Attitudes of Family Members and Caregivers Regarding Alzheimer's Disease Pre-Symptomatic Screening.

Background: In recent years, studies have examined the acceptability and attitudes that influence the intention to early screen for Alzheimer's disease (AD) in the general population, older people, carers, and asymptomatic individuals who report a family history of AD. However, it remains unclear what specific factors promote or reduce the acceptability of pre-symptomatic screening. Objective: The aim of this study is to explore the attitudes of family and non-family members as well as caregivers and non-caregivers toward the pre-symptomatic screening of AD. Methods: A total of 213 participants completed the Perceptions regarding pRE-symptomatic Alzheimer's Disease Screening (PRE-ADS) Questionnaire. Group comparisons using t-test and one-way ANOVA were used to examine differences in attitudes toward pre-symptomatic screening regarding age, family history, knowing someone with AD, influence of depression, and feelings of anxiety. The subscale "Acceptability of Screening" was developed to investigate the willingness to undergo pre-symptomatic screening. Results: Participants with a family history showed greater acceptance of pre-symptomatic screening while both caregivers and non-caregivers had similar attitudes. People with a family history as well as those with personal connections to dementia indicate a greater need for knowledge. The findings suggest that younger adults appear to perceive less harm from testing, whereas those who experience higher levels of anxiety and depression seem to perceive more testing harms. Conclusions: Comparing the attitudes of people with and without a family history as well as caregivers and non-caregivers toward pre-symptomatic screening of AD is critical to understand the differences between these groups and develop comprehensive screening programs.

The Reproductive Lifespan of Ovarian Follicle.

The functional unit within mammalian ovaries is the ovarian follicle. The development of the ovarian follicle is a lengthy process beginning from the time of embryogenesis, passing through multiple different stages of maturation. The purpose of this review is to describe the most basic events in the journey of ovarian follicle development, discussing the importance of ovarian reserve and highlighting the role of several factors that affect oocyte quality and quantity during aging including hormonal, genetic and epigenetic factors. Novel, promising anti-aging strategies are also discussed.

GLP-1 Receptor Agonists: A New Treatment in Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent data highlight similarities between neurodegenerative diseases, including PD and type 2 diabetes mellitus (T2DM), suggesting a crucial interplay between the gut-brain axis. Glucagon-like peptide-1 receptor (GLP-1R) agonists, known for their use in T2DM treatment, are currently extensively studied as novel PD modifying agents. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles and clinical trials regarding GLP-1R agonists and PD published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Many data on animal models and preclinical studies show that GLP1-R agonists can restore dopamine levels, inhibit dopaminergic loss, attenuate neuronal degeneration and alleviate motor and non-motor features of PD. Evidence from clinical studies is also very promising, enhancing the possibility of adding GLP1-R agonists to the current armamentarium of drugs available for PD treatment.

The Genetics behind Sulfation: Impact on Airway Remodeling.

In COPD, chronic inflammation and exposure to irritants, such as cigarette smoke, lead to the thickening of bronchial walls. This results from increased deposition of collagen and other extracellular matrix components, contributing to the narrowing of airways. Nevertheless, it is widely recognized that COPD is an inflammatory disorder marked by partially reversible airflow limitation wherein genetic factors interact with the environment. In recent years, numerous investigations have substantiated the correlation between gene polymorphisms and COPD. SUMF1 has been implicated in diverse cellular processes, including lysosomal function and extracellular matrix maintenance, both of which play pivotal roles in respiratory health. The genetic variations in SUMF1 could lead to an imbalanced sulfation in the extracellular matrix of lung tissue, potentially playing a role in the onset of COPD. Recent studies have uncovered a potential link between dysregulation of SUMF1 and COPD progression, shedding light on its involvement in the abnormal sulfatase activity observed in COPD patients. Through a comprehensive review of current literature and experimental findings, this article aims to contribute to the growing body of knowledge surrounding the genetic intricacies concerning sulfation of airway remodeling and possible pharmacological applications in COPD and asthma management.

Syndromic and Monogenic Obesity: New Opportunities Due to Genetic-Based Pharmacological Treatment.

Obesity is a significant health problem with a continuously increasing prevalence among children and adolescents that has become a modern pandemic during the last decades. Nowadays, the genetic contribution to obesity is well-established. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles, and meta-analyses regarding the genetics of obesity and current pharmacological treatment, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between December 2022 and December 2023. We used the terms "obesity", "genetics", "monogenic", "syndromic", "drugs", "autosomal dominant", "autosomal recessive", "leptin-melanocortin pathway", and "children" in different combinations. Recognizing the genetic background in obesity can enhance the effectiveness of treatment. During the last years, intense research in the field of obesity treatment has increased the number of available drugs. This review analyzes the main categories of syndromic and monogenic obesity discussing current data on genetic-based pharmacological treatment of genetic obesity and highlighting the necessity that cases of genetic obesity should follow specific, pharmacological treatment based on their genetic background.

The Genetic Landscape of Sleep Disorders in Parkinson's Disease.

Parknson's disease (PD) is the second most common neurodegenerative disease, affecting 1% of people aged over 60. PD is characterized by a wide range of motor symptoms, however the clinical spectrum of PD covers a wide range of non-motor symptoms, as well. Sleep disorders are among the most common non-motor symptoms of PD, can occur at any stage of the disease and significantly affect quality of life. These include rapid eye movement sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive sleep apnea (OSA) and circadian rhythm disturbances. One of the main challenges in PD research is identifying individuals during the prodromal phase of the disease. Combining genetic and prodromal data may aid the early identification of individuals susceptible to PD. This review highlights current data regarding the genetic component of sleep disorders in PD patients, focusing on genes that have currently been associated with this PD co-morbidity.

Current genetic data on depression and anxiety in Parkinson's disease patients.

Parkinson's disease (PD) is a common neurodegenerative disorder affecting about 1 % of the population over the age of 60 years. PD is characterized by a wide spectrum of symptomatology including not only motor symptoms but non-motor symptoms, as well. Depression is one of the most common non-motor manifestations, and the most frequent neuropsychiatric comorbidity in PD. Neuropsychiatric symptoms like depression and anxiety may precede the appearance of motor features, highlighting their importance in the early detection of the disease and its strategic management. This review discusses the possible genetic background of the development of these neuropsychiatric symptoms in PD patients analyzing current genetic data associated with this clinical entity.

Janus Kinase Inhibitors and Interstitial Lung Disease Associated With Pediatric Rheumatic Diseases: An Unexplored Field.

Rheumatic diseases are often complicated by lung disease, commonly presenting as interstitial lung disease (ILD), with potentially detrimental consequences for patient survival. Although less frequent in pediatric patients, pulmonary involvement may be observed in almost all childhood-onset rheumatic conditions. The development of biological disease-modifying anti-rheumatic drugs has significantly improved clinical outcomes. However, disease remission is not always complete or long-lasting, and treatment may need to be discontinued due to adverse effects. A novel class of drugs, namely Janus kinase inhibitors (JAKis), has been proposed to provide a significant survival benefit for patients with rheumatic diseases. Despite the ample literature on the efficacy and safety of JAKis in rheumatic disease, only a few studies have investigated the effectiveness of these drugs in patients with pulmonary involvement, and only two case reports have presented results in pediatric patients. We provide an overview of the rationale for using JAKis in ILDs associated with rheumatic disease and summarize the main studies evaluating their efficacy in both adult and pediatric patients. The present review highlights the need for controlled long-term studies to assess the efficacy and safety of JAKis in pediatric rheumatic disease complicated by lung disease.

Association of microRNA Polymorphisms with Toxicities Induced by Methotrexate in Children with Acute Lymphoblastic Leukemia.

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non-Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are nephrotoxicity, mucositis, and myelosuppression, especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5'-regulatory regions of genes. Recent studies have demonstrated a significant role of microRNAs (miRNAs) in the transport and metabolism of drugs and in the regulation of target genes. In the last few years, the number of annotated miRNAs has continually risen, in addition to the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects.

Attitudes, Motivations, and Barriers to Pre-Symptomatic Alzheimer's Disease Screening: Development and Validation of the 'Perceptions regarding pRE-symptomatic Alzheimer's Disease Screening' (PRE-ADS) Questionnaire.

BACKGROUND: Pre-symptomatic screening methods for detecting a higher risk of Alzheimer's disease (AD) are gaining popularity; thus, more people are seeking these tests. However, to date, not much is known about the attitudes toward pre-symptomatic AD screening. OBJECTIVE: The goal of this study is to examine the psychometric properties of a tool for assessing the attitudes, barriers, and motivations to pre-symptomatic AD screening. METHODS: This is a cross-sectional study performed on 208 Greek participants (189 students and 19 caregivers) provided with an online questionnaire. Psychometric properties were assessed through the examination of its construct validity (principal component analysis) and internal consistency. RESULTS: Exploratory factor analysis revealed the presence of four factors. The first factor is labeled as "Perceived harms of testing" (10 items), the second "Acceptance of testing" (5 items), the third "Perceived benefits of testing" (6 items), and the fourth factor "Need for knowledge" (4 items). The reliability (internal consistency) of each factor separately was acceptable to good (0.70-0.87) while the internal consistency of the overall questionnaire (25 items) was good (Cronbach's α=0.82). CONCLUSION: PRE-ADS is a valid questionnaire that might help in the research of peoples' attitudes related to the pros and cons of pre-symptomatic screening for AD, and the development of effective counseling programs and prevention strategies. However, future research is required in the target population.

Adenoviral Infections in Neonates: A Case-Based Literature Review.

Adenoviral infections in neonates are associated with high rates of mortality due to the lack of humoral immunity. A comprehensive search of published literature in PubMed, Google Scholar, and Science Direct electronic databases was conducted for case reports published between the years 1990 and 2021. The aim of our study is to investigate the risk factors, clinical manifestations, treatment, and outcomes of adenoviral infections in neonates. In our study, 36 cases were included. The most common type of infection was disseminated one (14/36, 38.8%), followed by adenoviral pneumonia (13/36, 36.1%). Cidofovir was administered in seven cases (19.4%), and death was reported in six of them. One preterm low birthweight neonate with disseminated adenoviral infection was treated with a combination of cidofovir, intravenous immune globulin, and haploidentical virus-specific T lymphocytes (VSTs) and survived. In this review, we found a statistically significant difference in the outcome based on the type of adenoviral infection (p=0.001). Disseminated infection and pneumonia are associated with the worst prognosis. In addition, mortality was observed to be higher in neonates with disseminated disease in contrast to neonates with localized infection (p=0.002). However, the antiviral treatment had no statistically significant effect on the mortality rate (p=0.137). There is a necessity for further investigation and randomized studies to validate the results of the present study.

SORL1 mutation in a Greek family with Parkinson's disease and dementia.

Whole exome sequencing and linkage analysis were performed in a three generational pedigree of Greek origin with a broad phenotypic spectrum spanning from Parkinson's disease and Parkinson's disease dementia to dementia of mixed type (Alzheimer disease and vascular dementia). We identified a novel heterozygous c.G1135T (p.G379W) variant in SORL1 which segregated with the disease in the family. Mutation screening in sporadic Greek PD cases identified one additional individual with the mutation, sharing the same 12.8Mb haplotype. Our findings provide support for SORL1 mutations resulting in a broad range of additional phenotypes and warrants further studies in neurodegenerative diseases beyond AD.

Novel Mutations Involved in Charcot-Marie-Tooth 4C and Intrafamilial Variability: Let's Not Miss the Forest for the Trees.

Charcot-Marie-Tooth 4C is characterized by early-onset, rapid progression, and mainly associated with SH3TC2 gene mutations. We reported a male patient carrying a novel heterozygous nonsense mutation in SH3TC2 gene along with a heterozygous known pathogenic mutation. Symptoms began at 15 months and by 14 years, he presented significant motor impairment. Both parents exhibited one of the mutations in the heterozygous state, while his 8-year-old brother carried the same compound heterozygosity, showing only a mild phenotype. In our case, we discussed the contribution of compound heterozygosity to intrafamilial variability in Charcot-Marie-Tooth and the role of modifying genes.

Pharmacogenetics and levodopa induced motor complications.

AIM: L-dopa remains the most effective symptomatic therapy for Parkinson's disease (PD) but unfortunately, its chronic use is often associated with motor complications. This review highlights the importance of pharmacogenetics in an individualised PD therapeutic approach. MATERIAL AND METHODS: review of the literature was done. RESULTS: PD patients show remarkable heterogeneity in their response to L-dopa and this profound interindividual heterogeneity suggests that there is a genetic predisposition. CONCLUSIONS: The impact of the genetic makeup of every individual on PD treatment appears to be of great importance in order to achieve not only the optimum therapeutic effect, but also with minimal side effects.

D620N mutation in the VPS35 gene and R1205H mutation in the EIF4G1 gene are uncommon in the Greek population.

Recently, vacuolar protein sorting 35 (VPS35) and eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) have been identified as new causal Parkinson's disease (PD) genes, with the VPS35 D620N and EIF4G1 R1205H mutations being identified in both autosomal dominant late-onset familial and sporadic PD patients. However, the frequencies of these two mutations among different ethnic groups vary. We studied the VPS35 D620N and EIF4G1 R1205H mutations in a total of 333 individuals, 202 Greek patients with sporadic PD and 131 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. None of our studied individuals carried these two mutations. Our data support that the VPS35 D620N and EIF4G1 R1205H mutations are not a common cause of PD in the Greek population.

Association Between rs2200733 Polymorphism on Chromosome 4q25 and Atrial Fibrillation in a Greek Population.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia with evidence of genetic susceptibility. The rs2200733 single-nucleotide polymorphism (SNP) in a non-coding region on chromosome 4q25 has been associated with AF. The purpose of this case-control study was to examine the possible association of the rs2200733 polymorphism with AF in the Greek population. METHODS: A total of 295 individuals, 167 AF patients and 128 controls, were genotyped for the presence of the rs2200733 polymorphism using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLPs) method. RESULTS: The T/T genotype and the T allele were detected more frequently in patients with AF compared to controls (13.2% vs. 2.3%, p=0.001, and 29.6% vs. 17.9%, p=0.001), suggesting that the rs2200733 polymorphism increases susceptibility to AF in the Greek population. In a multivariate stepwise analysis that included many conventional precipitating factors for AF, T/T genotype and left atrium (LA) diameter were the only independent predictors of AF (OR 1.74, 95% CI: 1.40-2.98, p=0.005, and OR 2.88, 95% CI: 1.835.62, p<0.001, respectively). A trend of association was observed between the T/T genotype and lone AF (p=0.08). CONCLUSIONS: Our results suggest that SNP rs2200733 confers a significant risk of AF in the Greek population, providing further support to the previously reported association between AF and rs2200733 polymorphism on chromosome 4q25.

Benign epilepsy with centrotemporal spikes: Relationship between type of seizures and response to medication in a Greek population.

PURPOSE: Benign epilepsy with centrotemporal spikes (BECTS) is considered to be the most common childhood epileptic syndrome. We studied the relationship between the type of seizures and response to medication in a Greek population. MATERIALS AND METHODS: We studied 60 neurodevelopmentally normal children diagnosed with BECTS. Children were subdivided into three groups, based on type of seizures: Group A comprised 32 children with generalized tonic-clonic seizures, Group B 19 children with focal seizures and Group C 9 children with focal seizures with secondary generalization. All patients in the present study were started on an antiepileptic medication after the third seizure (sodium valproate, carbamazepine, and oxcarbazepine), and we studied the response to medication. RESULTS: 10 from 13 (76.92%) of patients in Group A, 13 from 15 (86.66%) patients in Group B, and all 6 patients (100%) in Group C started carbamazepine or oxcarbazepine had a favorable respond. Similarly, 16 from 19 (84.2%) of patients in Group A, 3 from 4 patients (75%) in Group B, and 1 from 3 patients (33.3%) in Group C, started sodium valproate responded well to medication. CONCLUSIONS: The majority of children responded well to the first antiepileptic treatment and had a favorable outcome, regardless of type of seizures. 88.3% of children became seizure free by 1 or 2 years after seizure onset. These findings are indicative that the type of seizures has no major effect neither in response to antiepileptic treatment or in the final outcome. Further research in a larger number of children is needed.

Absence of association of FCGR2A gene polymorphism rs1801274 with Kawasaki disease in Greek patients.

Kawasaki disease is an acute, febrile syndrome in infancy, characterised by vasculitis of medium-sized arteries, and affects predominantly young children. Family-based studies on Kawasaki disease supports the contribution of genetic factors in disorder manifestation. In a recent genome-wide association study, the polymorphism rs1801274 of FCGR2A [Fc fragment of immunoglobulin G, low-affinity IIa, receptor] gene has been implicated in disease pathogenesis. The aim of the present study was to explore the association of this variant, for the first time, in a group of Kawasaki-diseased patients of Greek origin. A total of 47 Kawasaki-diseased children and 50 control subjects were enrolled in the study. Polymerase chain reaction-restriction fragment length polymorphism assay was performed in rs1801274 genotyping. No association was observed between this polymorphism genotypes' or alleles' distribution between Kawasaki-diseased patients and controls. Furthermore, no association was revealed between this polymorphism and cardiovascular complications in Kawasaki-diseased patients. In the literature, the reported data over this polymorphism association with Kawasaki disease in Caucasian patients are contradictory. In addition, the disease shows low prevalence in the Caucasian populations. Therefore, the independent genetic association studies on rs1801274 with Kawasaki disease in various Caucasian groups increase the amount of genetic data, which could be used in a future meta-analysis, increasing the statistical power of the resultant conclusions.