Signalling of the neuropeptide calcitonin gene-related peptide (CGRP) through RAMP1 promotes liver fibrosis via TGFß1/Smad2 and YAP pathways.

The liver is innervated by primary sensory nerve fibres releasing the neuropeptide calcitonin gene-related peptide (CGRP). Elevated plasma levels of CGRP have been found in patients with liver fibrosis or cirrhosis. We hypothesised that signalling of CGRP and its receptors might regulate liver fibrosis and propose a novel potential target for the treatment. In this study, hepatic expression of CGRP and its receptor component, the receptor activity-modifying protein 1 (RAMP1), was dramatically increased in diseased livers of patients. In a murine liver fibrosis model, deficiency of RAMP1 resulted in attenuated fibrogenesis characterized by less collagen deposition and decreased activity of hepatic stellate cells (HSC). Mechanistically, activity of the TGFß1 signalling core component Smad2 was severely impaired in the absence of RAMP1, and Yes-associated protein (YAP) activity was found to be diminished in RAMP1-deficient liver parenchyma. In vitro, stimulation of the HSC line LX-2 cells with CGRP induces TGFß1 production and downstream signalling as well as HSC activation documented by increased α-SMA expression and collagen synthesis. We further demonstrate in LX-2 cells that CGRP promotes YAP activation and its nuclear translocation subsequent to TGFß1/Smad2 signals. These data support a promotive effect of CGRP signalling in liver fibrosis via stimulation of TGFß1/Smad2 and YAP activity.

Physical activity based on daily steps in patients with chronic musculoskeletal pain: evolution and associated factors.

BACKGROUND: People with chronic musculoskeletal pain (CMSP) often have low physical activity. Various factors can influence the activity level. The aim of this study was to monitor physical activity, assessed by the number of steps per day, over time in people with CMSP and identify factors that could be associated with this activity feature. METHODS: This prospective study involved people undergoing rehabilitation following an orthopedic trauma that had led to CMSP. At entry, participants completed self-reported questionnaires assessing pain, anxiety, depression, catastrophyzing, kinesiophobia, and behavioural activity patterns (avoidance, pacing and overdoing). They also underwent functional tests, assessing walking endurance and physical fitness. To determine daily step counts, participants wore an accelerometer for 1 week during rehabilitation and 3 months post-rehabilitation. The number of steps per day was compared among three time points: weekend of rehabilitation (an estimate of pre-rehabilitation activity; T1), weekdays of rehabilitation (T2), and post-rehabilitation (T3). Linear regression models were used to analyze the association between daily steps at T2 and at T3 and self-reported and performance-based parameters. RESULTS: Data from 145 participants were analyzed. The mean number of steps was significantly higher during T2 than T1 and T3 (7323 [3047] vs. 4782 [2689], p < 0.001, Cohen's d = 0.769, and 4757 [2680], p < 0.001, Cohen's d = 0.693), whereas T1 and T3 results were similar (p = 0.92, Cohen's d = 0.008). Correlations of number of steps per day among time points were low (r ≤ 0.4). Multivariable regression models revealed an association between daily steps at T2 and pain interfering with walking, anxiety and overdoing behaviour. Daily steps at T3 were associated with overdoing behaviour and physical fitness. CONCLUSIONS: Despite chronic pain, people in rehabilitation after an orthopedic trauma increased their physical activity if they were given incentives to do so. When these incentives disappeared, most people returned to their previous activity levels. A multimodal follow-up approach could include both therapeutic and environmental incentives to help maintain physical activity in this population.

Magnetic field and initial stress on a rotating photothermal semiconductor medium with ramp type heating and internal heat source.

This manuscript addresses a significant research gap in the study by employing a mathematical model of photo thermoelastic wave propagation in a rotator semiconductor medium under the effect of a magnetic field and initial stress, as well as ramp-type heating. The considered model is formulated during the photothermal theory and in two-dimensional (2D) electronic-elastic deformation. The governing equations represent the interaction between the primary physical parameters throughout the process of photothermal transfer. Computational simulations are performed to determine the temperature, carrier density, displacement components, normal stress, and shear stress using the application of Lame's potential and normal mode analysis. Numerical calculations are carried out and graphically displayed for an isotropic semiconductor like silicon (Si) material. Furthermore, comparisons are made with the previous results obtained by the others, as well as in the presence and absence of magnetic field, rotation, and initial stress. The obtained results illustrate that the rotation, initial stress, magnetic field, and ramp-type heating parameter all have significant effects. This investigation provides valuable insights into the synergistic dynamics among a magnetization constituent, semiconducture structures, and wave propagation, enabling advancements in nuclear reactors' construction, operation, electrical circuits, and solar cells.

Effects of different slopes on hip and ankle biomechanics of replaced and non-replaced limbs of patients with total knee arthroplasty during incline ramp walking.

Although knee biomechanics has been examined, hip and ankle biomechanics in incline ramp walking has not been explored for patients with total knee arthroplasty (TKA). The purpose of this study was to investigate the hip and ankle joint kinematic and kinetic biomechanics of different incline slopes for replaced limbs and non-replaced limbs in individuals with TKA compared to healthy controls. Twenty-five patients with TKR and ten healthy controls performed walking trials on four slope conditions of level (0°), 5°, 10° and 15° on a customized instrumented ramp system. A 3x4 (limb x slope) repeated analysis of variance was used to evaluate selected variables. The results showed a greater peak ankle dorsiflexion angle in the replaced limbs compared to healthy limbs. No significant interactions or limb main effect for other ankle and hip variables. The peak dorsiflexion angle, eversion angle and dorsiflexion moment were progressively higher in each comparison from level to 15°. The peak plantarflexion moment was also increased with each increase of slopes. Both the replaced and non-replaced limbs of patients with TKA had lower hip flexion moments than the healthy control limbs. Hip angle at contact and hip extension range of motion increased with each increase of slopes. Peak hip loading-response internal extension moment increased with each increase in slope and peak hip push-off internal flexion moment decreased with each increase of slope. Our results showed increased dorsiflexion in replaced limbs but no other compensations of hip and ankle joints of replaced limbs compared to non-replaced limbs and their healthy controls during incline walking, providing further support of using incline walking in rehabilitation for patients with TKA.

[Early-term effectiveness comparison of suture hook suture via double posteromedial approaches and Fast-Fix total internal suture in treatment of Ramp lesions].

Objective: To compare the short-term effectiveness of suture hook suture via double posteromedial approaches and Fast-Fix total internal suture in treatment of Ramp lesions. Methods: A clinical data of 56 patients with anterior cruciate ligament rupture combined with Ramp lesions, who met the selection criteria and admitted between December 2021 and February 2023, was retrospectively analyzed. The Ramp lesions were sutured using suture hook via double posteromedial approaches under arthroscopy in 28 cases (group A) and treated with Fast-Fix total internal suture under arthroscopy in 28 cases (group B). There was no significant difference in age, gender, cause of injury, type of injury, time from injury to operation, side of injury, body mass index, and preoperative Lysholm score, visual analogue scale (VAS) score, and Tegner score between the two groups ( P>0.05). The patients were followed up regularly after operation, and the clinical and imaging healing of the Ramp lesion was evaluated according to the Barrett clinical healing standard and the MRI evaluation standard. Lysholm score, VAS score, and Tegner score were used to evaluate the function and pain degree of knee joint, and the results were compared with those before operation. Results: The incisions of the two groups healed by first intention. All patients were followed up 12-18 months (mean, 14.9 months). Postoperative McMurray tests were negative in both groups. The clinical healing rates of group A and group B were 71.4% (20/28) and 64.3% (18/28) at 6 months after operation, and 92.9% (26/28) and 82.1% (23/28) at 12 months after operation, respectively. The differences between the two groups was not significant ( χ 2=0.327, P=0.567; χ 2=0.469, P=0.225). There was no significant difference in Lysholm score, VAS score, and Tegner score between the two groups at each time point after operation ( P>0.05). The postoperative scores in the two groups significantly improved when compared with those before operation, and the scores at 12 months after operation further improved when compared with those at 6 months after operation, showing significant differences between the different time points in the two groups ( P<0.05). At last follow-up, MRI examination of the knee joint showed that there were 26 (92.9%), 2 (7.1%), and 0 (0) cases of complete healing, partial healing, and nonunion in the Ramp lesion of group A, and 25 (89.3%), 1 (3.6%), and 2 (7.1%) cases in group B, respectively. There was no significant difference between the two groups ( Z=-0.530, P=0.596). Conclusion: Suture hook suture via double posteromedial approaches and Fast-Fix total internal suture under arthroscopy are safe and reliable in the treatment of Ramp lesion, and the knee joint function significantly improves after operation.

Management of Meniscus Pathology with Concomitant Anterior Cruciate Ligament Injury.

PURPOSE OF REVIEW: The purpose of this review is to summarize current clinical knowledge on the prevalence and types of meniscus pathology seen with concomitant anterior cruciate ligament (ACL) injury, as well as surgical techniques, clinical outcomes, and rehabilitation following operative management of these pathologies. RECENT FINDINGS: Meniscus pathology with concomitant ACL injury is relatively common, with reports of meniscus pathology identified in 21-64% of operative ACL injuries. These concomitant injuries have been associated with increased age and body mass index. Lateral meniscus pathology is more common in acute ACL injury, while medial meniscus pathology is more typical in chronic ACL deficiency. Meniscus tear patterns associated with concomitant ACL injury include meniscus root tears, lateral meniscus oblique radial tears of the posterior horn (14%), and ramp lesions of the medial meniscus (8-24%). These meniscal pathologies with concomitant ACL injury are associated with increased rotational laxity and meniscal extrusion. There is a paucity of comparative studies to determine the optimal meniscus repair technique, as well as rehabilitation protocol, depending on specific tear pattern, location, and ACL reconstruction technique. There has been a substantial increase in recent publications demonstrating the importance of meniscus repair at the time of ACL repair or reconstruction to restore knee biomechanics and reduce the risk of progressive osteoarthritic degeneration. Through these studies, there has been a growing understanding of the meniscus tear patterns commonly identified or nearly missed during ACL reconstruction. Surgical management of meniscal pathology with concomitant ACL injury implements the same principles as utilized in the setting of isolated meniscus repair alone: anatomic reduction, biologic preparation and augmentation, and circumferential compression. Advances in repair techniques have demonstrated promising clinical outcomes, and the ability to restore and preserve the meniscus in pathologies previously deemed irreparable. Further research to determine the optimal surgical technique for specific tear patterns, as well as rehabilitation protocols for meniscus pathology with concomitant ACL injury, is warranted.

Secondary Meniscectomy Rates and Risk Factors for Failed Repair of Ramp Lesions Performed at the Time of Primary ACL Reconstruction: An Analysis of 1037 Patients From the SANTI Study Group.

BACKGROUND: Studies evaluating secondary meniscectomy rates and risk factors for failure of ramp repair are sparse and limited by small numbers and heterogeneity. PURPOSES/HYPOTHESIS: The purposes were to determine the secondary meniscectomy rate for failure of ramp repair performed using a posteromedial portal suture hook at the time of anterior cruciate ligament reconstruction (ACLR) and to identify risk factors for secondary meniscectomy. It was hypothesized that patients who underwent ACLR combined with a lateral extra-articular procedure (LEAP) would experience significantly lower rates of secondary meniscectomy compared with those undergoing isolated ACLR. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Patients undergoing primary ACLR and ramp repair between 2013 and 2020 were included in the study. Final follow-up for each patient was defined by his or her last appointment recorded in a prospective database (with a study end date of March 2023). The database and medical records were used to determine whether patients had undergone secondary meniscectomy for failure of ramp repair. Survivorship of ramp repair (using secondary meniscectomy as an endpoint) was determined using the Kaplan-Meier method. Multivariate analysis was used to investigate possible risk factors. RESULTS: A total of 1037 patients were included in the study. The secondary meniscectomy rate after ramp repair was 7.7% at a mean final follow-up of 72.4 months. Patients without combined ACLR + LEAP were >2-fold more likely to undergo a secondary medial meniscectomy compared with those with combined ACLR + LEAP (hazard ratio, 2.455; 95% CI, 1.457-4.135; P = .0007). Age, sex, preoperative Tegner score, and time between injury and surgery were not significant risk factors for failure. CONCLUSION: The rate of secondary meniscectomy after ramp repair performed through a posteromedial portal at the time of primary ACLR was low. Patients who underwent isolated ACLR (rather than ACLR + LEAP) were >2-fold more likely to undergo a secondary medial meniscectomy for failure of ramp repair. Additional risk factors for failure of ramp repair were not identified.

Involvement of RAMP1/p38MAPK signaling pathway in osteoblast differentiation in response to mechanical stimulation: a preliminary study.

OBJECTIVE: The present study aimed to investigate the underlying mechanism of mechanical stimulation in regulating osteogenic differentiation. MATERIALS AND METHODS: Osteoblasts were exposed to compressive force (0-4 g/cm2) for 1-3 days or CGRP for 1 or 3 days. Expression of receptor activity modifying protein 1 (RAMP1), the transcription factor RUNX2, osteocalcin, p38 and p-p38 were analyzed by western blotting. Calcium mineralization was analyzed by alizarin red straining. RESULTS: Using compressive force treatments, low magnitudes (1 and 2 g/cm2) of compressive force for 24 h promoted osteoblast differentiation and mineral deposition whereas higher magnitudes (3 and 4 g/cm2) did not produce osteogenic effect. Through western blot assay, we observed that the receptor activity-modifying protein 1 (RAMP1) expression was upregulated, and p38 mitogen-activated protein kinase (MAPK) was phosphorylated during low magnitudes compressive force-promoted osteoblast differentiation. Further investigation of a calcitonin gene-related peptide (CGRP) peptide incubation, a ligand for RAMP1, showed that CGRP at concentration of 25 and 50 ng/ml could increase expression levels of RUNX2 and osteocalcin, and percentage of mineralization, suggesting its osteogenic potential. In addition, with the same conditions, CGRP also significantly upregulated RAMP1 and phosphorylated p38 expression levels. Also, the combination of compressive forces (1 and 2 g/cm2) with 50 ng/ml CGRP trended to increase RAMP1 expression, p38 activity, and osteogenic marker RUNX2 levels, as well as percentage of mineralization compared to compressive force alone. This suggest that RAMP1 possibly acts as an upstream regulator of p38 signaling during osteogenic differentiation. CONCLUSION: These findings suggest that CGRP-RAMP1/p38MAPK signaling implicates in osteoblast differentiation in response to optimal magnitude of compressive force. This study helps to define the underlying mechanism of compressive stimulation and may also enhance the application of compressive stimulation or CGRP peptide as an alternative approach for accelerating tooth movement in orthodontic treatment.

Improving power ramp rate of a coal-fired power plant by a bypass steam accumulator.

The increasing penetration of high-volatility renewable energy sources in the power system presents higher demands for flexibility from coal-fired power plant (CFPP). To enhance the flexibility of CFPPs, researchers have conducted a significant amount of thermal-system-level research in recent years on increasing system peak shaving depth. However, the load ramp rate of CFPPs under deep peak shaving is rarely discussed, despite its significance to the overall flexibility performance of CFPPs. This paper proposes a steam accumulator storage system integrating to the turbine's bypass system. The steam accumulator charges directly with working fluid from the live steam or reheat systems and discharge to the turbine, responding quickly to power ramp commands. A steady state model and a dynamic model of the proposed system were built and validated, and the calculation shows that the proposed scheme provides a load change of +2.13 % Pe and -8.3%Pe during a round-trip with a power efficiency of 63.6 % at a unit load of 40 % THA. The unit's load increase rate under coordinated control was enhanced by 1.5 % Pe/min, reaching 3 % Pe/min, using the proposed steam accumulator without revising the original controls, and the load decrease rate reached at least 5 % Pe/min. The results indicate that the proposed system provides a straightforward, easy-to-implement, and efficient solution for enhancing the load ramp rate of CFPPs at low loads.

Identifying time-varying dynamics of heart rate and oxygen uptake from single ramp incremental running tests.

Objective.The fact that ramp incremental exercise yields quasi-linear responses for pulmonary oxygen uptake (V˙O2) and heart rate (HR) seems contradictory to the well-known non-linear behavior of underlying physiological processes. Prior research highlights this issue and demonstrates how a balancing of system gain and response time parameters causes linearV˙O2responses during ramp tests. This study builds upon this knowledge and extracts the time-varying dynamics directly from HR andV˙O2data of single ramp incremental running tests.Approach.A large-scale open access dataset of 735 ramp incremental running tests is analyzed. The dynamics are obtained by means of 1st order autoregressive and exogenous models with time-variant parameters. This allows for the estimates of time constant (τ) and steady state gain (SSG) to vary with work rate.Main results.As the work rate increases,τ-values increase on average from 38 to 132 s for HR, and from 27 to 35 s forV˙O2. Both increases are statistically significant (p< 0.01). Further, SSG-values decrease on average from 14 to 9 bpm (km·h-1)-1for HR, and from 218 to 144 ml·min-1forV˙O2(p< 0.01 for decrease parameters of HR andV˙O2). The results of this modeling approach are line with literature reporting on cardiorespiratory dynamics obtained using standard procedures.Significance.We show that time-variant modeling is able to determine the time-varying dynamics HR andV˙O2responses to ramp incremental running directly from individual tests. The proposed method allows for gaining insights into the cardiorespiratory response characteristics when no repeated measurements are available.

How to repair medial meniscal ramp lesions: A systematic review of surgical techniques.

Purpose: to provide a comprehensive overview of all the surgical techniques published in the literature for repairing meniscal ramp lesions focusing on the technical aspects and the pros and cons of every procedure. Such lesions can be managed using various approaches, each of this with its specific advantages and disadvantages. Methods: Pubmed Central, Scopus, and EMBASE databases were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines for studies on surgical techniques for repairing meniscal ramp lesions through May 2023. Overall, 32 articles matched the selection criteria and were included in the study. Results: Debridement alone may be sufficient for small stable meniscal ramp lesions but, for tears in the menisco-capsular junction that affect the stability of the medial meniscus, it seems reasonable to repair it, even though the clinical results available in literature are contrasting. All-inside sutures through anterior portals seems to be an effective solution for meniscal ramp lesions with MTL tears. All-inside sutures through posteromedial portals are particularly useful for large meniscal ramp lesions, in which an inside-out suture can also be performed. Conclusion: Meniscal ramp lesions can be managed using various approaches, each of this with its specific advantages and disadvantages. Further research is required to determine the optimal technique that can be considered as the gold standard and can provide the better results. Level of Evidence: Level III, systematic review.

Heavy-intensity priming exercise extends the V̇o2max plateau and increases peak-power output during ramp-incremental exercise.

This study investigated whether a heavy-intensity priming exercise precisely prescribed within the heavy-intensity domain would lead to a greater peak-power output (POpeak) and a longer maximal oxygen uptake (V̇o2max) plateau. Twelve recreationally active adults participated in this study. Two visits were required: 1) a step-ramp-step test [ramp-incremental (RI) control], and 2) an RI test preceded by a priming exercise within the heavy-intensity domain (RI primed). A piecewise equation was used to quantify the V̇o2 plateau duration (V̇o2plateau-time). The mean response time (MRT) was computed during the RI control condition. The delta (Δ) V̇o2 slope (S; mL·min-1·W-1) and V̇o2-Y intercept (Y; mL·min-1) within the moderate-intensity domain between conditions (RI primed minus RI control) were also assessed using a novel graphical analysis. V̇o2plateau-time (P = 0.001; d = 1.27) and POpeak (P = 0.003; d = 1.08) were all greater in the RI primed. MRT (P < 0.001; d = 2.45) was shorter in the RI primed compared with the RI control. A larger ΔV̇o2plateau-time was correlated with a larger ΔMRT between conditions (r = -0.79; P = 0.002). This study demonstrated that heavy-intensity priming exercise lengthened the V̇o2plateau-time and increased POpeak. The overall faster RI-V̇o2 responses seem to be responsible for the longer V̇o2plateau-time. Specifically, a shorter MRT, but not changes in RI-V̇o2-slopes, was associated with a longer V̇o2plateau-time following priming exercise.NEW & NOTEWORTHY It remains unclear whether priming exercise extends the maximal oxygen uptake (V̇o2max) plateau and increases peak-power output (POpeak) during ramp-incremental (RI) tests. This study demonstrates that a priming exercise, precisely prescribed within the heavy-intensity domain, extends the plateau at V̇o2max and leads to a greater POpeak. Specifically, the extended V̇o2max plateau was associated with accelerated RI-V̇o2 responses.

Identifying unstable ramp lesions using ultrasonography.

BACKGROUND: Patients with suspected ramp lesions on magnetic resonance imaging (MRI) or ultrasonography (US) healed and showed no instability based on intraoperative arthroscopic findings. The purpose of this study was to assess the use of US in evaluating ramp lesions preoperatively and intraoperatively. METHODS: Eighty-two knees that underwent anterior cruciate ligament (ACL) reconstruction between January 2022 and June 2023 were included to assess the ramp lesion complication rate and instability using arthroscopic findings. The detection rate of ramp lesions using US at the initial visit and preoperatively was also investigated. The test-retest reliability was assessed using the intraclass correlation coefficient and analyzed using two-way random effects and absolute agreement. The patients were divided into two groups based on the presence or absence of ramp lesions, and these data were compared using Student's t-test. Statistical significance was set at p < 0.05. RESULTS: On ultrasound examination, 90.0% of the cases had a ramp lesion at the initial examination, of which 22.2% were poorly delineated on the day of surgery. In the cases where the ramp lesion was unstable at the time of surgery, it could be delineated using US. In the cases where the ramp lesion was stable, it was difficult to delineate the lesion using US. CONCLUSIONS: Unstable ramp lesions complicating ACL injuries could be detected using US.

Tolerability and Safety of Large-Volume Hyaluronidase-Facilitated Subcutaneous Immunoglobulin 10% Administered with or without Dose Ramp-Up: A Phase 1 Study in Healthy Participants.

PURPOSE: Facilitated subcutaneous immunoglobulin (fSCIG; immune globulin infusion 10% [human] with recombinant human hyaluronidase [rHuPH20]) permits high-volume subcutaneous immunoglobulin (SCIG) infusion, shorter infusion times and reduced dosing frequency relative to conventional SCIG. It is initiated by gradually increasing infusion volumes over time (dose ramp-up) to achieve target dose level (TDL). Whether ramp-up strategies have tolerability or safety advantages over direct initiation at full TDL has not been evaluated clinically. METHODS: This phase 1 open-label study assessed tolerability and safety of fSCIG 10% with accelerated or no ramp-up compared with conventional ramp-up in healthy adults (NCT04578535). Participants were assigned to one of the three ramp-up arms to achieve TDLs of 0.4 or 1.0 g/kg/infusion. The primary endpoint was the proportion of infusions completed without interruption or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety was assessed as a secondary endpoint. RESULTS: Of 51 participants enrolled, 50 (98.0%) tolerated all fSCIG 10% infusions initiated (n = 174). Infusion rate was reduced in one participant owing to headache in the 0.4 g/kg/infusion conventional ramp-up arm. Study discontinuations were higher in the no ramp-up arm (70%) versus the conventional (0%) and accelerated (22%) arms at the 1.0 g/kg/infusion TDL. Safety outcomes did not substantially differ between treatment arms. CONCLUSION: The favorable tolerability and safety profiles of fSCIG 10% in healthy participants support initiating treatment with fSCIG 10% with accelerated ramp-up at TDLs up to 1.0 g/kg. Data support no ramp-up at TDLs close to 0.4 g/kg but additional data are needed for higher doses.

Investigation of the anatomic risk factors in acute anterior cruciate ligament ruptures to develop ramp lesions of the medial meniscus by quantitative MRI.

OBJECTIVE: To investigate the anatomic risk factors of knee in patients with acute non-contact anterior cruciate ligament (aACL) ruptures to develop ramp lesions. METHODS: A total of 202 subjects were retrospectively divided into three groups: (1) aACL ruptures combined with ramp lesions group (n = 76); (2) isolated ACL ruptures group (n = 56) and (3) normal controls group (n = 70). Quantitative morphological parameters on MRI were measured including: diameter of medial femoral condyle (MFC), anterior-posterior length and depth of medial tibial plateau (MTP AP length and depth), lateral posterior tibial slope (LPTS) and medial posterior tibial slope (MTPS), asymmetry of LPTS and MPTS (LMPTS), lateral meniscal slope (LMS), and medial meniscal slope (MMS). RESULTS: The MTP AP length, MTP AP length/MFC diameter ratio, MTP depth, LPTS and the asymmetry of LMPTS showed significant differences among the three groups (p < 0.001). The risk factors associated with the ramp lesions including a longer MTP AP length (OR 1.17, 95% CI 1.00-1.44, p = 0.044), increased MTP depth (OR 1.91, 95% CI 1.22-3.00, p = 0.005) and lager ratio (OR 1.11, 95% CI 1.01-1.22, p = 0.036). The highest AUC was the MTP AP length/MFC diameter ratio (0.74; 95% CI, 0.66-0.82). The combination model increased higher accuracy (0.80; 95% CI, 0.72-0.88). CONCLUSION: Several bony anatomic characteristics of the knee, especially the morphology of medial tibia plateau, are additional risk factors for aACL ruptures to develop ramp lesions. CRITICAL RELEVANCE STATEMENT: Predictive anatomic risk factors of the knee for patients with acute non-contact anterior cruciate ligament (aACL) ruptures to develop ramp lesions, especially the morphology of medial tibia plateau, are detectable by MRI. KEY POINTS: Ramp lesion development can complicate aACL ruptures and requires specific treatment. Longer AP length and increased MTP depth are risk factors for concurrent ramp lesions. Identification of ramp lesions allows for the most appropriate treatment.

RAMPing up knowledge of the translocon.

Advanced cryo-EM approaches reveal surprising insights into the molecular structure that allows nascent proteins to be inserted into the membrane of the endoplasmic reticulum.

Archaeomagnetic Dating of the Outer Revetment Wall at Tel Lachish.

The fortifications of Lachish, a key site in archaeology of the Iron Age Southern Levant, are the focus of ongoing debate. The Outer Revetment Wall, encircling nearly the entire site, was traditionally associated with Levels IV-III and was thought to have been in use during the Assyrian campaign in 701 BCE. It has recently been suggested that it was built a millennium earlier. Here we present archaeomagnetic dating of a mudbrick tower incorporated in this wall, indicating that it was burnt during the Iron Age and was most likely built during this period. Combining archaeological, historical and archaeomagnetic data reveals the intense fire that occurred during the 701 BCE Assyrian siege. This fire could have been set by the people of Lachish, in a desperate attempt to damage the Assyrian siege engines or siege ramp, as depicted in the well-known Lachish relief, or by the Assyrians as part of their siege tactics.

Biomechanical characteristics of the meniscocapsular junction of the posterior segment of the medial meniscus.

PURPOSE: Despite extensive literature available on the mechanical properties of knee ligaments and menisci, research on the mechanical properties of the meniscus-capsular junction (MCJ) is lacking. This study aims to investigate the biomechanical behavior of the MCJ of the medial meniscus using a tensile failure test. MATERIALS AND METHODS: Seven dissected cadaveric knees were used for biomechanical analysis. Tensile failure tests were performed using an INSTRON ElectroPuls E1000 stress system to measure stress/strain curves, maximum load at failure, elastic limit load, elongation at break, elongation at the elastic limit, and linear stiffness, were collected and analyzed. RESULTS: All ruptures occurred at the MCJ. The MCJ displayed similar mechanical properties to knee ligaments. Average values were: maximum load at failure (63.9 ± 3.2 N), yield load (52.9 N ± 2.6 N), elongation at break (2.5 mm ± 0.3 mm), elongation at the elastic limit (1.25 mm ± 0.15 mm), strain at break (47.0% ± 3.5%), strain at yield (23.2% ± 2.3%), and stiffness (56.6 ± 9. N/mm-1). CONCLUSION: The meniscus-capsular junction's mechanical properties are similar to other knee ligaments and may play a role in knee stability. The findings provide insights into the the behavior of the meniscus-capsular junction could have clinical implications for diagnosing and surgical treatment of meniscocapsular lesions.

Secondary restraints in ACL reconstruction: State-of-the-art.

At-risk patients continue to experience a high likelihood of graft rupture after anterior cruciate ligament (ACL) reconstruction (ACLR). This narrative review seeks to provide the reader with an evidence-based synopsis of state-of-the-art concepts related to secondary restraint lesions, and how addressing them surgically might result in improved outcomes of ACLR.

Muscle excitability testing.

Conventional electrophysiological methods, i.e. nerve conduction studies and electromyography are suitable methods for the diagnosis of neuromuscular disorders, however, they provide limited information about muscle fibre membrane properties and underlying disease mechanisms. Muscle excitability testing is a technique that provides in vivo information about muscle fibre membrane properties such as membrane potential and ion channel function. Since the 1960s, various methodologies have been suggested to examine muscle membrane properties but technical difficulties have limited its use. In 2009, an automated, fast and simple application, the so-called multi-fibre muscle velocity recovery cycles (MVRC) has accelerated the use of muscle excitability testing. Later, frequency ramp and repetitive stimulation protocols have been developed. Though this method has been used mainly in research for revealing disease mechanisms across a broad range of neuromuscular disorders, it may have additional diagnostic uses; value has been shown particularly in muscle channelopathies. This review will provide a description of the state-of-the art of methodological and clinical studies for muscle excitability testing.