New Triazoloquinoxaline Ligand and its Polymeric 1D Silver(I) complex Synthesis, Structure, and Antimicrobial activity

The organic ligand 4-Benzyl-1-(N,N-dimethylamino)-[1,2,4]triazolo[4,3a]quinoxaline 1 (L) and its polymeric silver(I) complex, [Ag2L(NO3)2]n (2), have been synthesized and characterized. The organic ligand 1 crystallizes in the triclinic space group P¯1. The unit cell contains two parallel-stacked molecules. The complex [Ag2L(NO3)2]n (2) crystallizes in the monoclinic space group P21/n. The structure contains two different silver(I) ions. Ag(2) is coordinated by three oxygens (involving two nitrate groups) and to a nitrogen of the triazole ring of 1. These ligands form a strongly distorted tetrahedral, nearly planar coordination sphere. Ag(1) has an approximately tetrahedral geometry. It is bonded to one oxygen of a nitrate anion and a nitrogen of two different L; this aspect giving rise to an infinite chain structure. A final bond to Ag(1) involves the carbon of a phenyl group. It is more weakly bonded to the phenyl carbons on either side of this, so that the Ag(1)-phenyl bonding has aspects of an Ag-allyl bond. Ag(1) and Ag(2) participate in bonding to a common nitrate anion and alternate, the two distinct modes of bridging between them lead to a zig-zag chain structure. In addition to spectroscopic studies, the biological activities of the ligand and of the complex were scanned over a wide range of Gram positive and Gram negative flesh- and bone-eating bacteria. The results are discussed in comparison with well-known antibiotics

Investigation of Phase Separation in Doped and Un-doped Sodium Borosilicate Glasses

The practical importance of phase separation for the optical and mechanical properties of many glass forming systems is well established. In the present contribution glasses within the immiscibility region of the sodium borosilicate system as well as samples to which 0.5 and 1 Mol% dopant ions (Eu³⁺ and P⁵⁺) have been added, were prepared under normal conditions. The separation process is monitored by UV-Vis transmittance and luminescence spectroscopy. The spectra are recorded after different intervals of heat-treatment in air. From the transmittance spectra chromaticity coordinates are obtained and the effect of heat treatment is depicted in chromaticity diagrams. From the luminescence spectra of the Eu³⁺ doped samples asymmetry ratios are obtained

Exploring the Paracrine Potential of Peri-Articular Muscle in Response to Knee Osteoarthritis Severity

Skeletal muscles such as the Articularis genu (AG) undergo disuse-mediated myofiber type redistribution, atrophy, and fibrosis attributable to knee osteoarthritis (KOA). Although peri-articular musculature can differentially secrete over 600 myokines in response to exercise or arthropathy, its paracrine influence on the symptomatic severity of KOA is largely underexplored. Myostatin (Mst) and irisin myokines have been of particular interest in cardiac research for their effective modulation of hypertrophic damage and endomysial fibrosis in cardiomyopathy, which are also hallmark structural features of the KOA musculature that can impair joint function. Measuring intra-articular concentrations of Mst and irisin in the synovial fluid (SF) of KOA patients can yield insight on the local inflammatory, hypertrophic, and fibrotic status of the quadriceps femoris, which can be histologically assessed by using the AG as a surrogate. We predict that Mst and irisin levels in the SF of KOA patients will align with clinical metrics of KOA symptomology and motility. Together with indicators of KOA severity such as synovitis histology validated with interleukin (IL)-6 levels in the SF for inflammation and collagen deposition measures validated with transforming growth factor (TGF) β-1 levels for fibrosis, measuring Mst and irisin will add to a panel of SF analytics after arthrocentesis to expand on KOA severity classification. We predict that lower concentrations of irisin with higher concentrations of Mst, IL-6, and TGFβ1 in the SF will correlate with worse range of motion and patient-reported outcome scores from a validated questionnaire. Refined assessment of the health status of peri-articular muscle before total knee arthroplasty would more precisely guide individualized strategies for peri-operative soft tissue conditioning such as the fine adjustment of frequencies during neuromuscular electrical stimulation. Ultimately, such measures and their association to symptomatic and structural KOA will help develop novel patient-centered approaches to maximize function and patient satisfaction. To test our hypothesis, SF collected from 80 patients during total knee arthroplasty and cryopreserved in liquid nitrogen will be used to measure the proposed analytes by high-sensitivity, sandwich enzymelinked immunosorbent assay (ELISA). SF will be thawed and divided into 100 µl aliquots for pretreatment with hyaluronidase and centrifugation to remove matrix macromolecules and cellular debris. Cleared aliquots will be diluted 10-25 times in high-performance ELISA buffer. SF dilutions will be optimized per assay based on the sensitivity and detection range of each ELISA kit. Samples will be assayed in duplicate against Mst, irisin, IL-6, and TGFβ1, output measured in a Biorad microplate reader, and readings analyzed against corresponding standard curves. We will compare myokine concentrations between patients grouped by poor (≤85º), fair (90º-110º), and good (≥115⁰) ROM using one-way ANOVA with α=0.05. Spearman’s ρ will be used to correlate ELISA values with retrospective histological metrics for synovitis and fibrosis and pre-operative scores from the symptoms section of the Knee Severity and Osteoarthritis Outcome Scores (KOOS) survey corresponding to each patient. This study will contribute to the overarching goal of better understanding the global and diverse effects of KOA on peri-articular muscle health and the potential development of a minimally invasive diagnostic tool to guide peri-operative soft tissue rehabilitation

Cardiorespiratory Responses to Exercise in Hypobaric versus Normobaric Hypoxia: A Randomized, Single-Blind, Crossover Study

Purpose: There is controversy whether there are meaningful physiological differences between hypobaric (HH) and normobaric hypoxia (NH). This study aimed to compare the cardiorespiratory responses to acute HH and NH under strictly controlled conditions. We hypothesized no differences at rest and during submaximal exercise, whereas during maximal exercise, a higher maximal ventilation (V̇Emax), peripheral oxygen saturation (SpO2) and maximal oxygen consumption (V̇O2max) in HH than in NH. Methods: In a randomized, single-blind, crossover design, eight young healthy subjects (three females) were studied in an environmental chamber in which either the barometric pressure (HH) or the inspired oxygen fraction (NH) was reduced to the equivalent of ~4000 m altitude. Measurements were taken at rest, during submaximal (moderate and high intensity) and maximal cycling exercise. Results: All resting parameters were similar between HH and NH, except for a lower root mean square of the successive R-R interval differences in HH (p < 0.05). SpO2 was 2% higher in HH at all exercise intensities (p < 0.05). During submaximal exercise, minute ventilation was similar between HH and NH. However, HH yielded a 7% lower tidal volume during moderate-intensity exercise (p < 0.05) and a lower respiratory exchange ratio during high-intensity exercise (p < 0.01). V̇Emax and V̇O2max were 11% and 6% higher in HH, respectively (p < 0.01 for both). SpO2 at maximal exercise was positively correlated with V̇Emax, V̇Emax/V̇O2max and V̇O2max. Conclusions: The higher V̇O2max found in HH than in NH can be attributed to the higher V̇Emax counteracting desaturation at maximal exercise. Conversely, submaximal SpO2 improved in HH through mechanisms other than increased ventilation. These findings are likely due to respiratory muscle unloading in HH, which operated through different mechanisms depending on exercise intensity

Classic Bioelectrical Impedance Vector Reference Values for Assessing Body Composition in Male and Female Athletes

Bioimpedance standards are well established for the normal healthy population and in clinical settings, but they are not available for many sports categories. The aim of this study was to develop reference values for male and female athletes using classic bioimpedance vector analysis (BIVA). In this study, 1556 athletes engaged in different sports were evaluated during their off-season period. A tetrapolar bioelectrical impedance analyzer was used to determine measurements of resistance (R) and reactance (Xc). The classic BIVA procedure, which corrects bioelectrical values for body height, was applied, and fat-free mass, fat mass, and total body water were estimated. In order to verify the need for specific references, classic bioelectrical values were compared to the reference values for the general male and female populations. Additionally, athletes were divided into three groups: endurance, velocity/power, and team sports. In comparison with the general healthy male and female populations, the mean vectors of the athletes showed a shift to the left on the R-Xc graph. Considering the same set of modalities, BIVA confidence graphs showed that male and female endurance athletes presented lower body fluids, fat mass, and fat-free mass than other sets of modalities. This study provides BIVA reference values for an athletic population that can be used as a standard for assessing body composition in male and female athletes

Effects of periodic breathing on sleep at high altitude: a randomized, placebo-controlled, crossover study using inspiratory CO2

Abstract: Hypoxia at high altitude facilitates changes in ventilatory control that can lead to nocturnal periodic breathing (nPB). Here, we introduce a placebo-controlled approach to prevent nPB by increasing inspiratory CO2 and used it to assess whether nPB contributes to the adverse effects of hypoxia on sleep architecture. In a randomized, single-blinded, crossover design, 12 men underwent two sojourns (three days/nights each, separated by 4 weeks) in hypobaric hypoxia corresponding to 4000 m altitude, with polysomnography during the first and third night of each sojourn. During all nights, subjects’ heads were encompassed by a canopy retaining exhaled CO2, and CO2 concentration in the canopy (i.e. inspiratory CO2 concentration) was controlled by adjustment of fresh air inflow. Throughout the placebo sojourn inspiratory CO2 was ≤0.2%, whereas throughout the other sojourn it was increased to 1.76% (IQR, 1.07%–2.44%). During the placebo sojourn, total sleep time (TST) with nPB was 54.3% (37.4%–80.8%) and 45.0% (24.5%–56.5%) during the first and the third night, respectively (P = 0.042). Increased inspiratory CO2 reduced TST with nPB by an absolute 38.1% (28.1%–48.1%), the apnoea–hypopnoea index by 58.1/h (40.1–76.1/h), and oxygen desaturation index ≥3% by 56.0/h (38.9.1–73.2/h) (all P < 0.001), whereas it increased the mean arterial oxygen saturation in TST by 2.0% (0.4%–3.5%, P = 0.035). Increased inspiratory CO2 slightly increased the percentage of N3 sleep during the third night (P = 0.045), without other effects on sleep architecture. Increasing inspiratory CO2 effectively prevented hypoxia-induced nPB without affecting sleep macro-architecture, indicating that nPB does not explain the sleep deterioration commonly observed at high altitudes. (Figure presented.). Key points: Periodic breathing is common during sleep at high altitude, and it is unclear how this affects sleep architecture. We developed a placebo-controlled approach to prevent nocturnal periodic breathing (nPB) with inspiratory CO2 administration and used it to assess the effects of nPB on sleep in hypobaric hypoxia. Nocturnal periodic breathing was effectively mitigated by an increased inspiratory CO2 fraction in a blinded manner. Prevention of nPB did not lead to relevant changes in sleep architecture in hypobaric hypoxia. We conclude that nPB does not explain the deterioration in sleep architecture commonly observed at high altitude

Mortality in Different Mountain Sports Activities Primarily Practiced in the Winter Season-A Narrative Review.

Annually, millions of people engage in mountain sports activities all over the world. These activities are associated with health benefits, but concurrently with a risk for injury and death. Knowledge on death rates is considered important for the categorization of high-risk sports in literature and for the development of effective preventive measures. The death risk has been reported to vary across different mountain sports primarily practiced in the summer season. To complete the spectrum, the aim of the present review is to compare mortality rates across different mountain sports activities primarily practiced in winter. A comprehensive literature search was performed on the death risk (mortality) during such activities, i.e., alpine (downhill) skiing, snowboarding, cross-country skiing, ski touring, and sledging. With the exception of ski touring (4.4 deaths per 1 million exposure days), the mortality risk was low across different winter sports, with small activity-specific variation (0.3-0.8 deaths per 1 million exposure days). Traumatic (e.g., falls) and non-traumatic (e.g., cardiac death) incidents and avalanche burial in ski tourers were the predominant causes of death. Preventive measures include the improvement of sport-specific skills and fitness, the use of protective gear, well-targeted and intensive training programs concerning avalanche hazards, and sports-medical counseling for elderly and those with pre-existing diseases

Influence of Inspiratory Muscle Training on Ventilatory Efficiency and Cycling Performance in Normoxia and Hypoxia

The aim of this study was to analyse the influence of inspiratory muscle training (IMT) on ventilatory efficiency, in normoxia and hypoxia, and to investigate the relationship between ventilatory efficiency and cycling performance. Sixteen sport students (23.05 +/- 4.7 years; 175.11 +/- 7.1 cm; 67.0 +/- 19.4 kg; 46.4 +/- 8.7 ml·kg-1·min-1) were randomly assigned to an inspiratory muscle training group (IMTG) and a control group (CG). The IMTG performed two training sessions/day [30 inspiratory breaths, 50% peak inspiratory pressure (Pimax), 5 days/week, 6-weeks]. Before and after the training period subjects carried out an incremental exercise test to exhaustion with gas analysis, lung function testing, and a cycling time trial test in hypoxia and normoxia. Simulated hypoxia (FiO2 = 16.45%), significantly altered the ventilatory efficiency response in all subjects (p < 0.05). Pimax increased significantly in the IMTG whereas no changes occurred in the CG (time group, p < 0.05). Within group analyses showed that the IMTG improved ventilatory efficiency (VE/VCO2 slope; EqCO2VT2) in hypoxia (p < 0.05) and cycling time trial performance [WTTmax (W); WTTmean (W); PTF(W)] (p < 0.05) in hypoxia and normoxia. Significant correlations were not found in hypoxia nor normoxia found between ventilatory efficiency parameters (VE/VCO2 slope; LEqCO2; EqCO2VT2) and time trial performance. On the contrary the oxygen uptake efficiency slope (OUES) was highly correlated with cycling time trial performance (r = 0.89; r = 0.82; p < 0.001) under both conditions. Even though no interaction effect was found, the within group analysis may suggest that IMT reduces the negative effects of hypoxia on ventilatory efficiency. In addition, the data suggest that OUES plays an important role in submaximal cycling performance.(VLID)3080991Version of recor

Using The Articularis Genu To Test Peri-articular Muscle Health During Knee Osteoarthritis

Knee osteoarthritis (OA) involves peri-articular sarcopenia. The infrapatellar articularis genu (AG) links to the quadriceps femoris (QF) and can be sampled from discarded tissue during arthroplasty. We predict disuse-mediated changes in AG myofiber type ratio and atrophy similar to reports on the QF during OA. OA AGs (n = 40) were preserved and grouped by poor (≤ 85°; n = 11), fair (90°–110°; n = 19), and good (≥ 115°; n = 10) range of motion (ROM). Immunolabeling of slow and fast myosin heavy chains in AG sections allowed comparing distribution and cross-sectional area (CSA) of type-I (T1) and type-II (T2) myofibers between groups and associating to ROM. T1/T2 ratios in fair and poor ROM groups was consistent with those published in OA QF. Increasing mean ± SD T2 percentages from good (43.31 ± 11.76), to fair (50.96 ± 5.85), and poor (60.02 ± 8.29) ROM groups was significant between poor versus fair (p = 0.018) and good (p \u3c 0.0001) in association with ROM deficits (r = − 0.729; p \u3c 0.0001). T1 and T2 CSA decreased with worsening ROM, which associates with lower symptom scores (r = 0.3198; p = 0.0472). In-depth evaluation of the OA AG as a surrogate for the OA QF relative to serum and/or synovial fluid biomarkers of sarcopenia could refine diagnostics of peri-articular muscle health to guide individualized strength rehabilitation after surgery

Photoionization efficiency spectroscopy and density functional theory investigations of RhHo2On, (n=0-2) clusters

The experimental and theoretical adiabatic ionization energies (IEs) of the rhodium-holmium bimetallic clusters RhHo(2)O(n) (n=0-2) have been determined using photoionization efficiency spectroscopy and density functional theory (DFT) calculations. Both sets of data show the IE of RhHo(2)O to be significantly lower than the values for RhHo(2) and RhHo(2)O(2), which are found to be similar. This indicates that there are significant changes in electronic properties upon sequential addition of oxygen atoms to RhHo(2). The DFT investigations show that the lowest energy neutral structures are a C(2v) triangle for RhHo(2), a C(2v) planar structure for RhHo(2)O where the O atom is doubly bridged to the Ho-Ho bond, and a C(2v) nonplanar structure for RhHo(2)O(2), where the O(2) is dissociative and each O atom is doubly bridged to the Ho-Ho bond in the cluster above and below the RhHo(2) trimer plane. Good correlation between the experimental and computational IE data imply that the lowest energy neutral structures calculated are the most likely isomers ionized in the molecular beam. In particular, the theoretical adiabatic IE for the dissociative RhHo(2)O(2) structure is found to compare better with the experimentally determined value than the corresponding lowest energy O(2) associative structure.Alexander S. Gentleman, Matthew A. Addicoat, Viktoras Dryza, Jason R. Gascooke, Mark A. Buntine, and Gregory F. Meth