Building an Institute to Translate Research into Practice: A Facilitation Model

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The Formal Dynamism of Categories: Stops vs. Fricatives, Primitivity vs. Simplicity

Minimalist Phonology (MP; Pöchtrager 2006) constructs its theory based on the phonological epistemological principle (Kaye 2001) and exposes the arbitrary nature of standard Government Phonology (sGP) and strict-CV (sCV), particularly with reference to their confusion of melody and structure. For Pöchtrager, these are crucially different, concluding that place of articulation is melodic (expressed with elements), while manner of articulation is structural. In this model, the heads (xN and xO) can license and incorporate the length of the other into their own interpretation, that is xN influences xO projections as well as its own and vice versa. This dynamism is an aspect of the whole framework and this paper in particular will show that stops and fricatives evidence a plasticity of category and that, although fricatives are simpler in structure, stops are the more primitive of the two. This will be achieved phonologically through simply unifying the environment of application of the licensing forces within Pöchtrager's otherwise sound onset structure. In doing so, we automatically make several predictions about language acquisition and typology and show how lenition in Qiang (Sino-Tibetan) can be more elegantly explained

Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association

Viloxazine, a Non-stimulant Norepinephrine Reuptake Inhibitor, for the Treatment of Attention Deficit Hyperactivity Disorder: A 3 Year Update.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Current treatment options for ADHD include pharmacological treatment (stimulants, non-stimulants, anti-depressants, anti-psychotics), psychological treatment (behavioral therapy with or without parent training, cognitive training, neurofeedback), and complementary and alternative therapies (vitamin supplementation, exercise). Central nervous system (CNS) stimulants are the primary pharmacological therapy used in treatment; however, these stimulant drugs carry a high potential for abuse and severe psychological/physical dependence. Viloxazine, a non-stimulant medication without evidence of drug dependence, is a selective norepinephrine reuptake inhibitor that has historically been prescribed as an anti-depressant medication. The extended-release (ER) form was approved by the US Food and Drug Administration (FDA) in April 2021 for the treatment of ADHD in pediatric patients aged 6-17 years. Phase 2 and 3 randomized control trials have demonstrated significant efficacy of viloxazine in improving ADHD symptoms versus placebo. Related to its long-standing use as an antidepressant, the safety profile and pharmacokinetics of viloxazine are well understood. Viloxazine appears to be a suitable alternative to current standard-of-care pharmacotherapy for ADHD, but the further investigation remains to be done in comparing its efficacy to that of current treatments

Observations of Reduced Electron Gyroscale Fluctuations in National Spherical Torus Experiment H-Mode Plasmas with Large E X B Flow Shear

Electron gyroscale fluctuation measurements in National Spherical Torus Experiment H-mode plasmas with large toroidal rotation reveal fluctuations consistent with electron temperature gradient (ETG) turbulence. Large toroidal rotation in National Spherical Torus Experiment plasmas with neutral beam injection generates ExB flow shear rates comparable to ETG linear growth rates. Enhanced fluctuations occur when the electron temperature gradient is marginally stable with respect to the ETG linear critical gradient. Fluctuation amplitudes decrease when the ExB flow shear rate exceeds ETG linear growth rates. The observations indicate that ExB flow shear can be an effective suppression mechanism for ETG turbulence.X1129sciescopu

Catatonia: Clinical overview of the diagnosis, treatment, and clinical challenges

Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hypo-natremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotrans-mission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia

Lumateperone tosylate, A Selective and Concurrent Modulator of Serotonin, Dopamine, and Glutamate, in the Treatment of Schizophrenia

Purpose of Review This is a comprehensive review of the literature regarding the use of Lumateperone tosylate for schizophrenia. This review presents the background, evidence, and indications for the use of lumateperone tosylate in the treatment of schizophrenia. Recent Findings Schizophrenia is a chronic mental health disorder that affects approximately 3.3 million people in the United States. Its symptoms, which must be present more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Lumateperone is a selective and concurrent modulator of serotonin, dopamine, and glutamate, which all mediate or modulate serious mental illness. Summary Schizophrenia is a complex, severe mental illness that affects how the brain processes information. There are many medications used to treat schizophrenia. One antipsychotic agent, lumateperone tosylate, is a newer agent that the FDA recently approved. The most common adverse effects are shown to be mild such as somnolence, constipation, sedation, and fatigue, with the 42 mg recommended dose. Lumateperone tosylate is an FDA-approved drug that can be given only at the 42mg dose once daily with no titration requirements

SMEI observations of previously unseen pulsation frequencies in γ Doradus

Aims. As g-mode pulsators, gamma-Doradus-class stars may naïvely be expected to show a large number of modes. Taking advantage of the long photometric time-series generated by the solar mass ejection imager (SMEI) instrument, we have studied the star gamma Doradus to determine whether any other modes than the three already known are present at observable amplitude. Methods. High-precision photometric data from SMEI taken between April 2003 and March 2006 were subjected to periodogram analysis with the PERIOD04 package. Results. We confidently determine three additional frequencies at 1.39, 1.87, and 2.743 d−1. These are above and beyond the known frequencies of 1.320, 1.364, and 1.47 d−1. Conclusions. Two of the new frequencies, at 1.39 and 1.87 d−1, are speculated to be additional modes of oscillation, with the third frequency at 2.743−1 a possible combination frequency

The antisense oligonucleotide nusinersen for treatment of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular degenerative disease characterized by loss of spinal cord motor neurons leading to progressive muscle wasting. The most common pathology results from a homozygous disruption in the survival motor neuron 1 (SMN1) gene on chromosome 5q13 via deletion, conversion, or mutation. SMN2 is a near duplicate of SMN1 that can produce full-length SMN mRNA transcripts, but its overall production capability of these mRNA transcripts is lower than that seen in SMN1. This leads to lower levels of functional SMN protein within motor neurons. The FDA approved nusinersen in December 2016 to treat SMA associated with SMN1 gene mutation. It is administered directly to the central nervous system by intrathecal injection. An antisense oligonucleotide (ASO) drug, nusinersen, provides an upcoming and promising treatment option for SMA and represents a novel pharmacological approach with a mechanism of action relevant for other neurodegenerative disorders. Nusinersen begins with four initial loading doses that are followed by three maintenance doses per year. Three major studies (CHERISH, ENDEAR, and NURTURE) have shown to improve motor function in early and late-onset individuals and reduce the chances of ventilator requirements in pre-symptomatic infants. Studies investigating the timing of drug delivery in mouse models of SMA report the best outcomes when drugs are delivered early before any significant motor function is lost. Nusinersen is a novel therapeutic approach with consistent results in all three studies and is proof of the novel concept for treating SMA and other neurodegenerative disorders in the future

Selective Serotonin Reuptake Inhibitors and Associated Bleeding Risks: A Narrative and Clinical Review.

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study