Design, stray light analysis, and fabrication of a compact head-mounted display using freeform prisms.

It has been a challenge to design an optical see-through head-mounted display that is compact, lightweight, and stray-light-suppressed by using freeform optics. A new type of design based on freeform prisms is presented. The system consists of three optical elements and a micro-display. Two prisms serve as near-eye viewing optics that magnify the image displayed by the micro-display, and the other freeform lens is an auxiliary element attached to the main wedge-shaped prism to provide an undistorted see-through view of a real-world scene. The overall thickness of the optical system does not exceed 9.5 mm, and the weight is less than 9.8 g per eye. The final system is based on a 0.49-inch micro-display and features a diagonal field of view of 38°, an F/number of 1.8, with a 10 mm × 7 mm exit pupil diameter, and a 19 mm eye relief. The causes of stray light in the optical-mechanical system are investigated, and effective solutions or theoretical suppression of stray light are given. The freeform optical elements are successfully fabricated, and the system performance is carefully investigated. The results show that the performance of the optical see-through head-mounted display is adequate for practical applications.

Stray light analysis and suppression method of a pancake virtual reality head-mounted display.

Pancake virtual reality head-mounted displays (VR-HMDs) have attracted the attention of researchers in both academia and industry because of the compact size and light weight. However, owing to the use of optical path folding, there exist various stray lights in the optical system, which seriously degrades user experience. In this study, we analyze the causes and effects of multiple types of stray light systematically and design a VR-HMD with low stray light, large exit pupil diameter (EPD), compact form and light weight. Subsequently, several effective stray light suppression solutions are proposed and implemented. Finally, a prototype of a compact pancake VR-HMD system is successfully demonstrated. The prototype has stray light of less than 2.3%, a diagonal field of view (FOV) of 96° and an EPD of 10 mm at an 11 mm eye relief (ERF).

Optical design and pupil swim analysis of a compact, large EPD and immersive VR head mounted display.

Virtual reality head-mounted displays (VR-HMDs) are crucial to Metaverse which appears to be one of the most popular terms to have been adopted over the internet recently. It provides basic infrastructure and entrance to cater for the next evolution of social interaction, and it has already been widely used in many fields. The VR-HMDs with traditional aspherical or Fresnel optics are not suitable for long-term usage because of the image quality, system size, and weight. In this study, we designed and developed a large exit pupil diameter (EPD), compact, and lightweight VR-HMD with catadioptric optics. The mathematical formula for designing the catadioptric VR optics is derived. The reason why this kind of immersive VR optics could achieve a compact size and large EPD simultaneously is answered. Various catadioptric forms are systematically proposed and compared. The design can achieve a diagonal field of view (FOV) of 96° at -1 diopter, with an EPD of 10 mm at 11 mm eye relief (ERF). The overall length (OAL) of the system was less than 20 mm. A prototype of a compact catadioptric VR-HMD system was successfully developed.

The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes.

The let-7 microRNA (miRNA) plays important roles in human liver development and diseases such as hepatocellular carcinoma, liver fibrosis and hepatitis wherein oxidative stress accelerates the progression of these diseases. To date, the role of the let-7 miRNA family in modulation of heme oxygenase 1 (HMOX1), a key cytoprotective enzyme, remains unknown. Our aims were to determine whether let-7 miRNA directly regulates Bach1, a transcriptional repressor of the HMOX1 gene, and whether indirect up-regulation of HMOX1 by let-7 miRNA attenuates oxidant injury in human hepatocytes. The effects of let-7 miRNA on Bach1 and HMOX1 gene expression in Huh-7 and HepG2 cells were determined by real-time qRT-PCR, Western blot, and luciferase reporter assays. Dual luciferase reporter assays revealed that let-7b, let-7c, or miR-98 significantly decreased Bach1 3'-untranslated region (3'-UTR)-dependent luciferase activity but not mutant Bach1 3'-UTR-dependent luciferase activity, whereas mutant let-7 miRNA containing base complementarity with mutant Bach1 3'-UTR restored its effect on mutant reporter activity. let-7b, let-7c, or miR-98 down-regulated Bach1 protein levels by 50-70%, and subsequently up-regulated HMOX1 gene expression by 3-4 fold, compared with non-specific controls. Furthermore, Huh-7 cells transfected with let-7b, let-7c or miR-98 mimic showed increased resistance against oxidant injury induced by tert-butyl-hydroperoxide (tBuOOH), whereas the protection was abrogated by over-expression of Bach1. In conclusion, let-7 miRNA directly acts on the 3'-UTR of Bach1 and negatively regulates expression of this protein, and thereby up-regulates HMOX1 gene expression. Over-expression of the let-7 miRNA family members may represent a novel approach to protecting human hepatocytes from oxidant injury.

Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.

5-Aminolevulinic acid synthase (ALAS-1) is the first rate controlling enzyme that controls cellular heme biosynthesis. Negative feedback regulation of ALAS-1 by the end product heme is well documented and provides the foundation for heme treatment of acute porphyrias, a group of diseases caused by genetic defects in the heme biosynthesis pathway and exacerbated by controlled up-regulation of ALAS-1. Heme is known to affect ALAS-1 activity by repressing gene transcription, accelerating mRNA degradation, and impeding pre-ALAS-1 mitochondrial translocation. In the current study, we examined the effect of heme on the rate of mature ALAS-1 protein turnover in human cells and tissues and explored the mediator involved in this new regulatory mechanism. We found that heme and other metalloporphyrins such as CoPP and CrPP decreased mitochondrial ALAS-1 protein through proteolysis. This degradative effect cannot be emulated by iron or free protoporphyrin, two major chemical components of the heme ring, and is independent of oxidative stress. Down-regulating the activity of mitochondrial LONP1, an ATP-dependent protease that controls the selective turnover of mitochondrial matrix proteins, with potent inhibitors and specific siRNA diminished the negative effect of heme on mitochondrial ALAS-1. Therefore, our data support the existence of a conserved heme feedback regulatory mechanism that functions on the mature form of ALAS-1 protein through the activity of a mitochondrial proteolytic system.

Mechanistic/mammalian target of rapamycin and side effects of antipsychotics: insights into mechanisms and implications for therapy.

Antipsychotic pharmacotherapy has been widely recommended as the standard of care for the treatment of acute schizophrenia and psychotic symptoms of other psychiatric disorders. However, there are growing concerns regarding antipsychotic-induced side effects, including weight gain, metabolic syndrome (MetS), and extrapyramidal motor disorders, which not only decrease patient compliance, but also predispose to diabetes and cardiovascular diseases. To date, most studies and reviews on the mechanisms of antipsychotic-induced metabolic side effects have focused on central nervous system mediation of appetite and food intake. However, disturbance in glucose and lipid metabolism, and hepatic steatosis induced by antipsychotic drugs might precede weight gain and MetS. Recent studies have demonstrated that the mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical regulatory role in the pathophysiology of antipsychotic drug-induced disorders of hepatic glucose and lipid metabolism. Furthermore, antipsychotic drugs promote striatal mTOR pathway activation that contributes to extrapyramidal motor side effects. Although recent findings have advanced the understanding of the role of the mTOR pathway in antipsychotic-induced side effects, few reviews have been conducted on this emerging topic. In this review, we synthesize key findings by focusing on the roles of the hepatic and striatal mTOR pathways in the pathogenesis of metabolic and extrapyramidal side effects, respectively. We further discuss the potential therapeutic benefits of normalizing excessive mTOR pathway activation with mTOR specific inhibitors. A deeper understanding of pathogenesis may inform future intervention strategies using the pharmacological or genetic inhibitors of mTOR to prevent and manage antipsychotic-induced side effects.

Bronze and Iron Age population movements underlie Xinjiang population history.

The Xinjiang region in northwest China is a historically important geographical passage between East and West Eurasia. By sequencing 201 ancient genomes from 39 archaeological sites, we clarify the complex demographic history of this region. Bronze Age Xinjiang populations are characterized by four major ancestries related to Early Bronze Age cultures from the central and eastern Steppe, Central Asian, and Tarim Basin regions. Admixtures between Middle and Late Bronze Age Steppe cultures continued during the Late Bronze and Iron Ages, along with an inflow of East and Central Asian ancestry. Historical era populations show similar admixed and diverse ancestries as those of present-day Xinjiang populations. These results document the influence that East and West Eurasian populations have had over time in the different regions of Xinjiang.

Zinc mesoporphyrin induces rapid proteasomal degradation of hepatitis C nonstructural 5A protein in human hepatoma cells.

BACKGROUND & AIMS: The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) plays a critical role in HCV replication and is an attractive target for the therapy of HCV infection. So far, little is known about the posttranslational regulation of NS5A protein and its precise role in HCV RNA replication. Our objectives were to elucidate the down-regulation of NS5A protein and HCV RNA replication by zinc mesoporphyrin (ZnMP) and the mechanism by which this process occurs. METHODS: Human hepatoma cells expressing HCV proteins were used to investigate the posttranslational regulation of ZnMP on NS5A protein by Western blots and immunoprecipitation. Real-time quantitative reverse transcription polymerase chain reaction was used to determine the effects of ZnMP on HCV RNA replication. RESULTS: ZnMP selectively and markedly down-regulated NS5A protein levels by increasing degradation of NS5A protein (half-life fell from 18.7 hours to 2.7 hours). The proteasome inhibitors epoxomicin and MG132 significantly abrogated degradation of NS5A protein by ZnMP without affecting levels of NS5A in the absence of ZnMP. Analysis of immunoprecipitates with an antiubiquitin antibody revealed polyubiquitination of NS5A, suggesting that ZnMP induces ubiquitination of NS5A protein. In addition, 10 micromol/L of ZnMP reduced HCV replication by approximately 63% in the Con1 replicon cells, approximately 70% in J6/Japanese fulminant hepatitis 1 HCV-transfected cells, and approximately 90% in J6/Japanese fulminant hepatitis 1 HCV-infected cells without affecting cell viability. CONCLUSIONS: ZnMP produces a rapid and profound down-regulation of the NS5A protein by enhancing its polyubiquitination and proteasome-dependent catabolism. ZnMP may hold promise as a novel agent to treat HCV infection.

MicroRNA-196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins.

UNLABELLED: Hepatitis C virus (HCV) directly induces oxidative stress and liver injury. Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has antioxidant and anti-inflammatory activities. microRNAs (miRNAs) are small noncoding RNAs ( approximately 22 nt) that are important regulators of gene expression. Whether and how miRNAs regulate Bach1 or HCV are largely unknown. The aims of this study were to determine whether miR-196 regulates Bach1, HMOX1, and/or HCV gene expression. HCV replicon cell lines (Con1 and 9-13) of the Con1 isolate and J6/JFH1-based HCV cell culture system were used in this study. The effects of miR-196 mimic on Bach1, HMOX1, and HCV RNA, and protein levels were measured by way of quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. The Dual Glo Luciferase Assay System was used to determine reporter activities. miR-196 mimic significantly down-regulated Bach1 and up-regulated HMOX1 gene expression and inhibited HCV expression. Dual luciferase reporter assays demonstrated that transfection of miR-196 mimic resulted in a significant decrease in Bach1 3'-untranslated region (UTR)-dependent luciferase activity but not in mutant Bach1 3'-UTR-dependent luciferase activity. Moreover, there was no detectable effect of mutant miR-196 on Bach1 3'-UTR-dependent luciferase activity. CONCLUSION: miR-196 directly acts on the 3'-UTR of Bach1 messenger RNA and translationally represses the expression of this protein, and up-regulates HMOX1. miR-196 also inhibits HCV expression in HCV replicon cell lines (genotype 1b) and in J6/JFH1 (genotype 2a) HCV cell culture system. Thus, miR-196 plays a role in both HMOX1/Bach1 expression and the regulation of HCV expression in human hepatocytes. Overexpression of miR-196 holds promise as a potential novel strategy to prevent or ameliorate hepatitis C infection, and to protect against liver injury in chronic HCV infection.

Contemporary clinical research of traditional Chinese medicines for chronic hepatitis B in China: an analytical review.

UNLABELLED: Chronic hepatitis B (CHB) is major global health problem. In China, where about 120,000,000 persons are chronically infected, CHB has been treated for centuries with traditional Chinese medicines (TCMs). This review summarizes and meta-analyzes the results of randomized controlled trials (RCTs) of TCM formulations reported in China in 1998-2008 for treatment of CHB. RCTs comparing either TCM formulations alone or in combination with interferon (IFN) or lamivudine (LAM) versus IFN or LAM were included. Chinese electronic databases were searched. The methodological quality of RCTs was assessed using the Jadad scale. TCMs had a greater beneficial effect (P = 0.0003) than IFN and a slightly better effect (P = 0.01) than LAM on the normalization of serum alanine aminotransferase. TCMs had a similar beneficial effect when compared with IFN or LAM for CHB on antiviral activity as evidenced by the loss of serum hepatitis B e antigen and hepatitis B virus (HBV) DNA. TCMs enhanced IFN and LAM antiviral activities and improvements of liver function. The quality of many studies was poor; reports often lacked information regarding methods of randomization or blinding and adverse events. CONCLUSION: Some TCMs seem effective as alternative remedies for patients with CHB, suggesting that further study of TCMs in the treatment of CHB is warranted, both in preclinical models of HBV infection and in higher quality RCTs worldwide.

Correlation Between Calcification Characteristics of Carotid Atherosclerotic Plaque and Plaque Vulnerability.

PURPOSE: To investigate the relationship between calcification characteristics of carotid atherosclerotic plaque and lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH). METHODS: Patients with severe carotid stenosis undergoing carotid endarterectomy (CEA) were selected. Ultrasound and CT angiography (CTA) were performed to evaluate the calcification characteristics of the plaque before the surgery. RESULTS: A total of 142 patients were included and 142 pathological specimens of postoperative plaque were obtained accordingly. There were 78 plaques (54.9%) with LRNC and 41 (28.9%) with IPH. The plaque with LRNC had higher calcification rate (93.6%) compared with the plaque with IPH (87.8%). LRNC was often found in multiple calcification (P = 0.003) and mixed type calcification (P = 0.001). Multiple calcification was more likely to combine with IPH (P = 0.008), while simple basal calcification was not likely to combine IPH (P = 0.002). Smaller granular calcification was more likely to be associated with IPH (P < 0.05). In multivariate regression analysis of IPH and calcification characteristics, simple basal calcification was still a protective factor for IPH (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005), while multiple calcification was closely related to the occurrence of IPH (OR, 3.58; 95% CI, 1.49-8.61; P = 0.004). CONCLUSION: Calcification characteristics of carotid atherosclerotic plaques are closely related to the vulnerability of plaques, especially multiple calcification and mixed type calcification.

Current Smoking is a Risk Factor for the Irregular Surface and Calcification of Carotid Plaque in Men.

OBJECTIVE: To explore whether current smoking could influence plaque characteristics and determine its correlation to the irregular surface and calcification of carotid plaque. METHODS: Three hundred and seventeen patients with severe carotid atherosclerosis stenosis (SCAS) detected by color duplex flow imaging (CDFI) and confirmed by CT angiography (CTA) were recruited. The results of laboratory parameters were collected by using electronic database of the hospital. Computerized tomography (CT) scanning and high-resolution ultrasonography were performed for assessment of plaque morphology, respectively. RESULTS: All enrolled smokers and non-smokers had no significant difference among all characteristics not related to smoking. CT scanning could efficiently identify the difference among enrolled smokers and non-smokers not only for the characteristics related to smoking but also the onsets of carotid plaque. Surface morphology was also efficiently detected by ultrasonography. Further ridge trace analysis showed that ultrasonography is efficient for diagnosis of calcified plaque compared with gold standard for plaque diagnosis. Further correlation analysis showed that ultrasonography parameters could offer reliable evidence for plaque scores, which was associated with age index. Ultrasonography parameters could efficiently differentiate plaque morphologies among enrolled smokers and never-smokers. CONCLUSION: Current smoking was positively associated with plaque calcification onsets, and smoking cessation could efficiently attenuate such injury. High-frequency ultrasound can clearly distinguish the details of calcification with promising clinical significance for current smoking patients.

Maternal genetic structure in ancient Shandong between 9500 and 1800 years ago.

Archaeological and ancient DNA studies revealed that Shandong, a multi-culture center in northern coastal China, was home to ancient populations having ancestry related to both northern and southern East Asian populations. However, the limited temporal and geographical range of previous studies have been insufficient to describe the population history of this region in greater detail. Here, we report the analysis of 86 complete mitochondrial genomes from the remains of 9500 to 1800-year-old humans from 12 archaeological sites across Shandong. For samples older than 4600 years before present (BP), we found haplogroups D4, D5, B4c1, and B5b2, which are observed in present-day northern and southern East Asians. For samples younger than 4600 BP, haplogroups C (C7a1 and C7b), M9 (M9a1), and F (F1a1, F2a, and F4a1) begin to appear, indicating changes in the Shandong maternal genetic structure starting from the beginning of the Longshan cultural period. Within Shandong, the genetic exchange is possible between the coastal and inland regions after 3100 BP. We also discovered the B5b2 lineage in Shandong populations, with the oldest Bianbian individual likely related to the ancestors of some East Asians and North Asians. By reconstructing a maternal genetic structure of Shandong populations, we provide greater resolution of the population dynamics of the northern coastal East Asia over the past nine thousand years.

Ancient Xinjiang mitogenomes reveal intense admixture with high genetic diversity.

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.

Lipidomics of the brain, retina, and biofluids: from the biological landscape to potential clinical application in schizophrenia.

Schizophrenia is a serious neuropsychiatric disorder, yet a clear pathophysiology has not been identified. To date, neither the objective biomarkers for diagnosis nor specific medications for the treatment of schizophrenia are clinically satisfactory. It is well accepted that lipids are essential to maintain the normal structure and function of neurons in the brain and that abnormalities in neuronal lipids are associated with abnormal neurodevelopment in schizophrenia. However, lipids and lipid-like molecules have been largely unexplored in contrast to proteins and their genes in schizophrenia. Compared with the gene- and protein-centric approaches, lipidomics is a recently emerged and rapidly evolving research field with particular importance for the study of neuropsychiatric disorders such as schizophrenia, in which even subtle aberrant alterations in the lipid composition and concentration of the neurons may disrupt brain functioning. In this review, we aimed to highlight the lipidomics of the brain, retina, and biofluids in both human and animal studies, discuss aberrant lipid alterations in correlation with schizophrenia, and propose future directions from the biological landscape towards potential clinical applications in schizophrenia. Recent studies are in support of the concept that aberrations in some lipid species [e.g. phospholipids, polyunsaturated fatty acids (PUFAs)] lead to structural alterations and, in turn, impairments in the biological function of membrane-bound proteins, the disruption of cell signaling molecule accessibility, and the dysfunction of neurotransmitter systems. In addition, abnormal lipidome alterations in biofluids are linked to schizophrenia, and thus they hold promise in the discovery of biomarkers for the diagnosis of schizophrenia.

Correlation between risk factors of cerebrovascular disease and calcified plaque characteristics in patients with atherosclerotic severe carotid stenosis.

Objectives: The aim of this study was to evaluate the relationship between the risk factors of cerebral vascular diseases (CVD) and the characteristics of calcified plaques in patients with severe carotid arteriosclerosis stenosis (SCAS).Methods: A total of 402 patients with SCAS who were treated in our hospital between January to December 2016 were included in this study. The patients were divided into calcified plaque group and non-calcified plaque group according to the ultrasonography and computerized tomography angiography (CTA) or digital subtraction angiography (DSA) imaging of SCAS-responsible plaque and the characteristics of calcified plaques evaluated by high-frequency ultrasound.Results: The patients with long-term diabetes mellitus or higher levels of fasting blood glucose were more likely to develop calcified plaques (P = 0.00 and P = 0.021, respectively). In addition, the patients with calcified plaques were mostly smokers (P = 0.016). Their smoking duration and accumulative smoking exposure were higher than those without calcified plaque (P = 0.006 and P = 0.007, respectively). The basal location of calcification (P = 0.004) and the type of patchy calcification (P = 0.00) were both easier to appear in smokers, while non-smokers were more likely to have small granular calcification (P = 0.002). Furthermore, the carotid plaque calcification with mixed-location were more frequently seen in patients with hypertension (P = 0.016). The risk factors independently associated with plaque calcification were significantly associated with smoking status, smoking age, and accumulative smoking exposure, as well as age and diabetes mellitus (all P < 0.05).Conclusion: Smoking, diabetes mellitus and age were independent risk factors for carotid plaque calcification. Smoking and hypertension were associated with specific locations and types of plaque calcification.

Circular RNAs in early brain development and their influence and clinical significance in neuropsychiatric disorders.

Neuropsychiatric disorders represent a set of severe and complex mental illnesses, and the exact etiologies of which are unknown. It has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric disorders. Currently, the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment, because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental illness. Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNA (ncRNA) with a closed-loop structure. In recent years, there have been tremendous advances in our understanding of the expression profiles and biological roles of circRNAs. In the brain, circRNAs are particularly enriched and are expressed more abundantly in contrast to linear counterpart transcripts. They are highly active at neuronal synapses. These features make circRNAs uniquely crucial for understanding brain health, disease, and neuropsychiatric disorders. This review focuses on the role of circRNAs in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric disorders. In addition, we discuss the potential for blood or cerebrospinal fluid circRNAs to be used as novel biomarkers in the early diagnosis of neuropsychiatric disorders. The findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

Zinc mesoporphyrin induces rapid and marked degradation of the transcription factor Bach1 and up-regulates HO-1.

Heme oxygenase 1 (HO-1) is the first and rate-controlling enzyme in heme degradation. Bach1 is a mammalian transcriptional repressor of HO-1. To understand how zinc mesoporphyrin (ZnMP) induces the expression of HO-1, we investigated the effects of ZnMP on Bach1 mRNA and protein levels in human hepatoma Huh-7 cells by quantitative RT-PCR and Western blots. We found that ZnMP markedly up-regulated HO-1 mRNA and protein levels, and rapidly and significantly decreased Bach1 protein levels by increasing degradation of Bach1 protein [half life (t(1/2)) from 19 h to 45 min], whereas ZnMP did not influence Bach1 mRNA levels. The proteasome inhibitors, epoxomicin and MG132, significantly inhibited degradation of Bach1 by ZnMP in a dose-dependent fashion, indicating that the degradation of Bach1 by ZnMP is proteasome-dependent. Purified Bach1 C-terminal fragment bound heme, but there was no evidence for binding of ZnMP to the heme-binding region of Bach1. In conclusion, ZnMP produces profound post-transcriptional down-regulation of Bach1 protein levels and transcriptional up-regulation of HO-1. Our results indicate that ZnMP up-regulates HO-1 gene expression by markedly increasing Bach1 protein degradation in a proteasome-dependent manner.

Surprising Anticancer Activities of Psychiatric Medications: Old Drugs Offer New Hope for Patients With Brain Cancer.

Despite decades of research and major efforts, malignant brain tumors remain among the deadliest of all cancers. Recently, an increasing number of psychiatric drugs has been proven to possess suppressing activities against brain tumors, and rapid progress has been made in understanding the potential mechanisms of action of these drugs. In particular, the traditional mood stabilizer valproic acid, the widely used antidepressants fluoxetine and escitalopram oxalate, and the atypical psychiatric drug aripiprazole have demonstrated promise for application in brain tumor treatment strategies through multiple lines of laboratory, preclinical, and clinical evidence. The unexpected discovery of the anticancer properties of these drugs has ignited interest in the repurposing of other psychiatric drugs to combat brain cancer. In this review, we synthesize recent progress in understanding the potential molecular mechanisms underlying the brain cancer-killing activities of representative psychiatric drugs. We also identify key limitations in the repurposing of these medications that must be overcome to enhance our ability to successfully prevent and treat brain cancer, especially in the most vulnerable groups of patients, such as children and adolescents, pregnant women, and those with unfavorable genetic variants. Moreover, we propose perspectives that may guide future research and provide long-awaited new hope to patients with brain cancer and their families.

Antipsychotic drugs and sudden cardiac death: A literature review of the challenges in the prediction, management, and future steps.

Sudden cardiac death (SCD) is relatively uncommon, yet it is a deadly consequence of some antipsychotic medications in patients with psychiatric disorders. The widespread concerns about the adverse cardiac effects associated with antipsychotics and their unpredictable nature have led to a restriction on the use of some antipsychotic medications. Recent progress has been made in the identification of important genetic factors that may contribute to the adverse complication of antipsychotic drugs, suggesting that high-risk individuals can be identified prior to initiating therapy. In addition, some high-tech smart wearable medical devices have recently been developed, allowing users to record and analyze the electrocardiogram (ECG) in couple with artificial intelligence (AI) technologies, and notifying of irregular heart rhythms or arrhythmias, a medical condition well documented in most SCD cases. In this literature review, we summarize recent advances in understanding the link between SCD and antipsychotic drug usage, as well as in utilizing wearable medical devices for monitoring of cardiac arrhythmias. New strategies for improving the care of patients receiving antipsychotic medications are proposed. As it is now possible to evaluate the risk of SCD in patients on antipsychotic medications, preventative measures and close monitoring may be used to detect the early signs of adverse cardiac events and SCD.