Background
Allergic diseases often develop jointly during early childhood but differ in timing of onset, remission, and progression. Their disease course over time is often difficult to predict and ...determinants are not well understood.
Objectives
We aimed to identify trajectories of allergic diseases up to adolescence and to investigate their association with early‐life and genetic determinants and clinical characteristics.
Methods
Longitudinal k‐means clustering was used to derive trajectories of allergic diseases (asthma, atopic dermatitis, and rhinitis) in two German birth cohorts (GINIplus/LISA). Associations with early‐life determinants, polygenic risk scores, food and aeroallergen sensitization, and lung function were estimated by multinomial models. The results were replicated in the independent Swedish BAMSE cohort.
Results
Seven allergic disease trajectories were identified: “Intermittently allergic,” “rhinitis,” “early‐resolving dermatitis,” “mid‐persisting dermatitis,” “multimorbid,” “persisting dermatitis plus rhinitis,” and “early‐transient asthma.” Family history of allergies was more prevalent in all allergic disease trajectories compared the non‐allergic controls with stronger effect sizes for clusters comprising more than one allergic disease (e.g., RRR = 5.0, 95% CI = 3.1–8.0 in the multimorbid versus 1.8 1.4–2.4 in the mild intermittently allergic cluster). Specific polygenic risk scores for single allergic diseases were significantly associated with their relevant trajectories. The derived trajectories and their association with genetic effects and clinical characteristics showed similar results in BAMSE.
Conclusion
Seven robust allergic clusters were identified and showed associations with early life and genetic factors as well as clinical characteristics.
We identified seven allergic disease trajectories up to adolescence, which are corresponding to clinical observation in the German GINIplus and LISA studies and replicated the results in the Swedish BAMSE cohort. The clusters can be characterized using polygenic risk scores and early‐life determinants, which support the hygiene hypothesis. The clusters also pose clinical implications for allergic sensitization, increasing with number of present allergic diseases, and lung function.Abbreviations: BAMSE, Barn/Child Allergy Milieu Stockholm Epidemiology; GINIplus, German Infant Study on the Influence of Nutrition Intervention plus Air pollution and Genetics on Allergy Development; LISA, Influence of Life‐style factors on Development of the Immune System and Allergies in East and West Germany study; PRS, polygenic risk score.
Intellectual disability (ID) is a common disorder, yet there is a wide spectrum of impairment from mild to profoundly affected individuals. Mild ID is seen as the low extreme of the general ...distribution of intelligence, while severe ID is often seen as a monogenic disorder caused by rare, pathogenic, highly penetrant variants. To investigate the genetic factors influencing mild and severe ID, we evaluated rare and common variation in the Northern Finland Intellectual Disability cohort (n = 1096 ID patients), a cohort with a high percentage of mild ID (n = 550) and from a population bottleneck enriched in rare, damaging variation. Despite this enrichment, we found only a small percentage of ID was due to recessive Finnish-enriched variants (0.5%). A larger proportion was linked to dominant variation, with a significant burden of rare, damaging variation in both mild and severe ID. This rare variant burden was enriched in more severe ID (p = 2.4e-4), patients without a relative with ID (p = 4.76e-4), and in those with features associated with monogenic disorders. We also found a significant burden of common variants associated with decreased cognitive function, with no difference between mild and more severe ID. When we included common and rare variants in a joint model, the rare and common variants had additive effects in both mild and severe ID. A multimodel inference approach also found that common and rare variants together best explained ID status (ΔAIC = 16.8, ΔBIC = 10.2). Overall, we report evidence for the additivity of rare and common variant burden throughout the spectrum of intellectual disability.
Background-Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While ...the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods-This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer's disease and pre-Alzheimer's disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions-Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.
Atopic eczema onset is described primarily in early childhood, and the frequency and characteristics of adult-onset disease remain controversial.
We sought to determine the proportion of subjects who ...report atopic eczema symptoms between birth and midadulthood and to examine demographic, immunologic, and genetic factors associated with period of symptom onset.
We conducted a longitudinal study using data from 2 nationally representative community-based birth cohorts from the United Kingdom: the British Cohort Studies 1958 and 1970. Subjects were followed from birth through age 42 to 50 years. The primary outcome was the age period of self-reported atopic eczema symptom onset based on repeated measures of self-reported atopic eczema at each survey wave.
The annual period prevalence of atopic eczema ranged from 5% to 15% in 2 cohorts of more than 17,000 participants each followed from birth through middle age. There was no clear trend in prevalence by age, and among adults reporting active atopic eczema during a given year, only 38% had symptom onset reported in childhood. When compared with subjects whose eczema started in childhood, those with adult-onset disease were more likely to be women, from Scotland or Northern England, of lower childhood socioeconomic group, smokers in adulthood, and less likely to have a history of asthma. In a subanalysis using data from the 1958 cohort only, genetic mutations previously associated with atopic eczema, including filaggrin-null mutations, and allergen-specific IgE were more common among those with childhood-onset disease.
Rates of self-reported atopic eczema remain high after childhood, and adult-onset atopic eczema has different risk factor associations than childhood-onset eczema.
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Skin pigmentation is negatively associated with circulating vitamin D (VD) concentration. Therefore, genetic factors involved in skin pigmentation could influence the risk of vitamin D deficiency ...(VDD). We evaluated the impact genetic variants related to skin pigmentation on VD in Mexican population. This cross-sectional analysis included 848 individuals from the Health Worker Cohort Study (ratio males to females ~ 1:3). Eight genetic variants: rs16891982 (SLC45A2), rs12203592 (IRF4), rs1042602 and rs1126809 (TYR), rs1800404 (OCA2), rs12913832 (HERC2), rs1426654 (SLC24A5), and rs2240751 (MFSD12); involved in skin pigmentation were genotyped. Skin pigmentation was assessed by self-report. Linear and logistic regression were used to assess the association between the variants of interest and VD and VDD, as appropriate. In our study, eight genetic variants were associated with skin pigmentation. A genetic risk score built with the variants rs1426654 and rs224075 was associated with lower VD levels (β = − 1.38, 95% CI − 2.59, − 0.17, p = 0.025). Nevertheless, when examining gene–gene interactions, we observed that rs2240751 × rs12203592 were associated with VD levels (P interaction = 0.021). Whereas rs2240751 × rs12913832 (P interaction = 0.0001) were associated with VDD. Our results suggest that skin pigmentation-related gene variants are associated with lower VD levels in Mexican population. These results underscore the importance of considering genetic interactions when assessing the impact of genetic polymorphisms on VD levels.
The circadian rhythm is a nearly 24‐h oscillation found in various physiological processes in the human brain and body that is regulated by environmental and genetic factors. It is responsible for ...maintaining body homeostasis and it is critical for essential functions, such as metabolic regulation and memory consolidation. Dysregulation in the circadian rhythm can negatively impact human health, resulting in cardiovascular and metabolic diseases, psychiatric disorders, and premature death. Emerging evidence points to a relationship between the dysregulation circadian rhythm and neurodegenerative diseases, suggesting that the alterations in circadian function might play crucial roles in the pathogenesis and progression of neurodegenerative diseases. Better understanding this association is of paramount importance to expand the knowledge on the pathophysiology of neurodegenerative diseases, as well as, to provide potential targets for the development of new interventions based on the dysregulation of circadian rhythm. Here we review the latest findings on dysregulation of circadian rhythm alterations in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia and multiple‐system atrophy, focusing on research published in the last 3 years.
Neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinocerebellar ataxia (SCA), and multiple‐system atrophy (MSA) dysregulate clock genes, which leads to sleep disturbances and can also exacerbate these diseases. In PD, the decrease in clock genes leads to oxidative stress. In AD, this disturbance leads to an increase in tau phosphorylation. In HD, it intensifies the accumulation of mutant huntingtin, and in MSA, it impairs dopaminergic signaling. These alterations act as a feedback loop, exacerbating neurodegenerative diseases.
Background Genetic factors have been implicated in the development of substance abuse disorders, but the role of pre-existing vulnerability in addiction is still poorly understood. Personality traits ...of impulsivity and sensation-seeking are highly prevalent in chronic drug users and have been linked with an increased risk for substance abuse. However, it has not been clear whether these personality traits are a cause or an effect of stimulant drug dependence. Method We compared self-reported levels of impulsivity and sensation-seeking between 30 sibling pairs of stimulant-dependent individuals and their biological brothers/sisters who did not have a significant drug-taking history and 30 unrelated, nondrug-taking control volunteers. Results Siblings of chronic stimulant users reported significantly higher levels of trait-impulsivity than control volunteers but did not differ from control volunteers with regard to sensation-seeking traits. Stimulant-dependent individuals reported significantly higher levels of impulsivity and sensation-seeking compared with both their siblings and control volunteers. Conclusions These data indicate that impulsivity is a behavioral endophenotype mediating risk for stimulant dependence that may be exacerbated by chronic drug exposure, whereas abnormal sensation-seeking is more likely to be an effect of stimulant drug abuse.
Cephalosporin antibiotics are widely used in clinical settings, but they can cause hypersensitivity reactions, which may be influenced by genetic factors such as the expression of Human leukocyte ...antigen (HLA) molecules. This study aimed to investigate whether specific HLA alleles were associated with an increased risk of adverse reactions to cephalosporins among individuals in the Taiwanese population. This retrospective case–control study analyzed data from the Taiwan Precision Medicine Initiative (TPMI) on 27,933 individuals who received cephalosporin exposure and had HLA allele genotyping information available. Using logistic regression analyses, we examined the associations between HLA genotypes, comorbidities, allergy risk, and severity. Among the study population, 278 individuals had cephalosporin allergy and 2780 were in the control group. Our results indicated that certain HLA alleles, including HLA-B*55:02 (OR = 1.76, 95% CI 1.18–2.61, p = 0.005), HLA-C*01:02 (OR = 1.36, 95% CI 1.05–1.77, p = 0.018), and HLA-DQB1*06:09 (OR = 2.58, 95% CI 1.62–4.12, p < 0.001), were significantly associated with an increased risk of cephalosporin allergy reactions. Additionally, the HLA-C*01:02 allele genotype was significantly associated with a higher risk of severe allergy (OR = 2.33, 95% CI 1.05–5.15, p = 0.04). This study identified significant associations between HLA alleles and an increased risk of cephalosporin allergy, which can aid in early detection and prediction of adverse drug reactions to cephalosporins. Furthermore, our study highlights the importance of HLA typing in drug safety and expanding our knowledge of drug hypersensitivity syndromes.
A review of keratoacanthoma
British journal of dermatology (1951),
September 2021, 2021-09-00, 20210901, Letnik:
185, Številka:
3
Journal Article
Recenzirano
Linked article: Tisack et al. Br J Dermatol 2021; 185:487–498.
In this study, our team from the USA reviewed what is known about a skin growth called keratoacanthoma. Keratoacanthoma is a somewhat ...controversial skin lesion because it has very similar clinical and microscopic features to a type of skin cancer called cutaneous squamous cell carcinoma (cSCC), which can potentially spread internally (metastasize) whereas keratoacanthoma behaves in a benign (non‐worrisome) manner.
Owing to the similar appearance of keratoacanthoma and cSCC, a keratoacanthoma is often diagnosed as a cSCC and treated as such with surgical removal to ensure a cSCC skin cancer is not undertreated. The lack of diagnostic certainty between keratoacanthoma and cSCC may result in additional surgeries for patients who may have been treated otherwise with less invasive treatment approaches more appropriate for keratoacanthoma.
Our team searched the literature for information about keratoacanthoma and we included over 150 papers in our review. We concluded that keratoacanthoma is likely a benign skin tumour different from cSCC. Our conclusions about keratoacanthoma were based on the following: their clinical behaviour, appearance under the microscope, genetic factors and how the immune system responds to them. All of these are different in keratoacanthoma compared with cSCC. We also reviewed different therapeutic approaches for successfully treating keratoacanthoma.
Although numerous factors may help differentiate keratoacanthoma from cSCC, we also found that there is still no way to tell the difference between keratoacanthoma and cSCC absolutely conclusively in many cases. We hope our findings will set the stage for future research to discover a method to tell apart these two lesions better.
Linked article: Tisack et al. Br J Dermatol 2021; 185:487–498.
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