Anti-Inflammatory Effects of Bioactive Compounds from Seaweeds, Bryozoans, Jellyfish, Shellfish and Peanut Worms.

Inflammation is a defense mechanism of the body in response to harmful stimuli such as pathogens, damaged cells, toxic compounds or radiation. However, chronic inflammation plays an important role in the pathogenesis of a variety of diseases. Multiple anti-inflammatory drugs are currently available for the treatment of inflammation, but all exhibit less efficacy. This drives the search for new anti-inflammatory compounds focusing on natural resources. Marine organisms produce a broad spectrum of bioactive compounds with anti-inflammatory activities. Several are considered as lead compounds for development into drugs. Anti-inflammatory compounds have been extracted from algae, corals, seaweeds and other marine organisms. We previously reviewed anti-inflammatory compounds, as well as crude extracts isolated from echinoderms such as sea cucumbers, sea urchins and starfish. In the present review, we evaluate the anti-inflammatory effects of compounds from other marine organisms, including macroalgae (seaweeds), marine angiosperms (seagrasses), medusozoa (jellyfish), bryozoans (moss animals), mollusks (shellfish) and peanut worms. We also present a review of the molecular mechanisms of the anti-inflammatory activity of these compounds. Our objective in this review is to provide an overview of the current state of research on anti-inflammatory compounds from marine sources and the prospects for their translation into novel anti-inflammatory drugs.

A Conceptual Framework to Design Connected Mental Health Solutions in the United Arab Emirates: Questionnaire Study.

BACKGROUND: Connected mental health (CMH) is a field presenting information and communications technology-based mental care interventions that could help overcome many mental care delivery barriers. Culture and background influence people's attitudes, preferences, and acceptance of such solutions. Therefore, the suitability of CMH solutions to the targeted population is an important factor in their successful adoption. OBJECTIVE: The aim of this study is to develop a framework for the design and creation of CMH solutions suitable for the UAE context. The framework is based on investigating enablers and barriers of CMH adoption in the United Arab Emirates, from the mental health professional's (MHP) perspective and from related literature. METHODS: A survey of literature on relevant studies addressing the use of technology for mental care in Arab countries, and a web-based questionnaire-based survey with 17 MHPs practicing in the United Arab Emirates investigating their attitudes and views toward CMH was conducted. Results from the questionnaire and from related studies were analyzed to develop the design framework. RESULTS: On the basis of findings from the literature survey and analyzing MHP answers to the web-based survey, a framework for the design of CMH solutions for the UAE population was developed. The framework presents four types of recommendation categories: favorable criteria, which included blended care, anonymity, and ease of use; cultural factors including availability in multiple languages, mainly Arabic and English, in addition to religious and cultural considerations; technical considerations, including good-quality communication, availability in formats compatible with mobile phones, and providing technical support; and users' health and data safety considerations, including users' suitability testing, confidentiality, and ensuring MHP integrity. CONCLUSIONS: CMH has the potential to help overcome many mental care barriers in the United Arab Emirates in particular and in the Arab world in general. CMH adoption in the United Arab Emirates has a potential for success. However, many factors should be taken into account, mainly cultural, religious, and linguistic aspects.

A Biofeedback-Based Mobile App With Serious Games for Young Adults With Anxiety in the United Arab Emirates: Development and Usability Study.

BACKGROUND: Following the outbreak of COVID-19, several studies have reported that young adults encountered a rise in anxiety symptoms, which could negatively affect their quality of life. Promising evidence suggests that mobile apps with biofeedback, serious games, breathing exercises, and positive messaging, among other features, are useful for anxiety self-management and treatment. OBJECTIVE: This study aimed to develop and evaluate the usability of a biofeedback-based app with serious games for young adults with anxiety in the United Arab Emirates (UAE). METHODS: This study consists of two phases: Phase I describes the design and development of the app, while Phase II presents the results of a usability evaluation by experts. To elicit the app's requirements during Phase I, we conducted (1) a survey to investigate preferences of young adults in the UAE for mobile games for stress relief; (2) an analysis of serious games for anxiety; and (3) interviews with mental health professionals and young adults in the UAE. In Phase II, five experts tested the usability of the developed app using a set of Nielsen's usability heuristics. RESULTS: A fully functional biofeedback-based app with serious games was co-designed with mental health professionals. The app included 4 games (ie, a biofeedback game, card game, arcade game, and memory game), 2 relaxation techniques (ie, a breathing exercise and yoga videos), and 2 additional features (ie, positive messaging and a mood tracking calendar). The results of Phase II showed that the developed app is efficient, simple, and easy to use. Overall, the app design scored an average of 4 out of 5. CONCLUSIONS: The elicitation techniques used in Phase I resulted in the development of an easy-to-use app for the self-management of anxiety. Further research is required to determine the app's usability and effectiveness in the target population.

Outcomes of guideline-based medical therapy in patients with acute heart failure and reduced left ventricular ejection fraction: Observations from the Gulf acute heart failure registry (Gulf CARE).

ABSTRACT: This study aimed to report on the use, predictors and outcomes of guideline-based medical therapy (GBMT) in patients with acute heart failure (HF) with reduced ejection fraction of <40% (HFrEF), from seven countries in the Arabian Gulf.Patients with acute HFrEF (N = 2680), aged 18 years or older, and hospitalized February-November 2012 were recruited and data were collected post discharge at 3 months (n = 2477) and 1 year (n = 2418). The use and doses of GBMT were evaluated as per European, American and Canadian HF guidelines. Analyses were performed using multivariate logistic regression. This study was registered at clinicaltrials.gov (NCT01467973).The majority of patients were on dual (39%) and triple (39%) GBMT modalities, 14% received one GBMT medication, while 7.2% were not on any GBMT medications. On admission, 80% of patients were on renin-angiotensin system (RAS) blockers, 75% on b-blockers and 56% on mineralocorticoid receptor antagonists (MRAs), with a small proportion of these patients were taking target doses (RAS blockers 13%, b-blockers 7.3%, MRAs 14%). Patients taking triple GBMT were younger (P < .001), less likely to have comorbidities such as diabetes mellitus (P < .001) and CKD/dialysis (P < .001), less likely to receive in-hospital invasive treatments (P < .001), and more likely to be treated by a cardiologist (P < .001), than patients on a single medication. Patients taking triple GBMT showed significantly reduced all-cause mortality both at 3-months (P = .048), and at 12-months (P = .003), compared to patients taking no GBMT.Triple GBMT prescribing and dosing in patients with HFrEF were suboptimal in the Arabian Gulf. Further studies are required to investigate GBMT utilization and dosing in the outpatient setting.

Neural Processing of Dynamic Animated Social Interactions in Young Children With Autism Spectrum Disorder: A High-Density Electroencephalography Study.

Background: Atypical neural processing of social visual information contributes to impaired social cognition in autism spectrum disorder. However, evidence for early developmental alterations in neural processing of social contingencies is scarce. Most studies in the literature have been conducted in older children and adults. Here, we aimed to investigate alterations in neural processing of social visual information in children with autism spectrum disorder compared to age-matched typically developing peers. Methods: We used a combination of 129-channel electroencephalography and high-resolution eye-tracking to study differences in the neural processing of dynamic cartoons containing human-like social interactions between 14 male children with autism spectrum disorder and 14 typically developing male children, aged 2-5 years. Using a microstate approach, we identified four prototypical maps in both groups and compared the temporal characteristics and inverse solutions (activation of neural sources) of these maps between groups. Results: Inverse solutions of the group maps that were most dominant during free viewing of the dynamic cartoons indicated decreased prefrontal and cingulate activation, impaired activation of the premotor cortex, and increased activation of parietal, temporal, occipital, and cerebellar regions in children with autism spectrum disorder compared to their typically developing peers. Conclusions: Our findings suggest that impairments in brain regions involved in processing social contingencies embedded in dynamic cartoons are present from an early age in autism spectrum disorder. To the best of our knowledge, this is the first study to investigate neural processing of social interactions of children with autism spectrum disorder using dynamic semi-naturalistic stimuli.

Abnormal development of early auditory processing in 22q11.2 Deletion Syndrome.

The 22q11.2 Deletion Syndrome (22q11.2 DS) is one of the highest genetic risk factors for the development of schizophrenia spectrum disorders. In schizophrenia, reduced amplitude of the frequency mismatch negativity (fMMN) has been proposed as a promising neurophysiological marker for progressive brain pathology. In this longitudinal study in 22q11.2 DS, we investigate the progression of fMMN between childhood and adolescence, a vulnerable period for brain maturation. We measured evoked potentials to auditory oddball stimuli in the same sample of 16 patients with 22q11.2 DS and 14 age-matched controls in childhood and adolescence. In addition, we cross-sectionally compared an increased sample of 51 participants with 22q11.2 DS and 50 controls divided into two groups (8-14 and 14-20 years). The reported results are obtained using the fMMN difference waveforms. In the longitudinal design, the 22q11.2 deletion carriers exhibit a significant reduction in amplitude and a change in topographic patterns of the mismatch negativity response from childhood to adolescence. The same effect, reduced mismatch amplitude in adolescence, while preserved during childhood, is observed in the cross-sectional study. These results point towards functional changes within the brain network responsible for the fMMN. In addition, the adolescents with 22q11.2 DS displayed a significant increase in amplitude over central electrodes during the auditory N1 component. No such differences, reduced mismatch response nor increased N1, were observed in the typically developing group. These findings suggest different developmental trajectories of early auditory sensory processing in 22q11.2 DS and functional changes that emerge during the critical period of increased risk for schizophrenia spectrum disorders.

Investigating the microstructural and neurochemical environment within the basal ganglia of current methamphetamine abusers.

BACKGROUND: Methamphetamine is a highly addictive psychostimulant and the medical, social, and economic consequences associated with its use have become a major international problem. Current evidence has shown methamphetamine to be particularly neurotoxic to dopamine neurons and striatal structures within the basal ganglia. A previous study from our laboratory demonstrated larger putamen volumes in actively using methamphetamine-dependent participants. The purpose of this current study was to determine whether striatal structures in the same sample of participants also exhibit pathology on the microstructural and molecular level. METHODS: Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were carried out in current methamphetamine users (n = 18) and healthy controls (n = 22) to investigate diffusion indices and neurometabolite levels in the basal ganglia. RESULTS: Contrary to findings from previous DTI and MRS studies, no significant differences in diffusion indices or metabolite levels were observed in the basal ganglia regions of current methamphetamine users. CONCLUSIONS: These findings differ from those reported in abstinent users and the absence of diffusion and neurochemical abnormalities may suggest that striatal enlargement in current methamphetamine use may be due to mechanisms other than edema and glial proliferation.

The effects of methylphenidate on cognitive control in active methamphetamine dependence using functional magnetic resonance imaging.

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18-46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects.

Functional and structural brain changes associated with methamphetamine abuse.

Methamphetamine (MA) is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET) and functional and structural magnetic resonance imaging (MRI). The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

Striatal volume increases in active methamphetamine-dependent individuals and correlation with cognitive performance.

The effect of methamphetamine (MA) dependence on the structure of the human brain has not been extensively studied, especially in active users. Previous studies reported cortical deficits and striatal gains in grey matter (GM) volume of abstinent MA abusers compared with control participants. This study aimed to investigate structural GM changes in the brains of 17 active MA-dependent participants compared with 20 control participants aged 18-46 years using voxel-based morphometry and region of interest volumetric analysis of structural magnetic resonance imaging data, and whether these changes might be associated with cognitive performance. Significant volume increases were observed in the right and left putamen and left nucleus accumbens of MA-dependent compared to control participants. The volumetric gain in the right putamen remained significant after Bonferroni correction, and was inversely correlated with the number of errors (standardised z-scores) on the Go/No-go task. MA-dependent participants exhibited cortical GM deficits in the left superior frontal and precentral gyri in comparison to control participants, although these findings did not survive correction for multiple comparisons. In conclusion, consistent with findings from previous studies of abstinent users, active chronic MA-dependent participants showed significant striatal enlargement which was associated with improved performance on the Go/No-go, a cognitive task of response inhibition and impulsivity. Striatal enlargement may reflect the involvement of neurotrophic effects, inflammation or microgliosis. However, since it was associated with improved cognitive function, it is likely to reflect a compensatory response to MA-induced neurotoxicity in the striatum, in order to maintain cognitive function. Follow-up studies are recommended to ascertain whether this effect continues to be present following abstinence. Several factors may have contributed to the lack of more substantial cortical and subcortical GM changes amongst MA-dependent participants, including variability in MA exposure variables and difference in abstinence status from previous studies.

Subjective effects in humans following administration of party pill drugs BZP and TFMPP alone and in combination.

The use of piperazine derivatives, colloquially named 'party pills', has been escalating in New Zealand and worldwide since their introduction in the 1990s. Benzylpiperazine (BZP) is often used alone, or can be combined with trifluoromethylphenylpiperazine (TFMPP). Taken together as an oral dose, they have been reported to produce effects similar to 3, 4-methylenedioxymethamphetamine (MDMA). While the pharmacokinetic data have recently been published, little research has been conducted on the subjective effects of these piperazines on humans. This paper outlines the subjective effects observed following oral doses of BZP (200 mg) and TFMPP (60 mg) alone, or in combination (100/30 mg) compared to placebo. Participants were asked to comment on the subjective effects of each drug using three subjective rating scales-the Addiction Center Research Inventory (ARCI), the Profile of Mood States (POMS), and the Visual Analog Scales (VAS)-before and approximately 120 min after a single dose. BZP showed significant dexamphetamine-like stimulant effects, inducing euphoria, sociability, and drug liking, whereas TFMPP induced fewer stimulant-like effects and increased anxiety, via its serotonergic effects. The combination of BZP and TFMPP induced similar subjective effects, along with well-characterized dexamphetamine- and MDMA-like effects. These subjective data allow for obvious comparisons to be made between party pill drugs and other commonly known stimulants. However, despite estimates of over 20 million doses sold in New Zealand alone and increasing seizures by the Drug Enforcement Administration in the USA, there are no published cases of dependence worldwide. The long-term effects of regular party pill use are also unknown, and create the potential for future research.

Determining the subjective and physiological effects of BZP combined with TFMPP in human males.

RATIONALE: 'Party Pills' containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been used in a recreational context since the 1990s and, prior to April 2008, were legally available in New Zealand. Taken together, they have been reported to produce a 'high' similar to that produced by 3,4-methylenedioxymethamphetamine (MDMA). OBJECTIVES: There has been little research on the subjective effects of piperazines in humans. The purpose of this study is to further investigate the subjective and physiological responses following an oral dose of BZP combined with TFMPP in males. METHODS: In a randomised, double-blind, placebo-controlled study the subjective and physiological effects of BZP/TFMPP were investigated in 36 healthy, non-smoking males (mean age 22 ± 4 years). Participants were tested before and approximately 120 min after administration of a single dose of placebo (n = 16) or 100/30 mg BZP/TFMPP (n = 20). Participants were required to comment on the subjective effects using three rating scales­the Addiction Research Centre Inventory (ARCI), the Visual Analogue Scale (VAS) and the Profile of Mood States (POMS). Participants' blood pressure, heart rate and body temperature were also measured. RESULTS: Statistical analysis using repeated-measures analysis of variance (ANOVA) and planned comparisons revealed that BZP/TFMPP significantly increases blood pressure and heart rate (p < 0.05). Likewise, the subjective rating scales revealed that BZP/TFMPP has significant dexamphetamine-like effects, increases dysphoria and feelings of self-confidence (p < 0.05). CONCLUSION: These physiological and subjective data reflect clear similarities between the effects of BZP/TFMPP and commonly known stimulants such as dexamphetamine and MDMA.

Determining the subjective effects of TFMPP in human males.

RATIONALE: Trifluoromethylphenyl piperazine (TFMPP) is an active constituent of a relatively new group of recreational drugs known as 'party pills'. TFMPP has been anecdotally reported to induce mild psychedelic effects similar to lysergic acid diethylamide and psilocybin. There has been no research about the subjective effects of TFMPP in humans. OBJECTIVES: This study aimed to investigate the subjective effects of TFMPP in human males. METHODS: A randomised, double-blind, placebo-controlled trial design was used to investigate the subjective effects of TFMPP in 30 healthy, non-smoking male volunteers (mean age 24 +/- 4 years). Participants were randomised into two groups and given either TFMPP 60 mg (n = 15) or placebo (n = 15). Each participant completed three rating scales, the Addiction Research Centre Inventory (ARCI), the Profile of Mood States (POMS) and the Visual Analogue Scales (VAS), both before and 120 min after drug administration. RESULTS: Results from the ARCI indicated that TFMPP produced increases in 'dysphoria' and 'dexamphetamine-like effects'. TFMPP also increased ratings of 'tension/anxiety' and 'confusion/bewilderment' as rated on the POMS. Results from the VAS indicated increases in 'drug liking', 'high' and 'stimulated' ratings relevant to placebo. CONCLUSIONS: Increased ratings of 'dexamphetamine-like effects', 'tension/anxiety', 'stimulated' and 'high' following TFMPP administration resemble the subjective effects of common amphetamine-type stimulants. However, increases in 'dysphoria' and 'confusion/bewilderment' ratings following TFMPP are more commonly associated with drugs that have greater effects on serotonin release, binding and reuptake such as 1-[3-chlorophenyl]-piperazine, fenfluramine and lysergic acid diethylamide.