Multidimensional Rietveld refinement of high-pressure neutron diffraction data of PbNCN.

High-pressure neutron powder diffraction data from PbNCN were collected on the high-pressure diffraction beamline SNAP located at the Spallation Neutron Source (SNS) of Oak Ridge National Laboratory (Tennessee, USA). The diffraction data were analyzed using the novel method of multidimensional (two dimensions for now, potentially more in the future) Rietveld refinement and, for comparison, employing the conventional Rietveld method. To achieve two-dimensional analysis, a detailed description of the SNAP instrument characteristics was created, serving as an instrument parameter file, and then yielding both cell and spatial parameters as refined under pressure for the first time for solid-state cyanamides/carbodi-imides. The bulk modulus B 0 = 25.1 (15) GPa and its derivative B'0 = 11.1 (8) were extracted for PbNCN following the Vinet equation of state. Surprisingly, an internal transition was observed beyond 2.0 (2) GPa, resulting from switching the bond multiplicities (and bending direction) of the NCN2- complex anion. The results were corroborated using electronic structure calculation from first principles, highlighting both local structural and chemical bonding details.

The impact of acyl-CoA:cholesterol transferase (ACAT) inhibitors on biophysical membrane properties depends on membrane lipid composition.

Acyl-coenzyme A: cholesterol acyltransferases are enzymes which are involved in the homeostasis of cholesterol. Impaired enzyme activity is associated with the occurrence of various diseases like Alzheimer's disease, atherosclerosis, and cancers. At present, mitotane is the only inhibitor of this class of enzymes in clinical use for the treatment of adrenocortical carcinoma but associated with common and severe adverse effects. The therapeutic effect of mitotane depends on its interaction with cellular membranes. The search for less toxic but equally effective compounds is hampered by an incomplete understanding of these biophysical properties. In the present study, the interaction of the three ACAT inhibitors nevanimibe, Sandoz 58-035, and AZD 3988 with membranes has been investigated using lipid model membranes in conjunction with biophysical experimental (NMR, ESR, fluorescence) and theoretical (MD simulations) approaches. The data show, that the drugs (i) incorporate into lipid membranes, (ii) differently influence the structure of lipid membranes; (iii) affect membrane structure depending on the lipid composition; and (iv) do not cause hemolysis of red blood cells. The results are discussed with regard to the use of the drugs, in particular to better understand their efficacy and possible side effects.

Conversion of UKA to TKA using identical standard implants-How does it compare to primary UKA, primary TKA and revision TKA?

BACKGROUND: UKA is a well-established treatment option for anteromedial osteoarthritis of the knee, resulting in superior functional outcomes but also higher revision rates than TKA. This study aimed to compare the outcomes of UKA, TKA, UKA converted to TKA using identical standard implants and revised TKA to support clinical decision-making. METHODS: In this study, we retrospectively examined 116 patients who underwent UKA, 77 patients who received TKA, 28 patients whose UKA was converted to TKA using identical standard implants, and 21 patients who had a one-stage revision of TKA. The mean age at operation was 66.5 years (39-90 years), with a mean BMI of 28.8 kg/m2 (17.4-58.8) and a mean follow-up period of four years (0.9-9.9 years). We assessed various PROMs, including Oxford Knee Score, UCLA score, KSS score, and a modified WOMAC-Score as well as patient satisfaction and ability to resume daily activities, work, and sports. RESULTS: The highest patient satisfaction was seen in the UKA. All scores were significantly higher for UKA than for TKA, converted UKA, and revised TKA. None of the scores showed a significant inferiority of converted UKA to TKA. In the case of revision, two scores showed significantly better results for converted UKA than for revised TKA. CONCLUSIONS: Our results indicated that patients initially treated with UKA did not have significantly worse functional outcomes after conversion to TKA, given the use of identical standard implants. This highlights the effectiveness of UKA as a therapeutic option with outcomes superior to those of primary TKA and the importance of a bone-sparing procedure. Conversely, revision TKA is linked to poorer functional outcomes compared to both primary arthroplasties.

Borafluorene-Mediated Sulfur Activation: Isolation of Boryl-Linked S7 and S8 Catenates and Related Chalcogenide Molecules.

Although the activation of elemental sulfur by main group compounds is well-documented in the literature, the products of such reactions are often heterocyclic in nature. However, the isolation and characterization of sulfur catenates (i.e., acyclic sulfur chains) is significantly less common. In this study, we report the activation of elemental sulfur by the 9-CAAC-9-borafluorene radical (1) and anion (2) (CAAC = (2,6-diisopropylphenyl)-4,4-diethyl-2,2-dimethyl-pyrrolidin-5-ylidene) to form boron-sulfur catenates (3-6). From the isolation of the octasulfide-bridged compound 3, a sulfur extrusion reaction using 1,3,4,5-tetramethylimidazol-2-ylidene (IMe4) was used to decrease the sulfide chain length from eight to seven (4). Bonding analysis of compounds 3-6 was performed using density functional theory, which elucidated the nature of the sulfur-sulfur bonding observed within these compounds. We also report the synthesis of a series of borafluorene-chalcogenide species (7-9), via diphenyl dichalcogenide activation, which portray characteristics described by an internal heavy atom effect. Compounds 7-9 each exhibit blue fluorescence, with the lowest energy emissive process (S2 → S0) at 436 nm (7 and 8) and 431 nm (9). The S1 → S0 emission is not observed experimentally due to a Laporte forbidden transition. Density functional theory was employed to investigate the frontier molecular orbitals and absorption and emission profiles of compounds 7-9.

Comparison of Biological Augmentation in Rotator Cuff Repair Using Inflamed Versus Noninflamed Bursal Tissue in Rats.

PURPOSE: To examine how augmentation of a rotator cuff repair with inflamed versus noninflamed bursal tissue affects tendon-to-bone healing in a rat model of rotator cuff repair. METHODS: A total of 136 Sprague-Dawley rats were randomly assigned to an inflamed or noninflamed bursal tissue application group. After detachment, the supraspinatus tendon was reattached with bursal tissue sewn onto the tendon-to-bone interface. The specimens were analyzed biomechanically 6 and at 7 weeks and immunohistologically at 1 and at 7 weeks after surgery. RESULTS: Immunohistological results showed no significant difference in the percentage of collagen type II in the tendon-to-bone interface at 1 (P = .87) and 7 weeks (P = .42) when using autologous noninflamed bursal tissue in comparison with inflamed bursal tissue specimens. The inflamed bursa group also showed no significant difference in collagen I to III quotient (P = .14) after surgery in comparison with noninflamed bursa groups after surgery. Biomechanical assessment showed that tendon stiffness (P = .87 inflamed versus noninflammed (resp.) P = .1) and the tendon viscoelasticity (P = .12 resp. P = .07) was the same after 6 and 7 weeks when we compared the inflamed bursa with the noninflamed bursa group. There was no significant difference (P = .8 resp. P = .87) in load to failure between in both inflamed and noninflamed bursa groups after 6 and 7 weeks. CONCLUSIONS: Autologous inflamed bursal tissue derived from the Achilles bursa and implanted to the tendon-to-bone interface after rotator cuff repair facilitates the same histologic and biomechanical healing response as using a noninflamed bursa interposition in rats. CLINICAL RELEVANCE: During augmentation of a rotator cuff repair, it is irrelevant whether the bursa tissue is inflamed.

Pentacyclic fused diborepinium ions with carbene- and carbone-mediated deep-blue to red emission.

Designing molecules that can undergo late-stage modifications resulting in specific optical properties is useful for developing structure-function trends in materials, which ultimately advance optoelectronic applications. Herein, we report a series of fused diborepinium ions stabilized by carbene and carbone ligands (diamino-N-heterocyclic carbenes, cyclic(alkyl)(amino) carbenes, carbodicarbenes, and carbodiphosphoranes), including a detailed bonding analysis. These are the first structurally confirmed examples of diborepin dications and we detail how distortions in the core of the pentacyclic fused system impact aromaticity, stability, and their light-emitting properties. Using the same fused diborepin scaffold, coordinating ligands were used to dramatically shift the emission profile, which exhibit colors ranging from blue to red (358-643 nm). Notably, these diborepinium ions access expanded regions of the visible spectrum compared to known examples of borepins, with quantum yields up to 60%. Carbones were determined to be superior stabilizing ligands, resulting in improved stability in the solution and solid states. Density functional theory was used to provide insight into the bonding as well as the specific transitions that result in the observed photophysical properties.

Zinc Dicyanamide: A Potential High-Capacity Negative Electrode for Li-Ion Batteries.

We demonstrate that the ß-polymorph of zinc dicyanamide, Zn[N(CN)2]2, can be efficiently used as a negative electrode material for lithium-ion batteries. Zn[N(CN)2]2 exhibits an unconventional increased capacity upon cycling with a maximum capacity of about 650 mAh·g-1 after 250 cycles at 0.5C, an increase of almost 250%, and then maintaining a large reversible capacity of more than 600 mAh·g-1 for 150 cycles. Such an increased capacity is primarily attributed to the increased level of activity in the conversion reaction. A combination of conversion-type and alloy-type mechanisms is revealed in this anode material via advanced characterization studies and theoretical calculations. This mechanism, observed here for the first time in transition-metal dicyanamides, is probably responsible for the outstanding electrochemical performance. We believe that this study guides the development of new high-capacity anode materials.

Persistent sodium currents in neurons: potential mechanisms and pharmacological blockers.

Persistent sodium current (INaP) is an important activity-dependent regulator of neuronal excitability. It is involved in a variety of physiological and pathological processes, including pacemaking, prolongation of sensory potentials, neuronal injury, chronic pain and diseases such as epilepsy and amyotrophic lateral sclerosis. Despite its importance, neither the molecular basis nor the regulation of INaP are sufficiently understood. Of particular significance is a solid knowledge and widely accepted consensus about pharmacological tools for analysing the function of INaP and for developing new therapeutic strategies. However, the literature on INaP is heterogeneous, with varying definitions and methodologies used across studies. To address these issues, we provide a systematic review of the current state of knowledge on INaP, with focus on mechanisms and effects of this current in the central nervous system. We provide an overview of the specificity and efficacy of the most widely used INaP blockers: amiodarone, cannabidiol, carbamazepine, cenobamate, eslicarbazepine, ethosuximide, gabapentin, GS967, lacosamide, lamotrigine, lidocaine, NBI-921352, oxcarbazepine, phenytoine, PRAX-562, propofol, ranolazine, riluzole, rufinamide, topiramate, valproaic acid and zonisamide. We conclude that there is strong variance in the pharmacological effects of these drugs, and in the available information. At present, GS967 and riluzole can be regarded bona fide INaP blockers, while phenytoin and lacosamide are blockers that only act on the slowly inactivating component of sodium currents.

A New Methodology for the Accurate Measurement of Tibiofemoral Kinematics in Human Cadaveric Knees: An Evaluation of the Anterior-Posterior Laxity Pre- and Post-Cruciate Ligament Resection.

Anterior-posterior (AP) stability is an important measure of knee performance after total knee arthroplasty (TKA). To improve the stabilizing effect of implants designed to compensate for the loss of the cruciate ligaments, it is important to understand the tibiofemoral contact situation within the native ligamentous situation of the knee and how it changes after cruciate ligament resection. This in vitro study introduces a new approach to accurately measure the tibiofemoral kinematics in a six-degrees-of-freedom joint motion simulator by tracking landmark-based coordinate systems and their corresponding bone geometries. The tibiofemoral contact situation was investigated by projecting the medial and lateral flexion facet centers onto the tibial plateau under AP shear forces across various flexion angles in thirteen knees. Tests were conducted pre- and post-cruciate ligament resection. Post-cruciate ligament resection, the femoral condyles shifted closer to or even exceeded the posterior border of the tibial plateau, but only slightly closer to the anterior border. This study presents a new methodology for measuring the tibiofemoral kinematics that can be applied to multiple loading profiles. It provides a basis for further investigations, including passive or active muscle forces, to enhance the design of total knee protheses and improve surgical outcomes.

Epigenetic Histone Modifications H3K36me3 and H4K5/8/12/16ac Induce Open Polynucleosome Conformations via Different Mechanisms.

Nucleosomes are the basic compaction unit of chromatin and nucleosome structure and their higher-order assemblies regulate genome accessibility. Many post-translational modifications alter nucleosome dynamics, nucleosome-nucleosome interactions, and ultimately chromatin structure and gene expression. Here, we investigate the role of two post-translational modifications associated with actively transcribed regions, H3K36me3 and H4K5/8/12/16ac, in the contexts of tri-nucleosome arrays that provide a tractable model system for quantitative single-molecule analysis, while enabling us to probe nucleosome-nucleosome interactions. Direct visualization by AFM imaging reveals that H3K36me3 and H4K5/8/12/16ac nucleosomes adopt significantly more open and loose conformations than unmodified nucleosomes. Similarly, magnetic tweezers force spectroscopy shows a reduction in DNA outer turn wrapping and nucleosome-nucleosome interactions for the modified nucleosomes. The results suggest that for H3K36me3 the increased breathing and outer DNA turn unwrapping seen in mononucleosomes propagates to more open conformations in nucleosome arrays. In contrast, the even more open structures of H4K5/8/12/16ac nucleosome arrays do not appear to derive from the dynamics of the constituent mononucleosomes, but are driven by reduced nucleosome-nucleosome interactions, suggesting that stacking interactions can overrule DNA breathing of individual nucleosomes. We anticipate that our methodology will be broadly applicable to reveal the influence of other post-translational modifications and to observe the activity of nucleosome remodelers.

Neutrophil-specific expression of JAK2-V617F or CALRmut induces distinct inflammatory profiles in myeloproliferative neoplasia.

BACKGROUND: Neutrophils play a crucial role in inflammation and in the increased thrombotic risk in myeloproliferative neoplasms (MPNs). We have investigated how neutrophil-specific expression of JAK2-V617F or CALRdel re-programs the functions of neutrophils. METHODS: Ly6G-Cre JAK2-V617F and Ly6G-Cre CALRdel mice were generated. MPN parameters as blood counts, splenomegaly and bone marrow histology were compared to wild-type mice. Megakaryocyte differentiation was investigated using lineage-negative bone marrow cells upon in vitro incubation with TPO/IL-1ß. Cytokine concentrations in serum of mice were determined by Mouse Cytokine Array. IL-1α expression in various hematopoietic cell populations was determined by intracellular FACS analysis. RNA-seq to analyse gene expression of inflammatory cytokines was performed in isolated neutrophils from JAK2-V617F and CALR-mutated mice and patients. Bioenergetics of neutrophils were recorded on a Seahorse extracellular flux analyzer. Cell motility of neutrophils was monitored in vitro (time lapse microscopy), and in vivo (two-photon microscopy) upon creating an inflammatory environment. Cell adhesion to integrins, E-selectin and P-selection was investigated in-vitro. Statistical analysis was carried out using GraphPad Prism. Data are shown as mean ± SEM. Unpaired, two-tailed t-tests were applied. RESULTS: Strikingly, neutrophil-specific expression of JAK2-V617F, but not CALRdel, was sufficient to induce pro-inflammatory cytokines including IL-1 in serum of mice. RNA-seq analysis in neutrophils from JAK2-V617F mice and patients revealed a distinct inflammatory chemokine signature which was not expressed in CALR-mutant neutrophils. In addition, IL-1 response genes were significantly enriched in neutrophils of JAK2-V617F patients as compared to CALR-mutant patients. Thus, JAK2-V617F positive neutrophils, but not CALR-mutant neutrophils, are pathogenic drivers of inflammation in MPN. In line with this, expression of JAK2-V617F or CALRdel elicited a significant difference in the metabolic phenotype of neutrophils, suggesting a stronger inflammatory activity of JAK2-V617F cells. Furthermore, JAK2-V617F, but not CALRdel, induced a VLA4 integrin-mediated adhesive phenotype in neutrophils. This resulted in reduced neutrophil migration in vitro and in an inflamed vessel. This mechanism may contribute to the increased thrombotic risk of JAK2-V617F patients compared to CALR-mutant individuals. CONCLUSIONS: Taken together, our findings highlight genotype-specific differences in MPN-neutrophils that have implications for the differential pathophysiology of JAK2-V617F versus CALR-mutant disease.

Discussion on "Bayesian meta-analysis of penetrance for cancer risk" by Thanthirige Lakshika M. Ruberu, Danielle Braun, Giovanni Parmigiani, and Swati Biswas.

Ruberu et al. (2023) introduce an elegant approach to fit a complicated meta-analysis problem with diverse reporting modalities into the framework of hierarchical Bayesian inference. We discuss issues related to some of the involved parametric model assumptions.

Ergosterol promotes aggregation of natamycin in the yeast plasma membrane.

Polyene macrolides are antifungal substances, which interact with cells in a sterol-dependent manner. While being widely used, their mode of action is poorly understood. Here, we employ ultraviolet-sensitive (UV) microscopy to show that the antifungal polyene natamycin binds to the yeast plasma membrane (PM) and causes permeation of propidium iodide into cells. Right before membrane permeability became compromised, we observed clustering of natamycin in the PM that was independent of PM protein domains. Aggregation of natamycin was paralleled by cell deformation and membrane blebbing as revealed by soft X-ray microscopy. Substituting ergosterol for cholesterol decreased natamycin binding and caused a reduced clustering of natamycin in the PM. Blocking of ergosterol synthesis necessitates sterol import via the ABC transporters Aus1/Pdr11 to ensure natamycin binding. Quantitative imaging of dehydroergosterol (DHE) and cholestatrienol (CTL), two analogues of ergosterol and cholesterol, respectively, revealed a largely homogeneous lateral sterol distribution in the PM, ruling out that natamycin binds to pre-assembled sterol domains. Depletion of sphingolipids using myriocin increased natamycin binding to yeast cells, likely by increasing the ergosterol fraction in the outer PM leaflet. Importantly, binding and membrane aggregation of natamycin was paralleled by a decrease of the dipole potential in the PM, and this effect was enhanced in the presence of myriocin. We conclude that ergosterol promotes binding and aggregation of natamycin in the yeast PM, which can be synergistically enhanced by inhibitors of sphingolipid synthesis.

Fragment Orbitals Extracted from First-Principles Plane-Wave Calculations.

Decomposing extended structures into smaller, molecular, even functional groups or simple fragments has a long tradition in chemistry because it allows for understanding certain electronic peculiarities in truly chemical terms. By doing so, invaluable property information is chemically accessible, for example, needed to rationalize catalytic or magnetic or optical nature. In order to also follow that train of thought for periodic materials, we have developed a tool which in a straightforward manner derives fragment molecular orbitals from plane-wave electronic-structure data of whatever kind of solid-state material. We here report on the mathematical apparatus of the method dubbed linear combination of fragment orbitals (LCFO) used for that purpose, implemented within the LOBSTER code. The method is illustrated from various sorts of molecular entities contained in such crystalline materials, together with an assessment of both accuracy and robustness of the new tool.

Extending the new era of genomic testing into pregnancy management: A proposed model for Australian prenatal services.

BACKGROUND: Trio exome sequencing can be used to investigate congenital abnormalities identified on pregnancy ultrasound, but its use in an Australian context has not been assessed. AIMS: Assess clinical outcomes and changes in management after expedited genomic testing in the prenatal period to guide the development of a model for widespread implementation. MATERIALS AND METHODS: Forty-three prospective referrals for whole exome sequencing, including 40 trios (parents and pregnancy), two singletons and one duo were assessed in a tertiary hospital setting with access to a state-wide pathology laboratory. Diagnostic yield, turn-around time (TAT), gestational age at reporting, pregnancy outcome, change in management and future pregnancy status were assessed for each family. RESULTS: A clinically significant genomic diagnosis was made in 15/43 pregnancies (35%), with an average TAT of 12 days. Gestational age at time of report ranged from 16 + 5 to 31 + 6 weeks (median 21 + 3 weeks). Molecular diagnoses included neuromuscular and skeletal disorders, RASopathies and a range of other rare Mendelian disorders. The majority of families actively used the results in pregnancy decision making as well as in management of future pregnancies. CONCLUSIONS: Rapid second trimester prenatal genomic testing can be successfully delivered to investigate structural abnormalities in pregnancy, providing crucial guidance for current and future pregnancy management. The time-sensitive nature of this testing requires close laboratory and clinical collaboration to ensure appropriate referral and result communication. We found the establishment of a prenatal coordinator role and dedicated reporting team to be important facilitators. We propose this as a model for genomic testing in other prenatal services.

Highly Contorted Rigid Nitrogen-Rich Nanographene with Four Heptagons.

Nucleophilic substitution of 9,10-dichlorooctafluoroanthracene with 3,4-diethylpyrrole and subsequent Scholl reaction give the annularly fused decapyrrollyl anthracene. Single crystal X-ray analysis revealed a highly contorted geometry induced by a combination of adjacent heptagons, forming a unique 7-7-6-7-7 topology. The end-to-end twist angle along the acene moiety is 90°. Cyclic voltammetry studies reveal 6-electron oxidation waves. Density functional theory calculations provided further insights into the aromaticity and electronic properties of this highly twisted, nitrogen-rich nanographene. The structural rigidity and high racemization energy barrier have been studied theoretically and experimentally by VT-NMR.

[Functional outcomes and return to sports, work, and daily activities after revision UKA compared to primary UKA and TKA]. / Funktionelle Ergebnisse und Wiederaufnahme von Sport, Arbeit und Alltagsaktivitäten nach Revision eines Monoschlittens im Vergleich zur Primärimplantation eines Mono- und Doppelschlittens.

BACKGROUND: Unicompartmental knee arthroplasty (UKA), in addition to total knee arthroplasty (TKA), has been shown to be effective in the surgical treatment of knee osteoarthritis with appropriate patient selection. In clinical studies, it has demonstrated superior functional results with lower complication rates. In clinical practice, these advantages must be weighed against the disadvantage of an increased revision rate, especially in younger patients with sports and work activities. OBJECTIVES: The aim of this study was to compare the functional outcome as well as the time to return to daily activities, work, and sports after revision of UKA to TKA with those of primary UKA and primary TKA using a matched-pair analysis. MATERIALS AND METHODS: The study was based on a matched-pair analysis at two defined time points, always comparing 28 patients who underwent either revision of a UKA to a TKA, primary UKA, or primary TKA. Patients completed the Oxford Knee Score, UCLA score, Knee Society score, and WOMAC score during standardized follow-up. In addition, postoperative patient satisfaction and return to activities of daily living, work, and sports were recorded in a standardized manner, and a clinical examination was performed. RESULTS: The four functional scores studied showed a common trend in favor of UKA, followed by primary TKA and revision TKA. The differences between converted UKA and primary TKA were not significant. However, at 3.2 years after the last surgery, the results of the converted UKA were significantly lower than those of the primary UKA. Return to work and sports tended to occur the earliest after UKA, followed by TKA and the revision group. All groups showed a tendency to engage in low-impact sports. CONCLUSION: The functional results of revised UKA were significantly inferior to those of primary UKA based on a 3-year follow-up. Return to work, sports, and activities of daily living tended to take longer after revision than after primary implantation of either a UKA or a TKA.

Management after acute injury of the anterior cruciate ligament (ACL). Part 3: Recommendation on surgical treatment.

PURPOSE: The aim of this consensus project was to give recommendations regarding surgical treatment of the anterior cruciate ligament (ACL) injured patient. METHODS: For this consensus process, an expert, steering and rating group was formed. In an initial online meeting, the steering group, together with the expert group, formed various key topic complexes for which multiple questions were formulated. For each key topic, a structured literature search was performed by the steering group. The results of the literature review were sent to the rating group with the option to give anonymous comments until a final consensus voting was performed. Sufficient consensus was defined as 80% agreement. RESULTS: During this consensus process, 30 topics regarding the surgical management and technique of ACL reconstruction were identified. The literature search for each key question resulted in 30 final statements. Of these 30 final statements, all achieved consensus. CONCLUSIONS: This consensus process has shown that surgical treatment of ACL injury is a complex process. Various surgical factors influence patient outcomes. The proposed treatment algorithm can be used as a decision aid for the surgeon. LEVEL OF EVIDENCE: Level V.

Follow-up Treatment after Cartilage Therapy of the Knee Joint - a Recommendation of the DGOU Clinical Tissue Regeneration Working Group. / Nachbehandlung nach Knorpeltherapie am Kniegelenk ­ eine Empfehlung der AG Klinische Geweberegeneration der DGOU.

The first follow-up treatment recommendation from the DGOU's Clinical Tissue Regeneration working group dates back to 2012. New scientific evidence and changed framework conditions made it necessary to update the follow-up treatment recommendations after cartilage therapy.As part of a multi-stage member survey, a consensus was reached which, together with the scientific evidence, provides the basis for the present follow-up treatment recommendation.The decisive criterion for follow-up treatment is still the defect localisation. A distinction is made between femorotibial and patellofemoral defects. In addition, further criteria regarding cartilage defects are now also taken into account (stable cartilage edge, location outside the main stress zone) and the different methods of cartilage therapy (e. g. osteochondral transplantation, minced cartilage) are discussed.The present updated recommendation includes different aspects of follow-up treatment, starting with early perioperative management through to sports clearance and resumption of contact sports after cartilage therapy has taken place.