Disease Risk Reduction Research Articles

Sodium Intake and Sodium to Potassium Ratio among New York City Adults in the 2018 Heart Follow-Up Study

BackgroundHigh sodium and low potassium intake are positively associated with blood pressure, a significant risk factor for cardiovascular disease. The mean intake of sodium among United States adults exceeds the chronic disease risk reduction level of 2300 mg/d, whereas potassium intake remains lower than the recommended levels. From 2008 through 2019, there were several local and national initiatives to reduce sodium in New York City (NYC). ObjectivesWe aimed to update and compare estimates of sodium intake among NYC adults overall and by covariates from the 2010 Heart Follow-Up Study (HFUS) with the 2018 HFUS. We also estimated the 2018 sodium-to-potassium ratio to understand overall diet quality among demographic groups. MethodsThis cross-sectional study used sodium and potassium measurements from 24-h urine collection and self-reported data from 2509 and 1656 participants in the 2018 and 2010 HFUS, respectively. The weighted mean daily intake of sodium and the sodium-to-potassium ratio were estimated. T-tests and multivariable linear regression models with tests for interactions were used to compare changes in sodium intake. ResultsThe mean sodium intake of adult New Yorkers in 2018 was 3292 mg/d. Sodium intake did not change from 2010 (3234 mg/d, P = 0.45) to 2018 in the overall population, although there was a decrease in sodium intake among adults 18–24 y old (3445 mg/d to 2957 mg/d, P = 0.05). The daily mean sodium-to-potassium ratio was 1.7 mg/mg. The highest sodium-to-potassium ratios were among Black females 18–44 y old (2.0) and 45–64 y old (2.2) and Black (2.1) and Latino (2.1) males between 18 and 44 y old. ConclusionsThe lack of population-level changes in sodium intake and the high sodium-to-potassium ratios among Black females and younger Black and Latino males suggest that further efforts to reduce sodium in the food supply and address persistent inequities are needed.

Is "tobacco harm reduction" possible? Other countries' experiences and perspectives, and how they could inform tobacco control in Japan

"Tobacco harm reduction" is defined as a method to minimize harm and risk of death and disease without eliminating tobacco and nicotine use. In Japan, where heated tobacco products (HTPs) are prevalent, the tobacco industry is progressively endorsing the concept of "tobacco harm reduction." Therefore, stakeholders in tobacco control must urgently share perspectives and experiences surrounding this issue. This discussion paper aimed to propose four requirements for effectively implementing "tobacco harm reduction" as a public health measure: (1) disease risk reduction, (2) cigarette smoking cessation, (3) no additional public health concerns, and (4) regulatory authorities held by health agencies, and compile information on them regarding nicotine-containing electronic cigarettes (e-cigarettes) and HTPs. Another aim was to summarize policies related to "tobacco harm reduction" adopted by an international organization (World Health Organization (WHO) and health authorities in foreign countries (the United States of America (USA), the United Kingdom (UK), Australia, Italy, and the Republic of Korea) to explore the implications of these requirements on Japan's approach. Regarding the first three requirements, scientific evidence indicated that e-cigarettes offers some level of risk reduction and can assist with cigarette smoking cessation. The potential uptake of e-cigarettes among youth and their possibility to serve as a gateway to combusted cigarette use is a concern, though a definitive causal link is yet to be established between the uptake of e-cigarette in youth and the subsequent use of different tobacco products. There is insufficient scientific evidence for any of the three requirements for HTPs. Regarding the official policies, WHO took the position that the same regulations should be applied to all tobacco products. Only the UK and USA officially established a health system based on the concept of "tobacco harm reduction"; even in Italy and the Republic of Korea, where HTPs are relatively widespread, health authorities denied any risk reduction by introducing HTPs. The UK officially adopted a smoking cessation policy with e-cigarettes. The USA established a modified risk tobacco product system under federal legislation enacted in 2009, whereas of June 2023, no HTP or e-cigarettes were recognized as explicitly reducing health risk. Regarding the fourth requirement, the UK and USA institutionalized "tobacco harm reduction" under health authorities' regulation independent of the tobacco industry. The introduction of a tobacco harm reduction policy in Japan should be considered only in line with health authorities' regulation and implementation of comprehensive tobacco control measures independent of the tobacco industry.

Abstract P299: Alteration of Cardiac Autonomic Function Through Inhalation of Biogenic Volatile Organic Compounds

Background: There is an inverse relationship between exposure to greenspaces and prevalence of cardiovascular disease and cardiovascular disease risk factors. More specifically, green exposure is associated with electrocardiogram (ECG) changes, suggesting a potential alteration of cardiac autonomic balance. One proposed mechanism by which cardiac autonomic balance may be altered is a direct physiologic effect of inhalable plant derived compounds, or biogenic volatile organic compounds (bVOCs), including limonene, α- and β-pinene which are commonly released from vegetation. Therefore, we examined the relationship between acute exposure of isolated bVOCs and cardiac autonomic tone. Hypothesis: We hypothesize that controlled exposure to isolated individual bVOCs will decrease cardiac sympathetic tone. Methods: Under controlled conditions after a bVOC washout period, healthy adults ages 18-70 were exposed to limonene (n=32), α-pinene (n=24), β-pinene (n=17), and a control (room air, n=9). Exposure consisted of one inhalation every 30 seconds for a total of 5 minutes (10 inhalations total). Pre- and post-exposure measurements of supine heart rate variability (HRV) were conducted following a 10-minute rest period. HRV was analyzed using a clean, 5-minute epoch with >95% effective data length. Statistical analysis was performed using paired t-tests to determine changes in HR and HRV. Significance level was set at p<0.05, a priori . Results: Our population was primarily female (56%, 18 of 32), white (53%, 17 of 32), high income (47%, 15 of 32), and had an education higher than a 4-year degree (62.5%, 20 of 32). There were significant decreases in HR when exposed to limonene (pre: 64.87±9.86bpm vs. post: 63.26±9.10bpm, p<.001) and α-pinene (pre: 63.98±9.32bpm vs. post: 61.64±9.72bpm, p=.008), along with trends seen in β-pinene (pre: 65.78±10.60bpm vs. post: 63.74±9.65bpm, p=.066). Control exposure showed no difference (pre: 65.40±8.38bpm vs. post: 64.14±9.35bpm, p=.301). Normalized low- (LF) and high-frequency (HF) HRV parameters showed no change across isolated bVOCs, however the LF/HF ratio scores decreased significantly following β-pinene exposure (pre: 1.62±1.69 vs. post: 0.96±0.96, p=.039). HRV time-domain parameters RMSSD and SDNN did not change following isolate exposure. Conclusions: Post-exposure decreases in HR and LFHF ratios indicate the potential for cardiovascular disease risk reduction from bVOC exposure leading to decreased sympathetic tone. Additional work is required to determine the mechanism of exposure-related changes.

Unveiling potential drug targets for hyperparathyroidism through genetic insights via Mendelian randomization and colocalization analyses

Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.

Exercise positively impacts global longitudinal strain in women at risk of developing cardiovascular disease

AbstractCardiovascular (CV) disease accounts for one third of deaths in females, with hypertension (HTN) and type 2 diabetes mellitus (T2DM) risk factors for its development. Global longitudinal strain (GLS) is a strong prognostic indicator for future CV dysfunction and can be impaired in women with HTN and T2DM. This study aimed to determine if exercise impacts GLS in women with HTN or T2DM. A randomized crossover trial was conducted with 15 women (aged 64.1 ± 4.7) diagnosed with HTN (n = 12) or T2DM (n = 3). Participants completed an 8‐week exercise and 8‐week non‐exercising control period, separated by a 21.6 ± 14.2‐week washout period. Resting echocardiography and exercise testing were performed pre and post each arm to measure GLS and aerobic fitness (VO2peak). GLS (%) improved significantly following exercise (−16.8 ± 1.5 to −18.4 ± 1.8; p ≤ 0.001, d = 0.98), but not control (−17.2 ± 2.0 to −16.9 ± 1.4; p = 0.585, d = −0.14). Similarly, VO2peak (mL/kg/min) increased following exercise (18.0 ± 2.1 to 19.2 ± 2.6; p ≤ 0.001, d = 0.53), but not control (17.5 ± 2.7–17.2 ± 2.7; p = 0.269, d = −0.12). There were significant between‐group differences for GLS (p ≤ 0.001, d = 1.02) and VO2peak (p = 0.011, d = 0.63). Aerobic exercise positively impacts GLS and VO2peak in women with HTN and T2DM. GLS may inform exercise professionals regarding the early effectiveness of an aerobic exercise intervention and infer a reduction in CV disease risk.

Intensive Blood Pressure Lowering in Individuals With Low Diastolic Blood Pressure and Elevated Troponin Levels in SPRINT.

Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels. A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for interaction=0.57). In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study.

Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01). Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

Beyond Statins: Novel Lipid-Lowering Agents for Reducing Risk of Atherosclerotic Cardiovascular Disease

Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials.

A short-term, randomized, controlled, feasibility study of the effects of different vegetables on the gut microbiota and microRNA expression in infants

The complementary diet influences the gastrointestinal (gut) microbiota composition and, in turn, host health and, potentially, microRNA (miRNA) expression. This study aimed to assess the feasibility of altering the gut microbial communities with short-term food introduction and to determine the effects of different vegetables on the gut microbiota and miRNA expression in infants. A total of 11 infants were randomized to one of the following intervention arms: control, broccoli, or carrot. The control group maintained the milk diet only, while the other groups consumed either a broccoli puree or a carrot puree on days 1–3 along with their milk diet (human milk or infant formula). Genomic DNA and total RNA were extracted from fecal samples to determine the microbiota composition and miRNA expression. Short-term feeding of both broccoli and carrots resulted in changes in the microbiota and miRNA expression. Compared to the control, a trend toward a decrease in Shannon index was observed in the carrot group on days 2 and 4. The carrot and broccoli groups differed by weighted UniFrac. Streptococcus was increased on day 4 in the carrot group compared to the control. The expression of two miRNAs (i.e., miR-217 and miR-590-5p) trended towards decrease in both the broccoli and carrot groups compared to the control, whereas increases in eight and two different miRNAs were observed in the carrot and broccoli groups, respectively. Vegetable interventions differentially impacted the gut microbiota and miRNA expression, which may be a mechanism by which total vegetable intake and variety are associated with reduced disease risk.

Probiotics: Health benefits, food application, and colonization in the human gastrointestinal tract

AbstractProbiotics have become increasingly popular over the past two decades due to the continuously expanding scientific evidence indicating their beneficial effects on human health. Therefore, they have been applied in the food industry to produce functional food, which plays a significant role in human health and reduces disease risk. However, maintaining the viability of probiotics and targeting the successful delivery to the gastrointestinal tract remain two challenging tasks in food applications. Specifically, this paper reviews the potentially beneficial properties of probiotics, highlighting the use and challenges of probiotics in food application and the associated health benefits. Of foremost importance, this paper also explores the potential underlying molecular mechanisms of the enhanced effect of probiotics on gastrointestinal epithelial cells, including a discussion on various surface adhesion‐related proteins on the probiotic cell surface that facilitate colonization.

The Importance of Eating Healthy and Nutritionally Balanced Food for Elementary School Children

&#x0D; Health and well-being are important aspects of human life. One of the key factors that affect health is diet. The food we consume directly affects our physical and mental state. This activity aims to increase elementary school children's knowledge of the importance of eating healthy and nutritionally balanced foods. Method As an alternative solution to the problems that have been identified, counselling activities are carried out on the importance of eating healthy and nutritionally balanced foods in elementary school children. The method to increase this knowledge is counselling on the importance of eating healthy and nutritionally balanced foods. The techniques used in this activity include advising on the importance of eating healthy, nutritionally balanced foods and distributing leaflets. Based on the evaluation results, there has been a significant increase in knowledge about eating healthy and nutritionally balanced foods. Education and awareness about a healthy and nutritionally balanced diet are very important. The public needs to be adequately informed about the nutritional value of food and ways to adopt a healthy diet. Thus, it is expected to improve the quality of life, reduce disease risk, and create a healthier and more productive society overall.&#x0D;

Phosphodiesterase Type 5 Inhibitors in Men With Erectile Dysfunction and the Risk of Alzheimer Disease: A Cohort Study.

Repurposing phosphodiesterase type 5 inhibitors (PDE5Is) as drugs for Alzheimer disease (AD) risk reduction has shown promise based on animal studies. However, evidence in humans remains inconclusive. Therefore, we conducted a cohort study to evaluate the association between PDE5I initiation compared with nonuse and the risk of developing AD in men with erectile dysfunction (ED). Using electronic health records from IQVIA Medical Research Data UK (formerly known as the THIN database), we identified men aged ≥40 years with a new diagnosis of ED between 2000 and 2017. Individuals with a previous diagnosis of dementia, cognitive impairment, confusion, or prescription for dementia symptoms were excluded. The occurrence of incident AD was identified using diagnostic read codes. To minimize immortal-time bias, PDE5I initiation was treated as a time-varying exposure variable. Potential confounders were adjusted using inverse probability of treatment weighting based on propensity scores. Cox proportional hazard models were used to estimate the adjusted hazard ratio (HR) with 95% CIs. A secondary analysis explored the association between AD and the cumulative number of PDE5I prescriptions. Sensitivity analyses included lag (delay) periods of 1 and 3 years after cohort entry to address the prodromal stage of AD. The study included 269,725 men, with 1,119 newly diagnosed with AD during a median follow-up of 5.1 (interquartile range 2.9-8.9) years. The adjusted HR in PDE5I initiators compared with nonuse was 0.82 (95% CI 0.72-0.93). The associated risk of AD decreased in individuals issued >20 prescriptions: HR 0.56 (95% CI 0.43-0.73) for 21-50 prescriptions and HR 0.65 (95% CI 0.49-0.87) for >50 prescriptions. Sensitivity analysis with a 1-year lag period supported the primary findings (HR 0.82, 95% CI 0.72-0.94), but the results differed with the inclusion of a 3-year lag period (HR 0.93, 95% CI 0.80-1.08). PDE5I initiation in men with ED was associated with a lower risk of AD, particularly in those most frequently issued prescriptions. The differences between primary and sensitivity analyses highlight the need to explore the optimal lag period. To enhance the generalizability of our findings, a randomized controlled trial including both sexes and exploring various PDE5I doses would be beneficial to confirm the association between PDE5I and AD.

The Role of Functional Foods and Nutraceuticals in Disease Prevention and Health Promotion

Functional foods containing bioactive compounds may help prevent chronic conditions and promote wellness beyond basic nutrition. Likewise, dietary nutraceutical supplements show promise for reducing disease risk. This review synthesizes current evidence regarding effects of key functional foods and nutraceuticals on outcomes related to cardiovascular disease, cancer, inflammation, immunity, microbiome health, and integrative markers of metabolic health. We specifically summarize findings from clinical trials and experimental studies on foods (e.g. fatty fish, soy, cocoa, nuts, berries, yogurt) and nutritional supplements (e.g. probiotics, vitamins, omega fatty acids, phytochemicals). Collectively, data supports that achieving optimal intake of certain bioactive functional food components may help reduce morbidity and mortality from highly prevalent chronic illnesses. However, further research should continue investigating mechanisms of action, safe effective dosages, nutrigenomic responses, and strategies to improve consumer selection and adherence. Ultimately nutrition-based lifestyle approaches emphasizing functional foods and nutraceuticals aligned with dietary guidance have potential to significantly impact public health by filling nutritional gaps, regulating disease pathways, and promoting protective responses.

Functional Foods for Better Health

Food is very important for human beings in health and disease. To larger extent, human beings struggle to obtain food in day today life . Apart from this food struggle and shortage, the human face nutritional deficiency diseases. The nutritional diseases are protein energy malnutrition, endemic goitre, nutritional anemia, nutritional blindness and other related diseases affects individual life. Functional food plays a vital role in providing essential nutrients to the human and their well-being. The simple meaning of functional food is that food which provide health benefits that is basic nutrients. The basic nutrients include micronutrients and macro nutrients such as vitamins minerals, fat and protein. The concept of functional foods was first developed and introduced in Japan in the mid 1980’s. Since then there is no clear meaning and definition for functional foods. It includes the primary categories of foods like conventional, modified food ingredients. Normally foods are considered as functional when it contains a bio active component and non – nutrients. Bioactive components are nutrients like vitamins, minerals, protein etc., and non- nutrients are phyto chemicals like poly phenols, prebiotic dietary, fibers etc. which affects the individual physiological functions in the body. This improves the well-being and health reduces disease risk and improves the disease outcomes. Thus, functional foods include nutraceuticals, dietary supplements, and medical foods. The consumption of functional food helps to achieve specific health benefits. This functional food leads to follow a healthy dietary pattern. This healthy dietary pattern is important for maintaining optimal health and reduce chronic disease risk. So, an attempt is made to study the functionals foods for better health in India.

Equity in Cancer and Chronic Disease Prevention through a Multi-Pronged Network Intervention: Works-in-Progress.

The increasing rates of cancer incidence are disproportionately borne by populations that are ineligible for screening and historically marginalized populations. To address this need, our community-centered model seeks to catalyze the widespread diffusion of evidence-based information and resources (e.g., community-based organizations, federally qualified health centers) to reduce the risks of cancer, chronic disease, and other conditions. In this study, we tested whether improving personal health literacy (i.e., confidence in seeking information) and enabling successful information transfer (i.e., intention to share the specific information learned through the program) among community residents could contribute to greater diffusion intention (i.e., number of network members with whom residents plan to share information and resources). The current study used post-intervention surveys, which were administered to Chicago residents who were 18 years or older and had participated in the program. Among the 1499 diverse Chicago residents, improved personal health literacy was associated with greater diffusion intention (ORs = 2.00-2.68, 95% CI [1.27-4.39], p ≤ 0.003). Successful information transfer was associated with greater diffusion, especially for cancer and other chronic disease risk reductions (ORs = 3.43-3.73, 95% CI [1.95-6.68], p < 0.001). The findings highlight the potential gains for health equity through sustainable, scalable, multi-sectoral partnerships.

Transcriptomic Analysis Reveals the Potential Mechanisms for Improving Carotenoid Production in Rhodosporidium toruloides Z11 under Light Stress.

Carotenoids, as a type of tetraterpene compound, have been widely used in food, medical, and health areas owing to their antioxidant, immune enhancement, and disease risk reduction effects. Rhodosporidium toruloides is a promising oleaginous red yeast that can industrially synthesize carotenoids. In this study, the effects of different light exposure times and intervals on carotenoid production by R. toruloides Z11 were first investigated. Results showed that a higher carotenoid content (1.29 mg/g) can be achieved when R. toruloides Z11 was exposed to light for 12 h per day, which was increased by 1.98 times compared with that of dark cultivation. Transcriptome profiling revealed that light stress could effectively promote the gene expression levels of GGPS1 and AL1 in the carotenoid biosynthesis pathway and phr in the DNA photolysis pathway of R. toruloides. This work will provide a molecular foundation to further improve the production efficiency of carotenoids by genetic engineering.

The SARS-CoV-2 Mpro Dimer-Based Screening System: A Synthetic Biology Tool for Identifying Compounds with Dimerization Inhibitory Potential.

The COVID-19 endemic remains a global concern. The search for effective antiviral candidates is still needed to reduce disease risk. However, the availability of high biosafety level laboratory facilities for drug screening is limited in number. To address this issue, a screening system that could be utilized at lower biosafety levels remains essential. This study aimed to develop a novel SARS-CoV-2 main protease (Mpro) dimer-based screening system (DBSS) utilizing synthetic biology in Escherichia coli BL21(DE3). We linked the SARS-CoV-2 Mpro with the DNA-binding domain of AraC regulatory protein, which regulates the reporter gene expression. Protein modeling and molecular docking showed that saquinavir could bind to AraC-Mpro both in its monomer and dimer forms. The constructed DBSS assay indicated the screening system could detect saquinavir inhibitory activity at a concentration range of 4-10 μg/mL compared to the untreated control (P ≤ 0.05). The Vero E6 cell assay validated the DBSS result that saquinavir at 4-10 μg/mL exhibited antiviral activity against SARS-CoV-2. Our DBSS could be used for preliminary screening of numerous drug candidates that possess a dimerization inhibitor activity of SARS-CoV-2 Mpro and also minimize the use of a high biosafety level laboratory.

Proanthocyanidins-Based Synbiotics as a Novel Strategy for Nonalcoholic Fatty Liver Disease (NAFLD) Risk Reduction.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, is a spectrum of liver abnormalities ranging from steatosis to nonalcoholic steatohepatitis (NASH) characterized by excessive lipid accumulation. The prevalence of NAFLD is predicted to increase rapidly, demanding novel approaches to reduce the global NAFLD burden. Flavonoids, the most abundant dietary polyphenols, can reduce the risk of NAFLD. The majority of dietary flavonoids are proanthocyanidins (PACs), which are oligomers and polymers of the flavonoid sub-group flavan-3-ols. The efficacy of PAC in reducing the NAFLD risk can be significantly hindered by low bioavailability. The development of synbiotics by combining PAC with probiotics may increase effectiveness against NAFLD by biotransforming PAC into bioavailable metabolites. PAC and probiotic bacteria are capable of mitigating steatosis primarily through suppressing de novo lipogenesis and promoting fatty acid β-oxidation. PAC and probiotic bacteria can reduce the progression of steatosis to NASH mainly through ameliorating hepatic damage and inflammation induced by hepatic oxidative stress, endoplasmic reticulum stress, and gut microbiota dysbiosis. Synbiotics of PAC are superior in reducing the risk of NAFLD compared to independent administration of PAC and probiotics. The development of PAC-based synbiotics can be a novel strategy to mitigate the increasing incidence of NAFLD.

Non-linear effects of non-host diversity on the removal of free-living infective stages of parasites

Among the ecological functions and services of biodiversity is the potential buffering of diseases through dilution effects where increased biodiversity results in a reduction in disease risk for humans and wildlife hosts. Whether such effects are a universal phenomenon is still under intense debate and diversity effects are little studied in cases when non-host organisms remove free-living parasite stages during their transmission from one host to the next by consumption or physical obstruction. Here, we investigated non-host diversity effects on the removal of cercarial stages of trematodes, ubiquitous parasites in aquatic ecosystems. In laboratory experiments using response surface designs, varying both diversity and density at same time, we compared three combinations of two non-hosts at four density levels: predatory crabs that actively remove cercariae from the water column via their mouth parts and gills, filter feeding oysters that passively filter cercariae from the water column while not becoming infected themselves, and seaweed which physically obstructs cercariae. The addition of a second non-host did not generally result in increased parasite removal but neutralised, amplified or reduced the parasite removal exerted by the first non-host, depending on the density and non-host combination. These non-linear non-host diversity effects were probably driven by intra- and interspecific interactions and suggest the need to integrate non-host diversity effects in understanding the links between community diversity and infection risk.

Multiprofessional Approach for Chronic Kidney Disease (CKD) Risk Reduction and Prophylaxis in the Kushiro Medical Area

Chronic kidney disease (CKD) is closely related to disorders of various organs of the body and is also a factor in increasing social security costs such as medical costs for dialysis. Multiprofessional public health associations in Kushiro City jointly manage CKD-targeted action as "Kushiro CKD network" composed of medical/dental physicians, nurses, nutritionists and pharmacists. Pharmacists have played a central role in affixing a CKD sticker to a patient's medicine notebook when the patient's estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2, in order to highlight the risk of CKD for those patients and related medical staff. There are many drugs that require dose reduction considering for renal function, but we had found cases where renal function was not monitored and pharmaceutical dispensation adjusted before the CKD network started. Therefore, we took this opportunity to investigate the impact of CKD stickers on pharmacists' work. During the period from August 2018 to August 2021, about 3200 CKD stickers were affixed by pharmacists, and about 4500 cases of decreased renal function were detected at pharmacies. In addition, there were 334 cases in which renal function deterioration was identified by the CKD stickers and led to further inquiries, of which 265 cases, or about 80%, resulted in prescription changes. Based on these results, it is considered that CKD stickers are effective method for pharmacies understand renal function deterioration and conduct appropriate prescription reviews. Finally, and perhaps most importantly, the use of CKD stickers can help assure that patients with renal impairment care treated with appropriate medication doses.