Clinical and Analytical Toxicology of Dietary Supplements: A Case Study and a Review of the Literature

The use of dietary supplements has grown dramatically in the last decade. A large number of dietary and herbal supplements escape regulatory and quality control; components of these preparations are poisonous and may contain, among other toxins, heavy metals. Uncontrolled use of dietary and herbal supplements by special populations, such as the military, may therefore pose a health risk. Clinical symptoms are not always properly attributed to dietary supplements; patients often do not mention supplement use to their health care provider. Therefore, a health risk estimate is hard to make on either the individual or the population level. The literature on this issue was reviewed and discussed in the light of a representative clinical-chemical case study. This case study was performed on a host of preparations that were used by one single individual in the military. Both essential (chromium, copper, zinc, and iron) and poisonous (arsenic, lead, and nickel) trace elements were determined using inductively coupled plasma combined with optical emission spectrometry (ICP-OES) or with mass spectrometry (ICP-MS). Arsenic and lead were detected at exposure levels associated with health risks. These health risks were detected predominantly in hormone-containing supplements and the herbs and botanicals used for performance enhancement. To the extent that this is a representative sample, there is an underestimation of supplement use and supplement risk in the US military, if not in the general population. Since clinical symptoms may be attributed to other causes and, unless patients are specifically asked, health care providers may not be aware of their patients' use of dietary supplements, a strong support of laboratory diagnostics, such as a toxicological screening of blood or urine, is required. In addition, screening of the preparations themselves may be advised.     

Consumer Risk Assessment Associated with Intake of Pesticide Residues in Food of Plant Origin from the Retail Market in Poland

The aim of this study was to characterize short- and long-term risk for consumers associated with dietary intake of pesticide residues in fruits, vegetables, and other foodstuffs available on the Polish market based on 2010–2013 official surveillance results. Among 779 samples collected from 2010 to 2013 no pesticide residue was found in 39.7% samples while 58.5% contained residues at or below the EU Maximum Residue Levels (MRLs). Non-compliances (residues above the respective MRLs) were found in 14 samples (1.8%). Most of the estimated daily intakes were well below 1% of respective acceptable daily intake (ADI) values. The highest intake for children and adults was about 7% and 1.5% of ADI, respectively. For non-compliant results acute risk was characterized. Predicted short-term intakes for children and adults ranged from 0.7% to 425%, and from 0.2% to 100% of respective acute reference dose, respectively. Results of chronic risk characterization show that consumers in Poland are adequately protected; however, incidental cases where residue levels may potentially pose a threat to consumers’ health due to acute exposure cannot be excluded.     

Improving the Use of Toxicity Reference Values in Wildlife Food Chain Modeling and Ecological Risk Assessment

Ecological risk assessments often include mechanistic food chain models based on toxicity reference values (TRVs) and a hazard quotient approach. TRVs intended for screening purposes or as part of a larger weight-of-evidence (WOE) assessment are readily available. However, our experience suggests that food chain models using screening-level TRVs often form the primary basis for risk management at smaller industrial sites being redeveloped for residential or urban parkland uses. Iterative improvement of a food chain model or the incorporation of multiple lines of evidence for these sites are often impractical from a cost-benefit perspective when compared to remedial alternatives. We recommend risk assessors examine the assumptions and factors in the TRV derivation process, and where appropriate, modify the TRVs to improve their ecological relevance. Five areas where uncertainty likely contributes to excessively conservative hazard quotients are identified for consideration.     

Exploring the Determinants of the Perceived Risk of Food Allergies in Canada

Food allergies are emerging health risks in much of the Western world, and some evidence suggests prevalence is increasing. Despite lacking scientific consensus around prevalence and management, policies and regulations are being implemented in public spaces (e.g., schools). These policies have been criticized as extreme in the literature, in the media, and by the non-allergic population. Backlash appears to be resulting from different perceptions of risk between different groups. This article uses a recently assembled national dataset (n = 3,666) to explore how Canadians perceive the risks of food allergy. Analyses revealed that almost 20% self-report having an allergic person in the household, while the average respondent estimated the prevalence of food allergies in Canada to be 30%. Both of these measures overestimate the true clinically defined prevalence (7.5%), indicating an inflated public understanding of the risks of food allergies. Seventy percent reported food allergies to be substantial risks to the Canadian population. Multivariate logistic regression models revealed important determinants of risk perception including demographic, experience-based, attitudinal, and regional predictors. Results are discussed in terms of understanding emerging health risks in the post-industrial era, and implications for both policy and risk communication.     

Assessment of Hazard Risk Associated with the Intravenous Use of Viral Vectors in Rodents

Viral vectors are emerging as potent basic research tools and gene therapy vehicles in many laboratory animal models. However, little information is available on the potential shedding of these vectors and the consequent exposure risk to investigators and animal care staff from animals over time. This study provides empirical information to Institutional Biosafety Committees and animal care programs, to enhance their ability to perform risk management of laboratory animals treated with viral vectors. Control experiments evaluated the limit of detection of third-generation lentivirus, recombinant adeno-associated virus, and E1-deleted adenovirus tested directly from stocks and after application onto cage plastic or bedding. After inoculation of ICR or NOD-SCID mice, we quantified the recovery of viral vector genomes directly from blood, urine, and fecal samples and assessed the persistence of infectious vector at the site of injection and from soiled bedding at different time points after inoculation. No differences were seen between ICR and NOD-SCID mice. We saw no evidence of vector amplification after in vivo inoculation. The most environmentally persistent vector was recombinant adeno-associated virus, which has no known pathogenicity in humans. In light of these data, we conclude that commonly used replication-deficient viral vectors pose minimal exposure risk by 72 h after inoculation. Prudent precautions at Animal Biosafety Level 2 are warranted during initial administration, but Level 1 safety measures may be sufficient after cage changing and biosafety evaluation.Abbreviations: Ad, adenovirus; CMV, cytomegalovirus; EGFP, enhanced green fluorescent protein; LV, third-generation lentivirus; qPCR, qualitative PCR; rAAV, recombinant adeno-associated virusThe era of customizable transgenic mice and molecular manipulation of viruses to deliver targeted genes has revolutionized our ability to study gene-specific functions. A typical viral vector is engineered by separating the wildtype virus genome onto multiple nonoverlapping plasmids, with the minimal coding sequences necessary for replication provided in trans to the transgene construct, which contains only those cis-acting viral elements necessary to direct packaging into a noninfectious virion. Large portions of the genome necessary for pathogenicity are completely removed. The resulting engineered viral vectors offer the ability to specifically target tissues and genes and are emerging as potent gene therapy vehicles. With these tools for basic research, we are equipped to answer questions about the effects of genes and proteins on development, behavior, sensation, and organ function and in disease.Each viral vector has unique properties and targets defined cell populations (Figure 1).^1,18 For example, lentiviral (LV) vectors are used for in vivo gene delivery because they efficiently transduce both dividing and nondividing cells and stably integrate into the host genome, providing long-term transgene expression. Lentiviral vectors typically are based on HIV1 that has been substantially debilitated to provide multiple safeguards against the production of replication-competent lentivirus.^6,32 Third-generation lentiviral vectors have deletions in the promoter region of the long terminal repeats, rendering these vectors self-inactivating after proviral integration. In addition, they include deletions in all 6 major genes involved in pathogenesis—including the genes for Env, Vpr, Vpu, Vif, Nef, Rev, and (in some versions) Tat. Typically, vesicular stomatitis virus glycoprotein is substituted for the native viral Env protein. The transient packaging system contains less than 30% of the original viral genome, and the produced replication-deficient self-inactivating vector particles integrate less than 8% of the HIV genome into infected cells. Such an HIV1-based vector, pseudotyped with the vesicular stomatitis virus glycoprotein as its major envelope protein, is the most commonly used lentiviral vector and is available commercially from most major life-science vendors and from core facilities at various scientific institutions.Open in a separate windowFigure 1.Viral vector characteristics.Adenoviral vectors are small (90 nm) nonenveloped icosahedral vectors with a linear double-stranded DNA genome. They infect dividing and nondividing cells but do not actively integrate into the host cell genome; therefore, expression is transient in actively dividing cells and tissues. Long-term transgene expression in nondividing cells and tissues has been achieved as well. Adenoviral vectors are most commonly derived from adenoviral serotype 5 (Ad5).⁹ Helper-free, replication-defective recombinant Ad5 vectors often are generated through deletion of the essential E1a/b and nonessential E3 regions of the viral genome. Removal of these sequences allows the introduction of a gene of interest into the deleted region, with a packaging capacity of approximately 8 kb. Adenoviral replication is dependent on the E1a/b region of the viral genome; as such, recombinant Ad5 vectors are unable to replicate, and packaging of replication-defective Ad5 vector particles is achieved through the transfection of a linearized plasmid containing the recombinant Ad5 vector genome into HEK293/17 cells, or derivatives of this cell line, which stably express the Ad5 E1a gene. With E1a/b- and E3-deleted Ad5 vectors, 2 separate recombination events would need to occur during packaging to generate replication-competent wildtype virus. ‘Gutless’ (that is, helper-dependent) Ad5 viral vector systems have also been developed; in these systems, all viral genes have been removed from the recombinant vector genome. This manipulation greatly increases the packaging capacity of these vectors—from approximately 8 kb to 36 kb—and markedly reduces immune responses in vivo. Helper virus is required for the production of gutless adenoviral vector, and various strategies have been developed to remove this helper virus from the subsequent viral vector preparation.²⁵Recombinant adeno-associated viral (rAAV) vectors are derived from the AAV2 virus, a very small (20 nm) icosahedral nonenveloped virus with a linear single-stranded DNA genome that does not actively integrate into the host cell genome. Wildtype AAV2 is not a known human pathogen, and coinfection with a helper virus, such as adenovirus, is required for AAV2 to replicate within a host cell. All of the wildtype viral genome has been deleted from rAAV2 vectors, except for the 5′ and 3′ inverted terminal repeat regions, which are the only cis acting, noncoding viral sequences necessary for packaging of a recombinant vector genome into replication-defective particles. rAAV2 vectors typically are produced in a helper-virus-free system.³⁴ The recombinant rAAV2 genome expressing the gene of interest, adenoviral helper genes, and the AAV coding sequences for the rep and cap proteins are provided on separate plasmids and are transiently transfected into producer cells, such as HEK293T/17. The packaging capacity of rAAV2 vectors is approximately 4.7 kb, although larger genomes have successfully been packaged or expressed in vivo. The produced, replication-defective rAAV2 vector particles can also be cross-packaged with capsid proteins from other AAV serotypes²² as well as engineered capsid proteins,^15,31,33 offering attractive systems for altering the cell and tissue tropism of the produced vector.Institutional Biosafety Committees serve a critical function in providing oversight and balanced risk assessment of hazard use in research facilities, effectively managing the risk associated with viral vector use, both in the laboratory and in vivo after treatment of laboratory animals. Decisions related to the biosafety of viral vector use often are based on the known pathogenic properties of the parental wildtype viruses, in combination with case-by-case determination of additional risks related to the characteristics of the particular viral vector subtype and the biologic activity (if known) of the expressed transgene or regulatory nucleic acid to be packaged. Similar strategies are used to further classify these agents into 1 of 4 specific risk groups.³ Replication-deficient Ad and LV vectors currently are classified in section III-D-3-a as group 2 viruses, and experiments with these agents involving animals are categorized into section III-D-4-b.²⁰ Although AAV vectors are classified as group 1 viruses, the biologic activity of the expressed transgene may lead an Institutional Biosafety Committee to mandate the use of Biosafety Level 2 or Animal Biosafety Level 2 precautions with rAAV vectors. To date, few published reports address direct measurement of the exposure risk from animals treated with different viral vectors have been available to Institutional Biosafety Committee members. Given this paucity of information, recommendations frequently are made based on the biologic properties of the parent (often virulent and replicative) strains of these vectors. These biologic properties most specifically relate to virulence, pathogenicity, infectious dose, environmental stability, route of spread, and communicability of the wildtype strain.³⁰Several potential risks are associated with these agents, including transmission of the viral vector itself, homologous recombination resulting in the generation of replication-competent vector or virulent wildtype-like virus, contamination by residual helper viruses (if used during vector preparation), and adverse effects of the inserted gene or regulatory nucleic acid (for example, oncogenesis).^17,27 The wildtype, parental HIV and adenovirus strains can be stable for a month or longer in a laboratory setting.²⁹ Although important in the context of traditional virus research, these guidelines are only broadly applicable to advanced, later-generation agents that have been specifically and rationally modified to deliver target genes without generating associated vector-induced disease or uncontrolled replication.Managing these vector agents in rodents according to Animal Biosafety Level 2 guidelines can sometimes be problematic when the use of primary engineering controls (for example, a biologic safety cabinet) is impractical or impossible. The ability to incorporate suggested safety measures may be limited, in part, because of the experimental design, infrastructural limitation, and work processes. Examples of these procedures include behavioral testing, breeding, bioimaging, MRI and CT scanning, and other specialized research activities that require the use of large or immobile equipment. In addition, routine practices in vivaria may increase the potential for contamination thorough direct contact with infected animals, fomite contamination, or potential aerosolization through handling of soiled bedding.A group of investigators at our institution are developing and using novel or modified viral vectors in various unconventional ways. These methodologies are expanding rapidly to other disciplines, and many institutions are witnessing the expansion of ‘gray areas’ in risk assessment and containment. Guidance in evaluating the safety and use of LV vectors is available,¹⁹ but few reports detailing empirical data are available to support these concepts. If the real threat of shedding or infection can be quantified, it then would be feasible to establish accurately the risk associated with treated animals and enhance laboratory and vivarium safety practices.We hypothesized that risks associated with viral vectors in mice may be lower than those generally associated with the parent viruses. Once given to animals, the current state-of-the-art replication-deficient viral gene therapy and targeting vectors likely pose minimal risk of exposure to staff, and application of standard Animal Biosafety Level 2 biohazard precautions when working with rodents carrying viral vectors may not be necessary indefinitely. We report here our evaluation of the risk of the shedding of several classes of genetically modified viral vectors from rodents and subsequent potential for human exposure to these vectors.     

Use of Toxicological Data in Estimating Reference Values for Risk Assessment

A number of programs within the U.S. Environmental Protection Agency (USEPA) currently set less-than-lifetime exposure limits in addition to the chronic reference dose (RfD) and reference concentration (RfC). A review of procedures within the USEPA for setting reference values suggests that less-thanlifetime reference values should be more routinely developed and captured in the USEPA's online IRIS database where chronic RfDs and RfCs, as well as cancer slope factors, are currently available. A review of standard testing study protocols was conducted to determine what data were available for setting acute, short-term, and longer-term reference values, as well as chronic values. This review was done from the point of view of endpoints assessed for specific organ systems (both structural and functional), life stages covered by exposure and outcome, durations of exposure covered and the outcomes evaluated for each, and evaluation of latency to response and/or reversibility of effects. This review revealed a number of data gaps and research needs, including the need for an acute and/or short-term testing protocol that can be used to set acute and shortterm reference values, a strategy for when to conduct more extensive testing based on initial screening data or other information (e.g., chemical class, pharmacokinetics, mode of action), additonal standard testing guidlines protocols to allow more complete assessment of certain organ systems and life stages, development of pharmacokinetic data for different life stages, toxicity related to aging, and latency to response, particularly long-term latency as a result of developmental exposures. The implications of this review are discussed relative to characterizing hazard data for setting reference values, and the potential effects on uncertainty factors and low-dose extrapolation.     

Trace Metals (Cd,Co, Cr,Cu, Hg,Ni, Pb,and Zn) in Food Supplements of Marine Origin

We determined the concentrations of Cd, Co, Cr, Cu, Hg, Ni, Pb, and Zn in dietary supplements of marine origin. Four supplement categories were studied; algae, coral, krill, and shark cartilage. A direct mercury analyzer was used for Hg determinations while acid digestions and ICP-AES were used for Cr analysis and ICP-MS for the other trace metals. Algae are the supplements showing the highest concentrations of Pb, Cr, and Ni with respective means of 1.6 mg Pb/kg dry weight (d.w.), 3.2 Cr mg/kg d.w., and 8.0 mg Ni/kg d.w. Krill supplements have the highest levels of Cd, Cu, and Zn with 0.65 mg Cd/kg d.w., 63 mg Cu/kg d.w., and 50 mg Zn/kg d.w., respectively. Shark cartilage supplements show the highest levels of Hg and Co with mean concentrations of 160 μg Hg/kg d.w. and 73 ± 51 μg Co/kg d.w., respectively. No samples in our study exceeded the provisional tolerable daily intakes set by Health Canada, the joint committee of the World Health Organization/Food and Agricultural Organization, or the U.S. Environmental Protection Agency. Nevertheless, Ni and Pb in algae and Hg in shark cartilage may end up contributing to a very significant portion of the allowable daily intake—leaving little room for normal intake through food consumption and other exposure pathways.     

Use of Renin-Angiotensin System Inhibitors Is Associated with Reduction of Fracture Risk in Hemodialysis Patients

Background

Patients with chronic kidney disease, especially those undergoing dialysis treatment and having secondary hyperparathyroidism, have a high risk of bone fracture. The renin-angiotensin system (RAS) is associated with osteoclastic bone resorption. We aimed to examine whether the use of RAS inhibitors reduces the incidence of fracture in hemodialysis patients.

Methods and Findings

This was a multicenter, 3-year, prospective, observational study. From 2008 to 2011, maintenance hemodialysis patients with secondary hyperparathyroidism (N = 3,276) treated with angiotensin converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) at baseline were followed for a mean of 2.7 years. The association between the use of ACEI/ARB and hospitalization rate owing to fracture was examined by using Cox regression models. Effect modifications by the severity of secondary hyperparathyroidism (intact parathyroid hormone [iPTH] level), sex, and systolic blood pressure were also examined. The incidence proportion of fracture-related hospitalization was 5.42% throughout the observation period. ACEI/ARB use was associated with a lower rate of fracture-related hospitalization (adjusted hazard ratio, 0.65; 95% confidence interval [CI], 0.45–0.92). This association was not significantly affected by sex (P = 0.56) or systolic blood pressure levels (P = 0.87). The hazard ratios adjusted by iPTH levels were qualitatively different, but not statistically significant (P = 0.11): 0.77 (95% CI, 0.42–1.39), 0.38 (95% CI, 0.20–0.73), 0.59 (95% CI, 0.29–1.21), and 1.29 (95% CI, 0.58–2.42) for the first, second, third and fourth quartiles of iPTH, respectively.

Conclusions

Use of RAS inhibitors is associated with a lower rate of fracture-related hospitalization in hemodialysis patients with secondary hyperparathyroidism.

Trial Registration

ClinicalTrials.gov NCT00995163     

Providing chicks with extra food lowers male but not female provisioning in the House Sparrow Passer domesticus

We assessed whether adult House Sparrows Passer domesticus adjusted their provisioning in response to an experimental increase in the nutritional condition of their nestlings. When we supplemented chicks directly with additional food, male parents, but not female parents, reduced their provisioning. The results for males, but not females, run contrary to a previous experiment in this species. In addition, female provisioning was positively associated with both brood size and the age of the brood. In contrast, whereas male provisioning was positively associated with brood size, males did not increase provisioning as their chicks grew older. Males, but not females, exhibited repeatability in their provisioning. Food supplementation had a larger positive effect upon nestling survival in smaller broods than in larger broods. Overall, there appear to be fundamental differences between males and females in how decisions regarding the level of parental investment in the current brood are made.     

Seroprevalence and Potential Risk Factors Associated with Neospora spp. Infection among Asymptomatic Horses in Jordan

This study aimed to determine the seroprevalence and to identify risk factors associated with Neospora spp. infection in horses in Jordan. Management related data were collected from each farm and individual horses. Sera from 227 horses from 5 of 6 climatic regions in Jordan were analyzed for the presence of antibodies to Neospora spp. by ELISA kit. The study was performed during spring of 2010. The association between seropositivity and risk factors was analyzed. A total of 7 (3%) of 227 sera had antibodies for Neospora spp. There was a significant regional difference (P=0.018) between the 5 climatic regions. Positive cases were located in Amman and Irbid, while the other regions (Zarqa, Jordan Valley, and Wadi Mousa) had zero prevalence. The use of anthelmintics at least once a year resulted in a significant reduction of the seroprevalence to Neospora spp. (1.6% vs 9.8%). However, this might be a phenomenon by chance and a better hygiene since owners can invest in anthelmintics. Other risk factors such as age, gender, breed, usage, body condition score, grazing, presence of other animals mixed with the horses in the same property, and a history of previous diseases were not significantly associated with the seroprevalence to Neospora spp. infection. This is the first study to report on the presence of Neospora seropositive horses in Jordan. Further studies are warranted to better understand the role of certain risk factors in the transmission of Neospora spp. among horse population and to determine which Neospora spp. are responsible for the infection.     

Problems and Strategies Associated with Long-term Use of Nematode Resistant Cultivars

Plant-parasitic nematodes are obligate parasites, and planting cultivars that are highly resistant to these organisms places extensive selection pressure on the target species and affects nontarget nematodes as well. Problems encountered with long-term planting of cultivars resistant to nematodes include shifts in nematode races or species and the occurrence of multiple species of nematodes within the same field. These problems can be alleviated to some extent when crop management is used to lessen the selection pressure for change on the nematode populations. Race shifts within populations and possibly shifts between nematode species can be delayed by rotating susceptible cultivars and nonhost crops with resistant cultivars. Nematicides in conjunction with resistant cultivars may be used to limit damage by multiple species of nematodes. Some cultivars have resistance to multiple species of nematodes, but greatly increased research effort is needed in this area. More intensive plant breeding effort will be required to make nematode resistant cultivars competitive in quality and yield with more productive, susceptible cultivars.     

A Preliminary Human Health Risk Assessment of Organochlorine Pesticide Residues Associated with Aquatic Organisms from the Rangsit Agricultural Area,Central Thailand

Food consumption is one of the main routes of human exposure to organochlorine pesticide residues (OCPRs). To assess the potential health risks associated with OCPRs contaminants due to freshwater organism consumption, a number of vegetables, prawn, snail, and fish were collected from Khlong 7 (canal), Rangsit agricultural area, Pathum-Thani Province, Thailand. The samples were extracted using a multiresidue extraction method and then analyzed by gas chromatography with microelectron capture detector (μ -ECD). The results show that low concentrations of OCPRs were detected in parts per billion (ppb) levels. Based on a plausible worst-case scenario, the local population could be at risk for cancer due to consumption of fish contaminated by α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, dieldrin, DDD, DDE, and DDT. Likewise, individuals may be at risk from consumption of Lanchester's freshwater prawn Macrobrachium lanchesteri, freshwater snail Filopaludina mertensi, swamp morning-glory Ipomomea aquatica, neptunia Neptunia oleracea, and water lily Nymphaea lotus because these species all contained elevated concentrations of α -, β -HCH, heptachlor, heptachlor epoxide, aldrin, and dieldrin.     

Food provisioning alters infection dynamics in populations of a wild rodent

While pathogens are often assumed to limit the growth of wildlife populations, experimental evidence for their effects is rare. A lack of food resources has been suggested to enhance the negative effects of pathogen infection on host populations, but this theory has received little investigation. We conducted a replicated two-factor enclosure experiment, with introduction of the bacterium Bordetella bronchiseptica and food supplementation, to evaluate the individual and interactive effects of pathogen infection and food availability on vole populations during a boreal winter. We show that prior to bacteria introduction, vole populations were limited by food availability. Bordetella bronchiseptica introduction then reduced population growth and abundance, but contrary to predictions, primarily in food supplemented populations. Infection prevalence and pathological changes in vole lungs were most common in food supplemented populations, and are likely to have resulted from increased congregation and bacteria transmission around feeding stations. Bordetella bronchiseptica-infected lungs often showed protozoan co-infection (consistent with Hepatozoon erhardovae), together with more severe inflammatory changes. Using a multidisciplinary approach, this study demonstrates a complex picture of interactions and underlying mechanisms, leading to population-level effects. Our results highlight the potential for food provisioning to markedly influence disease processes in wildlife mammal populations.     

Quantification of Locomotion and the Effect of Food Deprivation on Locomotor Activity in Drosophila

A new method to quantify locomotor behavior in Drosophila is presented, and compared with previous methods. It is based upon a radar wave, reflected by moving flies. A problem associated with the new apparatus is that its output is dependent on fly size. However, for the case the weight of the experimental flies has been determined, a correction is proposed. The method has been used by studying the effect of starvation upon locomotion in Drosophila melanogaster. It was found that starved flies are much more active than well fed flies. The importance of this effect under several conditions is discussed.     

Mapping the Influence of Food Waste in Food Packaging Environmental Performance Assessments

Scrutiny of food packaging environmental impacts has led to a variety of sustainability directives, but has largely focused on the direct impacts of materials. A growing awareness of the impacts of food waste warrants a recalibration of packaging environmental assessment to include the indirect effects due to influences on food waste. In this study, we model 13 food products and their typical packaging formats through a consistent life cycle assessment framework in order to demonstrate the effect of food waste on overall system greenhouse gas (GHG) emissions and cumulative energy demand (CED). Starting with food waste rate estimates from the U.S. Department of Agriculture, we calculate the effect on GHG emissions and CED of a hypothetical 10% decrease in food waste rate. This defines a limit for increases in packaging impacts from innovative packaging solutions that will still lead to net system environmental benefits. The ratio of food production to packaging production environmental impact provides a guide to predicting food waste effects on system performance. Based on a survey of the food LCA literature, this ratio for GHG emissions ranges from 0.06 (wine example) to 780 (beef example). High ratios with foods such as cereals, dairy, seafood, and meats suggest greater opportunity for net impact reductions through packaging‐based food waste reduction innovations. While this study is not intended to provide definitive LCAs for the product/package systems modeled, it does illustrate both the importance of considering food waste when comparing packaging alternatives, and the potential for using packaging to reduce overall system impacts by reducing food waste.     

Balkans’ Asteraceae Species as a Source of Biologically Active Compounds for the Pharmaceutical and Food Industry

Herbal drugs are a useful source of different bioactive compounds. Asteraceae species, as the most widespread vascular plants, can be used both as food and as medicine due to the great diversity of recorded chemical components – different phenolic compounds, terpenes, carotenoids, vitamins, alkaloids, etc. The Balkan Peninsula is characterized by great diversity of plants from Asteraceae family, including presence of rare and endemic species. In this review, results of the survey of chemical composition and biological activity, mainly focusing on antioxidant, antimicrobial and anticancer effects of selected Balkans’ Asteraceae species were provided. In addition, information on edible plants from Asteraceae family is presented, due to growing interest for the so‐called ‘healthy diet’ and possible application of Balkans’ Asteraceae species as food of high nutritional value or as a source of functional food ingredients.     

Risk of Ischemic Stroke Associated with the Use of Antipsychotic Drugs in Elderly Patients: A Retrospective Cohort Study in Korea

Objective

Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs.

Method

We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference.

Results

Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97–5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18–3.14), quetiapine (HR = 1.23, 95% CI, 0.78–2.12), and olanzapine (HR = 1.12, 95% CI, 0.59–2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83–6.02) than those who took it for a shorter period of time.

Conclusions

A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics.     

Risk Factors Associated with the Development of Atopic Sensitization in Indonesia

Background

The prevalence of allergic diseases has increased not only in high income but also in low-to-middle income countries. However, risk factors for their development are still not well established, particularly in the latter.

Objective

To assess prevalence and identify risk factors for sensitization to two major inhalant allergens among children from semi-urban and rural areas in Indonesia.

Method

A cross-sectional survey was performed among 1,674 school children aged 5–15 years old. Information on potential risk factors and reported allergic symptoms were obtained by questionnaire. Helminth infections were assessed. Skin prick tests (SPT) were performed, total IgE as well as allergen-specific IgE for house dust mite (HDM) and cockroach were measured.

Result

The prevalence of allergic skin sensitization to both aeroallergens was significantly higher in the semi-urban than in the rural area. However, serum IgE against HDM and cockroach as well as total IgE were significantly lower in semi-urban than in rural children. In the semi-urban area, there was a significant positive association between SPT to HDM and higher paternal education but a negative one with hookworm infection. The risk factors linked to cockroach sensitization were different: being of a farmer offspring and lacking access to piped water were associated with an increased risk for a positive SPT to cockroach. No significant associations between measured risk factors and having a positive SPT were found in the rural area.

Conclusion

Sensitization to HDM and cockroach is common in Indonesia, more often translating into a positive SPT in the semi-urban than in the rural setting. Whereas high paternal education and low hookworm infection were associated with increased risk of SPT to HDM, we were surprised to find parameters of lower SES were identified as risk factor for cockroach SPT.     

Food availability,temperature, and day length drive seasonal variations in the positional behavior of white‐headed langurs in the limestone forests of Southwest Guangxi,China

Information on positional behavior contributes to the understanding of the ecological adaptation mechanisms in animals. We collected data on the positional behavior of white‐headed langurs (Trachypithecus leucocephalus) at the Guangxi Chongzuo White‐Headed Langur National Nature Reserve from September 2016 to August 2017 via instantaneous scan sampling method. This study aimed to examine the importance of positional behavior flexibility in limestone forests characterized by seasonal variations in climate and food resources. Our results indicated that langurs adopted leaping (47.92% ± 5.50%) and vertical climbing (40.13% ± 6.20%) as their predominant locomotor modes and sitting (83.08% ± 4.70%) as their predominant posture. Their positional behavior exhibited marked seasonal variations. More specifically, langurs used quadrupedal walking more frequently during the dry season than during the rainy months. In the stationary state, they sat more frequently during the dry season, whereas they laid and suspended more often during the rainy season. Their positional behavior was affected by fruit availability, day length, and temperature. Quadrupedal walking increased with the decrease in fruit availability, whereas leaping was positively correlated with fruit availability. Moreover, sitting was positively correlated with average temperature but negatively correlated with day length. Lying was also negatively correlated with temperature but positively correlated with day length. We conclude that white‐headed langurs adapt to limestone forests with positional behavior flexibility in response to seasonality. Our research provides evidence of the effects of food availability, ambient temperature, and day length on the positional behavior of white‐headed langurs, highlighting the need to understand their behavioral ecology and the influence of ecological factors on behavioral adaptation.