The Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of guar gum (E 412) as a food additive. In the EU, guar gum was evaluated ...by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1970, 1974 and 1975, who allocated an acceptable daily intake (ADI) ‘not specified’. Guar gum has been also evaluated by the Scientific Committee for Food (SCF) in 1977 who endorsed the ADI ‘not specified’ allocated by JECFA. Following the conceptual framework for the risk assessment of certain food additives re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that adequate exposure and toxicity data were available. Guar gum is practically undigested, not absorbed intact, but significantly fermented by enteric bacteria in humans. No adverse effects were reported in subchronic and carcinogenicity studies at the highest dose tested; no concern with respect to the genotoxicity. Oral intake of guar gum was well tolerated in adults. The Panel concluded that there is no need for a numerical ADI for guar gum (E 412), and there is no safety concern for the general population at the refined exposure assessment of guar gum (E 412) as a food additive. The Panel considered that for uses of guar gum in foods intended for infants and young children the occurrence of abdominal discomfort should be monitored and if this effect is observed doses should be identified as a basis for further risk assessment. The Panel considered that no adequate specific studies addressing the safety of use of guar gum (E 412) in food categories 13.1.5.1 and 13.1.5.2 were available. Therefore, the Panel concluded that the available data do not allow an adequate assessment of the safety of guar gum (E 412) in infants and young children consuming these foods for special medical purposes.
Following a request from European Commission, the EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of locust bean gum ...(E 410) as a food additive. Locust bean gum (E 410) is an authorised food additive in the EU. Locust bean gum (E 410) as specified in the Commission Regulation (EU) No 231/2012 is derived from the ground endosperm of the seeds of the strains of carob tree, Ceratonia siliqua (L.) Taub. (Family Leguminosae). An acceptable daily intake (ADI) ‘not specified’ was allocated by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA) in 1981. Although not evaluated by the Scientific Committee for Food (SCF), it was accepted by the SCF in 1991 for use in weaning food, and in 1994, in infant formulae for special medical purposes. Locust bean gum is practically undigested, not absorbed intact, but significantly fermented by enteric bacteria in humans. No adverse effects were reported in 90‐day toxicity and carcinogenicity studies in rodents at the highest doses tested and there was no concern with respect to the genotoxicity and to reproductive and developmental toxicity of locust bean gum (E 410). The Panel concluded that there is no need for a numerical ADI for locust bean gum (E 410), and that there is no safety concern for the general population at the refined exposure assessment for its reported uses as a food additive. However, infants and young children consuming foods for special medical purposes may show a higher susceptibility to gastrointestinal effects of locust bean gum due to their underlying medical condition. The Panel concluded that the available data do not allow an adequate assessment of the safety of locust bean gum (E 410) in these foods for infants and young children.
The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of agar (E 406) as a food additive. In the European Union (EU), agar ...(E 406) has been evaluated by the Scientific Committee for Food (SCF) in 1989, who allocated to agar a not specified acceptable daily intake (ADI), and by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1974, who considered very few data to conclude to a not limited ADI. According to the conceptual framework for the risk assessment of certain food additives re‐evaluated under Commission Regulation (EU) No 257/2010, the Panel considered that the safety assessment is limited to the use and use levels received from industry in 7 food categories for which data were considered in this opinion out of the 70 food categories in which agar (E 406) is authorised; an indicative high refined exposure assessment up to 26 mg/kg body weight (bw) per day has been calculated in toddlers at the 95th percentile (non‐brand‐loyal scenario); agar is unlikely to be absorbed unchanged and slightly fermented by intestinal microbiota; sufficient toxicity data were available; there was no concern with respect to the genotoxicity of agar; no carcinogenic effects were reported in carcinogenicity studies in mice and rats at the doses of 4,500 mg/kg bw per day and 2,500 mg/kg bw per day, respectively, the highest doses tested; oral intake of agar (4,500 mg/person corresponding to 64 mg/kg bw per day) was tolerated in humans for 12 weeks without noticeable side effects. Therefore, the Panel concluded that there is no need for a numerical ADI for agar and that there is no safety concern for the general population at the refined exposure assessment for the reported uses of agar as a food additive.
Following a request from the European Commission, the EFSA Panel on Food Additives and Nutrient sources added to Food (ANS) was asked to deliver a scientific opinion on the re‐evaluation of karaya ...gum (E 416) as a food additive. Karaya gum (E 416) is an authorised food additive in the EU. Karaya gum (E 416) as specified in the Commission Regulation (EU) No 231/2012 is derived from the exudates from the stems and branches of strains of Sterculia urens Roxburgh and other species of Sterculia (family Sterculiaceae) or from Cochlospermum gossypium A.P. De Candolle or other species of Cochlospermum (family Bixaceae). An acceptable daily intake (ADI) ‘not specified’ was allocated by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives (JECFA), whereas the Scientific Committee for Food (SCF) allocated an ADI of 12.5 mg/kg body weight (bw) per day. Karaya gum is practically undigested and not degraded by intestinal microflora and it is most probably not or only negligibly absorbed unchanged in humans. There is no concern with respect to the genotoxicity of karaya gum from Sterculia spp. Karaya gum (E 416) from Sterculia spp. did not induce toxic effects in animals at dose levels up to 1,250 mg/kg bw per day, the highest dose tested. Karaya gum from Sterculia spp. was well tolerated in humans at dose about 100 mg/kg bw per day for 4 weeks. The Panel concluded that there is no safety concern at the refined exposure assessment for the use of karaya gum as a food additive and that there is no need for a numerical ADI for karaya gum. The Panel further concluded that exposure to karaya gum by the use of this food additive should not exceed 7,000 mg/person per day in adults, the level at which some experienced abdominal discomfort.
The purpose of the study was to examine differences between documented and undocumented Latino immigrants in the prevalence of three immigration-related challenges (separation from family, ...traditionality, and language difficulties), which were made more severe after the passage of restrictive immigration legislation in 1996. Specifically, the study sought to determine the combined and unique associations of legal status, the three immigration-related challenges listed above, and fear of deportation to acculturative stress related to family and other social contexts. Participants in the study consisted of 416 documented and undocumented Mexican and Central American immigrants living in two major cities in Texas. The Hispanic Stress Inventory—Immigrant form was used to assess acculturative stress in the sample. Results indicated that although undocumented immigrants reported higher levels of the immigration challenges of separation from family, traditionality, and language difficulties than documented immigrants, both groups reported similar levels of fear of deportation. Results also indicated that the immigration challenges and undocumented status were uniquely associated with extrafamilial acculturative stress but not with intrafamilial acculturative stress. Only fear of deportation emerged as a unique predictor of both extrafamililal and intrafamilial acculturative stress.
Assessing the risk of common, complex diseases requires consideration of clinical risk factors as well as monogenic and polygenic risks, which in turn may be reflected in family history. Returning ...risks to individuals and providers may influence preventive care or use of prophylactic therapies for those individuals at high genetic risk.
To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores, monogenic risks, family history, and clinical risk assessments via a genome-informed risk assessment (GIRA) report and will assess uptake of care recommendations after return of results.
GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports. The return of high-risk GIRA to individuals and providers includes guidelines for care and lifestyle recommendations. Assembling the GIRA required infrastructure and workflows for ingesting and presenting content from multiple sources. Recruitment began in February 2022.
Return of a novel report for communicating monogenic, polygenic, and family history-based risk factors will inform the benefits of integrated genetic risk assessment for routine health care.
VIA is recommended for triage of HPV-positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or ...worse (CIN3+) among HPV-positive women was evaluated. Women aged 30-64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive. At colposcopy visit, study-trained midwives/nurses/GPs performed VIA ahead of colposcopy. VIA was considered positive if acetowhite lesions were observed in or close to the transformation zone. Ablative treatment eligibility was assessed for VIA positives. Performance indicators were estimated. Three thousand one hundred and forty-two HPV-positive women were included. Sensitivity for CIN3+ was 85.9% (95% CI 81.2-89.5) among women <50 years and, although not significant, slightly lower in women 50+ (78.0%, 95% CI 65.9-86.6). Overall specificity was 58.6% (95% CI 56.7-60.5) and was significantly higher among women 50+ (70.3%, 95% CI 66.8-73.5) compared to women <50 (54.3%, 95% CI 52.1-56.5). VIA positivity was lower among women 50+ (35.2%, 95% CI 31.9-38.6) compared to women <50 (53.2, 95% CI 51.1-55.2). Overall eligibility for ablative treatment was 74.5% and did not differ by age. VIA sensitivity, specificity, and positivity, and ablative treatment eligibility varied highly by provider (ranges: 25%-95.4%, 44.9%-94.4%, 8.2%-65.3%, 0%-98.7%, respectively). VIA sensitivity for cervical precancer detection among HPV-positive women performed by trained providers was high with an important reduction in referral rates. However, scaling-up HPV screening triaged by VIA will be challenging due to the high variability of VIA performance and providers' need for training and supervision.
As the world faces an obesity “epidemic,” the mechanisms by which overweight is translated into insulin resistance, hypertension, and diabetes need to be better understood. Although the processes of ...transition remain uncertain, overactivity of the sympathetic nervous system appears pivotal. In obesity, there is stimulation of sympathetic outflow to the kidneys, evident in increased rates of spillover of noradrenaline into the renal veins, and to skeletal muscle vasculature, demonstrated with microneurography. The cause is unclear, but possibly involves the stimulatory action of leptin released from adipose tissue, or from within the brain, for which there is recent evidence in human obesity. The high renal sympathetic tone contributes to hypertension development by stimulating renin secretion and through promoting renal tubular reabsorption of sodium. Neurally mediated skeletal muscle vasoconstriction reduces glucose delivery and uptake in muscle. Impairment of glucose uptake by skeletal muscle is a hallmark of insulin resistance syndromes.
Pharmacologic sympathetic nervous suppression within the central nervous system with imidazoline receptor-binding agents such as rilmenidine is a logical therapeutic approach for lowering blood pressure (BP) in patients with essential hypertension, in whom sympathetic activity is often increased. In addition, drugs of this class appear to have the capacity to favorably modify insulin sensitivity, which has particular relevance in the treatment of hypertensive diabetic patients. In the hypertension accompanying maturity onset obesity, with recent recommendations from advisory bodies setting lower goal BP, and with these lower targets often being reached only with combinations of antihypertensive agents, it is advisable that all drugs used in combination therapy have a favorable or at least a neutral effect on insulin resistance.
Central nervous system (CNS)-targeted products are an important category of pediatric pharmaceuticals. In view of the significant postnatal maturation of the CNS, juvenile animal studies (JAS) are ...performed to support pediatric development of these new medicines. In this project, the design and results of juvenile toxicity studies from 15 drug compounds for the treatment of neurologic or psychiatric conditions were analyzed. Studies were conducted mostly in rats; sometimes in addition in dogs and monkeys. The study design of the pivotal JAS was variable, even for compounds with a similar therapeutic indication. Age of the juvenile animals was not consistently related to the starting age of the intended patient population. Of 15 compounds analyzed, 6 JAS detected more severe toxicities and 6 JAS evidenced novel CNS effects compared to their adult counterparts. The effects of CNS on acoustic startle and learning and memory were observed at high dosages. Reversibility was tested in most cases and revealed some small effects that were retained or only uncovered after termination of treatment. The interpretation of the relevance of these findings was often hampered by the lack of matching end points in the adult studies or inappropriate study designs. Detailed clinical observation and motor activity measures were the most powerful end points to detect juvenile CNS effects. The need for more detailed behavioral examinations in JAS, for example, on learning and memory, should, therefore, be decided upon on a case-by-case basis, based on specific concerns in order to avoid overloading the studies.
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