Indium(III)-Catalyzed Stereoselective Synthesis of Tricyclic Frameworks by Cascade Cycloisomerization Reactions of Aryl 1,5-Enynes

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUGThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.1c00825 (https://pubs.acs.org/doi/suppl/10.1021/acs.joc.1c00825/suppl_file/jo1c00825_si_001.pdf)[Abstract] The indium(III)-catalyzed cascade cycloisomerization reaction of 1,5-enynes with pendant aryl nucleophiles is reported. The reaction proceeds in cascade under mild reaction conditions, using InI₃ (5 mol %) as a catalyst with a range of 1,5-enynes furnished with aryl groups (phenyl and phenol) at alkene (E and Z isomers) and with terminal and internal alkynes. Using 1-bromo-1,5-enynes, a one-pot sequential indium-catalyzed cycloisomerization and palladium-catalyzed cross-coupling with triorganoindium reagents were developed. The double cyclization is stereospecific and operates via a biomimetic cascade cation-olefin through 1,5-enyne cyclization (6-endo-dig) and subsequent C–C hydroarylation or C–O phenoxycyclization. Density functional theory (DFT) computational studies on 1,5-enynyl aryl ethers support a two-step mechanism where the first stereoselective 1,5-enyne cyclization produces a nonclassical carbocation intermediate that evolves to the tricyclic reaction product through a SᴇAr mechanism. Using this approach, a variety of tricyclic heterocycles such as benzo[b]chromenes, phenanthridines, xanthenes, and spiroheterocyclic compounds are efficiently synthesized with high atom economy.We thank the Spanish Ministerio de Ciencia, Innovación y Universidades (PGC2018-097792-B-I00 and PID 2019-110008GB-I00), Xunta de Galicia (GRC2018/039), IZO-SGI SGIker of UPV/EHU, and EDRF funds for financial and human supportXunta de Galicia; GRC2018/039https://pubs.acs.org/doi/suppl/10.1021/acs.joc.1c00825/suppl_file/jo1c00825_si_001.pd

Effectiveness of surgical hand antisepsis using chlorhexidine digluconate and parachlorometaxylenol hand scrub

[Abstract] Background: Chlorhexidine and parachlorometaxylenol (PCMX) are antiseptics recommended for surgical hand antisepsis. To our knowledge, PCMX has not been evaluated for bactericidal efficacy “in vivo. Methods: We conducted a randomized, double-blind, controlled crossover trial to compare the bacterial loads on fingertips and fingernails under laboratory conditions after use of antiseptic test products, including chlorhexidine digluconate 4%, PCMX 3%, and a reference solution of propan-1-ol 60% (P-1). We assessed bacterial load after a prewash with soft soap, immediately after application of an antiseptic, and 3 hours after application and wearing of sterile, powder-free gloves. Our procedures followed those specified by European Norm (EN) 12791 for evaluating surgical hand antiseptics and using cotton swab for fingertips and fingernails. Results: Chlorhexidine digluconate 4% and PCMX 3% did not decrease bacterial load on the hands. The bactericidal performances of chlorhexidine digluconate 4% and PCMX 3% did not differ significantly. Chlorhexidine digluconate 4% and PCMX 3% increased bacterial load on the fingertips after participants had worn gloves for 3 hours. Fingernails had greater bacterial loads than skin on the fingertips. Conclusions: Chlorhexidine digluconate 4% and PCMX 3% had similar bactericidal efficacy, but they failed to meet the EN 12791 efficacy standard. Fingernails should be a particular focus of antisepsis in preparation for surgery. The trial was registered at ClinicalTrials.gov (ID: NCT02500758)

Commercial Blood Cell Separation Systems Versus Tube Centrifugation Methods for the Preparation of Platelet-Rich Plasma: A Preliminary Cross-Sectional Study

[Abstract] OBJECTIVE: Clinical studies claim that platelet-rich plasma (PRP) accelerates tissue healing due to its high concentration of growth factors and that the combination with leukocytes improves the antimicrobial effect of the concentrate. Most of these studies obtained PRP using different separation systems, and few analyzed the content of the PRP used for treatment. This study characterized the composition of PRP and white blood cells (WBC) from a single donor produced by three commercially available PRP separation systems and two anticoagulated general analytical tubes. METHODS: Five patients donated 50 mL of blood, which was processed to produce PRP and WBC using three PRP concentration systems (i.e., Easy PRP Kit, GloPRP, and Wego) and two tubes for general analysis anticoagulated with ethylenediaminetetraacetic acid (EDTA) and citrate. Platelets and WBC in combination with their concentrates were analyzed by automated systems in a clinical laboratory. RESULTS: There were no significant differences in the average concentrations of PRP platelets and WBC between GloPRP and the tubes for general analysis with EDTA and citrate; however, the Easy PRP Kit gave results much superior to the rest of the methods, especially comparing it with the Wego Kit, whose concentrates were especially low, even nonexistent for WBC. CONCLUSIONS: The Easy PRP Kit concentrates WBC-rich PRP, resulting in increased WBC concentrations, compared with low WBC-low PRP of GloPRP and general tube methods for EDTA and citrate analysis and the even lower concentration of PRP from the Wego Kit, with the absence of leukocyte

Influence of the center of pressure on baropodometric gait pattern variations in the adult population with flatfoot: A case-control study

[Abstract] Background: Adult flatfoot is considered an alteration in the foot bone structure characterized by a decrease or collapse of the medial arch during static or dynamic balance in the gait pattern. The aim of our research was to analyze the center of pressure differences between the population with adult flatfoot and the population with normal feet. Methods: A case-control study involving 62 subjects was carried out on 31 adults with bilateral flatfoot and 31 healthy controls. The gait pattern analysis data were collected employing a complete portable baropodometric platform with piezoresistive sensors. Results: Gait pattern analysis showed statistically significant differences in the cases group, revealing lower levels in the left foot loading response of the stance phase in foot contact time (p = 0.016) and contact foot percentage (p = 0.019). Conclusion: The adult population with bilateral flatfoot evidenced higher contact time data in the total stance phase compared to the control group, which seems to be linked to the presence of foot deformity in the adult population

Influence of Sexual Dimorphism, Aging, and Differential Cell Capture Efficiency of Blood Separation Systems on the Quality of Platelet-Rich Plasma

[Abstract] Few studies have checked the impact of the hormonal/immunological dimorphism of patients on the cellular composition of platelet-rich plasma products (PRP). Whole blood (WB) from 26 volunteers was concentrated using a device previously characterized. Platelet and white blood cell (WBC) counts in WB and PRP were compared between genders, and after the population was split into pre (≤50 years)- and post (>50 years)-menopausal ages. In WB, platelet-total WBC densities were comparable in men and women. The phagocytic cell composition differed (p ≤ 0.04). After dividing by ages, phagocytic cell discrepancies were linked to women > 50 years (p ≤ 0.05), and differences emerged in lymphocyte counts (lower in >50 years groups, within and between genders, p ≤ 0.05). In PRP, densities were significantly higher, but the PRP/WB ratios varied according to blood cell (lower for phagocytic cells) and between subjects (more favorable at a lower density of a particular blood cell in WB). This "system compensatory efficiency" reduced/reverted PRP differences in the leukocyte composition between genders/age-sex groups in WB. In PRP, neutrophils were higher in younger men than older women (p < 0.05). WB lymphocyte differences between age-sex groups persisted. Age is a more determining factor than sex in the preparation of PRP. Post-menopause, sexual dimorphism strongly influences the composition of leukocytes, also conditioned by the capture efficiency of the system

Commercial blood cell separation systems versus tube centrifugation methods for the preparation of platelet-rich plasma: a preliminary cross-sectional study

[EN] OBJECTIVE: Clinical studies claim that platelet-rich plasma (PRP) accelerates tissue healing due to its high concentration of growth factors and that the combination with leukocytes improves the antimicrobial effect of the concentrate. Most of these studies obtained PRP using different separation systems, and few analyzed the content of the PRP used for treatment. This study characterized the composition of PRP and white blood cells (WBC) from a single donor produced by three commercially available PRP separation systems and two anticoagulated general analytical tubes. METHODS: Five patients donated 50 mL of blood, which was processed to produce PRP and WBC using three PRP concentration systems (i.e., Easy PRP Kit, GloPRP, and Wego) and two tubes for general analysis anticoagulated with ethylenediaminetetraacetic acid (EDTA) and citrate. Platelets and WBC in combination with their concentrates were analyzed by automated systems in a clinical laboratory. RESULTS: There were no significant differences in the average concentrations of PRP platelets and WBC between GloPRP and the tubes for general analysis with EDTA and citrate; however, the Easy PRP Kit gave results much superior to the rest of the methods, especially comparing it with the Wego Kit, whose concentrates were especially low, even nonexistent for WBC. CONCLUSIONS: The Easy PRP Kit concentrates WBC-rich PRP, resulting in increased WBC concentrations, compared with low WBC-low PRP of GloPRP and general tube methods for EDTA and citrate analysis and the even lower concentration of PRP from the Wego Kit, with the absence of leukocytes.S

Influence of Sexual Dimorphism, Aging, and Differential Cell Capture Efficiency of Blood Separation Systems on the Quality of Platelet-Rich Plasma

[EN] Few studies have checked the impact of the hormonal/immunological dimorphism of patients on the cellular composition of platelet-rich plasma products (PRP). Whole blood (WB) from 26 volunteers was concentrated using a device previously characterized. Platelet and white blood cell (WBC) counts in WB and PRP were compared between genders, and after the population was split into pre (≤50 years)- and post (>50 years)-menopausal ages. In WB, platelet–total WBC densities were comparable in men and women. The phagocytic cell composition differed (p ≤ 0.04). After dividing by ages, phagocytic cell discrepancies were linked to women > 50 years (p ≤ 0.05), and differences emerged in lymphocyte counts (lower in >50 years groups, within and between genders, p ≤ 0.05). In PRP, densities were significantly higher, but the PRP/WB ratios varied according to blood cell (lower for phagocytic cells) and between subjects (more favorable at a lower density of a particular blood cell in WB). This “system compensatory efficiency” reduced/reverted PRP differences in the leukocyte composition between genders/age–sex groups in WB. In PRP, neutrophils were higher in younger men than older women (p < 0.05). WB lymphocyte differences between age–sex groups persisted. Age is a more determining factor than sex in the preparation of PRP. Post-menopause, sexual dimorphism strongly influences the composition of leukocytes, also conditioned by the capture efficiency of the system.S

Age-Based Inter-Subject Variability in Platelet and Whiteblood Cell Concentrations of Platelet-Rich Plasma Preparedusing a New Application to Blood Separation System

[Abstract] The benefit of autologous platelet-rich plasma (PRP) treatment is still underdiscussion. Variations in PRP products, consequence of the lack of astandardised protocol for the multitude of commercially available blood sepa-ration systems and the lack of knowledge of the optimal composition of PRPor its suitability for the proposed indication are some of the reasons behindclinical inconsistencies. The impact of inter-subject variability in PRP hasreceived less attention in comparison. The purpose of this study was to deter-mine the inter-subject variability, based on age, in the concentrates preparedby a new blood concentration system. Twenty-six healthy volunteers of bothgenders (29-93 years) were enrolled. Whole blood (WB) was collected fromeach participant to prepare PRP using the Easy PRP kit. Platelets and whiteblood cells (WBC) from WB and PRP were analysed after split population byage; patients younger than 65 years (n=13) and patients≥65 years old(n=13). Among the demographic characteristics tested, only age was signifi-cantly different between the groups. Cell capture efficiency of the system wasspecific for each type of blood cell and identical for both age groups. Plateletsand WBC in PRP were higher than in WB (P< .001). In WB, platelets andWBC concentrations were significantly lower in older group (P≤.035). Thesedifferences persisted in the prepared PRP (P≤.004). The ageing of populationhas a strong influence on the haematocrit and therefore on the composition ofPRP. Because the efficiency of blood separator system seems to be constantacross individuals, the inter-subject haematocrit variability based on age couldbe used as a predictor of resulting PRP. The clinical application of PRP shouldbe restricted to the specific cell capture capacity of the different commercialdevice

Skin Bioimpedance Analysis to Determine Cellular Integrity by Phase Angle in Women with Fibromyalgia: A Cross-Sectional Study.

Oxidative stress has been proposed as a significant part of the pathogenesis of fibromyalgia, and the phase angle in bioelectrical impedance analysis has been explored as a potential technique to screen oxidative abnormalities. This study recruited 35 women with fibromyalgia and 35 healthy women, who underwent bioelectrical impedance analysis and maximum isometric handgrip strength tests. Women with fibromyalgia showed lower bilateral handgrip strength (right hand: 16.39 ± 5.87 vs. 27.53 ± 4.09, p < 0.001; left hand: 16.31 ± 5.51 vs. 27.61 ± 4.14, p < 0.001), as well as higher body fat mass (27.14 ± 10.21 vs. 19.94 ± 7.25, p = 0.002), body fat percentage (37.80 ± 8.32 vs. 30.63 ± 7.77, p < 0.001), and visceral fat area (136.76 ± 55.31 vs. 91.65 ± 42.04, p < 0.01) compared with healthy women. There was no statistically significant difference in muscle mass between groups, but women with fibromyalgia showed lower phase angles in all body regions when compared with healthy control women (right arm: 4.42 ± 0.51 vs. 4.97 ± 0.48, p < 0.01; left arm: 4.23 ± 0.48 vs. 4.78 ± 0.50, p < 0.001; trunk: 5.62 ± 0.77 vs. 6.78 ± 0.84, p < 0.001; right leg: 5.28 ± 0.56 vs. 5.81 ± 0.60, p < 0.001; left leg: 5.07 ± 0.51 vs. 5.69 ± 0.58, p < 0.001; whole body: 4.81 ± 0.47 vs. 5.39 ± 0.49, p < 0.001). Moreover, whole-body phase-angle reduction was only predicted by the presence of fibromyalgia (R 2 = 0.264; β = 0.639; F(1,68) = 24.411; p < 0.001). Our study revealed significantly lower phase angle values, lower handgrip strength, and higher fat levels in women with fibromyalgia compared to healthy controls, which are data of clinical relevance when dealing with such patients.post-print1,25 M

Impact of chronic foot pain related quality of life: a retrospective case-control study

Clinical trial[Abstract] Background: Chronic foot pain (CFP) is a widespread condition worldwide; however, few studies that relate CFP and foot health-related quality of life have been reported. Objective: The aim of this study was to describe the impact of foot health and health in general in a sample of adult people with CFP compared with a control group. Study design: This study was designed as a retrospective case-control study. Setting: Podiatric section of a care center. Methods: Two hundred adults were included in the study. Patients were divided into CFP patient (n = 100) and control groups (n = 100). All of them regularly attended a private podiatric clinic to take care of their foot health. Self-reported data and medical histories for people with and without CFP were evaluated. All findings were compared with quality of life (QoL) scores based on the Foot Health Status Questionnaire, Spanish version. Results: Adults with CFP (compared to the control group) showed reductions in QoL linked to overall health and foot health in particular and were statistically significant with respect to several domains: (1) foot pain, (2) foot function, (3) general health, and (4) physical activity. These differ-ences were evaluated with a t-test for independent samples, and statistical significance was consid-ered a P value of P < 0.05. Limitations: The study was not a randomized controlled trial. Although primary outcome data were self-reported, the assessor was not blinded. Conclusions: CFP patients, regardless of gender, recorded a negative influence on QoL-related foot health that seems to be linked with the presence of this chronic condition