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Mollusks have been widely investigated for antimicrobial peptides because their humoral defense against pathogens is mainly based on these small biomolecules. In this report, we describe the identification of three novel antimicrobial peptides from the marine mollusk Nerita versicolor. A pool of N. versicolor peptides was analyzed with nanoLC-ESI-MS-MS technology, and three potential antimicrobial peptides (Nv-p1, Nv-p2 and Nv-p3) were identified with bioinformatical predictions and selected for chemical synthesis and evaluation of their biological activity. Database searches showed that two of them show partial identity to histone H4 peptide fragments from other invertebrate species. Structural predictions revealed that they all adopt a random coil structure even when placed near a lipid bilayer patch. Nv-p1, Nv-p2 and Nv-p3 exhibited activity against Pseudomonas aeruginosa. The most active peptide was Nv-p3 with an inhibitory activity starting at 1.5 µg/mL in the radial diffusion assays. The peptides were ineffective against Klebsiella pneumoniae, Listeria monocytogenes and Mycobacterium tuberculosis. On the other hand, these peptides demonstrated effective antibiofilm action against Candida albicans, Candida parapsilosis and Candida auris but not against the planktonic cells. None of the peptides had significant toxicity on primary human macrophages and fetal lung fibroblasts at effective antimicrobial concentrations. Our results indicate that N. versicolor-derived peptides represent new AMP sequences and have the potential to be optimized and developed into antibiotic alternatives against bacterial and fungal infections.

Designing entirely new protein structures remains challenging because we do not fully understand the biophysical determinants of folding stability. Yet some protein folds are easier to design than others. Previous work identified the 43-residue □ββ□ fold as especially challenging: the best designs had only a 2% success rate, compared to 39-87% success for other simple folds (1). This suggested the □ββ□ fold would be a useful model system for gaining a deeper understanding of folding stability determinants and for testing new protein design methods. Here, we designed over ten thousand new □ββ□ proteins and found over three thousand of them to fold into stable structures using a high-throughput protease-based assay. Nuclear magnetic resonance, hydrogen-deuterium exchange, circular dichroism, deep mutational scanning, and scrambled sequence control experiments indicated that our stable designs fold into their designed □ββ□ structures with exceptional stability for their small size. Our large dataset enabled us to quantify the influence of universal stability determinants including nonpolar burial, helix capping, and buried unsatisfied polar atoms, as well as stability determinants unique to the □ββ□ topology. Our work demonstrates how large-scale design and test cycles can solve challenging design problems while illuminating the biophysical determinants of folding.SignificanceMost computationally designed proteins fail to fold into their designed structures. This low success rate is a major obstacle to expanding the applications of protein design. In previous work, we discovered a small protein fold that was paradoxically challenging to design (only a 2% success rate) even though the fold itself is very simple. Here, we used a recently developed high-throughput approach to comprehensively examine the design rules for this simple fold. By designing over ten thousand proteins and experimentally measuring their folding stability, we discovered the key biophysical properties that determine the stability of these designs. Our results illustrate general lessons for protein design and also demonstrate how high-throughput stability studies can quantify the importance of different biophysical forces.

We demonstrate the ability to perform fast ultraviolet photoacoustic remote sensing microscopy of tissue margins using a mosaic scanning approach where a camera-based system is used to determine scan coordinates within a 2-mm margin.

Host defense peptides (HDPs) exhibit a broad range of antimicrobial and immunomodulatory activities. In this sense, both functions are like different sides of the same coin. The direct antimicrobial side was discovered first, and widely studied for the development of anti-infective therapies. In contrast, the immunomodulatory side was recognized later and in the last 20 years the interest in this field has been continuously growing. Different to their antimicrobial activities, the immunomodulatory activities of host defense peptides are more effective in vivo. They offer a great opportunity for new therapeutic applications in the fields of anti-infective therapy, chronic inflammatory diseases treatment, novel vaccine adjuvants development and anticancer immunotherapy. These immune related functions of HDPs includes chemoattraction of leukocytes, modulation of inflammation, enhancement of antigen presentation and polarization of adaptive immune responses. Our attempt with this review is to make a careful evaluation of different aspects of the less explored, but attractive immunomodulatory side of the HDP functional coin.

Background The popularity and prevalence of electronic cigarette (EC) usage has continued to surge to 35 million worldwide, with one-half of users younger than 34 years. Despite emerging research suggesting deleterious oral health effects, the perceptions of EC users concerning oral health effects remain unknown. The purpose of this study was to explore knowledge, attitudes, and practices of young adults regarding the impact of EC use on oral health. Methods A cross-sectional survey used a validated tool to investigate vaping and oral health knowledge, attitudes, and practices among a convenience sample of EC users (N = 220). Outcomes were analyzed using descriptive and inferential statistics. Results People 18 through 24 years (N =168) indicated a lack of knowledge (mean [standard deviation {SD}], 2.9 [1.7]) and familiarity with oral health effects of vaping (mean [SD], 2.7 [1.7]). Participants expressed willingness to discuss oral health effects of vaping with dental care professionals (n = 111 [66%]), and most (n = 109 [65%]) would potentially reduce (30%) or quit (24%) if they believed it was harmful to their oral health. Participants 18 through 24 years were more likely to agree they would quit (n = 54 [68%]) than those 25 through 34 years (n = 36 [42%]; χ2 = 11.03; P = .004; φ = 0.26). Those who visit their dental care professional every 6 months (n = 82 [57%]) agreed they would quit vaping versus those who do not (n = 26 [37%]; χ2 = 9.84; P = .007; φ, 0.22). Conclusions Respondents reported low knowledge regarding the implications of vaping on oral health but expressed a willingness to discuss vaping with their dental care professionals. Practical Implications Most EC users are willing to accept guidance from dental care professionals regarding quitting use.

Although a history of lumbar spine fusion (LSF) is associated with increased dislocation risk following total hip arthroplasty (THA), the effect of LSF following THA is not well described. This study sought to describe the dislocation-free survival experience of patients with THA undergoing LSF, compare this to similar patients not undergoing LSF, and assess factors associated with dislocation risk following LSF.Center for Medicare Service billing data from 2005 to 2014 was analyzed utilizing the PearlDiver platform. Patients without evidence of hip instability, defined as no dislocation event within at least 6 months following THA, were identified and stratified by having subsequent LSF. Kaplan-Meier curves were used to describe dislocation-free survival of these groups and assess factors associated with dislocation.Among 17,223 patients without history of hip instability following THA, there was no spike in dislocations following LSF with patients having a persistent and stable rate of dislocation of 0.7% per year. This experience was of similar shape but increased hazard when compared to that of 863,182 patients not undergoing LSF who had a dislocation rate of 0.4% per year (P.001). Dislocations were not strongly associated with gender, age, comorbidities, or fusion length.Patients without evidence of hip instability following THA subsequently undergoing LSF do not have a spike in dislocations in the perioperative period but do assume a persistently elevated risk of dislocation. Future research should identify factors responsible for this increased risk to determine whether they may be modifiable.

Background Highly cross-linked polyethylene (XLPE) is reported to have low rates of linear and volumetric wear at 10-14 years. In a prior study, larger (36 and 40 mm) femoral heads were associated with more volumetric wear, but there were only 12 hips with these heads. Methods We evaluated 107 hips (93 patients, with a mean age of 76 years) with one design of uncemented acetabular component, a 36 (90 hips) or 40 mm (17 hips) metal femoral head, and one electron beam 100 kGy irradiated and remelted XLPE at a mean follow-up of 8 years (range 5-13 years). Selection of these femoral heads was based on several factors, including the perceived risk of dislocation, the outer diameter size of the acetabular component, and liner availability. Measurements of linear and volumetric wear were performed in one experienced laboratory by the Martell method and analyzed using the first-to-last method. Standard radiographs, with additional Judet views, were used to detect periprosthetic osteolysis. Clinical records were used to determine the complications of dislocation, liner fracture, and painful trunnion corrosion. Results For the entire cohort, the median linear wear rate was 0.041 mm/y (95% confidence interval, 0.031-0.057) and the median volumetric wear rate was 34.6 mm 3 /y (95% confidence interval, 31.4-53.5). With the numbers available, there was no difference in linear or volumetric wear between the 36 and 40 mm head sizes. Small, asymptomatic osteolytic lesions were noted in 3 hips (2%). There were 3 patients (3%) with dislocation (2 early and 1 late), but these have not had a revision. There were no revisions for loosening, no liner fracture, and no patient with symptomatic trunnion corrosion. Conclusion This acetabular component and XLPE with large metal heads had low rates of linear and volumetric wear. Large metal femoral heads did not lead to liner fracture, loosening, or symptomatic trunnion corrosion in this patient population. However, we recommend longer clinical follow-up studies and caution in the routine use of larger metal femoral heads in other, younger patient populations.

The mechanism of the oxidation of methanol on the surface of heat treated CeO2 nanoparticles was studied using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The study was carried out under high vacuum to ensure no interference from unreacted physisorbed methanol and compared to a similar analysis under pseudo-flow conditions. When methanol reacts with the CeO2 surface, it either chemisorbs to a single cerium atom creating monobound (m) methoxy or to two neighboring cerium atoms forming bridged (b) methoxy groups. From the evacuated analysis, formate production depends directly on the presence and transformation of b-methoxy groups. Hydroxyls are found to facilitate the formation of the two surface methoxy groups, react with m-methoxy groups creating additional b-methoxy groups, and enable the transformation of b-methoxy groups to bidentate formate groups. The reaction mechanism is elucidated through the use of temperature dependent peak height analysis of the collected DRIFTS spectra which are correlated to the transforming surface bound species.

Background Prostheses with varus-valgus constraint (VVC) are increasingly utilized in primary total knee arthroplasty (TKA) to address coronal malalignment and instability though little is known regarding the association between added constraint and aseptic loosening. We sought to systematically review the literature for reports of VVC in primary TKA and meta-analyze clinical results and implant survival. Methods PubMed was searched using broad terms to identify articles reporting VVC in primary TKA. Any article reporting clinical or survival outcomes was included. Clinical scores, close to 2 years postoperatively were converted to standardized mean differences, and the latest survival estimates were weighted using the inverse of their variance and meta-analyzed. Results Three hundred ninety-two search results were reviewed identifying 30 relevant articles reporting on 3620 knees in total. The estimate for the improvement in clinical scores postoperatively was 3.1 standard deviations (95% confidence interval 2.6-3.6). The estimate for implant revision slowly increased from 1% at 2 years to 2% at 6 years and then began to increase more rapidly beyond this point. The estimated revision rate was 9% by 12 years and 28% by 20 years. This revision rate estimate was stable with and without the inclusion of outlying studies. Conclusion VVC in primary TKA is associated with significant clinical improvement without significant risk of early failure. Meta-regression estimates raise concerns for significant revision risk with extended follow-up, especially beyond 5 years. In the absence of new data, VVC should continue to be used cautiously in the primary TKA.

Temperature control in buildings is usually driven by energy conservation although the occupants’ comfort is also important considering its impact on productivity and health. However, energy efficiency and comfort are opposing objectives and therefore this type of problem can be resolved by means of a multiobjective optimization approach. The simulations we carried out indicate that set points optimization has the potential to reduce energy consumption in the order of 10% while also providing a comfortable work environment for the occupants.

Background We report on the midterm linear and volumetric wear of highly cross-linked polyethylene (HXLPE) and survivorship of 2 prospective young total hip arthroplasty (THA) cohorts that differed by the size of ceramic femoral head used: 28 vs 32 mm. Methods We prospectively analyzed 220 consecutive primary THAs in patients aged ≤50 years who received a cementless THA with a ceramic femoral head on HXLPE liner (C-HXLPE). There were 101 patients (46%) with 28-mm heads and 119 patients (54%) who received 32-mm heads at a mean follow-up of 5.5 years (range, 60-109 months). Wear was calculated using Martell Software. Results The 28-mm C-HXLPE cohort demonstrated average linear and volumetric wear of 0.020 mm/y (standard deviation [SD], 0.074; 95% CI, 0.003-0.037) and 18.775 mm 3 /y (SD, 21.743; 95% CI, 13.773-23.778) compared with 0.032 mm/y (SD, 0.087; 95% CI, 0.013-0.050]) and 29.847 mm 3 /y (SD, 35.441; 95% CI, 22.294-37.401) in the 32-mm C-HXLPE group. Subgroup analysis by gender and head size discovered significantly greater wear in females with 32-mm heads compared with 28-mm heads in both linear (0.01, 95% CI = −0.014 to 0.033 vs 0.048, 95% CI = 0.022-0.074 mm/y, P = .004) and volumetric wear (14.11, 95% CI = 8.957-19.271] vs 29.71, 95% CI = 17.584-41.840] mm 3 /y, P = .009). We found a 96% (95% CI = 92.30%-97.94%]) survivorship by Kaplan-Meier analysis at minimum 5 years with no failures because of osteolysis. Conclusions Ceramic on HXLPE demonstrates extremely low wear properties in young patients at midterm follow-up. We identified a gender-dependent difference in wear based on head size, with 32-mm heads being associated with increased wear in females.

A systematic computational investigation of hydrogen abstraction by OH from the full series of fluorinated ethyl methyl ethers (EME) containing at least one H and one F, C2HnX5-nOCHmX3-m (n=0–5, m=0–3; and n=m=0 not allowed), including 147 reactants and 469 transition states, has been carried out, employing the MP2/6-31G(d) level of theory. Results for optimized geometries, including evidence of intramolecular hydrogen bonding in transition states, and barrier heights are presented. Trends pertaining to the number of fluorines substituted, key bond lengths, barrier heights, and key bond angles were found with good correlations and were investigated. An increase in the number of F increases the barrier height of the reaction. An increase in some parameters such as C–H length of TS, relative change in C–H from reactants to TS, ∠COC of reactants, ∠HOH in the TS, and relative change in ∠HOH between TS and free water bond angle also correlates with increased barrier height. An increase in other parameters like C–H length in the reactants and hydrogen bonding can decrease the barrier height.

Background Highly cross-linked polyethylene (HXLPE) is the most commonly used bearing surface in total hip arthroplasty (THA) because of its superior wear properties, but long-term results in young patients are limited. Mid-term survivorship has been promising; however, polyethylene wear rates and need for revision surgeries remain a concern in this population. The purpose of our study is to investigate polyethylene wear rates, implant survivorship, wear-related revisions, and patient-reported outcomes in a young patient cohort at 15-year follow-up. Methods We performed a retrospective study of a prospective longitudinal cohort of 82 consecutive patients (89 hips) who underwent primary THA with an HXLPE acetabular liner and a cobalt-chromium femoral head. The mean age at the time of surgery for the cohort was 38.8 years (range 12-50). All patients received HXLPE liners with a cementless acetabular component coupled with a cobalt-chrome femoral head through a posterior approach with a cementless femoral component. All components were from a single manufacturer. We recorded University of California, Los Angeles Activity, and modified Harris Hip Scores. Wear calculations were made using the Martell Hip Analysis Suite (Version 8.0.4.3). Results At average 15 years (range 13.1-18.5), there was a revision-free survivorship of 97.8% in our HXLPE group with no wear-related revisions. We observed a linear wear rate of 0.0185 mm/y (standard deviation 0.05) after accounting for a 1-year bedding-in period. The volumetric wear rate was found to be 12.80 mm3/y (standard deviation 22.69). These numbers are registered as clinically undetectable and are comparable to steady state wear rates in the same cohort of patients at earlier time points. We found no radiographic changes concerning osteolysis. We observed excellent patient-reported outcomes at this time point with improvements in modified Harris Hip Scores (35.3 [22.5], P Conclusion At 15-year follow-up, we demonstrated that HXLPE bearings in this young cohort had excellent wear properties, maintained superior clinical improvements, and underwent no wear-related revision operations. The HXLPE and cobalt-chrome bearing couple continues to be extremely effective 15 years after primary THA in patients less than 50 years. Level of Evidence IV.

Metabolic phenotype can be affected by multiple factors, including allelic variation and interactions with inhibitors. Human CYP2D6 is responsible for approximately 20% of cytochrome P450-mediated drug metabolism but consists of more than 100 known variants; several variants are commonly found in the population, whereas others are quite rare. Four CYP2D6 allelic variants-three with a series of mutations distal to the active site (*34, *17-2, *17-3) and one ultra-metabolizer with mutations near the active site (*53), along with reference *1 and an active site mutant of *1 (Thr309Ala)-were expressed, purified, and studied for interactions with the typical substrates dextromethorphan and bufuralol and the inactivator SCH 66712. We found that *34, *17-2, and *17-3 displayed reduced enzyme activity and NADPH coupling while producing the same metabolites as *1, suggesting a possible role for Arg296 in NADPH coupling. A higher-activity variant, *53, displayed similar NADPH coupling to *1 but was less susceptible to inactivation by SCH 66712. The Thr309Ala mutant showed similar activity to that of *1 but with greatly reduced NADPH coupling. Overall, these results suggest that kinetic and metabolic analysis of individual CYP2D6 variants is required to understand their possible contributions to variable drug response and the complexity of personalized medicine.

Background Total hip arthroplasty (THA) remains a successful procedure for most patients. However, there is a paucity of information regarding the long-term performance of conventional polyethylene (CPE) bearings in young patients undergoing THA. Methods After accounting for incomplete follow-up of a prospective cohort of 123 THAs in patients ≤50 years, we performed a retrospective review of 101 hips in 84 patients (82.1%) with an average 17.1-year follow-up (14.7-19.6 years). Outcomes of interest included linear and volumetric wear, clinical outcome scores, implant survivorship, and patient mortality. Wear rates were calculated using Martell Software. Results Wear analysis revealed median linear and volumetric wear rates of 0.106 mm/y (confidence interval, 0.079-0.133) and 43.58 mm3/y (confidence interval, 33.4-53.75). The modified Harris hip scores improved by 36 points while University of California, Los Angeles activity scores improved by 2.0 points at 15-year follow-up (P Conclusion Because CPE was commonly used in THA over the last 25 years, it is important to understand its implications on the growing revision burden. Significant concerns exist with regard to the long-term durability of CPE bearings in young, moderately active patients 15 years after THA. These patients should be followed closely for wear-related problems. Our results should be used as a comparison when evaluating the outcomes of more modern bearing surface combinations.

Patients 50 years or younger are at high risk for wear-related complications of their total hip arthroplasty (THA) because of their generally higher levels of activity. Highly crosslinked polyethylene (HXLPE) is believed to be more durable for this population than conventional polyethylene because of its improved wear; however, limited information is available on the wear of HXLPE in this population, particularly the wear of HXLPE when it articulates with alternative bearings like Oxinium (SmithNephew, Memphis, TN, USA).The purpose of this study was to evaluate two questions relative to this population of patients undergoing THA. First, what was the linear and volumetric wear rate of HXLPE in patients 50 years or younger at a minimum followup of 9 years and was osteolysis observed in any of these hips? Given the potential for damage to the Oxinium femoral head surface, was the wear of HXLPE in the patients with this material similar to the other bearings or was there accelerated or runaway wear that was visible in any of the patients?From November 1999 to April 2005, 105 THAs were performed in 95 patients 50 years of age or younger (mean, 42 years; range, 20-50 years). The mean body mass index was 30 kg/m(2) (range, 17-51 kg/m(2)).The mean followup was 12 years (range, 9-14 years). Two patients died, five patients (one bilateral) were lost to followup, and one hip was revised elsewhere for pain. The patients' information was not included in the study, which left 87 patients with 96 hips for analysis. Highly crosslinked polyethylene was the acetabular bearing for all of the hips. We analyzed the linear and volumetric wear of all of the hips using the Martell method. Eighty hips had the same diameter head (28 mm) allowing us to more accurately compare the different bearing materials. The type of femoral head used was related to our sequential use of materials beginning with cobalt chrome (14), ceramic (23) followed by Oxinium (43) in the hips with 28-mm heads. Although cobalt-chrome was used early in this study, our previous experience with ceramic on polyethylene encouraged us to use it as an alternative bearing. The Oxinium was used consecutively for the remaining hips.The mean wear of the HXLPE after 1 year of bedding-in (true linear wear)was 0.022 mm/year (95% confidence interval [CI], 0.015-0.030 mm/year). The mean volumetric wear of HXLPE after 1 year of bedding-in (true volumetric wear) was 9 mm(3)/year (95% CI, 4-14 mm(3)/year). None of the hip radiographs had evidence of loosening or osteolysis. Wear was not associated with femoral head material (p = 0.58 for linear wear/year versus head material and p = 0.52 for volumetric wear/year versus head material).In our study of patients 50 years of age or younger undergoing THA, the linear and volumetric wear rates of HXLPE were very low regardless of the bearing surface material. The laboratory concerns of Oxinium surface damage are serious but at this time we have not seen high wear of the HXLPE or osteolysis in this population.Level III, therapeutic study.

Although cemented all polyethylene (PE) cups have been routinely used in total hip arthroplasty for decades, no computer-assisted method for measurement of radiographic wear has ever been specifically validated for these implants. Using a validated hip phantom model, AP plain hip radiographs were obtained consecutively for eight simulated wear positions. A version of Martell's Hip Analysis Suite software dedicated to all polyethylene sockets was used by three different examiners of varied experience. Bias (mean, standard deviation and 95% confidence interval limit), repeatability (standard deviation and 95% limit) and reproducibility (standard deviation and 95% limit) for two-dimensional wear measurements were assessed, as recommended by the current ASTM guidelines. Using this protocol, the dedicated software showed an overall mean bias of 0.089 ± 0.060 mm (mean ± SD), and 0.118 mm for 95% CI limit. Repeatability (intra examiner) standard deviation and 95% limit were respectively 0.106 mm and 0.292 mm. Reproducibility (inter examiner) standard deviation and 95% limit were respectively 0.112 mm and 0.308 mm. Martell Hip Analysis for all PE cemented cups is a reliable and low-cost instrument in the assessment of wear, despite being less precise than its original version dedicated to cementless components. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???–???, 2015.

Background: A comprehensive evaluation of hip radiographs in the young adult with hip pain has become increasingly complex and time consuming. The interobserver reliability of manually performed measurements of femoroacetabular impingement, including the alpha angle, has been questioned. Methods to improve the reliability of a radiographic evaluation may increase the clinical utility of these parameters. Purpose: To determine the interobserver and intraobserver reliability of a computer-assisted radiographic analysis of the young adult hip in a clinically relevant setting. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A reliability study of a comprehensive computer-assisted radiographic evaluation was performed, which included 25 radiographic parameters of proximal femoral morphology, acetabular morphology, hip osteoarthritis, and pelvic tilt/rotation. Anteroposterior pelvis and 45° Dunn lateral radiographs of 70 consecutive patients undergoing hip preservation surgery were included. Each radiograph was analyzed by 4 experienced hip surgeons. The reliability of continuous measurements was analyzed using intraclass correlation coefficients (ICCs), while categorical parameters were analyzed using κ values and percentages of agreement. Results: The interobserver reliability of the parameters of proximal femoral morphology, acetabular morphology, and osteoarthritis was generally substantial to excellent. Parameters with lesser interobserver reliability included the alpha angle (ICC, 0.43), Tönnis osteoarthritis classification (κ = 0.22), and classification of pelvic tilt (using the coccyx or sacrococcygeal joint) (κ = 0.43 and 0.61, respectively). Conclusion: A computer-assisted analysis of young adult hip radiographs generally demonstrates substantial to excellent levels of interobserver reliability for most parameters. However, alpha angle measurements demonstrated only moderate interobserver reliability, despite excellent intraobserver reliability. Measurements of the joint space width appear to be significantly more reliable than the use of the Tönnis osteoarthritis classification in this population. The classification of pelvic tilt utilizing the coccyx or sacrococcygeal joint is only moderately reliable.

2-(Benzylthio)- N {pyridine-4-ylmethylidene}aniline was prepared by reaction of S -benzyl ortho -aminothiophenol with 4-pyridine carboxaldehyde and characterized by NMR, IR and Raman spectroscopy and mass spectrometry. The structure and the vibrational analysis of the series of 2-, 3-, and 4-pyridine derivatives was performed based on a comparative computational methodology study with the density functionals B3LYP and B3PW91 and the basis sets LanZ2DZ and 6-31++G(d,p). Comparison of computational results with single crystal X-ray diffraction results of 2-(benzylthio)- N {pyridine-3-ylmethylidene}aniline allowed the evaluation of structure predictions and confirmed B3PW91/6-31++G(d,p) as most accurate for structure determination of the four investigated levels of theories. B3LYP and B3PW91 with the LanL2DZ basis set consistently outperformed calculations for IR and Raman vibrational estimations when compared to level of theories using the 6-31++G(d,p) basis set. Application of scaling factors for IR and Raman frequency predictions showed excellent agreement with experimental values and supported the assignment of the major contributors of the vibration modes of the three pyridine pendant compounds. Overall, B3PW91/LanL2DZ level of theory showed best performance in accuracy and low computational cost for structural and vibrational analysis for the series of 2-(benzylthio)- N -{pyridinylmethylidene}anilines.

Two different reaction types for the photolysis of pyridoxine-aromatic ring-opening and photodissociation-have been studied in the Density Functional Theory (DFT) framework. Our results show that neither photolytic ring-opening, dehydroxymethylation, demethylation nor dehydroxylation from the aromatic ring can be induced spontaneously in UV-irradiated pyridoxine, due to the high barriers along the reaction coordinates in the excited states. However, the simultaneous dehydroxylation of the C4-bound hydroxymethyl group and dehydrogenation of the ring bound hydroxyl substituent, selectively generating ortho-quinone methide and water, does occur after UV exposure. The findings correlate very well with available experimental data. The geometries of pyridoxine, its various transition states and products are optimized in the ground and first excited states in vacuum within the TD-DFT formalism.

Geometries for five naphthalimide (NI) derivatives proposed as photoactive redox units in cancer treatment, have been optimized in the ground state, reduced and oxidized states using density functional theory (DFT) with the B3LYP hybrid functional and the 6-31G (d,p) basis set. The bond lengths of the N-[3-(dimethylamino)propyl]-1,8-naphthalimide derivative showed the most variation from the other four NI derivatives due to the nature of its substituent. An examination of atomic charges and spin densities shows in general that the ring carbons are most significant, except in the N-(propyl)-1,8-naphthalimide,3′-phosphoric acid derivative, where charges and densities are localized in the phosphate group. Single point energy calculations, both in vacuum and solution were performed for each NI derivative. The adiabatic and vertical electron affinities and ionization potentials are given for each of the NI derivatives in the ground state. The results suggest that none of the five NI derivatives studied can oxidize DNA nucleobases via direct electron transfer from the ground states, and that the dark toxicity of the compounds is thus most likely very low.

Periprosthetic osteolysis is a disease attributed to the body's reaction to fine polyethylene wear debris shed from total hip replacements. The purpose of this preliminary study was to investigate the ability of radiographic texture analysis (RTA) to characterize the trabecular texture patterns on pelvic images for osteolysis and normal total hip arthroplasty (THA) cases.Fourier-based and fractal-based texture features were calculated for a database of digitized radiographs from 202 THA cases, 70 of which developed osteolysis. The features were calculated from regions of interest selected at two time points: less than 1 month after surgery, and at the first clinical indication of osteolysis (or randomly selected follow-up time for normal cases). Receiver operating characteristic (ROC) analysis was used to compare feature performance at baseline and follow-up for osteolysis and normal cases.Separation between the RTA features for osteolysis and normal cases was negligible at baseline and increased substantially for the follow-up images. The directional Fourier-based feature provided the best separation with an A(z) value from ROC analysis of 0.75 for the follow-up images, in the task of distinguishing between normal and osteolytic cases.The results from this preliminary analysis indicate that qualitative changes in trabecular patterns from immediately after surgery to the eventual detection of osteolysis correspond to quantitative changes in RTA features. It therefore appears that RTA provides information that could potentially be useful to aid in the detection of this disease.

Periprosthetic osteolysis is one of the most serious long-term problems in total hip arthroplasty. It has been primarily attributed to the body's inflammatory response to submicron polyethylene particles worn from the hip implant, and it leads to bone loss and structural deterioration in the surrounding bone. It was previously demonstrated that radiographic texture analysis (RTA) has the ability to distinguish between osteolysis and normal cases at the time of clinical detection of the disease; however, that analysis did not take into account the changes in texture over time. The goal of this preliminary analysis, however, is to assess the ability of temporal radiographic texture analysis (tRTA) to distinguish between patients who develop osteolysis and normal cases. Two tRTA methods were used in the study: the RTA feature change from baseline at various follow-up intervals and the slope of the best-fit line to the RTA data series. These tRTA methods included Fourier-based and fractal-based features calculated from digitized images of 202 total hip replacement cases, including 70 that developed osteolysis. Results show that separation between the osteolysis and normal groups increased over time for the feature difference method, as the disease progressed, with area under the curve (AUC) values from receiver operating characteristic analysis of 0.65 to 0.72 at 15 years postsurgery. Separation for the slope method was also evident, with AUC values ranging from 0.65 to 0.76 for the task of distinguishing between osteolysis and normal cases. The results suggest that tRTA methods have the ability to measure changes in trabecular structure, and may be useful in the early detection of periprosthetic osteolysis.

Background Quantifying ideal component position for the acetabulum and stem during total hip arthroplasty (THA) has been described by many methods. A new imaging method using low-dose digital stereoradiography, the EOS imaging system, is a biplanar low-dose X-ray system that allows for 3-dimensional modeling of lower limbs and semiautomated measurement of pelvic parameters and implant alignment. Methods Twenty-five patients who underwent primary THA by a single surgeon between October 2014 and December 2014 were retrospectively selected. Only patients with unilateral THA without associated spine pathologies were included, totaling 16 right hips and 9 left hips. There were 8 men and 17 women in the cohort, with a mean age of 67 years (range, 53-82). Three individuals performed measurements of pelvic parameters and implant alignment on 3 separate occasions. An interclass correlation of >0.75 was accepted as evidence of excellent agreement and a confirmation of measurement reliability. Results Before reviewing patient radiographs, 4 pelvic phantom models were analyzed using the EOS 3-dimensional software to verify accuracy. All anatomic and implant measurements performed by the 3 independent reviewers showed interobserver and intraobserver agreement with interclass correlation >0.75. Conclusion Three-dimensional modeling of hip implants with the EOS imaging system is a reasonable option for the evaluation of component position after THA.

Highly cross-linked polyethylene (HXLPE) is the most commonly used bearing surface in total hip arthroplasty (THA) because of its superior wear properties, but long-term results in young patients are limited. We report on the clinical outcome, radiographic wear patterns and survivorship of 72 patients ≤50 years old who had a 28-millimeter cobalt-chromium femoral head on HXLPE acetabular liner. Mean and median true linear wear rates at average ten-year follow-up were 0.0104 and 0.01 mm per year ± 0.07 mm. Mean and median two-dimensional volumetric wear rates were 12.79 mm(3) and 5.834 mm(3) per year ± 26.1mm(3) as determined by Martell analysis. As a result of the minimal wear profile, there was no evidence of radiographic osteolysis and no wear-related revisions.

Highly crosslinked polyethylene (XLPE) was introduced to decrease periprosthetic osteolysis related to polyethylene wear, a major reason for revision of total hip arthroplasty. However, there are few reports of wear and osteolysis at 10 years postoperatively.(1) What are the linear and volumetric wear rates of XLPE at 10 to 14 years? (2) What is the relationship among linear wear, volumetric wear, and femoral head size? (3) What proportion of hips developed osteolysis and was there a relationship between osteolysis and femoral head size or polyethylene wear?We evaluated a previously reported cohort of 84 hips (72 patients) with one design of an uncemented acetabular component and one electron beam 10-kGy irradiated and remelted XLPE at a mean followup of 11 years (range, 10-14 years). The choice of femoral head size was based on several factors, including the outer diameter size of the acetabular component implanted, the perceived risk of dislocation (including the history of alcohol abuse and patient age), and liner availability from the manufacturer. The femoral head sizes used were 26 mm in 10 hips (12%), 28 mm in 31 hips (37%), 32 mm in 31 hips (37%), 36 mm in eight hips (10%), and 40 mm in four hips (5%). Measurements of linear and volumetric wear were performed in one experienced laboratory by the Martell method and analyzed using the first-to-last method. Standard radiographs, with additional Judet views, were used to detect periprosthetic osteolysis. Statistical analysis of wear and osteolysis compared with head size was performed.For the entire cohort, the median linear wear rate as 0.024 mm/year (95% confidence interval [CI], 0.016-0.030) and the median volumetric wear rate was 12.19 mm(3)/year (95% CI, 6.6-15.7). With the numbers available, we found no association between femoral head size and linear wear rate. However, larger femoral heads were associated with more volumetric wear; 36/40-mm femoral heads had higher volumetric wear (median 26.1; 95% CI, 11.3-47.1) than did 26-mm heads (median 3.1; 95% CI, 0.7-12.3), 28-mm heads (median 12.3; 95% CI, 3.0-19.3), and 32-mm heads (median 12.9; 95% CI, 6.6-16.8; p = 0.02). Small osteolytic lesions were noted in 12 hips (14%), but with the numbers available, there was no association with head size or volumetric wear rates.This uncemented acetabular component and this particular XLPE had low rates of linear and volumetric wear. Small osteolytic lesions were noted at 10 to 14 years but were not related to femoral head size or linear or volumetric wear rates. We recommend additional longer-term clinical followup studies and perhaps alternative imaging studies of patients with XLPE and osteolysis.Level III, therapeutic study.

We compared clinical outcomes and polyethylene wear for 2 young primary THA patient cohorts (3, p

Steady-state penetration rates were determined on 53 total hip arthroplasties with a minimum 3-year follow-up using electron beam highly cross-linked melted polyethylene by determining the femoral head penetration occurring after the first year in vivo. These data were compared with that of a matched control group. The average steady-state penetration rate of the control group was 144 ± 191 μ m/y, significantly higher than that of the highly cross-linked polyethylene group, 25 ± 99 μ m/y ( P = .0001). Linear regression analysis indicated that the magnitude of femoral head penetration did not increase with time in the cross-linked groups. Also, no significant difference existed between the steady-state wear rates of the highly cross-linked groups with two head sizes (28 vs 32 mm, P = .39).

UNLABELLED Radiostereometry has high precision and accuracy measuring polyethylene wear in total hip arthroplasty but requires a specialized setup. The Martell method is simpler and can be used on larger populations. The hypothesis that the radiostereometry analysis and the Martell analysis would yield comparable wear data from the same group of patients having total hip arthroplasty was tested. A group of twenty-five total hip arthroplasty patients who had both radiostereometry and standard anterior-posterior pelvic and cross-table lateral radiographs of sufficient quality for analysis were identified. The films were taken at postoperative periods of 6 weeks, 1 year, 2 years, and 5 years. Femoral head penetration was measured by both methods at each time point. The median penetration rates measured by each method decreased over time. Penetration results were affected by method of analysis, time, and dimension, with greater penetration for Martell compared with radiostereometry at each time point, greater penetration with increasing time for each method, and larger three-dimensional magnitude compared with two-dimensional analysis. LEVEL OF EVIDENCE Case series Level IV. See Guidelines for Authors for a complete description of levels of evidence.

Quantitative genetic studies frequently utilize inbred strains of animals as tools for partitioning the direct and indirect effects of genes from environmental effects in generating an observed phenotype, however, this approach is rarely applied to behavioral studies. Guppies, Poecilia reticulata, perform a set of anti-predator behaviors that may provide an ideal system to study how complex behavioral traits are generated. To assess the utility of ornamental guppies in quantitative genetics studies of behavior, we assayed five morphologically distinct strains of ornamental guppies for response to predator cues and for variation in response among strains. Despite individual variation, all five strains responded to predator cues and differences among strains were found for all assayed behaviors, including measures of boldness and predator avoidance.

BACKGROUND: Studies of acetabular reconstruction with use of cement and bulk bone graft have demonstrated increasing rates of cup failure in patients with dysplastic hips seven years after total hip arthroplasty. Comparable data on the long-term results of bulk bone-grafting done in conjunction with cementless implants are limited. The aim of this study was to review the clinical and radiographic results of autologous bulk bone-grafting in conjunction with a cementless cup. METHODS: From 1987 to 1992, forty-seven patients (forty women and seven men, with an average age of 50.4 years) who had developmental dysplasia of the hip underwent fifty-six total hip arthroplasties and received a structural graft in combination with a cementless Harris-Galante type-I cup. All patients were followed prospectively. In fifty-five hips, implant migration was measured with single-image radiographic analysis. RESULTS: After an average duration (and standard deviation) of 10.2 ± 2.9 years, three patients (four hips) had died. In the surviving patients, four implants had been revised and two had radiographic evidence of loosening. With use of revision and loosening as end points, the eleven-year survival rates were 91.6% and 88.9%, respectively. Of the fifty implants that had no loosening, fourteen had measurable cup migration, thirty-five had no migration, and one implant could not be measured. All migrations but one were progressive. With loosening used as the end point, the survival rate at eleven years was 100% for the implants with no migration; however, the survival rate for the cups that had migrated was 69.3% (p = 0.0012). CONCLUSIONS: The eleven-year survival rate for the spherical press-fit cups in combination with bulk bone-grafting is satisfactory, given the complexity of these reconstructions. However, the difference between the survival of the implants that had migrated and those that had not was significant. We expect that the thirteen implants with progressive acetabular migration at the time of the latest follow-up are at risk for loosening, which will increase the revision rate for this series in the coming years.

Due to the uneven and often inadequate quality of cross-table lateral hip radiographs, many radiographic studies of femoral head penetration into polyethylene in total hip arthroplasty are limited to the two-dimensional measurement of femoral head penetration using the A/P film only. We postulated that the use of two oblique frontal projections at 90 degrees to each other would improve the three-dimensional evaluation. Using an established hip phantom, the idealized accuracy and precision of the three-dimensional Martell method was evaluated, contrasting the standard A/P and cross-table lateral projections versus a pair of oblique projections by four independent readers. Accuracy and precision resulting from the use of two oblique projections (average accuracy +/-63 microm, precision +/-26 microm) were similar to that obtained using the conventional A/P and cross-table lateral views (accuracy +/-54 microm, precision +/-22 microm), though the results of the two oblique views were slightly more variable. These observations suggest that by using two oblique A/P projections, the major disadvantage of using the cross-table lateral films, namely the variable quality of the images, is avoided. Perhaps, therefore, the utility and availability of three-dimensional data in comparable clinical studies may be improved.

We report the 2-year results for a prospective randomized trial comparing highly cross-linked with standard polyethylene in total hip replacements. In our study, 46 hips were available for radiographic analysis at 2- and 3-year follow-up. Femoral bearings were 28-mm cobalt chrome with the polyethylene insert randomly selected at the time of implantation to be highly cross-linked polyethylene (Crossfire; Stryker Howmedica Osteonics, Allendale, NJ) or standard polyethylene (N(2)/Vac, Stryker Howmedica Osteonics). Polyethylene wear rates were measured based on anterior-posterior (AP) and lateral pelvis radiographs at 6 weeks and at yearly intervals using a validated computer-assisted edge-detection method. Wear rates between the 2 groups were compared using the nonparametric Mann-Whitney test at the 95% level. A significant reduction in 2- and 3-dimensional linear wear rates (42% and 50%) was found in the highly cross-linked group (P =.001 and P =.005).

The accurate determination of acetabular polyethylene wear in vivo is necessary to assess the clinical performance of the bearing surfaces of total hip replacements. Our objective in this study was to determine the clinical performance of two and three-dimensional computerized wear analysis and to assess the implications of this performance on requirements for patient enrollment in studies designed to detect wear of total hip prostheses.Two and three-dimensional digital computerized analyses of acetabular polyethylene wear were performed on 153 hips in 140 patients. The acetabular components consisted of a polyethylene insert in a titanium shell, articulating with a 28-mm cobalt-chromium femoral component. The average duration of radiographic follow-up was 8.4 years. The correlation coefficient for two-dimensional versus three-dimensional analysis was calculated, as was the difference between the wear detected by the two techniques. The same observer analyzed each image twice, allowing an assessment of the repeatability of the two-dimensional and three-dimensional analyses. The impact of the clinical performance of each technique on the sample size needed for adequate power in prospective studies was evaluated.There was a high correlation between two-dimensional and three-dimensional wear analysis (r (2) = 0.933). In thirty-one (5.2%) of 595 observations, the wear values derived with the two-dimensional and three-dimensional techniques were not consistent. Logistic regression demonstrated that acetabular anteversion had a significant effect on the likelihood of such inconsistency occurring. The two-dimensional technique detected 90.1% of the total linear wear subsequently detected by the three-dimensional analysis. The average wear value was 1.09 mm as detected by two-dimensional analysis and 1.21 mm as detected by three-dimensional analysis. The two-dimensional technique was four times more repeatable than the three-dimensional technique. Power analysis indicated that up to 1.4 times more patients need to be enrolled if the three-dimensional technique is used for wear analysis.While three-dimensional analysis detected 10% more wear, its repeatability was four times worse than that of the two-dimensional technique and, as a consequence, patient enrollment requirements for wear detection were higher. The poor quality of the lateral radiographs contributed to the decrease in the repeatability of the three-dimensional analysis. Three-dimensional analysis may be useful for highly anteverted cups, but the limited improvement in wear detection achieved with that technique, coupled with its inferior repeatability, limits its clinical value.

Density functional theory, DFT, and high-level conventional ab initio calculations, together with RRKM calculations, have been employed to study the nature of the transition state geometry for 1,2 elimination of HF from 1,1,1-trifluoroethane-d0,-d3; these serve as test cases for 1,2-HF elimination from fluorocarbons. Quantities calculated include structural parameters, bond indices, energies, atomic charges, vibrational frequencies, and moments of inertia for the reactant and the transition state geometry. The threshold energies for HF and DF elimination were computed and the vibrational frequencies and moments of inertia data were used with the RRKM theory to calculate the entropies of activation, preexponential factors for thermal activation, and also rate constants and the kinetic isotope effect for both thermally and chemically activated 1,1,1-trifluoroethane-d0,-d3. Of all the methods employed, the hybrid DFT methods incorporating either the three-parameter exchange functional of Becke with the corre...