Genome-wide Association Studies in Ancestrally Diverse Populations: Opportunities, Methods, Pitfalls, and Recommendations.

Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multi-ancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.

Clinical and genetic contributions to medical comorbidity in bipolar disorder: a study using electronic health records-linked biobank data.

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk.

Antidepressants that increase mitochondrial energetics may elevate risk of treatment-emergent mania.

Preclinical evidence suggests that antidepressants (ADs) may differentially influence mitochondrial energetics. This study was conducted to investigate the relationship between mitochondrial function and illness vulnerability in bipolar disorder (BD), specifically risk of treatment-emergent mania (TEM). Participants with BD already clinically phenotyped as TEM+ (n = 176) or TEM- (n = 516) were further classified whether the TEM associated AD, based on preclinical studies, increased (Mito+, n = 600) or decreased (Mito-, n = 289) mitochondrial electron transport chain (ETC) activity. Comparison of TEM+ rates between Mito+ and Mito- ADs was performed using generalized estimating equations to account for participants exposed to multiple ADs while adjusting for sex, age at time of enrollment into the biobank and BD type (BD-I/schizoaffective vs. BD-II). A total of 692 subjects (62.7% female, 91.4% White, mean age 43.0 ± 14.0 years) including 176 cases (25.3%) of TEM+ and 516 cases (74.7%) of TEM- with previous exposure to Mito+ and/or Mito- antidepressants were identified. Adjusting for age, sex and BD subtype, TEM+ was more frequent with antidepressants that increased (24.7%), versus decreased (13.5%) mitochondrial energetics (OR = 2.21; p = 0.000009). Our preliminary retrospective data suggests there may be merit in reconceptualizing AD classification, not solely based on monoaminergic conventional drug mechanism of action, but additionally based on mitochondrial energetics. Future prospective clinical studies on specific antidepressants and mitochondrial activity are encouraged. Recognizing pharmacogenomic investigation of drug response may extend or overlap to genomics of disease risk, future studies should investigate potential interactions between mitochondrial mechanisms of disease risk and drug response.

Chemical and Bioactive Evaluation of Essential Oils from Edible and Aromatic Mediterranean Lamiaceae Plants.

The Lamiaceae family, which includes several well-known aromatic plants, is scientifically relevant due to its essential oils (EOs). In this work, four EOs from Mediterranean species, namely Origanum vulgare L., Rosmarinus officinalis L., Salvia officinalis L., and Thymus vulgaris L., were evaluated for their volatile profiles and the biological activity in vitro to assess their potential use in the food and cosmetic sector. GC/MS analysis revealed dominant compounds, such as carvacrol, thymol, and eucalyptol. Regarding biological action, the samples exhibited antioxidant, cytotoxic, anti-inflammatory, antimicrobial, and antifungal activities, with O. vulgare and T. officinalis standing out. T. vulgaris showed the lowest EC50 in the reducing power assay, and O. vulgare had the lowest EC50 in the DPPH assay. Most EOs also displayed excellent anti-inflammatory responses and antifungal properties, with O. vulgare and T. vulgaris also demonstrating antibacterial activity. All EOs from Mediterranean species showed cytotoxicity against tumoral cell lines. Overall, the selected EOs stood out for their interesting bioactivities, with the obtained results underscoring their potential as natural preservatives and bioactive agents in various industrial applications, including food, pharmaceuticals, and cosmetics.

A cross-scale analysis to understand and quantify the effects of photosynthetic enhancement on crop growth and yield across environments.

Photosynthetic manipulation provides new opportunities for enhancing crop yield. However, understanding and quantifying the importance of individual and multiple manipulations on the seasonal biomass growth and yield performance of target crops across variable production environments is limited. Using a state-of-the-art cross-scale model in the APSIM platform we predicted the impact of altering photosynthesis on the enzyme-limited (Ac ) and electron transport-limited (Aj ) rates, seasonal dynamics in canopy photosynthesis, biomass growth, and yield formation via large multiyear-by-location crop growth simulations. A broad list of promising strategies to improve photosynthesis for C3 wheat and C4 sorghum were simulated. In the top decile of seasonal outcomes, yield gains were predicted to be modest, ranging between 0% and 8%, depending on the manipulation and crop type. We report how photosynthetic enhancement can affect the timing and severity of water and nitrogen stress on the growing crop, resulting in nonintuitive seasonal crop dynamics and yield outcomes. We predicted that strategies enhancing Ac alone generate more consistent but smaller yield gains across all water and nitrogen environments, Aj enhancement alone generates larger gains but is undesirable in more marginal environments. Large increases in both Ac and Aj generate the highest gains across all environments. Yield outcomes of the tested manipulation strategies were predicted and compared for realistic Australian wheat and sorghum production. This study uniquely unpacks complex cross-scale interactions between photosynthesis and seasonal crop dynamics and improves understanding and quantification of the potential impact of photosynthesis traits (or lack of it) for crop improvement research.

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

BACKGROUND: The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. METHODS: Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model. RESULTS: Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters. CONCLUSION: Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.

Advances on delta 5-unsaturated-polymethylene-interrupted fatty acids: Resources, biosynthesis, and benefits.

Though the knowledge on delta 5-unsaturated-polymethylene-interrupted fatty acids (Δ5-UPIFAs) is being updated, the issue of their integration still exists within the field. Thus, this review systematically summarizes the sources, biosynthesis and metabolism, analytical methods, preparation, and health-promoting roles of Δ5-UPIFAs. In plants, the content of Δ5-UPIFAs is higher, which is an ideal source. In animals, although the content of Δ5-UPIFAs is not high, there are many species, which is the possible source of some special Δ5-UPIFAs. At present, although the extraction of Δ5-UPIFAs is mainly from plants, the fermentation by organisms, especially for genetically modified microorganisms engineering maybe be a substitue of pepration of Δ5-UPIFAs. Δ5-UPIFAs have been proved to possess multi-beneficial effects, such as lipid lowering, anti-inflammation and so on, so it has a certain potential application value. However, related knowledge of the underlying molecular mechanisms regarding Δ5-UPIFAs limited, and how Δ5-UPIFAs work is not clear. Further clinical and human studies about Δ5-UPIFAs are also needed. Studies on tapping new resources, developing structured lipide rich in Δ5-UPIFA and enhancing delivery were quite deficient. This review emphasizes the further directions on Δ5-UPIFAs with scientific suggestions to pay more attention to the applications of Δ5-UPIFAs in food, pharmaceutical and cosmetic industries.

Applications of algae to obtain healthier meat products: A critical review on nutrients, acceptability and quality.

Meat constitutes one the main protein sources worldwide. However, ethical and health concerns have limited its consumption over the last years. To overcome this negative impact, new ingredients from natural sources are being applied to meat products to obtain healthier proteinaceous meat products. Algae is a good source of unsaturated fatty acids, proteins, essential amino acids, and vitamins, which can nutritionally enrich several foods. On this basis, algae have been applied to meat products as a functional ingredient to obtain healthier meat-based products. This paper mainly reviews the bioactive compounds in algae and their application in meat products. The bioactive ingredients present in algae can give meat products functional properties such as antioxidant, neuroprotective, antigenotoxic, resulting in healthier foods. At the same time, algae addition to foods can also contribute to delay microbial spoilage extending shelf-life. Additionally, other algae-based applications such as for packaging materials for meat products are being explored. However, consumers' acceptance for new products (particularly in Western countries), namely those containing algae, not only depends on their knowledge, but also on their eating habits. Therefore, it is necessary to further explore the nutritional properties of algae-containing meat products to overcome the gap between new meat products and traditional products, so that healthier algae-containing meat can occupy a significant place in the market.

Bioactive compounds, health benefits, and industrial applications of Tartary buckwheat (Fagopyrum tataricum).

Tartary buckwheat belongs to the family Polygonaceae, which is a traditionally edible and medicinal plant. Due to its various bioactive compounds, the consumption of Tartary buckwheat is correlated to a wide range of health benefits, and increasing attention has been paid to its potential as a functional food. This review summarizes the main bioactive compounds and important bioactivities and health benefits of Tartary buckwheat, emphasizing its protective effects on metabolic diseases and relevant molecular mechanisms. Tartary buckwheat contains a wide range of bioactive compounds, such as flavonoids, phenolic acids, triterpenoids, phenylpropanoid glycosides, bioactive polysaccharides, and bioactive proteins and peptides, as well as D-chiro-inositol and its derivatives. Consumption of Tartary buckwheat and Tartary buckwheat-enriched products is linked to multiple health benefits, e.g., antioxidant, anti-inflammatory, antihyperlipidemic, anticancer, antidiabetic, antiobesity, antihypertensive, and hepatoprotective activities. Especially, clinical studies indicate that Tartary buckwheat exhibits remarkable antidiabetic activities. Various tartary buckwheat -based foods presenting major health benefits as fat and blood glucose-lowering agents have been commercialized. Additionally, to address the safety concerns, i.e., allergic reactions, heavy metal and mycotoxin contaminations, the quality control standards for Tartary buckwheat and its products should be drafted and completed in the future.

Emerging Technologies to Extract Fucoxanthin from Undaria pinnatifida: Microwave vs. Ultrasound Assisted Extractions.

Macroalgae are an extensive resource for the obtention of bioactive compounds, mainly phenolic compounds, phlorotannins, and pigments. Fucoxanthin (Fx) is the most abundant pigment present in brown algae and has shown several useful bioactivities that can be used to fortify products in the food and cosmetic industries. Nevertheless, to date, there is still insufficient literature reporting on the extraction yield of Fx from U. pinnatifida species from green technologies. In this regard, the present study aims to optimize the extraction conditions to obtain the highest Fx yield from U. pinnatifida through emerging techniques, namely microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE). These methods will be compared with the conventional methodologies of heat-assisted extraction (HAE) and Soxhlet-assisted extraction (SAE). According to our results, even though the extraction yield could be slightly higher when using MAE than UAE, the Fx concentration obtained from the alga was double when using UAE. Thus, the Fx ratio in the final extract reached values of 124.39 mg Fx/g E. However, the optimal conditions should also be considered since UAE needed 30 min to perform the extraction, whereas MAE was able to obtain 58.83 mg Fx/g E in only 3 min and 2 bar, meaning less energy expenditure and minimum cost function. To our knowledge, this study obtains the highest concentrations of Fx ever reported (58.83 mg Fx/g E for MAE and 124.39 mg Fx/g E for UAE), with low energy consumption and short times (3.00 min for MAE and 35.16 min for UAE). Any of these results could be selected for further experiments and proposed for industrial scaling-up.

Kinetic Extraction of Fucoxanthin from Undaria pinnatifida Using Ethanol as a Solvent.

Fucoxanthin (Fx) has been proven to exert numerous biological properties, which makes it an interesting molecule with diverse industrial applications. In this study, the kinetic behavior of Fx was studied to optimize three variables: time (t-3 min to 7 days), temperature (T-5 to 85 °C), and concentration of ethanol in water (S-50 to 100%, v/v), in order to obtain the best Fx yield from Undaria pinnatifida using conventional heat extraction. The Fx content (Y1) was found through HPLC-DAD and expressed in µg Fx/g of algae sample dry weight (AS dw). Furthermore, extraction yield (Y2) was also found through dry weight analysis and was expressed in mg extract (E)/g AS dw. The purity of the extracts (Y3) was found and expressed in mg Fx/g E dw. The optimal conditions selected for Y1 were T = 45 °C, S = 70%, and t = 66 min, obtaining ~5.24 mg Fx/g AS; for Y2 were T = 65 °C, S = 60%, and t = ~10 min, obtaining ~450 mg E/g AS; and for Y3 were T = 45 °C, S = 70%, and t = 45 min, obtaining ~12.3 mg Fx/g E. In addition, for the selected optimums, a full screening of pigments was performed by HPLC-DAD, while phenolics and flavonoids were quantified by spectrophotometric techniques and several biological properties were evaluated (namely, antioxidant, antimicrobial, and cholinesterase inhibitory activity). These results could be of interest for future applications in the food, cosmetic, or pharmaceutical industries, as they show the Fx kinetic behavior and could help reduce costs associated with energy and solvent consumption while maximizing the extraction yields.

Susceptibility and transcriptomic response to plasma-activated water of Listeria monocytogenes planktonic and sessile cells.

Plasma-Activated Water (PAW) was generated from tap water using a surface dielectric barrier discharge at different discharge power (26 and 36 W) and activation time (5 and 30 min). The inactivation of a three-strain Listeria monocytogenes cocktail in planktonic and biofilm state was evaluated. PAW generated at 36 W-30 min showed the lowest pH and the highest hydrogen peroxide, nitrates, nitrites contents and effectiveness against cells on planktonic state, resulting in 4.6 log reductions after a 15-min treatment. Although the antimicrobial activity in biofilms formed on stainless steel and on polystyrene was lower, increasing the exposure time to 30 min allowed an inactivation >4.5 log cycles. The mechanisms of action of PAW were investigated using chemical solutions that mimic its physico-chemical characteristics and also RNA-seq analysis. The main transcriptomic changes affected carbon metabolism, virulence and general stress response genes, with several overexpressed genes belonging to the cobalamin-dependent gene cluster.

Power Disturbance Monitoring through Techniques for Novelty Detection on Wind Power and Photovoltaic Generation.

Novelty detection is a statistical method that verifies new or unknown data, determines whether these data are inliers (within the norm) or outliers (outside the norm), and can be used, for example, in developing classification strategies in machine learning systems for industrial applications. To this end, two types of energy that have evolved over time are solar photovoltaic and wind power generation. Some organizations around the world have developed energy quality standards to avoid known electric disturbances; however, their detection is still a challenge. In this work, several techniques for novelty detection are implemented to detect different electric anomalies (disturbances), which are k-nearest neighbors, Gaussian mixture models, one-class support vector machines, self-organizing maps, stacked autoencoders, and isolation forests. These techniques are applied to signals from real power quality environments of renewable energy systems such as solar photovoltaic and wind power generation. The power disturbances that will be analyzed are considered in the standard IEEE-1159, such as sag, oscillatory transient, flicker, and a condition outside the standard attributed to meteorological conditions. The contribution of the work consists of the development of a methodology based on six techniques for novelty detection of power disturbances, under known and unknown conditions, over real signals in the power quality assessment. The merit of the methodology is a set of techniques that allow to obtain the best performance of each one under different conditions, which constitutes an important contribution to the renewable energy systems.

Bioactive Natural Pigments' Extraction, Isolation, and Stability in Food Applications.

Color in food has multiple effects on consumers, since this parameter is related to the quality of a product, its freshness, and even its nutrient content. Each food has a characteristic color; however, this can be affected by the technological treatments that are applied during its manufacturing process, as well as its storage. Therefore, the development of new food products should take into account consumer preferences, the physical properties of a product, food safety standards, the economy, and applications of technology. With all of this, the use of food additives, such as dyes, is increasingly important due to the interest in the natural coloring of foods, strict regulatory pressure, problems with the toxicity of synthetic food colors, and the need for globally approved colors, in addition to current food market trends that focus on the consumption of healthy, organic, and natural products. It is for this reason that there is a growing demand for natural pigments that drives the food industry to seek or improve extraction techniques, as well as to study different stability processes, considering their interactions with the food matrix, in order to meet the needs and expectations of consumers.

Application of smart packaging for seafood: A comprehensive review.

Nowadays, due to the changes in lifestyle and great interest of consumers in a healthy life, people have started increasing their seafood consumption. But due to their short shelf life, experts are looking for a new packaging called smart packaging (SMP) for seafood. There are different indicators/sensors in SMP; one of the effective indices is time-temperature, which can show consumers the best time of using seafood based on their shelf life and experienced temperature. Another one is radio-frequency identification (RFID) that is a transmission device that represents a separate form of the electronic information-based SMP systems. RFID does not belong to any of the categories of markers or sensors; it is an auto recognition system that applies cordless sensors to indicate segments and collect real-time information without manual interposition. This review covers the use of SMP in all marine foods, including fish, due to its high consumption and high content of polyunsaturated fatty acids, eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3), which are the considerable factors of n-3 polyunsaturated fatty acids for human.

Polygenic prediction of bipolar disorder in a Latin American sample.

To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity-related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities.

Chlorophyll f can replace chlorophyll a in the soluble antenna of dinoflagellates.

Chlorophyll f is a new type of chlorophyll isolated from cyanobacteria. The absorption and fluorescence characteristics of chlorophyll f permit these oxygenic-photosynthetic organisms to thrive in environments where white light is scarce but far-red light is abundant. To explore the ligand properties of chlorophyll f and its energy transfer profiles we established two different in vitro reconstitution systems. The reconstituted peridinin-chlorophyll f protein complex (chlorophyll f-PCP) showed a stoichiometry ratio of 4:1 between peridinin and chlorophyll f, consistent with the peridinin:chlorophyll a ratio from native PCP complexes. Using emission wavelength at 712 nm, the excitation fluorescence featured a broad peak at 453 nm and a shoulder at 511 nm confirming energy transfer from peridinin to chlorophyll f. In addition, by using a synthetic peptide mimicking the first transmembrane helix of light-harvesting chlorophyll proteins of plants, we report that chlorophyll f, similarly to chlorophyll b, did not interact with the peptide contrarily to chlorophyll a, confirming the accessory role of chlorophyll f in photosystems. The binding of chlorophyll f, even in the presence of chlorophylls a and b, by PCP complexes shows the flexibility of chlorophyll-protein complexes and provides an opportunity for the introduction of new chlorophyll species to extend the photosynthetic spectral range.

Association of Bipolar Disorder With Major Adverse Cardiovascular Events: A Population-Based Historical Cohort Study.

OBJECTIVE: This study aimed to assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACEs) after adjusting for established cardiovascular disease (CVD) risk factors. METHODS: We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients older than 30 years with a clinical encounter from 1998 to 2000 with no prior MACE, atrial fibrillation, or heart failure were followed up through March 1, 2016. BD diagnosis was validated by chart review. Cox proportional hazards regression models were adjusted for established CVD risk factors, alcohol use disorder, other substance use disorders (SUDs), and major depressive disorder (MDD). RESULTS: The cohort included 288 individuals with BD (0.81%) and 35,326 individuals without BD as the reference group (Ref). Median (interquartile range) follow-up was 16.5 (14.6-17.5) years. A total of 5636 MACE events occurred (BD, 59; Ref, 5577). Survival analysis showed an association between BD and MACE (median event-free-survival rates: BD, 0.80; Ref, 0.86; log-rank p = .018). Multivariate regression adjusting for age and sex also yielded an association between BD and MACE (hazard ratio [HR] = 1.93; 95% confidence interval [CI] = 1.43-2.52; p < .001). The association remained significant after further adjusting for smoking, diabetes mellitus, hypertension, high-density lipoprotein cholesterol, and body mass index (HR = 1.66; 95% CI = 1.17-2.28; p = .006), and for alcohol use disorder, SUD, and MDD (HR = 1.56; 95% CI = 1.09-2.14; p = .010). CONCLUSIONS: In this study, BD was associated with an increased risk of MACE, which persisted after adjusting for established CVD risk factors, SUDs, and MDD. These results suggest that BD is an independent risk factor for major clinical cardiac disease outcomes.

Clinical Phenotype of Tardive Dyskinesia in Bipolar Disorder.

PURPOSE: Recognizing the negative impact that antipsychotic-induced movement disorders have on the quality of life and treatment outcomes in bipolar disorder (BD), this study aimed to assess clinical correlates and antipsychotic use patterns of tardive dyskinesia (TD+) in BD. MATERIALS AND METHODS: Participants with and without TD were included. Clinical variables were compared using t-test and χ2 test. Antipsychotic use patterns in TD+, including number of trials, mean doses, and estimated cumulative exposure, were assessed in a case-only analysis. RESULTS: The prevalence rate of TD was 5.1%. In comparison to the TD- group (n = 1074), TD+ participants (n = 58) were older, more likely to be female and have type I bipolar illness. There were 60.3% of the TD+ group that continued using antipsychotics at study entry and had a mean cumulative exposure to antipsychotics of 18.2 ± 15.6 years. Average dose, in haloperidol equivalents, was 5.9 ± 3.5 mg and 77.7% of the trials were second-generation antipsychotics. CONCLUSIONS: This study confirms previously identified TD risk factors, such as age, sex, and bipolar subtype in a large BD cohort. Limitations included a cross-sectional design and the lack of tardive illness severity assessment. As atypical antipsychotics continue to be primary mood stabilization treatment, attempting to harmonize large data sets to identify additional biomarkers of tardive risk will optimize individualized care for patients with BD.

The role of additives on acrylamide formation in food products: a systematic review.

Acrylamide (AA) is a toxic substance formed in many carbohydrate-rich food products, whose formation can be reduced by adding some additives. Furthermore, the type of food consumed determines the AA intake. According to the compiled information, the first route causing AA formation is the Maillard reaction. Some interventions, such as reducing AA precursors in raw materials, (i.e., asparagine), reducing sugars, or decreasing temperature and processing time can be applied to limit AA formation in food products. The L-asparaginase is more widely used in potato products. Also, coatings loaded with proteins, enzymes, and phenolic compounds are new techniques for reducing AA content. Enzymes have a reducing effect on AA formation by acting on asparagine; proteins by competing with amino acids to participate in Maillard, and phenolic compounds through their radical scavenging activity. On the other hand, some synthetic and natural additives increase the formation of AA. Due to the high exposure to AA and its toxic effects, it is essential to recognize suitable food additives to reduce the health risks for consumers. In this sense, this study focuses on different additives that are proven to be effective in the reduction or formation of AA in food products.