ABSTRACT
Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a neuropsychiatric condition in which susceptible alleles along with epigenetic states contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism, as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Humans , Autism Spectrum Disorder/genetics , Alleles , Biological Evolution , Epigenesis, GeneticABSTRACT
The human brain is constantly exposed to air pollutants, some of which might be disruptive or even lethal to certain neurons implicated in abstract features of cognitive function. In this review, we present new evidence from behavioral and neural studies in humans, suggesting a link between indoor fine particulate matter and decision-making behavior. To illustrate this relationship, we use qualitative sources, such as historical documents of the Vietnam War to develop hypotheses of how aerial transmission of pollutants might obstruct alternative choices during the evaluation of policy decisions. We first describe the neural circuits driving decision-making processes by addressing how neurons and their cognate receptors directly evaluate and transduce physical phenomena into sensory perceptions that allow us to decide the best course of action among competing alternatives. We then raise the possibility that indoor air pollutants might also impact cell-signaling systems outside the brain parenchyma to further obstruct the computational analysis of the social environment. We also highlight how particulate matter might be pathologically integrated into the brain to override control of sensory decisions, and thereby perturb selection of choice. These lines of research aim to extend our understanding of how inhalation of airborne particulates and toxicants in smoke, for example, might contribute to cognitive impairment and negative health outcomes.
ABSTRACT
An estimated 95-97% of Parkinson's disease (PD) cases are idiopathic, emphasizing the absence of a clear etiologic linkage for this debilitating, neurodegenerative, and progressive motor disease. Increasing evidence suggests a peripheral disease origin and the gradual transition of a pathological process along the gut-brain axis and olfactory routes into the brain. This disease pattern is reminiscent of an infectious process and suggests the presence of one or multiple infectious agents, such as bacteria, viruses, fungi, or prion-like proteins. This unusual paradigm, known as Braak's hypothesis, was first described by the scientist who developed the staging standard for cellular PD pathology and. Here, we describe a case where the small, anaerobic, Gram-positive Cutibacterium acnes was recurrently isolated from intraoperative spinal tissues in a patient with early-onset PD. C. acnes is also the bacterium that we previously isolated from cadaveric PD brain tissue. Both observations are consistent with Braak's hypothesis underscoring the importance of homeostasis and maintained immune-competence for healthy aging of the body and mind.
ABSTRACT
Oxytocin plays an important role in the regulation of parturition as this peptide hormone promotes uterine smooth muscle contractility in gravid women undergoing labor. Here, we review the impact of Pitocin administration on behavioral outcomes in the pediatric population. Pitocin is a synthetic preparation of oxytocin widely used in the obstetric practice for the management of labor and postpartum hemorrhage. We begin by tracing the neuroanatomy of oxytocin-containing cells from an evolutionary perspective and then summarize key findings on behavioral and neural activity reported from offspring dosed with Pitocin during vaginal delivery. Finally, we discuss future directions that are experimentally tractable for understanding the developmental consequences of Pitocin administration on a small but growing subset of children worldwide. Given that fetal past experiences can shape the future behavior of the adult, further work on oxytocin signaling pathways will provide valuable references and insights for early-brain development and state-dependent regulation of behavioral outcome.
ABSTRACT
Tumors of salivary glands are uncommon and comprise of about 2%-4% of all head and neck tumors. About 75%-80% of these tumors are benign and include pleomorphic adenoma, monomorphic adenoma, oncocytoma, and papillary cystadenoma lymphomatosum. Mucoepidermoid carcinoma is the most common malignant tumor of salivary glands, representing 5-10% of all salivary gland tumors. Although known to be metastatic to local lymph nodes, distant metastases are rare (especially, with low and intermediate grade tumors). Histologic grade and the expression of various mucin glycoproteins are useful prognostic indicators. We present a case of mucoepidermoid carcinoma of parotid gland origin with distant metastases which is an uncommon occurrence with intermediate grade tumors. Also, this is the first reported case of humoral hypercalcemia of malignancy secondary to mucoepidermoid carcinoma.
ABSTRACT
A 34-year-old man presented to the hospital with right-sided headache. He was diagnosed with GBM. He underwent resection of the tumor with placement of carmustine impregnated wafers. Then he underwent adjuvant chemotherapy with temozolamide. Before the completion of chemotherapy he had a recurrence. He underwent re-resection with placement of carmustine impregnated wafers. Subsequently he had eighteen cycles of salvage biochemotherapy with bevacizumab and irinotecan. To date, routine MRI scans of the brain have not shown evidence of recurrence. He continues to be in remission three years after treatment with bevacizumab and irinotecan.
