Abnormal glucose metabolism in virus associated sepsis.

Sepsis is identified as a potentially lethal organ impairment triggered by an inadequate host reaction to infection (Sepsis-3). Viral sepsis is a potentially deadly organ impairment state caused by the host's inappropriate reaction to a viral infection. However, when a viral infection occurs, the metabolism of the infected cell undergoes a variety of changes that cause the host to respond to the infection. But, until now, little has been known about the challenges faced by cellular metabolic alterations that occur during viral infection and how these changes modulate infection. This study concentrates on the alterations in glucose metabolism during viral sepsis and their impact on viral infection, with a view to exploring new potential therapeutic targets for viral sepsis.

A New CURE in Molecular Biology: Testing a Novel Pyrrolidine Compound to Determine Mechanism of Action in an Upper-Division Molecular Biology Course

The COVID-19 pandemic shut down forced introductory biology and chemistry laboratory courses online at DePauw University from March 2020-June 2021, leaving multiple classes of students without the opportunity to learn basic laboratory skills that are essential for the molecular biology laboratory. In an effort to provide students with both basic laboratory skills and advanced molecular biology skills, a new course-based undergraduate research experience (CURE) was developed for the 2022-23 academic year. In collaboration with Dr. Jeff Hansen in the Chemistry and Biochemistry department, novel compounds with potential anti-tumor properties were identified. The CURE in Molecular Biology was designed to have students use Saccharomyces cerevisiae as a model system to evaluate possible cellular pathways affected by the compound, including: cytoskeleton and cell migration, nucleotide biosynthesis, glucose metabolism, apoptosis, and cell cycle regulation. Students learned techniques DNA isolation and PCR, transformation, RNA isolation, cDNA synthesis, qPCR, and Western Blotting, while contributing to an active research project. At the conclusion of the project, students were surveyed about their comfort with molecular techniques and data analysis.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Post-COVID-19 Sydenham Chorea: A Case Report

Background: Sydenham chorea, or rheumatic chorea, is a movement disorder that is more prevalent among young people, with a mean age at symptom onset between 8 and 9 years. The condition is more common in females. Sydenham chorea is associated with rheumatic fever and is considered the most common cause of acute chorea in children. We believe that the present case is worth reporting since the occurrence of Sydenham chorea as a post-COVID-19 sequela has not been described in Brazil. Case Presentation: We report here the case of a 14-year-old girl with symptoms of acute chorea that emerged 15 days after treatment resolution of COVID-19 (SARS-CoV-2 or severe acute respiratory syndrome coronavirus 2). Brain computed tomography (CT) and magnetic resonance imaging scans showed no changes, and the laboratory tests revealed no signs of an active infectious process. In contrast, neurological positron-emission tomography/CT showed mild glycolytic hypometabolism in the bilateral mesial frontal region. Administration of an oral anticonvulsant resulted in a marked improvement in her symptoms. Conclusion(s): Despite major efforts of the scientific community for discovering treatments, preventive methods, mechanisms of action, and possible sequelae of SARS-CoV-2, there is still a long way to go to better understand this devastating pathological agent that has affected the global population.Copyright © 2023 Camargo and Morcillo.

Transcriptome Profiling in Autoimmune Diseases

Autoimmune diseases are a group of different inflammatory disorders characterized by systemic or localized inflammation, affecting approximately 0.1–1% of the general population. Several studies suggest that genetic risk loci are shared between different autoimmune diseases and pathogenic mechanisms may also be shared. The strategy of performing differential gene expression profiles in autoimmune disorders has unveiled new transcripts that may be shared among these disorders. Microarray technology and bioinformatics offer the most comprehensive molecular evaluations and it is widely used to understand the changes in gene expression in specific organs or in peripheral blood cells. The major goal of transcriptome studies is the identification of specific biomarkers for different diseases. It is believed that such knowledge will contribute to the development of new drugs, new strategies for early diagnosis, avoiding tissue autoimmune destruction, or even preventing the development of autoimmune disease. In this review, we primarily focused on the transcription profiles of three typical autoimmune disorders, including type 1 diabetes mellitus (destruction of pancreatic islet beta cells), systemic lupus erythematosus (immune complex systemic disorder affecting several organs and tissues), and multiple sclerosis (inflammatory and demyelinating disease of the nervous system). © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Postprandial Thermogenesis Is Reduced in Obesity

Background and Aims: Postprandial thermogenesis is thought to be important for the control of metabolism. This process could be reflected by minute changes in body temperature after glucose load. In this study, we measured body temperature before and its change during a glucose challenge and investigated the relationships with anthropometric and glycemic traits. Methods: We prospectively studied 383 volunteers (251 females, 132 males) with a mean age of 46.6 (SD ± 16) years and a BMI of 27.9 kg/m2 (SD ± 5.9). All participants underwent a 75 g oral glucose tolerance test (OGTT) and repeated bilateral measurements of intra-auricular temperature at time points 0, 30 and 120 minutes during the OGTT using a tympanic thermometer (Covidien Genius 2). Results: Baseline temperature was 0.17°C lower in males compared to females (p = 0.001) and inversely associated with age (p < 0.0001). During the OGTT, there was a significant increase in body temperature (0.18 ± 0.34°C). This response was present in females and males. BMI was negatively associated with the increase of temperature during the OGTT (p = 0.0147). Participants with higher BMI displayed higher fasting temperatures, but less increase of temperature during the OGTT. Body temperature was not associated with glycemia, insulin sensitivity or insulin secretion, neither in females nor males. Conclusions: There is a robust increase in body temperature during a glucose load that can be captured by intra-auricular temperature measurements. We did not detect any associations of the body temperature with glucose metabolism, arguing against a major contribution of the variability of body temperature in the pathogenesis of diabetes. However, the rise in temperature in response to oral glucose is reduced in obesity and might therefore be involved in body weight regulation.

Trained innate immunity and diseases: Bane with the boon

Emerging research shows that innate immunity can also keep the memory of prior experiences, challenging the long-held notion that immunological memory is only the domain of the adaptive immune cells. However, the absence of immunological memory in innate immune responses has recently been brought into question. Now it is known that after a few transient activations, innate immune cells may acquire immunological memory phenotype, resulting in a stronger response to a subsequent secondary challenge. When exposed to particular microbial and/or inflammatory stimuli, trained innate immunity is characterized by the enhanced non-specific response, which is regulated by substantial metabolic alterations and epigenetic reprogramming. Trained immunity is acquired by two main reprogramming, namely, epigenetic reprogramming and metabolic adaptation/reprogramming. Epigenetic reprogramming causes changes in gene expression and cell physiology, resulting in internal cell signaling and/or accelerated and amplified cytokine release. Metabolic changes due to trained immunity induce accelerated glycolysis and glutaminolysis. As a result, trained immunity can have unfavorable outcomes, such as hyper inflammation and the development of cardiovascular diseases, autoinflammatory diseases, and neuroinflammation. In this review, the current scenario in the area of trained innate immunity, its mechanisms, and its involvement in immunological disorders are briefly outlined.Copyright © 2022

New Onset Diabetes Mellitus in Post Covid Patients - an Observational Study

Background and Aims: The novel coronavirus,binds to angiotensin- converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, small intestine and kidneys. COVID-19 is attributed to the cytokine storm, followed by pancreatic cell damage.Thus, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism that could complicate the pathophysiology of pre-existing diabetes or lead to new onset Diabetes Mellitus.Thus, the study aims to analyze the development of new onset diabetes in post covid patients Methods: Serum glucose level of 500 patients, between the age of 18 to 50 who were previously normoglycemic and recovered from COVID-19 was measured and incidence of new onset diabetes mellitus was obtained. Result(s): Out of 500previously normoglycemic COVID-19 patients selected for the study, 97 patients (19.4%) developed new onset diabetes mellitus after recovering from COVID-19 disease. Conclusion(s): The results of this study show that a significant amount of people developed new onset type 2 diabetes mellitus after having recovered from COVID-19. Blood glucose control is important not only for prediabetics affected with COVID but also for those affected with no previous status of diabetes mellitus. The results of this paper could be useful in screening and diagnosis of new onset diabetes mellitus at an early stage can be beneficial to avoid further worsening of the patient's health.

A SURGE OF TYPE 1 DIABETES MELLITUS AMONG NIGERIAN CHILDREN DURING THE COVID-19 PANDEMIC.

Background: A substantial increase in Type 1 Diabetes Mellitus (T1DM) has been reported globally among children following the discovery of COVID-19. This study reports a similar trend among Nigerian children. Methods: A twelve-year (2010-2021) retrospective review of T1DM cases admitted in the Paediatric wing of a tertiary hospital in South-East Nigeria. Results: During the twelve-year study, 21 T1DM patients were seen: 9 (43%) males and 12 (57%) females. Approximately 60% of these cases presented during the pandemic (2020-2021). The mean age of subjects with T1DM was 10.5 ± 4.1 years, with females being slightly older than the male subjects (11.6 ± 3.7 years vs 9.2 ± 4.3 years respectively; p=0.176). Prior to the pandemic, females were significantly older than males (11.6 ± 3.7 years vs 4.5 ± 2.1 years respectively; p=0.042), but no age difference was observed during the pandemic (11.6 ± 4.1 years vs 10.4 ± 3.9 years respectively; p=0.597). 80% of all males in this study were seen during the pandemic and were older than the males seen before the pandemic (10.4 ± 3.9 years vs 4.5 ± 2.1 years; p=0.078). Following adjustments for age and gender, older children and males had an increased odd of developing T1DM during the pandemic but this was not statistically significant. Conclusion: This study highlights the need for increased awareness and high index of suspicion of T1DM among children during this pandemic. In the interim, more robust multi-centre studies are required to investigate the underlying relationship between COVID-19 and T1DM.

Steroids - Exploitation

Corticosteroids, more specifically glucocorticoids are one of the most prescribed drugs. Corticosteroids are adrenal hormones that serve significant physiologic activities such as modulating glucose metabolism, protein catabolism, calcium metabolism, bone turnover control, immunosuppression, and down-regulation of inflammatory cascade. Corticosteroids are regarded life-saving due to their various effects and have been used therapeutically to treat broad range of auto-immune, rheumatologic, inflammatory, neoplastic, and viral illnesses.However, the therapeutic benefits of glucocorticoids are restricted by the adverse effects. The most serious side effects of corticosteroids are associated with the use of higher doses for longer periods and OTC availability in specific pharmacies, which leads to dependency, as well as its usage in mild and moderate server instances, which is contrary to guidelines. In the recent times the use of corticosteroids has been multiplied with the emergence of the Covid -19 pandemic. WHO and the standard guidelines has recommended the usage of corticosteroids in critically ill covid-19 patients but their usage in mild and moderate cases caused more harm than benefit. This illicit usage has resulted in the development of opportunistic fungal illnesses such as mucormycosis, posing an extra risk to patients in terms of quality of life and finances. Other adverse effects of systemic corticosteroids include morphological changes, increased blood sugar levels, delayed wound healing, infections, decreased bone density, truncal obesity, cataracts, glaucoma, blood pressure abnormalities, and muscle fibre atrophy.In this review we want to discuss the significance and detrimental effects of corticosteroids emphasizing on the recent times i.e., COVID-19.

Brain FDG PET imaging of patients with persistent post- COVID-19 fatigue

Aim/Introduction: A recent report prepared by the Centers for Disease Control and Prevention indicates that 71% of patients experience persistent fatigue even after recovery from the acute phase of COVID-19 infection. We investigated if post-COVID-19 fatigue is associated with alterations in brain metabolism and microstructure to better understand the underlying neurobiological mechanism. Material(s) and Method(s): Brain F-18 FDG PET and diffusion tensor magnetic resonance imaging (DTIMR) were performed in 12 patients experiencing persistent post- COVID-19 fatigue that lasted more than six weeks post-discharge from hospitalization or discontinued home isolation after acute SARS-CoV-2 infection (fatigue group, Male:Female = 6:6, mean > SD age 35.7 > 13.8 years, Chalder fatigue scale score 8.3 > 2.2, time since COVID-19 diagnosis 7.9 > 5.5 months) and 9 recovered patients without such fatigue (non-fatigue group, M:F = 3:6, age 25.6 > 9.2, fatigue score 1.6 > 1.5, time since COVID-19 diagnosis 8.0 > 6.0 months). A commercially available normative brain FDG PET database (MIMneuro, v7.0.5, MIM Software, Inc.) was used to derive z scores for regional cerebral glucose metabolism. Fractional anisotropy (FA) values were extracted from DTI-MR datasets. Twotailed t-tests were performed for group comparison and P < 0.05 was considered statistically significant. Result(s): The fatigue group demonstrated significantly higher regional cerebral glucose metabolism in the left inferior and middle cerebellar peduncle (P = 0.001 and 0.043, respectively), left middle temporal gyrus (P = 0.002), left parahippocampal gyrus (P = 0.029), primary visual cortex (P = 0.031), supplementary motor area (P = 0.036), supramarginal gyrus (P = 0.044), and lower metabolism in the left precentral gyrus (P = 0.001) when compared to the non-fatigue group. The fatigue group also demonstrated significantly higher FA values in the left and right middle frontal gyrus (P = 0.014 and 0.038, respectively), left precentral gyrus (P = 0.024), right superior frontal gyrus (P =0.032), right postcentral gyrus (P = 0.047), left superior parietal gyrus (P = 0.048), and corpus callosum (P = 0.016) when compared to the nonfatigue group. Conclusion(s): Patients experiencing persistent fatigue after recovering from acute SARS-CoV-2 infection demonstrated significant changes in regional cerebral glucose metabolism and microstructure, when compared to those individuals without on-going fatigue symptoms. The altered cerebral metabolic and microstructural profile may help to better understand the neurobiological mechanism for management of patients suffering from lingering post-COVID-19 fatigue.

FDG-avid lymph nodes (LN) in response to vaccines for SARS-CoV-2

Aim/Introduction: Vaccines against SARS-CoV-2 virus were developed due to the impetuous coronavirus pandemic. Vaccines hold a possibility to provoke side effects. The aim of our study was to examine the impact of COVID-19 vaccination on the incidence and duration of false-positive FDG-avid lymphadenopathy after vaccination with different types of vaccines and to determine its relationship with age, gender, and vaccine type. Material(s) and Method(s): The retrospective study included 103 patients who met the following criteria:18F-FDG PET/CT scan performed (in the period from August 2021 to December 2021) for staging or restaging of diagnosed oncological diseases at different time periods after vaccination Pfizer-BioNTech, Moderna-BioNTech and Oxford-AstraZeneca. Exclusion criteria were incomplete information about vaccination, patients with a diagnosed malignant lymphoproliferative disease, concomitant benign pathology of the lymphatic system, history of acute viral infection up to 3 months from the date of PET/CT. Result(s): False-positive reactive lymphadenopathy was identified in 35 (34%) of 103 patients included in our study cohort, which occurred during the first 2 weeks to 12 weeks after vaccination and manifested as increased metabolic activity in regional non-enlarged lymph nodes: ipsilateral axillary lymph nodes of levels I-III, as well as cervical LN of levels IV and VB). A significant moderate decline in metabolic activity in the LN over time was reported, as well as a decrease in the detection rate of PET-positive reactive findings with time. The results showed a trend of a positive relationship - the occurrence of reactive lymphadenopathy more often in women than in men. The detection rate, as well as the intensity of the activity of glucose metabolism, were higher in patients under the age of 50 compared to those >= 50 years. However, we did not find significant differences between the studied types of vaccines (p >0.05). Conclusion(s): Multidisciplinary physician awareness is essential regarding the possibility of false-positive FDG lymphadenopathy in relation to local inflammation and as a manifestation of the immune response due to COVID-19 RNA vaccination and adenoviral vector-based vaccine up to 12 weeks after injection, in order to optimize the clinical interpretation of hybrid scan results that determine the subsequent therapeutic approach of cancer patients. The results of the present study demonstrate the importance of vaccination on the contralateral side of the tumor drainage, as well as taking a thorough anamnesis. Keywords: FDG PET/CT, false positive lymphadenopathy, vaccination.

Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine.

BACKGROUND: Heterologous effects of vaccines are mediated by 'trained immunity' whereby myeloid cells are metabolically and epigenetically reprogrammed resulting in heightened responses to subsequent insults. Adenovirus vaccine vector has been reported to induce trained immunity in mice. Therefore, we sought to determine if the ChAdOx1 nCoV-19 vaccine (AZD1222), which uses an adenoviral vector, could induce trained immunity in vivo in humans. METHODS: Ten healthy volunteers donated blood on the day before receiving the ChAdOx1 nCoV-19 vaccine and on day 14, 56 and 90 post vaccination. Monocytes were purified from PBMC; cell phenotype was determined by flow cytometry, expression of metabolic enzymes were quantified by RT-qPCR and production of cytokines and chemokine in response to stimulation ex vivo were analyzed by multiplex ELISA. RESULTS: Monocyte frequency and count were increased in peripheral blood up to 3 months post vaccination compared with their own pre-vaccine control. Expression of HLA-DR, CD40 and CD80 was enhanced on monocytes for up to 3 months following vaccination. Moreover, monocytes had increased expression of glycolysis-associated enzymes 2 months post vaccination. Upon stimulation ex vivo with unrelated antigens, monocytes produced increased IL-1ß, IL-6, IL-10, CXCL1, and MIP-1α, and decreased TNF, compared with pre-vaccine controls. Resting monocytes produced more IFN-γ, IL-18, and MCP-1 up to 3 months post vaccination compared with pre-vaccine controls. CONCLUSION: These data provide evidence for the induction of trained immunity following a single dose of the ChAdOx1 nCoV-19 vaccine. FUNDING: This work was funded by The Health Research Board (EIA-2019-010) and Science Foundation Ireland Strategic Partnership Programme (Proposal ID 20/SPP/3685).

Brain FDG PET imaging of patients with persistent post- COVID-19 fatigue

Aim/Introduction: A recent report prepared by the Centers for Disease Control and Prevention indicates that 71% of patients experience persistent fatigue even after recovery from the acute phase of COVID-19 infection. We investigated if post-COVID-19 fatigue is associated with alterations in brain metabolism and microstructure to better understand the underlying neurobiological mechanism. Material(s) and Method(s): Brain F-18 FDG PET and diffusion tensor magnetic resonance imaging (DTIMR) were performed in 12 patients experiencing persistent post- COVID-19 fatigue that lasted more than six weeks post-discharge from hospitalization or discontinued home isolation after acute SARS-CoV-2 infection (fatigue group, Male:Female = 6:6, mean > SD age 35.7 > 13.8 years, Chalder fatigue scale score 8.3 > 2.2, time since COVID-19 diagnosis 7.9 > 5.5 months) and 9 recovered patients without such fatigue (non-fatigue group, M:F = 3:6, age 25.6 > 9.2, fatigue score 1.6 > 1.5, time since COVID-19 diagnosis 8.0 > 6.0 months). A commercially available normative brain FDG PET database (MIMneuro, v7.0.5, MIM Software, Inc.) was used to derive z scores for regional cerebral glucose metabolism. Fractional anisotropy (FA) values were extracted from DTI-MR datasets. Twotailed t-tests were performed for group comparison and P < 0.05 was considered statistically significant. Result(s): The fatigue group demonstrated significantly higher regional cerebral glucose metabolism in the left inferior and middle cerebellar peduncle (P = 0.001 and 0.043, respectively), left middle temporal gyrus (P = 0.002), left parahippocampal gyrus (P = 0.029), primary visual cortex (P = 0.031), supplementary motor area (P = 0.036), supramarginal gyrus (P = 0.044), and lower metabolism in the left precentral gyrus (P = 0.001) when compared to the non-fatigue group. The fatigue group also demonstrated significantly higher FA values in the left and right middle frontal gyrus (P = 0.014 and 0.038, respectively), left precentral gyrus (P = 0.024), right superior frontal gyrus (P =0.032), right postcentral gyrus (P = 0.047), left superior parietal gyrus (P = 0.048), and corpus callosum (P = 0.016) when compared to the nonfatigue group. Conclusion(s): Patients experiencing persistent fatigue after recovering from acute SARS-CoV-2 infection demonstrated significant changes in regional cerebral glucose metabolism and microstructure, when compared to those individuals without on-going fatigue symptoms. The altered cerebral metabolic and microstructural profile may help to better understand the neurobiological mechanism for management of patients suffering from lingering post-COVID-19 fatigue.

FDG-avid lymph nodes (LN) in response to vaccines for SARS-CoV-2

Aim/Introduction: Vaccines against SARS-CoV-2 virus were developed due to the impetuous coronavirus pandemic. Vaccines hold a possibility to provoke side effects. The aim of our study was to examine the impact of COVID-19 vaccination on the incidence and duration of false-positive FDG-avid lymphadenopathy after vaccination with different types of vaccines and to determine its relationship with age, gender, and vaccine type. Material(s) and Method(s): The retrospective study included 103 patients who met the following criteria:18F-FDG PET/CT scan performed (in the period from August 2021 to December 2021) for staging or restaging of diagnosed oncological diseases at different time periods after vaccination Pfizer-BioNTech, Moderna-BioNTech and Oxford-AstraZeneca. Exclusion criteria were incomplete information about vaccination, patients with a diagnosed malignant lymphoproliferative disease, concomitant benign pathology of the lymphatic system, history of acute viral infection up to 3 months from the date of PET/CT. Result(s): False-positive reactive lymphadenopathy was identified in 35 (34%) of 103 patients included in our study cohort, which occurred during the first 2 weeks to 12 weeks after vaccination and manifested as increased metabolic activity in regional non-enlarged lymph nodes: ipsilateral axillary lymph nodes of levels I-III, as well as cervical LN of levels IV and VB). A significant moderate decline in metabolic activity in the LN over time was reported, as well as a decrease in the detection rate of PET-positive reactive findings with time. The results showed a trend of a positive relationship - the occurrence of reactive lymphadenopathy more often in women than in men. The detection rate, as well as the intensity of the activity of glucose metabolism, were higher in patients under the age of 50 compared to those >= 50 years. However, we did not find significant differences between the studied types of vaccines (p >0.05). Conclusion(s): Multidisciplinary physician awareness is essential regarding the possibility of false-positive FDG lymphadenopathy in relation to local inflammation and as a manifestation of the immune response due to COVID-19 RNA vaccination and adenoviral vector-based vaccine up to 12 weeks after injection, in order to optimize the clinical interpretation of hybrid scan results that determine the subsequent therapeutic approach of cancer patients. The results of the present study demonstrate the importance of vaccination on the contralateral side of the tumor drainage, as well as taking a thorough anamnesis. Keywords: FDG PET/CT, false positive lymphadenopathy, vaccination.

Characterization of glucose metabolism in obese and overweight children and adolescents during COVID-19 pandemic period

Background: COVID-19 restriction measurements have enhanced the obesity status in the pediatric population which might further contribute to obesity related glucose-insulin metabolism alterations. Therefore, we retrospectively compared anthropometric and OGTT data on obese children during the 13 years before and during the COVID-19 pandemic period. Subjects/Methods: Data from 741 obese/overweight children were retrieved and clustered into 7 groups starting from year 2008- 2009 until 2020-2021. Differences in anthropometric measurements and glucose/insulin metabolism were evaluated between the different groups. Result(s): Overweight/obese children in the COVID-19 restriction group did not present increased values of SDS-Body Mass Index (BMI). Significantly higher values for Waist Circumference (WC), SDS-WC, Waist/Height ratio (WHtR) and body mass fat were detected in these children (all P<0.01). Fasting glycaemia, glucose and insulin excursions during OGTT were significantly higher compared to pre-pandemic children (all P<0.01). Fasting and post-load insulin resistance indexes were higher while insulin secretion was lower (all P<0.01) during OGTT determining a significantly higher percentage of impaired glucose tolerance in the COVID-19 restriction group (P<0.002). Furthermore, High Density Lipoprotein (HDL) cholesterol was significantly lower (P<0.01) and SDS for systolic and diastolic blood pressure values were significantly higher (P=0.03 and P=0.02, respectively). Conclusion(s): COVID-19 restriction measurements determined profound alterations in glucose and insulin metabolism in obese/overweight children. Urgent strategies are needed in order to reverse COVID-19 restriction measures effects on glucose and insulin metabolism.

Subject Index Volume 13

Insulin degludec/insulin aspart Low fasting glucose-to-estimated average glucose ratio was associated with superior response to insulin degludec/aspart compared with basal insulin in patients with type 2 diabetes, Jang 85-93. Type 1 diabetes mellitus Impact of flash glucose monitoring on glycemic control varies with the age and residual -cell function of patients with type 1 diabetes mellitus, Zhang 552-559. Diabetes mellitus type 2 Current status of oral antidiabetic drug prescribing patterns based on the body mass index for Japanese type 2 diabetes mellitus patients and yearly changes in diabetologists' prescribing patterns from 2002 to 2019 (JDDM61), Yagi 65-73. 2A protease Immunohistochemical detection of enteroviruses in pancreatic tissues of patients with type 1 diabetes using a polyclonal antibody against 2A protease of Coxsackievirus, Jimbo 435-442. Type 2 diabetes mellitus Bariatric surgery versus medical treatment in mildly obese patients with type 2 diabetes mellitus in Japan: Propensity score-matched analysis on real-world data, Seki 74-84. [Extracted from the article]

AMPK directly phosphorylates TBK1 to integrate glucose sensing into innate immunity.

Nutrient sensing and damage sensing are two fundamental processes in living organisms. While hyperglycemia is frequently linked to diabetes-related vulnerability to microbial infection, how body glucose levels affect innate immune responses to microbial invasion is not fully understood. Here, we surprisingly found that viral infection led to a rapid and dramatic decrease in blood glucose levels in rodents, leading to robust AMPK activation. AMPK, once activated, directly phosphorylates TBK1 at S511, which triggers IRF3 recruitment and the assembly of MAVS or STING signalosomes. Consistently, ablation or inhibition of AMPK, knockin of TBK1-S511A, or increased glucose levels compromised nucleic acid sensing, while boosting AMPK-TBK1 cascade by AICAR or TBK1-S511E knockin improves antiviral immunity substantially in various animal models. Thus, we identify TBK1 as an AMPK substrate, reveal the molecular mechanism coupling a dual sensing of glucose and nuclei acids, and report its physiological necessity in antiviral defense.

European Safety Analysis of mRNA and Viral Vector COVID-19 Vaccines on Glucose Metabolism Events: An International Journal of Medical Toxicology and Drug Experience

Introduction: COVID-19 is a complex disease with several clinical phases of progression, affecting many organs apart from the respiratory tract that has shown a worst prognosis in both patients with type 1 and type 2 diabetes mellitus [1]. Based on these considerations, the vaccination for COVID-19 is a priority for this subpopulation [2]. However, few data have been published on the effects of impaired glucose metabolism induced by COVID-19 vaccines. Objective: We decided to perform a study to describe Individual Case Safety Reports (ICSRs) of impaired glucose metabolism events reported in the European database (Eudravigilance, EV). Methods: ICSRs were retrieved for the period from January 1st, 2021 to December 11th, 2021. An ICSR related to events of impaired glucose metabolism was identified by using selected preferred terms (PTs) from Standardized MedDRA Queries "Hyperglycaemia/new onset diabetes mellitus" and "Hypoglycaemia". Impaired glucose metabolism events were described and analyzed based on the Diabetologists' classification into nine groups: "diabetes in pregnancy", "acute complications of diabetes", "pre-diabetes", "type 1 diabetes mellitus", "type 2 diabetes mellitus", "high glucose levels", "diabetes mellitus inadequate control", "diabetes melli-tus not specified", and "hypoglycaemia". The reporting odds ratios were computed to assess the reporting frequency for COVID-19 mRNA vaccines compared to COVID-19 viral vector-based vaccines. Results: During the study period, 3,917 ICSRs with a COVID-19 vaccine as suspected and at least an event of impaired glucose metabolism were retrieved from the EV, of which 2,027 (51.75%) referred to Pfizer-BioNTech vaccine, 586 (14.96%) to Moderna vaccine, 1,163 (29.70%) to Oxford-AstraZeneca vaccine, and 141 (3.59%) to Janssen vaccine. From 3,917 ICSRs, we observed 4,275 impaired glucose metabolism events (1.09 adverse events per ICSR). Most adverse events were classified as serious (2,694;63.02%), and the most reported events were related to "high glucose levels" (2,012;47.06%). The mRNA vaccines were associated with an increased reporting frequency of "type 1 diabetes mellitus" (ROR 1.86;95% CI 1.33-2.60), "type 2 diabetes mellitus" (ROR 1.58;95% CI 1.03-2.42), "high glucose levels" (ROR 1.16;95% CI 1.06-1.27), "diabetes mellitus inadequate control" (ROR 1.63;95% CI 1.25-2.11), and "hypoglycemia" (ROR 1.62;95% CI 1.41-1.86) compared to viral vector-based vaccines. The highest reporting rate per 100,000 was observed for Oxford-AstraZeneca vaccine (1.87;95% CI 1.77-1.97). Conclusion: In conclusion, mRNA COVID-19 vaccines were associated with an increased reporting frequency of alterations of glucose homeostasis compared to viral-vector COVID-19 vaccines. Clinicians should be aware of these events to better manage glycaemic perturbations. Larger nationwide studies are warranted to verify these findings.

Association between Levels of vitamin D concentrations and inflammatory state in COVID 19

Hypovitaminosis D was shown to be prevalent in this research of 124 people who were COVID-19 positive. With a p-value of 0.001, greater serum concentrations of inflammatory markers like COVID-19 were significantly related with lower vitamin D levels (D-dimer, CRP, and ferritin). One way to gauge the severity of COVID-19 infection is by looking at the serum vitamin D level. An increased risk of acute respiratory infection is linked to vitamin D deficiency. The processes through which vitamin D influences the immune system are complex. The usual immunomodulatory activity appears to be inhibited with reduced serum vitamin D concentrations, favoring a pro-inflammatory phase. Less effective macrophage activity and antigen presentation may be caused by insufficient vitamin D levels. As a result, low vitamin D levels may potentially contribute to a delayed or dysregulated response to the body's initial contact with SARS-CoV-2 or prevent the construction of an effective defense in cases of established SARS-CoV-2 infection. Inflammation and the biological functions of the innate and adaptive immune systems are linked to vitamin D. Coronavirus illness risk or severity have been observed to be inversely correlated with blood 25-hydroxyvitamin D (25(OH)D) levels in observational studies (COVID-19). The significance of vitamin D in COVID-19 has been attributed to a number of pathways, such as the modulation of immunological and inflammatory responses, control of the renin-angiotensin-aldosterone systems, and participation in glucose metabolism and the cardiovascular system. Patients with COVID-19 may be more likely to experience catastrophic consequences if their 25(OH)D levels are low, not only because of the hyperinflammatory state that is often present but also because it aggravates cardiovascular disease and impaired glucose metabolism that already exist. Some randomized controlled trials have demonstrated that supplementing with vitamin D is helpful for lowering coronavirus 2 RNA positivity in SARS, but not for lowering intensive care unit admission or all-cause death in patients with moderate-to-severe COVID-19. According to the most recent research, taking a vitamin D supplement to keep your serum 25(OH)D level at or above 30 ng/mL (recommended range: 40–60 ng/mL) may help lower your risk of developing COVID-19 and its serious consequences, such as death. According to worldwide recommendations, it is prudent to suggest vitamin D supplements to those who have vitamin D shortage or insufficiency during the COVID-19 pandemic, even though additional well-designed research are necessary.

Gut microbiota and host genetics modulate the effect of diverse diet patterns on metabolic health.

Metabolic diseases are major public health issues worldwide and are responsible for disproportionately higher healthcare costs and increased complications of many diseases including SARS-CoV-2 infection. The Western Diet (WD) specifically is believed to be a major contributor to the global metabolic disease epidemic. In contrast, the Mediterranean diet (MeD), Ketogenic diet (KD), and Japanese diet (JD) are often considered beneficial for metabolic health. Yet, there is a growing appreciation that the effect of diet on metabolic health varies depending on several factors including host genetics. Additionally, poor metabolic health has also been attributed to altered gut microbial composition and/or function. To understand the complex relationship between host genetics, gut microbiota, and dietary patterns, we treated four widely used metabolically diverse inbred mouse strains (A/J, C57BL/6J, FVB/NJ, and NOD/ShiLtJ) with four human-relevant diets (MeD, JD, KD, WD), and a control mouse chow from 6 weeks to 30 weeks of age. We found that diet-induced alteration of gut microbiota (α-diversity, ß-diversity, and abundance of several bacteria including Bifidobacterium, Ruminococcus, Turicibacter, Faecalibaculum, and Akkermansia) is significantly modified by host genetics. In addition, depending on the gut microbiota, the same diet could have different metabolic health effects. Our study also revealed that C57BL/6J mice are more susceptible to altered gut microbiota compared to other strains in this study indicating that host genetics is an important modulator of the diet-microbiota-metabolic health axis. Overall, our study demonstrated complex interactions between host genetics, gut microbiota, and diet on metabolic health; indicating the need to consider both host genetics and the gut microbiota in the development of new and more effective precision nutrition strategies to improve metabolic health.