Sugar-Sweetened Beverages and Adverse Human Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies.

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health.

State assault weapons bans are associated with fewer fatalities: analysis of US county mass shooting incidents (2014-2022).

BACKGROUND: The need for evidence to inform interventions to prevent mass shootings (MS) in the USA has never been greater. METHODS: Data were abstracted from the Gun Violence Archive, an independent online database of US gun violence incidents. Descriptive analyses consisted of individual-level epidemiology of victims, suspected shooters and weapons involved, trends and county-level choropleths of population-level incident and fatality rates. Counties with and without state-level assault weapons bans (AWB) were compared, and we conducted a multivariable negative binomial model controlling for county-level social fragmentation, median age and number of gun-related homicides for the association of state-level AWB with aggregate county MS fatalities. RESULTS: 73.3% (95% CI 72.1 to 74.5) of victims and 97.2% (95% CI 96.3 to 98.3) of shooters were males. When compared with incidents involving weapons labelled 'handguns', those involving a weapon labelled AR-15 or AK-47 were six times more likely to be associated with case-fatality rates greater than the median (OR=6.1, 95% CI 2.3 to 15.8, p<0.00001). MS incidents were significantly more likely to occur on weekends and during summer months. US counties in states without AWB had consistently higher MS rates throughout the study period (p<0.0001), and the slope for increase over time was significantly lower in counties with AWB (beta=-0.11, p=0.01). In a multivariable negative binomial model, counties in states with AWB were associated with a 41% lower incidence of MS fatalities (OR=0.58, 95% CI 0.37 to 0.97, p=0.02). CONCLUSIONS: Counties located in states with AWB were associated with fewer MS fatalities between 2014 and 2022.

Probing Regio- and Enantioselectivity in the Formal [2 + 2] Cycloaddition of C(1)-Alkyl Ammonium Enolates with ß- and α,ß-Substituted Trifluoromethylenones.

The isothiourea-catalyzed regio- and enantioselective formal [2 + 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates with ß- and α,ß-substituted trifluoromethylenones has been developed. In all cases, preferential [2 + 2]-cycloaddition over the alternative [4 + 2]-cycloaddition is observed, giving ß-lactones with excellent diastereo- and enantioselectivity (34 examples, up to >95:5 dr, >99:1 er). The regioselectivity of the process was dictated by the nature of the substituents on both reaction components. Solely [2 + 2] cycloaddition products are observed when using α,ß-substituted trifluoromethylenones or α-trialkylsilyl acetic acid derivatives; both [2 + 2] and [4 + 2] cycloaddition products are observed when using ß-substituted trifluoromethylenones and α-alkyl-α-trialkylsilyl acetic acids as reactants, with the [2 + 2] cycloaddition as the major reaction product. The beneficial role of the α-silyl substituent within the acid component in this protocol has been demonstrated by control experiments.

The Role of the Fused Ring in Bicyclic Triazolium Organocatalysts: Kinetic, X-ray, and DFT Insights.

Bicyclic triazolium scaffolds are widely employed in N-heterocyclic carbene (NHC) organocatalysis. While the incorporation of a fused ring was initially for synthetic utility in accessing chiral, modular triazolyl scaffolds, recent results highlight the potential for impact upon reaction outcome with the underpinning origins unclear. The common first step to all triazolium-catalyzed transformations is C(3)-H deprotonation to form the triazolylidene NHC. Herein, we report an analysis of the impact of size of the fused (5-, 6-, and 7-membered, n = 1, 2, and 3, respectively) ring on the C(3) proton transfer reactions of a series of bicyclic triazolium salts. Rate constants for the deuteroxide-catalyzed C(3)-H/D-exchange of triazolium salts, kDO, were significantly influenced by the size of the adjacent fused ring, with the kinetic acidity trend, or protofugalities, following the order kDO (n = 1) > kDO (n = 2) ≈ kDO (n = 3). Detailed analyses of X-ray diffraction (XRD) data for 20 triazolium salts (including 16 new structures) and of computational data for the corresponding triazolylidene NHCs provide insight on structural effects of alteration of fused ring size. In particular, changes in internal triazolyl NCN angle and positioning of the most proximal CH2 with variation in fused ring size are proposed to influence the experimental protofugality order.

Effectiveness of nutrition and dietary interventions for people with serious mental illness: systematic review and meta-analysis.

OBJECTIVE: To review recent published trials of nutrition and dietary interventions for people with serious mental illness; to assess their effectiveness in improving metabolic syndrome risk factors. STUDY DESIGN: Systematic review and meta-analysis of randomised and non-randomised controlled trials of interventions with a nutrition/diet-related component delivered to people with serious mental illness, published 1 January 2010 - 6 September 2021. Primary outcomes were weight, body mass index (BMI), and waist circumference. Secondary outcomes were total serum cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglyceride, and blood glucose levels. DATA SOURCES: MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL databases. In addition, reference lists of relevant publications were examined for further additional studies. DATA SYNTHESIS: Twenty-five studies encompassing 26 intervention arms were included in our analysis. Eight studies were at low or some risk of bias, seventeen were deemed to be at high risk. Eight of seventeen intervention arms found statistically significant intervention effects on weight, ten of 24 on BMI, and seven of seventeen on waist circumference. The pooled effects of nutrition interventions on metabolic syndrome risk factors were statistically non-significant. However, we identified small size effects on weight for interventions delivered by dietitians (five studies; 262 intervention, 258 control participants; standardised mean difference [SMD], -0.28; 95% CI, -0.51 to -0.04) and interventions consisting of individual sessions only (three studies; 141 intervention, 134 control participants; SMD, -0.30; 95% CI, -0.54 to -0.06). CONCLUSIONS: We found only limited evidence for nutrition interventions improving metabolic syndrome risk factors in people with serious mental illness. However, they may be more effective when delivered on an individual basis or by dietitians. PROSPERO REGISTRATION: CRD42021235979 (prospective).

A Desilylative Approach to Alkyl Substituted C(1)-Ammonium Enolates: Application in Enantioselective [2+2] Cycloadditions.

The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96 % yield and >99 : 1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75 % yield and >99 : 1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (±)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.

Evolution and change in paradigm of hemodialysis in children: a systematic review.

BACKGROUND: There are similarities in hemodialysis (HD) between adults and children and also unique pediatric aspects. In this systematic review, we evaluated the existing HD literature, including vascular access, indications, parameters, and outcomes as a reflection on real-life HD practices. METHODS: Medline, Embase, CINAHL, Web of Science, and Cochrane Library were systematically searched for literature on HD in children (1-20 years). Two reviewers independently assessed the literature and data on indications; vascular access, outcomes, and specific parameters for HD were extracted. RESULTS: Fifty-four studies (8751 patients) were included in this review. Studies were stratified into age groups 1-5, 6-12, and 13-20 years based on median/mean age reported in the study, as well as era of publication (1990-2000, 2001-2010, and 2011-2019). Across all age groups, both arteriovenous fistulas and central venous catheters were utilized for vascular access. Congenital abnormalities and glomerulopathy were the most common HD indications. HD parameters including HD session duration, dialysate and blood flow rates, urea reduction ratio, and ultrafiltration were characterized for each age group, as well as common complications including catheter dysfunction and intradialytic hypotension. Median mortality rates were 23.3% (3.3), 7.6% (14.5), and 2.0% (3.0) in ages 1-5, 6-12, and 13-20 years, respectively. Median transplantation rates were 41.6% (38.3), 52.0% (32.0), and 21% (25.6) in ages 1-5, 6-12, and 13-20, respectively. CONCLUSION: This comprehensive systematic review summarizes available literature on HD in children and young adults, including best vascular access, indications, technical aspects, and outcomes, and reflects on HD practices over the last three decades.

Assessing the feasibility of an m-Health intervention for changing diet quality and mood in individuals with depression: the My Food & Mood program.

Recent randomized controlled trials have shown that improving diet quality reduces symptoms in those with depression. The provision of digital health interventions that can support dietary change in those with depression has important benefits with respect to reach, accessibility convenience and cost. The My Food & Mood study used single arm cohort design to test the feasibility of such an intervention. Participants with current depressive symptoms were recruited and enrolled online to use the My Food & Mood m-Health (smartphone delivered) program for 8 weeks. Participants completed depression (PHQ-8) and dietary questionnaires (MEDAS) at baseline, week 4 and week 8. Metrics of use and intensity of use engagement measures were calculated from system logs and data entries. There was a significant change in both MEDAS score (t = 8.147, df = 44, p < 0.001) and PHQ-8 score (t = -7.199, df = 44, p < 0.001) throughout the study. There was a moderate positive association between change in MEDAS score and activities completed, goals and weeks engaged, and a strong inverse association between change in MEDAS score and change in PHQ-8 score. An m-Health program targeting dietary intervention in those with depression was feasible. Dietary change was associated with higher engagement and reduced depressive symptoms.

Enantioselective Synthesis of α-Aryl-ß2 -Amino-Esters by Cooperative Isothiourea and Brønsted Acid Catalysis.

The synthesis of α-aryl-ß2 -amino esters through enantioselective aminomethylation of an arylacetic acid ester in high yields and enantioselectivity via cooperative isothiourea and Brønsted acid catalysis is demonstrated. The scope and limitations of this process are explored (25 examples, up to 94 % yield and 96:4 er), with applications to the synthesis of (S)-Venlafaxine⋅HCl and (S)-Nakinadine B. Mechanistic studies are consistent with a C(1)-ammonium enolate pathway being followed rather than an alternative dynamic kinetic resolution process. Control studies indicate that (i) a linear effect between catalyst and product er is observed; (ii) an acyl ammonium ion can be used as a precatalyst; (iii) reversible isothiourea addition to an in situ generated iminium ion leads to an off-cycle intermediate that can be used as a productive precatalyst.

Reducing unnecessary caesarean sections: scoping review of financial and regulatory interventions.

BACKGROUND: Caesarean sections (CS) are increasing worldwide. Financial incentives and related regulatory and legislative factors are important determinants of CS rates. This scoping review examines the evidence base of financial, regulatory and legislative interventions intended to reduce CS rates. METHODS: We searched MEDLINE, EMBASE, CINAHL and two trials registers in June 2019. Both experimental and observational intervention studies were eligible for inclusion. Primary outcome measures were: CS, spontaneous vaginal and instrumental birth rates. We assessed quality of evidence using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. RESULTS: We identified 9057 articles and assessed 65 full-texts. We included 16 observational studies. Most of the studies were conducted in high-income countries. Three studies assessed payment methods for health workers: equalising physician fees for vaginal and caesarean delivery reduced CS rates in one study; however, little or no difference in CS rates was found in the remaining two studies. Nine studies assessed payment methods for health organisations: There was no difference in CS rates between diagnosis-related group (DRG) payment system compared to fee-for-service system in one study. However, DRG system was associated with lower odds for CS in another study. There was little or no difference in CS rates following implementation of global budget payment (GBP) system in two studies. Vaginal birth after caesarean section (VBAC) increased after implementation of a case-based payment system in one study. Caesarean section increased while VBAC rates decreased following implementation of a cap-based payment system in another study. Financial incentive for providers to promote vaginal delivery combined with free vaginal delivery policy was found to reduce CS rates in one study. Studied regulatory and legislative interventions (comprising legislatively imposed practice guidelines for physicians in one study and multi-faceted strategy which included policies to control CS on maternal request in another study) were found to reduce CS rates. The GRADE quality of evidence varied from very low to low. CONCLUSIONS: Available evidence on the effects of financial and regulatory strategies intended to reduce unnecessary CS is inconclusive given inconsistency in effects and low quality of the available evidence. More rigorous studies are needed.

Isothiourea-Catalyzed Atropselective Acylation of Biaryl Phenols via Sequential Desymmetrization/Kinetic Resolution.

Axially chiral phenols are attractive targets in organic synthesis. This motif is central to many natural products and widely used as precursors to, or directly, as chiral ligands and catalysts. Despite their utility few simple catalytic methods are available for their synthesis in high enantiopurity. Herein the atropselective acylation of a range of symmetric biaryl diols is investigated using isothiourea catalysis. Studies on a model biaryl diol substrate shows that the high product er observed in the process is a result of two successive enantioselective reactions consisting of an initial enantioselective desymmetrization coupled with a second chiroablative kinetic resolution. Extension of this process to a range of substrates, including a challenging tetraorthosubstituted biaryl diol, led to highly enantioenriched products (14 examples, up to 98:2 er), with either HyperBTM or BTM identified as the optimal catalyst depending upon the substitution pattern within the substrate. Computation has been used to understand the factors that lead to high enantiocontrol in this process, with maintenance of planarity to maximize a 1,5-S⋅⋅⋅O interaction within the key acyl ammonium intermediate identified as the major feature that determines atropselective acylation and thus product enantioselectivity.

The Importance of 1,5-Oxygen⋠⋠⋠Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis.

The importance of 1,5-O⋅⋅⋅chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch=O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O⋅⋅⋅Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density functional theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.

Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition-lactonisations.

An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition-lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).

Role of Lipoprotein Apheresis in Cardiovascular Disease Risk Reduction.

BACKGROUND AND AIM: Elevated low-density lipoprotein cholesterol and/or lipoprotein(a) are established risk factors for cardiovascular disease (CVD). Management of hypercholesterolemia consists of drug therapies, including statins and proprotein convertase subtilisin/kexin type 9 inhibitors. In patients with familial hypercholesterolemia (FH), lipoprotein apheresis (LA) is utilized to control lipid levels. However, LA is not currently a standard therapy for non-FH. This review summarizes the literature regarding LA therapy in CVD prevention. METHODS: PubMed/MEDLINE databases were searched using the keywords "LA" and "CVD". Citations were individually reviewed for relevance. RESULTS: The efficacy of LA was clearly demonstrated, largely based on evidence from observational studies. In patients who are unresponsive to traditional lipid-lowering medications, LA effectively reduced serum lipoprotein levels and adverse cardiovascular events. CONCLUSION: It was concluded that LA is a safe and effective technique that could be considered in the management of hypercholesterolemia and future risk. Randomized control trials would further support a role for LA as a therapeutic option.

Efficacy of online lifestyle interventions targeting lifestyle behaviour change in depressed populations: A systematic review.

BACKGROUND: It is well established that depression and non-communicable diseases are highly co-morbid and bi-directional in nature. 'Lifestyle medicine' has recently gained traction in the field of psychiatry, aimed at improvement of both physical and mental health. Online interventions can be an effective and inexpensive alternative or supplement to therapy that is delivered using more traditional modes, overcoming barriers that may prohibit people from accessing treatment by promoting flexibility and accessibility. METHODS: This systematic review evaluates the existing evidence for the efficacy or effectiveness of lifestyle interventions for (1) individuals with depressive symptoms, (2) clinically depressed populations or discussing the outcomes of depression within a subset of a larger cohort that are delivered online or via smart phone. Included studies were randomised controlled trials, with active comparator conditions, in adult populations and with reported lifestyle and depression-related outcomes. The analysis examined attrition, engagement, adherence and behaviour change techniques employed to achieve the target behaviours. RESULTS: Seven studies were included in the review and targeted behaviour change in five domains: alcohol reduction, improved sleep quality/insomnia reduction, increased physical activity, reduced/cessation of substance abuse and smoking cessation. Four of the studies achieved significant improvements in the targeted behaviour; of these three also reported significant improvements in depressive symptoms. No studies reported significant improvements in depressive symptoms without a change in the target lifestyle behaviour. CONCLUSION: The results of this review highlight the potential of online lifestyle interventions as adjunctive treatments for depression, and the possibility of achieving significant improvements in depressive symptoms when targeting lifestyle behaviour change.

Advanced Model Compounds for Understanding Acid-Catalyzed Lignin Depolymerization: Identification of Renewable Aromatics and a Lignin-Derived Solvent.

The development of fundamentally new approaches for lignin depolymerization is challenged by the complexity of this aromatic biopolymer. While overly simplified model compounds often lack relevance to the chemistry of lignin, the direct use of lignin streams poses significant analytical challenges to methodology development. Ideally, new methods should be tested on model compounds that are complex enough to mirror the structural diversity in lignin but still of sufficiently low molecular weight to enable facile analysis. In this contribution, we present a new class of advanced (ß-O-4)-(ß-5) dilinkage models that are highly realistic representations of a lignin fragment. Together with selected ß-O-4, ß-5, and ß-ß structures, these compounds provide a detailed understanding of the reactivity of various types of lignin linkages in acid catalysis in conjunction with stabilization of reactive intermediates using ethylene glycol. The use of these new models has allowed for identification of novel reaction pathways and intermediates and led to the characterization of new dimeric products in subsequent lignin depolymerization studies. The excellent correlation between model and lignin experiments highlights the relevance of this new class of model compounds for broader use in catalysis studies. Only by understanding the reactivity of the linkages in lignin at this level of detail can fully optimized lignin depolymerization strategies be developed.

Enantioselective isothiourea-catalysed trans-dihydropyridinone synthesis using saccharin-derived ketimines: scope and limitations.

The catalytic enantioselective synthesis of a range of trans-dihydropyridinones from aryl-, heteroaryl- and alkenylacetic acids and saccharin-derived ketimines with good to excellent stereocontrol (15 examples, up to >95 : 5 dr, up to >99 : 1 er) is reported. After extensive optimisation, HyperBTM proved the optimal isothiourea catalyst for this transformation at -78 °C, giving trans-dihydropyridones with generally excellent levels of diastereo- and enantioselectivity.

Exploiting the Imidazolium Effect in Base-free Ammonium Enolate Generation: Synthetic and Mechanistic Studies.

N-Acyl imidazoles and catalytic isothiourea hydrochloride salts function as ammonium enolate precursors in the absence of base. Enantioselective Michael addition-cyclization reactions using different α,ß-unsaturated Michael acceptors have been performed to form dihydropyranones and dihydropyridinones with high stereoselectivity. Detailed mechanistic studies using RPKA have revealed the importance of the "imidazolium" effect in ammonium enolate formation and have highlighted key differences with traditional base-mediated processes.

Resident Support Network: a supportive approach to resident physician wellness.

The Resident Support Network (RSN) is a formal network of residents and medical faculty, with additional training and resources in resident wellness. RSN is accessible to residents to approach with their wellness concerns. It aims to support residents during a period of medical training that is associated with high trainee burnout rates. Implementing individual-focused and organizational strategies in residency programs has been found to reduce burnout. The RSN, in the McMaster University Pediatrics Residency program, was initiated based on the need to help address gaps in supporting resident wellness. Implementation of an RSN would likely provide similar benefits for residents in other universities and specialties by enhancing resident wellness.

Le Resident Support Network (RSN) est un réseau formel de résidents et de professeurs de médecine, avec une formation et des ressources supplémentaires sur le bien-être des résidents. Les résidents peuvent s'adresser au RSN pour faire part de leurs préoccupations en matière de bien-être. Il vise à soutenir les résidents pendant une période de leur formation médicale qui est associée à des taux élevés d'épuisement professionnel. La mise en œuvre de stratégies individuelles et organisationnelles dans les programmes de résidence s'est avérée efficace pour réduire l'épuisement professionnel. Le RSN, dans le programme de résidence en pédiatrie de l'Université McMaster, a été mis en place en raison de la nécessité de combler les lacunes en matière de soutien au bien-être des résidents. La mise en œuvre d'un RSN apporterait probablement des avantages similaires aux résidents d'autres universités et spécialités en améliorant le bien-être des résidents.

Dopaminergic Neurons in Zona Incerta Drives Appetitive Self-Grooming.

Dopaminergic (DA) neurons are known to play a key role in controlling behaviors. While DA neurons in other brain regions are extensively characterized, those in zona incerta (ZITH or A13) receive much less attention and their function remains to be defined. Here it is shown that optogenetic stimulation of these neurons elicited intensive self-grooming behaviors and promoted place preference, which can be enhanced by training but cannot be converted into contextual memory. Interestingly, the same stimulation increased DA release to periaqueductal grey (PAG) neurons and local PAG antagonism of DA action reduced the elicited self-grooming. In addition, A13 neurons increased their activity in response to various external stimuli and during natural self-grooming episodes. Finally, monosynaptic retrograde tracing showed that the paraventricular hypothalamus represents one of the major upstream brain regions to A13 neurons. Taken together, these results reveal that A13 neurons are one of the brain sites that promote appetitive self-grooming involving DA release to the PAG.