Repair Site Research Articles

CO2 protects cells from iron-Fenton oxidative DNA damage in Escherichia coli and humans

While hydroxyl radical is commonly named as the Fenton product responsible for DNA and RNA damage in cells, here we demonstrate that the cellular reaction generates carbonate radical anion due to physiological bicarbonate levels. In human and Escherichia coli models, their transcriptomes were analyzed by RNA direct nanopore sequencing of ribosomal RNA and chromatography coupled to electrochemical detection to quantify oxidation products in order to follow the bicarbonate dependency in H2O2-induced oxidation. These transcriptomic studies identified physiologically relevant levels of bicarbonate focused oxidation on the guanine base favorably yielding 8-oxo-7,8-dihydroguanine (OG). In human cells, the bicarbonate-dependent oxidation was further analyzed in the metabolome by mass spectrometry, and a glycosylase-dependent qPCR assay to quantify oxidation sites in telomeres. These analyses further identify guanine as the site of oxidation when bicarbonate is present upon H2O2 exposure. Labile iron as the catalyst for forming carbonate radical anion was demonstrated by repeating the bicarbonate-dependent oxidations in cells experiencing ferroptosis, which had a >fivefold increase in redox-active iron, to find enhanced overall guanine-specific oxidation when bicarbonate was present. The complete profiling of nucleic acid oxidation in the genome, transcriptome, and metabolome supports the conclusion that a cellular Fe(II)-carbonate complex redirects the Fenton reaction to yield carbonate radical anion. Focusing H2O2-induced oxidative modification on one pathway is consistent with the highly evolved base excision repair suite of enzymes to locate G-oxidation sites for repair and gene regulation in response to oxidative stress.

Bone-marrow-based augmentation in rotator cuff repair—from microfracture to bone marrow aspirate concentrate

AbstractRotator cuff tears are a major cause of shoulder dysfunction, and relatively high rates of rotator cuff re-tear persist despite surgical advancements, particularly in patients with poor biological healing potential. Bone-marrow-based augmentation techniques, specifically bone marrow stimulation (BMS) and bone marrow aspirate concentrate (BMAC), have been introduced to enhance the biological environment at the repair site, potentially improving outcomes. Bone marrow stimulation, commonly achieved through microfracture, stimulates the release of growth factors and mesenchymal stem cells (MSCs) from the bone marrow to promote tendon-to-bone integration. Although simple and cost-effective, clinical results for BMS augmentation in rotator cuff repair (RCR) are mixed, with most recent meta-analyses not demonstrating a clinically significant superiority over conventional RCR. Augmentation with BMAC offers a more sophisticated approach, concentrating MSCs and anti-inflammatory cytokines to directly enhance the healing process. Preclinical studies have shown promising results with BMAC augmentation, demonstrating improved tendon integrity and biomechanical strength. The existing clinical studies suggest BMAC may reduce re-tear rates and enhance tendon healing, although outcomes are not yet universally optimal. The current evidence highlights the potential of these techniques, particularly as a potential treatment option in biologically challenging cases. However, the variability in clinical outcomes underscores the need for further research to refine these methods and establish their role in routine clinical practice.

Duhuo Jisheng Decoction in reduction of inflammatory response via Transforming growth factor-β/Smad signaling pathway for repairing rabbit articular cartilage Injury: A Randomized Controlled Trial

ObjectiveThis study aims to investigate the mechanism underlying the effect of Duhuo Jisheng Decoction on the repair of rabbit articular cartilage injury through a reduction in the inflammatory response mediated by the Transforming growth factor (TGF)-β/Smad signaling pathway. MethodsA rabbit articular cartilage injury model was constructed using a ring bone extraction drill. Twenty-four Japanese white rabbits were randomly divided into six groups, namely Sham operation, model, low-dose Duhuo Jisheng Decoction, medium-dose Duhuo Jisheng Decoction, high-dose Duhuo Jisheng Decoction, and positive control groups. The treatment lasted 12 weeks. Gross observation, International Cartilage Repair Society score, Wakitani score, and Micro-computed tomography analysis were used to evaluate the structural repair of cartilage injury. Histology and immunohistochemistry were used to observe the proteoglycan, P-TβRII, P-Smad2, and type II collagen expression levels. Enzyme-linked immunosorbent assay was used to analyze the concentrations of Matrix Metalloproteinase-13 and Syndecan-4 in the joint fluid; and RT-PCR and Western Blot were used to observe the mRNA and protein expressions of ALK5, Sox-9, P-Smad3, and TGF-β1 at the injury repair site. ResultsThe repair effect of cartilage injury, as seen through gross observation and quantitative scoring, was better in all the Duhuo Jisheng Decoction treatment groups than in the model group. The medium dose group of Duhuo Jisheng Decoction had the best repair effect. We observed remarkable structural restoration of cartilage injury in the medium-dose Duhuo Jisheng Decoction group, with the subchondral bone presenting a distinct hierarchy, and parameters such as bone volume fraction and trabecular separation/spacing being significantly augmented. We found high expression levels of proteoglycans, P-TβRII, P-Smad2, and type II collagen. The concentrations of Matrix Metalloproteinase-13 and Syndecan-4 in the joint fluid were significantly lower following treatment. The low gene expression levels of ALK5, Sox-9, P-Smad3, and TGF-β1 in the injury site of the model group could be reversed in the medium-dose Duhuo Jisheng Decoction group. ConclusionDuhuo Jisheng Decoction can repair rabbit cartilage injury and reverse the levels of inflammatory factors in the joint fluid. The mechanism underlying its therapeutic effect is related to the activation of the TGF-β/Smad signaling pathway. This study provides a reliable basis for using Duhuo Jisheng Decoction to treat cartilage injury following knee osteoarthritis.

Preferential motor reinnervation is modulated by both repair site and distal nerve environments

To restore function after nerve injury, axons must regenerate from the injury site to the periphery, then reinnervate appropriate end organs when they arrive. Only 10 % of adults who suffer nerve injury will regain normal function, often because axons regenerate to functionally inappropriate targets (Brushart, 2011). The peripheral destination of these axons is largely determined by the pathways they enter at the site of nerve repair. To improve clinical outcomes, it is thus critical to improve the accuracy of axon pathfinding. In rodents, motor axons regenerating in mixed nerve preferentially reinnervate pathways leading to muscle, a process termed preferential motor reinnervation (PMR). Previous experiments have shown that PMR can be enhanced by predegenerating nerve grafts to enhance growth factor production and remove inhibitory factors (Abdullah et al., 2013). The current experiments explore the relative contributions of motor pathways, sensory pathways, and the repair environment to this enhancement. Sensory and/or motor pathways within rat femoral nerve grafts were predegenerated for 3 weeks to optimize growth factor production (Brushart et al., 2013) or for 12 weeks to deplete it. Optimizing the environment within previously motor Schwann cell tubes promoted PMR, regardless of whether adjacent sensory pathways were optimized or chronically denervated. However, this positive effect was abolished when sensory pathways were undergoing acute Wallerian degeneration immediately after nerve repair. The repair environment thus precluded motor axon pathfinding in spite of an optimized distal motor pathway. When sensory pathways were optimized and motor pathways were chronically denervated, not only was PMR abolished, but motoneurons failed to respond to the greater volume of growth factors in the sensory nerve. Small sensory neurons, however, selectively reinnervated cutaneous nerve under these conditions. These experiments thus strengthen the concept that, in adult rats, sensory and motor pathways have unique identities capable of influencing both sensory and motor axon regeneration. Furthermore, they demonstrate that, in the rat, delaying nerve repair for 3 weeks to enhance growth factor production and clear the products of acute Wallerian degeneration can enhance regeneration specificity without the need for exogenous treatments.

Modelling the Repair of Carbon-Centered Protein Radicals by Phenolic Antioxidants.

Oxidative stress is a biological process that has been linked to many diseases, hence understanding how to prevent and repair it is essential to medicine. The thermodynamics and kinetics of the repair reactions of radically damaged leucine (a lateral chain in a simplified protein environment) by twenty phenolic antioxidants are studied at the M06-2X(SMD)/6-31++G(d,p) level of theory in water and pentyl ethanoate. The two repair mechanisms modelled are formal-hydrogen atom transfer (f-HAT) and single electron transfer (SET). Although all f-HAT reactions are thermodynamically favourable, only one of the phenols produced rate constants in the diffusion limit, exhibiting biological relevance. SET is not suspected to be an important repair pathway for the phenols studied. We show that the Bell-Evans-Polanyi principle, which relates thermodynamics and kinetics properties for a reaction, breaks down when comparing between the solvents, protein repair sites, and the phenolic antioxidants. While thermodynamic data can be used as valuable screening tools, the kinetic calculation of rate constants in solution is crucial for enhancing the biological relevance of theoretical studies.

The Sternocleidomastoid Muscle Reverse Pad: A "Safety Net" in Catastrophic Tracheal Surgery Situation.

This paper presents the outcomes of employing the inferiorly based rotated sternocleidomastoid muscle flap in complex tracheal reconstruction/repair scenarios, focusing on the key objectives of ensuring stable airway, functional digestive tract and patient survival. A retrospective analysis was performed for patients treated at two medical centers (A.O. San Camillo Forlanini, Rome, and A.O.U. Careggi, Florence) from 2011 to 2023, in which the sternocleidomastoid muscle (SCM) flap, detached from the mastoid and basicranium, was rotated on the lower pivot directly onto the repair site and pedicled to the sternal origin to ensure the continuity of the airway. Average postoperative hospital stay, follow-up period and patient survival were analyzed. Follow-up assessments encompassed bronchoscopies and CT scans conducted at intervals of 15 and 28 days, and subsequently at 3 and 9 months. A total of five patients were enrolled in this study. These cases included one patient with anterior tracheal wall lesions with abundant tissue loss, one patient with an anterior wall necrosis due to descending cervical mediastinitis and three patients with extra-long tracheoesophageal fistulas (TEFs) (greater than 4.5 cm or >30% of the total tracheal length). In the case of the direct repair of a TEF with a proximal tracheal stenosis, the sternocleidomastoid muscle was used to reconstruct the tissue deficit caused by extensive loss of substance in the left lateral side of the tracheal wall. In case of repair through exclusion of the TEF, the sternocleidomastoid muscle was interposed between the visceral sutures after exclusion of the TEF by an endomechanical device, in one case even substituting the membranous part of the tracheal wall. Our technique allows rotation on the sternal head of the sternocleidomastoid muscle with the lowest rotation radius, pedicled to the sternal origin, detached from the mastoid process and superior nuchal line, thus providing optimal vascularization from the superior thyroid artery/external carotid artery and accessory vasculature from the suprascapular artery. Patients exhibited uneventful postoperative recovery concerning airway and digestive patency. The mean postoperative hospitalization duration was 41 days. The follow-up assessments were negative for postoperative complications. The use of sternocleidomastoid muscle flap was proposed to ensure repair and protection of the suture margin or to constitute a portion, as a scaffold, of the wall by leveraging the muscle's vascularization and thickness. This technique may be considered a leading component in managing complex situations in tracheal surgery.

A novel solvent-extruded tacrolimus-eluting suture for attenuated inflammation and scarring in skin repair

This study aimed to design an absorbable suture that locally delivers the immunosuppressive agent, tacrolimus (FK506), to attenuate scar tissue formation by modulating inflammation. As the suture degrades, it releases FK506 directly into the repair site. The poly (l-lactide-co-caprolactone) (PLLA-PCL) polymer and 0.2 % wt FK506 were co-extruded using a solvent extrusion technique to generate the drug-eluting sutures. The properties of the generated sutures were assessed regarding FK506 release in vitro, wound closure in an in vivo murine model, murine skin histology for structural and inflammatory markers, and mechanical strength of both sutures and healed murine skin. The generated suture consistently released FK506 at ≤10 ng/day rates. Following annealing, the sutures retained 60 % of their anticipated tensile strength, exhibiting enhanced ductility. The histological examination and in vivo murine study indicated that wounds treated with FK506-eluting PLLA-PCL sutures produced a thinner epidermal layer, enhanced integrin β4 expression, increased keratinocyte presence, attenuated inflammation, and reduced scarring, demonstrating healed tissue improvements compared with those treated with the placebo, poly (glycolic-co-caprolactone) (PGCL), sutures. Mechanical evaluations of healed tissue indicated that drug-PLLA-PCL sutures did not reduce the mechanical strength of the skin compared to placebo PGCL sutures. The FK506-eluting PLLA-PCL sutures show promising results in advancing wound healing by offering targeted drug delivery. This innovative method can improve wound healing and provide a streamlined approach to scar management. Continued research, optimization, and broad-scale studies are needed to refine the manufacturing process and ensure that the properties of the suture meet clinical requirements.

Iatrogenic Female Genitourinary Fistula in Uganda: Etiology, Twelve-Year Trends, and Risk Factors for Development Following Cesarean Section.

To describe the magnitude and trend of the iatrogenic genitourinary fistula in Uganda, and the risk factors for development following the Cesarean Section (CS). A retrospective review of charts of women with a confirmed diagnosis of genitourinary fistula at four regional fistula repair sites in Uganda between 2010 and 2021 was conducted. A fistula was classified as iatrogenic if it was; ureteric, vesico-cervical, vesico-uterine, or vaginal vault fistula that followed an obstetric or gynecological surgery. The annual proportions for the ischemic and iatrogenic fistula over the study period were compared. A sub group analysis of women with genitourinary fistula delivered by CS was done to determine the factors associated with iatrogenic fistula. Multivariable log binomial regression was performed to determine the independent risk factors. There were 521 women who presented with genito-urinary fistula of which, 169 (32.4%) were iatrogenic. Most of the iatrogenic fistulae followed CS (71%). The proportions of iatrogenic fistulae increased from 8/52 (9.6%) in 2010 to 38/88 (43.2%) in 2020. The risk factors for iatrogenic fistula following CS were; Grand-multiparity (OR = 5.8; 95% CI: 2.1-15.4), Repeat CS (OR = 4.1; 95% CI: 1.8-9.3), CS performed by an intern doctor (OR = 4.8; 95% CI: 1.5-15.5) and CS done at a Health Centre IV (OR = 4.5; 95% CI: 1.2-16.7). The magnitude of the iatrogenic genitourinary fistula in Uganda is high and most follow CS. There is an observed rising trend in iatrogenic fistula. The risk factors for iatrogenic fistula following CS are grandmultiparity, repeat CS, CS performed by intern doctors and CS performed at lower health facilities. There is a need for continuous training and supervision of lower cadre doctors involved in CS to reduce on the rising trend of iatrogenic fistula.

Carotid versus axillary artery cannulation for descending aorta remodeling in type A acute aortic dissection.

Arterial cannulation sites for the surgical repair of type A aortic dissection (AAD) have evolved from right axillary artery (AA) cannulation to bilateral carotid artery (CA) based of femoral artery (FA) cannulation. Postoperative descending aorta remodeling is closely linked to the false lumen area ratio (FLAR), defined as false lumen area/aortic area, as well as to the incidence of renal replacement therapy (RRT). To investigate the effect of the updated arterial cannulation strategy on descending aortic remodeling. A total of 443 AAD patients who received FA combined cannulation between March 2015 and March 2023 were included in the study. Of these, 209 received right AA cannulation and 234 received bilateral CA cannulation. The primary outcome was the change in FLAR, as calculated from computed tomography angiography in three segments of the descending aorta: Thoracic (S1), upper abdominal (S2), and lower abdominal (S3). Secondary outcomes were the incidence of RRT and the serum inflammation response, as observed by the levels of high sensitivity C reaction protein (hs-CRP) and Interleukin-6 (IL-6). The postoperative/preoperative ratio of FLAR in S2 and S3 was higher in the AA group compared to the CA group (S2: 0.80 ± 0.08 vs 0.75 ± 0.07, P < 0.001; S3: 0.57 ± 0.12 vs 0.50 ± 0.12, P < 0.001, respectively). The AA group also had a significantly higher incidence of RRT (19.1% vs 8.5%, P = 0.001; odds ratio: 2.533, 95%CI: 1.427-4.493) and higher levels of inflammation cytokines 24 h after the procedure [hr-CRP: 117 ± 17 vs 104 ± 15 mg/L; IL-6: 129 (103, 166) vs 83 (69, 101) pg/mL; both P < 0.001] compared to the CA group. The CA cannulation strategy was associated with better abdominal aorta remodeling after AAD repair compared to AA cannulation, as observed by a greater change in FLAR and lower incidence of RRT.

Indocyanine Green Fluorescence Angiography (ICG-FA) in the management of intestinal injuries following penetrating abdominal trauma: a case-control study comparing postoperative outcomes.

The surgical management of penetrating hollow visceral injuries includes primary repair or exteriorization. Tissue perfusion at the site of gastrointestinal suture repair may be challenging to assess and is vulnerable to local energy transfer-related injury, micro- or macro-circulatory insufficiency, or splanchnic vasoconstriction for various reasons. Breakdown of suture lines can lead to potentially life-threatening complications. The intraoperative use of Indocyanine Green Fluorescence Angiography (ICG-FA) may reduce the risk of postoperative morbidity and mortality by ensuring optimal tissue perfusion at the chosen site of suture repair. We conducted a retrospective review of the postoperative complications, length of Intensive Care (ICU) stay, and length of hospital stay in patients undergoing laparotomy, with and without ICG-FA for penetrating abdominal trauma at a Level One Trauma Center in Cape Town, South Africa. One hundred patients were included in the study, of which 20 underwent laparotomy with ICG-FA, and 80 did not. The overall complication rate was significantly lower in the ICG-FA group (OR 0.336, p-value=0.0412). The anastomotic leak rates in the ICG-FA and control groups were 0% and 6.25%, respectively (p-value=0.5799). Revision surgery was required in 2 and 14 patients in the ICG-FA and control groups, respectively (OR 0.524, p-value=0.516). The mean length of stay in hospital showed no statistical difference, 8.6 and 5.3 days for the ICG-FA and control groups, respectively (p-value=0.092). The mean length of ICU stay was 6.3 and 2.3 days for the ICG-FA and control groups, respectively (p-value=0.1642). Lower levels of overall postoperative complications and lower rates of revision surgery in patients undergoing laparotomy with ICG-FA are promising. Non-significant findings regarding the relationship between the usage of ICG-FA and anastomotic leak rates suggest the need for larger randomized studies.

INO80 regulates chromatin accessibility to facilitate suppression of sex-linked gene expression during mouse spermatogenesis.

The INO80 protein is the main catalytic subunit of the INO80-chromatin remodeling complex, which is critical for DNA repair and transcription regulation in murine spermatocytes. In this study, we explored the role of INO80 in silencing genes on meiotic sex chromosomes in male mice. INO80 immunolocalization at the XY body in pachytene spermatocytes suggested a role for INO80 in the meiotic sex body. Subsequent deletion of Ino80 resulted in high expression of sex-linked genes. Furthermore, the active form of RNA polymerase II at the sex chromosomes of Ino80-null pachytene spermatocytes indicates incomplete inactivation of sex-linked genes. A reduction in the recruitment of initiators of meiotic sex chromosome inhibition (MSCI) argues for INO80-facilitated recruitment of DNA repair factors required for silencing sex-linked genes. This role of INO80 is independent of a common INO80 target, H2A.Z. Instead, in the absence of INO80, a reduction in chromatin accessibility at DNA repair sites occurs on the sex chromosomes. These data suggest a role for INO80 in DNA repair factor localization, thereby facilitating the silencing of sex-linked genes during the onset of pachynema.

Deficient functional wound closure as measured by elevated trans-epidermal water loss predicts chronic wound recurrence: An exploratory observational study

A single-center, prospective, observational pilot study was performed to evaluate wound healing endpoint and recurrence by measuring transepidermal water loss (TEWL) post-closure at the site of wound repair. Patients with clinically-defined chronic wounds (such as pressure ulcers, diabetic ulcers, and trauma wounds) who visited the Plastic Surgery outpatient department or were in-patients at the All India Institute of Medical Sciences, Rishikesh, India, and were referred for chronic wound management, were enrolled. Non-invasive point-of-care TEWL measurements were obtained, from closed wound-site and contralateral healthy skin site, starting from confirmation of closure (post-closure, V0) continuing every 2 weeks for a maximum of five visits or until the wound recurred. Statistical analyses of the data involved logistic regression and likelihood ratio chi-square tests to assess differences in TEWL at visit 0 (V0) between the closed wound site and reference skin, with the TEWL score as the sole predictor of recurrence. Of the 72 subjects that completed the study, 44 (61%) showed no recurrence and 28 (39%) had wounds that recurred over a period of 12 weeks. A significant association was found between the V0 (post-closure) TEWL score and the odds of wound recurrence, both in univariate analysis (OR [95%CI] = 1.26[1.14,1.42] (p < 0.001) and after adjusting for covariates in multivariable analysis (OR [95%CI] = 1.34[1.19,1.61] (p < 0.001). The likelihood ratio chi-square analysis demonstrated that the V0 TEWL score is a significant universal predictor of recurrence across all wound types studied. Cases of closed wounds with subsequent recurrence showed an overall higher post-closure V0 TEWL score, compared to those who did not have a wound recurrence, across visits. The TEWL score cut-off value predictive of recurrence was 24.1 g.m–2.h–1 (AUC = 0.967). The outcome of this pilot study on a wide range of chronic wounds leads to the hypothesis that post-closure TEWL at the site of wound healing is a reliable biomarker of wound recurrence. It also raises the question whether the clinical endpoint of wound closure should include re-establishment of skin barrier function as additional criterion. The current standard of care wound closure endpoint calls for re-epithelialization of the wound with no discharge for two consecutive weeks disregarding the functional parameter of restoration of skin barrier function at the wound-site.

The Effect of Ethanol on Rotator Cuff Repairs in a Rodent Model

BackgroundAlcohol consumption is a significant risk factor for both the occurrence and severity of rotator cuff tears. However, there is limited supporting evidence to suggest alcohol use is associated with suboptimal outcomes following operative repair of rotator cuff tears. Rat shoulders have been demonstrated as consistent and reliable models for studying rotator cuff disease. Hypothesis/PurposePerioperative alcohol exposure will negatively impact biomechanical and histologic properties of surgically repaired rotator cuffs in rats. MethodsRats were randomized to receive a 20% ethanol or isocaloric control solution as their primary source of drinking water. A tenotomy of the supraspinatus tendon from bone was performed surgically and then immediately repaired with a transosseous technique. Following surgery, rats were continued on the same exposure solution until animals were humanely euthanized at 7, 14, or 21 days postoperatively. The surgically-repaired shoulders underwent biomechanical testing to assess load to failure and failure strain. Histological evaluation of tendon-to-bone healing was performed by a blinded pathologist using a qualitative grading system. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on total RNA from tendon-to-bone interface tissue was performed to quantify the mRNA expression of Type I & III collagen, and transforming growth factor-beta 1 (TGF-B1) & 3 (TGF-B3) at the repair site. ResultsBiomechanical testing showed that repaired shoulder constructs in rats exposed to ethanol had significantly lower load to failure at 7 days postop relative to repairs in rats exposed to a control solution. No other biomechanical parameters or time points reached statistical significance. TGF-B3 mRNA expression was found in significantly higher quantities at the repair sites of rats exposed to ethanol at 7 days postop relative to control rat repair sites. No other time points or factors reached statistical significance. No significant differences were identified amongst time points or groups at the healing tendon-to-bone interface. ConclusionAlcohol exposure significantly decreases biomechanical load to failure of rotator cuff repairs in the early postoperative period in rat models. In the later postoperative period, alcohol exposure was not associated with a decrease in biomechanical load to failure compared to controls. Additionally, rats exposed to ethanol have significantly higher TGF-B3 expression at repair sites on postoperative day 7. This data suggests that ethanol consumption does deleteriously affect rotator cuff and bone healing. Future study is needed to validate the clinical significance of these findings in humans.

Significantly smaller lateral extrusion was observed within 24 weeks after all-inside suture repairs of radial tear in the middle segment of lateral meniscus compared to inside-out repairs.

To evaluate the postoperative meniscal extrusion between all-inside suture (AIS) and trans-capsular suture (TCS) repair techniques. Thirteen patients (mean age, 19.4 years) underwent AIS repairs using only sutures (AIS group) for radial tears in the middle segment of the lateral meniscus (RTMLM), and seven patients (mean age, 20.3 years) underwent inside-out repairs among TCS (TCS group). For all cases, lateral (LE), anterior (AE) and posterior (PE) meniscal extrusions of the lateral meniscus were measured during preoperative and 3-, 12- and 24-week postoperative MRIs. Then, the change of each extrusion from preoperative to each postoperative period was calculated as ∆LE, ∆AE and ∆PE. There was no significant difference between the AIS and TCS groups in the preoperative extrusions. As for postoperative extrusions, only ∆LEs in the AIS group was significantly smaller than those in the TCS group at all postoperative periods (-1.5 ± 1.7 vs. 0.9 ± 0.7 mm at 3-week, -0.9 ± 0.9 vs. 0.4 ± 0.9 mm at 12-week and -0.3 ± 1.0 vs. 0.6 ± 1.1 mm at 24-week postoperation). In ∆AEs and ∆PEs, at all three postoperative periods, there were no significant differences. Postoperative LE, AE and PE on MRIs after AIS and TCS repairs for RTMLM were investigated. Significantly smaller lateral extrusion was observed within 24 weeks after AIS repairs of RTMLM compared to TCS repairs, which could lead to stabilization of the repair site and prevent degenerative changes. Case-control study, retrospective comparative study, Level Ⅲ.

Applied and expert research on fire and industrial safety of main pipelines

The article provides an analytical assessment of the consequences of violations of industrial and fire safety rules during repair work on the example of main oil pipelines. The issue is urgent due to explosions and fires, as well as staff injuries, which requires an analysis and assessment of the causes of their occurrence and reliability improvement during repair work at hazardous production facilities in Irkutsk region. The factual basis of the study is data on incidents related to the personnel training and repair sites, explosions (pops), the dynamics of the emergency situation and consequences for personnel and the economy. The study concludes that in terms of eliminating explosions and fires and minimizing their consequences, the industrial and fire safety system has not been properly developed for repair and other works at hazardous production facilities.

Outcomes After Osteochondral Allograft Transplantation of the Medial Femoral Condyle in Patients With Varus and Nonvarus Alignment

Background: Fresh osteochondral allograft (OCA) transplantation is an effective technique for the treatment of focal chondral and osteochondral defects in the knee. Coronal-plane malalignment leads to increased contact forces within a compartment and subsequently the cartilage repair site and may lead to higher failure rates. However, the magnitude of the effect of coronal-plane malalignment on graft survivorship and clinical outcomes has not been well characterized. Purpose: To evaluate how varus malalignment affects graft survival and patient-reported outcomes after isolated OCA transplantation of the medial femoral condyle (MFC). Study Design: Cohort study; Level of evidence, 3. Methods: A total of 70 patients (74 knees) who underwent primary OCA transplantation of the MFC between 2005 and 2019 were identified from a prospectively collected single-surgeon cartilage registry with a minimum 2-year follow-up. Coronal-plane alignment was evaluated utilizing standing hip-to-ankle radiographs. OCA failure, defined as removal of the graft or conversion to arthroplasty, and reoperations were recorded. Patient-reported outcomes were obtained preoperatively and postoperatively using the International Knee Documentation Committee score, Knee injury and Osteoarthritis Outcome Score, modified Merle d’Aubigné–Postel score, and overall patient satisfaction score. Results: The mean mechanical tibiofemoral angle for patients with varus alignment was 3.9° of varus (range, 1.1° to 8.9°) and for patients with nonvarus alignment it was 0.02° of valgus (range, 3.6° varus to 4.6° valgus). Graft survivorship was 95.3% in the varus group and 95.8% in the nonvarus group (P = .918) at 5 years postoperatively. Reoperations after OCA transplantation occurred in 14.0% of the varus group and 22.6% of the nonvarus group (P = .336). The mean International Knee Documentation Committee total score improved from 45.2 preoperatively to 74.8 at latest follow-up in the varus group and from 40.5 preoperatively to 72.3 at latest follow-up in the nonvarus group. Patient satisfaction was >85%. Conclusion: Patients undergoing isolated OCA transplantation of the MFC had high rates (>90%) of graft survivorship and significant improvements in pain and function. Patients with mild preexisting varus malalignment were found to have no difference in the failure rate or clinical outcomes compared with patients with nonvarus alignment.

Biological Patch in the Repair of Rotator Cuff Tears: Functional and Clinical Evaluation of Twenty-Three Cases with a Mean Follow-Up of Six Years.

Background: Rotator cuff (RC) repair leads to less than optimal results when dealing with massive lesions, so the use of scaffolds as biological support has been proposed to improve RC repair site biology. The present study aims to evaluate the clinical and radiographical outcomes of a series of patients suffering from massive or irreparable RC tears treated with patch (porcine or human scaffolds) repair (augmentation or bridging). Methods: Twenty-three patients with a minimum follow-up of 24 months were subjectively, clinically, and radiographically assessed before and after surgery. Three different patient-related outcome measurements (PROMs) (American Shoulder and Elbow Surgeons score, Constant score, visual analog scale) were used for the subjective and clinical evaluation, while plain radiographs and magnetic resonance imaging where employed for radiographical follow-up. Results: Regardless of the technique (augmentation or bridging) or type of scaffold (porcine or human) employed, at follow-up, all patients experienced a statistically significant improvement in all PROMs and clinically. Conclusions: Patch repair represents a valid salvage procedure in massive or irreparable RC tears, improving the quality of life and eventually delaying the need for prosthetic replacement.

Modulation of Annexin-Induced Membrane Curvature by Cholesterol and the Anionic Lipid Headgroup during Plasma Membrane Repair.

Annexins (ANXAs), calcium-sensitive phospholipid-binding proteins, are pivotal for cellular membrane repair, which is crucial for eukaryotic cell survival under membrane stress. With their unique trimeric arrangements and crystalline arrays on the membrane surface, ANXA4 and ANXA5 induce membrane curvature and rapidly orchestrate plasma membrane resealing. However, the influence of cholesterol and anionic lipid headgroups on annexin-induced membrane curvature remains poorly understood at the molecular level. Using all-atom molecular dynamics simulations, we measured the local curvature-induced underneath ANXA4 and ANXA5 monomers and trimers when they bind to lipid bilayers of distinct lipid compositions: PSPC (20% POPS, 80% POPC), PAPC (20% POPA, 80% POPC), and PSPCCHL (14% POPS, 56% POPC, 30% cholesterol). Laser injury experiments were conducted on MCF7 cells transfected to transiently express fluorescently labeled ANXA4 or ANXA5 to facilitate the examination of protein and lipid accumulation at the damage site. Annexin trimers induce higher curvature than monomers, particularly with cholesterol present. Annexin trimers induce similar curvatures on both PAPC and PSPC membranes. Notably, among monomers, ANXA5 induces the highest curvature on PAPC, suggesting more efficient recruitment of ANXA5 compared with ANXA4 in the early stages of membrane repair near a lesion. Laser injury experiments confirm rapid coaccumulation of phosphatidic acid lipids with ANXA4 and ANXA5 at repair sites, potentially enhancing the accumulation of annexins in the early stages of membrane repair.

Nucleotide excision repair of aflatoxin-induced DNA damage within the 3D human genome organization.

Aflatoxin B1 (AFB1), a potent mycotoxin, is one of the environmental risk factors that cause liver cancer. In the liver, the bioactivated AFB1 intercalates into the DNA double helix to form a bulky DNA adduct which will lead to mutation if left unrepaired. Here, we adapted the tXR-seq method to measure the nucleotide excision repair of AFB1-induced DNA adducts at single-nucleotide resolution on a genome-wide scale, and compared it with repair data obtained from conventional UV-damage XR-seq. Our results showed that transcription-coupled repair plays a major role in the damage removal process. We further analyzed the distribution of nucleotide excision repair sites for AFB1-induced DNA adducts within the 3D human genome organization. Our analysis revealed a heterogeneous AFB1-dG repair across four different organization levels, including chromosome territories, A/B compartments, TADs, and chromatin loops. We found that chromosomes positioned closer to the nuclear center and regions within A compartments have higher levels of nucleotide excision repair. Notably, we observed high repair activity around both TAD boundaries and loop anchors. These findings provide insights into the complex interplay between AFB1-induced DNA damage repair, transcription, and 3D genome organization, shedding light on the mechanisms underlying AFB1-induced mutagenesis.

Cost-based performance optimization of a single system under a hierarchical imperfect maintenance policy

Abstract Due to the influence from external factors such as repair sites and seasonal climate change, it is difficult to restore the system performance to any intermediate level between perfect maintenance and minimal maintenance through imperfect maintenance. This article first categorizes the states of the system just before repair into three classes based on its internal degradation level: failure, major defect, and minor defect, with three corresponding thresholds. Subsequently, the corresponding repairs are carried out to dwindle the system’s degradation to different levels. In detail, if the internal degradation level of the system just before repair is recognized as minor defect, an imperfect repair, termed as type I imperfect repair, is implemented to scale down the degradation level below the minor defect threshold. If the degradation level is identified as major defect, an upgraded imperfect repair, termed as type II imperfect repair, is executed to only lower the degradation to the level between the minor defect threshold and major defect threshold. Otherwise, if the degradation before repair is beyond the failure threshold, replacement will be carried out instead of these imperfect repairs. Thus, a novel hierarchical imperfect maintenance structure is introduced. Then, a multi-variable repair cost model is constructed when considering the related costs incurred from inspection, type I imperfect repair, type II imperfect repair, replacement, and even system downtime. Finally, with the aid of the stationary law of Markov chains and the semi-regenerative process, the cost-based performance optimization with three parameters, including the inspection interval, minor defect threshold, and major defect threshold, is explored through a numerical experiment, and the closed expression of the optimal cost rate is provided.