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Scientific Reports Jun 2024HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was...
Determinants of hemoglobin level and time to default from Highly Active Antiretroviral Therapy (HAART) for adult clients living with HIV under treatment; a retrospective cohort study design.
HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was conducted to investigate the joint predictors of hemoglobin level and time to default from treatment for adult clients living with HIV/AIDS under HAART at the University of Gondar Comprehensive and Specialized Hospital, North-west Ethiopia. The study was conducted using a retrospective cohort design from the medical records of 403 randomly selected adult clients living with HIV whose follow-ups were from September 2015 to March 2022. Hemoglobin level was projected using Sahli's acid-hematin method. Hence, the hemoglobin tube was filled with N/10 hydrochloric acid up to 2 g % marking and the graduated tube was placed in Sahli's hemoglobin meter. The blood samples were collected using the finger-pick method, considering 22 G disposable needles. The health staff did this. From a total of 403 adult patients living with HIV/AIDS included in the current study, about 44.2% defaulted from therapy. The overall mean and median estimated survival time of adult clients under study were 44.3 and 42 months respectively. The patient's lymphocyte count (AHR = 0.7498, 95% CI: (0.7411: 0.7587), p-value < 0.01), The weight of adult patients living with HIV/AIDS (AHR = 0.9741, 95% CI: (0.9736: 0.9747), p-value = 0.012), sex of adult clients (AHR = 0.6019, 95% CI: (0.5979, 0.6059), p-value < 0.01), WHO stages III compared to Stage I (AHR = 1.4073, 95% CI: (1.3262, 1.5078), p-value < 0.01), poor adherence level (AHR = 0.2796, 95% CI: (0.2082, 0.3705) and p-value < 0.01), bedridden patients (AHR = 1.5346, 95% CI: (1.4199, 1.6495), p-value = 0.008), and opportunistic infections (AHR = 0.2237, 95% CI: (0.0248, 0.4740), p-value = 0.004) had significant effect on both hemoglobin level and time to default from treatment. Similarly, other co-morbidity conditions, disclosure status of the HIV disease, and tobacco and alcohol addiction had a significant effect on the variables of interest. The estimate of the association parameter in the slope value of Hgb level and time default was negative, indicating that the Hgb level increased as the hazard of defaulting from treatment decreased. A patient with abnormal BMI like underweight, overweight, or obese was negatively associated with the risk of anemia (lower hemoglobin level). As a recommendation, more attention should be given to those patients with abnormal BMI, patients with other co-morbidity conditions, patients with opportunistic infections, and low lymphocytes, and bedridden and ambulatory patients. Health-related education should be given to adult clients living with HIV/AIDS to be good adherents for medical treatment.
Topics: Humans; Male; Adult; Female; Retrospective Studies; HIV Infections; Antiretroviral Therapy, Highly Active; Hemoglobins; Middle Aged; Ethiopia; Young Adult; Anti-HIV Agents; Undertreatment
PubMed: 38942753
DOI: 10.1038/s41598-024-62952-w -
Cell Death & Disease Jun 2024Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the...
Aging and obesity pose significant threats to public health and are major contributors to muscle atrophy. The trends in muscle fiber types under these conditions and the transcriptional differences between different muscle fiber types remain unclear. Here, we demonstrate distinct responses of fast/glycolytic fibers and slow/oxidative fibers to aging and obesity. We found that in muscles dominated by oxidative fibers, the proportion of oxidative fibers remains unchanged during aging and obesity. However, in muscles dominated by glycolytic fibers, despite the low content of oxidative fibers, a significant decrease in proportion of oxidative fibers was observed. Consistently, our study uncovered that during aging and obesity, fast/glycolytic fibers specifically increased the expression of genes associated with muscle atrophy and inflammation, including Dkk3, Ccl8, Cxcl10, Cxcl13, Fbxo32, Depp1, and Chac1, while slow/oxidative fibers exhibit elevated expression of antioxidant protein Nqo-1 and downregulation of Tfrc. Additionally, we noted substantial differences in the expression of calcium-related signaling pathways between fast/glycolytic fibers and slow/oxidative fibers in response to aging and obesity. Treatment with a calcium channel inhibitor thapsigargin significantly increased the abundance of oxidative fibers. Our study provides additional evidence to support the transcriptomic differences in muscle fiber types under pathophysiological conditions, thereby establishing a theoretical basis for modulating muscle fiber types in disease treatment.
Topics: Aging; Obesity; Animals; Gene Expression Profiling; Glycolysis; Male; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Transcriptome; Muscle Fibers, Slow-Twitch; Humans
PubMed: 38942747
DOI: 10.1038/s41419-024-06851-y -
Journal of Clinical Lipidology May 2024In recent years, scientific interest in triglyceride-rich lipoproteins (TRL) and remnant cholesterol has increased, focusing on the evidence that these lipoproteins are...
BACKGROUND AND AIMS
In recent years, scientific interest in triglyceride-rich lipoproteins (TRL) and remnant cholesterol has increased, focusing on the evidence that these lipoproteins are a causal factor for developing atherosclerotic cardiovascular disease (ASCVD). Furthermore, a high remnant concentration (>38 mg/dL) has been associated with several non-cardiovascular risks. We aimed in this study to describe the percentile distribution of remnant cholesterol. Additionally, we evaluated the association between remnant cholesterol plasma concentration and epidemiologically relevant cardio-metabolic outcomes such as hypertension, type 2 diabetes (T2D), and ASCVD.
METHODS
We analyzed data from 9,591 adults from the National Survey of Health and Nutrition (ENSANUT) 2018 with fasting blood samples and complete medical history questionnaires. We built multivariate models to evaluate the association between chronic diseases and blood remnant concentration. To compare our 2018-sub-sample against a population reference, we used the NHANES (2005-2014) publicly available datasets by ethnicity.
RESULTS
Remnants were independently associated with cardiovascular risk, diabetes, hypertension, obesity, and metabolic syndrome. For all outcomes, the blood remnant concentration was a stronger predictor than LDL. At all deciles, the blood remnant concentration was higher in ENSANUT-2018.
CONCLUSIONS
A remnant blood concentration above 38 mg/dL was highly prevalent among Mexicans. Remnants were significantly associated with a higher risk of diabetes, hypertension, obesity, and cardiovascular risk. This association occurred independently of other lipid markers.
PubMed: 38942690
DOI: 10.1016/j.jacl.2024.05.002 -
Aging Jun 2024Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress...
Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.
PubMed: 38942607
DOI: 10.18632/aging.205970 -
RMD Open Jun 2024The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and...
INTRODUCTION
The nature of the relationship between inflammation, cardiovascular (CV) risk factors and atherosclerosis in axial spondyloarthritis (axSpA) remains largely unknown and sex differences in this regard are yet to be assessed.
METHODS
Study including 611 men and 302 women from the Spanish multicentre AtheSpAin cohort to assess CV disease in axSpA. Data on CV disease risk factors were collected both at disease diagnosis and at enrolment, and data on disease activity, functional indices and carotid ultrasonography only at enrolment.
RESULTS
After a median disease duration of 9 years, patients of both sexes who at disease diagnosis had elevated acute phase reactants (APRs), more frequently had hypertension and obesity. The same occurred with dyslipidaemia in men and with diabetes mellitus in women. At enrolment, CV risk factors were independently associated with APR and with activity and functional indices, with various sex differences. C reactive protein (CRP) values were inversely associated with HDL-cholesterol in men (β coefficient: -1.2 (95% CI: -0.3 to -0.07) mg/dL, p=0.001), while erythrocyte sedimentation rate values were positively associated with triglycerides in women (β coefficient: 0.6 (95% CI: 0.04 to 1) mg/dL, p=0.035). Furthermore, only women showed an independent relationship between insulin resistance parameters and APR or disease activity. Both men and women with high-very high CV risk according to the Systematic Assessment of Coronary Risk Evaluation 2 and CRP levels higher than 3 mg/L at diagnosis of the disease presented carotid plaques significantly more frequently than those with normal CRP levels at disease diagnosis.
CONCLUSION
Inflammation is associated with atherosclerosis and CV disease in axSpA. A gender-driven effect is observed in this relationship.
Topics: Humans; Male; Female; Atherosclerosis; Middle Aged; Inflammation; Adult; Heart Disease Risk Factors; Sex Factors; Axial Spondyloarthritis; Risk Factors; Biomarkers; Cardiovascular Diseases; C-Reactive Protein
PubMed: 38942590
DOI: 10.1136/rmdopen-2024-004187 -
Progress in Molecular Biology and... 2024Obesity, diabetes, and other metabolic disorders place a huge burden on both the physical health and financial well-being of the community. While the need for effective... (Review)
Review
Obesity, diabetes, and other metabolic disorders place a huge burden on both the physical health and financial well-being of the community. While the need for effective treatment of metabolic disorders remains urgent and the reality is that traditional drug development involves high costs and a very long time with many pre-clinical and clinical trials, the need for drug repurposing has emerged as a potential alternative. Scientific evidence has shown the anti-diabetic and anti-obesity effects of old drugs, which were initially utilized for the treatment of inflammation, depression, infections, and even cancers. The drug library used modern technological methods to conduct drug screening. Computational molecular docking, genome-wide association studies, or omics data mining are advantageous and unavoidable methods for drug repurposing. Drug repurposing offers a promising avenue for economic efficiency in healthcare, especially for less common metabolic diseases, despite the need for rigorous research and validation. In this chapter, we aim to explore the scientific, technological, and economic issues surrounding drug repurposing for metabolic disorders. We hope to shed light on the potential of this approach and the challenges that need to be addressed to make it a viable option in the treatment of metabolic disorders, especially in the future fight against metabolic disorders.
Topics: Drug Repositioning; Humans; Metabolic Diseases; Animals
PubMed: 38942542
DOI: 10.1016/bs.pmbts.2024.02.006 -
The Journal of Pain Jun 2024Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing...
Chronic pain (CP) significantly impacts quality of life and increases non-communicable disease risk, with recent U.S. data showing a 6.3% incidence rate, surpassing diabetes, depression, and hypertension. International studies suggest higher mortality in CP populations, yet prior U.S. data is inconclusive. To investigate CP's mortality risk, we analyzed National Health Interview Survey (NHIS) and National Death Index (NDI) data. We hypothesized individuals with CP and high-impact CP (HICP, (≥1 activity limitation) would exhibit higher mortality rates. NHIS provided demographics, pain reporting, lifestyle, and psychosocial data, matched with NDI mortality records. Chi-Square analyses explored relationships between CP/HICP and demographics, lifestyle factors, psychosocial variables, and mortality. Cox proportional hazards models assessed mortality risk between groups. The weighted sample was 245,899,776; 20% reported CP and 8% HICP, both groups exhibiting higher mortality rates than pain-free individuals (CP: 5.55%, HICP: 8.79%, total: 2.82%). Hazard ratios indicated nearly double the mortality risk for CP and two-and-a-half times higher risk for HICP compared to those without these conditions. Adjusting for lifestyle and psychosocial factors reduced mortality risk but remained elevated compared to non-CP individuals. Heart disease, malignant neoplasms, and chronic lower respiratory diseases accounted for a higher percentage of deaths in CP cases. CP individuals showed higher rates of smoking, alcohol consumption, obesity, inactivity, depression, anxiety, emotional problems, and sleep disturbances. CP and HICP significantly influence mortality outcomes, leading to excess deaths compared to pain-free individuals. Given the relationship between pain, lifestyle, psychosocial variables, and mortality, further investigations are needed into CP causation and prevention strategies. PERSPECTIVE: This article presents evidence regarding the relationship between chronic pain, high impact chronic pain, and mortality. Additional findings are discussed regarding the impact of demographics, lifestyle, and psychosocial variables on mortality in those with versus without chronic pain and high impact chronic pain. These findings are crucial for informing future research, prevention, and healthcare management strategies.
PubMed: 38942415
DOI: 10.1016/j.jpain.2024.104620 -
Life Sciences Jun 2024This review aimed to investigate the different types of microparticles playing role in obesity-related diseases. Additionally, the factors participating in changing the... (Review)
Review
AIMS
This review aimed to investigate the different types of microparticles playing role in obesity-related diseases. Additionally, the factors participating in changing the microparticles amount in obese people will also be discussed.
MATERIAL & METHODS
The authors collected the relevant articles published until 2023 and these are carefully selected from three scientific databases based on keywords.
KEY FINDINGS
It has been revealed that exercise might change the microparticle content in the body. The other factor which participates in obesity process is the oxidative stress which is increased in microparticles. Moreover, the obesity is implicated in metabolic conditions including diabetes and cardiovascular diseases.
SIGNIFICANCE
More than one-third of people on the planet today are known as overweight individuals. Microparticles (MPs) are small membrane-bound vesicles that are found in healthy people's blood and are elevated in patients with pathological conditions such as obesity. MPs mostly come from platelets, leukocytes, endothelial cells, and vascular smooth muscle cells. Considering the effect of obesity on microparticles, these small membrane-bound vesicles might play a crucial role in preventing or treatment of obesity.
PubMed: 38942357
DOI: 10.1016/j.lfs.2024.122876 -
Biochimica Et Biophysica Acta.... Jun 2024Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a...
Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant). After infection, the WD-fed K18 mice lost significantly more body weight and had more severe lung inflammation than normal chow (NC)-fed mice. Bulk RNA-seq analysis of lungs and adipose tissue revealed a diverse landscape of various immune cells, inflammatory markers, and pathways upregulated in the infected WD-fed K18 mice when compared with the infected NC-fed control mice. The transcript levels of IL-6, an important marker of COVID-19 disease severity, were upregulated in the lung at 6-9 days post-infection in the WD-fed mice when compared to NC-fed mice. Transcriptome analysis of the lung and adipose tissue obtained from deceased COVID-19 patients found that the obese patients had an increase in the expression of genes and the activation of pathways associated with inflammation as compared to normal-weight patients (n = 2). The K18 mouse model and human COVID-19 patient data support a link between inflammation and an obesity-accelerated COVID-19 disease phenotype. These results also indicate that obesity-accelerated severe COVID-19 caused by SARS-CoV-2 WA1 infection in the K18 mouse model would be a suitable model for dissecting the cellular and molecular mechanisms underlying pathogenesis.
PubMed: 38942338
DOI: 10.1016/j.bbadis.2024.167322 -
Metabolism: Clinical and Experimental Jun 2024The molecular control of feeding after fasting is essential for maintaining energy homeostasis, while overfeeding usually leads to obesity. Identifying non-coding...
OBJECTIVE
The molecular control of feeding after fasting is essential for maintaining energy homeostasis, while overfeeding usually leads to obesity. Identifying non-coding microRNAs (miRNAs) that control food intake could reveal new oligonucleotide-based therapeutic targets for treating obesity and its associated diseases. This study aims to identify a miRNA modulating food intake and its mechanism in neuronal regulation of food intake and energy homeostasis.
METHODS
A comprehensive genome-wide miRNA screening in the arcuate nucleus of the hypothalamus (ARC) of fasted mice and ad libitum mice was performed. Through stereotactic virus injections, intracerebroventricular injections, and miRNA sponge technology, miR-7a-5p was inhibited specifically in AgRP neurons and the central nervous system, and metabolic phenotypes were monitored. Quantitative real-time PCR, Western blotting, immunofluorescence, whole-cell patch-clamp recording, and luciferase reporter assay were used to investigate the mechanisms underlying miR-7a-5p's regulation of food intake.
RESULTS
We found a significant increase in miR-7a-5p levels after fasting. miR-7a-5p was highly expressed in the ARC, and inhibition of miR-7a-5p specifically in AgRP neurons reduced food intake and body weight gain. miR-7a-5p inhibited S6K1 gene expression by binding to its 3'-UTR. Furthermore, the knockdown of ribosomal S6 kinase 1 (S6K1) in AgRP neurons can partially reverse the effects caused by miR-7a-5p inhibition. Importantly, intracerebroventricular administration of the miR-7a-5p inhibitor could also reduce food intake and body weight gain.
CONCLUSION
Our findings suggest that miR-7a-5p responds to energy deficit and regulates food intake by fine-tuning mTOR1/S6K1 signaling in the AgRP neurons, which could be a promising oligonucleotide-based therapeutic target for treating obesity and its associated diseases.
PubMed: 38942170
DOI: 10.1016/j.metabol.2024.155959