Metallaphotoredox aryl and alkyl radiomethylation for PET ligand discovery.

Positron emission tomography (PET) radioligands (radioactively labelled tracer compounds) are extremely useful for in vivo characterization of central nervous system drug candidates, neurodegenerative diseases and numerous oncology targets1. Both tritium and carbon-11 radioisotopologues are generally necessary for in vitro and in vivo characterization of radioligands2, yet there exist few radiolabelling protocols for the synthesis of either, inhibiting the development of PET radioligands. The synthesis of such radioligands also needs to be very rapid owing to the short half-life of carbon-11. Here we report a versatile and rapid metallaphotoredox-catalysed method for late-stage installation of both tritium and carbon-11 into the desired compounds via methylation of pharmaceutical precursors bearing aryl and alkyl bromides. Methyl groups are among the most prevalent structural elements found in bioactive molecules, and so this synthetic approach simplifies the discovery of radioligands. To demonstrate the breadth of applicability of this technique, we perform rapid synthesis of 20 tritiated and 10 carbon-11-labelled complex pharmaceuticals and PET radioligands, including a one-step radiosynthesis of the clinically used compounds [11C]UCB-J and [11C]PHNO. We further outline the direct utility of this protocol for preclinical PET imaging and its translation to automated radiosynthesis for routine radiotracer production in human clinical imaging. We also demonstrate this protocol for the installation of other diverse and pharmaceutically useful isotopes, including carbon-14, carbon-13 and deuterium.

The digitization of organic synthesis.

Organic chemistry has largely been conducted in an ad hoc manner by academic laboratories that are funded by grants directed towards the investigation of specific goals or hypotheses. Although modern synthetic methods can provide access to molecules of considerable complexity, predicting the outcome of a single chemical reaction remains a major challenge. Improvements in the prediction of 'above-the-arrow' reaction conditions are needed to enable intelligent decision making to select an optimal synthetic sequence that is guided by metrics including efficiency, quality and yield. Methods for the communication and the sharing of data will need to evolve from traditional tools to machine-readable formats and open collaborative frameworks. This will accelerate innovation and require the creation of a chemistry commons with standardized data handling, curation and metrics.

It's time to broaden what we consider a 'blue carbon ecosystem'.

Photoautotrophic marine ecosystems can lock up organic carbon in their biomass and the associated organic sediments they trap over millennia and are thus regarded as blue carbon ecosystems. Because of the ability of marine ecosystems to lock up organic carbon for millennia, blue carbon is receiving much attention within the United Nations' 2030 Agenda for Sustainable Development as a nature-based solution (NBS) to climate change, but classically still focuses on seagrass meadows, mangrove forests, and tidal marshes. However, other coastal ecosystems could also be important for blue carbon storage, but remain largely neglected in both carbon cycling budgets and NBS strategic planning. Using a meta-analysis of 253 research publications, we identify other coastal ecosystems-including mud flats, fjords, coralline algal (rhodolith) beds, and some components or coral reef systems-with a strong capacity to act as blue carbon sinks in certain situations. Features that promote blue carbon burial within these 'non-classical' blue carbon ecosystems included: (1) balancing of carbon release by calcification via carbon uptake at the individual and ecosystem levels; (2) high rates of allochthonous organic carbon supply because of high particle trapping capacity; (3) high rates of carbon preservation and low remineralization rates; and (4) location in depositional environments. Some of these features are context-dependent, meaning that these ecosystems were blue carbon sinks in some locations, but not others. Therefore, we provide a universal framework that can evaluate the likelihood of a given ecosystem to behave as a blue carbon sink for a given context. Overall, this paper seeks to encourage consideration of non-classical blue carbon ecosystems within NBS strategies, allowing more complete blue carbon accounting.

The association between ultra-processed foods and conventional markers of cardiovascular risk in an adult Iranian population.

BACKGROUND AND AIMS: According to the NOVA classification system, ultra-processed foods result from extensive industrial processing and use ingredients derived from food and non-food products, which can negatively impact on cardiovascular disease risk factors. Despite this, few studies have investigated UPFs in Middle Eastern populations regardless of high consumption in this region. METHODS AND RESULTS: This cross-sectional study was conducted on data from the Prospective Epidemiological Research Studies in Iran Kharemeh cohort (n = 6611). Food frequency questionnaires were assessed and the ratio of total UPFs energy/total energy intake was calculated. Data was categorized into tertiles of UPF consumption using the NOVA classification system. Kruskal-Wallis tests were used to assess differences in nutrient and food intakes between tertiles and logistic regression analysis was applied to assess the associations between UPFs and CVD risk factors. After adjustment for potential confounders the logistic regression analysis revealed significant positive relationships between intakes of UPFs and waist circumference (WC) (T2: OR; 1.34, 95% CI; 1.13-1.60 - T3: OR; 1.41, 95% CI; 1.18-1.69, P ˂0.001), low-density lipoprotein cholesterol (LDL-C) (T2: OR; 1.20, 95% CI; 1.05-1.37 - T3: OR; 1.27, 95% CI; 1.11-1.45, P ˂0.001), non-high-density lipoprotein cholesterol (non-HDL) (T2: OR; 1.21, 95% CI; 1.07-1.37 - T3: OR; 1.24, 95% CI; 1.10-1.41, P ˂0.001) and LDL-C to HDL-C ratio (T2: OR; 1.15, 95% CI; 1.02-1.31 - T3: OR; 1.21, 95% CI; 1.07-1.38, P = 0.002). CONCLUSION: The consumption of UPFs was positively associated with WC and atherogenic blood lipids. However, increased intakes of fiber and unsaturated fats were also found in those consuming more UPFs, which was not expected. These findings offer insights into an understudied population and warrant further research.

Higher global diet quality score is related to lower prevalence of depression and poor quality of life among adolescent girls.

BACKGROUND: Adolescence is a key time for the development of depression symptoms and the diet quality may be associated with mental health conditions. The present study examined the association between depression and quality of life (QoL) and the global diet quality score (GDQS) as a simple and standardized metric diet quality in Iranian adolescents. METHODS: This cross-sectional study was conducted on 733 adolescent girls recruited using a random cluster sampling method. A 147-item food frequency questionnaire (FFQ) was used for dietary intake assessment. The GDQS is gained by summing points of all the 25 food groups, ranged from 0 to 49. Depression symptoms were assessed using a Persian version of the Beck Depression Inventory (BDI). For assessment of health-related QoL, the Short Form 12 Survey-version 2 (SF-12v2) questionnaire was employed. Multivariable logistic regression examined the association of depression and QoL with GDQS in crude and adjusted models. RESULTS: Adolescent girls in the highest tertile of GDQS score compared with the lowest tertile had a 41% lower odds of depressive symptoms (OR: 0.59; 95% CI: 0.39-0.90, P = 0.01). The participants in the third tertile of GDQS score had lower odds of poor QoL compared with the first tertile (OR: 0.56; 95% CI: 0.37-0.85, P < 0.01). These associations remained significant (both P = 0.01) after adjustment for age, energy intake, body mass index (BMI), physical activity, and menstruation (depressive symptoms: OR: 0.59; 95% CI: 0.38-0.92; QoL: OR: 0.59; 95% CI: 0.38-0.91, P = 0.01). CONCLUSION: We found that adolescent girls with a higher score of the GDQS had lower odds of depression and poor QoL Prospective and interventional investigations are needed to reach a clear vision.

Short amplicon reverse transcription-polymerase chain reaction detects aberrant splicing in genes with low expression in blood missed by ribonucleic acid sequencing analysis for clinical diagnosis.

Use of blood RNA sequencing (RNA-seq) as a splicing analysis tool for clinical interpretation of variants of uncertain significance (VUSs) found via whole-genome and exome sequencing can be difficult for genes that have low expression in the blood due to insufficient read count coverage aligned to specific genes of interest. Here, we present a short amplicon reverse transcription-polymerase chain reaction(RT-PCR) for the detection of genes with low blood expression. Short amplicon RT-PCR, is designed to span three exons where an exon harboring a variant is flanked by one upstream and one downstream exon. We tested short amplicon RT-PCRs for genes that have median transcripts per million (TPM) values less than one according to the genotype-tissue expression database. Median TPM values of genes analyzed in this study are SYN1 = 0.8549, COL1A1 = 0.6275, TCF4 = 0.4009, DSP = .2894, TTN = 0.2851, COL5A2 = 0.1036, TERT = 0.04452, NTRK2 = 0.0344, ABCA4 = 0.00744, PRPH = 0, and WT1 = 0. All these genes show insufficient exon-spanning read coverage in our RNA-seq data to allow splicing analysis. We successfully detected all genes tested except PRPH and WT1. Aberrant splicing was detected in SYN1, TCF4, NTRK2, TTN, and TERT VUSs. Therefore, our results show short amplicon RT-PCR is a useful alternative for the analysis of splicing events in genes with low TPM in blood RNA for clinical diagnostics.

Higher dietary glycemic load is inversely associated with stress prevalence among Iranian adults.

BACKGROUND: Psychological disorders including depression, anxiety, and stress comprise a huge public health problem. The aim of this cross-sectional study is to assess the relationship between dietary glycemic index (DGI) and glycemic load (DGL) and mental disorders. METHOD: Participants (n = 10,000) aged 20-69 were randomly selected from 200 clusters in Yazd from the recruitment phase of Yazd Health Study. The dietary intake of study participants was collected by a reliable and validated food frequency questionnaire consisting of 178 food items. DGI and DGL were calculated from the FFQ data using previously published reference values. To assess psychological disorders an Iranian validated short version of a self-reported questionnaire Depression Anxiety Stress Scales 21 was used. RESULTS: There were no significant associations between DGI and DGL with odds of depression or anxiety in crude and adjusted models. However, individuals in the highest quartiles of DGL had the lowest odds of stress (OR: 0.69; 95% CI 0.47-1, P-trend = 0.023). This association remained significant after adjustment for potential confounding variables in model I (OR: 0.45; 95% CI 0.22-0.9, P-trend = 0.023), model II (OR: 0.46; 95% CI 0.22-0.96, P-trend = 0.039) and model III (OR: 0.46; 95% CI 0.22-0.96, P-trend = 0.042). CONCLUSION: In conclusion, consumption of foods with higher GL was associated with lower odds of stress; however, no significant association was found between DGI or DGL and risk of depression and anxiety. Performing further studies with longitudinal design is suggested to confirm these results.

Bioavailability and conversion of plant based sources of omega-3 fatty acids - a scoping review to update supplementation options for vegetarians and vegans.

Omega-3 (n-3) fatty acids offer a plethora of health benefits with the majority of evidence showing beneficial effects from marine sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Emerging research examines the effects of n-3 dietary intakes on blood markers of vegetarians and vegans, but official guidance for plant based marine alternatives is yet to reach consensus. This scoping review provides an overview of trials investigating bioavailability of plant n-3 oils including EPA and DHA conversion. Searches of MEDLINE, PubMed, CINAHL and clinical trial registers identified randomized controlled trials from January 2010 to September 2020. The 'Omega-3 index' (EPA + DHA (O3I)), was used to compare n-3 status, metabolic conversion and bioavailability. Two reviewers independently screened articles and extracted data on outcomes. From 639 identified articles, screening and eligibility checks gave 13 articles. High dose flaxseed or echium seed oil supplements, provided no increases to O3I and some studies showed reductions. However, microalgal oil supplementation increased O3I levels for all studies. Findings indicate preliminary advice for vegetarians and vegans is regular consumption of preformed EPA and DHA supplements may help maintain optimal O3I. Further studies should establish optimum EPA and DHA ratios and dosages in vegetarian and vegan populations.

Nutrient patterns are associated with discordant apoB and LDL: a population-based analysis.

Individuals with discordantly high apoB to LDL-cholesterol levels carry a higher risk of atherosclerotic CVD compared with those with average or discordantly low apoB to LDL-cholesterol. We aimed to determine associations between apoB and LDL-cholesterol discordance in relation to nutrient patterns (NP) using National Health and Nutrition Examination Survey data. Participants were grouped by established LDL-cholesterol and apoB cut-offs (Group 1: low apoB/low LDL-cholesterol, Group 2: low apoB/high LDL-cholesterol, Group 3: high apoB/low LDL-cholesterol, Group 4: high apoB/high LDL-cholesterol). Principle component analysis was used to define NP. Machine learning (ML) and structural equation models were applied to assess associations of nutrient intake with apoB/LDL-cholesterol discordance using the combined effects of apoB and LDL-cholesterol. Three NP explained 63·2 % of variance in nutrient consumption. These consisted of NP1 rich in SFA, carbohydrate and vitamins, NP2 high in fibre, minerals, vitamins and PUFA and NP3 rich in dietary cholesterol, protein and Na. The discordantly high apoB to LDL-cholesterol group had the highest consumption of the NP1 and the lowest consumption of the NP2. ML showed nutrients that had the greatest unfavourable dietary contribution to individuals with discordantly high apoB to LDL-cholesterol were total fat, SFA and thiamine and the greatest favourable contributions were MUFA, folate, fibre and Se. Individuals with discordantly high apoB in relation to LDL-cholesterol had greater adherence to NP1, whereas those with lower levels of apoB, irrespective of LDL-cholesterol, were more likely to consume NP3.

Lifetime serum concentration of 25-hydroxyvitamin D 25(OH) is associated with hand grip strengths: insight from a Mendelian randomisation.

Clinical trials have suggested that increased 25-hydroxyvitamin D (25(OH)D) has positive effect on hand grip strength. This Mendelian randomisation (MR) was implemented using summary-level data from the largest genome-wide association studies on vitamin D (n = 73,699) and hand grip strength. Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, MR-Egger and leave-one-out were applied as sensitivity analysis. Results showed that genetically higher-serum 25(OH)D levels had a positive effect on both right hand grip (IVW = Beta: 0.038, P = 0.030) and left hand grip (IVW = Beta: 0.034, P = 0.036). There was a low likelihood (statistically insignificant) of heterogeneity and pleiotropy, and the observed associations were not driven by single single-nucleotide polymorphisms. Furthermore, MR pleiotropy residual sum and outlier did not highlight any outliers. In conclusion, our results highlighted the causal and beneficial effect of serum 25(OH) D on right- and left-hand grip strengths.

The role of adiposity, diet and inflammation on the discordance between LDL-C and apolipoprotein B.

BACKGROUND AND AIMS: While low-density lipoprotein cholesterol (LDL-C) is a good predictor of atherosclerotic cardiovascular disease, apolipoprotein B (ApoB) is superior when the two markers are discordant. We aimed to determine the impact of adiposity, diet and inflammation upon ApoB and LDL-C discordance. METHODS AND RESULTS: Machine learning (ML) and structural equation models (SEMs) were applied to the National Health and Nutrition Examination Survey to investigate cardiometabolic and dietary factors when LDL-C and ApoB are concordant/discordant. Mendelian randomisation (MR) determined whether adiposity and inflammation exposures were causal of elevated/decreased LDL-C and/or ApoB. ML showed body mass index (BMI), dietary saturated fatty acids (SFA), dietary fibre, serum C-reactive protein (CRP) and uric acid were the most strongly associated variables (R2 = 0.70) in those with low LDL-C and high ApoB. SEMs revealed that fibre (b = -0.42, p = 0.001) and SFA (b = 0.28, p = 0.014) had a significant association with our outcome (joined effect of ApoB and LDL-C). BMI (b = 0.65, p = 0.001), fibre (b = -0.24, p = 0.014) and SFA (b = 0.26, p = 0.032) had significant associations with CRP. MR analysis showed genetically higher body fat percentage had a significant causal effect on ApoB (Inverse variance weighted (IVW) = Beta: 0.172, p = 0.0001) but not LDL-C (IVW = Beta: 0.006, p = 0.845). CONCLUSION: Our data show increased discordance between ApoB and LDL-C is associated with cardiometabolic, clinical and dietary abnormalities and that body fat percentage is causal of elevated ApoB.

How the love of muscle can break a heart: Impact of anabolic androgenic steroids on skeletal muscle hypertrophy, metabolic and cardiovascular health.

It is estimated 6.4% of males and 1.6% of females globally use anabolic-androgenic steroids (AAS), mostly for appearance and performance enhancing reasons. In combination with resistance exercise, AAS use increases muscle protein synthesis resulting in skeletal muscle hypertrophy and increased performance. Primarily through binding to the androgen receptor, AAS exert their hypertrophic effects via genomic, non-genomic and anti-catabolic mechanisms. However, chronic AAS use also has a detrimental effect on metabolism ultimately increasing the risk of cardiovascular disease (CVD). Much research has focused on AAS effects on blood lipids and lipoproteins, with abnormal concentrations of these associated with insulin resistance, hypertension and increased visceral adipose tissue (VAT). This clustering of interconnected abnormalities is often referred as metabolic syndrome (MetS). Therefore, the aim of this review is to explore the impact of AAS use on mechanisms of muscle hypertrophy and markers of MetS. AAS use markedly decreases high-density lipoprotein cholesterol (HDL-C) and increases low-density lipoprotein cholesterol (LDL-C). Chronic AAS use also appears to cause higher fasting insulin levels and impaired glucose tolerance and possibly higher levels of VAT; however, research is currently lacking on the effects of AAS use on glucose metabolism. While cessation of AAS use can restore normal lipid levels, it may lead to withdrawal symptoms such as depression and hypogonadism that can increase CVD risk. Research is currently lacking on effective treatments for withdrawal symptoms and further long-term research is warranted on the effects of AAS use on metabolic health in males and females.

The best possible self-intervention as a viable public health tool for the prevention of type 2 diabetes: A reflexive thematic analysis of public experience and engagement.

BACKGROUND: Public health initiatives seek to modify lifestyle behaviours associated with risk (e.g., diet, exercise, and smoking), but underpinning psychological and affective processes must also be considered to maximize success. OBJECTIVE: This study aimed to qualitatively assess how participants engaged with and utilized the best possible self (BPS)-intervention specifically as a type 2 diabetes (T2D) prevention tool. DESIGN AND METHODS: Fourteen participants engaged with a tailored BPS intervention. Reflexive thematic analysis analysed accounts of participant's experiences and feasibility of use. RESULTS: All participants submitted evidence of engagement with the intervention. The analysis considered two main themes: Holistic Health and Control. The analysis highlighted several nuanced ways in which individuals conceptualized their health, set goals, and received affective benefits, offering insights into how people personalized a simple intervention to meet their health needs. CONCLUSIONS: To our knowledge, this is the first study to tailor the BPS intervention as a public health application for the prevention of T2D. The intervention enabled users to identify their best possible selves in a way that encouraged T2D preventive behaviours. We propose that our tailored BPS intervention could be a flexible and brief tool to assist public health efforts in encouraging change to aid T2D prevention. PUBLIC CONTRIBUTION: The format, language and application of the BPS intervention were adapted in response to a public consultation group that developed a version specifically for application in this study.

Fishing within offshore wind farms in the North Sea: Stakeholder perspectives for multi-use from Scotland and Germany.

Offshore wind power generation requires large areas of sea to accommodate its activities, with increasing claims for exclusive access. As a result, pressure is placed on other established maritime uses, such as commercial fisheries. The latter sector has often been taking a back seat in the thrust to move energy production offshore, thus leading to disagreements and conflicts among the different stakeholder groups. In recognition of the latter, there has been a growing international interest in exploring the combination of multiple maritime activities in the same area (multi-use; MU), including the re-instatement of fishing activities within, or in close proximity to, offshore wind farms (OWFs). We summarise local stakeholder perspectives from two sub-national case studies (East coast of Scotland and Germany's North Sea EEZ) to scope the feasibility of combining multiple uses of the sea, such as offshore wind farms and commercial fisheries. We combined a desk-based review with 15 semi-structured qualitative interviews with key knowledge holders from both industries, regulators, and academia to aggregate key results. Drivers, barriers and resulting effects (positive and negative) for potential multi-use of fisheries and OWFs are listed and ranked (57 factors in total). Factors are of economic, social, policy, legal, and technical nature. To date, in both case study areas, the offshore wind industry has shown little interest in multi-use solutions, unless clear added value is demonstrated and no risks to their operations are involved. In contrast, the commercial fishing sector is proactive towards multi-use projects and acts as a driving force for MU developments. We provide a range of management recommendations, based on stakeholder input, to support progress towards robust decision making in relation to multi-use solutions, including required policy and regulatory framework improvements, good practice guidance, empirical studies, capacity building of stakeholders and improvements of the consultation process. Our findings represent a comprehensive depiction of the current state and key stakeholder aspirations for multi-use solutions combining fisheries and OWFs. We believe that the pathways towards robust decision making in relation to multi-use solutions suggested here are transferable to other international locations.

Association between wasting and food insecurity among children under five years: findings from Nepal demographic health survey 2016.

BACKGROUND: Wasting is a consequence of food insecurity, inappropriate dietary practices, and inadequate caring and feeding practices. The present study assessed association between wasting and household food insecurity among under 5 years old children, along with other socio-demographic characteristics. METHODS: This study is a secondary analysis of the Nepal Demographic and Health Survey 2016. The survey is cross-sectional in design with use of standardized tools. The sampling frame used is an updated version of the frame from the 2011 National Population and Housing Census. The participants were children under 5 years of age (n = 2414). Logistic regression was carried out to identify the odds of being wasted for children belonging to different levels of food insecure households using odds ratio and 95% confidence intervals. RESULTS: The prevalence of wasting increased with the level of food insecurity, from mild (9.4%) to moderate (10.8%) and to severe (11.3%). The highest proportions of wasted children were in Province 2 (14.3%), from rural areas (10.1%), born to mothers with no education (12.4%) and from a richer quintile (11.3%). Children belonging to severe food insecure households had 1.36 (95%CI 0.72-2.57) adjusted odds of being wasted and those belonging to mild food insecure and moderately food insecure households had 0.98 (95%CI 0.64-1.49) and 1.13 (95%CI 0.65-1.97) odds of being wasted respectively. Province 1 (AOR 2.06, 95%CI 1.01-4.19) and Province 2 (AOR 2.45, 95%CI 1.22-4.95) were significantly associated with wasting. CONCLUSION: Considering the increment in childhood wasting as per level of food insecurity, an integrated intervention should be developed in Nepal that, 1. addresses improving knowledge and behavior of community people with respect to diet and nutrition; 2. reduce the problem of food insecurity through agricultural interventions.

Exclusion of tidal influence on ambient sound measurements.

Growing concern about the impacts of anthropogenic noise on marine life has led to a global increase in the number of acoustic monitoring programmes aiming to quantify underwater soundscapes. However, low-frequency measurements in coastal sites may be affected by flow noise that is not actually present in the environment, but is caused by tidal flow turbulence around the hydrophone. At present, there is no standard way of removing this contaminating noise. This study presents an approach to exclude tidal influences (flow noise and other tidal-related acoustic self-noise) on ambient sound measurements, using data recorded at ten Scottish coastal sites between 2013 and 2017, and with a focus on the 63 and 125 Hz 1/3-octave bands. The annual ambient sound pressure levels (SPL) of the full and "tidal influence excluded" datasets of the three most tidally affected sites were compared against hypothetical noise thresholds. For the 63 Hz 1/3-octave band, results revealed: Site-specific patterns in the amount of data excluded (28.2%-89.2%), decreases in SPL (0.7-8.5 dB), and differences in the percentage of time that noise thresholds were exceeded. The described approach may serve as a standardised way of excluding tidal influence on soundscape descriptors.

A Narrative Review on Female Physique Athletes: The Physiological and Psychological Implications of Weight Management Practices.

Physique competitions are events in which aesthetic appearance and posing ability are valued above physical performance. Female physique athletes are required to possess high lean body mass and extremely low fat mass in competition. As such, extended periods of reduced energy intake and intensive training regimens are used with acute weight loss practices at the end of the precompetition phase. This represents an increased risk for chronic low energy availability and associated symptoms of relative energy deficiency in sport, compromising both psychological and physiological health. Available literature suggests that a large proportion of female physique athletes report menstrual irregularities (e.g., amenorrhea and oligomenorrhea), which are unlikely to normalize immediately postcompetition. Furthermore, the tendency to reduce intakes of numerous essential micronutrients is prominent among those using restrictive eating patterns. Following competition, reduced resting metabolic rate, and hyperphagia, is also a concern for these female athletes, which can result in frequent weight cycling, distorted body image, and disordered eating/eating disorders. Overall, female physique athletes are an understudied population, and the need for more robust studies to detect low energy availability and associated health effects is warranted. This narrative review aims to define the natural female physique athlete, explore some of the physiological and psychological implications of weight management practices experienced by female physique athletes, and propose future research directions.

A General Strategy for Site-Selective Incorporation of Deuterium and Tritium into Pyridines, Diazines, and Pharmaceuticals.

Methods to incorporate deuterium and tritium atoms into organic molecules are valuable for medicinal chemistry. The prevalence of pyridines and diazines in pharmaceuticals means that new ways to label these heterocycles will present opportunities in drug design and facilitate absorption, distribution, metabolism, and excretion (ADME) studies. A broadly applicable protocol is presented wherein pyridines, diazines, and pharmaceuticals are converted into heterocyclic phosphonium salts and then isotopically labeled. The isotopes are incorporated in high yields and, in general, with exclusive regioselectivity.

Post-Synthetic Modification of Oligonucleotides via Orthogonal Amidation and Copper Catalyzed Cycloaddition Reactions.

An efficient multicomponent orthogonal protocol was developed for post-synthetic oligonucleotide modification using commercially available 2'- O-methyl ester and 2'- O-propargyl nucleoside scaffolds. Amidation of methyl esters with primary amines was achieved in the presence of 2'-propargyl groups which were utilized for subsequent copper catalyzed cycloaddition with GalNAc-azide. The methodology was applied to generate siRNA composed of multiple amide and triazole conjugates. Computational methods were used to illustrate the impact of substitution at the 2'-position. This a powerful post-oligomerization technique for rapidly introducing diversity to oligonucleotide design.

Determinants of takeaway and fast food consumption: a narrative review.

Out-of-home foods (takeaway, take-out and fast foods) have become increasingly popular in recent decades and are thought to be a key driver in increasing levels of overweight and obesity due to their unfavourable nutritional content. Individual food choices and eating behaviours are influenced by many interrelated factors which affect the results of nutrition-related public health interventions. While the majority of research based on out-of-home foods comes from Australia, the UK and USA, the same issues (poor dietary habits and increased prevalence of non-communicable disease) are of equal concern for urban centres in developing economies undergoing 'nutrition transition' at a global scale. The present narrative review documents key facets, which may influence out-of-home food consumption, drawn from biological, societal, environmental, demographic and psychological spheres. Literature searches were performed and references from relevant papers were used to find supplementary studies. Findings suggest that the strongest determinants of out-of-home food availability are density of food outlets and deprivation within the built environment; however, the association between socio-economic status and out-of-home food consumption has been challenged. In addition, the biological and psychological drives combined with a culture where overweight and obesity are becoming the norm makes it 'fashionable' to consume out-of-home food. Other factors, including age group, ethnicity and gender demonstrate contrasting effects and a lack of consensus. It is concluded that further consideration of the determinants of out-of-home food consumption within specific populations is crucial to inform the development of targeted interventions to reduce the impact of out-of-home foods on public health.