Toward the interpretation of the combined effect of size and body weight on the tribological performance of total knee prostheses

Purpose

The research questions of the present study were: (1) Is total knee prosthesis wear behaviour influenced by implant size, body weight and their combined effect? (2) Are these findings significant and helpful from a clinical point of view?

Methods

Two very different sizes of the same total knee prosthesis (TKP), previously tested with ISO 14243 parameters, were tested on a knee simulator for a further two million cycles using a modified ISO 14243 load waveform. Roughness examination was performed on the metallic components. Gravimetric and micro-Raman spectroscopic analyses were carried out on the polyethylene inserts.

Results

The average volumetric mass loss was 69 ± 3 mm³ and 88 ± 4 mm³ for smaller and bigger size, respectively. Bigger TKPs are little influenced by an increased load, while the wear trend of the smaller TKP showed a redoubled slope, and more significant morphology changes were observed. However, the two sizes seem to behave similarly when subjected to a load increase of 15 %; the slope of the volumetric mass loss trend was comparable for the two sets of inserts, which did not appear significantly different also at the molecular level. Roughness average parameters of the lateral femoral condyle support this evidence.

Conclusions

It can be asserted that the body weight and implant size are relevant to the understanding of TKP wear behaviour. A post-implantation body weight increase in a patient with smaller knee dimensions could results in more critical effects on prosthesis long-term performance.     

Bone marrow derived stem cells in joint and bone diseases: a concise review

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients’ life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a “reservoir” of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called “stem cell niche” was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.     

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

Comparative modeling and ab initio multiconfigurational quantum chemistry are combined to investigate the reactivity of the human nonvisual photoreceptor melanopsin. It is found that both the thermal and photochemical isomerization of the melanopsin 11-cis retinal chromophore occur via a space-saving mechanism involving the unidirectional, counterclockwise twisting of the =C11H-C12H= moiety with respect to its Lys340-linked frame as proposed by Warshel for visual pigments [Warshel A (1976) Nature 260(5553):679–683]. A comparison with the mechanisms documented for vertebrate (bovine) and invertebrate (squid) visual photoreceptors shows that such a mechanism is not affected by the diversity of the three chromophore cavities. Despite such invariance, trajectory computations indicate that although all receptors display less than 100 fs excited state dynamics, human melanopsin decays from the excited state ∼40 fs earlier than bovine rhodopsin. Some diversity is also found in the energy barriers controlling thermal isomerization. Human melanopsin features the highest computed barrier which appears to be ∼2.5 kcal mol⁻¹ higher than that of bovine rhodopsin. When assuming the validity of both the reaction speed/quantum yield correlation discussed by Warshel, Mathies and coworkers [Weiss RM, Warshel A (1979) J Am Chem Soc 101:6131–6133; Schoenlein RW, Peteanu LA, Mathies RA, Shank CV (1991) Science 254(5030):412–415] and of a relationship between thermal isomerization rate and thermal activation of the photocycle, melanopsin turns out to be a highly sensitive pigment consistent with the low number of melanopsin-containing cells found in the retina and with the extraretina location of melanopsin in nonmammalian vertebrates.For a long time it was assumed that the human retina contains only two types of photoreceptor cells: the rods and cones responsible for dim-light and daylight vision, respectively. However, recent studies have revealed the existence of a small number of intrinsically photosensitive retinal ganglion cells (ipRGCs) that regulate nonvisual photoresponses (1). ipRGCs express an atypical opsin-like protein named melanopsin (2, 3) which plays a role in the regulation of unconscious visual reflexes and in the synchronization of endogenous physiological responses to the dawn/dusk cycle (circadian rhythms) (4, 5).Melanopsins are unique among vertebrate photoreceptors because their amino acid sequence shares greater similarity to invertebrate than vertebrate rhodopsin (i.e., the photoreceptor of rods) (6, 7). Like rhodopsins, melanopsins feature an up–down bundle architecture of seven transmembrane α-helices incorporating the 11-cis isomer of retinal as a covalently bound protonated Schiff base (PSB11 in Fig. 1A). Light-induced (i.e., photochemical) isomerization of PSB11 to its all-trans isomer (PSBAT) triggers an opsin conformational change that, ultimately, activates the receptor and signaling cascade (8, 9). However, similar to invertebrate and in contrast to vertebrate rhodopsins, melanopsins are bistable (10). Indeed, although vertebrate rhodopsins need a retinoid cycle (11) to regenerate PSB11, melanopsins have an intrinsic light-driven chromophore regeneration function via PSBAT back-isomerization. Furthermore, past studies have shown that melanopsins use an invertebrate-like signal transduction cascade (12).Open in a separate windowFig. 1.PSB11 chromophore reactivity. (A) Chromophore structure and isomerization to PSBAT. (B) Schematic representation of the photochemical (full arrows) and thermal (dashed arrows) isomerization paths. The CI is located energetically above the TS, features a different geometrical structure, and drives a far-from-equilibrium process. ΔE_S1-S0, τ_cis→trans, and Ea^T (in red) are the fundamental quantities computed in the present work.Melanopsins are held responsible for photoentrainment, using the changes of irradiance and spectral composition to adjust the circadian rhythm (13). The different studies carried out so far on melanopsin light sensitivity do not lead to consistent results. Although Do et al. (14) argue that ipRGCs work at extremely low irradiation intensities showing a single-photon response larger than rods, Ferrer et al. (15) conclude that the melanopsin has a reduced sensitivity relative to visual pigments. On the other hand, these photoreceptors would be expected to display high light sensitivity (14). In the vertebrate retina their density is 10⁴ times lower than that of rhodopsins. Moreover, the receptor is not confined in a dedicated cellular domain such as the outer segment of rods and cones, resulting in a ipRGCs photon capture more than 10⁶-fold lower than that of rods and cones per unit of retina illumination. A high sensitivity of melanopsins would also be consistent with their presence in extraretina locations such as in pineal complex, deep brain, and derma of nonmammalian vertebrates (e.g., amphibian) (16–18). The amount of light that can penetrate into such regions is limited and enriched in the red component due to light scattering by the surrounding tissues (14).The molecular-level understanding of the primary light response of melanopsin is a prerequisite for the comprehension of more complex properties such as its activation and sensitivity. Despite numerous studies carried out since its discovery (16), there is presently little information on the molecular mechanism of melanopsin activation. The common PSB11 chromophore of melanopsins and rhodopsins does not guarantee that the same mechanism operates in both photoreceptors. This not only concerns light-induced activation but also thermal activation: a process whose rate limits the photoreceptor light sensitivity and that is currently associated with thermal, rather than photochemical, PSB11 isomerization (19–24).The mechanism of light-induced PSB11 isomerization in vertebrate rhodopsins has been extensively investigated. Spectroscopic studies have shown that in bovine rhodopsin (Rh) the isomerization occurs on a subpicosecond timescale (25–27). Moreover, the observation of ground state (S₀) vibrational coherence (28) is consistent with a direct transfer of the excited state (S₁) population to the photoproduct (Fig. 1B) passing through a conical intersection (CI). Such a path has been located along the S₁ potential energy surface by constructing a multiconfigurational quantum chemistry (MCQC) based computer model of the photoreceptor (29–31) and spectroscopically supported by probing in the infrared (31). More recently (32), the same computer model has been used to map the Rh thermal isomerization path (Fig. 1B) providing information on the transition states controlling the reaction.Here we present a computational study focusing on the mechanism of photochemical and thermal isomerization of human melanopsin (hMeOp). This would require the construction of a computer model of hMeOp starting from the receptor crystal structure. However, the lack of hMeOp crystallographic data does not allow the use of the protocol previously applied in Rh studies. The significant sequence similarity between squid rhodopsin (sqRh), whose crystal structure is available (PDB code: 2Z73) (33), and hMeOp (40%, SI Appendix, Fig. S1) provides the fundamentals for constructing a structural model of hMeOp at a significant atomic resolution. Building on a study by Batista and coworkers (34) on murine melanopsin, we combine comparative modeling of hMeOp with MCQC to construct a quantum mechanics/molecular mechanics (QM/MM) computer model capable of simulating the photochemical and thermal isomerization reactions of hMeOp. The results are then compared with those found using Rh and sqRh models constructed using the same protocol. Such a comparison is expected to provide information on the differences in spectral and functional properties of these evolutionary distant pigments. As we will show below, the models indicate that hMeOp has a faster photochemical isomerization dynamics and a higher thermal isomerization barrier than both Rh and sqRh.     

Bactericide effect of methylene blue associated with low-level laser therapy in <Emphasis Type="Italic">Escherichia coli</Emphasis> bacteria isolated from pressure ulcers

The present study analyzed the bactericidal effect of methylene blue associated with low-level lasers on Escherichia coli isolated from a pressure ulcer. Microbiological material from a pressure ulcer was isolated using an aseptic swab, and antimicrobial activity was verified using the diffusion disc method. Methylene blue was used at concentrations of 0.001 and 0.005%, and low-level lasers of 670, 830, and 904 nm, with the energy densities of 4, 8, 10, and 14 J/cm², were tested on three plates each and combined with methylene blue of each concentration. In addition, three control plates were used, with each concentration and energy density separated without any interventions. The results were analyzed using the paired sample t test to determine the bactericidal effect of the methylene blue and using the ANOVA test to compare the effects of the energy densities and wavelengths among the low-level laser treatment protocols. The results showed bacterial reduction at wavelengths of 830 and 904 nm and more proliferation in wavelengths of 670 nm. In wavelength of 830 nm, a bacterial reduction was observed in the conditions with 0.001% methylene blue in all energy density utilized, with 0.005% methylene blue in energy density of 10 J/cm², and without methylene blue in energy density at 10 J/cm². And in a wavelength of 904 nm, all condition showed bacterial reduction with or without methylene blue. We concluded that the low-level lasers of 904 and 830 nm have bactericidal effects and at better energy densities (10 and 14 J/cm²).     

Health-related quality of life and cost-effectiveness analysis of gum chewing in patients undergoing colorectal surgery: results of a randomized controlled trial

Background: Postoperative ileus (POI) and anastomotic leakage (AL) following colorectal surgery severely increase healthcare costs and decrease quality of life. This study evaluates the effects of reducing POI and AL via perioperative gum chewing compared to placebo (control) on in-hospital costs, health-related quality of life (HRQoL), and assesses cost-effectiveness.

Methods: In patients undergoing elective, open colorectal surgery, changes in HRQoL were assessed using EORTC-QLQ-C30 questionnaires and costs were estimated from a hospital perspective. Incremental cost-effectiveness ratios were estimated.

Results: In 112 patients, mean costs for ward stay were significantly lower in the gum chewing group when compared to control (€3522 (95% CI €3034–€4010) versus €4893 (95% CI €3843–€5942), respectively, p?=?.020). No differences were observed in mean overall in-hospital costs, or in mean change in any of the HRQoL scores or utilities. Gum chewing was dominant (less costly and more effective) compared to the control in more than 50% of the simulations for both POI and AL.

Conclusion: Reducing POI and AL via gum chewing reduced costs for ward stay, but did not affect overall in-hospital costs, HRQoL, or mapped utilities. More studies with adequate sample sizes using validated questionnaires at standardized time points are needed.