Cellular and molecular mechanisms of action of transcranial direct current stimulation: evidence from in vitro and in vivo models.

Transcranial direct current stimulation is a noninvasive technique that has been experimentally tested for a number of psychiatric and neurological conditions. Preliminary observations suggest that this approach can indeed influence a number of cellular and molecular pathways that may be disease relevant. However, the mechanisms of action underlying its beneficial effects are largely unknown and need to be better understood to allow this therapy to be used optimally. In this review, we summarize the physiological responses observed in vitro and in vivo, with a particular emphasis on cellular and molecular cascades associated with inflammation, angiogenesis, neurogenesis, and neuroplasticity recruited by direct current stimulation, a topic that has been largely neglected in the literature. A better understanding of the neural responses to transcranial direct current stimulation is critical if this therapy is to be used in large-scale clinical trials with a view of being routinely offered to patients suffering from various conditions affecting the central nervous system.

The morphological and molecular changes of brain cells exposed to direct current electric field stimulation.

BACKGROUND: The application of low-intensity direct current electric fields has been experimentally used in the clinic to treat a number of brain disorders, predominantly using transcranial direct current stimulation approaches. However, the cellular and molecular changes induced by such treatment remain largely unknown. METHODS: Here, we tested various intensities of direct current electric fields (0, 25, 50, and 100V/m) in a well-controlled in vitro environment in order to investigate the responses of neurons, microglia, and astrocytes to this type of stimulation. This included morphological assessments of the cells, viability, as well as shape and fiber outgrowth relative to the orientation of the direct current electric field. We also undertook enzyme-linked immunosorbent assays and western immunoblotting to identify which molecular pathways were affected by direct current electric fields. RESULTS: In response to direct current electric field, neurons developed an elongated cell body shape with neurite outgrowth that was associated with a significant increase in growth associated protein-43. Fetal midbrain dopaminergic explants grown in a collagen gel matrix also showed a reorientation of their neurites towards the cathode. BV2 microglial cells adopted distinct morphological changes with an increase in cyclooxygenase-2 expression, but these were dependent on whether they had already been activated with lipopolysaccharide. Finally, astrocytes displayed elongated cell bodies with cellular filopodia that were oriented perpendicularly to the direct current electric field. CONCLUSION: We show that cells of the central nervous system can respond to direct current electric fields both in terms of their morphological shape and molecular expression of certain proteins, and this in turn can help us to begin understand the mechanisms underlying the clinical benefits of direct current electric field.

BERNN: Enhancing classification of Liquid Chromatography Mass Spectrometry data with batch effect removal neural networks.

Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful method for profiling complex biological samples. However, batch effects typically arise from differences in sample processing protocols, experimental conditions, and data acquisition techniques, significantly impacting the interpretability of results. Correcting batch effects is crucial for the reproducibility of omics research, but current methods are not optimal for the removal of batch effects without compressing the genuine biological variation under study. We propose a suite of Batch Effect Removal Neural Networks (BERNN) to remove batch effects in large LC-MS experiments, with the goal of maximizing sample classification performance between conditions. More importantly, these models must efficiently generalize in batches not seen during training. A comparison of batch effect correction methods across five diverse datasets demonstrated that BERNN models consistently showed the strongest sample classification performance. However, the model producing the greatest classification improvements did not always perform best in terms of batch effect removal. Finally, we show that the overcorrection of batch effects resulted in the loss of some essential biological variability. These findings highlight the importance of balancing batch effect removal while preserving valuable biological diversity in large-scale LC-MS experiments.

Association of COVID-19 Lockdown With Increased Rate of Cyclops Syndrome in Patients With Unexpected Home-Based Self-Guided Rehabilitation After ACL Reconstruction.

Background: The risk of cyclops syndrome increases significantly after anterior cruciate ligament (ACL) reconstruction (ACLR) if complete extension is not recovered before the sixth postoperative week. The lockdown in France due to the COVID-19 pandemic led to an absence of supervised rehabilitation, requiring unexpected self-rehabilitation in patients who underwent ACLR just before lockdown. Purpose: To determine the rate of cyclops syndrome after ACLR in patients who underwent self-rehabilitation during lockdown. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 75 patients receiving a hamstring graft for ACLR during the COVID-19 pandemic between February 10, 2022, and March 16, 2020, carried out self-rehabilitation during part of their first 6 postoperative weeks using exercise videos on a dedicated website. Clinical examination was performed at a minimum 1-year follow-up with International Knee Documentation Committee (IKDC), Lysholm, Tegner, and ACL-Return to Sport after Injury (ACL-RSI) scores. This group was compared with a matched-pair control group of 72 patients who underwent surgery in 2019 and completed postoperative supervised rehabilitation with a physical therapist. Rates and reasons for second surgery (arthrolysis, meniscal procedure) were also recorded. Results: In the COVID group (n = 72; 3 patients were lost to follow-up), the mean follow-up was 14.5 ± 2.1 months (range, 13-21) and rate of reoperation for clinical cyclops syndrome was 11.1% (n = 8). The rate of cyclops syndrome was significantly lower (1.4%) in the control group (P = .01). In the COVID group, 8 patients underwent anterior arthrolysis at a mean of 8.6 months after the primary surgery, and 4 patients underwent another surgical intervention (meniscal procedure [n = 3], device removal [n = 1]). In the COVID group, mean Lysholm was 86.6 ± 14.1 (range, 38-100), Tegner was 5.6 ± 2.3 (range, 1-10), subjective IKDC was 80.3 ± 14.7 (range, 32-100) and ACL-RSI score was 77.3 ± 19.7 (range, 33-100). Conclusion: The rate of cyclops syndrome after ACLR was significantly greater in the COVID group versus the matched controls. The dedicated website was not effective at supporting self-guided rehabilitation and could benefit from interactive improvements so it is at least as effective as supervised rehabilitation.

Enhancing Classification of liquid chromatography mass spectrometry data with Batch Effect Removal Neural Networks (BERNN).

Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful method for profiling complex biological samples. However, batch effects typically arise from differences in sample processing protocols, experimental conditions and data acquisition techniques, significantlyimpacting the interpretability of results. Correcting batch effects is crucial for the reproducibility of proteomics research, but current methods are not optimal for removal of batch effects without compressing the genuine biological variation under study. We propose a suite of Batch Effect Removal Neural Networks (BERNN) to remove batch effects in large LC-MS experiments, with the goal of maximizing sample classification performance between conditions. More importantly, these models must efficiently generalize in batches not seen during training. Comparison of batch effect correction methods across three diverse datasets demonstrated that BERNN models consistently showed the strongest sample classification performance. However, the model producing the greatest classification improvements did not always perform best in terms of batch effect removal. Finally, we show that overcorrection of batch effects resulted in the loss of some essential biological variability. These findings highlight the importance of balancing batch effect removal while preserving valuable biological diversity in large-scale LC-MS experiments.

Rehabilitation protocol after suturing the medial meniscus of a stable knee, a retrospective series of the Francophone Arthroscopy Society.

INTRODUCTION: Surgical meniscal lesions are common and 80% of cases involve the medial meniscus of a stable knee. There is a lack of consensus regarding postoperative rehabilitation protocols and a wide variation between restrictive and accelerated rehabilitation protocols exists. The main objective of this study was to report the functional results and the failure rate of the various rehabilitation protocols of the retrospective series of the French Society of Arthroscopy (SFA) after suturing the medial meniscus of a stable knee, considering whether the tear is stable or unstable. HYPOTHESIS: Our hypothesis was that accelerated rehabilitation was not associated with an increased risk of failure. MATERIALS AND METHODS: This retrospective, multicenter study was conducted across 10 centers (6 private hospitals and 4 public hospitals) including all patients tested for a medial meniscus suture in a stable knee between January 1, 2005 and November 31, 2017 for a minimum follow-up of 5years. Demographic, imaging, suturing, rehabilitation protocol, and functional TEGNER and KOOS scores were collected. Failure was defined as performing a secondary meniscectomy. RESULTS: Three hundred and sixty-seven patients were analyzed with an average follow-up of 82months. Immediate weight bearing was allowed in 85% of cases, the wearing of a brace was present in almost 74% of cases and flexion was limited in 97% of cases. Inter-group comparisons found a higher suture failure rate in the group with immediate weight bearing (35.6% vs. 20%, p=0.011) and in the group with a brace (36.9% vs. 22.4%, p<0.001). There was no difference in the 90° flexion group. The TEGNER score was higher in the non-weight bearing group (6.5 vs. 5.4, p=0.028) and the KOOS QOL score was higher in the group without a brace (82.2 vs. 66.8, p=0.025). According to a multivariate analysis, immediate weight bearing (OR=3.6, [1.62; 7.98], p=0.0016) and wearing a brace (OR=2.83, [1.54; 5.02], p<0.001) were associated with a higher failure rate. In the group of stable lesions, the use of a brace (OR=3.73, [1.62; 8.56], p=0.0019) was associated with a higher failure rate. CONCLUSION: No consensus regarding rehabilitation protocols has been established to date and the results of this retrospective series of the SFA affirm the great variability of practices at a national level. Although accelerated rehabilitation protocols are presently favored, the resumption of immediate full weight bearing should be considered with caution, being associated with a higher risk of failure in this series. Deferring weight bearing for 1 month can be considered in the event of a large tear or in the event of damage to the circumferential fibers. Wearing a brace does not seem to have any influence, while limited flexion achieved a consensus. LEVEL OF EVIDENCE: IV, retrospective study.

The frequency of medial meniscal repairs in stable knees during one year of arthroscopic activity (2021-2022) - comparison with a retrospective study (prior to 2017).

INTRODUCTION: There has been a significant increase in the use of conservative treatment for meniscal lesions due to raised awareness around the need for meniscal preservation. However, sutures of the medial meniscus (MM) in stable knees remain less frequently used. The objective of this study was to, firstly, identify the MM suture rate over one year of activity; secondly, to identify and compare the distribution of MM sutures in stable, and stabilized, knees on this prospective series; and thirdly, to compare the evolution of practices with a retrospective series of more than 5 years follow-up. HYPOTHESIS: The number of MM sutures in stable knees represents a small percentage of annual arthroscopic activity. MATERIAL AND METHODS: This multicenter study was carried out in 10 reference centers participating in the 2022 symposium of the Francophone Society of Arthroscopy (Bordeaux, Caen, Lille, Lille Louvière, Lyon, Marseille, Toulouse, Saint-Étienne, Strasbourg, Versailles). This study included a prospective series on interventions performed under arthroscopy during one year of activity. The inclusion criteria were patients operated on via an arthroscopic technique and aged over 18 at the time of the operation. Demographic data, as well as the circumstances leading to the injury, were collected. A register of the lesions found was established in order to list the lesions of the MM, the lateral meniscus (LM), the anterior cruciate ligament (ACL), the associated chondral lesions; as well as the treatment performed: meniscal suture of the MM and/or LM, meniscectomy of the MM and/or LM and ligamentoplasty of the ACL. This study also included a retrospective series comprised of only MM sutures in stable knees at more than 5 years of follow-up. RESULTS: Of the 4154 patients included, 1919 patients (46.2%) underwent surgery for ACL reconstruction and 2235 for arthroscopy without associated ligament surgery. MM sutures (in stable knees and in knees with ACL reconstruction) represented 14% of the overall arthroscopic activity (583 MM sutures) versus 8.6% for LM (360 sutures). In cases of ACL surgery, there were 895 associated meniscal lesions (337 LM and 558 MM) and 66% of MM tears (371 MM sutures) were sutured. In stable knees, MM tears were weaker (212 MM sutures out of 1359 lesions, i.e. 15%). Of all the arthroscopic procedures performed over the course of a year, MM suturing in stable knees represented 5.1% of the activity. Compared to the retrospective series (n=367), the patients were older (37 years versus 28 years) and the management of ramp lesions or root tears was noted. In both series, these tears were related to sports trauma in more than 70% of cases. CONCLUSION: MM suturing in stable knees represents a small part of annual arthroscopic activity and it occurs less frequently than during ACL reconstruction surgery. LEVEL OF EVIDENCE: IV.

Medial meniscal repair in stable knees: Survival rate and risk factors for failure at a minimum of 5 years.

INTRODUCTION: The menisci play a major role in the protection of the knee against osteoarthritis. A medial meniscus (MM) tear occurring in a stable knee is more at risk of repair failure than a suture concomitant with reconstruction of the anterior cruciate ligament. HYPOTHESIS: The survival of MM sutures in stable knees depends on the type of lesion. MATERIALS AND METHODS: This retrospective study was carried out as part of the 2022 Francophone Arthroscopy Society's symposium, across 10 centers (Bordeaux-Mérignac, Caen, Lille, Lille Louvière, Lyon, Marseille, Toulouse, Saint-Étienne, Strasbourg and Versailles) including medial meniscus sutures in stable knees performed before the end of 2017 (minimum 5 years of follow-up) with a collection of demographic, imaging, suture and postoperative protocol data, and a functional evaluation using the Knee injury and Osteoarthritis Outcome score (KOOS). The aim of this study was to analyze the medial meniscus sutures in stable knees and to evaluate their survival and their risk factors for failure according to the type of lesion; failure being defined by the use of a meniscectomy. RESULTS: Three-hundred and sixty-seven MM sutures, including 122 bucket-handle tears, were included. The KOOS score was improved by the meniscal suture by an average of 22.2 points for each sub-score (p<0.05), with an improvement, which was more marked for the bucket-handle tears. The failure rate, defined by revision surgery by meniscectomy, was 33% on average (42% for bucket-handles tears, 26% for others). The probability of survival was reduced for bucket-handle tears (62% at 5 years versus 77% for the other types). For all lesions, the main risk factor identified for failure was immediate weight-bearing [OR=3.6 (1.62; 7.98), p=0.0016]. Smoking was a failure risk factor for bucket-handle tears [OR=5.76 (1.81; 18.35), p=0.003]. CONCLUSION: MM sutures in stable knees improve knee function but present a different risk of failure depending on the type of lesion treated with a higher risk of failure for bucket-handle tears with the need for caution to be applied with regards to weight-bearing and smoking. LEVEL OF EVIDENCE: IV; retrospective series.

Improvement in the primary and secondary prevention of osteoporosis by a Fracture Liaison Service: feedback from a single French center care pathway.

Osteoporosis is responsible for fragility fractures, thus causing significant morbidity and mortality. This study shows that care pathways, such as Le Mans General Hospital Fracture Liaison Service, are useful and efficient in improving the prevention of osteoporosis and of its consequences. INTRODUCTION: Osteoporosis is a major public health concern, causing significant morbidity and mortality. Care pathways, called Fracture Liaison Services, have demonstrated their utility in preventing osteoporosis-associated morbidity and mortality. The aim of this study was to analyze the activity of one such care pathway. METHODS: This was a retrospective, observational, cohort study, in which 272 patients who had fragility fractures between January 2012 and December 2016 were included. Screening of the medical records and data analyses were performed to characterize the population and the medical care received related to osteoporosis, and to compare these data with those of another study carried out from January 2010 to January 2011 on 54 patients in the same Fracture Liaison Service. RESULTS: There was no statistically significant difference between the two cohorts concerning their demographic characteristics, with 92.3% women and a mean age of 68.7 in our cohort. Secondary prevention was improved, as shown by a reduction in the number of vertebral fractures detected by systematic assessment and fewer low-energy fractures. This study also demonstrated a decline in the percentage of patients with a first-degree parental history of hip fracture and a trend towards a decline in the rate of those having vitamin D insufficiency. CONCLUSIONS: Communication with patients and healthcare professionals through the Fracture Liaison Service was beneficial for patients in terms of fracture prevention. This study supports the development of similar care pathways in other healthcare institutions.

Photographic capture-recapture sampling for assessing populations of the Indian gliding lizard Draco dussumieri.

The usage of invasive tagging methods to assess lizard populations has often been criticised, due to the potential negative effects of marking, which possibly cause increased mortality or altered behaviour. The development of safe, less invasive techniques is essential for improved ecological study and conservation of lizard populations. In this study, we describe a photographic capture-recapture (CR) technique for estimating Draco dussumieri (Agamidae) populations. We used photographs of the ventral surface of the patagium to identify individuals. To establish that the naturally occurring blotches remained constant through time, we compared capture and recapture photographs of 45 pen-marked individuals after a 30 day interval. No changes in blotches were observed and individual lizards could be identified with 100% accuracy. The population density of D. dussumieri in a two hectare areca-nut plantation was estimated using the CR technique with ten sampling occasions over a ten day period. The resulting recapture histories for 24 individuals were analysed using population models in the program CAPTURE. All models indicated that nearly all individuals were captured. The estimated probability for capturing D. dussumieri on at least one occasion was 0.92 and the estimated population density was 13±1.65 lizards/ha. Our results demonstrate the potential for applying CR to population studies in gliding lizards (Draco spp.) and other species with distinctive markings.