Genetic modifiers of cognitive decline in PSEN1 E280A Alzheimer's disease.

Introduction: Rate of cognitive decline (RCD) in Alzheimer's disease (AD) determines the degree of impairment for patients and of burden for caretakers. We studied the association of RCD with genetic variants in AD.

Methods: RCD was evaluated in 62 familial AD (FAD) and 53 sporadic AD (SAD) cases, and analyzed by whole-exome sequencing for association with common exonic functional variants.

Positive affect dysregulation and its relation to binge eating size and frequency.

Negative affect is an established predictor of binge eating, yet less is known about positive affect. Low positive affect has been theorized to increase binge eating, but a better understanding is needed on the relationship between positive affect and binge eating frequency and size. Participants were 182 treatment-seeking adults (76% self-identified as female; 45% self-identified their race as Black and 40% as White; and 25% self-identified their ethnicity as Hispanic/Latino) with self-reported recurrent binge eating (≥12 binge episodes in the past 3  months).

Monthly correlates of longitudinal child mental health during the COVID-19 pandemic according to children and caregivers.

Multiple reviews identify the broad, pervasive initial impact of the global COVID-19 pandemic on the mental health of children, who may be particularly vulnerable to long-term psychiatric sequelae of the ongoing pandemic. However, limited longitudinal research examines persistence of, or change in, children's distress or psychiatric symptomatology. From June 2020 through December 2021, we enrolled two cohorts of families of children aged 8-13 from Southwestern Ontario into a staggered baseline, longitudinal design that leveraged multi-informant report (N = 317 families).

Impulsive and Omission Errors: Potential Temporal Processing Endophenotypes in ADHD.

Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in individuals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 individuals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms.

Children's Mental Health in Southwestern Ontario during Summer 2020 of the COVID-19 Pandemic.

Objective: COVID-19 presents an unprecedented global crisis. Research is critically needed to identify the impact of the pandemic on children's mental health including psychosocial factors that predict resilience, recovery, and persistent distress. The present study collected data in June-July 2020 to describe children's mental health during the initial phase of the pandemic, including the magnitude and nature of psychiatric and psychological distress in children, and to evaluate social support as a putative psychosocial moderator of children's increased distress.

Case Report: Cytoreductive Surgery and HIPEC Associated With Liver Electrochemotherapy in a Cholangiocarcinoma Patient With Peritoneal Carcinomatosis and Liver Metastasis Case Report.

Cholangiocarcinoma (CCA) is the second most common primary tumor of the liver, and the recurrence after hepatic resection (HR), the only curative therapy, is linked with a worse prognosis. Systemic chemotherapy (SC) and liver loco-regional treatments, like trans-arterial chemoembolization (TACE) or radio embolization (TARE), have been employed for the treatment of unresectable intrahepatic metastasis (IM) with benefit on overall survival (OS), but SC has a limited effect on peritoneal metastasis (PM). In the last years, novel treatments like electrochemotherapy (ECT) with bleomycine (BLM) for IM and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) for PM have been applied in small series but with encouraging results.

A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer's disease.

Presenilin-1 (PSEN1) mutations cause familial Alzheimer's disease (FAD) characterized by early age of onset (AoO). Examination of a large kindred harboring the PSEN1-E280A mutation reveals a range of AoO spanning 30 years. The pathophysiological drivers and clinical impact of AoO variation in this population are unknown.

Mutations in sphingolipid metabolism genes are associated with ADHD.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk.

Familial Alzheimer's Disease and Recessive Modifiers.

Alzheimer's disease (AD) is progressive brain disorder that affects ~ 50 million people worldwide and has no current effective treatment. AD age of onset (ADAOO) has shown to be critical for the identification of genes that modify the appearance of AD signs and symptoms in a specific population. We clinically characterized and whole-exome genotyped 71 individuals with AD from the Paisa genetic isolate, segregating the (PSEN1) E280A dominant fully penetrant mutation, and analyzed the potential recessive effects of ~ 50,000 common functional genomic variants to the ADAOO.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Comprehensive Review.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology that is recognized by the World Health Organization (WHO) and the United States Center for Disease Control and Prevention (US CDC) as a disorder of the brain. The disease predominantly affects adults, with a peak age of onset of between 20 and 45 years with a female to male ratio of 3:1. Although the clinical features of the disease have been well established within diagnostic criteria, the diagnosis of ME/CFS is still of exclusion, meaning that other medical conditions must be ruled out.

Experimental Models of Glaucoma: A Powerful Translational Tool for the Future Development of New Therapies for Glaucoma in Humans-A Review of the Literature.

Glaucoma is a common complex disease that leads to irreversible blindness worldwide. Even though preclinical studies showed that lowering intraocular pressure (IOP) could prevent retinal ganglion cells loss, clinical evidence suggests that lessening IOP does not prevent glaucoma progression in all patients. Glaucoma is also becoming more prevalent in the elderly population, showing that age is a recognized major risk factor.

Uveitis and Multiple Sclerosis: Potential Common Causal Mutations.

Uveitis, defined as inflammation of the uveal tract of the eye, is a leading cause of blindness and visual impairment throughout the world. The etiology of uveitis is complex, and autoimmunity plays a major role in its pathogenesis. Intermediate uveitis (IU), a subtype of ocular inflammation, has been associated with systemic autoimmune disorders, specifically with multiple sclerosis (MS).

Congenital Leptin Deficiency and Leptin Gene Missense Mutation Found in Two Colombian Sisters with Severe Obesity.

Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity. It is caused by mutations in the leptin () gene, which encodes the protein product leptin. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities.

Generation of one iPSC line (IMEDEAi006-A) from an early-onset familial Alzheimer's Disease (fAD) patient carrying the E280A mutation in the PSEN1 gene.

The mutation E280A in PSEN1 (presenilin-1) is the most common cause of early-onset familial Alzheimer's Disease (fAD). It presents autosomal dominant inheritance and frequently leads to the manifestation of the disease in relatively young individuals. Here we report the generation of one PSEN1 E280A iPSC line derived from an early-onset patient.

ADGRL3 (LPHN3) variants predict substance use disorder.

Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD.

Short-term antidepressant treatment has long-lasting effects, and reverses stress-induced decreases in bone features in rats.

Antidepressants are among the most-prescribed class of drugs in the world and though weight gain is a common outcome of antidepressant treatment, that effect is not well understood. We employed an animal model comprised of 2 weeks of chronic restraint stress with antidepressant treatment, followed by diet-induced obesity. We showed that short-term antidepressant treatment had long-lasting effects, not only leading to weight gain, but also enhancing trabecular and cortical bone features in rats; therefore, weight gain in this model was different from that of the classic diet-induced obesity.

Neuroimmunomodulation in Major Depressive Disorder: Focus on Caspase 1, Inducible Nitric Oxide Synthase, and Interferon-Gamma.

Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its incidence is expected to increase. Despite tremendous efforts to understand its underlying biological mechanisms, MDD pathophysiology remains elusive and pharmacotherapy outcomes are still far from ideal. Low-grade chronic inflammation seems to play a key role in mediating the interface between psychological stress, depressive symptomatology, altered intestinal microbiology, and MDD onset.

Leptin: role over central nervous system in epilepsy.

Adipose tissue is a dynamic organ with different effects on the body. Many of these effects are mediated by leptin, a hormone strongly involved in regulation of feeding and energy metabolism. It has an important role as a mediator of neuronal excitatory activity and higher brain functions.

Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease.

The identification of novel genetic variants contributing to the widespread in the age of onset (AOO) of Alzheimer's disease (AD) could aid in the prognosis and/or development of new therapeutic strategies focused on early interventions. We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia, Colombia. These individuals belong to the world largest multigenerational and extended pedigree segregating AD as a consequence of a dominant fully penetrant mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the late 1970s.

Assessing opportunities and challenges for establishing a national program to distribute cord blood for research.

Background: Research is needed to enhance cord blood (CB) transplantation outcomes and to develop new clinical applications. Based on quality criteria for transplantation, CB collected by public CB banks (CBBs) is often unsuitable for banking, but may still be valuable for research. Canadian researchers have described a need for a centralized program providing ethically sourced CB for research projects.

Genetics of non-syndromic childhood obesity and the use of high-throughput DNA sequencing technologies.

Background: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors.

Objectives: To review recent advances in the field of the genetics of obesity.