Individual and neighborhood-level social and deprivation factors impact kidney health in the GLOMMS-CORE study.

Prospective cohort studies of kidney equity are limited by a focus on advanced rather than early disease and selective recruitment. Whole population studies frequently rely on area-level measures of deprivation as opposed to individual measures of social disadvantage. Here, we linked kidney health and individual census records in the North of Scotland (Grampian area), 2011-2021 (GLOMMS-CORE) and identified incident kidney presentations at thresholds of estimated glomerular filtration rate (eGFR) under 60 (mild/early), under 45 (moderate), under 30 ml/min/1.73m2 (advanced), and acute kidney disease (AKD). Household and neighborhood socioeconomic measures, living circumstances, and long-term mortality were compared. Case-mix adjusted multivariable logistic regression (living circumstances), and Cox models (mortality) incorporating an interaction between the household and the neighborhood were used. Among census respondents, there were 48546, 29081, 16116, 28097 incident presentations of each respective eGFR cohort and AKD. Classifications of socioeconomic position by household and neighborhood were related but complex, and frequently did not match. Compared to households of professionals, people with early kidney disease in unskilled or unemployed households had increased mortality (adjusted hazard ratios: 95% confidence intervals) of (1.26: 1.19-1.32) and (1.77: 1.60-1.96), respectively with adjustment for neighborhood indices making little difference. Those within either a deprived household or deprived neighborhood experienced greater mortality, but those within both had the poorest outcomes. Unskilled and unemployed households frequently reported being limited by illness, adverse mental health, living alone, basic accommodation, lack of car ownership, language difficulties, and visual and hearing impairments. Thus, impacts of deprivation on kidney health are spread throughout society-complex, serious, and not confined to those living in deprived neighborhoods.

Thrombosis in the Neonatal Intensive Care Unit.

Neonates, particularly critically ill and premature infants, have one of the highest risks of thromboembolic complications, particularly venous thromboembolism (VTE), in the pediatric population. Recent data suggest that the incidence of VTE has significantly increased in neonates over the last few decades. Critically ill and premature infants exhibit multiple risk factors that place them at a high risk for thromboembolic events including developmental hemostasis, propensity to infections, and frequent need for central venous access. The clinical presentation, diagnostic modalities, and treatment strategies for thromboembolic complications in neonates vary based on several factors, including the etiology of the thromboembolic event, the anatomic site affected, and the patient's underlying comorbidities. Although guidelines for management are available, they are mostly based on consensus recommendations and on extrapolation from adult data due to a lack of high-quality data in the neonatal population. Current guidelines recommend anticoagulation for specific scenarios. More studies are necessary to elucidate optimal management strategies for newborns with thromboembolic complications.

Stereoelectronic Influence of a "Spectator" Propargylic Substituent Can Override Aromaticity Effects in Radical Peri-Cyclizations en Route to Expanded Polyaromatics.

Computational analysis quantifies key trends in " peri"-radical cyclizations, a recently developed type of ring-forming reaction for the expansion of polyaromatic systems at the zigzag edge. Comparison of vinyl radical attack on the peri-position versus a topologically similar six-membered ring formation at the armchair edge reveals that the barriers for the peri-ring closure are slightly higher, even though the peri-attack is more exergonic. On the other hand, the intramolecular competition between the formation of a five-membered ring by ortho-attack at the armchair edge and formation of a six-membered ring by peri-attack at the zigzag edge clearly favors six-membered ring formation. The key novel finding is the unprecedented sensitivity of peri-cyclization to the presence and spatial orientation of a "spectator" propargylic -OMe substituent. Remarkably, formation of cis-products proceeds, in general, through a significantly (∼2-4 kcal/mol) lower barrier than formation of the trans-products, even when the cis-products are less stable. The origin of this unexpected effect is clearly stereoelectronic. These findings identify such remote substitution as a conceptually new tool for the control of rate and selectivity of radical reactions. The correlations of activation barriers for vinyl radical attack with aromaticity of the target show the expected relationship in phenanthrenes and pyrenes but not in anthracenes. In the latter case, the attack at the less aromatic ring corresponds to a higher barrier because a steric penalty on the stereoelectronically favorable cis-TS negates the accelerating influence of the properly aligned C-O and C-Sn bonds.

Radical Alkyne peri-Annulation Reactions for the Synthesis of Functionalized Phenalenes, Benzanthrenes, and Olympicene.

Radical cyclization reactions at a peri position were used for the synthesis of polyaromatic compounds. Depending on the choice of reaction conditions and substrate, this flexible approach led to Bu3 Sn-substituted phenalene, benzanthrene, and olympicene derivatives. Subsequent reactions with electrophiles provided synthetic access to previously inaccessible functionalized polyaromatic compounds.

Substituent effects on stereoselectivity of dihalocarbene reactions with cyclohexadiene and on the reactivity of bis-dihalocyclopropanes in electrophilic nitrations en route to pyrimidine N-oxides.

Tricyclic bis-adducts of cyclohexa-1,4-diene with bromofluorocarbene and non-symmetric adducts with both bromofluoro- and dichlorocarbenes were synthesised selectively. The treatment of the bis-adducts with nitrating reagents in acetonitrile affords the products of heterocyclization of a sole dihalogenocyclopropane into 4-fluoropyrimidine N-oxide. The difference in the reactivity of bis-cyclopropanes with different sets of halogen substituents leads to selective heterocyclization of bromofluorocyclopropanes without affecting the dichlorocyclopropane moiety.

Traceless directing groups in radical cascades: from oligoalkynes to fused helicenes without tethered initiators.

We report the first example of a traceless directing group in a radical cascade. The chemo- and regioselectivity of the initial attack in skipped oligoalkynes is controlled by propargyl OR moiety. Radical translocations lead to the boomerang return of the radical center to the site of initial attack where it assists the elimination of the directing functionality via ß-scission in the last step of the cascade. The Bu3Sn moiety continues further via facile reactions with electrophiles as well as Stille and Suzuki cross-coupling reactions. This selective radical transformation opens a new approach for the controlled transformation of skipped oligoalkynes into polycyclic ribbons of tunable dimensions.

Exo-dig radical cascades of skipped enediynes: building a naphthalene moiety within a polycyclic framework.

Cascade radical transformations of acyclic precursors open efficient, convenient and atom-economical access to functionalized compounds of increased structural complexity. This report describes a selective sequence of 5-exo-dig and 6-exo-dig cyclizations followed by attack at a pendant aromatic moiety and rearomatization.