Efficacy and safety of recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with autologous bone for the treatment of long bone nonunion: A report of a prospective case series.

INTRODUCTION: Recombinant human Bone morphogenetic proteins have been used for the treatment of nonunions with promising results. We have been investigating both experimentally and clinically the efficacy of the rhBMP-2 with the macro / micro-porous hydroxyapatite carrier granules on the potency on the reconstruction of long bone defect. The purpose of this study was to prospectively evaluate the efficacy and safety of this specific rhBMP-2 with HA carrier granules mixed with autologous cancellous bone in patients with nonunion and bone defect resulted from the fracture related infection. MATERIALS AND METHODS: This was a retrospective review of a prospective cohort at a university hospital. Patients diagnosed with nonunion under the definition of the United States Food and Drug Administration with bone defect after long bone fractures were enrolled from January 2020 to February 2021. We included patients with atrophic and oligotrophic nonunion, and hypertrophic nonunion with malalignment that needed to be corrected. The other patient group was consisted of segmental bone defect resulted from FRI. The maximum amount of rhBMP-2 allowed in this clinical study was 6 mg and was added to autologous bone at a 1:1 ratio. Autologous bone was added to the mixture if the volume of mixed graft was insufficient to fill the bone defect. Patients were followed 3, 6, and 12 months post-operatively. Each visit, a radiograph was taken for assessment. Visual analog scale (VAS), questionnaire for quality of life (SF-12 physical component summary [PCS], mental component summary [MCS]), and weight-bearing status were collected for functional outcome assessment. Drug safety was assessed by examining BMP-2 antibodies. RESULTS: Of the 24 enrolled patients (mean age: 57 years), 15 (62.5 %), 2 (8.33 %), and 7 (29.17 %) presented atrophic nonunion, hypertrophic nonunion with deformity, and bone defect after fracture related infection, respectively. Thirteen patients had nonunion in the femur, 9 in the tibia, and 1 in the humerus and radius. The average amount of harvested autologous bone was 9.25 g and 4.96 mg of rhBMP-2. All 24 patients achieved union after 1-year follow up. The union rate was 95.83 % and 100 % at 6 and 12 months postoperatively, respectively. Preoperative SF-12 PCS (mean: 34.71) improved at 6 and 12 months postoperatively, respectively. Preoperative SF-12 MCS (mean: 42.89) improved 12 months postoperatively (49.13, p = 0.0338). Change of VAS was statistically significant 3 months postoperatively (p = 0.0012). No adverse effects or development of BMP-2 antibodies were observed. CONCLUSION: BMP-2 combined with autogenous bone resulted in excellent radiographical and functional outcomes in a relatively small prospective series of patients with nonunion and bone defect, without adverse effects. Further investigations are necessary to support our finding and optimize treatment strategies in nonunion patients.

Shallow-level defect passivation by 6H perovskite polytype for highly efficient and stable perovskite solar cells.

The power conversion efficiency of perovskite solar cells continues to increase. However, defects in perovskite materials are detrimental to their carrier dynamics and structural stability, ultimately limiting the photovoltaic characteristics and stability of perovskite solar cells. Herein, we report that 6H polytype perovskite effectively engineers defects at the interface with cubic polytype FAPbI3, which facilitates radiative recombination and improves the stability of the polycrystalline film. We particularly show the detrimental effects of shallow-level defect that originates from the formation of the most dominant iodide vacancy (VI+) in FAPbI3. Furthermore, additional surface passivation on top of the hetero-polytypic perovskite film results in an ultra-long carrier lifetime exceeding 18 µs, affords power conversion efficiencies of 24.13% for perovskite solar cells, 21.92% (certified power conversion efficiency: 21.44%) for a module, and long-term stability. The hetero-polytypic perovskite configuration may be considered as close to the ideal polycrystalline structure in terms of charge carrier dynamics and stability.

Pure varus posteromedial rotatory instability of the elbow: Radiographic findings, treatment, and outcomes.

INTRODUCTION: Although varus posteromedial rotatory instability (VPMRI) is a subtle elbow injury that involves anteromedial coronoid facet (AMCF) fracture and ligamentous injuries, treatment options and outcomes of VPMRI remains controversial. The aim of this study was to investigate radiographic findings, treatments, and outcomes of a large series of VPMRI. METHODS: We retrospectively reviewed 91 pure VPMRI cases with AMCF fracture (O'Driscoll classification anteromedial type) which were treated at 6 hospitals. Clinical and radiographic outcomes were investigated with a mean follow-up period of 46.8 months using the Mayo elbow performance score (MEPS), and the Quick Disabilities of the Arm, Shoulder and Hand (Quick-DASH) score, and serial plain radiographs. RESULTS: In AMCF fracture, there were 4 cases of subtype 1, 67 cases of subtype 2, and 20 cases of subtype 3. On MRI, complete tears of lateral collateral ligament and medial collateral ligament were observed in 83.1 % (59/71 cases) and 33.8 % (24/71 cases). Operative treatment was performed in 68 cases (74.7 %) including both side fixation in 40 cases (58.8 %), medial side fixation only in 17 cases (25.0 %), and lateral side fixation only in 11 cases (16.2 %). Nonoperative treatment was performed in 23 cases (25.3 %). The mean final MEPS and Quick-DASH scores were 93.7 and 7.9. The overall complication and reoperation rates were 22.0 % and 15.4 %. No significant differences regarding final clinical scores and range of motions were observed between the operative group and the nonoperative group, but significant differences were observed regarding number (p = 0.019) and displacement (p = 0.002) of coronoid fragment, and complication rate (p < 0.001) between the two groups. CONCLUSION: Depending on the pattern of coronoid fragment and the degree of ligamentous injuries, operative treatment of unstable VPMRI using various fixation techniques including coronoid fixation and ligament repair yielded satisfactory final clinical outcomes. However, surgeons should be aware of the high complication and reoperation rates after operative treatment. Stable VPMRI with AMCF fracture involving minimal displacement or small number of fragments can be treated nonoperatively.

Strain-Sensor-In-Pixel Technology for Resolution-Sustainable Stretchable Displays.

One of the limitations of stretchable displays is the severe degradation of resolution or the decrease in the number of pixels per unit area when stretched. Hence, we suggest a strain-sensor-in-pixel (S-SIP) system through the adoption of hidden pixels that are activated only during the stretch mode for maintaining the density of on-state pixels. For the S-SIP system, the gate and source electrodes of InGaZnO thin-film transistors (TFTs) in an existing pixel are connected to a resistive strain sensor through the facile and selective deposition of silver nanowires (AgNWs) via electrohydrodynamic-jet-printing. With this approach, the strain sensor integrated TFT functions as a strain-triggered switch, which responds only to stretching along the designated axes by finely tuning the orientation and cycles of AgNW printing. The strain sensor-integrated TFT remains in an off-state when unstretched and switches to an on-state when stretched, exhibiting a large negative gauge factor of -1.1 × 1010 and a superior mechanical stability enduring 6000 cycles, which enables the efficient structure to operate hidden pixels without requiring additional signal processing. Furthermore, the stable operation of the S-SIP in a 5 × 5-pixel array is demonstrated via circuit simulation, implying the outstanding applicability and process compatibility to the conventional active-matrix display backplanes.

Green production of functionalized few-layer borophene decorated with cerium-doped iron oxide nanoparticles for repeatable hydrogen peroxide detection.

Functionalized few-layer borophene (FFB) was prepared using gallnut extract and coffee waste extract as natural exfoliating and stabilizing agents in an environmentally friendly ultrasonic and high shear exfoliation. Here, a facile precipitation method was employed to grow iron oxide nanoparticles doped with cerium (Ce-FeONPs) onto the surface of FFB. This intriguing combination of materials yielded Ce-FeONPs nanoparticles that exhibited exceptional peroxidase-like activity, efficiently catalyzing the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue oxidized TMB (oxTMB) in the presence of hydrogen peroxide (H2O2). Additionally, the introduction of FFB contributes a reducibility effect to the catalytic oxidation of TMB, facilitating the restoration of the oxTMB to TMB. Thus, FFB-Ce-FeONPs showcase intriguing properties encompassing both oxidative and reductive characteristics, suggesting their potential as a reagent for repeated detection of H2O2. Moreover, a colorimetric sensing system enabled the liner detection of H2O2 spanning a concentration range from 0.08 to 1 mM, with a detection limit of 0.03 mM. Noteworthily, FFB-Ce-FeONPs demonstrated sustained efficacy over ten successive recycling cycles, as indicated by consistent slopes and observable color changes. In summary, this work reports the first application of nanoenzymes in repetitive H2O2 detection. Even after ten multiple cycles, the detection limit remains virtually unaltered, underscoring the robustness and enduring effectiveness of the engineered nanomaterial. The proposed simultaneous oxidation and reduction strategies for detecting H2O2 showed a commendable capability in ten cycles of H2O2 detection, thus providing a promising approach in the field of H2O2 detection.

Effect of Microsphere Concentration on Catechin Release from Microneedle Arrays.

In this work, microspheres were developed by cross-linking glutaraldehyde in an aqueous gelatin solution with a surfactant and solvent. A poly(vinyl alcohol) (PVA) solution was produced and combined with catechin-loaded microspheres. Different microsphere concentrations (0%, 5%, 10%, and 15%) were applied to the PVA microneedles. The moisture content, particle size, swelling, and drug release percentage of microneedles were studied using various microsphere concentrations. Fourier transform infrared and scanning electron microscopy (SEM) investigations validated the structure of gelatin microspheres as well as their decoration in microneedles. The SEM scans revealed that spherical microspheres with a wrinkled and folded morphology were created, with no physical holes visible on the surface. The gelatin microspheres generated had a mean particle size of 20-30 µm. Ex vivo release analysis indicated that microneedles containing 10% microspheres released the most catechin, with 42.9% at 12 h and 84.4% at 24 h.

Constructed wetlands for the removal of organic micropollutants from wastewater: Current status, progress, and challenges.

In this work, the practical utility of constructed wetlands (CWs) is described as a promising treatment option for micropollutants (MPs) in wastewater with the aid of their eco-friendly, low-energy, economically feasible, and ecologically sustainable nature. This paper offers a comprehensive review on CW technology with respect to the key strategies for MP removal such as phytoremediation, substrate adsorption, and microbial degradation. It explores the important factors controlling the performance of CWs (e.g., in terms of configurations, substrates, plant-microbe interactions, temperature, pH, oxygen levels, hydraulic loading rate, and retention time) along with the discussions on the pivotal role of microbial populations in CWs and plant-microbe cooperative remediation dynamics, particularly in relation to diverse organic MP patterns in CWs. As such, this review aims to provide valuable insights into the key strategies for optimizing MP treatment and for enhancing the efficacy of CW systems. In addition, the process-based models of constructed wetlands along with the numerical simulations based on the artificial neural network (ANN) method are also described in association with the data exploratory techniques. This work is thus expected to help open up new possibilities for the application of plant-microbe cooperative remediation approaches against diverse patterns of organic MPs present in CWs.

Optimization of gearbox housing shape for agricultural UTV using structural-acoustic coupled analysis.

In this study, gearbox radiated noise was successfully reduced through housing shape optimization. First, dynamic and structural-acoustic coupled analysis models of an agricultural UTV gearbox were developed. Then, the test equipment was configured to match that of the simulation model, and a test was conducted. The analysis and test results showed errors within 0.1 dB for vibration and 0.2 dB(A) for noise, indicating that the models were reliable. The housing design was then optimized using topology optimization based on the developed structural-acoustic coupling analysis model. The sound pressure level around the housing was used as an objective function for topology optimization. The optimal distribution of materials for the housing was also derived to reduce the radiated noise. Lastly, the housing rib was designed based on the optimization result, and an improvement in the radiated noise by approximately 2.43 dB(A) was confirmed in the operation area.

Site-specific effects of dobutamine on cardiac conduction and refractoriness.

BACKGROUND: Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature. OBJECTIVE: To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS. METHODS: From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing. RESULTS: For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted. CONCLUSION: In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.

Outcomes and complications after treatment for anteromedial facet fracture of the coronoid process: A systematic review.

BACKGROUND: Fracture of the anteromedial facet (AMF) of the coronoid process is associated with varus posteromedial rotatory instability (VPMRI). However, there is still controversy regarding the optimal treatment for AMF fracture. The purpose of this study is to report on a systematic review of the outcomes and complications after treatment for AMF fracture. METHODS: This study was conducted using electronic databases, PubMed, EMBASE and Scopus. Studies reporting outcome scores and complications were included. Studies that did not utilize O'Driscoll classification for AMF fractures were excluded. Through conduct of a thorough review of included studies, definite VPMRI were identified and cases involving other injury mechanisms were excluded. RESULTS: Fifteen articles reporting on 246 patients were included. According to O'Driscoll classification, 6.2% of cases were anteromedial subtype I, 73.7% were subtype II, and 20.1% were subtype III. Two-hundred sixteen patients (87.8%) were treated surgically and 30 patients (12.2%) were treated conservatively. Lateral collateral ligament (LCL) injuries were 76.2% (157/206) and medial collateral ligament injuries were 16.9% (33/195). Among 216 cases who underwent surgical treatment, depending on the fragment size, displacement, and instability, coronoid fixation was performed in 189 cases and LCL repair alone was performed in 27 cases. The mean final Mayo Elbow Performance Score was 92.1 and the Broberg & Morrey score was 89.5. The overall complication and reoperation rates were 17.7% (41/232) and 12.9% (26/202). CONCLUSIONS: Both surgical and conservative treatment for AMF fractures resulted in satisfactory final clinical outcomes. However, high complication and reoperation rates were observed.

Is the Direct Fixation of Displaced Quadrilateral Plates in Acetabular Fractures Necessary?

Quadrilateral plate fractures represent a heterogeneous group of acetabular fractures. Accurate reduction is required to prevent post-traumatic arthritis. The purpose of this study is to determine the reduction effect of the direct fixation of quadrilateral plates in acetabular fractures, and to evaluate the strength of direct fixation compared to indirect fixation. Between 2005 and 2021, 49 patients underwent surgery for open reduction and internal fixation in acetabular fractures with severely displaced quadrilateral plates. Twenty-nine patients comprised the indirect fixation group, and twenty patients comprised the direct fixation group. In a comparison of primary outcome between two groups, 10 out of 29 indirect-group patients and 1 out of 20 direct-group patients developed post-traumatic osteoarthritis, wherein the difference between the two groups is statistically significant. In the assessment of postoperative Matta's radiological reduction status, 19 out of 20 patients in the direct group had achieved anatomical and congruent reduction. The treatment using a direct reduction and internal fixation improved the reduction quality of articular displacement and offered a better survivorship of the affected hip joint.

A holistic approach for process intensification of nicotinamide mononucleotide production via high cell density cultivation under exponential feeding strategy.

Nicotinamide mononucleotide (NMN) subsists in all living organisms and has drawn tremendous attention as a nutraceutical and pharmaceutical product for several diseases such as Alzheimer's, cancer, aging, and vascular dysfunction. Here, NMN was produced intracellularly in a high cell density bioreactor using an engineered Escherichiacoli strain via exponential feeding of co-substrates. Fed-batch culture via exponential feeding of co-substrate (glucose) and continuous feeding of substrate (nicotinamide) were performed using different cumulative nicotinamide concentrations. The highest concentration of 19.3 g/L NMN with a dry cell weight of 117 g/L was acquired from a cumulative nicotinamide concentration of 7.2 g/L with a conversion of 98 % from nicotinamide in 28 h. Further, liquid chromatography-mass spectrometry analysis validated the NMN production. This approach will be beneficial in achieving simultaneously low cost and ensuring high quality and quantity of NMN production.

Graphene Oxide Nanostructures as Nanoplatforms for Delivering Natural Therapeutic Agents: Applications in Cancer Treatment, Bacterial Infections, and Bone Regeneration Medicine.

Graphene, fullerenes, diamond, carbon nanotubes, and carbon dots are just a few of the carbon-based nanomaterials that have gained enormous popularity in a variety of scientific disciplines and industrial uses. As a two-dimensional material in the creation of therapeutic delivery systems for many illnesses, nanosized graphene oxide (NGO) is now garnering a large amount of attention among these materials. In addition to other benefits, NGO functions as a drug nanocarrier with remarkable biocompatibility, high pharmaceutical loading capacity, controlled drug release capability, biological imaging efficiency, multifunctional nanoplatform properties, and the power to increase the therapeutic efficacy of loaded agents. Thus, NGO is a perfect nanoplatform for the development of drug delivery systems (DDSs) to both detect and treat a variety of ailments. This review article's main focus is on investigating surface functionality, drug-loading methods, and drug release patterns designed particularly for smart delivery systems. The paper also examines the relevance of using NGOs to build DDSs and considers prospective uses in the treatment of diseases including cancer, infection by bacteria, and bone regeneration medicine. These factors cover the use of naturally occurring medicinal substances produced from plant-based sources.

Clinical outcome of rim-plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole.

Despite the variety of treatment methods, comminuted inferior pole fractures of the patella remain difficult and technically demanding to achieve stable internal fixation. The purpose of this study is to evaluate the clinical outcomes of rim plate-augmented separate vertical wiring with supplementary fixation in the management of comminuted inferior pole fractures, AO/OTA 34-A1, C2, and C3, which has the secondary horizontal fracture line on lower articular boundary. From our study, bony union was achieved in all patients at an average of 3.1 ± 1.4 months after surgery. There was no patient with loss of reduction, fixation failure, or infection during follow-up. The average final range of motion was 131.6° ± 7.2°. Lysholm knee scores gradually increased over 3, 6, 9, and 12 months postoperatively by 58.7, 74.0, 82.9, and 89.4, respectively. Isokinetic peak torque deficit of the knee extensor muscles in 3, 6, 9, and 12 months postoperatively was 59.9%, 49.7%, 35.7%, and 28.1%, respectively. The rim plate-augmented separate vertical wiring with supplementary fixation for the treatment of patellar fracture associated comminuted inferior pole is effective and can be safely applied AO/OTA 34-C2 or C3 with favorable outcomes.

The Clinical Efficacy of Contouring Periarticular Plates on a 3D Printed Bone Model.

We report our experience of preoperative plate contouring for periarticular fractures using three-dimensional printing (3DP) technology and describe its benefits. We enrolled 34 patients, including 11 with humerus midshaft fractures, 12 with tibia plateau fractures, 2 with pilon fractures, and 9 with acetabulum fractures. The entire process of plate contouring over the 3DP model was videotaped and retrospectively analyzed. The total time and number of trials for the intraoperative positioning of precontoured plates and any further intraoperative contouring events were prospectively recorded. The mismatch between the planned and postoperative plate positions was evaluated. The average plate contouring time was 9.2 min for humerus shaft, 13.8 min for tibia plateau fractures, 8.8 min for pilon fractures, and 11.6 min for acetabular fractures. Most precontoured plates (88%, 30/34) could sit on the planned position without mismatch. In addition, only one patient with humerus shaft fracture required additional intraoperative contouring. Preoperative patient specific periarticular plate contouring using a 3DP model is a simple and efficient method that may alleviate the surgical challenges involved in plate contouring and positioning.

Valorization of organic wastes using bioreactors for polyhydroxyalkanoate production: Recent advancement, sustainable approaches, challenges, and future perspectives.

Microbial polyhydroxyalkanoates (PHA) are encouraging biodegradable polymers, which may ease the environmental problems caused by petroleum-derived plastics. However, there is a growing waste removal problem and the high price of pure feedstocks for PHA biosynthesis. This has directed to the forthcoming requirement to upgrade waste streams from various industries as feedstocks for PHA production. This review covers the state-of-the-art progress in utilizing low-cost carbon substrates, effective upstream and downstream processes, and waste stream recycling to sustain entire process circularity. This review also enlightens the use of various batch, fed-batch, continuous, and semi-continuous bioreactor systems with flexible results to enhance the productivity and simultaneously cost reduction. The life-cycle and techno-economic analyses, advanced tools and strategies for microbial PHA biosynthesis, and numerous factors affecting PHA commercialization were also covered. The review includes the ongoing and upcoming strategies viz. metabolic engineering, synthetic biology, morphology engineering, and automation to expand PHA diversity, diminish production costs, and improve PHA production with an objective of "zero-waste" and "circular bioeconomy" for a sustainable future.

Green Synthesis of Controlled Shape Silver Nanostructures and Their Peroxidase, Catalytic Degradation, and Antibacterial Activity.

Nanoparticles with unique shapes have garnered significant interest due to their enhanced surface area-to-volume ratio, leading to improved potential compared to their spherical counterparts. The present study focuses on a biological approach to producing different silver nanostructures employing Moringa oleifera leaf extract. Phytoextract provides metabolites, serving as reducing and stabilizing agents in the reaction. Two different silver nanostructures, dendritic (AgNDs) and spherical (AgNPs), were successfully formed by adjusting the phytoextract concentration with and without copper ions in the reaction system, resulting in particle sizes of ~300 ± 30 nm (AgNDs) and ~100 ± 30 nm (AgNPs). These nanostructures were characterized by several techniques to ascertain their physicochemical properties; the surface was distinguished by functional groups related to polyphenols due to plant extract that led to critical controlling of the shape of nanoparticles. Nanostructures performance was assessed in terms of peroxidase-like activity, catalytic behavior for dye degradation, and antibacterial activity. Spectroscopic analysis revealed that AgNDs demonstrated significantly higher peroxidase activity compared to AgNPs when evaluated using chromogenic reagent 3,3',5,5'-tetramethylbenzidine. Furthermore, AgNDs exhibited enhanced catalytic degradation activities, achieving degradation percentages of 92.2% and 91.0% for methyl orange and methylene blue dyes, respectively, compared to 66.6% and 58.0% for AgNPs. Additionally, AgNDs exhibited superior antibacterial properties against Gram-negative E. coli compared to Gram-positive S. aureus, as evidenced by the calculated zone of inhibition. These findings highlight the potential of the green synthesis method in generating novel nanoparticle morphologies, such as dendritic shape, compared with the traditionally synthesized spherical shape of silver nanostructures. The synthesis of such unique nanostructures holds promise for various applications and further investigations in diverse sectors, including chemical and biomedical fields.