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

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00425-4

Cancer Stem Cells and Side Population Cells in Breast Cancer and Metastasis

In breast cancer it is never the primary tumour that is fatal; instead it is the development of metastatic disease which is the major cause of cancer related mortality. There is accumulating evidence that suggests that Cancer Stem Cells (CSC) may play a role in breast cancer development and progression. Breast cancer stem cell populations, including side population cells (SP), have been shown to be primitive stem cell-like populations, being long-lived, self-renewing and highly proliferative. SP cells are identified using dual wavelength flow cytometry combined with Hoechst 33342 dye efflux, this ability is due to expression of one or more members of the ABC transporter family. They have increased resistance to chemotherapeutic agents and apoptotic stimuli and have increased migratory potential above that of the bulk tumour cells making them strong candidates for the metastatic spread of breast cancer. Treatment of nearly all cancers usually involves one first-line agent known to be a substrate of an ABC transporter thereby increasing the risk of developing drug resistant tumours. At present there is no marker available to identify SP cells using immunohistochemistry on breast cancer patient samples. If SP cells do play a role in breast cancer progression/Metastatic Breast Cancer (MBC), combining chemotherapy with ABC inhibitors may be able to destroy both the cells making up the bulk tumour and the cancer stem cell population thus preventing the risk of drug resistant disease, recurrence or metastasis

Surgery: The Treatment of Choice for Hemangiomas

The management of hemangiomas has always been a matter of controversy. Traditionally, observation has been the mainstay of therapy, with the expectation that most of the lesions will disappear spontaneously. This treatment plan was based on the premise that surgical excision or other treatments might produce a worse result than simply waiting for the lesion to resolve with an acceptable cosmetic result. This plan has been challenged because of a growing number of specialty teams that address these lesions. This article examines various cases of pediatric hemangioma and evaluates the possibility of surgical excision as a first-choice treatment in these cases. One hundred fifteen cases of surgical excision of pediatric hemangiomas performed by a single surgeon over a period of 7 years were examined. Pre- and postoperative photographs were examined. Hemangioma location, size, and type; patient's age; and surgical technique are described. Acceptable cosmetic and functional results were achieved in all surgical cases. Early excision of hemangioma should be the procedure of choice in selected cases of hemangioma. Hemangiomas in areas where a significant cosmetic defect or functional defect might ensue should have surgical excision considered as first-line treatment

Children’s and Caregivers’ Review of a Guided Imagery Therapy Mobile App Designed to Treat Children With Functional Abdominal Pain Disorders: Leveraging a Mixed Methods Approach With User-Centered Design

BackgroundFunctional abdominal pain disorders (FAPDs) are highly prevalent and associated with substantial morbidity. Guided imagery therapy (GIT) is efficacious; however, barriers often impede patient access. Therefore, we developed a GIT mobile app as a novel delivery platform. ObjectiveGuided by user-centered design, this study captured the critiques of our GIT app from children with FAPDs and their caregivers. MethodsChildren aged 7 to 12 years with Rome IV–defined FAPDs and their caregivers were enrolled. The participants completed a software evaluation, which assessed how well they executed specific app tasks: opening the app, logging in, initiating a session, setting the reminder notification time, and exiting the app. Difficulties in completing these tasks were tallied. After this evaluation, the participants independently completed a System Usability Scale survey. Finally, the children and caregivers were separately interviewed to capture their thoughts about the app. Using a hybrid thematic analysis approach, 2 independent coders coded the interview transcripts using a shared codebook. Data integration occurred after the qualitative and quantitative data were analyzed, and the collective results were summarized. ResultsWe enrolled 16 child-caregiver dyads. The average age of the children was 9.0 (SD 1.6) years, and 69% (11/16) were female. The System Usability Scale average scores were above average at 78.2 (SD 12.6) and 78.0 (SD 13.5) for the children and caregivers, respectively. The software evaluation revealed favorable usability for most tasks, but 75% (12/16) of children and 69% (11/16) of caregivers had difficulty setting the reminder notification. The children’s interviews confirmed the app’s usability as favorable but noted difficulty in locating the reminder notification. The children recommended adding exciting scenery and animations to the session screen. Their preferred topics were animals, beaches, swimming, and forests. They also recommended adding soft sounds related to the session topic. Finally, they suggested that adding app gamification enhancements using tangible and intangible rewards for listening to the sessions would promote regular use. The caregivers also assessed the app’s usability as favorable but verified the difficulty in locating the reminder notification. They preferred a beach setting, and theme-related music and nature sounds were recommended to augment the session narration. App interface suggestions included increasing the font and image sizes. They also thought that the app’s ability to relieve gastrointestinal symptoms and gamification enhancements using tangible and intangible incentives would positively influence the children’s motivation to use the app regularly. Data integration revealed that the GIT app had above-average usability. Usability challenges included locating the reminder notification feature and esthetics affecting navigation. ConclusionsChildren and caregivers rated our GIT app’s usability favorably, offered suggestions to improve its appearance and session content, and recommended rewards to promote its regular use. Their feedback will inform future app refinements

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