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Purpose: To systematically examine the effects of radiofrequency (RF) ablation or coblation (controlled ablation) on chondrocyte viability following knee chondroplasty in preclinical literature to determine the effectiveness and safety of RF-based techniques. Methods: A literature search was performed in September 2022 using PubMed and Scopus using the following search terms combined with Boolean operators: “chondroplasty,” “radiofrequency,” “thermal,” “knee,” “chondral defect,” “articular cartilage,” and “cartilage.” The inclusion criteria consisted of preclinical studies examining the effect of RF ablation or coblation on chondrocytes during knee chondroplasty. Exclusion criteria consisted of studies reporting chondroplasty in joints other than the knee, clinical studies, in vitro studies using animal models, case reports, non–full-text articles, letters to editors, surveys, review articles, and abstracts. The following data were extracted from the included articles: author, year of publication, chondral defect location within the knee and chondral characteristics, RF probe characteristics, cartilage macroscopic description, microscopic chondrocyte description, and extracellular matrix characteristics. Results: A total of 17 articles, consisting of 811 cartilage specimens, were identified. The mean specimen age was 63.4 ± 6.0 (range, 37-89) years. Five studies used monopolar RF devices, 7 studies used bipolar RF devices, whereas 4 studies used both monopolar and bipolar RF devices. Time until cell death during ablation at any power was reported in 5 studies (n = 351 specimens), with a mean time to cell death of 54.4 seconds (mean range, 23.1-64) for bipolar RF and 56.3 seconds (mean range, 12.5-64) for monopolar RF devices. Chondrocyte cell death increased with increased wattage, while treatment time was positively correlated with deeper cell death. Conclusions: In this systematic review, histologic analysis demonstrated that RF-based chondroplasty creates a precise area of targeted chondrocyte death, with minimal evidence of necrosis outside the target zone. Caution must be exercised when performing RF-based chondroplasty due to the risk of cell death with increased application time and wattage. Clinical Relevance: Although RF ablation has demonstrated favorable results in preliminary trials, including smoother cartilage and less damage to the surrounding healthy tissue, the risks versus benefits of the procedure are largely unknown. Caution must be exercised when performing RF-based chondroplasty in the clinical setting due to the risk of cell death with increased application time and wattage.

Osteochondral allograft transplantation provides components of both cartilage and subchondral bone and can be used in large and multifocal defects where autologous procedures are limited by donor-site morbidity. Osteochondral allograft transplantation is particularly appealing in the management of failed cartilage repair, as larger defects and subchondral bone involvement are often present, and the use of multiple overlapping plugs might be considered. The described technique provides our preoperative workup and reproducible surgical approach for patients who have undergone previous osteochondral transplantation with graft failure and are young, active patients who would not be otherwise suited for a knee arthroplasty procedure.

Purpose: To investigate the type of questions patients undergoing hip arthroscopy for femoroacetabular impingement (FAI) are searching online and determine the type and quality of the online sources from the top results to each query by the “people also ask” Google algorithm. Methods: Three search strings pertaining to FAI were carried out through Google. The webpage information was manually collected from the “People also ask” Google algorithm. Questions were categorized using Rothwell’s classification method. Each website was assessed using Journal of the American Medical Association Benchmark Criteria for source quality. Results: A total of 286 unique questions were collected with their associated webpages. The most common questions included: “How do you treat femoroacetabular impingement and labral tears without surgery?” “What is the recovery process after hip arthroscopy and are there limitations after surgery?” and “How do you diagnose hip impingement and differentiate from other causes of hip pain?” The Rothwell Classification of questions were fact (43.4%), policy (34.3%), and value (20.6%). The most common webpage categories were Medical Practice (30.4%), Academic (25.8%), and Commercial (20.6%). The most common subcategories were Indications/Management (29.7%) and Pain (13.6%). Government websites had the highest average Journal of the American Medical Association score (3.42), whereas Single Surgeon Practice websites had the lowest (1.35). Conclusions: Commonly asked questions on Google regarding FAI and labral tears pertain to the indications and management of pathology as well as pain control and restrictions in activity. The majority of information is provided by medical practice, academic, and commercial sources, which have highly variable academic transparency. Clinical Relevance: By better understanding which questions patients ask online, surgeons can personalize patient education and enhance patient satisfaction and treatment outcomes after hip arthroscopy.

(1) Background: The expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), an immune checkpoint receptor on T cells, has been associated with dismal outcomes and advanced tumor stages in various solid tumors. The blockade of TIM-3 is currently under examination in several clinical trials. This study examines TIM-3 expression in high-risk soft tissue sarcomas (HR-STS). (2) Methods: Tumor cell expression of TIM-3 on protein level was analyzed in pre-treatment biopsies of patients with HR-STS. TIM-3 expression was correlated with clinicopathological parameters including tumor-infiltrating lymphocyte (TIL) counts, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PDL-1) expression in patients with HR-STS. Survival dependent on the expression of TIM-3 was analyzed. (3) Results: TIM-3 expression was observed in 101 (56%) out of 179 pre-treatment biopsies of patients with HR-STS. TIM-3 expression was significantly more often observed in undifferentiated pleomorphic sarcomas (UPS) compared to other histological subtypes (p < 0.001), high TIL counts (p < 0.001), and high PD-1 (p < 0.001) and PD-L1 expression (p < 0.001). TIM-3 expression did not have a prognostic impact on survival in patients with HR-STS. (4) Conclusions: This is the first study to demonstrate a significant tumor cell expression of TIM-3 in specific subsets of patients with HR-STS. TIM-3 qualifies as a potential immunotherapeutic target in HR-STS.

The lateral patellofemoral ligament acts to resist medial displacement of the patella. When medial subluxation occurs, it usually has an iatrogenic cause such as prior lateral release, an over-tightened medial patellofemoral ligament reconstruction, or detachment of the vastus lateralis from the patella. The justification for lateral retinacular release has historically been to address extensor mechanism issues such as imbalance of the mechanism due to increased retinacular tension. We present a Technical Note on the treatment of chronic medial patellar instability due to a previous lateral retinacular release using a soft-tissue reconstruction approach with a semitendinosus allograft.

Achievement of appropriate mechanical knee alignment is crucial to ensure optimal clinical outcomes following osteotomy procedures about the knee. The use of patient-specific instrumentation (PSI) to assist in preoperative planning and intraoperative realignment has gained increasing popularity. The purpose of this article is to describe a surgical technique involving a medial closing wedge high tibial osteotomy performed using three-dimensional (3D) PSI and cutting guide to revise residual valgus deformity following failed distal femoral osteotomy. The correction angle, 3D position of the hinge and wedge, as well as final plate and screw position are planned preoperatively using virtual software and computed tomography imaging to allow precise surgical execution.

Shoulder and elbow injuries during athletic participation are very common and may require operative intervention if refractory to conservative care. In recovering from these upper extremity injuries, proper postoperative rehabilitation and setting reasonable expectations regarding return to play are very important. This review article focuses on the most common surgically treated shoulder and elbow injuries, including rotator cuff tears, SLAP tears, anterior and posterior shoulder instability, and elbow ulnar collateral ligament tears. Rates of return to play after surgical intervention are encouraging in most professional and recreational athletes but are highly dependent on the severity of injury, as well as the demands and position in sport. Real-world strategies for staged successful rehabilitation are presented and discussed.

Background: Rotator cuff repair using graft augmentation for large-to-massive, full-thickness rotator cuff tears has been reported to have improved clinical outcomes relative to other therapeutic interventions. Although an effective and promising technique, graft augmentation can be technically challenging, particularly with deployment and positioning of the graft. CuffMend is a user-friendly rotator cuff augmentation technique that combines a decellularized dermal allograft with a novel graft deployment device, tendon anchor, and set of lateral knotless, tension-able anchors to allow for a reliable and stable implantation of the graft. Indications: Graft augmentation using CuffMend is indicated for tears with a high risk of retear or incomplete healing. This includes revision tears, poor-quality degenerative tissue, and massive full-thickness rotator cuff tears. Severe glenohumeral osteoarthritic change is the primary contraindication to this technique. Technique Description: The rotator cuff is reduced medially and secured using 3 anchors with sutures passed in a mattress configuration. Graft augmentation is then performed using the CuffMend graft spreader that facilitates placement and attachment of the graft onto the repaired tendon. Results: The patient is recovering as expected and started physical therapy 1 month postoperatively. He is able to perform light activities of daily living and reach the top of his head for daily self-care without pain. He will begin strengthening at 12 weeks postoperatively. Discussion/Conclusion: CuffMend is a new graft augmentation technique that uses a novel graft deployment device for consistent and precise deployment of a decellularized dermal allograft. This facilitates an expedited repair using the graft augmentation technique for optimal clinical and biomechanical outcomes in patients with rotator cuff tears with high risk of retear.

Fractures of the superior pubic ramus can be treated with screw insertion into the osseous fixation pathway (OFP) of the anterior column (AC). The entry point determines whether the screw exits the OFP prematurely. This can be harmful when it enters the hip joint or damages soft tissues inside the lesser pelvis. The exact entry point varies between patients and can be difficult to ascertain on fluoroscopy during surgery. The aim of this study was to determine variation in the location of the entry point. A retrospective single center study was performed at a level 1 trauma center in the Netherlands. Nineteen adult patients were included with an undisplaced fracture of the superior pubic ramus on computer tomography (CT)-scan. Virtual three-dimensional (3D) models of the pelvises were created. Multiple screws were placed per AC and the models were superimposed. A total of 157 screws were placed, of which 109 did not exit the OFP prematurely. A universally reproducible entry point could not be identified. A typical crescent shaped region of entry points did exist and was located more laterally in females when compared to males. Three-dimensional virtual surgery planning can be helpful to identify the ideal entry points in each case.

Controlled, reversible attachment is widely spread throughout the animal kingdom: from ticks to tree frogs, whose weights span from 2 mg to 200 g, and from geckos to mosquitoes, who stick under vastly different situations, such as quickly climbing trees and stealthily landing on human hosts. A fascinating and complex interplay of adhesive and frictional forces forms the foundation of attachment of these highly diverse systems to various substrates. In this review, we present an overview of the techniques used to quantify the adhesion and friction of terrestrial animals, with the aim of informing future studies on the fundamentals of bioadhesion, and motivating the development and adoption of new or alternative measurement techniques. We classify existing methods with respect to the forces they measure, including magnitude and source, i.e., generated by the whole body, single limbs, or by sub-structures. Additionally, we compare their versatility, specifically what parameters can be measured, controlled, and varied. This approach reveals critical trade-offs of bioadhesion measurement techniques. Beyond stimulating future studies on evolutionary and physicochemical aspects of bioadhesion, understanding the fundamentals of biological attachment is key to the development of biomimetic technologies, from soft robotic grippers to gentle surgical tools.

Averaged 7-day composite effluent wastewater samples from twelve wastewater treatment plants (WWTPs) in nine countries (Romania, Serbia, Hungary, Slovenia, Croatia, Slovakia, Czechia, Austria, Germany) in the Danube River Basin were collected. WWTPs' selection was based on countries' dominant technology and a number of served population with the aim to get a representative holistic view of the pollution status. Samples were analyzed for 2248 chemicals of emerging concern (CECs) by wide-scope target screening employing LC-ESI-QTOF-MS. 280 compounds were detected at least in one sample and quantified. Spatial differences in the concentrations and distribution of the compounds classes were discussed. Additionally, samples were analyzed for the possible agonistic/antagonistic potencies using a panel of in vitro transactivation reporter gene CALUX® bioassays including ERα (estrogenics), anti-AR (anti-androgens), GR (glucocorticoids), anti-PR (anti-progestins), PPARα and PPARγ (peroxisome proliferators) and PAH assays. The potency of the wastewater samples to cause oxidative stress and induce xenobiotic metabolism was determined using the Nrf2 and PXR CALUX® bioassays, respectively. The signals from each of the bioassays were compared with the recently developed effect-based trigger values (EBTs) and thus allowed for allocating the wastewater effluents into four categories based on their measured toxicity, proposing a putative action plan for wastewater operators. Moreover, samples were analyzed for antibiotics and 13 antibiotic-resistant genes (ARGs) and one mobile genetic element (intl1) with the aim to assess the potential for antibiotic resistance. All data collected from these various types of analysis were stored in an on-line database and can be viewed via interactive map at https://norman-data.eu/EWW_DANUBE. Keywords: Emerging substances, Wide-scope target screening, Effluent wastewater, Bioassays, Antibiotic resistant genes, Danube River Basin

Due to their robust antioxidant properties, phenolic acids and their analogs are extensively studied for their ability to activate cellular antioxidant pathways, including nuclear factor (erythroid-derived-2)-like 2 (Nrf2)-antioxidant response element (ARE) pathway. Caffeic, ferulic, and gallic acid are well-studied members of phenolic acids. Constant efforts are made to improve the pharmacological effects and bioavailability of phenolic acids by synthesizing their chemical derivatives. This study determines how modifications of the chemical structure of these phenolic acids affect their antioxidant and cytoprotective activities. We have selected six superior antioxidant compounds (12, 16, 26, 35, 42, and 44) of the 48 caffeic acid phenethyl ester (CAPE) analogs based on their ability to scavenge free radicals in vitro using standard antioxidant assays. These compounds exhibited minimal toxicity as indicated by cell cycle and cytochrome C release assays. Among these compounds, 44, the ketone analog of CAPE, exhibited the ability to increase p-Nrf2 (Ser40) levels in 293T cells (p < 0.05). Further, 44, exhibited its antioxidant effect in Drosophila Melanogaster as indicated by an increase in mRNA levels of Nrf2 and GPx (p < 0.05). Finally, the ability of 44 to activate the antioxidant pathway was abolished in the presence of extracellular signal-regulated kinase (ERK) inhibitor in 293T cells. Thus, we identify 44, the ketone analog of CAPE, as a unique antioxidant molecule with the function of ERK-mediated Nrf2 activation.

Molecular predictors of response to chemotherapy and survival have not been put into clinical practice in high-risk soft tissue sarcomas (HR-STS) by now. The expression of TOP2A and SIRT1 has implications for the mechanism of action of doxorubicin, which is the backbone of chemotherapy in HR-STS. Pre-treatment samples of 167 patients with HR-STS were collected. Protein expression levels of TOP2A and SIRT1 were evaluated with tissue microarrays and immunohistochemistry and correlated with clinicopathological parameters, including overall survival (OS). The expression of TOP2A and SIRT1 was seen in 47% and 60% of patients with HR-STS, respectively. TOP2A expression was associated with higher tumor grading and shorter 5-year OS. The expression of SIRT1 was correlated with a better 5- and 10-year OS. The combination of high SIRT1 and low TOP2A (“Top survivors”) significantly predicted a better OS compared to other biomarker combinations. A multivariate analysis confirmed the expression of SIRT1 and the “Top survivor” biomarker combination as independent predictive factors of OS. This is the first study to associate SIRT1 overexpression with a statistically significant prolongation of OS in HR-STS. Both individual markers and their combination can be used as predictive indicators for HR-STS patients scheduled for neoadjuvant anthracycline-based chemotherapy.

The aim of this retrospective study is to evaluate for the first time the impact of a nanocellulose-based wound dressing in the treatment of pediatric patients with both partial- and deep-thickness burns. Usability and effectiveness were defined based on parameters such as frequency of dressing changes under narcosis, duration of hospital stay, onset of complications, need for additional treatments, and follow up scar formation assessment. Fifty-six children who sustained burns in the year 2018 and were treated with a nanocellulose-based wound dressing were included in the trial. The mean stay in hospital was 6.7 days. Patients underwent dressing changes under narcosis 2.4 times on average, and none had wound-associated infection. In all, 82% of the patients were treated only with nanocellulose-based wound dressings, and reepithelialization occurred after ten days. The majority of patients had scars with normal pigmentation (98%), vascularization (91%), height (92%), and pliability (92%). In conclusion, using a nanocellulose-based wound dressing for the treatment of both superficial, partial-thickness and deep, full-thickness burns has several advantages. Compared with the results published in literature on other wound dressings, it requires a moderate number of dressing changes under narcosis and results in short hospital stays. Additionally, it has a low associated infection rate and promotes wound healing.

Coral reefs are a valuable and vulnerable marine ecosystem. The structure of coral reefs influences their health and ability to fulfill ecosystem functions and services. However, monitoring reef corals largely relies on 1D or 2D estimates of coral cover and abundance that overlook change in ecologically significant aspects of the reefs because they do not incorporate vertical or volumetric information. This study explores the relationship between 2D and 3D metrics of coral size. We show that surface area and volume scale consistently with planar area, albeit with morphotype specific conversion parameters. We use a photogrammetric approach using open-source software to estimate the ability of photogrammetry to provide measurement estimates of corals in 3D. Technological developments have made photogrammetry a valid and practical technique for studying coral reefs. We anticipate that these techniques for moving coral research from 2D into 3D will facilitate answering ecological questions by incorporating the 3rd dimension into monitoring.

Brachial cuff blood pressure (BP) is clinically important, but may be an inaccurate substitute for central BP. Many non-invasive devices have been developed that purport to estimate central BP from peripheral artery sites, yet with no standardized guidelines; the accuracy testing of these new devices has not been undertaken in a uniform fashion with comparable protocols. This is an abridged paper describing the recommendations reached by an international task force convened to identify issues that need to be addressed and reach consensus relating to methods for assessing and reporting the accuracy (validation) of central BP devices. The recommendations are endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society, as well as the European Society of Hypertension (ESH) Working Group on Arterial Structure and Function, and the ESH Working Group on Blood Pressure Monitoring and Cardiovascular Variability. Researchers interested in validating central BP monitors should read the full version of the statement.

To ensure delivery of microbiologically safe drinking water, the physical integrity of the distribution system is an important control measure. During repair works or an incident the drinking water pipe is open and microbiologically contaminated water or soil may enter. Before taking the pipe back into service it must be cleaned. The efficacy of flushing and shock chlorination was tested using a model pipe-loop system with a natural or cultured biofilm to which a microbial contamination (Escherichia coli, Clostridium perfringens spores and phiX174) was added. On average, flushing removed 1.5−2.7 log microorganisms from the water, but not the biofilm. In addition, sand added to the system was not completely removed. Flushing velocity (0.3 or 1.5 m/s) did not affect the efficacy. Shock chlorination (10 mg/L, 1−24 h) was very effective against E. coli and phiX174, but C. perfringens spores were partly resistant. Chlorination was slightly more effective in pipes with a natural compared to a cultured biofilm. Flushing alone is thus not sufficient after high risk repair works or incidents, and shock chlorination should be considered to remove microorganisms to ensure microbiologically safe drinking water. Prevention via hygienic working procedures, localizing and isolating the contamination source and issuing boil water advisories remain important, especially during confirmed contamination events.

Caffeic acid phenethyl ester (CAPE) is a bioactive component isolated from propolis. A series of CAPE analogues was synthesized and their antiradical/antioxidant effects analyzed. The effect of the presence of the double bond and of the conjugated system on the antioxidant effect is evaluated with the analogues obtained from 3-(3,4-dihydroxyphenyl) propanoic acid. Those obtained from 2-(3,4-dihydroxyphenyl) acetic acid and 3,4-dihydroxybenzoic acid allow the evaluation of the effect of the presence of two carbons between the carbonyl and aromatic system.

BACKGROUND: 5-lipoxygenase (5-LO) catalyses the transformation of arachidonic acid (AA) into leukotrienes (LTs), which are important lipid mediators of inflammation. LTs have been directly implicated in inflammatory diseases like asthma, atherosclerosis and rheumatoid arthritis; therefore inhibition of LT biosynthesis is a strategy for the treatment of these chronic diseases. METHODOLOGY/PRINCIPAL FINDINGS: Analogues of caffeic acid, including the naturally-occurring caffeic acid phenethyl ester (CAPE), were synthesized and evaluated for their capacity to inhibit 5-LO and LTs biosynthesis in human polymorphonuclear leukocytes (PMNL) and whole blood. Anti-free radical and anti-oxidant activities of the compounds were also measured. Caffeic acid did not inhibit 5-LO activity or LT biosynthesis at concentrations up to 10 µM. CAPE inhibited 5-LO activity (IC(50) 0.13 µM, 95% CI 0.08-0.23 µM) more effectively than the clinically-approved 5-LO inhibitor zileuton (IC(50) 3.5 µM, 95% CI 2.3-5.4 µM). CAPE was also more effective than zileuton for the inhibition of LT biosynthesis in PMNL but the compounds were equipotent in whole blood. The activity of the amide analogue of CAPE was similar to that of zileuton. Inhibition of LT biosynthesis by CAPE was the result of the inhibition of 5-LO and of AA release. Caffeic acid, CAPE and its amide analog were free radical scavengers and antioxidants with IC(50) values in the low µM range; however, the phenethyl moiety of CAPE was required for effective inhibition of 5-LO and LT biosynthesis. CONCLUSIONS: CAPE is a potent LT biosynthesis inhibitor that blocks 5-LO activity and AA release. The CAPE structure can be used as a framework for the rational design of stable and potent inhibitors of LT biosynthesis.

Arterial wave reflections (AWR) are determined by arterial pulse wave velocity (PWV), the distribution and distance of the reflection points (RP) from the heart and the magnitude of these reflections. Pulse waves are reflected at sites of changing impedance. Substantial changes in impedance occur at branching of arteries and when approaching microvascular beds, but the continuous change in impedance along the arterial tree also generates continuous, diffuse reflection patterns, complicating the overall interpretation of wave reflection. This shows that the conceptual view of pulse waves reflected at a discrete site is far too simple. Apart from structural aspects, also functional changes can largely influence AWR. Vasodilation decreases AWR by decreasing stiffness and moving the RP further from the heart. The opposite holds for vasoconstriction. With ageing, stiffness of elastic arteries is progressively increasing, while muscular arteries stiffen much less. This disturbs the progressive increase in arterial stiffness from central to more peripheral medium-sized arteries. Also in hypertension, at the operating pressure arterial stiffness increases in the elastic aorta while it remains unchanged in the muscular radial artery, again changing the progressive change in impedance. It has been speculated that this reduces the impedance mismatch between central and peripheral arteries, leading to higher pulsatile load of the microcirculation and hence contributing to target organ damage in the brain and kidney. These examples show that wave reflections and the consequent changes in arterial waveform and central blood pressure are influenced by a complex interplay between the large and small arteries.

Atherosclerotic cardiovascular disease is the current leading cause of death in industrialized countries. The vast majority of acute cardiovascular events (50–70%) are ascribed to thrombosis following rupture of a vulnerable plaque. Therefore there is an urgent need to discern vulnerable, unstable plaques from stable plaques. A variety of imaging modalities, both invasive and non-invasive, have been developed for the assessment of visualization and quantification of atherosclerosis. In this review, we discuss the advantages and limitations of the available imaging techniques, and their clinical potential for assessment of plaque vulnerability.