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Current Pain and Headache Reports Apr 2024In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development,... (Review)
Review
PURPOSE OF REVIEW
In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM).
RECENT FINDINGS
Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.
Topics: Humans; Genome-Wide Association Study; Migraine Disorders; Genetic Predisposition to Disease; Precipitating Factors; Sleep Wake Disorders
PubMed: 38363449
DOI: 10.1007/s11916-024-01228-4 -
Metabolites May 2024An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations.... (Review)
Review
An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors.
PubMed: 38786741
DOI: 10.3390/metabo14050264 -
Brain Connectivity Aug 2023Amyloid-beta (Aβ) pathology is the precipitating histopathological characteristic of Alzheimer's disease (AD). Although the formation of amyloid plaques in human...
Amyloid-beta (Aβ) pathology is the precipitating histopathological characteristic of Alzheimer's disease (AD). Although the formation of amyloid plaques in human brains is suggested to be a key factor in initiating AD pathogenesis, it is still not fully understood the upstream events that lead to Aβ plaque formation and its metabolism inside the brains. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been successfully introduced to study AD pathology in brain tissue both in AD mouse models and human samples. By using MALDI-MSI, a highly selective deposition of Aβ peptides in AD brains with a variety of cerebral amyloid angiopathy (CAA) involvement was observed. MALDI-MSI visualized depositions of shorter peptides in AD brains; Aβ1-36 to Aβ1-39 were quite similarly distributed with Aβ1-40 as a vascular pattern, and deposition of Aβ1-42 and Aβ1-43 was visualized with a distinct senile plaque pattern distributed in parenchyma. Moreover, how MALDI-MSI covered lipidomics of plaque pathology has been reviewed, which is of interest as aberrations in neuronal lipid biochemistry have been implicated in AD pathogenesis. In this study, we introduce the methodological concepts and challenges of MALDI-MSI for the studies of AD pathogenesis. Diverse Aβ isoforms including various C- and N-terminal truncations in AD and CAA brain tissues will be visualized. Despite the close relationship between vascular and plaque Aβ deposition, the current strategy will define cross talk between neurodegenerative and cerebrovascular processes at the level of Aβ metabolism.
Topics: Mice; Animals; Humans; Alzheimer Disease; Brain; Magnetic Resonance Imaging; Amyloid beta-Peptides; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Plaque, Amyloid; Mice, Transgenic
PubMed: 36905365
DOI: 10.1089/brain.2022.0057 -
Clinics in Liver Disease May 2024Hepatic encephalopathy (HE) remains both a clinical diagnosis and one of exclusion. Laboratory testing is largely focused on identifying precipitating factors. Ammonia... (Review)
Review
Hepatic encephalopathy (HE) remains both a clinical diagnosis and one of exclusion. Laboratory testing is largely focused on identifying precipitating factors. Ammonia levels in the blood can be helpful for the diagnosis of HE but are not required for confirmation. More recent literature is lending support to the prognostic capabilities of ammonia in cirrhosis, both in predicting future HE events and in determining outcomes in hospitalized patients. Accurate ammonia testing requires strict protocols to avoid common pitfalls in the measurement of this labile analyte. Future studies investigating the utility of other laboratory testing to diagnose, stage, or predict HE are encouraged.
Topics: Humans; Hepatic Encephalopathy; Ammonia; Hyperammonemia; Liver Cirrhosis
PubMed: 38548435
DOI: 10.1016/j.cld.2024.01.003 -
Frontiers of Medicine Apr 2024Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a... (Review)
Review
Osteoarthritis (OA) is a degenerative bone disease associated with aging. The rising global aging population has led to a surge in OA cases, thereby imposing a significant socioeconomic burden. Researchers have been keenly investigating the mechanisms underlying OA. Previous studies have suggested that the disease starts with synovial inflammation and hyperplasia, advancing toward cartilage degradation. Ultimately, subchondral-bone collapse, sclerosis, and osteophyte formation occur. This progression is deemed as "top to bottom." However, recent research is challenging this perspective by indicating that initial changes occur in subchondral bone, precipitating cartilage breakdown. In this review, we elucidate the epidemiology of OA and present an in-depth overview of the subchondral bone's physiological state, functions, and the varied pathological shifts during OA progression. We also introduce the role of multifunctional signal pathways (including osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B ligand (RANKL)/receptor activator of nuclear factor-kappa B (RANK), and chemokine (CXC motif) ligand 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4)) in the pathology of subchondral bone and their role in the "bottom-up" progression of OA. Using vivid pattern maps and clinical images, this review highlights the crucial role of subchondral bone in driving OA progression, illuminating its interplay with the condition.
Topics: Humans; Osteoarthritis; Disease Progression; Osteoprotegerin; Bone and Bones; RANK Ligand; Signal Transduction; Cartilage, Articular; Chemokine CXCL12; Receptors, CXCR4; Receptor Activator of Nuclear Factor-kappa B
PubMed: 38619691
DOI: 10.1007/s11684-024-1061-y -
The American Journal of Geriatric... May 2024This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the... (Review)
Review
This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the substantial heterogeneity among depressed older attempters, we suggest consideration of at least two distinct pathways to suicidal behavior in late life based on when the first suicidal crisis occurred. Specifically, we discuss the current state of research and the rationale behind the suggested early-late-onset categorization of late-life suicidal behavior. We summarize available evidence so far on early-onset and late-onset attempters, and the potential heterogeneity in the interplay of risk/precipitating factors. Certain risk factors for suicide, such as impulsivity and borderline traits, decrease with age, while memory and broader cognitive impairments increase with age. Research indicates that familial/social exposure to suicidal behavior, childhood trauma, impulsivity, maladaptive personality traits, longstanding interpersonal difficulties, and legal problems are found predominantly in attempters experiencing their first suicidal crisis between youth and early midlife. In contrast, dementia prodrome is one of the most promising but understudied candidates for late-onset suicide risk, especially in the context of other risk factors. Moreover, personality traits conferring increased vulnerability to late-onset suicidal behavior (such as high conscientiousness) are not the same as ones classically identified in younger attempters and in older suicide attempters who have early-onset suicidal behavior (such as neuroticism and Cluster B traits). We discuss methodological points about studying age of onset of suicidal behavior, outline clinical implications, share ideas for future directions, and call for research on this understudied topic.
Topics: Humans; Aged; Adolescent; Suicidal Ideation; Suicide, Attempted; Suicide; Impulsive Behavior; Neuroticism; Risk Factors
PubMed: 38182486
DOI: 10.1016/j.jagp.2023.12.007 -
Contemporary Clinical Dentistry 2023Estimation and correlation of plasma fibrinogen degradation product (FDP) and salivary fibrin precipitating factor (FPF) in oral sub mucous fibrosis (OSMF) patients,...
AIM AND OBJECTIVES
Estimation and correlation of plasma fibrinogen degradation product (FDP) and salivary fibrin precipitating factor (FPF) in oral sub mucous fibrosis (OSMF) patients, betel quid chewers without OSMF and healthy individuals. The study aims to evaluate whether FDP and FPF can be used as a marker for development and progression of OSMF and whether there is any correlation between the two.
METHODOLOGY
The study included 163 subjects grouped into three categories, Group 1, which included 54 control patients, Group 2, which included 55 betel quid chewers, and Group 3, which included 54 clinically confirmed OSMF patients. All of them were subjected to the estimation of plasma FDP and salivary FPF.
RESULTS
FDP was present in 52 (96.3%) patients in Group 3, 2 (3.6%) patients in Group 2, and 1 patient in Group 1 (1.9%). FPF was positive in eight patients. The correlation of FDP and FPF was done by Fisher's exact test and was found to be statistically nonsignificant.
CONCLUSION
In the present study, FDP was positive in 52 (96.3%) OSMF patients; hence, FDP may be used as an early indicator of OSMF. FDP was found to be positive in two patients with a habit of chewing betel quid without OSMF. It may be hypothesized that these patients are more likely to develop OSMF. Hence, the estimation of FDP may be used as a diagnostic test to predict an impending OSMF before it could manifest itself clinically. FPF was negative in some OSMF patients, may be because it is below the detectable range.
PubMed: 38344155
DOI: 10.4103/ccd.ccd_350_23 -
Clinica E Investigacion En... Apr 2024Imaging is instrumental in diagnosing and directing the management of atherosclerosis. In 1958 the first diagnostic coronary angiography (CA) was performed, and since... (Review)
Review
Imaging is instrumental in diagnosing and directing the management of atherosclerosis. In 1958 the first diagnostic coronary angiography (CA) was performed, and since then further development has led to new methods such as coronary CT angiography (CTA), optical coherence tomography (OCT), positron tomography (PET), and intravascular ultrasound (IVUS). Currently, CA remains powerful for visualizing coronary arteries; however, recent studies show the benefits of using other non-invasive techniques. This review identifies optimum imaging techniques for diagnosing and monitoring plaque stability. This becomes even direr now, given the rapidly rising incidence of atherosclerosis in society today. Many acute coronary events, including acute myocardial infarctions and sudden deaths, are attributable to plaque rupture. Although fatal, these events can be preventable. We discuss the factors affecting plaque integrity, such as increased inflammation, medications like statins, and increased lipid content. Some of these precipitating factors are identifiable through imaging. However, we also highlight significant complications arising in some modalities; in CA this can include ventricular arrhythmia and even death. Extending this, we elucidated from the literature that risk can also vary based on the location of arteries and their plaques. Promisingly, there are less invasive methods being trialled for assessing plaque stability, such as Cardiac Magnetic Resonance Imaging (CMR), which is already in use for other cardiac diseases like cardiomyopathies. Therefore, future research focusing on using imaging modalities in conjunction may be sensible, to bridge between the effectiveness of modalities, at the expense of increased complications, and vice versa.
PubMed: 38594128
DOI: 10.1016/j.arteri.2024.03.001 -
Journal of Sleep Research Dec 2023Insomnia is a stress-related sleep disorder conceptualised within a diathesis-stress framework, which it is thought to result from predisposing factors interacting with... (Review)
Review
Insomnia is a stress-related sleep disorder conceptualised within a diathesis-stress framework, which it is thought to result from predisposing factors interacting with precipitating stressful events that trigger the development of insomnia. Among predisposing factors genetics and epigenetics may play a role. A systematic review of the current evidence for the genetic and epigenetic basis of insomnia was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system. A total of 24 studies were collected for twins and family heritability, 55 for genome-wide association studies, 26 about candidate genes for insomnia, and eight for epigenetics. Data showed that insomnia is a complex polygenic stress-related disorder, and it is likely to be caused by a synergy of genetic and environmental factors, with stress-related sleep reactivity being the important trait. Even if few studies have been conducted to date on insomnia, epigenetics may be the framework to understand long-lasting consequences of the interaction between genetic and environmental factors and effects of stress on the brain in insomnia. Interestingly, polygenic risk for insomnia has been causally linked to different mental and medical disorders. Probably, by treating insomnia it would be possible to intervene on the effect of stress on the brain and prevent some medical and mental conditions.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Genome-Wide Association Study; Brain; Sleep; Epigenesis, Genetic
PubMed: 36918298
DOI: 10.1111/jsr.13868 -
Journal of Hepatology Apr 2024Given the increasing burden of liver cancer in Europe, it is crucial to investigate how social determinants of health (SDoH) affect liver cancer risk factors and access...
Given the increasing burden of liver cancer in Europe, it is crucial to investigate how social determinants of health (SDoH) affect liver cancer risk factors and access to care in order to improve health outcomes equitably. This paper summarises the available evidence on the differential distribution of liver cancer risk factors, incidence, and health outcomes in the European Economic Area and the United Kingdom from an SDoH perspective. Vulnerable and marginalised populations have low socio-economic and educational levels and are the most affected by liver cancer risk factors. Reasons for this include varied access to hepatitis B virus vaccination and limited access to viral hepatitis B and C screening, harm reduction, and treatment. Additionally, alcohol-related liver disease remains highly prevalent among individuals with low education, insecure employment, economic instability, migrants, and deprived populations. Moreover, significant variation exists across Europe in the proportion of adults with steatotic liver disease, overweight/obesity, and diabetes, based on geographical area, gender, socio-economic and educational background, and density of ultra-processed food outlets. Inequities in cirrhosis mortality rates have been reported, with the highest death rates among individuals living in socio-economically disadvantaged areas and those with lower educational levels. Furthermore, insufficient healthcare access for key populations with primary liver cancer is influenced by complex healthcare systems, stigmatisation, discrimination, low education, language barriers, and fear of disclosure. These challenges contribute to inequities in liver cancer care pathways. Future studies are needed to explore the different SDoH-interlinked effects on liver cancer incidence and outcomes in European countries. The ultimate goal is to develop evidence-based multilevel public health interventions that reduce the SDoH impact in precipitating and perpetuating the disproportionate burden of liver cancer in specific populations.
Topics: Adult; Humans; Europe; Risk Factors; Hepatitis B; Liver Cirrhosis; Liver Neoplasms
PubMed: 38237866
DOI: 10.1016/j.jhep.2023.12.031