No significant difference in skin contamination during anterior cruciate ligament reconstruction with and without preoperative skin cleaning.

PURPOSE: This prospective study aimed to assess whether preoperative antiseptic skin cleansing reduces bacterial contamination and surgical site infections (SSI) following anterior cruciate ligament reconstruction (ACLR). We hypothesized that antiseptic cleaning would lower bacterial load, reducing contamination and early infections. METHODS: One hundred and nineteen patients scheduled for ACLR were included in this prospective, nonrandomized study. Individuals were divided into two groups. Patients in the intervention group applied octenisan® wash lotion daily for three days before surgery and used the wash solution instead of their usual shower gel. Additionally, they swiped their leg with octenisan® soaked gloves on the morning of the operation. The control group followed their usual wash routine with no specific instructions. Fluid samples were taken before surgery from the irrigation bag and at 15-min intervals from the reservoir of the sterile surgical drape during the procedure. Suture material used for the ACL graft and meniscus repair were also collected for testing. The samples were subjected to a 14-day incubation period. Follow-up included outpatient visits at 6 weeks, 12 weeks and 6 months with a final evaluation at 12 months. RESULTS: Contamination rates showed no significant difference between the control and intervention groups. The mean contamination rate in the control group was 6.4% (n = 22) and 6.6% (n = 24) in the intervention group (p = 0.28). At 12-month follow-up, 110 out of 119 participants were included (52 control, 58 intervention). T tests for age (p = 0.19), BMI (p = 0.66), and surgery duration (p = 0.38) showed no significant differences. No early SSI were observed in either group postoperatively. CONCLUSION: Our results indicate that the use of antiseptic wash lotion and gloves does not influence the risk of bacterial contamination during surgery. LEVEL OF EVIDENCE: Level III.

Automated determination of 8-OHdG in cells and tissue via immunofluorescence using a specially created antibody.

Despite powerful DNA repair systems, oxidative damage/modification to DNA is an inevitable side effect of metabolism, ionizing radiation, lifestyle habits, inflammatory pathologies such as type-2 diabetes or metabolic syndrome, cancer and natural aging. One of the most common oxidative DNA modifications is 8-OHdG (8­hydroxy-2'-deoxyguanosine), which is the most widely used marker in research and clinical diagnostics. 8-OHdG is easily and specifically detectable in various samples such as urine, plasma, cells and tissues via a large variety of methods like ELISA, HPLC, chromatographic methods, and immunochemistry. Formed by oxidation of guanine and being representative for the degree of DNA damage, 8-OHdG can be also used as biomarker for risk assessment of various cancers as well as degenerative diseases. Here, we present a highly specific, self-developed 8-OHdG antibody in successful comparison to a commercially one, tested in cells (FF95, HCT116, and HT22) and intestinal tissue, focusing on automatized evaluation via fluorescence/confocal microscopy.

Autologous bone grafting in combination with autologous chondrocyte implantation yields favourable outcomes in the treatment of osteochondral defects of the knee: A systematic literature review.

PURPOSE: This study addresses the gap in the current literature by evaluating the combined treatment of autologous bone grafting and autologous chondrocyte implantation (ABCI) for osteochondral defects of the knee. It aims to evaluate clinical outcomes against methodological quality and to summarize histological results and surgical techniques. METHODS: A thorough search was conducted across Pubmed, Cochrane and Embase databases. Studies reporting clinical outcomes of ABCI for osteochondral defects of the knee were included. Patient-reported outcome measures (PROMs), failure rates, methodological quality and potential conflicts of interest were evaluated. Histological results and surgical techniques were summarized. RESULTS: Eighteen studies with 344 analyzed patients met the eligibility criteria for inclusion. All studies showed a significant improvement (p < 0.05) across different PROMs (subjective International Knee Documentation Committee score, Cincinnati Knee Rating System, Visual Analogue Scale, Lysholm Score, Tegner Activity Scale, Knee injury and Osteoarthritis Outcome Score and Knee Society Score) compared to the preoperative status. Failure rates ranged from 0% to 17.6%, with a mean follow-up of 73.2 months (range: 9.0-143.6 months). Methodological quality was low to medium, including only one comparative study. Six studies reviewed reported a potential conflict of interest. The histological assessment showed effective bonding between autologous chondrocytes and bone graft. A large degree of variability was observed in the operative technique used. CONCLUSION: The current literature suggests that ABCI yields good clinical outcomes at mid- to long-term follow-up with favourable histological results for osteochondral defects of the knee. However, future research should focus on high-quality comparative studies to better guide treatment choices. Introducing ABCI as the standard abbreviation may enhance clarity in future research. LEVEL OF EVIDENCE: Level IV.

An evaluation of a novel method for the MRI-based assessment of Caton-Deschamps index in the Knee.

INTRODUCTION: The radiographical assessment of patella height has historically been performed using X-Ray. The aim of this study was to evaluate a new method for the assessment of patella height using MRI and to assess the correlation with the X-Ray based assessment. MATERIALS AND METHODS: 159 patients who had both lateral radiographs and MRI images were included. Parameters measured included traditional radiographical CDI, MRI-based CDI, and TT-TG distance. On the basis of the TT-TG, the patients were divided into 2 groups. Two different methods were used to assess CDI using MRI: using a single slice image, and an alternative technique using two different cross-sectional images. The correlation of the two measurement methods was assessed using Pearson's correlation coefficient. The intraclass correlation coefficient (ICC) was determined from the measurements of the two investigators. RESULTS: The average TT-TG distance was 11.6 mm (± 4.6). In patients with a TT-TG < 15 mm, both measurement methods showed comparable correlation with measurements on X-Ray. In patients with a TT-TG of > 15 the the new cross-sectional imaging method showed higher correlation with traditional X-Ray assessment compared to CDI assessment using the traditional single slice method (r = 0.594, p < 0.001 vs. r = 0.302, p = 0.055). CONCLUSIONS: The assessment of CDI on MRI using a cross-sectional imaging method has a better correlation with traditional X-Ray assessment of CDI than single-slice assessment. This is particularly true in patients with elevated TT-TG and as such should be preferentially used in the assessment of Patellar height in this cohort.

Activity-Dependent Compensation at the Hip and Ankle at 8 Years After the Reconstruction of Isolated and Combined Posterior Cruciate Ligament Injuries.

BACKGROUND: After posterior cruciate ligament reconstruction (PCLR), functional deficits at the knee can persist. It remains unclear if neighboring joints compensate for the knee during demanding activities of daily living. PURPOSE: To assess long-term alterations in lower limb mechanics in patients after PCLR. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 28 patients who had undergone single-bundle unilateral isolated or combined PCLR performed stair navigation, squat, sit-to-stand, and stand-to-sit tasks at 8.2 ± 2.2 years after surgery. Motion capture and force plates were used to collect kinematic and kinetic data. Then, 3-dimensional hip, knee, and ankle kinematic data of the reconstructed limb were compared with those of the contralateral limb using statistical parametric mapping. RESULTS: Side-to-side differences at the knee were primarily found during upward-driven movements at 8 years after surgery. The reconstructed knee exhibited lower internal rotation during the initial loading phase of stair ascent versus the contralateral knee (P = .005). During the sit-to-stand task, higher flexion angles during the midcycle (P = .017) and lower external rotation angles (P = .049) were found in the reconstructed knee; sagittal knee (P = .001) and hip (P = .016) moments were lower in the reconstructed limb than the contralateral limb. In downward-driven movements, side-to-side differences were minimal at the knee but prominent at the ankle and hip: during stair descent, the reconstructed ankle exhibited lower dorsiflexion and lower external rotation during the midcycle versus the contralateral ankle (P = .006 and P = .040, respectively). Frontal hip moments in the reconstructed limb were higher than those in the contralateral limb during the stand-to-sit task (P = .010); during squats, sagittal hip angles in the reconstructed limb were higher than those in the contralateral limb (P < .001). CONCLUSION: Patients after PCLR exhibited compensations at the hip and ankle during downward-driven movements, such as stair descent, squats, and stand-to-sit. Conversely, residual long-term side-to-side differences at the knee were detected during upward-driven movements such as stair ascent and sit-to-stand. CLINICAL RELEVANCE: After PCLR, side-to-side differences in biomechanical function were activity-dependent and occurred either at the knee or neighboring joints. When referring to the contralateral limb to assess knee function in the reconstructed limb, concentric, upward-driven movements should be prioritized. Compensations at the hip and ankle during downward-driven movements lead to biases in long-term functional assessments.

Assessment of Quality and Readability of Information Provided by ChatGPT in Relation to Anterior Cruciate Ligament Injury.

The aim of our study was to evaluate the potential role of Artificial Intelligence tools like ChatGPT in patient education. To do this, we assessed both the quality and readability of information provided by ChatGPT 3.5 and 4 in relation to Anterior Cruciate Ligament (ACL) injury and treatment. ChatGPT 3.5 and 4 were used to answer common patient queries relating to ACL injuries and treatment. The quality of the information was assessed using the DISCERN criteria. Readability was assessed with the use of seven readability formulae: the Flesch-Kincaid Reading Grade Level, the Flesch Reading Ease Score, the Raygor Estimate, the SMOG, the Fry, the FORCAST, and the Gunning Fog. The mean reading grade level (RGL) was compared with the recommended 8th-grade reading level, the mean RGL among adults in America. The perceived quality and mean RGL of answers given by both ChatGPT 3.5 and 4 was also compared. Both ChatGPT 3.5 and 4 yielded DISCERN scores suggesting "good" quality of information, with ChatGPT 4 slightly outperforming 3.5. However, readability levels for both versions significantly exceeded the average 8th-grade reading level for American patients. ChatGPT 3.5 had a mean RGL of 18.08, while the mean RGL of ChatGPT 4 was 17.9, exceeding the average American reading grade level by 10.08 grade levels and 9.09 grade levels, respectively. While ChatGPT can provide both reliable and good quality information on ACL injuries and treatment options, the readability of the content may limit its utility. Additionally, the consistent lack of source citation represents a significant area of concern for patients and clinicians alike. If AI is to play a role in patient education, it must reliably produce information which is accurate, easily comprehensible, and clearly sourced.

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.

NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2-/- mice were protected from age-related OA development. Taken together, the TLR2-NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA.

Case report: Anti septin-5-encephalitis as a treatable cause of cerebellar ataxia and psychiatric symptoms.

Objectives: Anti-septin-5 encephalitis is a rare disease with only few published cases, mainly based on retrospective CSF and serum analyses. Predominant symptoms are cerebellar ataxia and oculomotor abnormalities. Due to the rareness of the disease, treatment recommendations are scarce. Herein, we prospectively describe the clinical course of a female patient with anti-septin-5 encephalitis. Methods: We describe diagnostic workup, treatment and follow-up of a 54-year-old patient presenting with vertigo, unsteady gait, lack of drive and behavioral changes. Results: Clinical examination revealed severe cerebellar ataxia, saccadic smooth pursuit, upbeat-nystagmus, and dysarthria. Additionally, the patient presented with a depressive syndrome. MRI of the brain and spinal cord were normal. CSF analysis showed lymphocytic pleocytosis (11 cells/µl). Extensive antibody testing revealed anti septin-5 IgG in both CSF and serum without coexisting anti-neuronal antibodies. PET/CT detected no signs of malignancy. Corticosteroids, plasma exchange, and rituximab led to transient clinical improvement followed by relapse. Re-applied treatment with plasma exchange followed by bortezomib resulted in moderate but sustained clinical improvement. Discussion: Anti septin-5 encephalitis represents a rare but treatable and therefore relevant differential diagnosis in patients with cerebellar ataxia. Psychiatric symptoms can be observed in anti septin-5 encephalitis. Immunosuppressive treatment including bortezomib is moderately effective.

Determination of the autophagic flux in murine and human peripheral blood mononuclear cells.

The autophagy lysosomal system (ALS) is crucial for cellular homeostasis, contributing to maintain whole body health and alterations are associated with diseases like cancer or cardiovascular diseases. For determining the autophagic flux, inhibition of lysosomal degradation is mandatory, highly complicating autophagy measurement in vivo. To overcome this, herein blood cells were used as they are easy and routinely to isolate. Within this study we provide detailed protocols for determination of the autophagic flux in peripheral blood mononuclear cells (PBMCs) isolated from human and, to our knowledge the first time, also from murine whole blood, extensively discussing advantages and disadvantages of both methods. Isolation of PBMCs was performed using density gradient centrifugation. To minimize changes on the autophagic flux through experimental conditions, cells were directly treated with concanamycin A (ConA) for 2 h at 37°C in their serum or for murine cells in serum filled up with NaCl. ConA treatment decreased lysosomal cathepsins activity and increased Sequestosome 1 (SQSTM1) protein and LC3A/B-II:LC3A/B-I ratio in murine PBMCs, while transcription factor EB was not altered yet. Aging further enhanced ConA-associated increase in SQSTM1 protein in murine PBMCs but not in cardiomyocytes, indicating tissue-specific differences in autophagic flux. In human PBMCs, ConA treatment also decreased lysosomal activity and increased LC3A/B-II protein levels, demonstrating successful autophagic flux detection in human subjects. In summary, both protocols are suitable to determine the autophagic flux in murine and human samples and may facilitate a better mechanistic understanding of altered autophagy in aging and disease models and to further develop novel treatment strategies.

The MyoPulser field stimulator, a do it yourself programmable electronic pacemaker for contracting cells and tissues.

After providing the free software MYOCYTER that analyzes a large amount of data from videos of contracting cells, tissues or organs, we now present an "Arduino"-based programmable, customizable and cost-effective electronic pacemaker ("MyoPulser") that triggers contraction by electric stimulation of the sample at arbitrary frequencies. In this work, construction, functions and application of the MyoPulser are explained in detail, the electronic pacemaker is also tested on isolated cardiomyocytes and HT22-cells to quantify biological effects of pacing. The device enables the user to select between different pulse types (monophasic, alternating, bi- and polyphasic) adjust the length of an applied pulse (1-200 ms), the gap between two consecutive pulses (20-2000 ms), application of irregular pulses with random length and gaps (simulation of arrhythmia) in a user-defined range, as well as manual pulsing, while extensive data are recorded for every single pulse during the experiment. Electrostimulation of isolated B6 cardiomyocytes showed very little deviation of the observed cellular contraction from the applied pulse settings of the device, while the carbon electrodes used proved to be biologically inert in long-term experiments. Due to the open source code and the expandable setup, the MyoPulser can be easily adapted to even highly specific requirements and together with the software MYOCYTER it represents a complete cardiomyophysiological measuring station.

Management after acute injury of the anterior cruciate ligament (ACL), part 2: management of the ACL-injured patient.

PURPOSE: The aim of this consensus project was to create a treatment algorithm for the management of the ACL-injured patient which can serve as an aid in a shared decision-making process. METHODS: For this consensus process, a steering and a rating group were formed. In an initial face-to-face meeting, the steering group, together with the expert group, formed various key topic complexes for which various 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, 15 key questions were identified. The literature search for each key question resulted in 24 final statements. Of these 24 final statements, all achieved consensus. CONCLUSIONS: This consensus process has shown that ACL rupture is a complex injury, and the outcome depends to a large extent on the frequently concomitant injuries (meniscus and/or cartilage damage). These additional injuries as well as various patient-specific factors should play a role in the treatment decision. The present treatment algorithm represents a decision aid within the framework of a shared decision-making process for the ACL-injured patient. LEVEL OF EVIDENCE: Level V.

[Influence of the COVID-19 pandemic on the physiotherapeutic and medical follow-up care after reconstructions of the anterior cruciate ligament]. / Einfluss der COVID-19-Pandemie auf die physiotherapeutische und ärztliche Nachsorge nach Rekonstruktionen des vorderen Kreuzbandes.

BACKGROUND: The aim of this study was to examine the influence of the COVID-19(coronavirus disease 2019) pandemic on the medical and physiotherapeutic follow-up care after reconstructions of the anterior cruciate ligament. METHODS: 116 patients (72 men and 44 women) who had received a reconstruction of the anterior cruciate ligament between September 2019 and December 2020 were included in this study. These patients were divided into two groups depending on the date of surgery: one group that had received surgery in 2019 before the COVID-19 pandemic and one group that had undergone surgery in 2020 and was directly affected by the COVID-19 pandemic. All patients were interviewed using a standardized questionnaire regarding the influence of the coronavirus pandemic on the medical and physiotherapeutic follow-up care, as well as the moment of return to work. In addition, the range of motion of the respective knee 3 months postoperatively was analysed based on physical examination. RESULTS: At 3 months postoperatively, patients who had undergone surgery in 2020 showed a clear trend towards a higher frequency of extension deficits of ≥ 5° (18.8% vs. 4.3%, p = 0.097) or an inability to bend the knee ≥ 120° (23.3% vs. 10%, p = 0.197) compared to those who had received surgery in 2019. Patients who had undergone surgery in 2020 reported significantly longer delays for appointments, a higher number of futile attempts to get an appointment and a higher number of cancelled appointments, regarding both medical and physiotherapeutic follow-up care. 34.9% of the patients who received surgery in 2020 indicated that they were able to reduce the duration of their sick leave due to the increased possibilities of working in a home-office situation during the pandemic. Alternative treatment options due to the pandemic were offered by 13.3% of the physiotherapists and 12.2% of the physicians. CONCLUSION: Although the physiotherapeutic and medical follow-up care was not directly affected by a "lockdown", the pandemic led to significant restrictions, which are also reflected in a clear trend towards worse clinical outcomes. Consequently, a further expansion of alternative treatment options, which were only offered by 12-13% of practices and that are presumably of comparable relevance for various other diseases, is needed.

The subjective knee value is a valid single-item survey to assess knee function in common knee disorders.

INTRODUCTION: The patient's perspective plays a key role in judging the effect of knee disorders on physical function. We have introduced the Subjective Knee Value (SKV) to simplify the evaluation of individual's knee function by providing one simple question. The purpose of this prospective study was to validate the SKV with accepted multiple-item knee surveys across patients with orthopaedic knee disorders. MATERIALS AND METHODS: Between January through March 2020, consecutive patients (n = 160; mean age 51 ± 18 years, range from 18 to 85 years, 54% women) attending the outpatient clinic for knee complaints caused by osteoarthritis (n = 69), meniscal lesion (n = 45), tear of the anterior cruciate ligament (n = 23) and focal chondral defect (n = 23) were invited to complete a knee-specific survey including the SKV along with the Knee Injury Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee subjective knee form (IKDC-S). The Pearson correlation coefficient was used to evaluate external validity between the SKV and each patient-reported outcome measure (PROM) separately. Furthermore, patient's compliance was assessed by comparing responding rates. RESULTS: Overall, the SKV highly correlated with both the KOOS (R = 0.758, p < 0.05) and the IKDC-S (R = 0.802, p < 0.05). This was also demonstrated across all investigated diagnosis- and demographic-specific (gender, age) subgroups (range 0.509-0.936). No relevant floor/ceiling effects were noticed. The responding rate for the SKV (96%) was significantly higher when compared with those for the KOOS (81%) and the IKDC-S (83%) (p < 0.05). CONCLUSION: At baseline, the SKV exhibits acceptable validity across all investigated knee-specific PROMs in a broad patient population with a wide array of knee disorders. The simplified survey format without compromising the precision to evaluate individual's knee function justifies implementation in daily clinical practice. LEVEL OF EVIDENCE: II, cohort study (diagnosis).

Bacterial contamination of irrigation fluid and suture material during ACL reconstruction and meniscus surgery : Low infection rate despite increasing contamination over surgery time.

PURPOSE: During knee arthroscopy, irrigation fluid from the surgical site accumulates in the sterile reservoir. Whether these fluid collections and also suture material used during the arthroscopic surgical processes show bacterial contamination over time during surgery remains unclear. The purpose of this study was to determine this contamination rate and to analyze its possible influence on postoperative infection. MATERIALS AND METHODS: In this study, 155 patients were included. Fifty-eight underwent reconstruction of the anterior cruciate ligament (ACL), 63 meniscal surgery and 34 patients combined ACL reconstruction and meniscus repair. We collected pooled samples of irrigation fluid from the reservoir on the sterile drape every 15 min during the surgery. In addition, we evaluated suture material of ACL graft and meniscus repair for bacterial contamination. Samples were sent for microbiological analysis, incubation time was 14 days. All patients were seen in the outpatient department 6, 12 weeks and 12 months postoperatively and examined for clinical signs of infection. RESULTS: A strong statistical correlation (R2 = 0.81, p = 0.015) was found between an advanced duration of surgery and the number of positive microbiological findings in the accumulated fluid. Suture and fixation material showed a contamination rate of 28.4% (29 cases). Despite the high contamination rate, only one infection was found in the follow-up examinations, caused by Staphylococcus lugdunensis. CONCLUSION: Since bacterial contamination of accumulated fluid increases over time the contact with the fluid reservoirs should be avoided. LEVEL OF EVIDENCE: IV.

Low-Grade Systemic Inflammation Interferes with Anabolic and Catabolic Characteristics of the Aged Human Skeletal Muscle.

Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein (CRP). Collective evidence suggests that elevated levels of inflammatory mediators such as CRP, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) are correlated with deteriorated skeletal muscle mass and function, though the molecular footprint of this observation in the aged human skeletal muscle remains obscure. Based on animal models showing impaired protein synthesis and enhanced degradation in response to LGSI, we compared here the response of proteolysis- and protein synthesis-related signaling proteins as well as the satellite cell and amino acid transporter protein content between healthy older adults with increased versus physiological blood hs-CRP levels in the fasted (basal) state and after an anabolic stimulus comprised of acute resistance exercise (RE) and protein feeding. Our main findings indicate that older adults with increased hs-CRP levels demonstrate (i) increased proteasome activity, accompanied by increased protein carbonylation and IKKα/ß phosphorylation; (ii) reduced Pax7+ satellite cells; (iii) increased insulin resistance, at the basal state; and (iv) impaired S6 ribosomal protein phosphorylation accompanied by hyperinsulinemia following an acute RE bout combined with protein ingestion. Collectively, these data provide support to the concept that age-related chronic LGSI may upregulate proteasome activity via induction of the NF-κB signaling and protein oxidation and impair the insulin-dependent anabolic potential of human skeletal muscle.

Gait Adaptations at 8 Years After Reconstruction of Unilateral Isolated and Combined Posterior Cruciate Ligament Injuries.

BACKGROUND: It remains unclear how posterior cruciate ligament (PCL) reconstruction influences long-term lower extremity joint biomechanics. PURPOSE: To determine whether patients who underwent PCL reconstruction exhibited long-term alterations in lower limb gait mechanics. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 26 patients underwent gait analyses at 8.2 ± 2.6 years after primary unilateral PCL reconstruction. Sex- and age-matched healthy controls were analyzed for comparison. Gait data were collected using motion capture and force plates. Hip, knee, and ankle angles and moments were compared during initial contact, early stance, and late stance for the reconstructed and uninjured contralateral limbs of patients who underwent PCL reconstruction (PCL group) as well as the limbs of healthy control participants (CON group). RESULTS: No side-to-side kinematic differences were noted between the reconstructed and contralateral limbs of the PCL group; some trivial differences were noted in knee and hip moments. However, major differences between the PCL and CON groups occurred at the knee. Reconstructed and contralateral limbs of the PCL group exhibited larger knee flexion angles during initial contact (Δ = 7.0° [P < .001] and Δ = 6.9° [P < .001], respectively), early stance (Δ = 5.8° [P = .003] and Δ = 6.7° [P < .001], respectively), and late stance (Δ = 7.9° [P < .001] and Δ = 8.0° [P < .001], respectively) compared with the CON group. During early stance, contralateral limbs of the PCL group displayed larger knee flexion moments (Δ = 0.20 N·m/kg; P = .014) compared with the CON group, and both reconstructed (Δ = 0.05 N·m/kg; P = .027) and contralateral (Δ = 0.07 N·m/kg; P = .001) limbs of the PCL group exhibited larger knee external rotation moments compared with the CON group. During late stance, reconstructed and contralateral limbs of the PCL group exhibited smaller knee extension moments (Δ = 0.24 N·m/kg [P < .001] and Δ = 0.26 N·m/kg [P < .001], respectively) and knee internal rotation moments (Δ = 0.06 N·m/kg [P < .001] and Δ = 0.06 N·m/kg [P < .001], respectively) compared with the CON group. No discrepancies were observed at the hip; minimal differences were noted in sagittal-plane ankle mechanics. CONCLUSION: Patients who underwent PCL reconstruction generally exhibited bilateral gait symmetry at 8 years after surgery. However, they exhibited important biomechanical deviations in both knees compared with healthy controls. These modifications likely reflect adaptive gait strategies to protect the PCL after reconstruction. CLINICAL RELEVANCE: Long-term follow-up analyses of patients who underwent PCL reconstruction should not use the uninjured contralateral limb as a "healthy" reference, as it also exhibits mechanical differences compared with controls. Results could inform the development of neuromuscular and strength training programs targeting the restoration of knee biomechanics similar to healthy controls to prevent early-onset degeneration that is frequently associated with altered biomechanics.

Hypertrophy-Reduced Autophagy Causes Cardiac Dysfunction by Directly Impacting Cardiomyocyte Contractility.

Cardiac remodeling and contractile dysfunction are leading causes in hypertrophy-associated heart failure (HF), increasing with a population's rising age. A hallmark of aged and diseased hearts is the accumulation of modified proteins caused by an impaired autophagy-lysosomal-pathway. Although, autophagy inducer rapamycin has been described to exert cardioprotective effects, it remains to be shown whether these effects can be attributed to improved cardiomyocyte autophagy and contractility. In vivo hypertrophy was induced by transverse aortic constriction (TAC), with mice receiving daily rapamycin injections beginning six weeks after surgery for four weeks. Echocardiographic analysis demonstrated TAC-induced HF and protein analyses showed abundance of modified proteins in TAC-hearts after 10 weeks, both reduced by rapamycin. In vitro, cardiomyocyte hypertrophy was mimicked by endothelin 1 (ET-1) and autophagy manipulated by silencing Atg5 in neonatal cardiomyocytes. ET-1 and siAtg5 decreased Atg5-Atg12 and LC3-II, increased natriuretic peptides, and decreased amplitude and early phase of contraction in cardiomyocytes, the latter two evaluated using ImageJ macro Myocyter recently developed by us. ET-1 further decreased cell contractility in control but not in siAtg5 cells. In conclusion, ET-1 decreased autophagy and cardiomyocyte contractility, in line with siAtg5-treated cells and the results of TAC-mice demonstrating a crucial role for autophagy in cardiomyocyte contractility and cardiac performance.

Surprisingly long survival of premature conclusions about naked mole-rat biology.

Naked mole-rats express many unusual traits for such a small rodent. Their morphology, social behaviour, physiology, and ageing have been well studied over the past half-century. Many early findings and speculations about this subterranean species persist in the literature, although some have been repeatedly questioned or refuted. While the popularity of this species as a natural-history curiosity, and oversimplified story-telling in science journalism, might have fuelled the perpetuation of such misconceptions, an accurate understanding of their biology is especially important for this new biomedical model organism. We review 28 of these persistent myths about naked mole-rat sensory abilities, ecophysiology, social behaviour, development and ageing, and where possible we explain how these misunderstandings came about.

Punicalagin Attenuates Palmitate-Induced Lipid Droplet Content by Simultaneously Improving Autophagy in Hepatocytes.

SCOPE: Several studies show that excessive lipid intake can cause hepatic steatosis. To investigate lipotoxicity on cellular level, palmitate (PA) is often used to highly increase lipid droplets (LDs). One way to remove LDs is autophagy, while it is controversially discussed if autophagy is also affected by PA. It is aimed to investigate whether PA-induced LD accumulation can impair autophagy and punicalagin, a natural autophagy inducer from pomegranate, can improve it. METHODS AND RESULTS: To verify the role of autophagy in LD degradation, HepG2 cells are treated with PA and analyzed for LD and perilipin 2 content in presence of autophagy inducer Torin 1 and inhibitor 3-Methyladenine. PA alone seems to initially induce autophagy-related proteins but impairs autophagic-flux in a time-dependent manner, considering 6 and 24 h PA. To examine whether punicalagin can prevent autophagy impairment, cells are cotreated for 24 h with PA and punicalagin. Results show that punicalagin preserves expression of autophagy-related proteins and autophagic flux, while simultaneously decreasing LDs and perilipin 2. CONCLUSION: Data provide new insights into the role of PA-induced excessive LD content on autophagy and suggest autophagy-inducing properties of punicalagin, indicating that punicalagin can be a health-beneficial compound for future research on lipotoxicity in liver.