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The Journal of Maternal-fetal &... Dec 2023N6-methyladenosine (m6A) is one of the predominant RNA epigenetic modifications that modify RNAs reversibly and dynamically by "writers" (methyltransferase), "erasers"... (Review)
Review
BACKGROUND
N6-methyladenosine (m6A) is one of the predominant RNA epigenetic modifications that modify RNAs reversibly and dynamically by "writers" (methyltransferase), "erasers" (demethylase), and "readers."
OBJECTIVE
This review aimed to provide a comprehensive understanding of the complexity of m6A regulation in the great obstetrical syndromes to understand its pathogenesis and potential therapeutic targets.
METHODS
The terms "placenta or trophoblast" and "m6A or N6-methyladenosine" were searched in PubMed databases (June 2023).
RESULTS
In this review, we discuss the regulatory role of m6A in the great obstetrical syndromes such as preeclampsia (PE), spontaneous abortion (SA), hyperglycemia in pregnancy (HIP) and fetal growth to emphasize the clinical relevance of m6A dysregulation in pregnancy. We also describe mechanisms that potentially involve the participation of m6A methylation, such as proliferation, invasion, migration, apoptosis, autophagy, endoplasmic reticulum stress, macrophage polarization, and inflammation.
CONCLUSION
We summarize the recent research progress on the role of m6A modification in the great obstetrical syndromes and placental function and provide a brief perspective on its prospective applications.
Topics: Pregnancy; Humans; Female; Placenta; Syndrome; Abortion, Spontaneous; Adenosine; Apoptosis
PubMed: 37474299
DOI: 10.1080/14767058.2023.2234541 -
The International Journal of Social... Mar 2024Since 2016, an array of claims and public discourse have circulated in the medical community over the origin and nature of a mysterious condition dubbed "Havana... (Review)
Review
BACKGROUND
Since 2016, an array of claims and public discourse have circulated in the medical community over the origin and nature of a mysterious condition dubbed "Havana Syndrome," so named as it was first identified in Cuba. In March 2023, the United States intelligence community concluded that the condition was a socially constructed catch-all category for an array of health conditions and stress reactions that were lumped under a single label.
AIMS
To examine the history of "Havana Syndrome" and the many factors that led to its erroneous categorization as a novel clinical entity.
METHOD
A review of the literature.
RESULTS/CONCLUSIONS
Several factors led to the erroneous classification of "Havana Syndrome" as a novel entity including the failure to stay within the limitations of the data; the withholding of information by intelligence agencies, the prevalence of popular misconceptions about psychogenic illness, the inability to identify historical parallels; the role of the media, and the mixing of politics with science.
Topics: Humans; United States; Syndrome; Cuba; Politics
PubMed: 38146090
DOI: 10.1177/00207640231208374 -
European Heart Journal Sep 2023Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated... (Meta-Analysis)
Meta-Analysis
AIMS
Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding.
METHODS AND RESULTS
A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002).
CONCLUSION
Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.
Topics: Humans; Aortic Valve; Angiodysplasia; Aortic Valve Stenosis; von Willebrand Diseases; Gastrointestinal Hemorrhage; Syndrome; von Willebrand Factor
PubMed: 37555393
DOI: 10.1093/eurheartj/ehad340 -
Biomolecules Oct 2023A recessive Short Tandem Repeat expansion in has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a...
A recessive Short Tandem Repeat expansion in has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients' blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method.
Topics: Humans; Cerebellar Ataxia; Peripheral Nervous System Diseases; Vestibular Diseases; Bilateral Vestibulopathy; Syndrome; Chromosome Mapping
PubMed: 37892228
DOI: 10.3390/biom13101546 -
Frontiers in Immunology 2023Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most frequent periodic fever syndrome in children. Its pathogenesis is still... (Clinical Trial)
Clinical Trial
INTRODUCTION
Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most frequent periodic fever syndrome in children. Its pathogenesis is still unknown, but some disease-modifying factors were observed. Several medications were tested for the long-term prophylaxis of inflammatory flares; however, none are standardly used.
METHODS
This prospective clinical trial enrolled 142 children (71 girls, 50%) meeting diagnostic criteria for PFAPA syndrome. We analysed selected clinical characteristics and compared laboratory parameters during the flare and attack-free period (at least two weeks after the attack). Moreover, we assessed the possible therapeutic effect of ketotifen on the duration of attack free-periods and clinical picture.
RESULTS
The mean age of patients was 6.81 ± 3.03 years and the mean age of onset of symptoms was 2.31 ± 2.02 years. No significant differences were observed between genders.We recorded a positive family history for PFAPA in 31.69% of patients. Attacks lasted for 2.8 ± 1.2 days, with intervals between attacks of 4 ± 1 weeks. We administered ketotifen in 111 (77.8%) patients, and a positive effect was observed in 86 (77.5%) of patients. We observed prolonged attack-free intervals in patients treated with ketotifen (14.7 ± 8.9 days in comparison with 4.4 ± 1.9 days before the treatment; p<0.001). The used dose of ketotifen was 0.08 ± 0.01 mg/kg/day. Mild side effects were observed in four patients (restlessness, irritability, agitation and constipation).
DISCUSSION
Our data supports the use of ketotifen for long-term prophylaxis in children with PFAPA syndrome with positive effects on the attenuation of disease activity and the prolongation of attack-free periods. Further well-designed studies should confirm the preliminary data.
Topics: Child; Humans; Male; Female; Child, Preschool; Infant; Ketotifen; Stomatitis, Aphthous; Pharyngitis; Lymphadenitis; Lymphadenopathy; Syndrome; Anti-Inflammatory Agents
PubMed: 38143757
DOI: 10.3389/fimmu.2023.1302875 -
Neurological Sciences : Official... Dec 2023Tremor is the most common movement disorder. Although clinical examination plays a significant role in evaluating patients with tremor, laboratory tests are useful to... (Review)
Review
INTRODUCTION
Tremor is the most common movement disorder. Although clinical examination plays a significant role in evaluating patients with tremor, laboratory tests are useful to classify tremors according to the recent two-axis approach proposed by the International Parkinson and Movement Disorders Society.
METHODS
In the present review, we will discuss the usefulness and applicability of the various diagnostic methods in classifying and diagnosing tremors. We will evaluate a number of techniques, including laboratory and genetic tests, neurophysiology, and neuroimaging. The role of newly introduced innovative tremor assessment methods will also be discussed.
RESULTS
Neurophysiology plays a crucial role in tremor definition and classification, and it can be useful for the identification of specific tremor syndromes. Laboratory and genetic tests and neuroimaging may be of paramount importance in identifying specific etiologies. Highly promising innovative technologies are being developed for both clinical and research purposes.
CONCLUSIONS
Overall, laboratory investigations may support clinicians in the diagnostic process of tremor. Also, combining data from different techniques can help improve understanding of the pathophysiological bases underlying tremors and guide therapeutic management.
Topics: Humans; Tremor; Movement Disorders; Syndrome; Essential Tremor
PubMed: 37814130
DOI: 10.1007/s10072-023-07108-w -
BMC Medicine Nov 2023Is disease demotion more important than health promotion? The question is crucial for the ethos of medicine and for priority setting in healthcare. When things get...
Is disease demotion more important than health promotion? The question is crucial for the ethos of medicine and for priority setting in healthcare. When things get tough, where should our attention and resources go: to health or disease? This study investigates two general perspectives on health and disease to address whether there is a stronger moral appeal from people's disease than from their health. While naturalist conceptions of health and disease are mute on moral appeal, normativist conceptions give diverse answers. Classical utilitarianism provides a symmetrical view of health and disease, according to which we have an equally strong moral appeal to further health as we have to reduce disease. Other normativist positions argue that there is an asymmetry between health and disease providing substantial support for a stronger moral appeal from disease than from health. This has a wide range of radical implications, especially within priority setting. In particular, treatment, palliation, and prevention of disease should have priority to the promotion and enhancement of health.
Topics: Humans; Morals; Health Promotion; Disease; Motivation
PubMed: 37926829
DOI: 10.1186/s12916-023-03110-3 -
Journal of the American Heart... Feb 2024Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the... (Review)
Review
Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of the immune system leads to a multiorgan involvement often affecting the heart. Cardiac involvement in multisystemic inflammatory syndrome in adults has been described mainly in young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, and myocarditis, with a nonnegligible risk of mortality (up to 7% of all cases). The heterogeneity of its clinical features and the absence of a clear case definition make the differential diagnosis with other postinfectious (eg, infective myocarditis) and hyperinflammatory diseases (eg, adult Still disease and macrophage activation syndrome) challenging. Moreover, the evidence on the efficacy of specific treatments targeting the hyperinflammatory response underlying this clinical condition (eg, glucocorticoids, immunoglobulins, and other immunomodulatory agents) is sparse and not supported by randomized clinical trials. In this review article, we aim to provide an overview of the clinical features and the diagnostic workup of multisystemic inflammatory syndrome in adults with cardiac involvement, highlighting the possible pathogenetic mechanisms and the therapeutic management, along with remaining knowledge gaps in this field.
Topics: Adult; Male; Humans; Myocarditis; Patients; Heart; COVID-19; Diagnosis, Differential; Syndrome
PubMed: 38348793
DOI: 10.1161/JAHA.123.032143 -
Genes May 2023SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and... (Review)
Review
SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan-Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin-Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the gene. Here we describe 18 new patients with variants in , most of them with the LLS phenotype, and reviewed 33 additional patients with variants in that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with .
Topics: Humans; Autism Spectrum Disorder; Intellectual Disability; Muscle Hypotonia; Phenotype; Syndrome
PubMed: 37372360
DOI: 10.3390/genes14061179 -
Endocrine-related Cancer Oct 2023This article is a summary of the plenary lecture presented by Jared Rosenblum that was awarded the Manger Prize at the Sixth International Symposium on... (Review)
Review
This article is a summary of the plenary lecture presented by Jared Rosenblum that was awarded the Manger Prize at the Sixth International Symposium on Pheochromocytoma/Paraganglioma held on 19-22 October 2022 in Prague, Czech Republic. Herein, we review our initial identification of a new syndrome of multiple paragangliomas, somatostatinomas, and polycythemia caused by early postzygotic mosaic mutations in EPAS1, encoding hypoxia-inducible factor 2 alpha (HIF-2α), and our continued exploration of new disease phenotypes in this syndrome, including vascular malformations and neural tube defects. Continued recruitment and close monitoring of patients with this syndrome as well as the generation and study of a corresponding disease mouse model as afforded by the pheochromocytoma/paraganglioma translational program at the National Institutes of Health has provided new insights into the natural history of these developmental anomalies and the pathophysiologic role of HIF-2α. Further, these studies have highlighted the importance of the timing of genetic defects in the development of related disease phenotypes. The recent discovery and continued study of this syndrome has not only rapidly evolved our understanding of pheochromocytoma and paraganglioma but also deepened our understanding of other developmental tumor syndromes, heritable syndromes, and sporadic diseases.
Topics: Animals; Mice; Pheochromocytoma; Syndrome; Paraganglioma; Basic Helix-Loop-Helix Transcription Factors; Adrenal Gland Neoplasms
PubMed: 37450881
DOI: 10.1530/ERC-23-0050