Setting sodium targets for pre-packaged foods in China - an exploratory study.

Introduction: Setting sodium targets for pre-packaged food has been a priority strategy for reducing population sodium intake. This study aims to explore the attitudes and considerations of researchers and key stakeholders toward implementing such policy in China. Methods: An exploratory study comprising a survey and a focus group discussion was conducted among 27 purposively selected participants including 12 researchers, 5 consumers, 4 administrators, 3 industry association representatives and 3 food producers. The survey/discussion covered the key questions considered when developing/promoting sodium targets. Free-text responses were manually classified and summarized using thematic analysis. Results: Two-thirds of the participants supported target-setting policy. Researchers and administrators were most supportive, and food producers and associations were least supportive. Adapted WHO food categorization framework was well accepted to underpin target-setting to ensure international comparability and applicability for Chinese products. Maximum values were the most agreed target type. The WHO benchmarks were thought to be too ambitious to be feasible given the current food supply in China but can be regarded as long-term goals. Initially, a reduction of sodium content by 20% was mostly accepted to guide the development of maximum targets. Other recommendations included implementing a comprehensive strategy, strengthening research, engaging social resources, establishing a systematic monitoring/incentive system, maintaining a fair competitive environment, and developing a supportive information system. Target-setting policy was acceptable by most stakeholders and should be implemented alongside strategies to reduce discretionary salt use. Discussion: Our findings provide detailed guidance for the Chinese government when developing a target-setting strategy. The methods and results of this study also provide meaningful references for other countries to set sodium targets for pre-packaged foods and implement other salt reduction strategies simultaneously.

Sodium content targets for pre-packaged foods, China: a quantitative study and proposal.

Objective: To determine the contribution of pre-packaged foods to population sodium intake in China, and to propose sodium content targets for food subcategories used for the World Health Organization's (WHO's) global sodium benchmarks. Methods: The impact of four different approaches to reducing the sodium content of pre-packaged foods on population sodium intake was estimated using data from national databases covering the nutrient content and ingredients of 51 803 food products and food consumption by 15 670 Chinese adults. We recategorized food products using a food categorization framework developed for WHO's global sodium benchmarks and adapted for China-specific foods. Findings: Pre-packaged foods, including condiments, contributed 1302.5 mg/day of sodium intake per adult in 2021, accounting for 30.1% of population sodium intake in China. Setting maximum sodium content levels using a 90th-percentile target would reduce sodium intake from pre-packaged foods by 96.2 mg/day, corresponding to a 1.9% reduction in population intake. Using the 75th-percentile, a fixed 20% reduction and WHO benchmark targets would further reduce intake by 262.0 mg/day (5.2% population intake), 302.8 mg/day (6.0% population intake) and 701.2 mg/day per person (13.9% population intake), respectively. Maximum sodium content levels based on revised 20% reduction targets were proposed because they should result in substantial and acceptable reductions in sodium content for most food subcategories: overall sodium intake would decline by 305.0 mg/day per person, and population intake by 6.1%. Conclusion: This study provides the scientific rationale for government policy on setting targets for food sodium content in China. Simultaneous action on discretionary salt use should also be taken.

Estimated Dietary and Health Impact of the World Health Organization's Global Sodium Benchmarks on Packaged Foods in Australia: a Modeling Study.

BACKGROUND: In 2021, the World Health Organization (WHO) set sodium benchmarks for packaged foods to guide countries in setting feasible and effective sodium reformulation programs. We modeled the dietary and health impact of full compliance with the WHO's sodium benchmarks in Australia and compared it to the potential impact of Australia's 2020 sodium reformulation targets. METHODS: We used nationally representative data on food and sodium intake, sodium levels in packaged foods, and food sales volume to estimate sodium intake pre- and post-implementation of the WHO and Australia's sodium benchmarks for 24 age-sex groups. Using comparative risk assessment models, we then estimated the potential deaths, incidence, and disability-adjusted life years averted from cardiovascular disease, chronic kidney disease, and stomach cancer based on the reductions in sodium intake. RESULTS: Compliance with the WHO's sodium benchmarks for packaged foods in Australia could lower mean adult sodium intake by 404 mg/day, corresponding to a 12% reduction. This could prevent about 1770 deaths/year (95% uncertainty interval 1168-2587), corresponding to 3% of all cardiovascular disease, chronic kidney disease, and stomach cancer deaths in Australia, and prevent some 6900 (4603-9513) new cases, and 25 700 (17 655-35 796) disability-adjusted life years/year. Compared with Australian targets, the WHO benchmarks will avert around 3 and a half times more deaths each year (1770 versus 510). CONCLUSIONS: Substantially greater health impact could be achieved if the Australian government strengthened its current sodium reformulation program by adopting WHO's more stringent and comprehensive sodium benchmarks.

A Global Review of National Strategies to Reduce Sodium Concentrations in Packaged Foods.

Strategies to reduce sodium concentrations in packaged foods are effective and cost-effective approaches to reducing the burden of disease attributable to high sodium intakes. This review aimed to comprehensively describe, and explore characteristics of, national strategies to reduce sodium concentrations in packaged foods, and assess progress toward achieving national goals. A secondary aim was to understand the number, type, and variation of food category sodium targets set by countries compared with WHO global sodium benchmarks. National sodium reduction reformulation strategies were identified from a search of peer-reviewed and gray literature up to December 2019 supplemented by verified information from key contacts and experts up to December 2020. Key characteristics of countries' strategies were extracted, synthesized, and descriptively analyzed, including details of reformulation strategies and evaluation data. Country targets were mapped to the WHO global sodium benchmarks, and the number and variation of country sodium targets by WHO food categories were determined. Sixty-two countries had reformulation strategies to reduce sodium in packaged foods, and 19 countries had evaluated their reformulation strategies. Forty-three countries had sodium targets, which varied in type of targets (maximum sodium concentration: n = 26; maximum concentration plus relative reduction/average/sales-weighted average: n = 8; relative reduction: n = 7; average: n = 2), number of food category targets (range: n = 1 to 150), and regulatory approach (voluntary: n = 28; mandatory: n = 9; both: n = 6). Eight of 34 countries mapped to the WHO benchmarks had targets for just 1 specified food category (bread products). One-third of all countries were implementing national strategies to reduce sodium concentrations in packaged foods including establishing targets and/or processes for industry engagement. This review determined that there is scope to improve most countries' strategies. There has been limited progress in implementing and evaluating strategies between 2014 and 2019, and regional and income-level disparities persist. The WHO global sodium benchmarks present an important opportunity to accelerate reformulation action globally.

Angiotensin-Converting Enzyme (ACE) 1 Gene Polymorphism and Phenotypic Expression of COVID-19 Symptoms.

The renin-angiotensin-aldosterone system (RAAS) appears to play an important role in SARS-CoV-2 infection. Polymorphisms within the genes that control this enzymatic system are candidates for elucidating the pathogenesis of COVID-19, since COVID-19 is not only a pulmonary disease but also affects many organs and systems throughout the body in multiple ways. Most striking is the fact that ACE2, one of the major components of the RAAS, is a prerequisite for SARS-COV-2 infection. Recently, we and other groups reported an association between a polymorphism of the ACE1 gene (a homolog of ACE2) and the phenotypic expression of COVID-19, particularly in its severity. The ethnic difference in ACE1 insertion (I)/deletion (D) polymorphism seems to explain the apparent difference in mortality between the West and East Asia. The purpose of this review was to further evaluate the evidence linking ACE1 polymorphisms to COVID-19. We searched the Medline database (2019-2021) for reference citations of relevant articles and selected studies on the clinical outcome of COVID-19 related to ACE1 I/D polymorphism. Although the numbers of patients are not large enough yet, most available evidence supports the notion that the DD genotype adversely influences COVID-19 symptoms. Surprisingly, small studies conducted in several countries yielded opposite results, suggesting that the ACE1 II genotype is a risk factor. This contradictory result may be the case in certain geographic areas, especially in subgroups of patients. It may also be due to interactions with other genes or to yet unexplained biochemical mechanisms. According to our hypothesis, such candidates are genes that are functionally involved in the pathophysiology of COVID-19, can act in concert with the ACE1 DD genotype, and that show differences in their frequency between the West and East Asia. For this, we conducted research focusing on Alu-related genes. The current study on the ACE1 genotype will provide potentially new clues to the pathogenesis, treatment, and diagnosis of SARS-CoV-2 infections.

Strong alkaline electrolyzed water efficiently inactivates SARS-CoV-2, other viruses, and Gram-negative bacteria.

Air spaces and material surfaces in a pathogen-contaminated environment can often be a source of infection to humans, and disinfection has become a common intervention focused on reducing the contamination levels. In this study, we examined the efficacy of SAIW, a unique electrolyzed water with chlorine-free, high pH, high concentration of dissolved hydrogen, and low oxygen reduction potential, for the inactivation of several viruses and bacteria. Infectivity assays revealed that initial viral titers of enveloped and non-enveloped viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus, herpes simplex virus type 1, human coronavirus, feline calicivirus, and canine parvovirus, were reduced by 2.9- to 5.5-log10 within 30 s of SAIW exposure. Similarly, the culturability of three Gram-negative bacteria (Escherichia coli, Salmonella, and Legionella) dropped down by 1.9- to 4.9-log10 within 30 s of SAIW treatment. Mechanistically, treatment with SAIW was found to significantly decrease the binding and subsequent entry efficiencies of SARS-CoV-2 on Vero cells. Finally, we showed that this chlorine-free electrolytic ion water had no acute inhalation toxicity in mice, demonstrating that SAIW holds promise for a safer antiviral and antibacterial disinfectant.

Does Genetic Predisposition Contribute to the Exacerbation of COVID-19 Symptoms in Individuals with Comorbidities and Explain the Huge Mortality Disparity between the East and the West?

The elderly and patients with several comorbidities experience more severe cases of coronavirus disease 2019 (COVID-19) than healthy patients without underlying medical conditions. However, it is unclear why these people are prone to developing alveolar pneumonia, rapid exacerbations, and death. Therefore, we hypothesized that people with comorbidities may have a genetic predisposition that makes them more vulnerable to various factors; for example, they are likely to become more severely ill when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To test this hypothesis, we searched the literature extensively. Polymorphisms of genes, such as those that encode angiotensin-converting enzyme 1 (ACE1), have been associated with numerous comorbidities, such as cardiovascular disease, hypertension, diabetes, chronic kidney disease, and obesity, and there are potential mechanisms to explain these associations (e.g., DD-type carriers have greater ACE1 activity, and patients with a genetic alpha-1 anti-trypsin (AAT) deficiency lack control over inflammatory mediators). Since comorbidities are associated with chronic inflammation and are closely related to the renin-angiotensin-aldosterone system (RAAS), these individuals may already have a mild ACE1/ACE2 imbalance before viral infection, which increases their risk for developing severe cases of COVID-19. However, there is still much debate about the association between ACE1 D/I polymorphism and comorbidities. The best explanation for this discrepancy could be that the D allele and DD subtypes are associated with comorbidities, but the DD genotype alone does not have an exceptionally large effect. This is also expected since the ACE1 D/I polymorphism is only an intron marker. We also discuss how polymorphisms of AAT and other genes are involved in comorbidities and the severity of SARS-CoV-2 infection. Presumably, a combination of multiple genes and non-genetic factors is involved in the establishment of comorbidities and aggravation of COVID-19.

HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: A Multicenter Cohort Study.

CONTEXT: High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. OBJECTIVE: We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and cardiovascular disease (RISC) study, a multicenter European clinical investigation, whose recruitment initiated in 2002, with a follow-up of 3 years. MAIN MEASURES: Insulin sensitivity was estimated from an oral glucose tolerance test at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich enzyme-linked immunosorbent assay (ELISA)-based method. RESULTS: The 2 HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (P-trend = 0.01), compared to the lowest quintile. No significant association was observed for total HDL, and very low density lipoprotein (VLDL) and low density lipoprotein (LDL) containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. CONCLUSION: Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.

SARS-CoV-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The relentless spread and pathogenicity of the virus have become a global public health emergency. One of the striking features of this pandemic is the pronounced impact on specific regions and ethnic groups. In particular, compared with East Asia, where the virus first emerged, SARS-CoV-2 has caused high rates of morbidity and mortality in Europe. This has not been experienced in past global viral infections, such as influenza, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and is unique to SARS-CoV-2. For this reason, we investigated the involvement of genetic factors associated with SARS-CoV-2 infection with a focus on angiotensin-converting enzyme (ACE)-related genes, because ACE2 is a receptor for SARS-CoV-2. We found that the ACE1 II genotype frequency in a population was significantly negatively correlated with the number of SARS-CoV-2 cases. Similarly, the ACE1 II genotype was negatively correlated with the number of deaths due to SARS-CoV-2 infection. These data suggest that the ACE1 II genotype may influence the prevalence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

Distinct Proteomic Signatures in 16 HDL (High-Density Lipoprotein) Subspecies.

Objective- HDL (high-density lipoprotein) in plasma is a heterogeneous group of lipoproteins typically containing apo AI as the principal protein. Most HDLs contain additional proteins from a palate of nearly 100 HDL-associated polypeptides. We hypothesized that some of these proteins define distinct and stable apo AI HDL subspecies with unique proteomes that drive function and associations with disease. Approach and Results- We produced 17 plasma pools from 80 normolipidemic human participants (32 men, 48 women; aged 21-66 years). Using immunoaffinity isolation techniques, we isolated apo AI containing species from plasma and then used antibodies to 16 additional HDL protein components to isolate compositional subspecies. We characterized previously described HDL subspecies containing apo AII, apo CIII, and apo E; and 13 novel HDL subspecies defined by presence of apo AIV, apo CI, apo CII, apo J, α-1-antitrypsin, α-2-macroglobulin, plasminogen, fibrinogen, ceruloplasmin, haptoglobin, paraoxonase-1, apo LI, or complement C3. The novel species ranged in abundance from 1% to 18% of total plasma apo AI. Their concentrations were stable over time as demonstrated by intraclass correlations in repeated sampling from the same participants over 3 to 24 months (0.33-0.86; mean 0.62). Some proteomes of the subspecies relative to total HDL were strongly correlated, often among subspecies defined by similar functions: lipid metabolism, hemostasis, antioxidant, or anti-inflammatory. Permutation analysis showed that the proteomes of 12 of the 16 subspecies differed significantly from that of total HDL. Conclusions- Taken together, correlation and permutation analyses support speciation of HDL. Functional studies of these novel subspecies and determination of their relation to diseases may provide new avenues to understand the HDL system of lipoproteins.

The presence of females induces elevated cortisol levels in an alpha male: Experimental evidence in chimpanzees.

OBJECTIVES: In group-living primates, it has been reported that the alpha male exhibits high concentrations of cortisol and testosterone in the context of mating competition. We investigated how the presence of females affected salivary cortisol and testosterone levels in males from a small captive group of chimpanzees (Pan troglodytes). Specifically, we assessed whether the presence of females resulted in a rapid increase in salivary cortisol and testosterone levels in the alpha male. MATERIALS AND METHODS: We compared the social behavior and salivary hormone concentrations of four males before and after the presentation of receptive females. Three times a day, we collected saliva samples, a useful matrix for investigating short-term hormonal changes, and measured cortisol and testosterone concentration by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: The frequency of inter-male aggression increased in the presence of females, indicating intense competition among males. Salivary cortisol levels increased in all males in the presence of females; however, the increase was significantly more pronounced in the alpha male. We found a complex three-way interaction among the presence of females, sampling timings, and male dominance rank in the analysis of salivary testosterone. Contrary to our prediction, a post hoc analysis revealed that salivary testosterone levels decreased after female introduction and that the alpha male did not show a higher level of salivary testosterone. CONCLUSIONS: Our study provides experimental evidence suggesting that the presence of females plays a significant role in the rank-related variation in the cortisol levels in male chimpanzees. Furthermore, our findings demonstrate the usefulness of salivary hormones for detecting short-term physiological changes in studies of socioendocrinology.

High density lipoprotein with apolipoprotein C-III is associated with carotid intima-media thickness among generally healthy individuals.

BACKGROUND AND AIMS: About 6-7% of high density lipoprotein (HDL) has a protein called apolipoprotein (apo) C-III that regulates lipoprotein metabolism and can provoke an inflammatory response. HDL without apoC-III is inversely associated with coronary heart disease (CHD), whereas HDL with apoC-III is directly associated with CHD. We investigated how the presence of apoC-III affects the association between HDL and early stages of atherosclerosis measured as carotid intima-media thickness (cIMT). METHODS: We examined the cross-sectional associations between the apoA-I concentrations of HDL subspecies with and without apoC-III and cIMT measured by high resolution B-mode carotid ultrasonography among 847 participants from the European multi-center Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study. RESULTS: HDL with and without apoC-III demonstrated significantly opposite associations with both cIMT indexes (p-heterogeneity of associations comparing the two subspecies was 0.002 for cIMT at common carotid artery (cIMT at CCA) and 0.006 for the maximum cIMT in any carotid segment (cIMT max)). Compared to the lowest quintile, the highest quintile of apoA-I in HDL without apoC-III was associated with 3.7% lower cIMT at CCA (p-trend = 0.01) or 7.3% lower cIMT max (p-trend = 0.003), while the highest quintile of apoA-I in HDL with apoC-III was associated with 4.4% higher cIMT at CCA (p-trend = 0.001) or 7.9% higher cIMT max (p-trend = 0.002). Total apoA-I as well as total HDL cholesterol was not associated with cIMT whereas higher levels of total apoC-III and apoC-III contained in HDL were significantly associated with higher cIMT (p-trend<0.01). CONCLUSIONS: HDL apoC-III is a promising target for atherosclerosis prevention and treatment.

In vivo and in vitro studies suggest a possible involvement of HPV infection in the early stage of breast carcinogenesis via APOBEC3B induction.

High prevalence of infection with high-risk human papilloma virus (HPV) ranging from 25 to 100% (average 31%) was observed in breast cancer (BC) patients in Singapore using novel DNA chip technology. Early stage of BC demonstrated higher HPV positivity, and BC positive for estrogen receptor (ER) showed significantly higher HPV infection rate. This unique association of HPV with BC in vivo prompted us to investigate a possible involvement of HPV in early stages of breast carcinogenesis. Using normal breast epithelial cells stably transfected with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase, APOBEC3B (A3B) which is reported to be a source of mutations in BC. HPV-induced A3B overexpression caused significant γH2AX focus formation, and DNA breaks which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly suggest an active involvement of HPV in the early stage of BC carcinogenesis via A3B induction.

Reactivation of lymphocryptovirus (Epstein-Barr virus chimpanzee) and dominance in chimpanzees.

Nine male chimpanzees originally reared in solitary cages were set up to form a group. Plasma viral load of the lymphocryptovirus (LCV) of chimpanzee [Epstein-Barr virus chimpanzee (EBVcmp)] was measured by real-time PCR. In the group formation (Form) period, the first-ranking male showed an imminent increase in plasma EBVcmp load compared with 1 week before (pre-Form) and 3 months after (post-Form) group formation. Other upper-ranking males such as the second-, third- and fourth-male also showed the highest level of viral load in the Form period. The kinetics of EBVcmp load in the Form period were statistically different from other periods (against pre-Form, t=-4.878, P<0.001; against post-Form, t=6.434, P<0.001). The effect of the male dominance rank did not differ between the pre-Form and post-Form periods (t=-1.557, P=0.12). Reactivation of LCV (EBV) as an immunological stress marker for humans might also be applied to chimpanzees.

Validation of salivary cortisol and testosterone assays in chimpanzees by liquid chromatography-tandem mass spectrometry.

Owing to its high temporal sensitivity, saliva has distinct advantages for measuring steroids, compared with other noninvasive samples such as urine and feces. Here, we report the validity of assaying salivary cortisol (C) and testosterone (T) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in captive male chimpanzees, Pan troglodytes. For both the C and T concentrations, we found positive relationships between saliva and plasma. The concentrations of C and T in saliva showed clear patterns of diurnal fluctuation, whereas those in urine and feces did not. These results suggest that the salivary steroid concentrations can be regarded as good indicators of circulating steroid levels. We also developed and validated an efficient method for collecting saliva samples from cotton rope. Although rope includes inherent steroid-like compounds and may affect the accuracy of steroid measurements, our rope-washing procedures effectively removed intrinsic steroidal materials. There was a significant association between the C and T concentrations measured from saliva collected from rope licked by the chimpanzees and those measured from saliva collected directly from the mouth. Salivary T values estimated by LC/MS-MS were similar to those measured by radioimmunoassay. The results indicate the usefulness of saliva as a noninvasive steroid measure and that steroids in the saliva of chimpanzees can be accurately measured by LC-MS/MS.

Polymorphisms in the ABO blood group gene in three populations in the New Georgia group of the Solomon Islands.

To examine genetic affinity among Oceanian populations, polymorphisms of exons six and seven of the ABO blood group gene (ABO) were investigated in three populations--Munda town, Paradise village, and Rawaki village--in the New Georgia group of the Solomon Islands. The Munda and Paradise populations consist of Austronesian (AN)-speaking Melanesians; the Rawaki population consists of AN-speaking Micronesians who migrated from the Gilbert Islands to the New Georgia Islands approximately 30 years ago. We recently described the polymorphisms of ABO in three other Oceanian populations--Balopa Islanders (AN-speaking Melanesians), Gidra (non-AN-speaking Melanesians), and Tongans (AN-speaking Polynesians). The results from these six Oceanian populations suggest: (1) the main alleles in Oceanian populations are ABO*A101, ABO*A102, ABO*B101, ABO*O01, and ABO*O02, among which the most predominant is ABO*O01, and (2) there are marked differences in the ABO allele frequency spectrum among Oceanian populations. The different geographical distribution of ABO alleles provides insight into the migration history of AN-speaking populations in Oceania.