyper-Responders' (LMHR) who exhibit increases in LDL cholesterol (LDL-C) in response to...
Recent research has identified a unique population of 'Lean Mass Hyper-Responders' (LMHR) who exhibit increases in LDL cholesterol (LDL-C) in response to carbohydrate-restricted diets to levels ≥ 200 mg/dL, in association with HDL cholesterol ≥ 80 mg/dL and triglycerides ≤ 70 mg/dL. This triad of markers occurs primarily in lean metabolically healthy subjects, with the magnitude of increase in LDL-C inversely associated with body mass index. The lipid energy model has been proposed as one explanation for LMHR phenotype and posits that there is increased export and subsequent turnover of VLDL to LDL particles to meet systemic energy needs in the setting of hepatic glycogen depletion and low body fat. This single subject crossover experiment aimed to test the hypothesis that adding carbohydrates, in the form of Oreo cookies, to an LMHR subject on a ketogenic diet would reduce LDL-C levels by a similar, or greater, magnitude than high-intensity statin therapy. The study was designed as follows: after a 2-week run-in period on a standardized ketogenic diet, study arm 1 consisted of supplementation with 12 regular Oreo cookies, providing 100 g/d of additional carbohydrates for 16 days. Throughout this arm, ketosis was monitored and maintained at levels similar to the subject's standard ketogenic diet using supplemental exogenous d-β-hydroxybutyrate supplementation four times daily. Following the discontinuation of Oreo supplementation, the subject maintained a stable ketogenic diet for 3 months and documented a return to baseline weight and hypercholesterolemic status. During study arm 2, the subject received rosuvastatin 20 mg daily for 6 weeks. Lipid panels were drawn water-only fasted and weekly throughout the study. Baseline LDL-C was 384 mg/dL and reduced to 111 mg/dL (71% reduction) after Oreo supplementation. Following the washout period, LDL-C returned to 421 mg/dL, and was reduced to a nadir of 284 mg/dL with 20 mg rosuvastatin therapy (32.5% reduction). In conclusion, in this case study experiment, short-term Oreo supplementation lowered LDL-C more than 6 weeks of high-intensity statin therapy in an LMHR subject on a ketogenic diet. This dramatic metabolic demonstration, consistent with the lipid energy model, should provoke further research and not be seen as health advice.
PubMed: 38276308
DOI: 10.3390/metabo14010073 -
Cureus Oct 2023With the burgeoning numbers of clinical trials, the competition among sponsors for research subjects has grown intensely. Many clinical trials fail to meet their...
With the burgeoning numbers of clinical trials, the competition among sponsors for research subjects has grown intensely. Many clinical trials fail to meet their recruitment goals. Contract research organizations (CROs) that help conduct all or portions of a clinical study have transitioned from highly specialized niches, such as biostatistical analysis or regulatory compliance, to more overall functions to keep a trial moving forward. CROs establish agreements with sponsors, including how much a site will be paid per study subject. CROs are locked into that pricing, but over the course of a study's recruitment period, sponsors with deeper pockets may step in and offer more compensation per subject. The result is a competitive market place that favors big sponsors and puts smaller CROs and start-ups at a disadvantage.
PubMed: 38022306
DOI: 10.7759/cureus.47819 -
Biochemistry. Biokhimiia Feb 2024Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more... (Review)
Review
Worldwide, interest in mitochondria is constantly growing, as evidenced by scientific statistics, and studies of the functioning of these organelles are becoming more prevalent than studies of other cellular structures. In this analytical review, mitochondria are conditionally placed in a certain cellular center, which is responsible for both energy production and other non-energetic functions, without which the existence of not only the eukaryotic cell itself, but also the entire organism is impossible. Taking into account the high multifunctionality of mitochondria, such a fundamentally new scheme of cell functioning organization, including mitochondrial management of processes that determine cell survival and death, may be justified. Considering that this issue is dedicated to the memory of V. P. Skulachev, who can be called mitocentric, due to the history of his scientific activity almost entirely aimed at studying mitochondria, this work examines those aspects of mitochondrial functioning that were directly or indirectly the focus of attention of this outstanding scientist. We list all possible known mitochondrial functions, including membrane potential generation, synthesis of Fe-S clusters, steroid hormones, heme, fatty acids, and CO2. Special attention is paid to the participation of mitochondria in the formation and transport of water, as a powerful biochemical cellular and mitochondrial regulator. The history of research on reactive oxygen species that generate mitochondria is subject to significant analysis. In the section "Mitochondria in the center of death", special emphasis is placed on the analysis of what role and how mitochondria can play and determine the program of death of an organism (phenoptosis) and the contribution made to these studies by V. P. Skulachev.
Topics: Mitochondria; Reactive Oxygen Species
PubMed: 38622092
DOI: 10.1134/S0006297924020044 -
Journal of Advanced Pharmaceutical... 2023Gout arthritis is an inflammatory condition that occurs suddenly in joints affected by high uric acid levels (hyperuricemia). The uric acid levels in this disease... (Review)
Review
Gout arthritis is an inflammatory condition that occurs suddenly in joints affected by high uric acid levels (hyperuricemia). The uric acid levels in this disease fluctuate throughout its various phases, resulting in frequent or recurrent attacks. This study aims to review some aspects of gout arthritis, such as its pathophysiology, treatment goals, and adverse drug reactions. This study employs review literature using articles published between 2017 and 2022 as the research methodology. Furthermore, articles under 2017 are used as references if they are relevant to the study's subject matter. The findings showed the importance of the pathogenesis of inflammation in the treatment of gout arthritis. It is also recommended to use anti-inflammatories such as colchicine and uric acid-lowering medications starting at a specific time to prevent unintended risks. Hence, pharmacotherapy management's adverse effects include nausea, vomiting, myalgia, neuropathy, and stomach pain.
PubMed: 37691999
DOI: 10.4103/japtr.japtr_144_23 -
Substance Abuse : Research and Treatment 2023Although it is common in academic and government research settings to speak of study participants as "subjects," this perspective piece argues against doing so. In...
Although it is common in academic and government research settings to speak of study participants as "subjects," this perspective piece argues against doing so. In particular, the relationship of the study physician with study participants is unique and still retains many elements of the usual patient-physician relationship that exists in general clinical practice.
PubMed: 37564695
DOI: 10.1177/11782218231191387 -
Physiology & Behavior Nov 2023Anxiety disorders pose a significant challenge in contemporary society, and their impact in terms of social and economic burden is overwhelming. Behavioral research... (Review)
Review
Anxiety disorders pose a significant challenge in contemporary society, and their impact in terms of social and economic burden is overwhelming. Behavioral research conducted on animal subjects is crucial for comprehending these disorders and, from a translational standpoint, for introducing innovative therapeutic approaches. In this context, the Hole-Board apparatus has emerged as a widely utilized test for studying anxiety-related behaviors in rodents. Although a substantial body of literature underscores the utility and reliability of the Hole-Board in anxiety research, recent decades have witnessed a range of studies that have led to uncertainties and misinterpretations regarding the validity of this behavioral assay. The objective of this review is twofold: firstly, to underscore the utility and reliability of the Hole-Board assay, and concurrently, to examine the underlying factors contributing to potential misconceptions surrounding its utilization in the study of anxiety and anxiety-related behaviors. We will present results from both conventional quantitative analyses and multivariate approaches, while referencing a comprehensive collection of studies conducted using the Hole-Board.
Topics: Humans; Animals; Reproducibility of Results; Behavior, Animal; Anxiety; Anti-Anxiety Agents; Anxiety Disorders; Exploratory Behavior
PubMed: 37690695
DOI: 10.1016/j.physbeh.2023.114346 -
Human Brain Mapping Dec 2023Decoding brain imaging data are gaining popularity, with applications in brain-computer interfaces and the study of neural representations. Decoding is typically...
Decoding brain imaging data are gaining popularity, with applications in brain-computer interfaces and the study of neural representations. Decoding is typically subject-specific and does not generalise well over subjects, due to high amounts of between subject variability. Techniques that overcome this will not only provide richer neuroscientific insights but also make it possible for group-level models to outperform subject-specific models. Here, we propose a method that uses subject embedding, analogous to word embedding in natural language processing, to learn and exploit the structure in between-subject variability as part of a decoding model, our adaptation of the WaveNet architecture for classification. We apply this to magnetoencephalography data, where 15 subjects viewed 118 different images, with 30 examples per image; to classify images using the entire 1 s window following image presentation. We show that the combination of deep learning and subject embedding is crucial to closing the performance gap between subject- and group-level decoding models. Importantly, group models outperform subject models on low-accuracy subjects (although slightly impair high-accuracy subjects) and can be helpful for initialising subject models. While we have not generally found group-level models to perform better than subject-level models, the performance of group modelling is expected to be even higher with bigger datasets. In order to provide physiological interpretation at the group level, we make use of permutation feature importance. This provides insights into the spatiotemporal and spectral information encoded in the models. All code is available on GitHub (https://github.com/ricsinaruto/MEG-group-decode).
Topics: Humans; Deep Learning; Brain; Magnetoencephalography; Brain Mapping; Brain-Computer Interfaces
PubMed: 37753636
DOI: 10.1002/hbm.26500 -
Ophthalmology Science Sep 2023To study the individual course of retinal changes caused by healthy aging using deep learning.
PURPOSE
To study the individual course of retinal changes caused by healthy aging using deep learning.
DESIGN
Retrospective analysis of a large data set of retinal OCT images.
PARTICIPANTS
A total of 85 709 adults between the age of 40 and 75 years of whom OCT images were acquired in the scope of the UK Biobank population study.
METHODS
We created a counterfactual generative adversarial network (GAN), a type of neural network that learns from cross-sectional, retrospective data. It then synthesizes high-resolution counterfactual OCT images and longitudinal time series. These counterfactuals allow visualization and analysis of hypothetical scenarios in which certain characteristics of the imaged subject, such as age or sex, are altered, whereas other attributes, crucially the subject's identity and image acquisition settings, remain fixed.
MAIN OUTCOME MEASURES
Using our counterfactual GAN, we investigated subject-specific changes in the retinal layer structure as a function of age and sex. In particular, we measured changes in the retinal nerve fiber layer (RNFL), combined ganglion cell layer plus inner plexiform layer (GCIPL), inner nuclear layer to the inner boundary of the retinal pigment epithelium (INL-RPE), and retinal pigment epithelium (RPE).
RESULTS
Our counterfactual GAN is able to smoothly visualize the individual course of retinal aging. Across all counterfactual images, the RNFL, GCIPL, INL-RPE, and RPE changed by -0.1 μm ± 0.1 μm, -0.5 μm ± 0.2 μm, -0.2 μm ± 0.1 μm, and 0.1 μm ± 0.1 μm, respectively, per decade of age. These results agree well with previous studies based on the same cohort from the UK Biobank population study. Beyond population-wide average measures, our counterfactual GAN allows us to explore whether the retinal layers of a given eye will increase in thickness, decrease in thickness, or stagnate as a subject ages.
CONCLUSION
This study demonstrates how counterfactual GANs can aid research into retinal aging by generating high-resolution, high-fidelity OCT images, and longitudinal time series. Ultimately, we envision that they will enable clinical experts to derive and explore hypotheses for potential imaging biomarkers for healthy and pathologic aging that can be refined and tested in prospective clinical trials.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found after the references.
PubMed: 37113474
DOI: 10.1016/j.xops.2023.100294