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NeuroImage. Clinical May 2024We previously reported that people with multiple sclerosis (pwMS) who have been using cannabis frequently over many years can have significant cognitive improvements...
We previously reported that people with multiple sclerosis (pwMS) who have been using cannabis frequently over many years can have significant cognitive improvements accompanied by concomitant task-specific changes in brain activation following 28 days of cannabis abstinence. We now hypothesize that the default Mode Network (DMN), known to modulate cognition, would also show an improved pattern of activation align with cognitive improvement following 28 days of drug abstinence. Thirty three cognitively impaired pwMS who were frequent cannabis users underwent a neuropsychological assessment and fMRI at baseline. Individuals were then assigned to a cannabis continuation (CC, n = 15) or withdrawal (CW, n = 18) group and the cognitive and imaging assessments were repeated after 28 days. Compliance with cannabis withdrawal was checked with regular urine monitoring. Following acquisition of resting state fMRI (rs-fMRI), data were processed using independent component analysis (ICA) to identify the DMN spatial map. Between and within group analyses were carried out using dual regression for voxel-wise comparisons of the DMN. Clusters of voxels were considered statistically significant if they survived threshold-free cluster enhancement (TFCE) correction at p < 0.05. The two groups were well matched demographically and neurologically at baseline. The dual regression analysis revealed no between group differences at baseline in the DMN. By day 28, the CW group in comparison to the CC group had increased activation in the left posterior cingulate, and right, angular gyrus (p < 0.05 for both, TFCE). A within group analysis for the CC group revealed no changes in resting state (RS) networks. Within group analysis of the CW group revealed increased activation at day 28 versus baseline in the left posterior cingulate, right angular gyrus, left hippocampus (BA 36), and the right medial prefrontal cortex (p < 0.05). The CW group showed significant improvements in multiple cognitive domains. In summary, our study revealed that abstaining from cannabis for 28 days reverses activation of DMN activity in pwMS in association with improved cognition across several domains.
PubMed: 38815510
DOI: 10.1016/j.nicl.2024.103622 -
ELife May 2024Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are...
Neurexins play diverse functions as presynaptic organizers in various glutamatergic and GABAergic synapses. However, it remains unknown whether and how neurexins are involved in shaping functional properties of the glycinergic synapses, which mediate prominent inhibition in the brainstem and spinal cord. To address these issues, we examined the role of neurexins in a model glycinergic synapse between the principal neuron in the medial nucleus of the trapezoid body (MNTB) and the principal neuron in the lateral superior olive (LSO) in the auditory brainstem. Combining RNAscope with stereotactic injection of AAV-Cre in the MNTB of neurexin1/2/3 conditional triple knockout mice, we showed that MNTB neurons highly express all isoforms of neurexins although their expression levels vary remarkably. Selective ablation of all neurexins in MNTB neurons not only reduced the amplitude but also altered the kinetics of the glycinergic synaptic transmission at LSO neurons. The synaptic dysfunctions primarily resulted from an impaired Ca sensitivity of release and a loosened coupling between voltage-gated Ca channels and synaptic vesicles. Together, our current findings demonstrate that neurexins are essential in controlling the strength and temporal precision of the glycinergic synapse, which therefore corroborates the role of neurexins as key presynaptic organizers in all major types of fast chemical synapses.
Topics: Animals; Mice, Knockout; Glycine; Mice; Trapezoid Body; Synaptic Transmission; Neural Cell Adhesion Molecules; Superior Olivary Complex; Brain Stem; Synapses; Neurons; Cell Adhesion Molecules, Neuronal; Nerve Tissue Proteins; Neurexins; Calcium-Binding Proteins
PubMed: 38814174
DOI: 10.7554/eLife.94315 -
PNAS Nexus May 2024C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and...
C-type lectins (CTLs) are a family of carbohydrate-binding proteins and an important component of mosquito saliva. Although CTLs play key roles in immune activation and viral pathogenesis, little is known about their role in regulating dengue virus (DENV) infection and transmission. In this study, we established a homozygous knockout mutant line using CRISPR/Cas9 to study the interaction between and viruses in mosquito vectors. Furthermore, mouse experiments were conducted to confirm the transmission of DENV by mutants. We found that was mainly expressed in the medial lobe of the salivary glands (SGs) in female . knockout increased DENV replication and accumulation in the SGs of female , suggesting that plays an important role in DENV transmission. We also found a reduced expression of immunodeficiency and Janus kinase/signal transducer and activator of transcription pathway components correlated with increased DENV viral titer, infection rate, and transmission efficiency in the mutant strain. The findings of this study provide insights not only for guiding future investigations on the influence of CTLs on immune responses in mosquitoes but also for developing novel mutants that can be used as vector control tools.
PubMed: 38813522
DOI: 10.1093/pnasnexus/pgae188 -
Turkish Journal of Medical Sciences 2023Developmental dysplasia of the hip (DDH) is the most common cause of secondary hip arthrosis. The primary purpose of this study was to assess the results of an oversized...
BACKGROUND/AIM
Developmental dysplasia of the hip (DDH) is the most common cause of secondary hip arthrosis. The primary purpose of this study was to assess the results of an oversized hemispherical cup via the press-fit technique used for Crowe type II and III DDH without screws and to determine if adequate medialization and initial stability of the acetabular component would allow us to avoid screw and graft use.
MATERIALS AND METHODS
Between February 2012 and May 2020, the current study analyzed 43 hips with Crowe type II and III DDH treated with a porous-coated cup by placing the press-fit technique or screw. The acetabular cup was fixed with the press-fit technique without additional screws in 27 hips and with screws in 16 hips. The inclusion criterion in this study was a minimum 2-year-period after the surgery.
RESULTS
The mean duration of follow-up was 6.83 2.67 years in the press-fit group and 6.21 2.01 years in the screw group. The mean age of the patients was 47.96 12.37 years in the press-fit group and 50.5 12.37 years in the screw group. Measurements revealed that the hip center of rotation (HCR) was located more medially and superiorly postoperatively than preoperatively in both groups. The mean cup coverage in the screw group was 85.58% 7.51% (75.3%-97.2%), while it was less than 90.41% 6.15% (76.3%-98.2%) in the press-fit group (p = 0.038). No component was revised because of loosening, and all of the implants were radiologically stable within the observation period. No statistically significant differences were observed regarding the postoperative limp-length discrepancy between the groups (p = 0.496).
CONCLUSION
Press-fit implantation of a porous-coated acetabular component without screws can also be used as an alternative method for THA in Crowe type II and III DDH. The initial stability was obtained using the press-fit technique with a small cup positioned more medially and superiorly, which may allow the surgeon to avoid screw and graft use.
Topics: Humans; Female; Male; Middle Aged; Adult; Arthroplasty, Replacement, Hip; Hip Prosthesis; Bone Screws; Bone Transplantation; Developmental Dysplasia of the Hip; Hip Dislocation, Congenital; Acetabulum; Treatment Outcome; Prosthesis Design
PubMed: 38813005
DOI: 10.55730/1300-0144.5712 -
IScience Jun 2024The cerebral cortex is widely considered part of the neural substrate of consciousness, but direct causal evidence is missing. Here, we tested in mice whether...
The cerebral cortex is widely considered part of the neural substrate of consciousness, but direct causal evidence is missing. Here, we tested in mice whether optogenetic activation of cortical neurons in posterior parietal cortex (PtA) or medial prefrontal cortex (mPFC) is sufficient for arousal from three behavioral states characterized by progressively deeper unresponsiveness: sleep, a coma-like state induced by muscimol injection in the midbrain, and deep sevoflurane-dexmedetomidine anesthesia. We find that cortical stimulation always awakens the mice from both NREM sleep and REM sleep, with PtA requiring weaker/shorter light pulses than mPFC. Moreover, in most cases light pulses produce both cortical activation (decrease in low frequencies) and behavioral arousal (recovery of the righting reflex) from brainstem coma, as well as cortical activation from anesthesia. These findings provide evidence that direct activation of cortical neurons is sufficient for behavioral and/or cortical arousal from sleep, brainstem coma, and anesthesia.
PubMed: 38812551
DOI: 10.1016/j.isci.2024.109919 -
Journal of Foot and Ankle Research Jun 2024Abnormal lower limb movement patterns have been observed during walking in individuals with limited ankle dorsiflexion. The purpose of this study was to investigate the...
PURPOSE
Abnormal lower limb movement patterns have been observed during walking in individuals with limited ankle dorsiflexion. The purpose of this study was to investigate the relationships of peak ankle dorsiflexion angle during the stance phase of walking with the lower extremity biomechanics at the corresponding moment and to determine a cutoff value of functional limited ankle dorsiflexion during walking.
METHODS
Kinematic and kinetic data of 70 healthy participants were measured during walking. Spearman's correlation coefficients were calculated to establish the association between peak ankle dorsiflexion and angle and moment of ankle, knee, and hip, ground reaction force, and pelvic movement at peak ankle dorsiflexion. All variables significantly related to peak ankle dorsiflexion were extracted as a common factor by factor analysis. Maximally selected Wilcoxon statistic was used to perform a cutoff value analysis.
RESULTS
Peak ankle dorsiflexion positively correlated with ankle plantar flexion moment (r = 0.432; p = 0.001), ankle external rotation moment (r = 0.251; p = 0.036), hip extension angle (r = 0.281; p = 0.018), hip flexion moment (r = 0.341; p = 0.004), pelvic ipsilateral rotation angle (r = 0.284; p = 0.017), and medial, anterior, and vertical ground reaction force (r = 0.324; p = 0.006, r = 0.543; p = 0.001, r = 0.322; p = 0.007), negatively correlated with knee external rotation angle (r = -0.394; p = 0.001) and hip adduction angle (r = -0.256; p = 0.032). The cutoff baseline value for all 70 participants was 9.03°.
CONCLUSIONS
There is a correlation between the peak ankle dorsiflexion angle and the lower extremity biomechanics during walking. If the peak ankle dorsiflexion angle is less than 9.03°, the lower limb movement pattern will change significantly.
Topics: Humans; Biomechanical Phenomena; Male; Female; Ankle Joint; Walking; Range of Motion, Articular; Adult; Lower Extremity; Young Adult; Hip Joint; Knee Joint; Ankle
PubMed: 38812103
DOI: 10.1002/jfa2.12027 -
Journal of Orthopaedic Surgery and... May 2024To evaluate the biomechanical characteristics of grafts from three different anterior cruciate ligament (ACL) reconstructive surgeries and to determine which method is... (Comparative Study)
Comparative Study
OBJECTIVE
To evaluate the biomechanical characteristics of grafts from three different anterior cruciate ligament (ACL) reconstructive surgeries and to determine which method is better at restoring knee joint stability.
METHODS
A 31-year-old female volunteer was enrolled in the study. According to the magnetic resonance imaging of her left knee, a three-dimensional model consisting of the distal femur, proximal tibia and fibula, ACL, posterior cruciate ligament, medial collateral ligament and lateral collateral ligament was established. Then, the ACL was removed from the original model to simulate the knee joint after ACL rupture. Based on the knee joint model without the ACL, single-bundle ACL reconstruction, double-bundle ACL reconstruction, and flat-tunnel ACL reconstruction were performed. The cross-sectional diameters of the grafts were equally set as 6 mm in the three groups. The bone tissues had a Young's modulus of 17 GPa and a Poisson's ratio of 0.36. The ligaments and grafts had a Young's modulus of 390 MPa and a Poisson's ratio of 0.4. Six probes were placed in an ACL or a graft to obtain the values of the equivalent stress, maximum principal stress, and maximum shear stress. After pulling the proximal tibia with a forward force of 134 N, the distance that the tibia moved and the stress distribution in the ACL or the graft, reflected by 30 mechanical values, were measured.
RESULTS
The anterior tibial translation values were similar among the three groups, with the double-bundle ACL reconstruction group performing the best, followed closely by the patellar tendon ACL reconstruction group. In terms of stress distribution, 13 out of 30 mechanical values indicated that the grafts reconstructed by flat bone tunnels had better performance than the grafts in the other groups, while 12 out of 30 showed comparable outcomes, and 5 out of 30 had worse outcomes.
CONCLUSION
Compared with traditional single-bundle and double-bundle ACL reconstructions, flat-tunnel ACL reconstruction has advantages in terms of stress dispersion. Additionally, flat-tunnel ACL reconstruction falls between traditional double-bundle and single-bundle ACL reconstructions in terms of restoring knee joint stability and is superior to single-bundle ACL reconstruction.
Topics: Humans; Anterior Cruciate Ligament Reconstruction; Female; Finite Element Analysis; Adult; Biomechanical Phenomena; Imaging, Three-Dimensional; Anterior Cruciate Ligament; Tibia; Stress, Mechanical; Knee Joint
PubMed: 38812053
DOI: 10.1186/s13018-024-04777-x -
Arthritis Research & Therapy May 2024Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte...
BACKGROUND
Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression.
METHODS
We screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus.
RESULTS
MiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice.
CONCLUSIONS
MiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.
Topics: MicroRNAs; Chondrocytes; Animals; Humans; Cellular Senescence; Osteoarthritis; Mice; Male; Interleukin-6; Mice, Inbred C57BL; STAT3 Transcription Factor; Cells, Cultured; Middle Aged; Female; Signal Transduction; Cartilage, Articular
PubMed: 38812033
DOI: 10.1186/s13075-024-03334-5 -
Journal of Neuroengineering and... May 2024The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain-computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia.
DESIGN
A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial.
METHODS
Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures.
RESULTS
A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P < 0.05), the mean zReHo of the right cuneus (r = 0.399, P < 0.05).
CONCLUSION
In conclusion, BCI therapy is effective and safe for arm rehabilitation after severe poststroke hemiparesis. The correlation of the zALFF of the contralateral precentral gyrus and the zReHo of the ipsilateral cuneus with motor improvements suggested that these values can be used as prognostic measures for BCI-based stroke rehabilitation. We found that motor function was related to visual and spatial processing, suggesting potential avenues for refining treatment strategies for stroke patients.
TRIAL REGISTRATION
The trial is registered in the Chinese Clinical Trial Registry (number ChiCTR2000034848, registered July 21, 2020).
Topics: Humans; Brain-Computer Interfaces; Male; Stroke Rehabilitation; Female; Middle Aged; Upper Extremity; Magnetic Resonance Imaging; Imagery, Psychotherapy; Stroke; Aged; Adult; Imagination; Cerebral Cortex
PubMed: 38812014
DOI: 10.1186/s12984-024-01387-w -
Scientific Reports May 2024Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between... (Observational Study)
Observational Study
Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412-3.694) and medial JSN (OR: 3.211, 95% CI: 2.040-5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177-2.941) and medial JSN (OR: 1.655, 95% CI: 1.053-2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (β: 0.029, 95% CI: 0.010-0.053; β: 0.022, 95% CI: 0.005-0.046) and beyond 24 months (β: 0.039, 95% CI: 0.016-0.068; β: 0.047, 95% CI: 0.020-0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.
Topics: Humans; Synovitis; Osteoarthritis, Knee; Female; Male; Middle Aged; Disease Progression; Aged; Magnetic Resonance Imaging; Menisci, Tibial; Meniscus; Radiography; Knee Joint
PubMed: 38811752
DOI: 10.1038/s41598-024-63291-6