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Materials Today. Bio Jun 2024Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance...
Osteogenic-osteoclast coupling processes play a crucial role in bone regeneration. Recently, strategies that focus on multi-functionalized implant surfaces to enhance the healing of bone defects through the synergistic regulation of osteogenesis and osteoclastogenesis is still a challenging task in the field of bone tissue engineering. The aim of this study was to create a dual-drug release-based core-shell nanofibers with the intent of achieving a time-controlled release to facilitate bone regeneration. We fabricated core-shell P/PCL nanofibers using coaxial electrospinning, where alendronate (ALN) was incorporated into the core layer and hydroxyapatite (HA) into shell. The surface of the nanofiber construct was further modified with mussel-derived polydopamine (PDA) to induce hydrophilicity and enhance cell interactions. Surface characterizations confirmed the successful synthesis of PDA@PHA/PCL-ALN nanofibers endowed with excellent mechanical strength (20.02 ± 0.13 MPa) and hydrophilicity (22.56°), as well as the sustained sequential release of ALN and Ca ions. experiments demonstrated that PDA-functionalized core-shell PHA/PCL-ALN scaffolds possessed excellent cytocompatibility, enhanced cell adhesion and proliferation, alkaline phosphatase activity and osteogenesis-related genes. In addition to osteogenesis, the engineered scaffolds also significantly reduced osteoclastogenesis, such as tartrate-resistant acid phosphatase activity and osteoclastogenesis-related gene expression. After 12-week of implantation, it was observed that PDA@PHA/PCL-ALN nanofiber scaffolds, in a rat cranial defect model, significantly promoted bone repair and regeneration. Microcomputed tomography, histological examination, and immunohistochemical analysis collectively demonstrated that the PDA-functionalized core-shell PHA/PCL-ALN scaffolds exhibited exceptional osteogenesis-inducing and osteoclastogenesis-inhibiting effects. Finally, it may be concluded from our results that the bio-inspired surface-functionalized multifunctional, biomimetic and controlled release core-shell nanofiber provides a promising strategy to facilitate bone healing.
PubMed: 38779556
DOI: 10.1016/j.mtbio.2024.101088 -
JAMA Network Open May 2024Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced...
IMPORTANCE
Teratogenic outcomes associated with valproic acid use represent a substantial concern for persons of childbearing age. Regulatory agencies worldwide have enhanced warnings or implemented risk minimization programs to reduce exposure during pregnancy.
OBJECTIVES
To determine pregnancy rates during valproic acid use and concomitant contraception use across indications.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study used data from the Merative MarketScan commercial claims databases from January 1, 2005, to December 31, 2020, to identify female patients aged 12 to 44 years who initiated valproic acid treatment and had continuous insurance enrollment 6 months before initiation and 9 months after treatment end. A treatment episode included consecutive prescription fills that occurred within 7 days from the end of the days' supply of the previous dispensing. Data were analyzed from March 1 to September 10, 2023.
MAIN OUTCOMES AND MEASURES
Treatment episodes were categorized by inferred indication using diagnoses preceding treatment initiation, including epilepsy, migraine or headache, mood disorders, and unknown or off-label uses. Pregnancy incidence rate ratios (IRRs) were calculated and were adjusted for age and calendar year. Contraceptive use (prescription contraceptives, intrauterine devices, and implants) during treatment was examined.
RESULTS
The cohort included 165 772 valproic acid treatment episodes among 69 390 women (mean [SD] age, 29.8 [10.0] years). Mood disorders (42.5%) were the most common indication, followed by migraine or headache (20.1%), with epilepsy playing a minor role (14.9%). Pregnancy incidence rates during valproic acid use remained unchanged, with a rate of 1.74 (95% CI, 1.14-2.53) per 100 person-years in 2005 and a rate of 1.90 (95% CI, 1.16-3.12) per 100 person-years in 2019. Compared with epilepsy, pregnancy rates were more than double for mood disorder (IRR, 2.16 [95% CI, 1.93-2.42]) and migraine or headache (IRR, 2.01 [95% CI, 1.92-2.09]). Few treatment episodes coincided with contraceptive use (37 012 [22.3%]), and oral dosage forms were the most common (27 069 [73.1%]).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients of childbearing age who used valproic acid, pregnancy rates during valproic acid use did not decrease despite enhanced US Food and Drug Administration safety communications, and contraception use remained low. Patients with migraine and mood disorders accounted for the largest proportion of valproic acid use and had the highest pregnancy rates, while patients with epilepsy had the lowest. These findings suggest a need to enhance efforts to mitigate prenatal exposure to valproic acid, especially for indications where the risk of use during pregnancy outweighs the benefit.
Topics: Humans; Female; Valproic Acid; Pregnancy; Adult; Retrospective Studies; Adolescent; Prenatal Exposure Delayed Effects; Epilepsy; Young Adult; Anticonvulsants; Child; Pregnancy Rate; Mood Disorders; Migraine Disorders; United States
PubMed: 38776082
DOI: 10.1001/jamanetworkopen.2024.12680 -
Infection and Drug Resistance 2024The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing...
OBJECTIVE
The diagnosis of tubercular orthopedic implant-associated infection (TB-IAI) is challenging. This study evaluated the value of metagenomic next-generation sequencing (mNGS) for the diagnosis of TB-IAI and developed a standardized diagnostic procedure for TB-IAI.
METHODS
The records of all patients with TB-IAI diagnosed and treated at our institution between December 2018 and September 2022 were retrospectively reviewed. Patient demographic characteristics, medical history, laboratory test, microbial culture, histopathology, and mNGS results, and time to diagnosis were recorded. The diagnostic efficiency of mNGS for TB-IAI was assessed by comparing the results and diagnostic time with that of other diagnostic modalities.
RESULTS
Ten patients were included in the analysis, including eight with prosthetic joint infections and two with fracture-related infections. The mNGS positivity rate was 100% (10/10), which was higher than that of TB-antibody (11%, 1/9), real-time quantitative polymerase chain reaction (22%, 2/9), T-SPOT.TB (25%, 2/8), purified protein derivative (50%, 4/8), microbial culture (50%, 5/10), and histopathology (20%, 2/10). mNGS shortened the time to diagnosis of TB-IAI. A standardized diagnostic procedure for TB-IAI was developed based on the findings.
CONCLUSION
mNGS is useful for the diagnosis of TB-IAI. mNGS is recommended in cases where it is difficult to identify a pathogen using routine diagnostic tests. The standardized diagnostic procedure might improve TB-IAI diagnosis.
IMPORTANCE
TB-IAI is a rare infection, which occurs after orthopedic surgery and hard to diagnose microbiologically. mNGS is a new detection technique not yet discussed in current literature as a means for TB-IAI diagnostics. Here we describe a cohort of patients with TB-IAI diagnosed by mNGS show high efficiency of mNGS for detection of this pathology and present a clinical algorithm supplementing conventional methods for TB-IAI assessment.
PubMed: 38774035
DOI: 10.2147/IDR.S441940 -
Scientific Reports May 2024GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound...
GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.
Topics: Animals; Rats; Drug Liberation; Hydrophobic and Hydrophilic Interactions; Delayed-Action Preparations; Anti-HIV Agents; Drug Delivery Systems; Ionic Liquids; Rats, Sprague-Dawley; Male; Solubility; HIV Infections; Anti-Retroviral Agents
PubMed: 38773172
DOI: 10.1038/s41598-024-58583-w -
Iranian Biomedical Journal Mar 2024Osteogenic, antioxidant and anti-inflammatory effects of Whey protein and M. oleifera gel prompted us to evaluate their role alone or in combination on osseointegration...
BACKGROUND
Osteogenic, antioxidant and anti-inflammatory effects of Whey protein and M. oleifera gel prompted us to evaluate their role alone or in combination on osseointegration in rabbits.
METHODS
In this study, 24 titanium implants were inserted in the femurs of six rabbits. One implant was placed without treatment, and another one was coated with a mixture of whey protein and M. oleifera gel for each side. The animals were divided into two groups of 2- and 6-week intervals and evaluated using histopathological and immunohistochemical techniques.
RESULTS
Histological evaluation revealed a significant difference between the experimental and the control groups after two weeks in osteoblast and osteocyte counts. The experimental group had mature bone development after six weeks of implantation, while the control group had a woven bone. Immunohistochemical results showed that the experimental group, compared to the control group, exhibited early positive expression of osteoblast cells at two weeks after the experiment. Based on histopathological observations, the experimental group showed a tiny area of collagenous fiber in 6th week after the implantation.
CONCLUSION
A mixture of whey protein and M. oleifera could accelerate osseointegration and healing processes.
Topics: Animals; Whey Proteins; Rabbits; Osseointegration; Moringa oleifera; Plant Extracts; Plant Leaves; Male; Osteoblasts; Femur; Osteogenesis
PubMed: 38770885
DOI: 10.61186/ibj.4025 -
BMC Women's Health May 2024Successful efforts to encourage uptake of subdermal contraceptive implants, with a lifespan of three to five years, necessitate planning to ensure that quality removal...
BACKGROUND
Successful efforts to encourage uptake of subdermal contraceptive implants, with a lifespan of three to five years, necessitate planning to ensure that quality removal services are available when desired. In Burkina Faso, implant use has tripled over the past 8 years and now comprises almost half of the contraceptive method mix. Population Monitoring for Action (PMA) surveys identified barriers to obtaining quality removal when desired, particularly when the implant is not palpable, or providers lack needed skills or supplies. The Expanding Family Planning Choices (EFPC) project supported ministries of health in four countries with evaluation and strengthening of implant removal services.
METHODS
An implant removal landscape assessment was conducted at 24 health facilities in three regions of Burkina Faso with high implant use that included provider observations of implant removal, interviews with providers and health facility managers, and facility readiness surveys. The project used landscape data to mobilize stakeholders through a series of participatory workshops to develop a collaborative roadmap and commit to actions supporting quality implant removals.
RESULTS
Landscape findings revealed key gaps in provision of quality removal services, including high levels of provider confidence for implant insertion and removal (82% and 71%, respectively), low competence performing simple and difficult removals (19.2% and 11.1%, respectively), inadequate supplies and equipment (no facilities had all necessary materials for removal), lack of difficult removal management systems, and a lack of standard data collection tools for removal. Exposure to the data convinced stakeholders to focus on removals rather than expanding insertion services. While not all roadmap commitments were achieved, the process led to critical investments in quality implant removals.
CONCLUSION
Landscape data revealed that facilities lack needed supplies and equipment, and providers lack skills needed to perform quality implant removals, limiting client reproductive choice. Disseminating this data enabled stakeholders to identify and commit to evidence-based priority actions. Stakeholders have since capitalized on program learnings and the roadmap, including following MOH guidance for implant removal supplies and health provider training. Our experience in Burkina Faso offers a replicable model of how data can direct collective action to improve quality of contraceptive implant removals.
Topics: Burkina Faso; Humans; Female; Device Removal; Drug Implants; Family Planning Services; Stakeholder Participation; Contraceptive Agents, Female; Health Facilities
PubMed: 38769558
DOI: 10.1186/s12905-024-03121-z -
Journal of Orthopaedic Surgery and... May 2024Periprosthetic joint infection is a serious complication following joint replacement. The development of bacterial biofilms bestows antibiotic resistance and restricts...
BACKGROUND
Periprosthetic joint infection is a serious complication following joint replacement. The development of bacterial biofilms bestows antibiotic resistance and restricts treatment via implant retention surgery. Electromagnetic induction heating is a novel technique for antibacterial treatment of metallic surfaces that has demonstrated in-vitro efficacy. Previous studies have always employed stationary, non-portable devices. This study aims to assess the in-vitro efficacy of induction-heating disinfection of metallic surfaces using a new Portable Disinfection System based on Induction Heating.
METHODS
Mature biofilms of three bacterial species: S. epidermidis ATCC 35,984, S. aureus ATCC 25,923, E. coli ATCC 25,922, were grown on 18 × 2 mm cylindrical coupons of Titanium-Aluminium-Vanadium (Ti6Al4V) or Cobalt-chromium-molybdenum (CoCrMo) alloys. Study intervention was induction-heating of the coupon surface up to 70ºC for 210s, performed using the Portable Disinfection System (PDSIH). Temperature was monitored using thermographic imaging. For each bacterial strain and each metallic alloy, experiments and controls were conducted in triplicate. Bacterial load was quantified through scraping and drop plate techniques. Data were evaluated using non-parametric Mann-Whitney U test for 2 group comparison. Statistical significance was fixed at p ≤ 0.05.
RESULTS
All bacterial strains showed a statistically significant reduction of CFU per surface area in both materials. Bacterial load reduction amounted to 0.507 and 0.602 Log10 CFU/mL for S. aureus on Ti6Al4V and CoCrMo respectively, 5.937 and 3.500 Log10 CFU/mL for E. coli, and 1.222 and 0.372 Log10 CFU/mL for S. epidermidis.
CONCLUSIONS
Electromagnetic induction heating using PDSIH is efficacious to reduce mature biofilms of S aureus, E coli and S epidermidis growing on metallic surfaces of Ti6Al4V and CoCrMo alloys.
Topics: Biofilms; Titanium; Alloys; Disinfection; Escherichia coli; Staphylococcus aureus; Prosthesis-Related Infections; Staphylococcus epidermidis; Joint Prosthesis; Arthroplasty, Replacement; Heating; Humans; Electromagnetic Phenomena; Vitallium
PubMed: 38769535
DOI: 10.1186/s13018-024-04785-x -
European Review For Medical and... May 2024Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve...
OBJECTIVE
Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification.
MATERIALS AND METHODS
Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments.
RESULTS
A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs.
CONCLUSIONS
A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.
Topics: Titanium; Surface Properties; Coated Materials, Biocompatible; Mesenchymal Stem Cells; Copper; Porosity; Cobalt; Animals; Corrosion; Materials Testing; Cells, Cultured; Prostheses and Implants
PubMed: 38766802
DOI: 10.26355/eurrev_202405_36184 -
Frontiers in Bioengineering and... 2024Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to...
Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.
PubMed: 38766649
DOI: 10.3389/fbioe.2024.1352023 -
Cureus Apr 2024The management of choroidal neovascularization (CNVM) in pregnant young females has been a lacuna due to the rarity of the condition as well as the non-availability of...
The management of choroidal neovascularization (CNVM) in pregnant young females has been a lacuna due to the rarity of the condition as well as the non-availability of comprehensive data to showcase the efficacy of currently available treatment regimes in order to achieve a positive outcome for both the growing fetus as well the patient herself. In a review of available literature, the condition has been treated with anti-vascular endothelial growth factors (anti-VEGF), laser photocoagulation, and intravitreal dexamethasone implants (IDI), with varied results ranging from the successful outcome in terms of pregnancy to abortions. When faced with such circumstances, healthcare professionals usually proceed cautiously, balancing the possible advantages against the hazards to the mother and the fetus. Here we present a case report of a young 30-year-old pregnant lady who developed idiopathic CNVM during her third month of gestation. Being a rare entity, CNVM in young pregnant women raises severe concerns due to potential consequences on the mother's and fetus's health. In certain previously documented cases, pregnant ladies with CNVM have been successfully treated with IDI. Hence, after much deliberation, we chose to go with IDI rather than anti-VEGF, which resulted in the successful management of her CNVM as well as achieving full-term normal delivery without any fetal anomalies. In this particular case, the pregnancy and the visual rehabilitation have both had favorable outcomes. There was no associated increased intraocular pressure (IOP) or changes to the lenticular structure. The literature review also suggests that IDI may still be as effective in managing CNVM during pregnancy, but at a lower risk than anti-VEGF drug. Even with the favorable outcomes revealed in case reports, larger-scale studies to properly examine IDI's safety profile would be required for regulatory clearance of its safety in pregnancy.
PubMed: 38765334
DOI: 10.7759/cureus.58458