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1.
Opt Express ; 32(12): 21042-21060, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859469

ABSTRACT

The backscattering of ultraviolet and visible light by a model organic (squalane) aerosol droplet (1.0

2.
EMBO J ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937634

ABSTRACT

Members of the SLC25 mitochondrial carrier family link cytosolic and mitochondrial metabolism and support cellular maintenance and growth by transporting compounds across the mitochondrial inner membrane. Their monomeric or dimeric state and kinetic mechanism have been a matter of long-standing debate. It is believed by some that they exist as homodimers and transport substrates with a sequential kinetic mechanism, forming a ternary complex where both exchanged substrates are bound simultaneously. Some studies, in contrast, have provided evidence indicating that the mitochondrial ADP/ATP carrier (SLC25A4) functions as a monomer, has a single substrate binding site, and operates with a ping-pong kinetic mechanism, whereby ADP is imported before ATP is exported. Here we reanalyze the oligomeric state and kinetic properties of the human mitochondrial citrate carrier (SLC25A1), dicarboxylate carrier (SLC25A10), oxoglutarate carrier (SLC25A11), and aspartate/glutamate carrier (SLC25A13), all previously reported to be dimers with a sequential kinetic mechanism. We demonstrate that they are monomers, except for dimeric SLC25A13, and operate with a ping-pong kinetic mechanism in which the substrate import and export steps occur consecutively. These observations are consistent with a common transport mechanism, based on a functional monomer, in which a single central substrate-binding site is alternately accessible.

3.
Elife ; 132024 May 23.
Article in English | MEDLINE | ID: mdl-38780415

ABSTRACT

Stramenopiles form a clade of diverse eukaryotic organisms, including multicellular algae, the fish and plant pathogenic oomycetes, such as the potato blight Phytophthora, and the human intestinal protozoan Blastocystis. In most eukaryotes, glycolysis is a strictly cytosolic metabolic pathway that converts glucose to pyruvate, resulting in the production of NADH and ATP (Adenosine triphosphate). In contrast, stramenopiles have a branched glycolysis in which the enzymes of the pay-off phase are located in both the cytosol and the mitochondrial matrix. Here, we identify a mitochondrial carrier in Blastocystis that can transport glycolytic intermediates, such as dihydroxyacetone phosphate and glyceraldehyde-3-phosphate, across the mitochondrial inner membrane, linking the cytosolic and mitochondrial branches of glycolysis. Comparative analyses with the phylogenetically related human mitochondrial oxoglutarate carrier (SLC25A11) and dicarboxylate carrier (SLC25A10) show that the glycolytic intermediate carrier has lost its ability to transport the canonical substrates malate and oxoglutarate. Blastocystis lacks several key components of oxidative phosphorylation required for the generation of mitochondrial ATP, such as complexes III and IV, ATP synthase, and ADP/ATP carriers. The presence of the glycolytic pay-off phase in the mitochondrial matrix generates ATP, which powers energy-requiring processes, such as macromolecular synthesis, as well as NADH, used by mitochondrial complex I to generate a proton motive force to drive the import of proteins and molecules. Given its unique substrate specificity and central role in carbon and energy metabolism, the carrier for glycolytic intermediates identified here represents a specific drug and pesticide target against stramenopile pathogens, which are of great economic importance.


All living organisms breakdown food molecules to generate energy for processes, such as growing, reproducing and movement. The series of chemical reactions that breakdown sugars into smaller molecules ­ known as glycolysis ­ is so important that it occurs in all life forms, from bacteria to humans. In higher organisms, such as fungi and animals, these reactions take place in the cytosol, the space surrounding the cell's various compartments. A transport protein then shuttles the end-product of glycolysis ­ pyruvate ­ into specialised compartments, known as the mitochondria, where most energy is produced. However, recently it was discovered that a group of living organisms, called the stramenopiles, have a branched glycolysis in which the enzymes involved in the second half of this process are located in both the cytosol and mitochondrial matrix. But it was not known how the intermediate molecules produced after the first half of glycolysis enter the mitochondria. To answer this question, Pyrihová et al. searched for transport protein(s) that could link the two halves of the glycolysis pathway. Computational analyses, comparing the genetic sequences of many transport proteins from several different species, revealed a new group found only in stramenopiles. Pyrihová et al. then used microscopy to visualise these new transport proteins ­ called GIC-1 and GIC-2 ­ in the parasite Blastocystis, which infects the human gut, and observed that they localise to mitochondria. Further biochemical experiments showed that GIC-1 and GIC-2 can physically bind these intermediate molecules, but only GIC-2 can transport them across membranes. Taken together, these observations suggest that GIC-2 links the two halves of glycolysis in Blastocystis. Further analyses could reveal corresponding transport proteins in other stramenopiles, many of which have devastating effects on agriculture, such as Phytophthora, which causes potato blight, or Saprolegnia, which causes skin infections in farmed salmon. Since human cells do not have equivalent transporters, they could be new drug targets not only for Blastocystis, but for these harmful pathogens as well.


Subject(s)
Blastocystis , Cytosol , Glycolysis , Mitochondria , Blastocystis/metabolism , Blastocystis/genetics , Humans , Mitochondria/metabolism , Cytosol/metabolism , Biological Transport , Protozoan Proteins/metabolism , Protozoan Proteins/genetics
4.
Biomed Mater ; 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38387053

ABSTRACT

Bioresorbable polymeric sutures are gaining interest from surgeons and patients as they reduce surgical stress and trauma. This study involves two bioresorbable polymers, namely, catgut and poly(4-hyrdorxybutyrate) (P4HB) that are used widely in cosmetic procedures. P4HB barbed sutures are favorably used in rhytidectomy (micro-facelifts) procedures while catgut sutures are widely used for external wound closure after surgical interventions. This study involves the mechanical fabrication of catgut and P4HB barbed sutures and compares their mechanical and anchoring properties. Barbed sutures were fabricated with two different barb geometries namely, straight and curved barbs. The mechanical properties were evaluated via tensile testing, and the anchoring performance was studied by means of a suture-tissue pull-out protocol using porcine dermis tissue which was harvested from the medial dorsal site. The fabricated barbed sutures of both materials showed a similar trend compared to non-barbed sutures of decreases in failure stress, strain at failure, and work to rupture or toughness which was reduced by about 70%. At the same time there was a 15% increase in the initial modulus or stiffness of the barbed sutures. The pull-out force for the barbed sutures with straight barbs was similar for both P4HB (5.04±0.8N) and catgut (4.47±3.8N), and as expected, were higher than that of non-barbed sutures of the same size. It was also observed that barbed sutures with curved barbs also required a higher pull-out force than those sutures with straight barbs. It was concluded that by barbing sutures with different barb shapes and geometries, a range of barbed suture products could be fabricated, each meeting the closure requirements for different types of tissue and therefore being suitable for different surgical procedures.

7.
Pract Radiat Oncol ; 2023 Dec 02.
Article in English | MEDLINE | ID: mdl-38043644

ABSTRACT

PURPOSE: Recently, a randomized trial demonstrated that a hyaluronic acid (HA) spacer placed before prostate hypofractionated intensity modulated radiation therapy improved rectal dosimetry and reduced acute grade 2+ gastrointestinal toxicity. However, 26.5% of patients receiving the spacer experienced a minimal clinically important decline (MCID) in bowel quality-of-life (QOL). The purpose of this study is to evaluate whether certain characteristics of the rectal spacer, as determined on postimplant imaging, were associated with change in bowel QOL at 3-months. METHODS AND MATERIALS: This is a secondary analysis of the 136 patients who received the HA spacer on the randomized trial. Postimplant spacer characteristics (ie, prostate-rectum spacing at superior/midgland/inferior/apex planes, symmetry, prostate volume, spacer volume) were systematically analyzed from structure sets using custom software code. Characteristics demonstrating significant associations with rectal V30 on multivariate linear regression were identified. Linear regression models were used to analyze the associations of such characteristics with change (baseline to 3 months) in both bowel and urinary QOL. RESULTS: Apical spacing (mean 9.4 (standard deviation 4.0)) was significantly smaller than spacing measurements at more superior planes. 95.6% of patients had a symmetrical implant. Apical spacing (P < .001) and prostate volume (P = .01) were significantly associated with rectal V30 on multivariate analysis. However, only apical spacing (0.38/mm; P = .01) was associated with change in bowel QOL, even with adjustment of baseline bowel score (-0.33; P < .01). Percentages of patients with bowel MCID were 14.8% for >= 10 mm versus 36.6% for <10 mm apical spacing (P = .01). Apical spacing was not associated with change in urinary QOL (-0.09; P = .72), when adjusted for baseline urinary QOL (-0.52; P < .01). CONCLUSION: Greater apical spacing was associated with improved rectal dosimetry and smaller decline in bowel QOL at 3-months. Further prospective data are needed to fully understand the ramifications of increased apical spacing.

8.
Bioeng Transl Med ; 8(6): e10565, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38023705

ABSTRACT

Postsurgical adhesions are a common complication of surgical procedures that can lead to postoperative pain, bowel obstruction, infertility, as well as complications with future procedures. Several agents have been developed to prevent adhesion formation, such as barriers, anti-inflammatory and fibrinolytic agents. The Food and Drug Administration (FDA) has approved the use of physical barrier agents, but they have been associated with conflicting clinical studies and controversy in the clinical utilization of anti-adhesion barriers. In this review, we summarize the human anatomy of the peritoneum, the pathophysiology of adhesion formation, the current prevention agents, as well as the current research progress on adhesion prevention. The early cellular events starting with injured mesothelial cells and incorporating macrophage response have recently been found to be associated with adhesion formation. This may provide the key component for developing future adhesion prevention methods. The current use of physical barriers to separate tissues, such as Seprafilm®, composed of hyaluronic acid and carboxymethylcellulose, can only reduce the risk of adhesion formation at the end stage. Other anti-inflammatory or fibrinolytic agents for preventing adhesions have only been studied within the context of current research models, which is limited by the lack of in-vitro model systems as well as in-depth study of in-vivo models to evaluate the efficiency of anti-adhesion agents. In addition, we explore emerging therapies, such as gene therapy and stem cell-based approaches, that may offer new strategies for preventing adhesion formation. In conclusion, anti-adhesion agents represent a promising approach for reducing the burden of adhesion-related complications in surgical patients. Further research is needed to optimize their use and develop new therapies for this challenging clinical problem.

9.
J Phys Chem A ; 127(42): 8922-8934, 2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37830513

ABSTRACT

Neutron reflectometry has been used to study the radical initiated oxidation of a monolayer of the lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) at the air-solution interface by aqueous-phase hydroxyl, sulfate, and nitrate radicals. The oxidation of organic films at the surface of atmospheric aqueous aerosols can influence the optical properties of the aerosol and consequently can impact Earth's radiative balance and contribute to modern climate change. The amount of material at the air-solution interface was found to decrease on exposure to aqueous-phase radicals which was consistent with a multistep degradation mechanism, i.e., the products of reaction of the DSPC film with aqueous radicals were also surface active. The multistep degradation mechanism suggests that lipid molecules in the thin film degrade to form progressively shorter chain surface active products and several reactive steps are required to remove the film from the air-solution interface. Bimolecular rate constants for oxidation via the aqueous phase OH radical cluster around 1010 dm3 mol-1 s-1. Calculations to determine the film lifetime indicate that it will take ∼4-5 days for the film to degrade to 50% of its initial amount in the atmosphere, and therefore attack by aqueous radicals on organic films could be atmospherically important relative to typical atmospheric aerosol lifetimes.

10.
Article in English | MEDLINE | ID: mdl-37679601

ABSTRACT

BACKGROUND: Biochemical recurrence (BCR) following primary interventional treatment occurs in approximately one-third of patients with prostate cancer (PCa). Next-generation imaging (NGI) can identify local and metastatic recurrence with greater sensitivity than conventional imaging, potentially allowing for more effective interventions. This narrative review examines the current clinical evidence on the utility of NGI for patients with BCR. METHODS: A search of PubMed was conducted to identify relevant publications on NGI applied to BCR. Given other relevant recent reviews on the topic, this review focused on papers published between January 2018 to May 2023. RESULTS: NGI technologies, including positron emission tomography (PET) radiotracers and multiparametric magnetic resonance imaging, have demonstrated increased sensitivity and selectivity for diagnosing BCR at prostate-specific antigen (PSA) concentrations <2.0 ng/ml. Detection rates range between 46% and 50%, with decreasing PSA levels for choline (1-3 ng/ml), fluciclovine (0.5-1 ng/ml), and prostate-specific membrane antigen (0.2-0.49 ng/ml) PET radiotracers. Expert working groups and European and US medical societies recommend NGI for patients with BCR. CONCLUSIONS: Available data support the improved detection performance and selectivity of NGI modalities versus conventional imaging techniques; however, limited clinical evidence exists demonstrating the application of NGI to treatment decision-making and its impact on patient outcomes. The emergence of NGI and displacement of conventional imaging may require a reexamination of the current definitions of BCR, altering our understanding of early recurrence. Redefining the BCR disease state by formalizing the role of NGI in patient management decisions will facilitate greater alignment across research efforts and better reflect the published literature.

11.
Article in English | MEDLINE | ID: mdl-37679602

ABSTRACT

BACKGROUND: Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing. OBJECTIVE: This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies. METHODS: PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT). RESULTS: European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects. CONCLUSIONS: Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.

12.
Med Phys ; 50(10): 5935-5943, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37665729

ABSTRACT

BACKGROUND: For trans-rectal ultrasound (TRUS)-based high dose rate (HDR) prostate brachytherapy, prostate contouring can be challenging due to artifacts from implanted needles, bleeding, and calcifications. PURPOSE: To evaluate the geometric accuracy and observer preference of an artificial intelligence (AI) algorithm for generating prostate contours on TRUS images with implanted needles. METHODS: We conducted a retrospective study of 150 patients, who underwent HDR brachytherapy. These patients were randomly divided into training (104), validation (26) and testing (20) sets. An AI algorithm was trained/validated utilizing the TRUS image and reference (clinical) contours. The algorithm then provided contours for the test set. For evaluation, we calculated the Dice coefficient between AI and reference prostate contours. We then presented AI and reference contours to eight clinician observers, and asked observers to select their preference. Observers were blinded to the source of contours. We calculated the percentage of cases in which observers preferred AI contours. Lastly, we evaluate whether the presence of AI contours improved the geometric accuracy of prostate contours provided by five resident observers for a 10-patient subset. RESULTS: The median Dice coefficient between AI and reference contours was 0.92 (IQR: 0.90-0.94). Observers preferred AI contours for a median of 57.5% (IQR: 47.5, 65.0) of the test cases. For resident observers, the presence of AI contours was associated with a 0.107 (95% CI: 0.086, 0.128; p < 0.001) improvement in Dice coefficient for the 10-patient subset. CONCLUSION: The AI algorithm provided high-quality prostate contours on TRUS with implanted needles. Further prospective study is needed to better understand how to incorporate AI prostate contours into the TRUS-based HDR brachytherapy workflow.

13.
Polymers (Basel) ; 15(18)2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37765673

ABSTRACT

Poly(ε-caprolactone) (PCL) is a hydrophobic, resorbable aliphatic polymer recognized for its low tenacity and extensive elongation at break, making it a popular choice for fabricating biodegradable tissue engineering scaffolds. PCL's slow degradation rate typically results in a complete resorption period of 2 to 3 years. While numerous studies have examined the degradation of PCL in various forms such as films and webs, no study to date has investigated its physiological degradation in multifilament yarn form. In this study, we subjected PCL multifilament yarn samples to physiological conditions in phosphate-buffered saline (PBS) maintained at a consistent temperature of 37 ± 2 °C and agitated at 45 rpm for a period of 32 weeks. We retrieved samples at five different intervals to analyze the degradation profile of the multifilament yarn. This allowed us to estimate the complete resorption time and rate under these in vitro conditions. Over the 32-week period, the multifilament yarn's mass decreased by 4.8%, its elongation at break declined by 42%, the tenacity dropped by 40%, and the peak load at break fell by 46.5%. Based on these findings, we predict that a scaffold structure incorporating PCL multifilament yarn would undergo complete resorption in approximately 14 months under physiological conditions, such as in PBS solution at a pH of approximately 7 and a temperature of 37 °C.

14.
ACS Appl Mater Interfaces ; 15(23): 27457-27470, 2023 Jun 14.
Article in English | MEDLINE | ID: mdl-37272781

ABSTRACT

Macrophages play a pivotal role in wound healing and tissue regeneration, as they are rapidly recruited to the site of injury or implanted foreign material. Depending on their interaction with the material, macrophages can develop different phenotypes, with the M1 pro-inflammatory and M2 pro-regenerative phenotypes being highly involved in tissue regeneration. M2 macrophages mitigate inflammation and promote tissue regeneration and extracellular matrix remodeling. In this study, we engineered a gelatin-heparin-methacrylate (GelMA-HepMA) hydrogel that gradually releases interleukin-4 (IL-4), a cytokine that modulates macrophages to adopt the M2 phenotype. Methacrylation of heparin improved the retention of both heparin and IL-4 within the hydrogel. The GelMA-HepMA hydrogel and IL-4 synergistically downregulated M1 gene expression and upregulated M2 gene expression in macrophages within 48 h of in vitro cell culture. However, the M2-like macrophage phenotype induced by the GelMA-HepMA-IL-4 hydrogel did not necessarily further improve endothelial cell proliferation and migration in vitro.


Subject(s)
Heparin , Interleukin-4 , Interleukin-4/pharmacology , Heparin/pharmacology , Heparin/metabolism , Macrophages/metabolism , Phenotype , Hydrogels/pharmacology , Hydrogels/metabolism
15.
EMBO Rep ; 24(8): e57127, 2023 08 03.
Article in English | MEDLINE | ID: mdl-37278158

ABSTRACT

The mitochondrial ADP/ATP carrier (SLC25A4), also called the adenine nucleotide translocase, imports ADP into the mitochondrial matrix and exports ATP, which are key steps in oxidative phosphorylation. Historically, the carrier was thought to form a homodimer and to operate by a sequential kinetic mechanism, which involves the formation of a ternary complex with the two exchanged substrates bound simultaneously. However, recent structural and functional data have demonstrated that the mitochondrial ADP/ATP carrier works as a monomer and has a single substrate binding site, which cannot be reconciled with a sequential kinetic mechanism. Here, we study the kinetic properties of the human mitochondrial ADP/ATP carrier by using proteoliposomes and transport robotics. We show that the Km/Vmax ratio is constant for all of the measured internal concentrations. Thus, in contrast to earlier claims, we conclude that the carrier operates with a ping-pong kinetic mechanism in which substrate exchange across the membrane occurs consecutively rather than simultaneously. These data unite the kinetic and structural models, showing that the carrier operates with an alternating access mechanism.


Subject(s)
Mitochondria , Mitochondrial ADP, ATP Translocases , Humans , Mitochondrial ADP, ATP Translocases/chemistry , Mitochondrial ADP, ATP Translocases/metabolism , Mitochondria/metabolism , Adenosine Triphosphate/metabolism , Adenosine Diphosphate/metabolism , Kinetics , Adenine Nucleotide Translocator 1/metabolism
16.
Arch Biochem Biophys ; 742: 109638, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37192692

ABSTRACT

Paratrimastix pyriformis is a free-living flagellate thriving in low-oxygen freshwater sediments. It belongs to the group Metamonada along with human parasites, such as Giardia and Trichomonas. Like other metamonads, P. pyriformis has a mitochondrion-related organelle (MRO) which in this protist is primarily involved in one-carbon folate metabolism. The MRO contains four members of the solute carrier family 25 (SLC25) responsible for the exchange of metabolites across the mitochondrial inner membrane. Here, we characterise the function of the adenine nucleotide carrier PpMC1 by thermostability shift and transport assays. We show that it transports ATP, ADP and, to a lesser extent, AMP, but not phosphate. The carrier is distinct in function and origin from both ADP/ATP carriers and ATP-Mg/phosphate carriers, and it most likely represents a distinct class of adenine nucleotide carriers.


Subject(s)
Parasites , Animals , Humans , Parasites/metabolism , Mitochondria/metabolism , Adenosine Monophosphate/metabolism , Mitochondrial Membranes/metabolism , Adenosine Triphosphate/metabolism
17.
Sci Adv ; 9(22): eadh4251, 2023 06 02.
Article in English | MEDLINE | ID: mdl-37256948

ABSTRACT

Mitochondrial uncoupling protein 1 (UCP1) gives brown adipose tissue of mammals its specialized ability to burn calories as heat for thermoregulation. When activated by fatty acids, UCP1 catalyzes the leak of protons across the mitochondrial inner membrane, short-circuiting the mitochondrion to generate heat, bypassing ATP synthesis. In contrast, purine nucleotides bind and inhibit UCP1, regulating proton leak by a molecular mechanism that is unclear. We present the cryo-electron microscopy structure of the GTP-inhibited state of UCP1, which is consistent with its nonconducting state. The purine nucleotide cross-links the transmembrane helices of UCP1 with an extensive interaction network. Our results provide a structural basis for understanding the specificity and pH dependency of the regulatory mechanism. UCP1 has retained all of the key functional and structural features required for a mitochondrial carrier-like transport mechanism. The analysis shows that inhibitor binding prevents the conformational changes that UCP1 uses to facilitate proton leak.


Subject(s)
Ion Channels , Protons , Humans , Cryoelectron Microscopy , Ion Channels/chemistry , Mitochondrial Proteins/metabolism , Purine Nucleotides , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolism
18.
Bioengineering (Basel) ; 10(4)2023 Mar 27.
Article in English | MEDLINE | ID: mdl-37106607

ABSTRACT

Surgical ligatures are a critical component of any surgical procedure since they are the device that provides immediate post-surgical tissue apposition. There have been several studies to improve the design and use of these wound closure devices for different surgical procedures. Yet, there is no standardized technique or device that can be used for any specific application. Over the last two decades, there has been an increased focus on the innovative surgical sutures known as knotless or barbed sutures, along with studies focusing on their advantages and disadvantages in clinical environments. Barbed sutures were invented to reduce the localized stress on the approximated tissues as well as facilitating the surgical technique and improving the clinical outcome for the patient. This review article discusses how barbed sutures evolved from the first patent published in 1964 and how these barbed sutures influence the surgical outcomes in different procedures ranging from cosmetic surgery to orthopedic surgery performed on both human patients and animals.

19.
Radiother Oncol ; 184: 109672, 2023 07.
Article in English | MEDLINE | ID: mdl-37059334

ABSTRACT

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.


Subject(s)
Brachytherapy , Prostatic Neoplasms , Male , Humans , Delphi Technique , Brachytherapy/adverse effects , Brachytherapy/methods , Prostate/pathology , Radiotherapy Dosage , Neoplasm Recurrence, Local/pathology , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/pathology , Salvage Therapy/methods
20.
Soft Matter ; 19(8): 1624-1641, 2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36752696

ABSTRACT

At the present time, there is no successful off-the-shelf small-caliber vascular graft (<6 mm) for the repair or bypass of the coronary or carotid arteries. In this study, we engineer a textile-reinforced hydrogel vascular graft. The textile fibers are circularly knitted into a flexible yet robust conduit to serve as the backbone of the composite vascular graft and provide the primary mechanical support. It is embedded in the hydrogel matrix which seals the open structure of the knitted reinforcement and mediates cellular response toward a faster reendothelialization. The mechanical properties of the composite vascular graft, including bursting strength, suture retention strength and radial compliance, significantly surpass the requirement for the vascular graft application and can be adjusted by altering the structure of the textile reinforcement. The addition of hydrogel matrix, on the other hand, improves the survival, adhesion and proliferation of endothelial cells in vitro. The composite vascular graft also enhances macrophage activation and upregulates M1 and M2 related gene expression, which further improves the endothelial cell migration that might favor the reendothelialization of the vascular graft. Taken together, the textile-reinforced hydrogel shows it potential to be a promising scaffold material to fabricate a tissue engineered vascular graft.


Subject(s)
Endothelial Cells , Macrophage Activation , Textiles , Hydrogels , Cell Proliferation , Macrophages , Tissue Engineering
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