Exposure of individuals aged 18-44 years to personal care products in Beijing, China: Exposure profiles, possible influencing factors, and risk assessment.

Personal care products (PCPs) are a class of emerging pollutants that have attracted public concern owing to their harmful effects on humans and the environment. Biomonitoring data is valuable for insight the levels of PCPs in the human body and can be crucial for identifying potential health hazards. To gain a better understanding of timely exposure profiles and health risk of reproductive-age population to PCPs, we determined six parabens, six benzophenone-type ultraviolet filters, and three disinfectants in 256 urine samples collected from young adults aged 18-44 years in Beijing, China. The urinary levels of benzophenone-3 (BP-3) and 4-hydroxybenzophenone (4-OHBP) were significantly higher in summer compared to winter, suggesting these compounds have different seasonal usage patterns. Moreover, the total concentration of 15 PCPs in female was 430 ng/mL, approximately two times higher than that in male. P­chloro-m-xylenol (PCMX), as a new type of antibacterial agent, has the greatest level among all target analytes, indicating the increasingly use of this antibacterial alternative recently. Five potential influencing factors that lead to the elevated exposure level of PCPs were identified. Over 19% of the target population had a high hazard index value (greater than 1) which was attributed to exposure to propyl paraben (PrP), benzophenone-1 (BP-1), BP-3 and PCMX, indicating that PCPs may pose a relatively high exposure risk at environmental levels that should be a cause for concern.

Ultrasound-triggered piezoelectric polyetheretherketone with boosted osteogenesis via regulating Akt/GSK3ß/ß-catenin pathway.

Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3ß/ß-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.

Surface topography changes and wear resistance of different non-metallic telescopic crown attachment materials in implant retained overdenture (prospective comparative in vitro study).

BACKGROUND: The purpose of this study was to evaluate the effect of using different types of metallic and non-metallic telescopic crown attachment materials on wear resistance and surface tomography changes in implant-retained mandibular overdentures. MATERIALS AND METHODS: Completely edentulous mandibular epoxy models were fabricated, in which two implants were placed in the canine region and retained to the implants with three different material combinations used for the construction of telescopic attachments. Thirty-three identical mandibular overdentures were fabricated using the conventional standardized technique. The study groups were divided into three categories according to the material used for the construction of the secondary copings. The primary copings in all the study groups were constructed of PEEK, while the secondary coping in group I was PEEK, group II was ZrO2 and CoCr for group III. Primary copings were cemented on a ready-made abutment. Secondary copings were placed over the primary copings in the desired path of insertion, then picked up into the intaglio surface of the overdentures. A cyclic loading machine was used to apply repeated insertion-removal cycles simulating nearly 10 years of clinical use. Stereomicroscope with a built-in camera was used to monitor the reduction in width of the primary copings to evaluate the wear resistance of each material combination. RESULTS: There was highly statistically significant difference between the study groups after the application of 1.000, 5.000 and 10.000 cycles. The highest level of wear resistance was recorded for the PEEK/PEEK combination, whereas PEEK/ZrO2 and PEEK/CoCr showed no significant differences. CONCLUSIONS: Implant retained overdenture with PEEK-PEEK telescopic crown attachment is associated with the highest wear resistance among all the study groups. PEEK-PEEK combination may be the treatment of choice for fabrication of telescopic attachment in implant retained overdenture as it provides better resistance to wear. It offers the advantages for geriatric patients as it decreases the possibility for repeated repair and replacement of attachment, increase long-term patient satisfaction and shelf life of prosthesis.

Poly-Ether-Ether-Ketone versus dead-soft coaxial bonded retainers: a randomized clinical trial. Part 2: periodontal health and microbial biofilm assessment.

BACKGROUND: Retainers have the potential to detrimentally impact periodontal health and contribute to tooth decay. OBJECTIVES: To investigate periodontal health and bacterial biofilm related to Poly-Ether-Ether-Ketone (PEEK) fixed retainers as compared to Dead-soft coaxial fixed retainer (DSC). TRIAL DESIGN: A two-arm parallel groups single-centre randomized clinical trial. METHODS: The trial included patients whose orthodontic treatment was completed and required retainers. Participants were randomly assigned into two retainer groups: PEEK retainers, prepared by computer-aided design and manufacturing into 0.8 mm wire form, and DSC retainers. The objectives included assessing periodontal health through plaque accumulation index (PI), bleeding on probing (BOP), periodontal pocket depth (PPD), gingival index (GI), calculus index (CI), and alveolar bone height (ABH) assessment. Biofilm assessment involved bacteriological screening of aerobic, facultative anaerobic, mutans streptococci, and lactobacilli. The periodontal indices and microbiological screening as well as were assessed at the debonding stage (T0), 1-month (T1), 3-month (T3), and 6-month (T6) after the commencement of the trial, except for the ABH, which was recorded using periapical radiograph at T0 and T6. BLINDING: Single blinding of participants in addition to the bacteriological specialist. RESULTS: Initially, the trial enrolled 46 participants, aged between 12 and 28 years, and were randomly assigned to two groups, with 23 participants in each group. Subsequently, one participant withdrew from the trial, resulting in a total of 45 participants whose data were analysed. Assessment of the periodontal indices, excluding the CI (P = .480), revealed statistically but not clinically significant differences between groups after 6-month of retention (P = .016 of PI, P = .020 of BOP, P = .05 of PPD, and P = .01 of GI). There was slight plaque accumulation, normal PPD (approximately 1 mm), healthy to mild gingivitis with a GI of less than 1 and BOP was around 10%. Concerning the ABH, there was a noticeable reduction in its score after 6 months, particularly in the PEEK group, although the difference was not statistically significant (P = .102). Furthermore, the bacteriological viable count did not show any significant difference between the groups during the recall visits. HARMS: There have been no reported negative consequences. LIMITATIONS: Blinding the assessor of periodontal indices was not feasible due to the nature of the intervention. The trial follow-up duration was limited. CONCLUSIONS: Both the PEEK and DSC retainers have comparable impacts on periodontal health and bacterial accumulation and composition during the retention period. TRIAL REGISTRATION: NCT05557136.

The World's first 3D-printed PEEK cranial implant: a new horizon in precision and personalized neurosurgery.

Cranioplasty is a reconstructive neurosurgical procedure that fixes the cranial bone defects after the craniotomy for brain surgeries like tumours, aneurysms, arterio-venous malformations, subdural empyemas and hematomas. Personalized 3D-printed implants offer various advantages, including anatomical accuracy, functional restoration, time-sparing surgery, excellent cosmetic outcomes through their impeccable adjustment to cranial vault defects, and better clinical outcomes. PEEK has a meritorious profile in terms of high success rate, low complication rate, fracture resistance and low toxicity profile, high strength, high toughness, and excellent biocompatibility in cranioplasty. On the other hand, the need for more cost-effective yet ideal biomaterials must be met for nations and patients with financial constraints. Nevertheless, this additively manufactured 3D-printed cranial implant marks the dawn of a new era in precision and personalized neurosurgery.

Point-of-Care 3-Dimensional-Printed Polyetheretherketone Customized Implants for Cranioplastic Surgery of Large Skull Defects.

BACKGROUND AND OBJECTIVES: 3-Dimensional (3D) printing has become a common tool to aid implant molding for cranioplastic surgery of large skull defects. Until now, 3D printing of cranial implants itself has not been used, mainly because of medicolegal concerns. With a 3D printer developed for printing medical applications and with implant-grade polyetheretherketone (PEEK) filament available, we established a workflow (in compliance with medical device regulations) to 3D print cranial implants for cranioplastic surgery directly at the point of care (POC). Here, we describe the implementation of 3D printing these PEEK implants for cranioplastic surgery at our academic hospital. METHODS: A thorough design and 3D printing process, in accordance with local medical device regulations, was developed. Implants are digitally designed based upon pre- and post-craniectomy cranial computed tomography scans by trained 3D printing experts from the department of medical engineering at our institution. Implants are then produced on a medical 3D printer with implant-grade PEEK filament using the fused filament fabrication process. After postprocessing and steam sterilization, implantation for reconstruction of the skull can be performed. RESULTS: Cranioplastic surgery with a 3D-printed PEEK implant was performed at our institution in a patient with a large frontotemporoparietal skull defect after traumatic brain injury with consecutive decompressive craniectomy. No intra- or post-operative complications occurred. Postoperative cranial computed tomography scans showed perfect reconstruction of precraniectomy skull shape. The aesthetic result was promising and satisfactory to the patient. CONCLUSION: This novel 3D printing workflow enables the production of patient-specific cranial implants from PEEK, to reconstruct large skull defects directly at the POC in accordance with the European Medical Device Regulation. This marks an unprecedented technological and legal advancement, enabling the hospital infrastructure not only to deliver the cranioplastic surgery itself, but also additive manufacturing of the implant directly at the POC.

AB081. Experience using CFR-PEEK implants in metastatic and primary spine tumour surgery: a single centre retrospective study.

BACKGROUND: Titanium has been the conventional implant material of choice for fixation in both primary and metastatic spine tumour surgeries (MSTS). However, these implants result in artefact generation during post-operative computed tomography (CT) or magnetic resonance imaging (MRI), resulting in poor planning of radiotherapy (RT) and suboptimal tumour surveillance. Carbon fibre-reinforced polyetheretherketone (CFR-PEEK) implants have gained momentum for instrumentation in MSTS due to their radiolucent properties. This in turn does not sacrifice the biomechanical strength of the implants. In this study, we compared the peri-operative outcomes, post operative imaging artefacts and dosimetricdata of CFR-PEEK implants to titanium implants to asses for potential benefits in post-operative RT planning in patients who underwent MSTS. METHODS: This is a retrospective study involving 42 patients operated for MSTS. Patient-related data including demographics, tumour pathology, intra-operative data, functional outcome, and RT-related data were collected for both groups. All patients were followed-up post-operatively for a minimum of 2 years or until demise, whichever was earlier. RESULTS: In our study, 20 (47.6%) patients had CFR-PEEK implants, while 22 (52.4%) of patients had titanium implants used for MSTS. Both groups of patients had similar clinical outcomes for pain and overall survival predictability pre-operatively (P>0.05). Mean number of levels instrumented by titanium screws were 6.8±2.93, while for the CFR-PEEK screws were 4.07±1.05. Mean volume of artefact generated during post operative CT was 75.1±43.4 mm3 in titanium group and 13.3±14.2 mm3 in CFR-PEEK group (P=0.005). The mean time taken to contour the artefacts was 17.3±5.84 minutes in the titanium group, while the CFR-PEEK group took 9.60±7.17 minutes (P=0.049). CONCLUSIONS: Our study suggests that carbon fibre reinforced PEEK screws significantly reduce artefact generation and the time taken to contour them during post-operative RT planning, while delivering equivalent clinical and functional outcomes as compared to standard titanium implants.

Graphene oxide-decorated microporous sulfonated polyetheretherketone for guiding osteoporotic bone regeneration.

Recent studies have indicated that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an ideal therapeutic target for osteoporosis because it affects the differentiation of osteoblasts and osteoclasts. RNA sequencing utilizing multifunctional graphene oxide (GO) nanosheets revealed a correlation between GO nanomaterials and the NLRP3 inflammasome, as well as osteogenic genes in macrophages. This study aimed to construct a bone microenvironment-responsive multifunctional two-dimensional GO coating on the surface of microporous sulfonated polyetheretherketone (SPEEK) via polydopamine modification (SPEEK@PDA-GO). In vitro analysis showed that the SPEEK@PDA-GO implants weakened the STAT3-mediated NLRP3/caspase-1/IL-1ß signaling pathway in macrophages and subsequently prevented the formation of an extracellular inflammatory microenvironment, which is crucial for osteoclastogenesis. SPEEK@PDA-GO displayed significantly higher expression of M2 macrophage markers and osteogenic genes, indicating that the multifunctional GO nanosheets could facilitate bone regeneration via their immunomodulatory properties. The ability of SPEEK@PDA-GO to stimulate new bone formation and block bone loss caused by estrogen loss due to ovariectomy was also analyzed. The findings of this study offer valuable information on the possible involvement of the NLRP3 inflammasome in the interaction between the immune system and bone health in patients with osteoporosis.

Comparison between CFR-PEEK and titanium plate for proximal humeral fracture: A meta-analysis.

OBJECTIVES: The aim of the present meta-analysis was to compare the efficacy and safety of the carbon fiber-reinforced polyetheretherketone (CFR-PEEK) and titanium plate for the treatment of proximal humeral fractures (PHFs) from clinical comparative trials. MATERIALS AND METHODS: A comprehensive search of English databases was carried out, such as PubMed, Web of Science, ScienceDirect, Springer and Cochrane Library databases. The RevMan version 5.1 software was applied for statistical analysis, and the mean difference (MD) and risk difference (RD) as the combined variables, and "95%" as the confidence interval (CIs). RESULTS: One randomized-controlled trial and five retrospective controlled studies including 282 PHFs were considered eligible and finally included. Meta-analysis demonstrated that there were significant differences in Constant score (CS) (MD=9.23; 95% CI: 5.02, 13.44; p<0.0001), anterior elevation (MD=18.83; 95% CI: 6.27, 31.38; p=0.003), lateral elevation (MD=18.42; 95% CI: 3.64, 33.19; p=0.01) and adduction (MD=3.53; 95% CI: 0.22, 6.84; p=0.04). No significant differences were observed regarding Constant score compared to the contralateral shoulder, Oxford Shoulder Score, internal rotation, external rotation, screw perforation and cutout, varus/valgus malalignment, humeral head collapse/necrosis, implant removal, and revision surgery between the two groups. CONCLUSION: Compared to titanium plate, CFR-PEEK plate showed better Constant score, anterior elevation, lateral elevation and adduction in treating PHFs. The complications are comparable to those achieved with conventional titanium plates.

Association between percutaneous absorption of benzophenone-3 and N, N-diethyl-m-toluamide among the general adult population.

BACKGROUND: Multiple studies have confirmed the mutual enhancement of percutaneous permeation of benzophenone-3 (BP-3) and N,N-diethyl-m-toluamide (DEET), which are effective ingredients in sunscreen products and insect repellents, respectively. However, the association between percutaneous absorption of BP-3 and DEET in a large general adult population remains to be elucidated. METHODS: This cross-sectional study included US adults who had available data on urinary BP-3 and two DEET metabolites, 3-(diethylcarbamoyl) benzoic acid (DCBA) and 3-(ethylcarbamoyl) benzoic acid (ECBA), from the National Health and Nutrition Examination Survey (NHANES) conducted in 2015-2016. We conducted three weighted multivariable linear regression models to investigate the potential correlation between percutaneous absorption of BP-3 and DEET, along with trend tests, smooth curve fitting, and subgroup analysis to assess the robustness of the findings. RESULTS: Weighted multivariable linear logistic regression revealed a positive correlation between log10 BP-3 and log10 DCBA (ß = 0.1678, 95 % CI: 0.0970 to 0.2386) as well as log10 ECBA (ß = 0.1416, 95 % CI: 0.0707 to 0.2125), after adjusting for all covariates. After converting log10 BP-3 from a continuous variable to a categorical variable (quartiles), the trend tests showed that the results were stable (all P for trend < 0.05). Smoothed curve fitting demonstrated a linear positive correlation between log10 BP-3 and both log10 DCBA and log10 ECBA. In subgroup analyses, the positive correlation between BP-3 and DEET metabolites was more pronounced in participants who were male, middle-aged, non-Hispanic white, had a moderate PIR level and reported always or most of the time using sunscreen. CONCLUSIONS: Our findings revealed a statistically significant linear and positive correlation between the percutaneous absorption of BP-3 and DEET in the general adult population.

[Application of polyetheretherketone rod semi-rigid pedicle screw internal fixation in lumbar non-fusion surgery].

OBJECTIVE: To investigate the effect of Polyetheretherketone (PEEK) rod semi-rigid pedicle screw fixation system in lumbar spine non-fusion surgery. METHODS: A total of 74 patients with tow-level lumbar degenerative diseases who underwent surgery from March 2017 to December 2019 were divided into PEEK rod group and titanium rod group. In the PEEK rod group, there were 34 patients, including 13 males and 21 females, aged from 51 to 79 years old with an average of (62.4±6.8) years old;There were 1 patient of L1-L3 segments, 7 patients of L2-L4 segments, 20 patients of L3-L5 segments and 6 patients of L4-S1 segments. In the titanium rod group, there were 40 patients, including 17 males and 23 females, aged from 52 to 81 years old with an average of (65.2±7.3) years old;There were 3 patient of L1-L3 segments, 11 patients of L2-L4 segments, 19 patients of L3-L5 segments and 7 patients of L4-S1 segments. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage was recorded. The visual analogue scale (VAS) for low back pain and Oswestry disability index (ODI) were compared in preoperatively and postoperatively(3 months, 12 months and last follow-up) between two groups. The change of range of motion (ROM) was observed by flexion and extension x-ray of lumbar. RESULTS: All patients successfully completed the operation. The follow-up time ranged from 22 to 34 months with an average of(26.8±5.6) months. The operative time (142.2±44.7) min and intraoperative blood loss(166.5±67.4)ml in PEEK group were lower than those in titanium group [(160.7±57.3) min、(212.8±85.4) ml](P<0.05). There was no significant differences in postoperative drainage between the two groups (P>0.05). At the final follow-up visit, in PEEK group and titanium group VAS of low back pain[(0.8±0.4) points vs (1.0±0.5) points], VAS for leg pain [ (0.7±0.4) points vs (0.8±0.5) points] and ODI [(9.8±1.6)% vs (12.1±1.5)%] were compared with preoperative [ (5.8±1.1) points vs (6.0±1.1)points], [ (7.2±1.7) points vs (7.0±1.6) points], [(68.5±8.9)% vs(66.3±8.2)%] were significantly different(P<0.05). There was no significant difference in VAS scores between the two groups at each postoperative time point (P>0.05). At 3 months after surgery, there was no difference in ODI between the two groups (P>0.05). There were significant differences in ODI between PEEK group and titanium rod group at 12 months [(15.5±2.1)% vs (18.4±2.4)%] and at the last follow-up [(9.8±1.6)% vs (12.1±1.5)%] (P<0.05). The total range of motion (ROM) of lumbar decreased in both groups after surgery. At 12 months after surgery and the last follow-up, the PEEK group compared with the titanium rod group, the total range of motion of lumbar was statistically significant (P<0.05). The range of motion (ROM) of the fixed segments decreased in both groups after surgery. The ROM of the fixed segments in PEEK group decreased from (9.5±4.6)° to (4.1±1.9)° at the last follow-up (P<0.05), which in the titanium rod group was decreased from (9.8±4.3)°to (0.9±0.5)° at the last follow-up (P<0.05). The range of motion (ROM) of upper adjacent segment increased in both groups, there was statistical significance in the ROM of upper adjacent segment between the two groups at 12 months after surgery and the last follow-up, (P<0.05). There was no screw loosening and broken rods in both groups during the follow-up period. CONCLUSION: The PEEK rod semi-rigid pedicle screw internal fixation system used in lumbar non-fusion surgery can retain part of the mobility of the fixed segment, showing comparable short-term clinical efficacy to titanium rod fusion. PEEK rod semi-rigid pedicle screw internal fixation system is a feasible choice for the treatment of lumbar spine degenerative diseases, and its long-term efficacy needs further follow-up observation.

Bone healing under different lay-up configuration of carbon fiber-reinforced PEEK composite plates.

Secondary healing of fractured bones requires an application of an appropriate fixator. In general, steel or titanium devices are used mostly. However, in recent years, composite structures arise as an attractive alternative due to high strength to weight ratio and other advantages like, for example, radiolucency. According to Food and Drug Administration (FDA), the only unidirectionally reinforced composite allowed to be implanted in human bodies is carbon fiber (CF)-reinforced poly-ether-ether-ketone (PEEK). In this work, the healing process of long bone assembled with CF/PEEK plates with cross- and angle-ply lay-up configurations is studied in the framework of finite element method. The healing is simulated by making use of the mechanoregulation model basing on the Prendergast theory. Cells transformation is determined by the octahedral shear strain and interstitial fluid velocity. The process runs iteratively assuming single load cycle each day. The fracture is subjected to axial and transverse forces. In the computations, the Abaqus program is used. It is shown that the angle-ply lamination scheme of CF/PEEK composite seems to provide better conditions for the transformation of the soft callus into the bone tissue.

Polyetheretherketone split post and core for restoration of multirooted molar with insufficient dental tissue remnants by digital techniques: a case report and 3-year follow up.

BACKGROUND: Multi-rooted teeth with extensive dental defects often face challenges in stability and biomechanical failure. High-performance polymer PEEK materials, with properties closer to dentin, show promise in reducing stress concentration and preserving tooth structure. This report aimed to explore the use of a highly retentive polyetheretherketone (PEEK) for manufacturing custom-made split post and core for the restoration of grossly destroyed endodontically treated molars. CLINICAL CONSIDERATIONS: A 40-year-old female patient presented with complaints of loss of tooth substance in the posterior mandibular tooth. This case involved the digital design and fabrication of PEEK split post and core to restore multirooted molar with insufficient dental tissue remnants. The restorations were evaluated over a 3-year follow-up using the World Federation criteria (FDI). The restoration was clinically evaluated through intraoral examination, radiographic assessment, and subjective patient satisfaction, and was deemed clinically good according to FDI criteria. CONCLUSION: The outstanding mechanical properties of PEEK, coupled with the structure of the split post, provide an effective treatment option for weakened multirooted teeth. Simultaneously, the restoration configuration effectively addressed the challenge of varying postinsertion directions, and the interlocking mechanism between the primary and auxiliary posts enhanced the stability of the post and core.

Five years of radiographic evaluation for the peri-implant bone changes of all-on-four implant prostheses constructed from different framework materials using different digital construction techniques.

BACKGROUND: There is insufficient evidence recommending a framework material and a CAD/CAM manufacturing technique for mandibular implant-supported prostheses. The study objective was to evaluate the clinical application of different materials and construction techniques used for mandibular All-on-4 prosthesis on circumferential peri-implant bony changes after 5 years. METHODS: Thirty-six male patients with all-on-4 mandibular implant-supported prostheses were recalled and divided into three groups. Group PK (patients with frameworks milled from PEEK blocks), Group PSM (patients with frameworks milled from soft metal blocks), and Group SLM (patients with frameworks constructed with additive manufacturing; selective laser melting). The circumferential bone level on all implant faces was assessed with a CBCT. Two-way repeated measures ANOVA was used to compare vertical bone loss (VBL) and horizontal bone loss (HBL) between different groups, implant positions, and observation times followed by Tukey's multiple comparisons. RESULTS: For all observation times, there was a significant difference in VBL between groups for both anterior and posterior implants (P < .001). For anterior implants, group PSM showed the lowest VBL while group PK showed the highest for anterior and posterior implants. For all groups, HBL significantly increased after 5 years for both anterior and posterior implants (P < .001). For anterior implants, group PSM showed the highest HBL. For posterior implants, group PK and SLM showed the highest. CONCLUSION: Within the study's limitations, mandibular implant-supported fixed frameworks fabricated with either milling from PEEK or soft metal blocks, or additive manufacturing (laser melting technology) exhibited significant vertical and horizontal bone height changes after 5 years. CLINICAL TRIAL REGISTRY NUMBER: (NCT06071689) (11/10/2023).

Designing a Novel Temperature- and Noncanonical Amino Acid-Controlled Biological Logic Gate in Escherichia coli.

Genetic code expansion (GCE) is a powerful strategy that expands the genetic code of an organism for incorporating noncanonical amino acids into proteins using engineered tRNAs and aminoacyl-tRNA synthetases (aaRSs). While GCE has opened up new possibilities for synthetic biology, little is known about the potential side effects of exogenous aaRS/tRNA pairs. In this study, we investigated the impact of exogenous aaRS and amber suppressor tRNA on gene expression in Escherichia coli. We discovered that in DH10ß ΔcyaA, transformed with the F1RP/F2P two-hybrid system, the high consumption rate of cellular adenosine triphosphate by exogenous aaRS/tRNA at elevated temperatures induces temperature sensitivity in the expression of genes regulated by the cyclic AMP receptor protein (CRP). We harnessed this temperature sensitivity to create a novel biological AND gate in E. coli, responsive to both p-benzoylphenylalanine (BzF) and low temperature, using a BzF-dependent variant of E. coli chorismate mutase and split subunits of Bordetella pertussis adenylate cyclase. Our study provides new insights into the unexpected effects of exogenous aaRS/tRNA pairs and offers a new approach for constructing a biological logic gate.

Mandibular biomechanics rehabilitated with different prosthetic restorations under normal and impact loading scenarios.

BACKGROUND: Restorative treatment options for edentulous patients range from traditional dentures to fixed restorations. The proper selection of materials greatly influences the longevity and stability of fixed restorations. Most prosthetic parts are frequently fabricated from titanium. Ceramics (e.g. zirconia) and polymers (e.g. PEEK and BIOHPP) have recently been included in these fabrications. The mandibular movement produces complex patterns of stress and strain. Mandibular fractures may result from these stresses and strains exceeding the critical limits because of the impact force from falls or accidents. Therefore, it is necessary to evaluate the biomechanical behavior of the edentulous mandible with different restorations under different loading situations. OBJECTIVE: This study analyzes the biomechanical behavior of mandibles after four prosthetic restorations for rehabilitation under normal and impact loading scenarios. MATERIAL AND METHODS: The mandibular model was constructed with a fixed restoration, which was simulated using various materials (e.g. Titanium, Zirconia & BIOHPP), under frontal bite force, maximum intercuspation, and chin impact force. From the extraction of tensile and compressive stresses and strains, as well as the total deformation of mandible segments, the biomechanical behavior and clinical situations were studied. RESULTS: Under frontal bite, the anterior body exhibited the highest tensile (60.34 MPa) and compressive (108.81 MPa) stresses using restoration 4, while the condyles and angles had the lowest tensile (7.12 MPa) and compressive (12.67 MPa) stresses using restoration 3. Under maximum intercuspation, the highest tensile (40.02 MPa) and compressive (98.87 MPa) stresses were generated on the anterior body of the cortical bone using restoration 4. Additionally, the lowest tensile (7.7 MPa) and compressive (10.08 MPa) stresses were generated on the condyles and angles, respectively, using restoration 3. Under chin impact, the highest tensile (374.57 MPa) and compressive (387.3 MPa) stresses were generated on the anterior body using restoration 4. Additionally, the lowest tensile (0.65 MPa) and compressive (0.57 MPa) stresses were generated on the coronoid processes using restoration 3. For all loading scenarios, the anterior body of the mandible had the highest stress and strain values compared with the other segments. Compared to the traditional titanium restoration.2, restoration.1(zirconia) increases the tensile and compressive stresses and strains on the mandibular segments, in contrast to restoration.3 (BIOHPP). In addition, zirconia implants exhibited higher displacements than the other implants. CONCLUSION: In the normal loading scenario, the tensile and compressive stresses and strains on the mandible were within the allowable limits when all restorations were used. Under the chin impact loading scenario, the anterior body of the mandible was damaged by restorations 1 and 4.

Spatial distribution of active compounds in stratum corneum-partitioning between corneocytes and lipid matrix.

The interaction of active substances with molecular structures in stratum corneum (SC) is crucial for the efficacy and safety of cosmetic formulations and topical drugs. However, the molecular architecture of SC is highly complex and methods to unambiguously localize exogenous molecules within SC are lacking. Consequently, little is known about the distribution of actives within SC, and proposed penetration mechanisms through SC are typically limited to simple diffusion via a tortuous (lipid only) or transverse (across corneocytes and lipid matrix) pathway. In this work, 3D mass spectrometry imaging is used to determine the spatial distributions of four active substances at subcellular resolution in SC, including partitioning between the corneocytes and the intercellular lipid matrix. The results indicate that caffeine, 2-methyl resorcinol and oxybenzone are homogeneously distributed in the corneocytes but largely absent in the lipid matrix, despite considerable differences in lipophilicity. In contrast, the distribution- of jasmonic acid derivative is more inhomogeneous and indicates considerable localization to both the lipid phase and the corneocytes.

Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

Biofilm formation of Staphylococcus aureus on various implants used for surgical treatment of destructive spondylodiscitis.

The incidence of spondylodiscitis has witnessed a significant increase in recent decades. Surgical intervention becomes necessary in case of bone destruction to remove infected tissue and restore spinal stability, often involving the implantation of a cage. Despite appropriate treatment, relapses occur in up to 20 percent of cases, resulting in substantial economic and social burdens. The formation of biofilm has been identified as a major contributor to relapse development. Currently, there is no consensus among German-speaking spinal surgeons or in the existing literature regarding the preferred choice of material to minimize relapse rates. Thus, the objective of this study is to investigate whether certain materials used in spinal implants exhibit varying degrees of susceptibility to bacterial attachment, thereby providing valuable insights for improving treatment outcomes.Eight cages of each PEEK, titanium-coated PEEK (Ti-PEEK), titanium (Ti), polyetherketoneketone (PEKK), tantalum (Ta) and antibiotic-loaded bone cement were incubated with 20% human plasma for 24 h. Subsequently, four implants were incubated with S. aureus for 24 h or 48 h each. The biofilm was then removed by sonication and the attained solution plated for Colony Forming Units (CFU) counting. Scanning electron microscopy was used to confirm bacterial attachment. The CFUs have been compared directly and in relation to the cages surface area. The surface area of the implants was PEEK 557 mm2, Ti-PEEK 472 mm2, Ti 985 mm2, PEKK 594 mm2, Ta 706 mm2, bone cement 123 mm2. The mean CFU count per implant and per mm2 surface area after 24 h and after 48 h was calculated. Bone cement was found to have significantly more CFUs per mm2 surface area than the other materials tested. When comparing the CFU count per implant, bone cement was statistically significantly more prone to biofilm formation than PEEK after 48 h. There was no statistical significance between the other materials when comparing both CFU count per mm2 surface area and CFU count per implant. The electron microscopic analysis showed the attachment of the bacteria, as well as production of extracellular polymeric substances (EPS) as a sign for beginning biofilm formation. Antibiotic-loaded bone cement has shown statistically significantly more bacterial attachment than the other examined materials. No difference was found between the other materials regarding bacterial attachment after 24 h and 48 h. Proposed hypotheses for further studies include testing whether differences become apparent after longer incubation or with different pathogens involved in the pathogenesis of pyogenic spondylodiscitis.

Peek@ZIF-8(CEL) as a Novel Bone Implant for Large Defect Repair and Enhanced Bone Healing via a Long-Term Stable Bioactive Releaser.

The repair of large bone defects poses a significant challenge in orthopedics. Polyetheretherketone (PEEK) is a promising bone substitute, while it suffers a lack of bioactivity. Although several studies have been performed to further improve the bioactivities of PEEK by various surface modifications, PEEK offering long-term, multifaceted biofunctionalities remains still desired. In this study, we introduced metal-organic frameworks (MOFs), specifically ZIF-8 loaded with celecoxib (ZIF-8(CEL)), onto the PEEK surface through dopamine adhesion. The resulting PEEK@ZIF-8(CEL) aims to achieve long-term stable release of Zn ions and CEL for enhanced bone integration. Material characterization and biological experiments confirmed the successful integration of ZIF-8(CEL) onto PEEK and its positive biomedical effects, including creating a positive bone immunological environment and promoting bone growth. This study demonstrates the potential of PEEK@ZIF-8(CEL) as a novel repair material for large bone defects, offering a promising alternative in orthopedic applications.