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Genetic features of alcohol dependence have been extensively investigated in recent years. A large body of studies has underlined the important role of genetic variants not only in metabolic pathways but also in the neurobiology of alcohol dependence, mediated by the neuronal circuits regulating reward and craving. Serotonin transporter (5-HTT), encoded by the SLC6A4 gene (Solute carrier family 6-neurotransmitter transporter-member 4), is targeted by antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs) and plays a pivotal role in serotoninergic transmission; it has been associated with psychiatric diseases and alcohol dependence. Transcriptional regulation and expression of 5-HTT depend not only on epigenetic modifications, among which DNA methylation (CpG and non-CpG) is primarily involved, but also on sequence variations occurring in intron/exon regions and in untranslated regions in 5′ and 3′, being the first sequences important for the splicing machinery and the last for the binding of transcription factors and micro RNAs. This work intends to shed light on the role of sequence variations known to affect the expression or function of 5-HTT in alcohol-dependent individuals. We found a statistically significant difference in the allelic (p = 0.0083) and genotypic (p = 0.0151) frequencies of the tri-allelic polymorphism, with higher function alleles and genotypes more represented in the control population. Furthermore, we identified three haplotypes more frequent in subjects with AUD (p < 0.0001) and one more frequent in the control population (p < 0.0001). The results obtained for the tri-allelic polymorphism in alcohol dependence confirm what is already present in part of the literature. The role of haplotypes requires further studies to be clarified. [ABSTRACT FROM AUTHOR]

Klinefelter syndrome (KS) is a male genetic disease caused by the presence of an extra X chromosome, causing endocrine disorders mainly responsible for a high rate of infertility and metabolic disorders in adulthood. Scientific research is interested in identifying new biomarkers that can be predictive or prognostic of alterations strictly connected to KS. Lipocalin-2 (LCN-2, also known as NGAL) is a small protein initially identified within neutrophils as a protein related to innate immunity. Serum LCN-2 estimation seems to be a useful tool in predicting the metabolic complications caused by several pathological conditions. However, little is known about its potential role in infertility conditions. The present pilot study aims to investigate the presence of LCN-2 in the serum of a group of pre-pubertal and post-pubertal children affected by KS, compared to healthy controls. We demonstrated for the first time the presence of elevated levels of LCN-2 in the serum of KS patients, compared to controls. This increase was accompanied, in pre-pubertal KS patients, by the loss of correlation with LH and HDL, which instead was present in the healthy individuals. Moreover, in all KS individuals, a positive correlation between LCN-2 and inhibin B serum concentration was found. Despite the limited size of the sample analyzed, our preliminary data encourage further studies to confirm the findings and to extend the study to KS adult patients, to verify the predictive/prognostic value of LCN-2 as new biomarker for metabolic diseases and infertility associated with the pathology. [ABSTRACT FROM AUTHOR]

Fetal Alcohol Spectrum Disorders (FASD) encompass a range of conditions caused by prenatal alcohol consumption, leading to physical, behavioral, and learning challenges. It is a significant cause of preventable mental disability, with a prevalence rate of 7.7 cases per 1,000 individuals in the Western world. FASD includes various categories such as alcohol-related neurodevelopmental disorders (ARND), alcohol-related birth defects (ARBD), partial fetal alcohol syndrome (pFAS), and FAS. Mortality is primarily linked to external causes and individuals with FAS may have a projected lifespan of around 34 years. This review highlights the key features of FASD, including neurological impact, behavioral abnormalities, placental and congenital malformations, organic abnormalities, and hormonal and immune disruption. Additionally, potential therapeutic approaches for FASD are briefly discussed based on the different manifestations. Prevention remains the most effective strategy to reduce its incidence, although the general population’s understanding of this topic is currently insufficient. Timely diagnosis and intervention are crucial as they can significantly enhance outcomes through appropriate support and management strategies. Increasing awareness among citizens about the detrimental effects of alcohol use disorders on newborn health is of utmost importance.

Fetal Alcohol Spectrum Disorders (FASD) encompass a spectrum of clinical manifestations resulting from maternal alcohol consumption during pregnancy. This condition presents with diverse anomalies including intrauterine and extrauterine growth retardation, phenotypic abnormalities, cerebral structural anomalies, cognitive delays, and behavioral abnormalities. Regrettably, FASD remains an irreversible and epigenetic condition, with total abstention from alcohol during pregnancy being the sole effective preventive measure due to the absence of a viable therapy. Diagnosis typically occurs postnatally, based on a combination of alcohol exposure history and the presence of aforementioned physical or behavioral abnormalities. The diagnosis is not always easy to make even in the post-natal period due to the different subtypes of existing FASD. Indeed, only some of these subtypes cause behavioral or neurodevelopmental abnormalities in the absence of pathognomic physical anomalies. Although the diagnostic criteria are useful, unfortunately, there is a heterogeneity resulting from the different guidelines that are used in different countries. The aim of our review, based on a literature search of online databases including Medline, Medline Complete, PubMed, and Google Scholar, is therefore to provide an overview of the diagnostic criteria used in Italy.

Fetal Alcohol Spectrum Disorders (FASD) are pervasive disorders that impact various domains of functioning, including self-esteem, familiar and peer relationships, and academic success. The high rate of comorbidity may contribute to delayed diagnosis and treatment. Early diagnosis and intervention that aim at primary symptoms may prevent secondary disabilities and improve the outcomes. No intervention emerged as maximally effective across all symptoms and domains. Consequently, the complex pathophysiology of FASD emphasizes the need for individualized assessment and treatment by using a multimodal approach to intervention.

Drinking alcohol during pregnancy can cause congenital disabilities. J. Roquette, P. Lemoine and K.L. Jones were the first to describe these effects. In 1973, Jones and Smith coined the term Fetal Alcohol Syndrome to describe children with facial anomalies, poor growth, and learning difficulties. The caution against drinking during pregnancy has existed for centuries, including in The Bible (Judges 13:3-4). Maternal alcohol consumption is linked to congenital disabilities. To ensure safety, it is advised to abstain from alcohol during pregnancy. Fetal Alcohol Spectrum Disorder (FASD) was observed in paintings from the mid-19th century when artists began depicting moments and characters from everyday life. In 2005-2006, Italy conducted a groundbreaking study on FASD, the first in Europe. The study resulted in valuable research on FASD, contributing to prevention efforts. Unfortunately, diagnosing FASD remains a challenge in Italy. Early diagnosis and treatment are critical, and increasing the number of authorized centers to diagnose FASD is necessary to improve care. Educating ourselves about FASD is the key to creating a world where affected children receive the care they need. These guidelines include nine works dealing with all FASD aspects such as prevention, the effects on cognition, the epidemiology, the diagnostic criteria, the clinical aspects, the general effects on the body, the available treatments and the methods of detecting alcohol abuse in pregnant women.

Fetal Alcohol Spectrum Disorders (FASD) is an encompassing term used to describe a range of afflictions brought about by the consumption of alcohol during gestation. The detrimental effects primarily manifest in the central nervous system, growth, and distinctive facial features. Given that there are no known treatments for FASD, the meticulous screening for this condition in the earliest stages of pregnancy bears immense significance, ensuring the avoidance of the grievous consequences stemming from exposure to alcohol in utero. Screening measures for FASD encompass the assessment of alcohol biomarkers such as Phosphatidylethanol (PEth) in the maternal bloodstream, Fatty Acid Ethyl Esters (FAEEs) in the meconium, and Ethyl Glucuronide (EtG) in the meconium, maternal urine and hair. In particular, urinary EtG is highly sensitive and could be routinely used in pregnant women for detecting also occasional drinking. Questionnaire evaluations including AUDIT-C, T-ACE, and TWEAK, alongside a detailed Food Diary method to identify alcohol misuse and high-risk pregnancies, are also available. However, these questionnaires might provide an inadequate reflection of alcohol consumption in women due to their inclination to dissemble to comply with prevailing sociocultural expectations. Hence, this comprehensive review advocates for the indispensable integration of alcohol biomarkers detection in the course of pregnancy monitoring, as it constitutes a valuable tool for facilitating FASD screening.

Alcohol consumption during pregnancy poses significant risks to maternal and fetal health, contributing to a range of adverse outcomes collectively known as Fetal Alcohol Spectrum Disorders (FASD). This article reviews evidence-based preventive strategies aimed at mitigating the detrimental effects of prenatal alcohol exposure. Drawing upon literature from various disciplines, interventions are categorized according to their level of prevention: universal, selective, and indicated. Training of personnel and availability of official guidelines are a pre-requisite for effective prevention. Universal prevention strategies include public health campaigns, educational initiatives, and policy interventions aimed at raising awareness about the risks of prenatal alcohol exposure and promoting abstinence during pregnancy. Integrating alcohol screening and brief intervention protocols into routine prenatal care settings can help identify and support women who may be at risk of alcohol use during pregnancy. Consequently, selective and indicated interventions, identifying drinking women, may provide targeted support to pregnant women at risk. Indicated prevention interventions also encompass treatment and rehabilitation strategies for women with a known alcohol abuse problem or who have already had alcohol-exposed pregnancies. Finally, ethical issues related to the stigma associated with alcohol consumption during pregnancy are highlighted, to be considered for an effective mother and child health promotion.

Fetal alcohol spectrum disorders (FASDs) refer to a group of clinical conditions that occur in a person exposed to alcohol before birth. Neuroimaging shows abnormalities in brain structure, cortical development, white matter microstructure, and functional connectivity in individuals with FASD. These abnormalities modify the normal developmental trajectories resulting in deficits in cognition and behavior across several domains, including general intelligence, memory, language, attention, learning, visuospatial abilities, executive functioning, fine and gross motor skills, and social and adaptive functioning. This paper provides a review of the cognitive and behavioral outcomes of prenatal alcohol exposure. Updates data on FASD-specific neurobehavioral profile and its potential as a diagnostic tool will then be presented.

Fetal Alcohol Spectrum Disorders (FASD) are a condition that arises when a person is exposed to alcohol during pregnancy. The main clinical manifestations include craniofacial anomalies, growth retardation, birth defects and change in brain structure and function. These alterations can result in deficits across various domains such as cognition, executive function, memory, vision, hearing, motor skills, behavior, and social adaptation. The effects of alcohol extend beyond the brain, affecting other systems including sensory organs, heart, and kidneys. Given that diagnosing FASD involves excluding other conditions, it is crucial for physicians to be familiar with its main characteristics to facilitate early identification and implement appropriate health strategies for the patient. Moreover, there is a pressing need for primary prevention strategies centered around raising awareness about the risks associated with alcohol consumption during pregnancy. The articles for this report aimed to analyze and evaluate studies focusing on the clinical features observed in FASD children were sourced from online databases such as Medline, Medline Complete and PubMed, covering literature published between 1981 and 2024, written in English, using search terms such as fetal alcohol spectrum disorders, fetal alcohol syndrome, prenatal alcohol exposure, and alcohol-related birth defects. The evidence gathered underscores that prenatal alcohol exposure primarily affects the brain and its functions, resulting in severe impacts. Furthermore, abnormalities in other vital organs such as the sensory, cardiovascular, and renal systems are frequently observed.

The umbrella term Fetal Alcohol Spectrum Disorders (FASD) brings together under its definition a heterogeneous continuum of disabilities linked by a common etiology and pathogenesis: exposure to alcohol during intrauterine life. Despite extensive research, definitive toxic thresholds remain elusive, underscoring the recommendation for complete alcohol abstinence during pregnancy and lactation. FASD poses diagnostic challenges due to its varied presentations and heterogeneous phenotype. Consequently, no singular diagnostic guideline exists, with multiple expert-driven diagnostic systems globally available. This review aims to synthesize recent and notable guidelines facilitating FASD diagnosis. While efforts were made to include the latest diagnostic systems, determining which scheme is best applied to each individual patient population necessitates clinician discretion. In Italy, the guidelines proposed by Hoyme, revised in 2016, are commonly utilized, yet comparative analysis among guidelines offers valuable insights into their historical context and diagnostic utility. Our discussion explores both similarities and discrepancies among systems for diagnosing FASD, shedding light on their evolution and practical application. The objective of our work was to compare in a practical and precise manner the various existing guidelines used globally regarding the diagnosis of FAS. Our review therefore proposes the diagnostic criteria used by the various working groups and compares them, trying to create a practical comparison between the various guidelines, identifying differences and similarities.

Introduction: Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women., Materials and Methods: We conducted a study of two cohorts of 1.5 year-old infants (of mothers without a history of alcohol abuse) with or without meconium samples positive to both EtG and FAEEs and we evaluated their cognitive-behavioral development by the Griffiths Mental Developmental Scale (GMDS) method. Our protocol included 8 infants with meconium positive to alcohol metabolites (EtG and FAEEs) and 7 with meconium negative to alcohol metabolites., Results: None of the 8 alcohol metabolites positive meconium infants exhibited distinctive facial features and growth retardation of severe FASD, showing that other factors may contribute to the FASD onset but elevations in EtG and FAEEs in the meconium were significantly associated with disrupted neurodevelopment and adaptive functions within the first year and a half of life. Indeed, we found out that infants with meconium positive for both EtG and FAEEs, although without displaying any FASD morphological features, had a delay in the fine regulation of their own locomotory capabilities., Conclusions: Further analyses and larger studies are needed to estimate the right link between prenatal alcohol exposure and the different range of disorders connected but this study provides an additional step in the field of FASD in order to suggest early treatments for at-risk newborns and infants.

Alcohol use disorders are responsible for 5.9% of all death annually and 5.1% of the global disease burden. It has been suggested that alcohol abuse can modify gene expression through epigenetic processes, namely DNA and histone methylation, histone acetylation, and microRNA expression. The alcohol influence on epigenetic mechanisms leads to molecular adaptation of a wide number of brain circuits, including the hypothalamus-hypophysis-adrenal axis, the prefrontal cortex, the mesolimbic-dopamine pathways and the endogenous opioid pathways. Epigenetic regulation represents an important level of alcohol-induced molecular adaptation in the brain. It has been demonstrated that acute and chronic alcohol exposure can induce opposite modifications in epigenetic mechanisms: acute alcohol exposure increases histone acetylation, decreases histone methylation and inhibits DNA methyltransferase activity, while chronic alcohol exposure induces hypermethylation of DNA. Some studies investigated the chromatin status during the withdrawal period and the craving period and showed that craving was associated with low methylation status, while the withdrawal period was associated with elevated activity of histone deacetylase and decreased histone acetylation. Given the effects exerted by ethanol consumption on epigenetic mechanisms, chromatin structure modifiers, such as histone deacetylase inhibitors and DNA methyltransferase inhibitors, might represent a new potential strategy to treat alcohol use disorder. Further investigations on molecular modifications induced by ethanol might be helpful to develop new therapies for alcoholism and drug addiction targeting epigenetic processes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Reactive oxygen species (ROS) are highly reactive molecules derived from molecular oxygen (O 2 ). ROS sources can be endogenous, such as cellular organelles and inflammatory cells, or exogenous, such as ionizing radiation, alcohol, food, tobacco, chemotherapeutical agents and infectious agents. Oxidative stress results in damage of several cellular structures (lipids, proteins, lipoproteins, and DNA) and is implicated in various disease states such as atherosclerosis, diabetes, cancer, neurodegeneration, and aging. A large body of studies showed that ROS plays an important role in carcinogenesis. Indeed, increased production of ROS causes accumulation in DNA damage leading to tumorigenesis. Various investigations demonstrated the involvement of ROS in gliomagenesis. The most common type of primary intracranial tumor in adults is represented by glioma. Furthermore, there is growing attention on the role of the Nerve Growth Factor (NGF) in brain tumor pathogenesis. NGF is a growth factor belonging to the family of neurotrophins. It is involved in neuronal differentiation, proliferation and survival. Studies were conducted to investigate NGF pathogenesis's role as a pro- or anti-tumoral factor in brain tumors. It has been observed that NGF can induce both differentiation and proliferation in cells. The involvement of NGF in the pathogenesis of brain tumors leads to the hypothesis of a possible implication of NGF in new therapeutic strategies. Recent studies have focused on the role of neurotrophin receptors as potential targets in glioma therapy. This review provides an updated overview of the role of ROS and NGF in gliomagenesis and their emerging role in glioma treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)