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Background: Arteriovenous malformations are abnormal tangles of blood vessels that cause irregular connections between arteries and veins. Rupture of arteriovenous malformations represents a frequent complication associated with a neurological impairment and physical disability.Methods: We investigated the relationship among coping dimensions and overall quality of life (QoL), and health status after surgical intervention in 20 patients affected by arteriovenous malformations. Each patient was administered a battery of self-report questionnaires (Short Form 12 Health Survey Questionnaire, Brief COPE Inventory, Beck Depression Inventory, and Hamilton Rating Scale for Anxiety).Results: We found that surgical treatment of arteriovenous malformations affected subjective well-being and emotional aspects. Coping ability influenced the QoL and the presence of anxiety and depressive symptoms. We found a significant correlation between depression and humor (r = -.47, P = .03) and between QoL and self-distraction (r = -.48, P = .03) and humor (r = .44, P = .05). In particular, humor was a significant predictor of mental health and physical health.Conclusions: The presence of anxiety and depression was the cause of deterioration of QoL, even if psychological resources used to deal with the disease significantly modified the subjective perception of well-being. The evaluation of the impact of cerebrovascular disease on QoL should be a basis for planning and evaluating therapeutic and psychological rehabilitative interventions. [ABSTRACT FROM AUTHOR]

Beyond their crucial role in energy production, mitochondria harbor a distinct genome subject to epigenetic regulation akin to that of nuclear DNA. This paper delves into the nascent but rapidly evolving fields of mitoepigenetics and mitoepigenomics, exploring the sophisticated regulatory mechanisms governing mitochondrial DNA (mtDNA). These mechanisms encompass mtDNA methylation, the influence of non-coding RNAs (ncRNAs), and post-translational modifications of mitochondrial proteins. Together, these epigenetic modifications meticulously coordinate mitochondrial gene transcription, replication, and metabolism, thereby calibrating mitochondrial function in response to the dynamic interplay of intracellular needs and environmental stimuli. Notably, the dysregulation of mitoepigenetic pathways is increasingly implicated in mitochondrial dysfunction and a spectrum of human pathologies, including neurodegenerative diseases, cancer, metabolic disorders, and cardiovascular conditions. This comprehensive review synthesizes the current state of knowledge, emphasizing recent breakthroughs and innovations in the field. It discusses the potential of high-resolution mitochondrial epigenome mapping, the diagnostic and prognostic utility of blood or tissue mtDNA epigenetic markers, and the promising horizon of mitochondrial epigenetic drugs. Furthermore, it explores the transformative potential of mitoepigenetics and mitoepigenomics in precision medicine. Exploiting a theragnostic approach to maintaining mitochondrial allostasis, this paper underscores the pivotal role of mitochondrial epigenetics in charting new frontiers in medical science. [Display omitted] • Elucidating the Complex Regulatory Mechanisms of mtDNA Through Mitoepigenetic Insights. • Showcasing Cutting-Edge Methodological Advancements in Mitoepigenetic Research. • Unveiling the Theragnostic Potential of Mitoepigenetics Across Various Diseases. [ABSTRACT FROM AUTHOR]

Abstract: The glutamatergic pathway has been consistently involved in the physiopathology of depressive disorder. However a complete dissection and integration of its role in the context of other known mechanisms is lacking. We summarized and integrated the evidence of various levels of interaction between glutamatergic and monoaminergic pathways (see videos). We identified six molecular pathways, some of which with specific regional distribution within the brain. From the six pathways we identified the key proteins and their coding genes, we then provided a detailed list of possible candidates with practical suggestions for association studies planning. [Copyright &y& Elsevier]

Abstract: Treatment resistant depression (TRD) is a significant clinical and public health problem. Among others, neuroplasticity and inflammatory pathways seem to play a crucial role in the pathomechanisms of antidepressant efficacy. The primary aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within two genes implicated in neuroplasticity and inflammatory processes (the mitogen activated protein kinase 1, MAPK1 (rs3810608, rs6928, rs13515 and rs8136867), and the cyclic AMP responsive element binding protein 1, CREB1 (rs889895, rs6740584, rs2551922 and rs2254137)) was associated with antidepressant treatment resistance (according to two different definitions), in 285 Major Depressive Disorder (MDD) patients. As secondary aims, we investigated the genetic modulation of the same SNPs on response, remission and other clinical features both in MDD patients and in a larger sample including 82 Bipolar Disorder (BD) patients as well. All patients were screened in the context of a European multicenter project. No association between both the investigated genes and treatment resistance and response was found in MDD patients. However, considering remission, higher rates of CREB1 rs889895 GG genotype were reported in MDD patients. Moreover, MAPK1 rs8136867 AG genotype was found to be associated with remission in the whole sample (MDD and BD). Present results suggest that some genetic polymorphisms in both CREB1 and MAPK1 could be associated with treatment remission. Although further research is needed to draw more definitive conclusions, such results are intriguing since suggest a potential role of two genes implicated in neuroplasticity and inflammatory processes in symptom remission after antidepressant treatment. [Copyright &y& Elsevier]

Abstract: Cerebral cavernous malformations (CCMs; OMIM 116860) are vascular anomalies mostly located in the central nervous system (CNS) and occasionally within the skin and retina. Main clinical manifestations are seizure, hemorrhage, recurrent headaches, focal neurological deficits and epileptic attacks. The CCMs can occur as sporadic or autosomal dominant conditions, although with incomplete penetrance and variable clinical expression. Familial CCMs were associated with causative mutations in the CCM1 [K-Rev interaction trapped 1 (KRIT1)], CCM2 (MGC4607) and CCM3 (PDCD10) genes. This study reports the identification of a previously undescribed deletion mutation in CCM2 gene exon 5, in an Italian family with multiple cerebral cavernous malformations and epilepsy. Mutation c.502_503delAG results in a frame shift causing a TGA stop codon. This truncates the mutant CCM2 gene protein, the malcavernin, to 233 amino acids, respect to 444 amino acids of the wild-type malcavernin. By using real-time RT-PCR, we have found that the mRNA resulting from two nucleotides deletion showed a 70% reduction relative to the wild-type transcript, indicating that it may be subject to a degradation mechanism such as nonsense-mediated decay (NMD). [Copyright &y& Elsevier]

Abstract: The N-oxygenation of amines by the human flavin-containing monooxygenase (form 3) (FMO3) represents an important means for the conversion of lipophilic nucleophilic heteroatom-containing compounds into more polar and readily excreted products. In healthy individuals, virtually all Trimethylamine (TMA) are metabolized to Trimethylamine N-oxide (TMAO). Several single nucleotide polymorphisms (SNPs) of the FMO3 gene have been described and result in an enzyme with decreased or abolished functional activity for TMA N-oxygenation thus leading to TMAU, or fish-like odor syndrome. Three coding region variants, c. G472A (p.E158K) in exon 4, c. G769A (p.V257M) in exon 6, and c.A923G (p.E308G) in exon 7, are common polymorphisms identified in all population examined so far and are associated with normal or slightly reduced TMA N-oxygenation activity. However, simultaneous occurrence of 158K and 308G variants results in a more pronounced decrease in FMO3 activity. A fourth polymorphism, c. G1424A (p.G475D) in exon 9, less common in the general population, was observed in individuals suffering severe or moderate trimethylaminuria. The aim of this study was to determine the allelic and genotypic distributions of these four FMO3 variants in 528 healthy individuals collected from the Sicilian and Sardinian populations together with haplotype and linkage analyses. Finally, we present data on the genotype–phenotype correlation by ESI-MS/MS TMA/TMAO urinary determination in 158KK/308EG individuals. Variant 158K shows the same frequency in Sicilian and Sardinian populations while variant 257M was not observed in the Sardinian sampling. No significant differences were found for 308G and 475D variants among two populations. Cis-linkage between 158K and 308G was confirmed with the compound variant (158K–308G) being found in a proportion of 0.9% and 0.3% of Sicilian subjects, and 0.01% and 0.5% in Sardinian population. Urinary determination of TMA/TMAO ratio in 158KK/308EG individuals showed a considerable reduction in FMO3 activity although they do not show the classical features of trimethylaminuria as a strong body odor and breath. Our data support the conclusion that trimethylaminuria is not always accompanied by a fish-like odor, despite the coexistence in the same individual of the two variants 158K and 308G, and other factors account for the expression of that phenotype. [Copyright &y& Elsevier]

Abstract: Inflammatory pathways play a crucial role in the pathomechanisms of antidepressant efficacy. The aim of this study was to investigate whether a set of single nucleotide polymorphisms (SNPs) within cyclooxygenase-2 (COX-2, rs5275 and rs20417) and oxytocin receptor (OXTR, rs53576 and rs2254298) genes was associated with antidepressant treatment resistance, response or remission. Three hundred seventy-two patients were recruited in the context of a multicenter resistant depression study. They were genotyped for COX-2 and OXTR SNPs. Treatment resistance (according to two different definitions), response and remission were recorded. We did not observe any association between the genotypes or alleles of the selected SNPs within COX-2 and OXTR genes and treatment resistance, response and remission in the whole sample. Our results are consistent with those of some studies but not with those of other ones. Indeed, several factors could be involved in the discrepancy observed across studies. They include sample size, environmental factors, differences in ethnicity, different study designs, and different definitions of treatment resistance. [Copyright &y& Elsevier]

Abstract: The present study explores whether some single nucleotide polymorphisms (SNPs) within CREB1 (rs2709377 and rs6740584), CREBBP (rs2239317, rs2239316, rs3025702, rs130021, rs130005, rs129974 and rs9392) and CREM (rs1148247, rs4934735, rs12775799, rs6481941 and rs16935888) could be associated with schizophrenia (SKZ) and whether they could predict clinical outcomes in Korean in-patients treated with antipsychotics. Two-hundred twenty one in-patients suffering from SKZ and 170 psychiatrically healthy controls were genotyped for 10 SNPs within CREB1, CREBBP and CREM. All patients were assessed for the severity of illness at baseline and at discharge by means of the Positive and Negative Symptoms Scale (PANSS). Our findings suggest the lack of influence of SNPs under investigation in the present study on the susceptibility to SKZ and on the response to antipsychotics. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions. [Copyright &y& Elsevier]

Abstract: In this study we investigated 36 single nucleotide polymorphisms within 10 genes previously associated with major depression and bipolar disorder, as well as with the response to their treatment (ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2). No association with mood disorders and clinical outcomes was observed. [Copyright &y& Elsevier]

Fingerprint detection and Short Tandem Repeat (STR) typing are two approaches used for identification of individuals. The main goal of forensic laboratories is the development of a standardized protocol to obtain an STR profile from latent fingerprints, by typing the DNA transferred onto touched objects. The results obtained in this field derive from studies conducted under controlled laboratory conditions. Here, for the first time, we report two different profiles obtained by DNA purified by latent fingerprints enhanced with dactyloscopic powders at a crime scene, 14 years previously. DNA extraction phase was optimized to improve removal of powder and automatically conducted. Despite the low concentration of purified DNA, it was not degraded. Even if quality of the profile is influenced by several factors such as the method of acquisition and storage conditions of the fingerprint, results obtained are adequately informative and could be uploaded to the CODIS database. [ABSTRACT FROM AUTHOR]