Search

Introduction: While anterior cruciate ligament (ACL) tears are commonly managed with ACL reconstruction (ACL-R), 35% of ACL-R individuals fail to return to the preinjury elite sport level. Persistent neuromuscular deficits in the hamstrings and quadriceps have been observed. It has been proposed that aquatic therapy can be used to optimize neuromuscular control after ACL-R. Objectives: (1) To compare muscle activity in ACL-R individuals during aquatic treadmill (ATM) running at different water depths and (2) to compare muscle activity during ATM running between ACL-R and healthy individuals. Methods: A total of 38 participants, including 18 ACL-R individuals (mean postoperative time [SD] = 25.8 [25.0] mo) and 20 healthy individuals were recruited. Muscle activity of biceps femoris (BF), rectus femoris (RF), tibialis anterior, and medial gastrocnemius during land treadmill and ATM running at mid-shin, mid-thigh, and waist levels were recorded using surface electromyography (sEMG). The sEMG signals of the selected muscles were normalized and expressed in % Maximal Voluntary Contraction (%MVC). Muscle activity of the ACL-R, ACL-contralateral, and healthy control limbs at different water depths was compared. Results: Among the 3 groups, the ACL-R group demonstrated the most prominent percentage increase of 101.97% (P = .001) at mid-shin level, 139.66% (P = .001) at mid-thigh level, and 141.97% (P < .001) at waist level, respectively, in %MVC when compared to land. In the ACL-R group, muscle activity of BF in the stance phase (BFSt) was significantly higher than the control group on land at all water depths. Muscle activity of RF in the swing phase (RFSw) in the ACL-R group significantly increased in all water depths immersion when compared to land, respectively. Conclusion: This study showed an increasing trend in muscle activity of BFSt and RFSw in ACL-R individuals during ATM running at increased water depths. ATM running could be implemented as neuromuscular training in rehabilitation after ACL-R.

An electrochemical synthesis of diazo compounds from hydrazones in yields as high as 99% was performed. This method was elaborated as a useful synthetic method and demonstrated on various diazo compounds (24 examples). Apart from exhibiting an efficiency that matched that of commonly used harsh and toxic chemical oxidants, this reaction is practically simple to set up, requires mild conditions, and is highly electron efficient (3 F/mol).

A new practical electrochemical method for the rapid, safe, and mild synthesis of tertiary hindered alkyl fluorides from easily accessed carboxylic acids has been developed without the need for hydrofluoric acid derivatives or non-glass reactors. In this anodic fluorination, collidinium tetrafluoroborate (Coll·HBF4) is advantageous as a supporting electrolyte and fluoride donor. A wide range of functional groups has been shown to be compatible with this new methodology. The possibility of scale-up using flow electrochemistry has also been demonstrated, thus representing a viable procedure for tertiary fluorination on a larger scale.

Purpose: To review the literature on branchio-oculo-facial syndrome and describe a new case. Methods: A girl presented with a de novo pathogenic mutation in the TFAP2A gene consistent with branchiooculo-facial syndrome. A systematic review was also performed to characterize the eye manifestations associated with the syndrome. Results: A total of 172 total patients were identified from the literature. Among these, 102 patients received molecular confirmation. The most common pathogenic variants reported were p.R255G, p.A256V, p.R254W, and p.G251E. Common eye abnormalities associated with the syndrome in total combined cases (represents individuals with a clinical diagnosis only of branchiooculo-facial syndrome plus those who additionally had molecular confirmation of the syndrome from genetic testing) were nasolacrimal duct stenosis (n = 98, 57%), coloboma (n = 76, 46%), anophthalmia/microphthalmia (n = 64, 37%), and cataracts (n = 27, 16%). Conclusions: This analysis provides a comprehensive review of genetic variants and ophthalmic findings to characterize the most common eye manifestations associated with branchio-oculo-facial syndrome. The report provides incentive to further investigate TFAP2A variants and identify genotype-phenotype correlations. [ J Pediatr Ophthalmol Strabismus . 20XX;XX(X):XX–XX.]

A new and practical two-step transition metal-free methodology for the C(sp3)-C(sp3) functionalisation of saturated N-heterocyclic systems is disclosed. First, aminal derivatives are generated through the anodic oxidation of readily accessible carboxylic acids. Then, in the presence of BF3·OEt2, iminium ions are unmasked and rapidly alkylated by organozinc reagents under flow conditions. Secondary, tertiary and quaternary carbon centers have been successfully assembled using this new methodology. Such an approach is especially relevant to drug discovery since it increases C(sp3)-functionalities rapidly within a molecular framework. As proof of concept, our new methodology was applied to derivatization of peptides and an API.

Guest Editors Kevin Lam, Shelley D. Minteer and Darren L. Poole introduce the Organic & Biomolecular Chemistry themed issue on synthetic electrochemistry.

Controversy surrounds whether to define resting diastolic blood pressure (DBP) as the onset of the fourth or fifth Korotkoff phase (K4, sound muffling, or K5, sound disappearance) in children and adolescents. Although undetectable in some children (due to sounds continuing to zero cuff pressure), K5 is currently recommended for consistency with adult practice and because K4 can be difficult to discern or undetectable. However, to our knowledge, no studies have specifically assessed the reliability of measuring DBP with K4 and K5 in children and adolescents under exercise conditions. We therefore measured DBP before and immediately after a Bruce protocol stress test in 90 children and adolescents aged 12.3 ± 3.5 years (mean ± SD) in a cardiology clinic setting. When detected, K4 and K5 were 63.5 ± 9.2 and 60.2 ± 12.6 mmHg, respectively, at rest and 59.2 ± 14.6 mmHg (p = 0.028 vs rest) and 52.9 ± 18.3 mmHg (p

The hybrid bidentate 1‐(2‐pyridyl)benzotriazole (pyb) ligand was introduced into 3d transition metal catalysis. Specifically, [CuII(OTf)2(pyb)2]⋅2 CH3CN (1) enables the synthesis of a wide range of propargylamines by the A3 coupling reaction at room temperature in the absence of additives. Experimental and high‐level theoretical calculations suggest that the bridging N atom of the ligand imposes exclusive trans coordination at Cu and allows ligand rotation, while the N atom of the pyridine group modulates charge distribution and flux, and thus orchestrates structural and electronic precatalyst control permitting alkyne binding with simultaneous activation of the C−H bond via a transient CuI species.

A mild electrochemical method for the regioselective preparation of 1‐tetralones under environmentally friendly conditions from readily available cyclobutanols was developed. A series of aromatic‐ and heteroaromatic‐fused 1‐tetralones was accessed through ring expansion of the functionalized cyclobutanols via electrochemical generation of alkoxy radicals and intramolecular cyclization.

Background: A large proportion of Alzheimer’s disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity. Objective: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD. Methods: We conducted a cross-sectional, region-of-interest-based analysis of 1) hyperintense white-matter signal abnormalities (WMSA) on T2-FLAIR and hypointense WMSA on T1-weighted MRI; 2) diffusion tensor imaging; 3) quantitative susceptibility mapping; and 4) effective transverse relaxation rate (R2*) in N = 17 participants (AD:5, SVaD:5, MixD:7). General linear model was used to explore group differences in these brain imaging measures. Results: Model findings suggested imaging characteristics specific to our MixD group, including 1) higher burden of WMSAs on T1-weighted MRI (versus both AD and SVaD); 2) frontal lobar preponderance of WMSAs on both T2-FLAIR and T1-weighted MRI; 3) higher fractional anisotropy values within normal-appear white-matter tissues (versus SVaD, but not AD); and 4) lower R2* values within the T2-FLAIR WMSA areas (versus both AD and SVaD). Conclusion: These findings suggest a preliminary picture of the location and type of brain imaging characteristics associated with MixD. Future imaging studies may employ region-specific hypotheses to distinguish MixD more rigorously from AD or SVaD.

Faraday and Kolbe's electrolysis of carboxylic acids is known to be the first reported electrochemical reaction involving the synthesis of organic molecules. Even though numerous electrochemical transformations have been developed, organic electrochemistry has remained underemployed in synthesis for a long time. Nevertheless, the growing need to look for greener and more affordable alternatives to classic synthetic methodologies has recently reinvigorated the interest in this old discipline. In this chapter, the main aspects of the Kolbe and non-Kolbe electrolysis will be discussed. It will also be shown how, almost 200 years after its discovery, the electrolysis of carboxylic acids still offers an incredible variety of synthetic opportunities.

We have investigated the reactions of chalcogenoureas derived from N-heterocyclic carbenes, referred to here as [E(NHC)], with halogens. Depending on the structure of the chalcogenourea and the identity of the halogen, a diverse range of reactivity was observed and a corresponding range of structures were obtained. Cyclic voltammetry was carried out to characterize the oxidation and reduction potentials of these [E(NHC)] species; selenoureas were found to be easier to oxidize than the corresponding thioureas. In some cases, a correlation was found between the oxidation potential of these compounds and the electronic properties of the corresponding NHC moiety. The reactivity of these chalcogenoureas with different halogenating reagents (Br2, SO2Cl2, I2) was then investigated, and products were characterized using NMR spectroscopy and single-crystal X-ray diffraction. X-ray analyses elucidated the solid-state coordination types of the obtained products, showing that a variety of possible adducts can be obtained. In some cases, we were able to extrapolate a structure/activity correlation to explain the observed trends in reactivity and oxidation potentials.

Background Myelin loss is a feature of cerebral small vessel disease (cSVD). Although physical activity levels may exert protective effects over cSVD pathology, its specific relationship with myelin content in people living with the cSVD is unknown. Thus, we investigated whether physical activity levels are associated with myelin in community-dwelling older adults with cSVD and mild cognitive impairment. Methods Cross-sectional data from 102 individuals with cSVD and mild cognitive impairment were analyzed (mean age [SD] = 74.7 years [5.5], 63.7% female). Myelin was measured using a magnetic resonance gradient and spin echo sequence. Physical activity was estimated using the Physical Activity Scale for the Elderly. Hierarchical regression models adjusting for total intracranial volume, age, sex, body mass index, and education were conducted to determine the associations between myelin content and physical activity. Significant models were further adjusted for white matter hyperintensity volume. Results In adjusted models, greater physical activity was linked to higher myelin content in the whole-brain white matter (R2change = .04, p = .048). Greater physical activity was also associated with myelin content in the sagittal stratum (R2change = .08, p = .004), anterior corona radiata (R2change = .04, p = .049), and genu of the corpus callosum (R2change = .05, p = .018). Adjusting for white matter hyperintensity volume did not change any of these associations. Conclusions Physical activity may be a strategy to maintain myelin in older adults with cSVD and mild cognitive impairment. Future randomized controlled trials of exercise are needed to determine whether exercise increases myelin content.

A new electrochemical methodology has been developed for the preparation of a wide variety of functionalized orthoesters under mild and green conditions from easily accessible dithiane derivatives. The new methodology also offers an unprecedented way to access tri(fluorinated) orthoesters, a class of compound that has never been studied before. This provides the community with a rapid and general method to prepare libraries of functionalized orthoesters from simple and readily available starting materials.

Alcoholic liver disease (ALD) is a leading cause of cirrhosis in the United States, which is characterized by extensive deposition of extracellular matrix proteins and formation of a fibrous scar. Hepatic stellate cells (HSCs) are the major source of collagen type 1 producing myofibroblasts in ALD fibrosis. However, the mechanism of alcohol‐induced activation of human and mouse HSCs is not fully understood. We compared the gene‐expression profiles of primary cultured human HSCs (hHSCs) isolated from patients with ALD (n = 3) or without underlying liver disease (n = 4) using RNA‐sequencing analysis. Furthermore, the gene‐expression profile of ALD hHSCs was compared with that of alcohol‐activated mHSCs (isolated from intragastric alcohol‐fed mice) or CCl4‐activated mouse HSCs (mHSCs). Comparative transcriptome analysis revealed that ALD hHSCs, in addition to alcohol‐activated and CCl4‐activated mHSCs, share the expression of common HSC activation (Col1a1 [collagen type I alpha 1 chain], Acta1 [actin alpha 1, skeletal muscle], PAI1 [plasminogen activator inhibitor‐1], TIMP1 [tissue inhibitor of metalloproteinase 1], and LOXL2 [lysyl oxidase homolog 2]), indicating that a common mechanism underlies the activation of human and mouse HSCs. Furthermore, alcohol‐activated mHSCs most closely recapitulate the gene‐expression profile of ALD hHSCs. We identified the genes that are similarly and uniquely up‐regulated in primary cultured alcohol‐activated hHSCs and freshly isolated mHSCs, which include CSF1R (macrophage colony‐stimulating factor 1 receptor), PLEK (pleckstrin), LAPTM5 (lysosmal‐associated transmembrane protein 5), CD74 (class I transactivator, the invariant chain), CD53, MMP9 (matrix metallopeptidase 9), CD14, CTSS (cathepsin S), TYROBP (TYRO protein tyrosine kinase‐binding protein), and ITGB2 (integrin beta‐2), and other genes (compared with CCl4‐activated mHSCs). Conclusion: We identified genes in alcohol‐activated mHSCs from intragastric alcohol‐fed mice that are largely consistent with the gene‐expression profile of primary cultured hHSCs from patients with ALD. These genes are unique to alcohol‐induced HSC activation in two species, and therefore may become targets or readout for antifibrotic therapy in experimental models of ALD., We identified genes in alcohol‐activated mHSCs from IG alcohol‐fed mice that are largely consistent with the gene‐expression profile of primary cultured hHSCs from patients with ALD. These genes are unique to alcohol‐induced HSC activation in two species, and therefore may become targets or readout for antifibrotic therapy in experimental models of ALD.

The growing impetus to develop greener and more cost-efficient synthetic methods has prompted Chemists to look for new ways to activate small organic molecules. Among them, electrosynthesis is one of the greenest and cheapest since it is possible to perform redox reactions without the need for any chemical reagents. Even though electrosynthesis is on the verge of a resurgence, it is far from being a new discipline. In fact, organic electrosynthesis was popularised by Manual Baizer in the early 60s while working at Monsanto. In this article, we will review the major, as well as the most recent, achievements in industrial organic electrosynthesis.

We have investigated the reactions of chalcogenoureas derived from

Experimental measurements of the thermal effects of the same osmolytes on two different globular proteins, C-reactive protein (CRP) and tumor necrosis factor alpha (TNFα), have shown that quantifying the change in the denaturing temperature leads to some results that are unique to each protein. In order to find osmolyte-dependent parameters that can be applied more consistently from protein to protein, this work considers, instead, the overall free energy change associated with that denaturation using coarse-grained models. This is enabled by using theoretical fluid equations that take into account the exclusion of water and osmolyte from the volume occupied by the protein in both its native and denatured forms. Assuming ideal geometric models of the two protein states whose sizes are based on the protein's surface area in each form, and taking into account the density of the aqueous osmolyte solution, the free energy change due to the change in geometry can be calculated. The overall change in free energy of the system is found from that quantity and other protein- and osmolyte-specific parameters, which are determined using the experimental concentration and temperature results. We find that these fitted parameters accurately reproduce experimental results and also show consistent patterns from protein to protein. We also consider two different model geometries of the denatured protein and find little impact on the use of one or the other. Defining the effects of the osmolyte in terms of free energy also allows for prediction of overall phase change behavior, including cold denaturation.

A reduction in sedentary behavior (SB) can contribute to the prevention of chronic diseases. This is the first umbrella review that summarizes the effectiveness and monetary costs of different types of interventions to reduce SB across all age groups and populations in different settings. We comprehensively searched seven databases for systematic reviews and meta-analyses and conducted an umbrella review of the effects of interventions to reduce SB. Additionally, we performed a meta-analysis of primary studies included in the umbrella review. Furthermore, we analyzed health economic aspects of interventions to reduce SB. We included 40 systematic reviews in our umbrella review, with 136 primary studies suitable for further meta-analyses. We found that interventions targeting the physical environment reduce SB most effectively in the majority of populations and settings. Workplace interventions reduced SB by -89.83 min/day (95% CI -124.58 to -55.09; p

The multistep synthesis of natural products has historically served as a useful and informative platform for showcasing the best, state-of-the-art synthetic methodologies and technologies. Over the last several decades, electrochemistry has proved itself to be a useful tool for conducting redox reactions. This is primarily due to its unique ability to selectively apply any oxidizing or reducing potential to a sufficiently conductive reaction solution. Electrochemical redox reactions are readily scaled and can be more sustainable than competing strategies based on conventional redox reagents. In this chapter, we summarize the examples where electrochemistry has been used in the synthesis of natural products. The chapter is organized by the reaction type of the electrochemical step and covers both oxidative and reductive reaction modes.

Introduction Several HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub‐Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community‐level HIV risk in predictive models and (3) examine predictive performance. Methods We searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub‐Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction and critical appraisal were conducted in duplicate. We used random‐effects meta‐analysis to summarize hazard ratios and the area under the receiver‐operating characteristic curve (AUC‐ROC). Results From 1563 initial search records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomized‐controlled trials, three among adolescent girls and young women (AGYW) and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% confidence interval: 1.17, 2.23], compared to above 25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV‐2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW, only STIs were consistently associated with higher incidence, but studies were limited (n = 3). Community‐level HIV prevalence or unsuppressed viral load strongly predicted incidence but was only considered in 3 of 11 multi‐site studies. The AUC‐ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC‐ROC 0.626 [0.588, 0.663] (I 2: 64.02%). Conclusions Younger age, non‐cohabiting and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individual factors should be considered to quantify HIV risk. However, HIV risk scores had only low‐to‐moderate discriminatory ability and uncertain generalizability, limiting their programmatic utility. Further evidence on the relative value of specific risk factors, studies populations not restricted to “at‐risk” individuals and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes. PROSPERO Number CRD42021236367

Eight ferrocene derivatives linked by either an ether, amine, or phenylacetylene moiety to a terminal ethynyl group were covalently deposited on glassy carbon electrodes by anodic electrochemical methods. The lithio activation method, in which the terminal hydrogen of the ethynyl group is replaced by a lithium atom before anodic oxidation, was successfully employed in all cases. Direct oxidation of the unactivated ethynyl group also resulted in surface deposition. Surface coverages between 1 x 10 ‐10 mol cm ‐2 and 14 x 10 ‐10 mol cm ‐2 were achieved. Cyclic voltammetry scans of the modified electrodes in pure electrolytes differed depending on the size of the supporting electrolyte anion, as little as half the current being measured for a [B(C 6 F 5 ) 4 ] ‐ vs. [PF 6 ] ‐ solution, suggesting differences in ion transport near the electrode surface. An ether‐linked ethynylferrocenium ion ( 5 + ) was isolated after electrolytic and chemical oxidation of 5 and characterized by X‐Ray crystallography as its [SbCl 6 ] ‐ salt.

We report a new electrochemical supporting-electrolyte-free method for synthesizing ureas, carbamates, and thiocarbamates via the oxidation of oxamic acids. This simple, practical, and phosgene-free route includes the generation of an isocyanate intermediate in situ via anodic decarboxylation of an oxamic acid in the presence of an organic base, followed by the one-pot addition of suitable nucleophiles to afford the corresponding ureas, carbamates, and thiocarbamates. This procedure is applicable to different amines, alcohols, and thiols. Furthermore, when single-pass continuous electrochemical flow conditions were used and this reaction was run in a carbon graphite Cgr/Cgr flow cell, urea compounds could be obtained in high yields within a residence time of 6 min, unlocking access to substrates that were inaccessible under batch conditions while being easily scalable.

Editorial - No abstract available.

IntroductionSeveral HIV risk scores have been developed to identify individuals for prioritised HIV prevention in sub-Saharan Africa. We systematically reviewed HIV risk scores to: (i) identify factors that consistently predicted incident HIV infection, (ii) review inclusion of community-level HIV risk in predictive models, and (iii) examine predictive performance.MethodsWe searched nine databases from inception until February 15, 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub-Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction, and critical appraisal were conducted in duplicate. We used random-effects meta-analysis to summarise hazard ratios and the area under the receiver-operating characteristic curve (AUC-ROC).ResultsFrom 1563 initial search records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomised-controlled trials, three among adolescent girls and young women (AGYW), and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% Confidence Interval: 1.17, 2.23], compared to above-25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV-2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW only STIs were consistently associated with higher incidence, but studies were limited (n=3). Community-level HIV prevalence or unsuppressed viral load strongly predicted incidence but were only considered in three of 11 multi-site studies. The AUC-ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC-ROC 0.626 [0.588, 0.663] (I2: 64.02%).ConclusionsYounger age, non-cohabiting, and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individual factors should be considered to quantify HIV risk. However, HIV risk scores had only low-to-moderate discriminatory ability and uncertain generalisability, limiting their programmatic utility.Further evidence on the relative value of specific risk factors, studies populations not restricted to ‘at-risk’ individuals, and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes.PROSPERO NumberCRD42021236367