Reactive Oxygen Species, Electrode Potential and pH Affect CoCrMo Alloy Corrosion and Semiconducting Behavior in Simulated Inflammatory Environments.

Crevice corrosion in modular taper junctions of hip or knee replacements using cobalt-chrome-molybdenum (CoCrMo) alloys remains a clinical concern. Non-mechanically-driven corrosion has been less explored compared to mechanically assisted crevice corrosion. This study hypothesized that solution chemistry within crevices, inflammation, and cathodic electrode potential shifts during fretting result in low pH and generate reactive oxygen species (ROS), affecting oxide film behavior. This study investigated how resistance and capacitance of the CoCrMo oxide film (i.e., corrosion resistance) are modified in simulated in vivo crevice environments of modular taper junctions. Six solutions were evaluated (two pH levels: 1 and 7.4 and four hydrogen peroxide (H2O2) concentrations: 0, 0.001, 0.01 and 0.1 M). Rp versus voltage and Mott-Schottky plots were created from symmetry-based electrochemical impedance spectroscopy (sbEIS). At pH 1, the semiconductor transition to p-type occurs at more anodic potentials and higher flat band potentials were found. H2O2 decreased the flat band potential and slope in the Mott-Schottky plot. Higher H2O2 in pH 7.4 solution significantly modified the oxide film, leading to increased donor density (p = 0.0004) and a 150-fold reduction in Rp in the cathodic potential range at -1 V (p = 0.0005). The most unfavorable condition (0.1 M H2O2 pH 1) resulted in a 250-fold lower resistance compared to phosphate buffered saline (PBS) pH 7.4 at -1 V (p = 0.0013). This study highlights the corrosion susceptibility of CoCrMo under adverse chemical and potential conditions, identifying increased defects in the oxide film due to ROS, hydrogen ions and electrode potential. STATEMENT OF SIGNIFICANCE: : Corrosion of cobalt chrome molybdenum alloy caused by direct chemical attack in the crevice region of hip replacements, such as modular taper junctions, remains a clinical concern. The junction environment contains adverse chemical compositions, including high acidity and reactive oxygen species (ROS) due to inflammatory responses against the corrosion products. We simulate inflammatory environments with different pH levels and hydrogen peroxide, representative of ROS. We employ electrochemical impedance spectroscopy and apply stepwise voltage over the range induced by tribocorrosion processes. We relate the effect of adverse chemical components on corrosion and semiconducting behavior of the oxide film using Mott-Schottky analysis. This study shows how pH and ROS concentration compromises the oxide film potentially leading to non-mechanically induced corrosion.

What is known about the use of weight loss medication in women with overweight/obesity on fertility and reproductive health outcomes? A scoping review.

Pregnancy during or soon after treatment with weight loss medication, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is contraindicated due to potential teratogenicity. The aim of this scoping review is to investigate what is known about the use of weight loss medication in women of childbearing age in relation to reproductive health outcomes, focusing on the three medications licenced in the United Kingdom at the time of the search. A systematic search of studies that assessed reproductive health outcomes in women taking either orlistat, liraglutide or semaglutide was undertaken in July 2023 and updated in January 2024 across MEDLINE, Embase, CINAHL, Scopus, ClinicalTrials.gov, PROSPERO, Epistemonikos and OpenGrey. Studies focused on polycystic ovarian syndrome, diabetes or animals were excluded. Titles and abstracts were screened, and data from included articles were extracted. After removal of duplicates, 341 titles remained, of which 318 were excluded. Of the final 18 articles included, there were five interventional trials, one retrospective case-control study, six narrative reviews, two systematic reviews, three systematic review protocols and one registry protocol yet to start recruitment. All five interventional trials involved orlistat given preconceptionally, showing no improvement in live birth rate, despite improvement in reproductive hormone levels. There were no studies with primary data about GLP-1 RAs. There were no qualitative studies. There is an absence of primary data about the role of GLP-1 RAs on the reproductive health of women of childbearing age without polycystic ovarian syndrome. Future research should explore short- and long-term effects on reproductive health, pregnancy outcomes and experiences.

Glutamate is a key nutrient for Porphyromonas gingivalis growth and survival during intracellular autophagic life under nutritionally limited conditions.

Porphyromonas gingivalis survives in special autophagic vacuoles that serve as major replicative habitats in human primary gingival epithelial cells (GECs). As an asaccharolytic strict anaerobe, P. gingivalis is dependent on amino acids and peptides for nutrient sources. However, it is largely unknown as to P. gingivalis' metabolic processing under the nutritionally limited intracellular environments such the vacuoles, especially the preferred amino acids and associated-metabolic machineries. Here we elucidate that a Glutamate (Glu) catabolic enzyme, glutamate dehydrogenase (GdhA) is highly enriched in the isolated P. gingivalis -containing vacuoles. Interestingly, we found that P. gingivalis induces conversion of intracellular glutamine pool to Glu determined by analyses of the P. gingivalis- containing vacuoles and the whole infected-GECs. Critically, exogenous Glu-Glu dipeptide, a simple precursor of Glu, significantly increases the size of isolated intact P. gingivalis containing-vacuoles and live wild-type P. gingivalis numbers in GECs. In contrast, the isogenic GdhA-deficient-strain, Δ gdhA displayed a significant growth defect with collapsed-vacuoles in GECs. Next, we confirmed that P. gingivalis uptakes 14 C-Glu and it preferentially utilizes Glu-Glu-dipeptide using a nutritionally reduced Tryptic-Soy-Broth (TSB) media supplemented with Glu-Glu. Contrary, Δ gdhA -strain showed no detectable growth especially in nutritionally reduced TSB media with Glu-Glu. Using Atomic-Force-Microscopy, we observed that, wild-type P. gingivalis but not Δ gdhA strain notably increased the cell volume upon Glu-Glu supplementation, an indicator of higher metabolism and growth. Utilization of a human gingiva-mimicking organoid-system further validated the importance of Glu as an essential nutrient for the intramucosal colonization of P. gingivalis via the protected replicative vacuoles in GECs. Importance: This study reveals that P. gingivalis heavily depends on preferential utilization of Glutamate (Glu) for autophagic vacuolar growth and survival in human GECs. Several novel observations are made to support this: (i) GdhA of P. gingivalis is highly enriched in these vacuoles, (ii) P. gingivalis induces a large conversion of intracellular glutamine to Glu, (iii) size of vacuoles are significantly increased in the presence of Glu-Glu in P. gingivalis wild-type strain infection which is opposite in a Δ gdhA strain, (iv) P. gingivalis uptakes 14 C-Glu and preferentially utilizes Glu-Glu dipeptide, (v) similarly, wild-type strain shows growth increase in a nutritionally reduced bacterial culture media, and (vi) finally, Glu-Glu supplementation increases bacterial cell-volume of P. gingivalis wild-type but not Δ gdhA strain, an indicator of higher metabolism and growth. Taken together, this study highlights the pathophysiological importance of Glu for P. gingivalis growth-rate, biomass induction and survival in nutritionally limited host subcellular environments.

Understanding the impacts of chronic pain on autistic adolescents and effective pain management: a reflexive thematic analysis adolescent-maternal dyadic study.

OBJECTIVE: Sensory elements are core features in chronic pain and autism, yet knowledge of the pain experience in autistic adolescents is limited. Little is known regarding how autistic adolescents experience chronic pain, manage their pain and perceive psychological treatment for their chronic pain. METHODS: Ten autistic adolescents (6 female, 3 male, and 1 self-identified as agender) with chronic pain and their mothers (n = 10) participated in semistructured interviews concerning their perceptions of living with chronic pain. Participants were recruited from U.K. pain management services. According to preference, interviews were conducted individually (n = 10) or dyadically (n = 10 participants across 5 dyads). Data were analyzed using inductive reflexive thematic analysis. RESULTS: Two themes were generated. Theme 1, "overstimulated and striving for control" described how adolescents' experience of heightened sensitivity enhanced adolescents' levels of anxiety and subsequent pain, illustrating a reciprocal relationship between anxiety, pain, and sensory elements. Theme 2, "not everyone fits the mold" captured how autistic adolescents positioned themselves as distinct from others due to the unique nature of being autistic and living with pain. This sense of difference negatively impacted adolescents' ability to engage with and benefit from the standard treatment for chronic pain. CONCLUSIONS: Findings suggest that autistic adolescents living with pain experience pain and face barriers to effective pain treatment. Our results identify the need for educational resources to facilitate clinicians to better understand the experience of autistic adolescents living with pain. In turn, such understanding may improve treatment and outcomes in this population.

Increasing temperature accelerates Ti-6Al-4V oxide degradation and selective dissolution: An Arrhenius-based analysis.

Ti-6Al-4V selective dissolution occurs in vivo on orthopedic implants as the leading edge of a pitting corrosion attack. A gap persists in our fundamental understanding of selective dissolution and pre-clinical tests fail to reproduce this damage. While CoCrMo clinical use decreases, Ti-6Al-4V and the crevice geometries where corrosion can occur remain ubiquitous in implant design. Additionally, most additively manufactured devices cleared by the FDA use Ti-6Al-4V. Accelerated preclinical testing, therefore, would aid in the evaluation of new titanium devices and biomaterials. In this study, using temperature, we (1) developed an accelerated pre-clinical methodology to rapidly induce dissolution and (2) investigated the structure-property relationship between the dissolving surface and the oxide layer. We hypothesized that solution temperature and H2O2 concentration would accelerate oxide degradation, increase corrosion kinetics and decrease experimental times. To assess this effect, we selected temperatures above (45 °C), below (24 °C), and at (37 °C) physiological levels. Then, we acquired electrochemical impedance spectra during active ß dissolution, showing significant decreases in oxide polarization resistance (Rp) both over time (p = 0.000) and as temperature increased (p = 0.000). Next, using the impedance response as a guide, we quantified the extent of selective dissolution in scanning electron micrographs. As the temperature increased, the corrosion rate increased in an Arrhenius-dependent manner. Last, we identified three surface classes as the oxide properties changed: undissolved, transition and dissolved. These results indicate a concentration and temperature dependent structure-property relationship between the solution, the protective oxide film, and the substrate alloy. Additionally, we show how supraphysiological temperatures induce structurally similar dissolution to tests run at 37 °C in less experimental time. STATEMENT OF SIGNIFICANCE: Within modular taper junctions of total hip replacement systems, retrieval studies document severe corrosion including Ti-6AL-4V selective dissolution. Current pre-clinical tests and ASTM standards fail to reproduce this damage, preventing accurate screening of titanium-based biomaterials and implant designs. In this study, we induce selective dissolution using accelerated temperatures. Building off previous work, we use electrochemical impedance spectroscopy to rapidly monitor the oxide film during dissolution. We elucidate components of the dissolution mechanism, where oxide degradation precedes pit nucleation within the ß phase. Using an Arrhenius approach, we relate these accelerated testing conditions to more physiologically relevant solution concentrations. In total, this study shows the importance of including adverse electrochemical events like cathodic activation and inflammatory species in pre-clinical testing.

Fretting and Fretting Corrosion Behavior of Additively Manufactured Ti-6Al-4V and Ti-Nb-Zr Alloys in Air and Physiological Solutions.

Additive manufacturing (AM) of orthopedic implants has increased in recent years, providing benefits to surgeons, patients, and implant companies. Both traditional and new titanium alloys are under consideration for AM-manufactured implants. However, concerns remain about their wear and corrosion (tribocorrosion) performance. In this study, the effects of fretting corrosion were investigated on AM Ti-29Nb-21Zr (pre-alloyed and admixed) and AM Ti-6Al-4V with 1% nano yttria-stabilized zirconia (nYSZ). Low cycle (100 cycles, 3 Hz, 100 mN) fretting and fretting corrosion (potentiostatic, 0 V vs. Ag/AgCl) methods were used to compare these AM alloys to traditionally manufactured AM Ti-6Al-4V. Alloy and admixture surfaces were subjected to (1) fretting in the air (i.e., small-scale reciprocal sliding) and (2) fretting corrosion in phosphate-buffered saline (PBS) using a single diamond asperity (17 µm radius). Wear track depth measurements, fretting currents and scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS) analysis of oxide debris revealed that pre-alloyed AM Ti-29Nb-21Zr generally had greater wear depths after 100 cycles (4.67 +/- 0.55 µm dry and 5.78 +/- 0.83 µm in solution) and higher fretting currents (0.58 +/- 0.07 µA). A correlation (R2 = 0.67) was found between wear depth and the average fretting currents with different alloys located in different regions of the relationship. No statistically significant differences were observed in wear depth between in-air and in-PBS tests. However, significantly higher amounts of oxygen (measured by oxygen weight % by EDS analysis of the debris) were embedded within the wear track for tests performed in PBS compared to air for all samples except the ad-mixed Ti-29Nb-21Zr (p = 0.21). For traditional and AM Ti-6Al-4V, the wear track depths (dry fretting: 2.90 +/- 0.32 µm vs. 2.51 +/- 0.51 µm, respectively; fretting corrosion: 2.09 +/- 0.59 µm vs. 1.16 +/- 0.79 µm, respectively) and fretting current measurements (0.37 +/- 0.05 µA vs. 0.34 +/- 0.05 µA, respectively) showed no significant differences. The dominant wear deformation process was plastic deformation followed by cyclic extrusion of plate-like wear debris at the end of the stroke, resulting in ribbon-like extruded material for all alloys. While previous work documented improved corrosion resistance of Ti-29Nb-21Zr in simulated inflammatory solutions over Ti-6Al-4V, this work does not show similar improvements in the relative fretting corrosion resistance of these alloys compared to Ti-6Al-4V.