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What level of Ras genes activity leads to the development of cancer?Alzheimer's disease (AD) is one of the major reasons for 60-80% of cases of senile dementia occurring as a result of the accumulation of plaques and tangles in the hippocampal and cortical neurons of the brain leading to neurodegeneration and cell death. The other pathological features of AD comprise of abnormal microvasculature, network abnormalities, interneuronal dysfunction, increased β-amyloid production, and reduced clearance, increased inflammatory response, elevated production of reactive oxygen species, impaired brain metabolism, hyperphosphorylation of tau, and disruption of acetylcholine signaling. Among all these pathologies, mitochondrial dysfunction (MD), regardless of being an inciting insult or a consequence of the alterations, is related to all the associated AD pathologies. Observed altered mitochondrial morphology, distribution, and movement increased oxidative stress, dysregulation of enzymes involved in mitochondrial functioning, impaired brain metabolism, and impaired mitochondrial biogenesis in AD subjects suggest the involvement of mitochondrial malfunction in the progression of AD. Various pre-clinical and clinical evidence establishing MD as a key mediator in the progression of neurodegeneration in AD are reviewed and discussed with an aim to foster future MD-based drug development research for the management of AD.Prematurity, observed in 15 million births worldwide each year, is a clinical condition that is a major cause of neonatal mortality and morbidity in short and long term. Preterm infants are at high risk for developing respiratory problems, sepsis, and other morbidities leading to neurodevelopmental impairment and neurobehavioral disorders. Perinatal glucocorticosteroids have been widely used for the prevention and treatment of adverse outcomes linked to prematurity. However, despite their shortterm benefits due to their maturational properties, some clinical trials have shown an association between steroids exposure and abnormal brain development in infants born preterm. Neuroinflammation has emerged as a preeminent factor for brain injury in preterm infants, and the major role of microglia, the brain resident immune cells, has been recently highlighted. Considering the role of microglia in the modulation of brain development, the aim of this review is to summarize the effects of endogenous and exogenous glucocorticosteroids on brain development and discuss the possible role of microglia as a mediator of these effects.Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are extremely versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. For these reasons, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by non-psychiatrists. For this reason, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.Advancements in programmable DNA-binding proteins (DBDs) that target the genome, such as zinc fingers, transcription activator-like effectors, and Cas9, have broadened drug target design beyond traditional protein substrates. Effective delivery methodologies remain a major barrier in targeting the central nervous system. Currently, adeno-associated virus is the most well-validated delivery system for the delivery of DBDs towards the central nervous with multiple, on-going clinical trials. While effective in transducing neuronal cells, viral delivery systems for DBDs remain problematic due to inherent viral packaging limits or immune responses that hinder translational potential. Direct administration of DBDs or encapsulation in lipid nanoparticles may provide alternative means towards delivering gene therapies into the central nervous system. This review will evaluate strengths and limitations in current DBD delivery strategies in-vivo. Furthermore, this review will discuss the use of adult stem cells as a putative delivery vehicle for DBDs and potential advantages that these systems have over previous methodologies.Curcuma longa (Turmeric) is a tropical herbaceous perennial plant of the family Zingiberaceae and contains curcuminoids, sesquiterpenoids and monoterpenoids as its major components. Given the broad range of activities that Curcuma Longa possesses and also its use as a traditional epilepsy remedy, this review attempts to systematically review the experimentally proven activities of Curcuma longa and its bioactive components, which are related to the management of epileptic seizures. Using the PRISMA model, five databases (Google Scholar, PubMed, ScienceDirect, SCOPUS and SpringerLink) were searched using the keywords ["Curcuma longa" AND "Epilepsy"] and ["Curcuma longa" AND "Seizures"], leaving with 34 articles that met the inclusion criteria. The present systematic review elaborated on the experimentally proven potential of Curcuma longa components, such as an aqueous extract of Curcuma longa itself, Curcuma longa oil and active constituents like curcuminoids and bisabolene sesquiterpenoids found in Curcuma longa with anti-seizure potential. Using human equivalent dose calculations, human treatment parameters were suggested for each component by analysing various studies in this review. This review also determined that the principal components possibly exert their anti-seizure effect via the reduction of corticosterone, modulation of neurotransmitters signalling, modulation of sodium ion channels, reduction of oxidative DNA damage, reduction of lipid peroxidation, upgregulation of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) mediated inhibition. It is anticipated that this review will help pave the way for future research into the development of Curcuma longa and its neuroactive constituents as potential drug candidates for the management of epilepsy.Sleep disorders are one of the most common non-motor symptoms in Parkinson's disease (PD). It can cause a notably decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. The most cited sleep disorders in PD included insomnia, restless legs syndrome (RLS), rapid eye movement (REM) sleep behavior disorders (RBD), excessive daytime sleepiness (EDS) and sleep disordered breathing (SDB), which can appear alone or several at the same time. In this review, we listed the recommended pharmacological treatments for common sleep disorders in PD, and discussed the recommended dosages, benefits and side effects of relative drugs. We also discussed non-pharmacological treatments to improve sleep quality, including sleep hygiene education, exercise, deep brain stimulation, cognitive behavior therapy and complementary therapies. We tried to find proper interventions for different types of sleep disorders in PD, while minimizing relative side effects.Traumatic injuries of the brain and spinal cord are a significant source of mortality and long-term disability. A recent systematic study in a rat model of spinal cord injury (SCI) indicates severe, destructive, and very protracted inflammation as the key mechanism initiated by the massive injury involving the white matter. Although the severe inflammation is localized and counteracted by astrogliosis, it has a damaging effect on the blood vessels in the surrounding spinal cord, leading to persistent vasogenic edema. To evaluate these injuries, imaging of the brain and spinal cord plays a crucial role in the acute trauma work-up, allowing clinicians to quickly identify abnormalities that require immediate medical or surgical intervention or to exclude them from the work-up. Recently, anti-inflammatory agents have been shown to inhibit and accelerate the elimination of post-SCI inflammation in preclinical studies, and an exciting potential has arisen for the use of anti-inflammatory drugs in clinical studies to achieve neuroprotection (i.e., inhibition of destruction caused by inflammation) and to inhibit vasogenic edema in SCI, traumatic brain injury, and stroke. In both subacute and chronic settings, imaging can be a guide to therapy and provide important prognostic information. In this review, we discuss the imaging work-up and evolving imaging findings of neurotrauma in the acute and chronic setting, including conventional and advanced imaging techniques. As neuroimaging is the primary mode of diagnostic analysis in neurotrauma, it is a critical component in future clinical trials evaluating neuroprotective therapies.

Increasing research reveals that long non-coding RNAs (lncRNAs) play an important role in various biological processes of human diseases. Nonetheless, only a handful of lncRNA-disease associations have been experimentally verified. The study of lncRNA-disease association prediction based on the computational model has provided a preliminary basis for biological experiments to a great degree so as to cut down the huge cost of wet lab experiments.

This study aims to learn the real distribution of lncRNA-disease association from a limited number of known lncRNA-disease association data. This paper proposes a new lncRNA-disease association prediction model called LDA-GAN based on a generative adversarial network (GAN).

Aiming at the problems of slow convergence rate, training instabilities, and unavailability of discrete data in traditional GAN, LDA-GAN utilizes the Gumbel-softmax technology to construct a differentiable process for simulating discrete sampling. Meanwhile, the generator and the discriminato several lncRNAs.In Elaine Theresa Jurkowski, Ph.D., MSW's Policy and Program Planning for Older Adults and People with Disabilities Practice Realities and Visions, the reader will find a well-sourced, well laid out, and well-organized text and reference manual that walks the reader, from start to finish, through the formation of policy as it relates to Older Adults and People with Disabilities.Friends and colleagues describe the legacy of and pay tribute to Lori Stiegel, elder justice champion, who died earlier this year.Objectives The Montessori Assessment System (MAS) is an assessment tool that aims at assessing preserved abilities in persons with moderate to severe dementia and to serve as basis for person-centered interventions. As responsive behaviors are highly frequent in this population, we assessed their possible influence on the MAS administration and results.Methods 193 persons with a diagnosis of dementia in the moderate to severe stages living in nursing homes completed the MAS. Responsive behaviors were assessed by the Neuropsychiatric Inventory (NPI).Results The NPI scores were heterogeneous, but responsive behaviors were present for at least 5 NPI domains in more than 50% of the participants. While NPI scores had weak relationships with MAS completion time and total score, primarily for the hallucinations, euphoria, and aberrant motor behaviors domains, a large majority of the participants fully completed the MAS.Conclusions The presence of responsive behaviors as assessed by the NPI does not limit MAS administration, despite minor influence on MAS score and completion time.