UCSF associate professor Vinay Prasad recently posted a YouTube video about his take on a new preprint study from UK, which shows that occurrence of myocarditis in men aged < 40 is more common after dose 2 and dose 3 of Pfizer COVID-19 vaccine and after dose 1 and dose 2 of Moderna COVID-19 vaccine than from COVID-19 infection. His blog also discusses this in detail.
Anyone successfully removed a preprint from ResearchSquare?
Study: https://www.medrxiv.org/content/10.1101/2021.11.17.21266415v1
Abstract
COVID-19 vaccination in pregnancy generates functional anti-Spike IgG antibodies that are known to cross the placenta. However, the durability of vaccine-induced maternal anti-S IgG in infant circulation, and how it compares to durability of antibody from maternal natural infection, is unknown. We quantified anti-S IgG in 92 2-month and 6-month-old infants whose mothers were vaccinated in pregnancy, and in 12 6-month-old infants after maternal natural infection with SARS-CoV-2. In the vaccinated group, 94% (58/62) of infants had detectable anti-S IgG at 2 months, and 60% (18/30) had detectable antibody at 6 months. In contrast, 8% (1/12) of infants born to women infected with SARS-CoV-2 in pregnancy had detectable anti-S IgG at the 6-month timepoint. Vaccination resulted in significantly higher maternal and cord titers at delivery and significantly greater antibody persistence in infants at 6 months, compared to natural infection.
https://www.medrxiv.org/content/10.1101/2021.12.20.21267966v2.article-info
https://preview.redd.it/0ek32klwff781.png?width=1013&format=png&auto=webp&s=f3a47e553aaa0c1a29ae463838b9bdd4f131ed06
Doubtlessly a number of confounders here (specifically risk aversion and age) but how does this constitute sufficient evidence for requiring boosters? Multiple preprints now showing very limited efficacy against Omicron, yet we're told that there's an overwhelming scientific rationale for requiring boosters, that the risk benefit assessment is unambiguously favorable to further vaccination... Come on...this is all about optics at this point.
Warning! Not peer reviewed!
https://www.biorxiv.org/content/10.1101/2022.01.04.474961v1
Summary
Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet, or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Further, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a non-metabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting.
Authors:
Daniel I. Benjamin, Pieter Both, Joel S. Benjamin, Christopher W. Nutter, Jenna H. Tan, Jengmin Kang, Leo A. Machado, Julian D. D. Klein, Antoine de Morree, Soochi Kim, Ling Liu, Hunter Dulay, Ludovica Feraboli, Sharon M Louie, Daniel K Nomura, Thomas A. Rando
Warning! Not peer reviewed!
https://www.preprints.org/manuscript/202105.0101/v1
pdf: https://www.preprints.org/manuscript/202105.0101/v1/download
Abstract
Glucose is the primary energy fuel used by the brain and is transported across the blood-brain barrier (BBB) by the glucose transporter type 1 and 2.[1] A GLUT1 genetic defect is responsible for glucose transporter type 1 deficiency syndrome (GLUT1DS). Patients with GLUT1DS may present with pharmaco-resistant epilepsy, developmental delay, microcephaly, and/or abnormal movements, with tremendous phenotypic variability. Diagnosis is made by the presence of specific clinical features, hypoglycorrhachia and an SLC2A1 gene mutation. Treatment with a ketogenic diet therapy (KDT) is the standard of care as it results in production of ketone bodies which can readily cross the BBB and provide an alternate energy source to the brain in the absence of glucose. KDTs have been shown to reduce seizures and abnormal movements in children diagnosed with GLUT1DS. However, little is known about the impact of KDT on cognitive function, seizures and movement disorders in adults newly diagnosed with GLUT1DS and started on a KDT in adulthood, or the appropriate ketogenic diet therapy to administer. This case report demonstrates the potential benefits of using a modified Atkins diet (MAD), a less restrictive ketogenic diet therapy on cognition, seizure control and motor function in an adult with newly-diagnosed GLUT1SD.
Authors:
Warning! Not peer reviewed!
https://www.researchsquare.com/article/rs-850464/v1
Abstract
Background: Probiotics and their metabolites regulate type 2 diabetes mellitus (T2DM) by promoting GLP-1 secretion, but the mechanism has not yet been fully clarified.
Results: In order to reveal the effect of Lactobacillus plantarum（L. plantarum）YZX21 on the regulation of T2DM, type 2 diabetic C57BL/6 mice induced by a high-fat diet and streptozotocin (STZ) were divided into different groups and were daily treated with L. plantarum YZX21 for 8 weeks. We identified that L.plantarum YZX21 reduced blood glucose, insulin levels and HOME-IR. Histopathology was found that L.plantarum YZX21 restored the mouse islet cells morphology and increased insulin secretion. The Elisa and immumohistochemical staining revealed concentration of glucagon-like peptide-1 (GLP-1) was increased in the mice colon. UPLC-MS/MS based widely-targeted metabolomics analysis was used to identify the differential intestinal metabolites in the mice colon. It was found that the metabolite β-Hydroxybutyrate(BHB) of L.plantarum YZX21 had a negative associated with T2DM. Subsequent, type 2 diabetic C57BL/6 mice was established and used to verify hpyerglycemic effest by daily treated with BHB for 8 weeks. It was found that BHB improved pathoglycemia, insulin resistance and increased the intestinal GLP-1 levels, especially reduced free fatty acid (FFA) levels. The expression of receptors G protein-coupled receptor (GPR) was verified by RT-PCR. The GPR109a receptor was significantly stimulated which was up-regulated the expression of GLP-1, but not GPR41 and GPR43 in the mice colon.
Conclusions: We found that the hypoglycemic effect of L.plantarum YZX21 was demonstrated by increasing the intestinal GLP-1 levels in the diabetic mice. Through the widely-targeted metabolomics, we identify the close correlation between serum concentrations of BHB and T2DM. In T2DM mice model, BHB reduced the FFA levels and increased the intestinal GLP-1 levels, which is associated with the downregulated expression of GPR109a. These results demonstrated that L.plantarum YZX21 alleviated T2DM by upregulating BHB/GPR109a/GLP-1 associated pathway.
Authors:
Zhe Zhang, Xi Liang, Lingjun Tong, Youyou Lv, Haiyan Lu, Maozhen Zhao, Pimin Gong, Tongjie Liu, Huaxi Yi, Lan Wei Zhang
Warning! Not Peer reviewed!
https://www.researchsquare.com/article/rs-355173/v2
Abstract
Background
Interventions that acutely increase blood ketone concentrations simultaneously lower blood glucose levels, although the explanation for this phenomenon is unknown. The hypoglycaemic effect of acute ketosis is greater in people with type 2 diabetes (T2D) in whom gluconeogenesis contributes significantly to hyperglycaemia. L-alanine is a gluconeogenic substrate secreted by skeletal muscle at higher levels in people with T2D. As infusion of ketones lower circulating L-alanine blood levels, we sought to determine whether supplementation with L-alanine would attenuate the hypoglycaemic effect of an exogenous ketone ester (KE) supplement.
Methods
This crossover study involved 10 healthy human volunteers who fasted for 24 hours prior to the ingestion of 25 g of D-β-hydroxybutyrate (βHB) in the form of a KE drink (ΔG®) on two separate visits. During one of the visits participants additionally ingested 2 g of L-alanine to see if L-alanine supplementation would attenuate the hypoglycaemic effect of the KE drink. Blood L-alanine, L-glutamine, glucose, βHB, free fatty acids (FFA), lactate, and C-peptide were measured every fifteen minutes for 120 minutes after ingestion of the KE, with or without L-alanine.
Findings
The KE drinks elevated blood βHB concentrations from negligible levels to 4.5 ± 1.24 mmol/L, lowered glucose from 4.97 to 3.77 ± 0.4 mmol/L, and lowered and L-alanine from 0.56 to 0.41 ± 0.9 mmol/L. L-alanine in the KE drink elevated blood L-Alanine to 0.68 ± mmol/L, but had no significant effect on blood βHB, L-glutamine, FFA, lactate, nor C-peptide concentrations. By contrast, L-alanine supplementation significantly attenuated the ketosis-induced drop in glucose from 28% to 16% (p<0.001).
Conclusions
The hypoglycaemic effect of acutely elevated βHB is partially due to βHB decreasing L-alanine availability as a substrate for gluconeogenesis
Authors:
- Adrian Soto Mota
- Nicholas Norwitz <--- !
- Rhys Evans
- Kieran Clarke
Warning! Not peer reviewed!
https://www.researchsquare.com/article/rs-500331/v1
Abstract
Purpose: Ketone body oxidation yields more ATP per mole of consumed oxygen than glucose. However, whether an increased ketone body supply in hypoxic cardiomyocytes and ischemic hearts is protective or not remains elusive. The goal of this study is to determine the effect of β-hydroxybutyrate (β-OHB), the main constituent of ketone bodies, on cardiomyocytes under hypoxic conditions and the effects of ketogenic diet (KD) on cardiac function in a myocardial infarction (MI) mouse model.
Methods: Adult mouse cardiomyocytes and MI mouse models fed a KD were used to research the effect of β-OHB on cardiac damage. qPCR, western blot analysis and immunofluorescence were used to detect the interaction between β-OHB and glycolysis. Live/dead cell staining and imaging, lactate dehydrogenase, Cell Counting Kit-8 assays, echocardiography and 2,3,5-triphenyltetrazolium chloride staining were performed to evaluate the cardiomyocyte death, cardiac function and infarct sizes.
Results: β-OHB level was significantly higher in acute MI patients and MI mice. Treatment with β-OHB exacerbated cardiomyocyte death and decreased glucose absorption and glycolysis under hypoxic conditions. These effects were partially ameliorated by inhibiting hypoxia-inducible factor 1α (HIF-1α) degradation via roxadustat administration in hypoxia-stimulated cardiomyocytes. Furthermore, β-OHB metabolisms were obscured in cardiomyocytes under hypoxic conditions. Additionally, MI mice fed a KD exhibited exacerbated cardiac dysfunction compared with control chow diet (CD)-fed MI mice.
Conclusion: Elevated β-OHB levels may be maladaptive to the heart under hypoxic/ischemic conditions. Administration of roxadustat can partially reverse these harmful effects by stabilizing HIF-1α and inducing a metabolic shift toward glycolysis for energy production.
Authors:
Xiurui Ma, Zhen Dong, jingyi Liu, Leilei Ma, Xiaolei Sun, Rifeng Gao, Lihong Pan, Jinyan Zhang, Dilan A, Jian An, Kai Hu, Aijun Sun, Junbo Ge
Warning! Not Peer reviewed!
https://www.researchsquare.com/article/rs-976505/v1
Abstract
Ketogenic diet (KD) and β-Hydroxybutyrate (βOHB) has been widely reported as an effective therapy for metabolic diseases. β-hydroxybutyrate dehydrogenase 1 (Bdh1) is the rate-limiting enzyme of ketone metabolism. In this study, we investigated the Bdh1-mediated βOHB metabolic pathway in pathogenesis of diabetic kidney disease (DKD). Human renal tubule epithelial cells (HK-2 cells) induced by high glucose (HG) or palmitic acid (PA) were used to transfect with Bdh1 siRNA or plasmid-flag-Bdh1. Reactive oxygen species (ROS) levels, nuclear factor red 2-related factor 2 (Nrf2) protein expression, and βOHB-acetoacetate (AcAc)-succinate-fumarate metabolic flux were detected. Five-week-old C57 BKS db/db obese diabetic mice (db/db) and their littermate controls (+/+) were treated with KD, βOHB, and adeno-associated virus (AAV9)-Bdh1, respectively. Renal function was determined by urinary albumin/creatinine ratio (ACR), and histopathological, immunohistochemistry (IHC), TUNEL staining of kidney were also performed. The renal expression of Bdh1 was down-regulated in DKD mouse models, diabetic patients and HG or PA induced HK-2 cells. Bdh1 overexpression or βOHB treatment protected HK-2 cells from glucotoxicity and lipotoxicity by inhibiting ROS overproduction. Mechanistically, Bdh1-mediated βOHB metabolism activated Nrf2 through enhancement of metabolic flux composed of βOHB-acetoacetate-succinate-fumarate. Moreover, in vivo studies showed that AAV9-mediated Bdh1 renal expression successfully reversed the fibrosis, inflammation and apoptosis in kidneys from C57 BKS db/db mice. Notably, either βOHB supplementation or KD feeding could elevate the renal expression of Bdh1 and reverse the progression of DKD. Our results revealed a Bdh1-mediated molecular mechanism in pathogenesis of DKD and identified Bdh1 as a potential therapeutic target for DKD.
Authors:
Sheng-rong Wan, Fang-yuan Teng, Wei Fan, Xin-yue Li, Bu-tuo Xu, Xiao-zhen Tan, Man Guo, Chen-lin Gao, Zong-zhe Jiang, Yong Xu
https://www.spektrum.de/news/welche-corona-schnelltests-sind-zuverlaessig/1954489?utm
vollständige Studie hier; aber nachdem auch unser Sozialministerium brav preprints für ihre Maßnahmen heranzieht, kanns ja net so falsch sein (Studie von P. Nordström über die Wirksamkeit der Impfstoffe über die Zeit)
https://www.medrxiv.org/content/10.1101/2021.12.08.21267162v1
The findings suggests that "at least 1,000 unvaccinated people likely need to be excluded to prevent one SARS-CoV-2 transmission event."
In other words, the benefit of having a passport is close to negligible if the assumptions in the paper are accurate.
