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Ligand-to-metal charge transfer (LMCT) is a mechanistic strategy that provides a powerful tool to access diverse open-shell species using earth abundant elements and has seen tremendous growth in recent years. However, among many reaction manifolds driven by LMCT reactivity, a general and catalytic protocol for modular difunctionalization of alkenes remains unknown. Leveraging the synergistic cooperation of iron-catalyzed ligand-to-metal charge transfer and radical ligand transfer (RLT), here we report a photocatalytic, modular difunctionalization of alkenes using inexpensive iron salts catalytically to function as both radical initiator and terminator. Additionally, strategic use of a fluorine atom transfer reagent allows for general fluorochlorination of alkenes, providing the first example of interhalogen compound formation using earth abundant element photocatalysis. Broad scope, mild conditions and versatility in converting orthogonal nucleophiles (TMSN 3 and NaCl) directly into corresponding open-shell radical species are demonstrated in this study, providing a robust means towards accessing vicinal diazides and homo-/hetero-dihalides motifs catalytically. These functionalities are important precursors/intermediates in medicinal and material chemistry. Preliminary mechanistic studies support the radical nature of these transformations, disclosing the tandem LMCT/RLT as a powerful reaction manifold in catalytic olefin difunctionalization., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Health researchers may struggle to choose suitable validated dietary assessment tools (DATs) for their target population. The aim of this review was to identify and collate information on validated UK DATs and validation studies for inclusion on a website to support researchers to choose appropriate DATs. Design: A systematic review of reviews of DATs was undertaken. DATs validated in UK populations were extracted from the studies identified. A searchable website was designed to display these data. Additionally, mean differences and limits of agreement between test and comparison methods were summarized by a method, weighting by sample size. Results: Over 900 validation results covering 5 life stages, 18 nutrients, 6 dietary assessment methods, and 9 validation method types were extracted from 63 validated DATs which were identified from 68 reviews. These were incorporated into www.nutritools.org. Limits of agreement were determined for about half of validations. Thirty four DATs were FFQs. Only 17 DATs were validated against biomarkers, and only 19 DATs were validated in infant/children/adolescents. Conclusions : The interactive www.nutritools.org website holds extensive validation data identified from this review and can be used to guide researchers to critically compare and choose a suitable DAT for their research question, leading to improvement of nutritional epidemiology research.

Background: Measuring dietary intake in children and adolescents can be challenging due to misreporting, difficulties in establishing portion size and reliance on recording dietary data via proxy reporters. The aim of this review was to present results from a recent systematic review of reviews reporting and comparing validated dietary assessment tools used in younger populations in the UK., Methods: Validation data for dietary assessment tools used in younger populations (≤18 years) were extracted and summarised using results from a systematic review of reviews of validated dietary assessment tools. Mean differences and Bland-Altman limits of agreement (LOA) between the test and reference tool were extracted or calculated and compared for energy, macronutrients and micronutrients., Results: Seventeen studies which reported validation of 14 dietary assessment tools (DATs) were identified with relevant nutrition information. The most commonly validated nutrients were energy, carbohydrate, protein, fat, calcium, iron, folate and vitamin C. There were no validated DATs reporting assessment of zinc, iodine or selenium intake. The most frequently used reference method was the weighed food diary, followed by doubly labelled water and 24 h recall. Summary plots were created to facilitate comparison between tools. On average, the test tools reported higher mean intakes than the reference methods with some studies consistently reporting wide LOA. Out of the 14 DATs, absolute values for LOA and mean difference were obtained for 11 DATs for EI. From the 24 validation results assessing EI, 16 (67%) reported higher mean intakes than the reference. Of the seven (29%) validation studies using doubly labelled water (DLW) as the reference, results for the test DATs were not substantially better or worse than those using other reference measures. Further information on the studies from this review is available on the www.nutritools.org website., Conclusions: Validated dietary assessment tools for use with children and adolescents in the UK have been identified and compared. Whilst tools are generally validated for macronutrient intakes, micronutrients are poorly evaluated. Validation studies that include estimates of zinc, selenium, dietary fibre, sugars and sodium are needed., Competing Interests: Competing interestsThe University of Leeds has established a spin-out company, Dietary Assessment Ltd. for myfood24, a new online dietary assessment tool; Professor Janet Cade is a director and shareholder of the company. Other authors declare no competing financial interests., (© The Author(s). 2019.)

Hypofunction of the serotonin (5-HT) 5-HT 2C receptor (5-HT 2C R) has been implicated in a variety of disorders including substance use disorders. As such, approaches to enhance 5-HT 2C R signaling display therapeutic potential. In the present study, we show that disruption of the 5-HT 2C R interaction with the protein phosphatase and tensin homolog (PTEN) via peptidomimetics enhances 5-HT 2C R-mediating signaling in vitro and potentiates selective 5-HT 2C R agonists in behavioral rodent models. Overall, the present study provides further evidence that 5-HT 2C R activity can be modulated through an allosteric protein-protein interaction. This work provides the groundwork for the continued exploration of protein-protein interactions that can allosterically modulate this critical receptor and other important G protein-coupled receptors (GPCRs) for new therapeutic development through mechanisms that may display clinical utility.

Background: Dietary assessment is complex, and strategies to select the most appropriate dietary assessment tool (DAT) in epidemiological research are needed. The DIETary Assessment Tool NETwork (DIET@NET) aimed to establish expert consensus on Best Practice Guidelines (BPGs) for dietary assessment using self-report., Methods: The BPGs were developed using the Delphi technique. Two Delphi rounds were conducted. A total of 131 experts were invited, and of these 65 accepted, with 48 completing Delphi round I and 51 completing Delphi round II. In all, a total of 57 experts from North America, Europe, Asia and Australia commented on the 47 suggested guidelines., Results: Forty-three guidelines were generated, grouped into the following four stages: Stage I. Define what is to be measured in terms of dietary intake (what? who? and when?); Stage II. Investigate different types of DATs; Stage III. Evaluate existing tools to select the most appropriate DAT by evaluating published validation studies; Stage IV. Think through the implementation of the chosen DAT and consider sources of potential biases., Conclusions: The Delphi technique consolidated expert views on best practice in assessing dietary intake. The BPGs provide a valuable guide for health researchers to choose the most appropriate dietary assessment method for their studies. These guidelines will be accessible through the Nutritools website, www.nutritools.org .

A systematic review and meta-analyses were conducted to evaluate the effects of interventions to reduce sugar-sweetened beverages (SSB) or increase water intakes and to examine the impact of behaviour change techniques (BCTs) in consumption patterns. Randomized and nonrandomized controlled trials published after January 1990 and until December 2016 reporting daily changes in intakes of SSB or water in volumetric measurements (mL d -1 ) were included. References were retrieved through searches of electronic databases and quality appraisal followed Cochrane principles. We calculated mean differences (MD) and synthesized data with random-effects models. Forty studies with 16 505 participants were meta-analysed. Interventions significantly decreased consumption of SSB in children by 76 mL d -1 (95% confidence interval [CI] -105 to -46; 23 studies, P < 0.01), and in adolescents (-66 mL d -1 , 95% CI -130 to -2; 5 studies, P = 0.04) but not in adults (-13 mL d -1 , 95% CI -44 to 18; 12 studies, P = 0.16). Pooled estimates of water intakes were only possible for interventions in children, and results were indicative of increases in water intake (MD +67 mL d -1 , 95% CI 6 to 128; 7 studies, P = 0.04). For children, there was evidence to suggest that modelling/demonstrating the behaviour helped to reduce SSB intake and that interventions within the home environment had greater effects than school-based interventions. In conclusion, public health interventions - mainly via nutritional education/counselling - are moderately successful at reducing intakes of SSB and increasing water intakes in children. However, on average, only small reductions in SSBs have been achieved by interventions targeting adolescents and adults. Complementary measures may be needed to achieve greater improvements in both dietary behaviours across all age groups., (© 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Objectives: To examine the incidence of meningococcal disease in a defined geographic area and relate this to rural/urban residence and material deprivation., Methods: Retrospective review of statutory notifications, laboratory records and death registrations from 1 January 1996 through 31 December 2001 in an English health area. Incidence of disease was analysed in two populations residing within the area, one rural and one urban. Deprivation was measured using the Townsend material deprivation score., Results: Altogether, 183 cases of meningococcal disease were identified. Average annual incidence was significantly higher (P=0.019) in the urban area (8.8/10(5)) compared to the rural area (6.2/10(5)). In 1996, the relative risk (RR) was greater in the urban area (RR 3.20 95% CI 1.40-7.32) compared to the rural area. During the study period a significant upward trend in disease incidence in the rural area (chi2 for trend P=0.018) was identified whereas a non-significant decrease was observed in the urban area. In the urban area, but not in the rural area, increasing deprivation was strongly associated with increasing disease incidence (chi2 for trend P=0.00010)., Conclusions: Meningococcal disease places a disproportionate disease burden on certain populations. Further research is required to identify measures to address the inequalities identified.

Groups of 90 (control) and 54 (treated) rats of each sex were given amaranth in their diet to provide daily intakes of 0 (control), 50, 250 or 1250 mg/kg for 111 wk (male) and 112 wk (female) after weaning. The rats had also been exposed to the same dose levels in utero, and their parents were exposed for 60 days before mating. The colouring had no adverse effects on fertility, haematological parameters, serum chemistry or incidence of tumours. All treated animals showed contamination of the fur and red colouring of the faeces and at the high dose only the faecal pellets were poorly formed. Rats in the high-dose group produced more pups, and the average pup weight was lower than that of the controls. Rats of the F1 generation given the highest dose level were slightly lighter than the controls despite a small increase in food and water intake. Both sexes given the highest dose level and males given 250 mg/kg/day had increased caecal weight. High-dose females excreted more protein in the urine after 18 months and on histopathological examination females in all treated groups showed an increased incidence of renal calcification and pelvic epithelial hyperplasia with degenerative changes. It is concluded that amaranth fed to rats at dose levels of up to 1250 mg/kg/day in the diet did not have any carcinogenic effect. However, because of the effect on the kidneys of the females it was not possible to establish a no-untoward-effect level in this study.

Groups of 48 male and 48 female rats were fed quillaia extract in the diet at levels of 0 (controls), 0.3, 1.0 and 3.0% for 2 yr. The material had no adverse effects on death rate, water consumption, serum chemistry or haematological parameters or on the incidence of histopathological findings, including tumours. In the males given the 3% dietary level, the death rate, total leucocyte count at wk 108, incidence of kidney lesions and weights of the kidneys, heart and thyroid were all below the control values. These differences were explicable, however, in terms of a lowered body weight consequent on a decreased food intake. It is concluded that, in rats, quillaia extract fed at levels up to 3.0% in the diet did not have any carcinogenic effect. The no-untoward-effect level established in this was 3.0% in the diet, approximately equivalent to an intake of 1.5 g/kg/day.

Chocolate Brown HT was given in the diet to groups of 3 male and 3 female pigs at dose levels of 0 (control), 5, 20 or 100 mg/kg/day for 13 weeks. No adverse effects were seen on body weight gain, urine composition of the incidence of histopathological lesions. The haemoglobin levels in all 3 treatment groups of male pigs at week 13 were significantly below the control values, but this effect was not considered to be attributable to treatment with Chocolate Brown HT. The no-untoward-effect level in this study was at least 100 mg/kg/day.

The cytotoxic and carcinogenic effects of MCP, the possible proximate metabolite of the alkaloid monocrotaline, were investigated in rats by the subcutaneous route. Sequential of MCP subcutaneously produced an acute inflammatory reaction with necrosis of the local tissue. A slight delay in connective-tissue repair occurred and markedly enlarged fibroblasts were a distinctive feature of the lesion. Four injection site sarcomas were produced after repeated injection of 60 mug MCP in tricaprylin. Injection of 30 mug MCP in tricaprylin twice weekly gave rise to three local tumours. Controls injected repeatedly with tricaprylin developed two sarcomas at the injection site. The significance of these findings is discussed and it is concluded that MCP is undoubtedly cytotoxic but that its carcinogenic potency is equivocal.

Mass cultures of primary rat kidney cells were exposed briefly to aqueous solutions of 20 chemicals and their subsequent growth rate and mitotic activity measured. Proximate carcinogens, and some chemicals with a defined inhibitory action biochemically, depressed the growth and division of the cultures. Non-carcinogenic compounds and precarcinogens did not interfere with the subsequent growth rate and mitotic activity of the cultures. It is suggested that the possession of growth inhibitory properties could give an indication of the carcinogenic activity of a chemical on a short-term basis.

The importance of the contaminant OTS in the promoting activity of commercial saccharin on rat bladder neoplasia was investigated. OTS, OTS-free and OTS-contaminated saccharin were administered in the drinking water or diet for 2 years to groups of rats pretreated with an intravesical instillation of MNU; OTS alone and OTS-free saccharin were also given to groups of rats not pretreated with MNU. Administration of OTS was not associated with changes in urinary pH, crystalluria or calculus formation, had no effect on the histology of normal rat bladder, and did not increase the incidence of bladder hyperplasia or neoplasia elicited by pretreatment with MNU. No differences could be found between the effect of OTS-free or OTS-contaminated saccharin on bladders of rats pretreated with MNU. These results indicate that OTS contamination played no part in the reported promoting activity of saccharin on the rat bladder. Administration of saccharin did not increase urinary pH, crystalluria or calculus formation, and failed to promote bladder neoplasia after a carcinogenic dose of MNU, though the numbers of proliferative lesions in the bladder were increased.

The sequential histological changes and neoplastic response occurring in the subcutaneous tissue of rats after injection of surfactants or carcinogens were compared. Twice weekly subcutaneous injections of the surfactants Blue VRS and Light Green SF elicited a deranged connective tissue repair with continued proliferation of fibroblasts and extensive collagen desposition. In contrast, the carcinogens N-methyl-N-nitrosourea (MNU) and N-nitroquinoline-N-oxide (NQO) appeared to inhibit connective tissue repair and produce morphologically abnormal fibroblasts. The spectrum of neoplastic response was also found to differ. Surfactants gave rise to local sarcomata only after about 47 weeks, whereas carcinogens produced local sarcomata and adenocarcinomata after 20 and 12 weeks respectively.

Four water-soluble carcinogens were injected at the same site subcutaneously into rats, mice or guinea-pigs, twice weekly for 5-8 weeks in order to study the evolution of the early tissue reaction. MNU was injected into rats as 0·1 ml. of 0·5% solution, and into mice as 0·1 ml. of 0·05% solution. NQO was administered to rats (0·1 or 0·2 ml. of 0·25 or 0·1%) mice (0·1 of 0·05%) and guinea-pigs (0·5 of 0·1%). Propane sultone and BEI were administered to rats only, the former as 0·1 ml. of 3% and the latter as 0·5 ml. of 2·0% solution.The principal features of the tissue reaction produced by each of the four compounds in rats were similar and consisted of destruction of subcutaneous tissue, deposition of fibrin and "fibrinoid", an abnormal pattern of fibroblastic proliferation with cytomegaly of some fibroblasts and deposition of mucopolysaccharide but little collagen formation. Moreover, the appearance of fibroblastic proliferation was delayed from the normal 2-5 days to 14-16 days.These features are consistent with the known early effects of carcinogens on proliferating target tissues, and differ considerably from those found in the early reactive lesions to repeated injection of solutions of substances possessing physical properties such as surface activity or hypertonicity, or which precipitate at the injection site.