Unintentional injury deaths associated with sport and recreation in Québec, Canada, 2006-2019.

OBJECTIVES: This study examined trends in the frequencies and rates of deaths associated with unintentional injuries in sport and recreation in Québec, Canada, for the period January 2006-December 2019. METHODS: In this descriptive retrospective study, data were extracted from the database of the Bureau du coroner du Québec. Incidence rates were calculated using participation data from the Étude des blessures subies au cours de la pratique d'activités récréatives et sportives au Québec (ÉBARS) and Canadian census population data. Poisson regression was used to investigate changes in death rates over the 14-year period by estimating incidence rate ratios. RESULTS: There were 1937 unintentional injury deaths and the population-based death rate was 1.72 per 100 000 person-years. The participation-based rate was 1.40 per 100 000 participant-years, considering the 24 matching activities in both ÉBARS' editions. Using both population-based and participation-based denominators, separate analyses consistently showed declining death rates in non-motorised navigation and cycling. Deaths related to all-terrain vehicles, snowmobiles, swimming, cycling, motorised navigation and non-motorised navigation activities accounted for 80.2% of all deaths. Drowning was documented as a cause of death in 39.3% of all fatalities. Males represented 86.8% of all deaths, with males aged 18-24 years and 65 and over having the highest rates. CONCLUSION: The death rates of unintentional injury deaths associated with non-motorised navigation and cycling declined, from January 2006 to December 2019. The characteristics and mechanisms of drowning deaths and fatalities that occurred in activities associated with higher death frequencies and rates need to be further investigated.

Coordinatively Unsaturated Amidotitanocene Cations with Inverted σ and π Bond Strengths: Controlled Release of Aminyl Radicals and Hydrogenation/Dehydrogenation Catalysis.

Cationic amidotitanocene complexes [Cp2 Ti(NPhAr)][B(C6 F5 )4 ] (Cp=η5 -C5 H5 ; Ar=phenyl (1 a), p-tolyl (1 b), p-anisyl (1 c)) were isolated. The bonding situation was studied by DFT (Density Functional Theory) using EDA-NOCV (Energy Decomposition Analysis with Natural Orbitals for Chemical Valence). The polar Ti-N bond in 1 a-c features an unusual inversion of σ and π bond strengths responsible for the balance between stability and reactivity in these coordinatively unsaturated species. In solution, 1 a-c undergo photolytic Ti-N cleavage to release Ti(III) species and aminyl radicals ⋅NPhAr. Reaction of 1 b with H3 BNHMe2 results in fast homolytic Ti-N cleavage to give [Cp2 Ti(H3 BNHMe2 )][B(C6 F5 )4 ] (3). 1 a-c are highly active precatalysts in olefin hydrogenation and silanes/amines cross-dehydrogenative coupling, whilst 3 efficiently catalyzes amine-borane dehydrogenation. The mechanism of olefin hydrogenation was studied by DFT and the cooperative H2 activation key step was disclosed using the Activation Strain Model (ASM).

Virtual unenhanced imaging of the liver derived from 160-mm rapid-switching dual-energy CT (rsDECT): Comparison of the accuracy of attenuation values and solid liver lesion conspicuity with native unenhanced images.

OBJECTIVES: To evaluate the reliability of attenuation values of the liver parenchyma and focal liver lesions on virtual unenhanced images from arterial (VUEart) and portal venous phases (VUEport) compared to native unenhanced (NU) attenuation values in patients referred for assessment of malignant liver lesions. METHODS: Seventy-three patients with confirmed primary or metastatic liver tumors who underwent a multiphase contrast-enhanced rapid-switching kVp dual-energy CT (rsDECT) were included in this IRB-approved retrospective study. Both qualitative and quantitative analyses - including the lesion-to-liver contrast-to-noise ratio (LL-CNR) - were performed and compared between NU and both VUEart and VUEport images. RESULTS: The mean liver attenuation values were significantly lower in VUEart images (56.7 ±â€¯6.7 HU) than in NU images (59.6 ±â€¯7.5 HU, p = 0.008), and were comparable between VUEart and VUEport images (57.9 ±â€¯6 UH, p = 0.38) and between VUEport and NU images (p = 0.051). The mean liver lesions attenuation values were comparable between NU, VUEart and VUEport images (p = 0.60). Strong and significant correlations values were found both in liver lesions and tumor-free parenchyma (r = 0.82-0.91, p < 0.01). The mean LL-CNR was significantly higher in VUEart and VUEport images than in NU images (1.7 ±â€¯1 and 1.6 ±â€¯1.1 vs 0.9 ±â€¯0.6; p < 0.001), but was comparable between VUEart and VUEport images (p > 0.9). Lesion conspicuity was significantly higher in VUEport images than in NU images (p < 0.001). CONCLUSION: VUEport images derived from 3rd generation rsDECT could confidently replace NU images in patients undergoing assessment for malignant liver lesions. These images provide comparable attenuation values in both liver lesions and liver parenchyma while reducing the radiation dose and scanning time.

The GRIA3 c.2477G > A Variant Causes an Exaggerated Startle Reflex, Chorea, and Multifocal Myoclonus.

BACKGROUND: Hemizygous mutations in GRIA3 encoding the GluA3 subunit of the amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are known to be associated with neurodevelopmental disorders, including intellectual disability, hypotonia, an autism spectrum disorder, sleep disturbances, and epilepsy in males. OBJECTIVE: To describe a new and consistent phenotype in 4 affected male patients associated with an undescribed deleterious variant in GRIA3. METHODS: We evaluated a large French family in which segregate a singular phenotype according to an apparent X-linked mode of inheritance. Molecular analyses using next generation sequencing and in vitro functional studies using 2-electrode voltage clamp recordings on Xenopus laevis oocytes and a ß-lactamase reporter assay in transfected human embryonic kidney (HEK293) cells were performed. RESULTS: In addition to mild intellectual disability and dysarthria, affected patients presented a tightly consistent early-onset movement disorder combining an exaggerated startle reflex with generalized chorea and multifocal myoclonus. The unreported GRIA3 missense variant c.2477G > A; p.(Gly826Asp) affecting the fourth transmembrane domain of the protein was identified in index patients and their unaffected mothers. Functional studies revealed that variant receptors show decreased current response evoked by agonist (ie, kainic acid and glutamate) and reduced expression on the cell surface in favor of pathogenicity by a loss-of-function mechanism. CONCLUSIONS: Taken together, our results suggest that apart from known GRIA3-related disorders, an undescribed mutation-specific singular movement disorder does exist. We thus advocate considering GRIA3 mutations in the differential diagnosis of hyperekplexia and generalized chorea with myoclonus. © 2020 International Parkinson and Movement Disorder Society.

Phosphasalen group IV metal complexes: synthesis, characterization and ring opening polymerization of lactide.

We report the synthesis of a series of Zr and Ti complexes bearing phosphasalen which differs from salen by the incorporation of two P atoms in the ligand backbone. The reaction of phosphasalen proligands (1a-1c)H2 with Zr(CH2Ph)4 led to different products depending on the nature of the N,N-linker in the ligand. In the case of ethylene-linked phosphasalen, octahedral Zr complex 2a formed as a single stereoisomer in trans geometry. With the phenylene linker, it was shown by dynamic NMR spectroscopy that complex 2b exists as a mixture of trans and cis-ß isomers in solution, both enantiomers (Δ and Λ) of the cis-ß isomer being in fast equilibrium with respect to the NMR time-scale. The use of a propylene-linked phosphasalen proligand 1cH2 led to a mixture of complexes among which a binuclear Zr complex 2c bridged only by one phosphasalen ligand could be isolated and characterized. Addition of 2 equiv. of iPrOH to 2a and 2b afforded diisoproxy Zr complexes 3a and 3b as a mixture of trans and cis-ß isomers, the latter undergoing fast Δ/Λ isomerization in solution. Addition of B(C6F5)3 to 2a and 2b gave cationic monobenzyl Zr complexes 4a and 4b which have been further converted into cationic alkoxy Zr complexes 5a-b and 6a-b by alcoholysis with iPrOH and (S)-methyl-lactate, respectively. The reaction of the phosphasalen proligands with Ti(NMe2)4 proceeded diastereoselectively giving rise to Ti complexes 7a-c in octahedral geometry with cis-ß wrapping of the ligand. The complexes have been tested for the ROP of rac-lactide. The neutral phosphasalen Ti and Zr complexes showed only poor activity probably due to the encumbered and electron donating nature of the phosphasalen ligand. In contrast, the cationic Zr alkoxides 5a, 6a and 6b are effective initiators for the controlled and hetero-selective ROP of rac-lactide.

Reappraising Schmidpeter's bis(iminophosphoranyl)phosphides: coordination to transition metals and bonding analysis.

The synthesis and characterization of a range of bis(iminophosphoranyl)phosphide (BIPP) group 4 and coinage metals complexes is reported. BIPP ligands bind group 4 metals in a pseudo fac-fashion, and the central phosphorus atom enables the formation of d0-d10 heterobimetallic complexes. Various DFT computational tools (including AIM, ELF and NCI) show that the phosphorus-metal interaction is either electrostatic (Ti) or dative (Au, Cu). A bridged homobimetallic Cu-Cu complex was also prepared and its spectroscopic properties were investigated. The theoretical analysis of the P-P bond in BIPP complexes reveals that (i) BIPP are closely related to ambiphilic triphosphenium (TP) cations; (ii) the P-P bonds are normal covalent (i.e. not dative) in both BIPP and TP.

Effects of inspiratory muscle warm-up on locomotor muscle oxygenation in elite speed skaters during 3000 m time trials.

PURPOSE: It has been shown that an inspiratory muscle warm-up (IMW) could enhance performance. IMW may also improve the near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation index (TSI) during cycling. However, there exists contradictory data about the effect of this conditioning strategy on performance and muscle oxygenation. We examined the effect of IMW on speed skating performance and studied the underpinning physiological mechanisms related to muscle oxygenation. METHODS: In a crossover, randomized, single-blind study, eight elite speed skaters performed 3000 m on-ice time trials, preceded by either IMW (2 × 30 breaths, 40% maximal inspiratory pressure) or SHAM (2 × 30 breaths, 15% maximal inspiratory pressure). Changes in TSI, oxyhemoglobin-oxymyoglobin ([O2HbMb]), deoxyhemoglobin-deoxymyoglobin ([HHbMb]), total hemoglobin-myoglobin ([THbMb]) and HHbMbdiff ([O2HbMb]-[HHbMb]) in the right vastus lateralis muscle were monitored by NIRS. All variables were compared at different time points of the race simulation with repeated-measures analysis of variance. Differences between IMW and SHAM were also analyzed using Cohen's effect size (ES) ± 90% confidence limits, and magnitude-based inferences. RESULTS: Compared with SHAM, IMW had no clear impact on skating time (IMW 262.88 ± 17.62 s vs. SHAM 264.05 ± 21.12 s, effect size (ES) 0.05; 90% confidence limits, - 0.22, 0.32, p = 0.7366), TSI, HbMbdiff, [THbMb], [O2HbMb] and perceptual responses. CONCLUSIONS: IMW did not modify skating time during a 3000 m time trial in speed skaters, in the conditions of our study. The unchanged [THbMb] and TSI demonstrate that the mechanisms by which IMW could possibly exert an effect on performance were unaffected by this intervention.

Multimodal Remote Monitoring of High Cardiovascular Risk Patients With OSA Initiating CPAP: A Randomized Trial.

BACKGROUND: The management of patients with high cardiovascular risk and OSA must target not only improving adherence to CPAP, but should also include strategies aimed at reducing BP and increasing physical activity. The study aims to evaluate the effectiveness of an integrated intervention using remote patient telemonitoring in reducing BP in high cardiovascular risk patients with OSA. METHODS: In a multicenter, open, randomized trial, patients with OSA were randomly assigned at CPAP initiation to usual care or multimodal telemonitoring for 6 months. Telemonitoring used electronic equipment collecting information about BP, symptoms, CPAP side effects, and physical activity with home care providers prespecified protocoled actions. The primary effectiveness outcome was assessed using home self-measured BP on 3 consecutive days. Secondary outcomes included CPAP compliance, symptoms, and physical activity. RESULTS: Of 306 patients with a median age of 61.3 years [interquartile range, 54.1; 66.1], who were predominantly men, 226 (74%) with a BMI of 32.0 [28.7; 35.6] kg/m2 and an apnea-hypopnea index of 46 [35; 61] events/h, 149 received usual care and 157 received telemonitoring. After 6 months of CPAP, home self-measured BP did not differ significantly between groups. In secondary analyses, there was no significant difference in steps per day, but a significant increase in CPAP adherence and an improvement in daytime sleepiness and quality of life in favor of the multimodal telemonitoring. CONCLUSIONS: In OSA patients with high cardiovascular risk, multimodal telemonitoring was not superior to usual CPAP care for improving home BP; however, telemonitoring improved adherence and patient-centered outcomes.

The Taming of Redox-Labile Phosphidotitanocene Cations.

Tame d0 phosphidotitanocene cations stabilized with a pendant tertiary phosphane arm are reported. These compounds were obtained by one-electron oxidation of d1 precursors with [Cp2 Fe][BPh4 ]. The electronic structure of these compounds was studied experimentally (EPR, UV/Vis, and NMR spectroscopy, X-ray diffraction analysis) and through DFT calculations. The theoretical analysis of the bonding situation by using the electron localization function (ELF) shows the presence of π-interactions between the phosphido ligand and Ti in the d0 complexes, whereas dπ-pπ repulsion prevents such interactions in the d1 complexes. In addition, CH-π interactions were observed in several complexes, both in solution and in the solid state, between the phosphido ligand and the phosphane arm. The d0 complexes were found to be light sensitive, and decompose through Ti-P bond homolysis to give TiIII species. A naked d0 phosphidotitanocene cation has been trapped by reaction with diphenylacetylene, yielding a Ti/P frustrated Lewis pair (FLP), which was found to be less reactive than a previously reported Zr analog.

Gold(I)-Coumarin-Caffeine-Based Complexes as New Potential Anti-Inflammatory and Anticancer Trackable Agents.

Three new gold(I)-coumarin-based trackable therapeutic complexes and two non-trackable analogues have been synthesised and fully characterised. They all display anti-proliferative properties on several types of cancer cell lines, including those of colon, breast, and prostate. Two complexes displayed significant anti-inflammatory effects; one displayed pro-inflammatory behaviour; this highlights the impact of the position of the fluorophore on the caffeine scaffold. Additionally, the three coumarin derivatives could be visualised in vitro by two-photon microscopy.

Combining Chronic Ischemic Preconditioning and Inspiratory Muscle Warm-Up to Enhance On-Ice Time-Trial Performance in Elite Speed Skaters.

Elite athletes in varied sports typically combine ergogenic strategies in the hope of enhancing physiological responses and competitive performance, but the scientific evidence for such practices is very scarce. The peculiar characteristics of speed skating contribute to impede blood flow and exacerbate deoxygenation in the lower limbs (especially the right leg). We investigated whether combining preconditioning strategies could modify muscular oxygenation and improve performance in that sport. Using a randomized, single-blind, placebo-controlled, crossover design, seven male elite long-track speed skaters performed on-ice 600-m time trials, preceded by either a combination of preconditioning strategies (COMBO) or a placebo condition (SHAM). COMBO involved performing remote ischemic preconditioning (RIPC) of the upper limbs (3 × 5-min compression at 180 mmHg and 5-min reperfusion) over 3 days (including an acute treatment before trials), with the addition of an inspiratory muscle warm-up [IMW: 2 × 30 inspirations at 40% maximal inspiratory pressure (MIP)] on the day of testing. SHAM followed the same protocol with lower intensities (10 mmHg for RIPC and 15% MIP). Changes in tissue saturation index (TSI), oxyhemoglobin-oxymyoglobin ([O2HbMb]), deoxyhemoglobin-deoxymyoglobin ([HHbMb]), and total hemoglobin-myoglobin ([THbMb]) in the right vastus lateralis muscle were monitored by near-infrared spectroscopy (NIRS). Differences between COMBO and SHAM were analyzed using Cohen's effect size (ES) and magnitude-based inferences. Compared with SHAM, COMBO had no worthwhile effect on performance time while mean Δ[HHbMb] (2.7%, ES 0.48; -0.07, 1.03) and peak Δ[HHbMb] (1.8%, ES 0.23; -0.10, 0.57) were respectively likely and possibly higher in the last section of the race. These results indicate that combining ischemic preconditioning and IMW has no practical ergogenic impact on 600-m speed-skating performance in elite skaters. The low-sitting position in this sport might render difficult enhancing these physiological responses.

Cytoprotective and antioxidant properties of organic selenides for the myelin-forming cells, oligodendrocytes.

Here a new series of twenty-one organoselenides, of potential protective activity, were synthesized and tested for their intrinsic cytotoxicity, anti-apoptotic and antioxidant capacities in oligodendrocytes. Most of the organoselenides were able to decrease the ROS levels, revealing antioxidant properties. Compounds 5b and 7b showed a high glutathione peroxidase (GPx)-like activities, which were 1.5 folds more active than ebselen. Remarkably, compound 5a diminished the formation of the oligodendrocytes SubG1 peak in a concentration-dependent manner, indicating its anti-apoptotic properties. Furthermore, based on the SwissADME web interface, we performed an in-silico structure-activity relationship to explore the drug-likeness of these organoselenides, predicting the pharmacokinetic parameters for compounds of interest that could cross the blood-brain barrier. Collectively, we present new organoselenide compounds with cytoprotective and antioxidant properties that can be considered as promising drug candidates for myelin diseases.

Time-Trial Performance in Elite Speed Skaters After Remote Ischemic Preconditioning.

PURPOSE: Speed skating leads to blood-flow restriction and deoxygenation in the lower limbs (especially the right leg) that may affect performance. Although the acute influence of such deoxygenation is not clearly understood, the authors tested whether remote ischemic preconditioning (RIPC) could modify muscular oxygenation and improve time-trial performance in that sport. METHODS: Using a randomized, single-blind, placebo-controlled, crossover design, 9 elite speed skaters performed 1000-m on-ice time trials preceded by either RIPC of the upper limbs (3 × 5-min compression/5-min reperfusion cycles at 30 mm Hg >arterial systolic pressure) or placebo treatment (SHAM; 10 mm Hg). Changes in tissue saturation index, oxyhemoglobin-oxymyoglobin, deoxyhemoglobin-deoxymyoglobin, and total hemoglobin-myoglobin in the right vastus lateralis muscle were monitored using near-infrared spectroscopy (NIRS). Differences between RIPC and SHAM were analyzed using Cohen effect size (ES) ± 90% confidence limits and magnitude-based inferences. RESULTS: Compared with SHAM, RIPC had a negligible effect on performance and NIRS variables. However, in a subgroup of sprinters (n = 5), RIPC likely lowered tissue saturation index at the beginning of the time trial (-6.1%; ES = -0.65) and likely increased deoxyhemoglobin-deoxymyoglobin at the beginning (3%; ES = 0.39), middle (2.9%; ES = 0.37), and end of the trial (-2.1%; ES = 0.27). In the middle section of the trial, these metabolic changes were concomitant with a possible increase in total hemoglobin-myoglobin. CONCLUSION: RIPC has no practical ergogenic impact on 1000-m long-track speed-skating performance in elite athletes. The relevance of using RIPC during training to increase physiological stress in sprinters particularly deserves further investigation.

Time-Trial Performance in World-Class Speed Skaters After Chronic Nitrate Ingestion.

PURPOSE: Nitrate supplementation can increase tolerance to high-intensity work rates; however, limited data exist on the recovery of performance. The authors tested whether 5 d of nitrate supplementation could improve repeated time-trial performance in speed skating. METHODS: Using a double-blind, placebo-controlled, crossover design, 9 international-level short-track speed skaters ingested 1 high (juice blend, ∼6.5 mmol nitrate; HI) or low dose (juice blend, ∼1 mmol nitrate; LO) per day on days 1-4. After a double dose of either HI or LO on day 5, athletes performed 2 on-ice 1000-m time trials, separated by 35 min, to simulate competition races. Differences between HI and LO were compared with the smallest practically important difference. RESULTS: Salivary [nitrate] and [nitrite] were higher in HI than LO before the first (nitrate: 81%, effect size [ES]: 1.76; nitrite: 72%, ES: 1.73) and second pursuits (nitrate: 81%, ES: 1.92; nitrite: 71%, ES: 1.78). However, there was no difference in performance in the first (LO: 90.92 [4.08] s; HI: 90.95 [4.06] s, ES: 0.01) or the second time trial (LO: 91.16 [4.06] s; HI: 91.55 [4.40] s, ES: 0.09). Plasma [lactate] measured after the trials (LO: 14.8 [1.1] mM; HI: 14.8 [1.2] mM, ES: 0.01) and at the end of the recovery period (LO: 9.8 [2.1] mM; HI: 10.2 [1.9] mM, ES: 0.05) was not different between treatments. CONCLUSION: Five days of high-dose nitrate supplementation did not change physiological responses and failed to improve single and repeated time-trial performances in world-class short-track speed skaters. These data suggest that nitrate ingestion up to 6.5 mmol does not enhance recovery from supramaximal exercise in world-class athletes.

Can dual-energy CT replace perfusion CT for the functional evaluation of advanced hepatocellular carcinoma?

OBJECTIVES: To determine the degree of relationship between iodine concentrations derived from dual-energy CT (DECT) and perfusion CT parameters in patients with advanced HCC under treatment. METHODS: In this single-centre IRB approved study, 16 patients with advanced HCC treated with sorafenib or radioembolization who underwent concurrent dynamic perfusion CT and multiphase DECT using a single source, fast kV switching DECT scanner were included. Written informed consent was obtained for all patients. HCC late-arterial and portal iodine concentrations, blood flow (BF)-related and blood volume (BV)-related perfusion parameters maps were calculated. Mixed-effects models of the relationship between iodine concentrations and perfusion parameters were computed. An adjusted p value (Bonferroni method) < 0.05 was considered significant. RESULTS: Mean HCC late-arterial and portal iodine concentrations were 22.7±12.7 mg/mL and 18.7±8.3 mg/mL, respectively. Late-arterial iodine concentration was significantly related to BV (mixed-effects model F statistic (F)=28.52, p<0.0001), arterial BF (aBF, F=17.62, p<0.0001), hepatic perfusion index (F=28.24, p<0.0001), positive enhancement integral (PEI, F=66.75, p<0.0001) and mean slope of increase (F=32.96, p<0.0001), while portal-venous iodine concentration was mainly related to BV (F=29.68, p<0.0001) and PEI (F=66.75, p<0.0001). CONCLUSIONS: In advanced HCC lesions, DECT-derived late-arterial iodine concentration is strongly related to both aBF and BV, while portal iodine concentration mainly reflects BV, offering DECT the ability to evaluate both morphological and perfusion changes. KEY POINTS: • Late-arterial iodine concentration is highly related to arterial BF and BV. • Portal iodine concentration mainly reflects tumour blood volume. • Dual-energy CT offers significantly decreased radiation dose compared with perfusion CT.

Gold(i)-BODIPY-imidazole bimetallic complexes as new potential anti-inflammatory and anticancer trackable agents.

Two new gold(i)-BODIPY-imidazole based trackable therapeutic bimetallic complexes have been synthesized and fully characterized. They display strong antiproliferative properties on several types of cancers including colon, breast, and prostate and one of them presents a significant anti-inflammatory effect. Additionally, the two compounds could be visualised in vitro by confocal microscopy in the submicromolar range.

Gold(I) Complexes of Ferrocenyl Polyphosphines: Aurophilic Gold Chloride Formation and Phosphine-Concerted Shuttling of a Dinuclear [ClAu···AuCl] Fragment.

A smart steric control of the metallocene backbone in bis- and poly(phosphino)ferrocene ligands favors intramolecular aurophilic interactions between [AuCl] fragments in polynuclear gold(I) complexes. We synthesized and characterized by multinuclear NMR and X-ray diffraction analysis mono-, di-, and polynuclear gold complexes of constrained ferrocenyl diphosphines, which bear either bulky tert-butyl groups or more flexible siloxane substituents at the cyclopentadienyl rings. The complexes meso-1,1'-bis(diphenylphosphino)-3,3'-di-tert-butylferrocene (4-m), rac-1,1'-bis[bis(5-methyl-2-furyl)phosphino]-3,3'-di-tert-butylferrocene (5-r), and rac-1,1'-bis(diphenylphosphino)-3,3'-bis[(tri-iso-propylsilyl)oxy]ferrocene (6-r) were used to form dinuclear gold complexes. Coordination of tert-butylated ferrocenyl phosphines generated aurophilic interactions in the corresponding dinuclear gold complexes, contrary to gold(I) complexes reported with 1,1'-bis(diphenylphosphino)ferrocene. The structurally related tetraphosphine 1,1',2,2'-tetrakis(diphenylphosphino)-4,4'-di-tert-butylferrocene (11) also gave access to mononuclear, dinuclear, and the original trinuclear gold chloride aurophilic complexes in which 14e- to 16e- gold centers coexist. In such complexes, nonbonded ("through-space") 31P-31P' nuclear spin couplings were evidenced by high-resolution NMR. In these interactions nuclear spin information is transferred between the lone-pair electron of an uncoordinated phosphorus P and a phosphorus P' that is involved in a σ covalent bond Au-P'. The dinuclear aurophilic complex displayed a concerted shuttling of its [ClAu···AuCl] fragment between the four phosphorus donors of the tetraphosphine ligand. Thus, an aurophilic Au···Au bond, which is assumed to be a weak energy interaction, can be conserved within a dynamic shuttling process at high temperature involving an intramolecular coordination-decoordination process of digold(I) at phosphorus atoms.

Obstructive Sleep Apnea: A Cluster Analysis at Time of Diagnosis.

BACKGROUND: The classification of obstructive sleep apnea is on the basis of sleep study criteria that may not adequately capture disease heterogeneity. Improved phenotyping may improve prognosis prediction and help select therapeutic strategies. OBJECTIVES: This study used cluster analysis to investigate the clinical clusters of obstructive sleep apnea. METHODS: An ascending hierarchical cluster analysis was performed on baseline symptoms, physical examination, risk factor exposure and co-morbidities from 18,263 participants in the OSFP (French national registry of sleep apnea). The probability for criteria to be associated with a given cluster was assessed using odds ratios, determined by univariate logistic regression. RESULTS: Six clusters were identified, in which patients varied considerably in age, sex, symptoms, obesity, co-morbidities and environmental risk factors. The main significant differences between clusters were minimally symptomatic versus sleepy obstructive sleep apnea patients, lean versus obese, and among obese patients different combinations of co-morbidities and environmental risk factors. CONCLUSIONS: Our cluster analysis identified six distinct clusters of obstructive sleep apnea. Our findings underscore the high degree of heterogeneity that exists within obstructive sleep apnea patients regarding clinical presentation, risk factors and consequences. This may help in both research and clinical practice for validating new prevention programs, in diagnosis and in decisions regarding therapeutic strategies.

Direct subphthalocyanine conjugation to bombesin vs. indirect conjugation to its lipidic nanocarrier.

Bombesin (BBN) was covalently bound to graftable subphthalocyanine (SubPc) or to a cholesterol derivative, a component of a liposome that encapsulates non-graftable SubPc. The latter bioconjugation approach was suitable to address the stability of SubPc and was achieved by copper-free click-chemistry on the outer-face of the liposome. Liposomes were purified (FPLC) and then analyzed in size (outer diameter about 60 nm measured by DLS). In vitro binding studies allowed to determine the IC50 13.9 nM for one component of the liposome, cholesterol, conjugated to BBN. Hence, azido- (or alkynyl-) liposomes give fluorophores with no reactive functional group available on their backbone a second chance to be (indirectly) bioconjugated (with bombesin).

BODIPY atropisomer interconversion, face discrimination, and superstructure appending.

A strategy was developed to append sterically hindered apical pickets on both faces of the BODIPY platform to prevent stacking and aggregation. Ortho-substitution of both the meso-phenyl ring and the boron-bound catechol affords the right directionality to append pickets, achieve face discrimination, featuring two interconvertible atropisomers, and is reminiscent of the picket-fence strategy in porphyrins.