Caffeine consumption and onset of alcohol use among early adolescents.

Preventing or delaying the onset of alcohol use among children and youth is an important public health goal. One possible factor in alcohol use onset among early adolescents is caffeine. The aim of this study was to assess the possible contribution of caffeine to the onset of alcohol use during early adolescence. We used data from the Young Mountaineer Health Study Cohort. Survey data were collected from 1349 (response rate: 80.7%) 6th grade students (mean age at baseline 11.5 years) in 20 middle schools in West Virginia during the fall of 2020, and again approximately 6 months later in spring of 2021. We limited our analyses to students reporting never having used any form of alcohol at baseline. Logistic regression was employed in multivariable analyses and both Odds Ratios and Relative Risks reported. At follow-up, almost 14% of participants reported having consumed alcohol at least once and 57% used caffeine of 100 mg + daily. In multivariable analyses we controlled for social and behavioral variables known to impact tobacco use. Caffeine use was operationalized as a three-level factor: no use, <100 mg per day, and 100 + mg per day, with the latter being the approximate equivalent of the minimum of a typical cup of coffee or can of energy drink. Caffeine use of 100 mg + per day was significantly related to alcohol use at 6-months follow-up (OR: 1.79, RR: 1.56, p = .037). We conclude that caffeine consumption among 11-12-year-old adolescents may be a factor in early onset of alcohol use.

Protein over-expression in Escherichia coli triggers adaptation analogous to antimicrobial resistance.

BACKGROUND: The E. coli pET system is the most widely used protein over-expression system worldwide. It relies on the assumption that all cells produce target protein and it is generally believed that integral membrane protein (IMP) over-expression is more toxic than their soluble counterparts. RESULTS: Using GFP-tagged proteins, high level over-expression of either soluble or IMP targets results in > 99.9% cell loss with survival rate of only < 0.03%. Selective pressure generates three phenotypes: large green, large white and small colony variants. As a result, in overnight cultures, ~ 50% of the overall cell mass produces no protein. Genome sequencing of the phenotypes revealed genomic mutations that causes either the loss of T7 RNAP activity or its transcriptional downregulation. The over-expression process is bactericidal and is observed for both soluble and membrane proteins. CONCLUSIONS: We demonstrate that it is the act of high-level over-expression of exogenous proteins in E. coli that sets in motion a chain of events leading to > 99.9% cell death. These results redefine our understanding of protein over-production and link it to the adaptive survival response seen in the development of antimicrobial resistance.

Adolescent caffeine consumption and aggressive behavior: A longitudinal assessment.

Background: Adolescent caffeine consumption has been linked to aggressive behaviors, although no longitudinal tests have been reported to date. The purpose of this study was to test the longitudinal relations between daily adolescent caffeine consumption and aggressive behaviors. Methods: Two waves of survey data collected 12 months apart in the spring of 2018 and 2019, from the 2004 birth cohort in the Icelandic LIFECOURSE study, were analyzed using structural equation modeling (N = 2,278). Both direct and mediated models were employed. Results: Caffeine use at time 1 (T1) was associated with aggressive behavior at time 2 (T2) (ß = .12, p < .001) independent of aggressive behavior at T1. A considerable added relation was observed between caffeine at T1 and aggressive behavior at T2 via indirect (i.e., mediated) effects of aggressive behavior at T1 (standardized ß = .20, p < .001). Over 64% of the standardized total effect (ß = .31) observed between caffeine at T1 and aggressive behavior at T2 was due to mediation. Conclusion: Adolescent caffeine consumption forecasts aggressive behaviors. Caffeine use at T1 increased the likelihood of self-reported aggressive behaviors 12 months later irrespective of level of reported aggressive behavior at T1 while controlling for common confounders.

Palatability Enhancement Potential of Hermetia illucens Larvae Protein Hydrolysate in Litopenaeus vannamei Diets.

Marine feed ingredients derived from cephalopods (e.g., squid) and crustaceans (e.g., krill) are commercially used to improve the palatability of shrimp diets. Increase in global demand for shrimps has resulted in overfishing of these marine organisms and is a matter of concern. Insect protein hydrolysate could be a sustainable alternative for the possible replacement of these marine feed ingredients. During this study, four formulations: diet A (control: not containing any palatability enhancer), diet B (containing squid meal and krill oil), diet C (containing 1% insect protein hydrolysate), and diet D (containing 2% insect protein hydrolysate) were tested for (1) time required by first subject to begin feeding (time to strike) and (2) palatability in Litopenaeus vannamei. Additionally, the chemical composition of all four diet formulations was also analyzed. Results indicate that all diets had similar crude composition. The major essential amino acids in all diets were leucine and lysine, whereas eicosapentaenoic acid was the major omega-3 fatty acid in all diets. There were no significant differences between the mean time to strike for all the tested formulations. Palatability of tested formulations was found in the following order: diet D > diet C > diet B = diet A (p < 0.05), indicating that addition of squid meal and krill oil has no effect on palatability in comparison to control, whereas inclusion of insect protein hydrolysates significantly improves the palatability of formulations. Palatability enhancement potential of insect protein hydrolysate could be attributed to the high free amino acid content and water solubility in comparison to squid meal.

Disclosing conflict of interest does not mitigate healthcare bias and harm: It is time to sever industry ties.

Disclosing conflict of interest is widely believed to mitigate bias and harm from industry entanglement in healthcare research, education and practice. However, evidence is lacking of disclosure-related mitigation. Radical and extensive severing of industry ties to health care is necessary to curtail industry-related bias and harm.

Can public financing of the private sector defeat antimicrobial resistance?

Public financing to incentivise private sector innovation in antimicrobial pharmaceuticals is believed by many to be necessary to defeat growing threats from antimicrobial resistance. Large cash incentives from the public sector are said to be essential to stimulate 'normal' market forces capable of unleashing much-needed innovation. However, there is little evidence to suggest that lack of innovation in drug development is peculiar to antimicrobials or that current deficits in the supply of antimicrobials is due to unique inefficiencies in the antimicrobial market. Neither the history of drug development in general nor of antimicrobial innovation in particular supports economic interventions intended to stimulate private sector supply of new antimicrobials. On the contrary, public underwriting of the private sector, which by definition is compelled to prioritise profit, risks dire consequences for future global health.

Reviving Cochrane's contribution to evidence-based medicine: bridging the gap between evidence of efficacy and evidence of effectiveness and cost-effectiveness.

Throughout the quarter century since the advent of evidence-based medicine (EBM), medical research has prioritized 'efficacy' (i.e. internal validity) using randomized controlled trials. EBM has consistently neglected 'effectiveness' and 'cost-effectiveness', identified in the pioneering work of Archie Cochrane as essential for establishing the external (i.e. clinical) validity of health care interventions. Neither Cochrane nor other early pioneers appear to have foreseen the extent to which EBM would be appropriated by the pharmaceutical and medical devices industries, which are responsible for extensive biases in clinical research due to selective reporting, exaggeration of benefits, minimization of risks, and misrepresentation of data. The promise of EBM to effect transformational change in health care will remain unfulfilled until (i) studies of effectiveness and cost-effectiveness are pursued with some of the same fervour that previously succeeded in elevating the status of the randomized controlled trial, and (ii) ways are found to defeat threats to scientific integrity posed by commercial conflicts of interest.

A gender-specific analysis of adolescent dietary caffeine, alcohol consumption, anger, and violent behavior.

Self-reported dietary caffeine and alcohol consumption were examined in relation to anger and violent behavior in Icelandic tenth-graders. Structural equation modeling (SEM) was used to investigate direct and indirect effects of measured and latent variables in the population sample of 3,670, controlling for parental financial standing, family structure, ADHD, and peer delinquency. Gender differences were observed that have not been reported previously, especially in relation to anger as a possible mediator of violent behavior against a background of caffeine and alcohol consumption. Study findings suggest the need to take account of caffeine consumption in relation to adolescent anger and violence.

Caffeinated sugar-sweetened beverages and common physical complaints in Icelandic children aged 10-12 years.

OBJECTIVE: Consumption of caffeinated sugar-sweetened beverages (CSSBs) among children and adolescents has increased markedly in recent years but the consequence of their consumption is not well understood. The objective of this study was to assess the prevalence of CSSBs in children aged 10­12 years and examine the relationship between CSSBs and common physical complaints. METHODS: Data from the 2013 cross-sectional population school survey Youth in Iceland (N=11,267, response rate: 90.1%, girls 49.7%)was used to assess the prevalence of cola and energy drink consumption and associations to headaches, stomachaches, sleeping problems and low appetite. RESULTS: Around 19% of boys and 8% of girls reported consuming cola drinks on a daily basis and 7% of boys and 3% of girls reported consuming energy drinks. A general trend of a dose­response relationship was observed between CSSBs and physical complaints for both types of beverages. These relationships were generally stronger for energy drinks than cola drinks. CONCLUSION: Our findings call into question the acceptability, availability, and marketing of CSSBs to 10­12 year-old children and adolescents. For validation purposes replications of these analyses are needed in other parts of the world, including studies using prospective longitudinal designs.

Adolescent caffeine consumption and self-reported violence and conduct disorder.

Caffeine is the most widely used psychoactive substance in the world and currently the only one legally available to children and adolescents. The sale and use of caffeinated beverages has increased markedly among adolescents during the last decade. However, research on caffeine use and behaviors among adolescents is scarce. We investigate the relationship between adolescent caffeine use and self-reported violent behaviors and conduct disorders in a population-based cross-sectional sample of 3,747 10th grade students (15-16 years of age, 50.2 % girls) who were enrolled in the Icelandic national education system during February 2012. Through a series of multiple regression models, while controlling for background factors, Attention Deficit Hyperactivity Disorder symptoms and current medication and peer delinquency, and including measures on substance use, our findings show robust additive explanatory power of caffeine for both violent behaviors and conduct disorders. In addition, the association of caffeine to the outcomes is significantly stronger for girls than boys for both violent behaviors and conduct disorders. Future studies are needed to examine to what extent, if at all, these relationships are causal. Indication of causal connections between caffeine consumption and negative outcomes such as those reported here would call into question the acceptability of current policies concerning the availability of caffeine to adolescents and the targeting of adolescence in the marketing of caffeine products.

Possible role of caffeine in nicotine use onset among early adolescents: Evidence from the Young Mountaineer Health Study Cohort.

BACKGROUND: Preventing nicotine use onset among children and youth is an important public health goal. One possible contributor that has received little empirical investigation is caffeine use. The goal of this study was to examine the possible contribution of caffeine to nicotine onset during early adolescence. METHODS: We used data from the Young Mountaineer Health Study Cohort. Survey data were collected from 1,349 (response rate: 80.7%) 6th grade students (mean age at baseline 11.5 years) in 20 middle schools in West Virginia during the fall of 2020 and spring of 2021. We limited our analyses to students reporting never having used any form of nicotine at baseline. Logistic regression was employed in analyses. RESULTS: Approximately 8% of participants reported having used nicotine at least once between baseline and the follow-up, and 4.7% reported solely using electronic nicotine delivery systems (ENDS) and no other forms of nicotine. In multivariable analyses, we controlled for many environmental, social, and behavioral variables known to influence nicotine use such as alcohol use, peer substance use, and perceived access to nicotine. We formulated our main independent variable, caffeine consumption, as continuous deciles. Any nicotine use, as well as ENDS use only at follow-up, were modeled as dependent variables. Caffeine was significantly associated with nicotine use in both models with ORs of 1.15 (1.04-1.27) and 1.13 (1.00-1.28). CONCLUSIONS: Caffeine consumption among 6th grade non-nicotine users was associated with nicotine use at approximately 6-months follow-up.

The supplementation of a prebiotic improves the microbial community in the gut and the skin of Atlantic salmon (Salmo salar).

Aquaculture growth is hindered by an increasing number of challenges, primarily infectious diseases and inappropriate or unsustainable fish nutrition. Hence it is critical to develop novel prevention strategies to minimise infectious diseases and pharmaceutical interventions. Nutritional challenges and the health of the fish could be improved by managing their microbial communities. Microbiomes can play a crucial role in fish physiology, particularly in digestion, by metabolizing largely indigestible feed components for the host or synthesis essential micronutrients. Beyond their nutritional role, microbiomes are considered the first line of defence against pathogens. In this study, a novel prebiotic mix (Selectovit), composed of 1,3/1,6-beta glucans, mannan-oligosaccharides, nucleic acids, nucleotides, medium chain fatty acids and single chain fatty acids, was tested at different inclusion levels (0.0; 0.5; 1.0; 2.0 g/kg) in the diet of Atlantic salmon (Salmo salar). Using experimental feed trials and 16 S rRNA microbiome profiling, the impact of the prebiotic blend on fish growth and microbial community within both the gastrointestinal tract and the skin was assessed. Overall, the supplement showed no significant impact on growth. However, we clearly demonstrate that the prebiotic can significantly manipulate the microbial community of the distal intestine and the skin. Several potential beneficial bacteria such as Bacillus and Mycoplasma spp. were significantly more abundant in the prebiotic-fed groups compared to the control. In contrast, putative pathogenic bacteria were less abundant in the salmon fed the prebiotic blend. Interestingly, the supplement induced more changes in the skin than in the gut. There is growing evidence in fish for highly complex interactions between the microbial communities of the digestive system and external mucosa, and with the host immune system. Further research in this field could lead to the creation of novel bacterial biomarkers and new non-invasive strategies for fish digestive health monitoring.

Risk and Resilience Pathways, Community Adversity, Decision-making, and Alcohol Use Among Appalachian Adolescents: Protocol for the Longitudinal Young Mountaineer Health Study Cohort.

BACKGROUND: Alcohol use impairs psychosocial and neurocognitive development and increases the vulnerability of youth to academic failure, substance use disorders, and other mental health problems. The early onset of alcohol use in adolescents is of particular concern, forecasting substance abuse in later adolescence and adulthood. To date, evidence suggests that youth in rural areas are especially vulnerable to contextual and community factors that contribute to the early onset of alcohol use. OBJECTIVE: The objective of the Young Mountaineer Health Study is to investigate the influence of contextual and health behavior variables on the early onset of alcohol use among middle school-aged youth in resource-poor Appalachian rural communities. METHODS: This is a program of prospective cohort studies of approximately 2200 middle school youth from a range of 20 rural, small town, and small city (population <30,000) public schools in West Virginia. Students are participating in 6 waves of data collection (2 per year) over the course of middle school (sixth to eighth grades; fall and spring) from 2020 to 2023. On the basis of an organizational arrangement, which includes a team of local data collection leaders, supervising contact agents in schools, and an honest broker system to deidentify data linked via school IDs, we are able to collect novel forms of data (self-reported data, teacher-reported data, census-linked area data, and archival school records) while ensuring high rates of participation by a large majority of youth in each participating school. RESULTS: In the spring of 2021, 3 waves of student survey data, 2 waves of data from teachers, and a selection of archival school records were collected. Student survey wave 1 comprised 1349 (response rate 80.7%) participants, wave 2 comprised 1649 (response rate 87%) participants, and wave 3 comprised 1909 (response rate 83.1%) participants. The COVID-19 pandemic has had a negative impact on the sampling frame size, resulting in a reduced number of eligible students, particularly during the fall of 2020. Nevertheless, our team structure and incentive system have proven vitally important in mitigating the potentially far greater negative impact of the pandemic on our data collection processes. CONCLUSIONS: The Young Mountaineer Health Study will use a large data set to test pathways linking rural community disadvantage to alcohol misuse among early adolescents. Furthermore, the program will test hypotheses regarding contextual factors (eg, parenting practices and neighborhood collective efficacy) that protect youth from community disadvantage and explore alcohol antecedents in the onset of nicotine, marijuana, and other drug use. Data collection efforts have been successful despite interruptions caused by the COVID-19 pandemic in 2020 and 2021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40451.

Adolescent substance use, sleep, and academic achievement: evidence of harm due to caffeine.

Using academic achievement as the key outcome variable, 7377 Icelandic adolescents were surveyed for cigarette smoking, alcohol use, daytime sleepiness, caffeine use, and potential confounders. Structural equation modeling (SEM) was used to examine direct and indirect effects of measured and latent variables in two models: the first with caffeine excluded and the second with caffeine included. A substantial proportion of variance in academic achievement, which might otherwise have been attributed to the harmful effects of cigarette smoking and alcohol use, was found to be attributable to caffeine. Evidence was obtained that daytime sleepiness, which was found to be independently associated with usage of licit substances (nicotine and alcohol) and caffeine, may be an important mediator of the negative impact of those substances on academic achievement. Findings suggest the importance of including measurements of caffeine consumption in future studies of adolescent substance use.

Maternal caffeine consumption and pregnancy outcomes: a narrative review with implications for advice to mothers and mothers-to-be.

OBJECTIVES: Caffeine is a habit-forming substance consumed daily by the majority of pregnant women. Accordingly, it is important that women receive sound evidence-based advice about potential caffeine-related harm. This narrative review examines evidence of association between maternal caffeine consumption and negative pregnancy outcomes, and assesses whether current health advice concerning maternal caffeine consumption is soundly based. METHODS: Database searches using terms linking caffeine and caffeinated beverages to pregnancy outcomes identified 1261 English language peer-reviewed articles. Screening yielded a total of 48 original observational studies and meta-analyses of maternal caffeine consumption published in the past two decades. The articles reported results for one or more of six major categories of negative pregnancy outcomes: miscarriage, stillbirth, low birth weight and/or small for gestational age, preterm birth, childhood acute leukaemia, and childhood overweight and obesity. RESULTS: Of 42 separate sets of findings reported in 37 observational studies, 32 indicated significantly increased caffeine-related risk and 10 suggested no or inconclusive associations. Caffeine-related increased risk was reported with moderate to high levels of consistency for all pregnancy outcomes except preterm birth. Of 11 studies reporting 17 meta-analyses, there was unanimity among 14 analyses in finding maternal caffeine consumption to be associated with increased risk for the four outcome categories of miscarriage, stillbirth, low birth weight and/or small for gestational age, and childhood acute leukaemia. The three remaining meta-analyses were also unanimous in reporting absence of a reliable association between maternal caffeine consumption and preterm birth. No meta-analyses were identified for childhood overweight and obesity, although four of five original observational studies reported significant associations linking maternal caffeine consumption to that outcome category. CONCLUSIONS: The substantial majority finding from observational studies and meta-analyses is that maternal caffeine consumption is reliably associated with major negative pregnancy outcomes. Reported findings were robust to threats from potential confounding and misclassification. Among both observational studies and meta-analyses, there were frequent reports of significant dose-response associations suggestive of causation, and frequent reports of no threshold of consumption below which associations were absent. Consequently, current evidence does not support health advice that assumes 'moderate' caffeine consumption during pregnancy is safe. On the contrary, the cumulative scientific evidence supports pregnant women and women contemplating pregnancy being advised to avoid caffeine.

Adolescent substance use, parental monitoring, and leisure-time activities: 12-year outcomes of primary prevention in Iceland.

OBJECTIVE: To examine 12-year changes in alcohol use and cigarette smoking in response to community-based prevention activities among Icelandic adolescents. METHODS: This study used a quasi-experimental, non-randomized control group design to compare outcomes in 4 Icelandic communities (n=3117) that participated in community-based substance use prevention activities designed to increase levels of parental monitoring and adolescent engagement in healthy leisure-time activities and a matched group of 7 comparison communities (n=1,907). Annual, nationwide, population-based cross-sectional surveys of the prevalence of adolescent substance use were conducted among cohorts of Icelandic adolescents, aged 14-15 years (N=5,024), in all communities from 1997 to 2009. RESULTS: Parental monitoring and adolescent participation in organized sports increased in communities that adopted the intervention program compared to communities that did not, whereas unmonitored idle hours and attendance at unsupervised parties decreased. Over time, alcohol use (OR=0.89, 95% CI 0.82, 0.98, p=0.012) and being intoxicated during the last 30 days (OR=0.86, 95% CI 0.78, 0.96, p=0.004) decreased more in the intervention than control communities. CONCLUSION: Community-based prevention designed to strengthen parental monitoring and participation in organized sports may confer some protection against adolescent substance use.