Structural Deformations in Cucurbit[n]urils: Analysis, Host-Guest Dependence, and Automated Ellipticity Measurements using ElliptiCB[n].

Cucurbit[n]urils (CB[n]s) are cyclic macrocycles with rich host-guest chemistry. In many cases, guest binding in CB[n]s results in structural deformations. Unfortunately, measuring such deformations remains a major challenge, with only a handful of manual estimations reported in the literature. To address this challenge, we have developed the public program ElliptiCB[n], which is available on GitHub, that provides a robust and automated method for measuring the elliptical deformations in CB[n] hosts. We outline the development and validation of this approach, apply ElliptiCB[n] to measure to the ellipticity of the 1113 available CB[n] structures from the Cambridge Structural Database (CSD), and directly investigate the structural deformations of CB[5], CB[6], CB[7], CB[8], and CB[10]. We also report the general landscape of accessible CB[n] elliptical deformations and compare ellipticity distributions across CB[n] hosts and host-guest complexes. We found that in almost all cases guest binding significant impacts the distribution of host ellipticity distributions and that ellipticity distributions are dissimilar across host-guest complexes of differently sized CB[n]s. We anticipate that this work will provide a useful approach for understanding of the flexibility of CB[n] hosts and will also enable future measurement and standardization of ellipticity measurements of CB[n]s.

Incision Closure for Direct Anterior Total Hip Arthroplasty: Is There a Difference in the Rate of Superficial Wound Complications With Suture Versus Staples?

Background Direct anterior total hip arthroplasty (DA-THA) has increased in popularity over recent decades. However, DA-THA has been reported to have a higher incidence of superficial wound complications, including infection and incisional dehiscence, compared to other surgical approaches to hip arthroplasty. While this indicates a need for optimal wound closure, little research exists on the preferred method of skin closure following DA-THA. This study aimed to determine if there was any difference in rates of superficial infection, wound dehiscence, or overall wound complications with skin closure using a running subcuticular 3-0 Monocryl® suture compared to surgical staples following DA-THA.  Methods Records of patients who underwent DA-THA at our institution between July 2017 to July 2022 were retrospectively reviewed. Data were abstracted on patient demographics, comorbidities, skin closure method, and wound complications from the electronic medical record. Superficial infection and wound dehiscence were classified based on explicit diagnosis in post-operative records and incision photographs taken during follow-up visits. Overall wound complications were classified in patients who experienced either superficial infection, incisional dehiscence, or both complications following surgery. Descriptive statistics and chi-squared measures were obtained from post-operative patient data, and significance was set at p [Formula: see text] 0.05. Results A total of 365 DA-THAs were completed in 349 patients. A running subcuticular 3-0 Monocryl® suture closed 207 surgeries (56.7%), while surgical staples closed 158 surgeries (43.3%). There was no significant difference in independent rates of superficial infection (p = 0.076) or wound dehiscence (p = 0.118) between suture and staple cohorts; however, suture closure (10, 2.7%) was associated with a significantly higher rate of overall wound complications compared to staple closure (1, 0.3%) (p = 0.020). Conclusion DA-THA carries the risk of overall wound complications, including superficial infection and wound dehiscence. Our findings suggest superficial skin closure with staples may be preferred over sutures due to lower rates of overall wound complications. Further studies are needed to determine the optimal method of skin closure following DA-THA.

The Predictors of Osteoarthritis Among U.S. Adults: National Health and Nutrition Examination Survey, 2005 to 2018.

Background Osteoarthritis (OA) is a leading cause of disability in the United States (U.S.) population, and its prevalence continues to rise. Traditionally, extreme joint loading was described as the leading cause of OA; however, recent studies suggest OA may arise from more complex mechanisms. This study aimed to identify the association between OA and various health predictors among U.S. adults. Methods National Health and Nutrition Examination Survey (NHANES) data of adult participants from 2005 to 2018 was reviewed. OA diagnosis was patient-reported, and other health variables were assessed based on patient-reported, laboratory, and examination data. A multivariable survey logistic regression model was used to estimate adjusted odds ratios and confidence intervals (95% CIs). Stratified analysis based on BMI category was additionally performed to assess the modifying effect of obesity on the association between OA and health predictors. Results A total of 42,143 participants were included in this study. OA prevalence was highest in patients ages [Formula: see text] 65 years, females, non-obese individuals, non-Hispanic Whites, and those with at least college education. After controlling for multiple confounding demographic variables and comorbidities, the odds of OA increased with aging, female sex, obesity, high cholesterol, hypertension, diabetes, depression, and thyroid disease. Non-Hispanic White patients and those with less than a high school education also had higher odds of OA. After stratified analysis, aging, female sex, and severe depression demonstrated similar associations with OA across each BMI strata. Having at least a college-level education additionally conferred a similar association with OA across each BMI strata. Conclusion The odds of OA increased with aging, female sex, obesity, less than high school education, high cholesterol, hypertension, diabetes, depression, and thyroid disease. Further studies are needed to characterize the mechanisms of these associations. Given the myriad of factors that influence OA development and progression, the utilization of multidisciplinary and holistic care of OA patients is recommended to limit the influence of other health predictors and reduce ensuing pain, disability, and other complications that result from OA.

The impact of the distal ureteral diameter ratio, bladder volume at onset of vesicoureteral reflux, and/or grade in predictive models of clinical outcomes in children with vesicoureteral reflux.

PURPOSE: Vesicoureteral reflux (VUR) grade has been used as a primary factor in assessing a child's risk of clinical outcomes. Unfortunately, grade has poor inter-observer reliability. We hypothesized that more objective and reliable VCUG parameters including the distal ureteral diameter ratio (UDR) and volume at onset of VUR (Vol) may either augment or replace the current grading system to provide more reliable prediction of clinical outcomes. MATERIALS AND METHODS: Multivariate clinical outcome models were analyzed to assess the impact on predictive accuracy by the addition of voiding cystourethrogram (VCUG) data including grade, UDR, and Vol, alone or in combinations. Clinical variables from retrospective review of 841 children's records included age, gender, presentation, VUR laterality, bowel and bladder dysfunction, history of febrile urinary tract infection (UTI), and number of UTIs. The primary outcomes assessed included VUR resolution or persistence and need for operative intervention. RESULTS: Grade, UDR, and Vol were independent predictors of resolution and operative intervention. Vol increased predictive accuracy in resolution models with grade or UDR alone; however, no significant difference occurred in models with the substitution of grade with UDR. CONCLUSIONS: A more reliable classification system for VUR, with improved predictive accuracy regarding clinical outcomes, may be developed incorporating UDR and Vol. Whether VUR grade can be completely replaced by Vol and UDR measurements requires further evaluation with larger number of patients.

Solubilization of elemental sulfur by surfactants promotes reduction to H2S by thiols.

Elemental sulfur (S8) may contribute to sulfane sulfur (S0) storage in biological systems. We demonstrate that surfactants can solubilize S8 in water and promote S8 reduction to H2S by thiols. Moreover, anionic and cationic surfactants interact differently with intermediate S0 carriers, highlighting how specific hydrophobic microenvironments impact reactive sulfur species.

The effects of conformation and intermolecular hydrogen bonding on the structure and IR spectra of flutamide; a study based on the matrix isolation technique, ab initio and DFT calculations.

In this study, stable conformers of flutamide referred to as an anticancer drug were searched through a relaxed potential energy surface scan carried out at the B3LYP/6-31G(d) level of theory. This was followed by geometry optimization and thermochemistry calculations performed with the HF-SCF, MP2, B3LYP methods and the 6-31G(d), 6-311++G(d,p), aug-cc-pvTZ basis sets for each of the determined minimum energy conformers. The results revealed that flutamide has at least five stable conformers and two of them provide the major contribution to the observed matrix isolation infrared (IR) spectra of the molecule. The effects of conformational variety and intermolecular hydrogen bonding interactions on the observed IR spectra of flutamide were interpreted in the light of the vibrational spectral data obtained for the most stable monomer and dimer forms of the molecule at the same levels of theory. Pulay's "Scaled Quantum Mechanical-Force Field (SQM-FF)" method was used in the refinement of the calculated harmonic wavenumbers, IR intensities and potential energy distributions. This scaling method which proved its superiority to both anharmonic frequency calculations and other scaling methods helped us to correctly interpret the remarkable differences between the matrix IR spectra of flutamide in argon and the condensed phase IR spectra of the molecule in solvents such as KBr, H2O, D2O, ethanol and methanol.

Supramolecular Activation of S8 by Cucurbiturils in Water and Mechanism of Reduction to H2S by Thiols: Insights into Biological Sulfane Sulfur Trafficking.

Reactive sulfur species (RSS) play critical roles in diverse chemical environments. Molecules containing sulfane sulfur (S0) have emerged as key species involved in cellular redox buffering as well as RSS generation, translocation, and action. Using cucurbit[7]uril (CB[7]) as a model hydrophobic host, we demonstrate here that S8 can be encapsulated to form a 1:1 host guest complex, which was confirmed by solution state experiments, mass spectrometry, and X-ray crystallography. The solid state structure of CB[7]/S8 shows that the encapsulated S8 is available to nucleophiles through the carbonyl portals of the host. Treatment of CB[7]/S8 with thiols results in efficient reduction of S8 to H2S in water at physiological pH. We establish that encapsulated S8 is attacked by a thiol within the CB[7] host and that the resultant soluble hydropolysulfide is ejected into solution, where it reacts further with thiols to generate soluble sulfane sulfur carriers and ultimately H2S. The formation of these intermediate is supported by observed kinetic saturation behavior, competitive inhibition experiments, and alkylative trapping experiments. We also demonstrate that CB[7]/S8 can be used to increase sulfane sulfur levels in live cells using fluorescence microscopy. More broadly, this work suggests a general activation mechanism of S8 by hydrophobic motifs, which may be applicable to proteins, membranes, or other bimolecular compartments that could transiently bind and solubilize S8 to promote reaction with thiols to solubilize and shuttle S8 back into the redox labile sulfane sulfur pool. Such a mechanism would provide an attractive manifold in which to understand the RSS translocation and trafficking.

An investigation on the structure and group vibrations of balenine molecule by matrix isolation IR spectroscopy, DFT and MP2 based calculations.

Stable conformers of neutral balenine were scanned through molecular dynamics simulations and energy minimizations using Allinger's MM2 force field. For each of the found minimum-energy conformers, geometry optimization and thermochemistry calculations were performed by using B3LYP, MP2, G3MP2B3 methods, 6-31G(d), 6-311++G(d,p) and aug-cc-pvTZ basis sets. The calculation results have indicated that balenine has about twenty stable conformers whose relative energies are in the range of 0-9.5 kcal/mol. Three of these are thought to provide the major contribution to matrix isolation IR spectra of the molecule. Our solvent calculations using the polarized continuum model revealed the stable zwitterion structures which are predicted to dominate IR spectra of balenine in water and heavy water (D2O) solvents. Pulay's SQM-FF method was used in scaling of the harmonic force constants and vibrational spectral data calculated for the neutral and zwitterion structures. These refined calculation data together with those obtained from anharmonic frequency calculations enabled us to correctly interpret the matrix isolation IR spectrum of balenine and the tautomerism-based changes observed in its KBr IR and solution (D2O) IR spectra. The results revealed the crucial role of conformation and zwitterionic tautomerism on the structure and vibrational spectral data of the molecule.

Hydrolysis-Based Small-Molecule Hydrogen Selenide (H2Se) Donors for Intracellular H2Se Delivery.

Hydrogen selenide (H2Se) is a central metabolite in the biological processing of selenium for incorporation into selenoproteins, which play crucial antioxidant roles in biological systems. Despite being integral to proper physiological function, this reactive selenium species (RSeS) has received limited attention. We recently reported an early example of a H2Se donor (TDN1042) that exhibited slow, sustained release through hydrolysis. Here we expand that technology based on the P═Se motif to develop cyclic-PSe compounds with increased rates of hydrolysis and function through well-defined mechanisms as monitored by 31P and 77Se NMR spectroscopy. In addition, we report a colorimetric method based on the reaction of H2Se with NBD-Cl to generate NBD-SeH (λmax = 551 nm), which can be used to detect free H2Se. Furthermore, we use TOF-SIMS (time of flight secondary ion mass spectroscopy) to demonstrate that these H2Se donors are cell permeable and use this technique for spatial mapping of the intracellular Se content after H2Se delivery. Moreover, these H2Se donors reduce endogenous intracellular reactive oxygen species (ROS) levels. Taken together, this work expands the toolbox of H2Se donor technology and sets the stage for future work focused on the biological activity and beneficial applications of H2Se and related bioinorganic RSeS.

A Photoprotective Effect by Cation-π-Interaction? Quenching of Singlet Oxygen by an Indole Cation-π Model System.

We investigated the effect of the cation-π interaction on the susceptibility of a tryptophan model system toward interaction with singlet oxygen, that is, type II photooxidation. The model system consists of two indole units linked to a lariat crown ether to measure the total rate of removal of singlet oxygen by the indole units in the presence of sodium cations (i.e. indole units subject to a cation-π interaction) and in the absence of this interaction. We found that the cation-π interaction significantly decreases the total rate of removal of singlet oxygen (kT ) for the model system, that is, (kT  = 2.4 ± 0.2) × 108  m-1  s-1 without sodium cation vs (kT  = 6.9 ± 0.9) × 107  m-1  s-1 upon complexation of sodium cation to the crown ether. Furthermore, we found that the indole moieties undergo type I photooxidation processes with triplet excited methylene blue; this effect is also inhibited by the cation-π interaction. The chemical rate of reaction of the indole groups with singlet oxygen is also slower upon complexation of sodium cation in our model system, although we were unable to obtain an exact ratio due to differences of the chemical reaction rates of the two indole moieties.

Chemistry of Singlet Oxygen with a Cadmium-Sulfur Cluster: Physical Quenching versus Photooxidation.

We investigated the chemistry of singlet oxygen with a cadmium-sulfur cluster, (Me4N)2[Cd4(SPh)10]. This cluster was used as a model for cadmium-sulfur nanoparticles. Such nanoparticles are often used in conjunction with photosensitizers (for singlet oxygen generation or dye-sensitized solar cells), and hence, it is important to determine if cadmium-sulfur moieties physically quench and/or chemically react with singlet oxygen. We found that (Me4N)2[Cd4(SPh)10] is indeed a very strong quencher of singlet oxygen with total rate constants for 1O2 removal of (5.8 ± 1.3) × 108 M-1 s-1 in acetonitrile and (1.2 ± 0.5) × 108 M-1 s-1 in CD3OD. Physical quenching predominates, but chemical reaction leading to decomposition of the cluster and formation of sulfinate is also significant, with a rate constant of (4.1 ± 0.6) × 106 M-1 s-1 in methanol. Commercially available cadmium-sulfur quantum dots ("lumidots") show similar singlet oxygen quenching rate constants, based on the molar concentration of the quantum dots.

Ram sperm motility after intermittent scrotal insulation evaluated by manual and computer-assisted methods.

AIM: To study whether additional measurements of motility characteristics of spermatozoa by computer assisted semen analysis (CASA) were more sensitive indicators of reduced semen quality than estimates of percentages of motile, rapid or progressive cells. METHODS: Intermittent scrotal insulation was applied to 6 rams for 16 h per day for 21 days or to 2 of these for 12 h per day for 28 days in the following year. Semen was collected and evaluated by CASA immediately and either frozen or stored at 30 degrees Celsius or 5 degrees Celsius before re-evaluation. RESULTS: Intermittent scrotal insulation caused falls in the percentage of motile, progressive and rapid sperm, as did freezing-thawing and storage at 30 degrees Celsius or 5 degrees Celsius. Motility characteristics (amplitude of lateral head displacement, mean path velocity, mean progressive velocity and curvilinear velocity), as determined by CASA fell only when the percentage of motile sperm was already reduced. Freezing and thawing or liquid storage of the semen from insulated rams caused a greater fall in the percentage of motile and rapid sperm than control semen, but only affected the motility characteristics when the percentage of motile sperm was already reduced. CONCLUSION: Intermittent scrotal insulation affected not only the motility of the freshly collected sperm, but also their ability to withstand the additional stress of storage. The additional data on motility characteristics obtained by CASA appeared to be no more a sensitive indicator than the percentage of motile cells of reductions in semen quality.

Surgical anatomy of the cervical sympathetic trunk.

Lack of knowledge of the anatomy of the cervical sympathetic trunk (CST) may complicate surgical procedures on the cervical spine. This study aims to define linear and angular relations of the CST with respect to consistent structures around it, including the number and size of the cervical ganglia, the distances between the CST and the longus colli muscle and the anterior tubercles of the transverse processes of cervical vertebrae. Morphometric parameters of the 24 CSTs of 12 adults were measured on both sides. The CST had superior, middle, and inferior (or cervicothoracic) ganglia in 20.8% of specimens; superior and inferior (or cervicothoracic) ganglia in 45.8%; superior, middle, vertebral, inferior, or cervicothoracic ganglia in 12.5%, and superior, vertebral, inferior or cervicothoracic ganglia in 20.8% of specimens. The superior ganglion was observed in all specimens, the middle ganglion and vertebral ganglion were each observed in 33.3%. There was no difference between the number of superior and vertebral ganglia between the right and left sides. The average distance between the CST and the medial border of the ipsilateral longus colli muscle (LCM) was 17.2 mm at C3 and 12.4 mm at C7. As the CSTs converged caudally, the LCMs diverged. The average distance between the anterior tubercles of transverse processes of the cervical vertebrae and the lateral borders of the ipsilateral CST was 3.4 mm at C4, 3.2 mm at C5, and 3.9 mm at C6. The presence of a vertebral ganglion and variations, such as the localization of the CST within the carotid sheath, are important. The anatomical landmarks described should assist the spinal surgeon to avoid injury of the CST.

Fetal development and gestational changes in Bos taurus and Bos indicus genotypes in the tropics.

Weights of the gravid uterus and fetus as well as the fetal measurements were determined at slaughter for 107 Bos taurus cows grazed on improved pastures and for 70 Bos indicus cows grazed on native pastures in northern Australia. The stage of gestation was assessed from palpation per rectum in early-to-mid gestation and at slaughter and from fetal development characteristics at slaughter. The age and breed of the cow and the sex of the fetus did not significantly affect any of the uterine components or fetal measurements. Growth curves had dominant, positive linear components but negative quadratic ones, which improved the fit, particularly for the later stages of gestation. Uterine components and fetal measurements were highly correlated (0.94 to 0.99). For Bos taurus cows, there were higher estimates at birth for weights of the gravid uterus and the fetus, but estimates for other fetal measurements were similar to those for Bos indicus cows. Major fetal growth occurred during the third trimester, with the length of the foreleg tending to change relatively slowly and the head width quite fast during the first trimester. Correction factors for cow liveweight to adjust to commonality for non-pregnancy were 5, 7, 10, 14, 20, 29, 43 and 65 kg for Bos taurus and 2, 4, 6, 10, 15, 23, 35 and 51 kg for Bos indicus at 2 to 9 months of gestation.

Cardiotonic effects of anthopleurin-A, a polypeptide from a sea anemone.

The positive inotropic effect of anthopleurin-A (AP-A) was studied in vitro on isolated cat heart papillary muscles and in vivo in anesthetized and conscious dogs. In vitro, in low Ca2+ solution (1.27 mM), AP-A increased the force of contractions of isolated cat heart papillary muscles at concentrations from 0.2 x 10(-8) M and higher; on a molar basis, AP-A was more than 200 times as potent as digoxin and on a weight basis, 33 times as potent. In vivo in anesthetized dogs, AP-A at 0.2 microgram/kg/min i.v. increased myocardial contractile force; the geometric mean dose of AP-A required to increase the contractile force by 25% was 2.6 micrograms/kg; the corresponding dose of digoxin (infused at 2.8 micrograms/kg/min) was 107.4 micrograms/kg. The geometric mean lethal dose of AP-A for 8 dogs was 19.3 and that of digoxin 263.2 micrograms/kg i.v. The therapeutic index of AP-A was significantly higher than that of digoxin. All animals that received either AP-A or digoxin died in ventricular fibrillation. The reversal of t-wave was typical for AP-A. As measured by left ventricular pressure telemetry, AP-A, 2 micrograms/kg i.v. single dose, increased LV dp/dt max in conscious dogs for longer than 2 hr.

2-(Substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines as nonacidic antiinflammatory agents.

Some 2-(substituted phenyl)oxazolo[4,5-b]pyridines and 2-(substituted phenyl)oxazolo[5,4-b]pyridines have good antiinflammatory and analgesic activity. A few possess activity comparable to phenylbutazone or indomethacin without producing the irritation in the gastrointestinal tract that acidic antiinflammatory compounds cause.

Biologically active derivatives of fatty acids: prostaglandins, thromboxanes, and endoperoxides.

The causal role assigned to the E and F prostaglandins in inflammatory processes, implied by the antiinflammatory action of prostaglandin synthetase inhibitors, is not consistent with the findings reported here that a compound (MK-447) capable of increasing levels of these prostaglandins is antiinflammatory in classical animal models of acute inflammation. That both MK-447 and prostaglandin synthetase inhibitors depress the enzymatic formation of PGG2 from arachidonic acid suggests that this endoperoxide plays a pivotal role in acute inflammation. However, in view of the intermediate nature of PGG2, it seems likely that such a pivotal role for this substance is a function of its ability to be converted to other inflammatory mediators. Possible candidates for a causal role are thromboxane A2 (TXA2) prostacyclin (PGI2), both of which derive from PGG2. However, direct evidence is presented to show that an oxygen equivalent released in the enzymatic conversion of PGG2 to PGH2 is a prime factor in inflammation.

Identification of the biologically active form of sulindac.

In five animal species, the only quantitatively significant biotransformations undergone by cis-5-fluoro-2-methyl-1-[p-(methylsulfinyl) benzylidene]indene-3-acetic acid (sulindac) are oxidation of its sulfinyl substituent to sulfone, and reduction to sulfide. The former metabolite is eliminated unchanged and elicits no pharmacological response. The sulfide, on the other hand, is readily reoxidized in vivo to sulindac. In each of seven in vivo models of inflammation, sulfide administered as such is more active than sulindac. The inference that the activity of sulindac might be attributed in whole or in part to the sulfide was tested directly by comparison of responses with concentrations of each reduction oxidation species in appropriate biological fluids. Regression analyses of circulation levels of sunlindac and sulfide vs. inhibition of rat paw edema, and of their levels in synovial fluid vs. response in the dog knee joint assay, show highly significant correlations only for sulfide. Sulindac thus appears to be a "latentiated" or "pro-drug," oral dosage with chich may circumvent the gastrointestinal side effects commonly associated with nonsteriod anti-inflammatory agents.