PathoClock and PhysioClock in mice recapitulate human multimorbidity and heterogeneous aging

Background: Multimorbidity is a public health concern and an essential component of aging and healthspan but understudied because investigative tools are lacking that can be translatable to capture similarities and differences of the aging process across species and variability between individuals and individual organs. Methods: To help address this need, body organ disease number (BODN) borrowed from human studies was applied to C57BL/6 (B6) and CB6F1 mouse strains at 8, 16, 24, and 32 months of age, as a measure of systems morbidity based on pathology lesions to develop a mouse PathoClock resembling clinically-based Body Clock in humans, using Bayesian inference. A mouse PhysioClock was also developed based on measures of physiological domains including cardiovascular, neuromuscular, and cognitive function in the same two mouse strains so that alignment with BODN was predictable. Results: Between- and within-age variabilities in PathoClock and PhysioClock, as well as between-strain variabilities. Both PathoClock and PhysioClock correlated with chronological age more strongly in CB6F1 than C57BL/6. Prediction models were then developed, designated as PathoAge and PhysioAge, using regression models of pathology and physiology measures on chronological age. PathoAge better predicted chronological age than PhysioAge as the predicted chronological and observed chronological age for PhysioAge were complex rather than linear. Conclusion: PathoClock and PhathoAge can be used to capture biological changes that predict BODN, a metric developed in humans, and compare multimorbidity across species. These mouse clocks are potential translational tools that could be used in aging intervention studies. Keywords: Multimorbidity, aging, pathology, physiology, pathoClock, physioClock, pathoAge, physioAge

The essential role of nesfatin-1 as a biological signal on the body systems

Nesfatin-1is first described in 2006 as an anorectic peptide and regulate food intake. In following years, the studies demonstrated the presence of nesfatin-1 in central and various peripheral tissues. Thus, nesfatin-1 popularity increasing widely in clinical medicine, especially in cardiology, neurology, reproduction, metabolic disorders, psychiatric disorders, gastrointestinal system. Today, the main point concerning nesfatin-1 action in body organ and systems is concentrate its biological signals effects. Thus the increasing knowledge in these area will be highlighted for future studies especially in serious health problem all over the world population.

In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract

Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies thus far have primarily focused on leaf and bark extracts of DM, and not much is yet known about the properties of either DM or DT sap. Therefore, here we performed in vivo toxicity and efficacy studies, in order to assess the biological effects of DT sap. To establish a safe dosage range, single dose or two-week daily administrations of various concentrations were performed for ICR mice. Measurements of survival ratio, body/organ weight, blood chemistry, histochemistry and Western blots were performed. A concentration of ≤0.5 mg/g DT sap was found to be safe for long-term administration. Interestingly, DT sap significantly reduced blood glucose in female mice. In addition, increasing concentrations of DT sap decreased phosphorylated (p) insulin receptor substrate (IRS)-1(ser1101)/IRS-1 in liver tissues, while increasing pAMP-activated protein kinase (AMPK)/AMPK in both the liver and spleen. To analyze its components, liquid chromatography-tandem mass spectrometry of DT sap was performed in comparison with Acer saccharum (AS) sap. Components such as estradiol, trenbolone, farnesol, dienogest, 2-hydroxyestradiol and linoleic acid were found to be highly enriched in DT sap compared to AS sap. Our results indicate DT sap exhibits hypoglycemic effects, which may be due to the abundance of the bioactive components.

Aeromedical Implications of Long-Term COVID-19 Sequelae

BACKGROUND: While many COVID-19 studies focus on acute effects of the infection, few examine the intermediate and long-term sequelae of the illness. Studies have shown that a good portion of patients have chronic effects in several body systems for several months or longer. Such effects can potentially adversely impact pilot performance in flight. We sought to determine the long-term effects of COVID-19 infection, how such effects can affect pilot performance, and how to best evaluate pilots for aeromedical flight clearance.METHODS: We used the PubMed literature search engine to review peer-reviewed articles that focused on the intermediate and long-term effects of COVID-19 infection. Chronic signs and symptoms were subdivided based on the particular body organ system affected. Merging information obtained from case reviews, article reviews, and aeromedical standards, we created a risk stratification guide to assist with the aeromedical disposition of affected pilots.RESULTS: Long-term effects of COVID-19 infection can last for several months or longer. The most common effects are fatigue, weakness, pulmonary diffusion defects, depression, and anxiety.DISCUSSION: This review article focuses on the most common intermediate- and long-term COVID-19 conditions of aeromedical significance and the corresponding course of actions recommended for the aeromedical examiner. Aeromedical evaluation should take into consideration factors related to the pilot, aircraft type, and specific aviation environment. Such evaluation may include diagnostic testing, medical specialist consultation, preflight simulation in an altitude chamber, human centrifuge testing, and/or a flight simulator checkride.Ko SY, Nguyen NK, Lee CL, Lee LA, Nguyen KUT, Lee EC. Aeromedical implications of long-term COVID-19 sequelae. Aerosp Med Hum Perform. 2021; 92(11):898-907.

PathoClock and PhysioClock in mice recapitulate human multimorbidity and heterogeneous aging

Multimorbidity is a public health concern and an essential component of aging and healthspan but understudied because investigative tools are lacking that can be translatable to capture similarities and differences of the aging process across species and variability between individuals and individual organs. To help address this need, body organ disease number (BODN) borrowed from human studies was applied to C57BL/6 (B6) and CB6F1 mouse strains at 8, 16, 24, and 32 months of age, as a measure of systems morbidity based on pathology lesions to develop a mouse PathoClock resembling clinically-based Body Clock in humans, using Bayesian inference. A mouse PhysioClock was also developed based on measures of physiological domains including cardiovascular, neuromuscular, and cognitive function in the same two mouse strains so that alignment with BODN was predictable. The results revealed between- and within-age variabilities in PathoClock and PhysioClock, as well as between-strain variabilities. Both PathoClock and PhysioClock correlated with chronological age more strongly in CB6F1 than C57BL/6. Prediction models were then developed, designated as PathoAge and PhysioAge, using regression models of pathology and physiology measures on chronological age. PathoAge better predicted chronological age than PhysioAge as the predicted chronological and observed chronological age for PhysioAge were complex rather than linear. In conclusion, PathoClock and PhathoAge can be used to capture biological changes that predict BODN, a metric developed in humans, and compare multimorbidity across species. These mouse clocks are potential translational tools that could be used in aging intervention studies.

IMPACT OF COVID-19 ON MULTIPLE BODY ORGAN FAILURE: A REVIEW

COVID-19 is a highly contagious disease caused by Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2); which is a novel single-stranded positive RNA infection which consist of cytokines that activate the pathogenic systems that cause high respiratory pain condition, and adversely affect on multiple body organ in humans as per their immunity standards to fight against the virus. SARS-CoV-2 enters the host cell through Angiotensin-Converting Enzyme 2 (ACE 2). ACE 2 is a sub-part of the Renin-Aldosterone Angiotensin System (RAAS), intelligently communicated in the body's kidney, heart, lungs, and malignant tissues. The malfunctioning of RAAS in the body leads to hypertension, cardiovascular sicknesses, endocrine system and negatively affects a brain-body communication channel. Treatments on the RAAS structure, 'thiazolidinedione's and smoking, toxemia, kidney, lungs disorder due to the SARS-CoV-2 attack on the host cell and notice the behavioral changes of body organs the arrival of cytokines that causes multi-organ damage. This paper involves the study of the effects of coronavirus disease on multiple body-organ injuries.

Amyloidosis in major body organs examined during autopsies at Mbarara Regional Referral Hospital

BackgroundAmyloidosis is an infrequent disease that occurs when an abnormal protein, called amyloid, deposits in body organs and disrupts their normal function. Amyloid is not normally found in the body but it can be formed from several different types of protein. Commonly affected organs include the heart, kidneys, gastrointestinal (GI) tract/liver or the peripheral or autonomic nervous system (NS). Amyloidosis can lead to diseases such as Alzheimer’s disease, spongiform encephalopathies and diabetes mellitus type 2. Main objectiveTo establish the prevalence of amyloidosis in major body organs examined during autopsies at Mbarara regional referral hospital and to correlate cause of death with amyloidosis. MethodsBrain, heart, kidney, and liver samples were obtained from 23 bodies during autopsies at Mbarara regional referral hospital which were then processed to produce 2 slides per tissue of each of the above organ samples. These slides were then stained using H&E and Congo red staining protocols and then examined for amyloidosis under the light microscope. ResultsThe mean age of the bodies was 61.26 of which 5 (21.7%) were female while 18 (78.3%) were male. 3 bodies (13.0%) tested positive for amyloidosis in the kidney; 2 males (8.70) and 1 female (4.35). All the other organs tested negative. ConclusionIn our study, body organ investigation revealed amyloid in the kidney of 3 bodies. The prevalence of amyloidosis was 13% therefore amyloidosis diagnosis ought to be put into consideration at Mbarara Regional Referral hospital.

Diseases of cardiovascular system in patients with severe and moderatesevere forms of psoriasis

Psoriasis is one of the most common chronic recurrent dermatoses, which is not limited to skin lesions, leading to a violation of the functions of various body organ systems. The article presents the results of the analysis of the medical histories of patients of Clinical dermatovenerologic dispensary (Krasnodar Region of Russia) with moderate-severe and severe forms of psoriasis and concomitant cardiological pathology. The article presents data from 70 case histories of patients with moderate to severe psoriasis, the analysis of which shows the clinical and practical significance of comorbidity of psoriasis. From the analysis, we conclude that there is a direct relationship between the severity of the course of the cutaneous pathological process and the aggravation of the cardiological diagnosis. The higher the severity of psoriasis, the higher the risk of developing acute coronary syndrome, myocardial infarction and other cardiac pathology.

Body Clock: Matching Personalized Multimorbidity and Fast Aging Using Information Entropy

With aging, most older adults are at risk of having more than two diseases, conventionally defined as multimorbidity. We determined body organ disease number (BODN) as a new multimorbidity index. We measured the degree to which each disease level, from mild to severe, predicts longitudinal BODN uncoupled from chronological age. We determined Body Clock using global disease levels burden from all systems predicting longitudinal BODN for each individual, which is a proxy of the personalized rate of biological aging. Change in Body Clock predicts late-life age-related outcomes and can be used for geriatric clinics and clinical trials for precision medicine.