Mahoneyadamsen7497
In this review, we summarize the genetics and mechanisms of sitosterolemia and sterol trafficking, and provide an update on the understanding of the prevalence of ABCG5 and ABCG8 variants and their role in human disease.
Defects in ABCG5/G8 result in the accumulation of xenosterols. It had been previously thought that near total LoF of one of the proteins was required to cause pathology. However, recently there was the first report of a patient with Sitosterolemia who was heterozygous for mutations in both genes. Moreover, large population studies have demonstrated the even simple heterozygous carriers are associated with altered lipid profiles and cardiovascular risk. Broader screening has added to the rapidly growing list of gene variants indicating that the prevalence of ABCG5/G8 variants is higher than previous thought, especially in patients with hypercholesterolemia.
These findings support a strategy of measuring xenosterol levels in patients with hypercholesterolemia to screen for ABCG5/G8 variants, and then tailoring treatment with a sterol absorption inhibitor, like ezetimibe, where indicated. Xenosterol trafficking affects remnant clearance and maybe pathogenically linked to the increased risk of atherosclerosis.
These findings support a strategy of measuring xenosterol levels in patients with hypercholesterolemia to screen for ABCG5/G8 variants, and then tailoring treatment with a sterol absorption inhibitor, like ezetimibe, where indicated. Xenosterol trafficking affects remnant clearance and maybe pathogenically linked to the increased risk of atherosclerosis.
This review scoped recent (2019-2020) literature investigating the association between urbanization and eating disorders, and the putative role of urbanization as a direct or indirect risk factor.
There are few epidemiological studies which investigated adequately direct or indirect association between urban domicile and eating disorders. Findings suggest that urbanization is a complex phenomenon and its effects on eating behaviour are indirect, for example, because of other important social and environmental features, such as the amount of 'green' space, 'Western' thin idealization, and poverty. The review also supports others indicating an increase of eating disorders in Africa and Asia. The majority of research includes only adolescent and young woman.
It does not seem likely that metropolitan dwelling in itself is a major risk factor for developing an eating disorder. However, when accompanied by other sociodemographic effects, there may well be an increase in eating disorder risk. There are opportunities for planners to design cities to be supportive of peoples' eating and mental health in general. More research investigating moderating and mediating effects on the associations between urban dwelling and eating disorder is needed as well as studies of more sexually and age diverse populations.
It does not seem likely that metropolitan dwelling in itself is a major risk factor for developing an eating disorder. However, when accompanied by other sociodemographic effects, there may well be an increase in eating disorder risk. There are opportunities for planners to design cities to be supportive of peoples' eating and mental health in general. Epacadostat More research investigating moderating and mediating effects on the associations between urban dwelling and eating disorder is needed as well as studies of more sexually and age diverse populations.
Agitation associated with schizophrenia remains an important clinical concern and if not managed effectively, can escalate into aggressive behavior. This is a review of the recent biomedical literature on agitation in individuals with schizophrenia.
Themes in the recent literature include consideration of comorbidities such as cigarette smoking and cannabis use. Surveys reveal that pharmacological approaches to manage agitation have changed little, with haloperidol remaining in common use and intramuscular administration of antipsychotics and/or benzodiazepines being frequently administered to more severely agitated/aggressive individuals. Of note, ketamine has been recently adopted for use in severe agitation in medical emergency departments, but the risk of this medication for people with schizophrenia is unclear. At present, inhaled loxapine remains the only rapidly acting noninjectable FDA-approved treatment for agitation associated with schizophrenia. In development is an intranasal formulation for olanzapine (a well characterized atypical antipsychotic already approved to treat agitation) and a sublingual film for dexmedetomidine (an α2-adrenergic agonist used as an anesthetic and now being repurposed).
Comorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.
Comorbidities can contribute to agitation and can make an accurate differential diagnosis challenging. The ongoing development of rapidly acting novel formulations of antiagitation medications, if successful, may facilitate clinical treatment by providing additional options.
Neurocognitive disorders are associated with tremendous burden at the level of the individual, the care giver, and society at large. No effective treatments have been discovered to date.
Noninvasive brain stimulation (NIBS) comprises several promising interventions that have been studied in Alzheimer's disease and related dementias. Most recent studies have tested transcranial direct current stimulation or repetitive transcranial magnetic stimulation on their own or in combination with other interventions, particularly cognitive training. While most studies were proof-of-principle studies with small sample sizes, combination and long-duration protocols seem to be promising approaches to pursue. Some studies also investigated novel neurophysiological markers as predictors of response to NIBS.
NIBS presents several interventional options that are ready to be evaluated using well powered, long-duration trials. These future studies should build on the promising leads from the current literature, including the potential advantage of combining NIBS with other interventions; the delivery of interventions for long durations to assess long-term impact; and the use of neurophysiological markers that could optimize the personalization and efficacy of NIBS.
NIBS presents several interventional options that are ready to be evaluated using well powered, long-duration trials. These future studies should build on the promising leads from the current literature, including the potential advantage of combining NIBS with other interventions; the delivery of interventions for long durations to assess long-term impact; and the use of neurophysiological markers that could optimize the personalization and efficacy of NIBS.
The COVID-19 infection results in various viral-related physical and mental health problems, joined with the long-term psychological impact of the pandemic in general. However, the accompanying neurocognitive changes remain poorly understood.
We synthetize the current knowledge of viral (SARS-CoV-2) induced inflammation, mechanisms to viral entry into the central nervous system and altered neurotransmitter systems to provide an informed neurobiological explanation for the rise of neurocognitive disorders (defined as per the DSM-5 criteria).
The mild and major neurocognitive disorder symptoms due to the COVID-19 pandemic provide a unique opportunity to address the early changes underlying neurocognitive impairment at both clinical and molecular level. We discuss the utilization of the available evidence for their management and future novel therapeutic opportunities.
The mild and major neurocognitive disorder symptoms due to the COVID-19 pandemic provide a unique opportunity to address the early changes underlying neurocognitive impairment at both clinical and molecular level. We discuss the utilization of the available evidence for their management and future novel therapeutic opportunities.
Over 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals.
Based on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients han. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.
Genetic mutations in animals advance our understanding of disease mechanisms and treatments of neurodevelopmental disorders. Research with mutant mouse models is being extended to nonhuman primates whose brain development is closer to that of humans. This review summaries advances in mouse and nonhuman primate models.
Mutant mouse models recapitulate key symptoms in neurodevelopmental disorders. However, successful phenotypic reversal of symptoms in mouse models has not been replicated in human studies; this failure may be because of differences in the structure and physiology of the brain between rodents and humans. Rett syndrome MECP2 models and Phelan-McDermid syndrome where reduced expression of SH3 and multiple ankyrin repeat domains 3 (SHANK3) models have been introduced in nonhuman primates and are underway in other neurodevelopmental disorders.
Mutant mouse models in neurogenetic disorders continued to be pursued along with gene-edited and cell-based models in nonhuman primates. Established ethical guidelines are being followed and infrastructure being established to facilitate dissemination of primate transgenic models as they become available.
Mutant mouse models in neurogenetic disorders continued to be pursued along with gene-edited and cell-based models in nonhuman primates. Established ethical guidelines are being followed and infrastructure being established to facilitate dissemination of primate transgenic models as they become available.
This review describes current understandings in the search for therapies to support children with Angelman syndrome. There is a rapid progression in particular in genetic therapies in this disorder supported by the Angelman community.
Recent papers shed light on the timing of therapies and novel genetic therapies coming to trial as well as potential therapies still in preclinical phases. Further understanding of UBE3A and its role in neuronal development and plasticity as well as other mechanisms contributing to the Angelman phenotype is offering an opportunity for novel therapeutics.
Greater understanding of the pathophysiology of the different phenotypes will offer an opportunity for novel therapeutics and may well change the course of this disorder over time where previously there has been minimal ability to intervene.
Greater understanding of the pathophysiology of the different phenotypes will offer an opportunity for novel therapeutics and may well change the course of this disorder over time where previously there has been minimal ability to intervene.
