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NeuroImage. Clinical Jun 2024Advanced age is the most important risk factor for Alzheimer's disease (AD), and carrier-status of the Apolipoprotein E4 (APOE4) allele is the strongest known genetic...
Advanced age is the most important risk factor for Alzheimer's disease (AD), and carrier-status of the Apolipoprotein E4 (APOE4) allele is the strongest known genetic risk factor. Many studies have consistently shown a link between APOE4 and synaptic dysfunction, possibly reflecting pathologically accelerated biological aging in persons at risk for AD. To test the hypothesis that distinct functional connectivity patterns characterize APOE4 carriers across the clinical spectrum of AD, we investigated 128 resting state functional Magnetic Resonance Imaging (fMRI) datasets from the Alzheimer's Disease Neuroimaging Initiative database (ADNI), representing all disease stages from cognitive normal to clinical dementia. Brain region centralities within functional networks, computed as eigenvector centrality, were tested for multivariate associations with chronological age, APOE4 carrier status and clinical stage (as well as their interactions) by partial least square analysis (PLSC). By PLSC analysis two distinct brain activity patterns could be identified, which reflected interactive effects of age, APOE4 and clinical disease stage. A first component including sensorimotor regions and parietal regions correlated with age and AD clinical stage (p < 0.001). A second component focused on medial-frontal regions and was specifically related to the interaction between age and APOE4 (p = 0.032). Our findings are consistent with earlier reports on altered network connectivity in APOE4 carriers. Results of our study highlight promise of graph-theory based network centrality to identify brain connectivity linked to genetic risk, clinical stage and age. Our data suggest the existence of brain network activity patterns that characterize APOE4 carriers across clinical stages of AD.
PubMed: 38941766
DOI: 10.1016/j.nicl.2024.103635 -
Science Advances Jun 2024Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic...
Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic function and neuronal excitability in the dorsal striatum, but it remains unclear how it affects BG output that is mediated by the substantia nigra pars reticulata (SNr). Here, we describe a neuronal subpopulation-specific synaptic organization of striatal and subthalamic (STN) inputs to the medial and lateral SNr. Chronic alcohol exposure (CIE) potentiated dorsolateral striatum (DLS) inputs but did not change dorsomedial striatum and STN inputs to the SNr. Chemogenetic inhibition of DLS direct pathway neurons revealed an enhanced role for DLS direct pathway neurons in execution of an instrumental lever-pressing task. Overall, we reveal a subregion-specific organization of striatal and subthalamic inputs onto the medial and lateral SNr and find that potentiated DLS-SNr inputs are accompanied by altered BG control of action execution following CIE.
Topics: Animals; Neuronal Plasticity; Basal Ganglia; Substantia Nigra; Ethanol; Corpus Striatum; Male; Mice; Neurons; Alcoholism; Neural Pathways
PubMed: 38941461
DOI: 10.1126/sciadv.adm6951 -
Medicine Jun 2024This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind...
BACKGROUND
This study aimed to evaluate the clinical and radiological features of the patella fixation technique using Toggleloc suspension system in a single ellipsoidal blind patellar tunnel during medial patellofemoral ligament (MPFL) reconstruction.
METHODS
This study included 52 patients (25 men, 27 women) who underwent MPFL reconstruction using a semitendinosus tendon graft. The graft was fixed to the ellipsoidal single blind tunnel opened on the medial side of the patella with an endobutton and was fixed to the femoral tunnel by using bioabsorbable screw. Clinical scores (Kujala score, Lysholm score, Tegner activity score and the visual analog scale [VAS] score) were evaluated preoperatively and at the end-follow up. Preoperative and postoperative radiological measurements (trochlea depth, sulcus angle, patellar height, patellar congruence angle, patellar tilt angle and lateral patellofemoral angle) were evaluated with X-ray (Merchant X-ray, anteroposterior and lateral radiography) and computed tomography (CT) of the knee.
RESULTS
Postoperative patellar redislocation or subluxation was not observed in any patient. Patellar congruence angle, patellar tilt angle and lateral patellofemoral angle mean values were found to return to normal values in the postoperative period and the results were statistically significant. Also statistically significant improvement in all clinical scores postoperatively. According to the Insall-Salvati index (ISI) and Caton-Deschamps index (CDI) on lateral radiography of the knee at 30° flexion, patellar height decreased in the postoperative period statistically significant. The CDI was above 1.3 in 17 (%32) of our patients. Thirteen of these values decreased to normal values. No radiological progression of patellofemoral osteoarthritis was observed in all patients at the final follow-up evaluation.
CONCLUSION
In cases of patellofemoral instability, fixation of the tendon graft in blind ellipsoid tunnel using the Toggleloc suspension system provides satisfactory patellar graft fixation strength, significant functional improvement and a low failure rate.
Topics: Humans; Female; Male; Adult; Patellofemoral Joint; Follow-Up Studies; Patella; Plastic Surgery Procedures; Young Adult; Ligaments, Articular; Treatment Outcome; Adolescent
PubMed: 38941440
DOI: 10.1097/MD.0000000000038379 -
PloS One 2024Pain changes how we move, but it is often confounded by other factors due to disease or injury. Experimental pain offers an opportunity to isolate the independent effect...
Pain changes how we move, but it is often confounded by other factors due to disease or injury. Experimental pain offers an opportunity to isolate the independent effect of pain on movement. We used cutaneous electrical stimulation to induce experimental knee pain during locomotion to study the short-term motor adaptions to pain. While other models of experimental pain have been used in locomotion, they lack the ability to modulate pain in real-time. Twelve healthy adults completed the single data collection session where they experienced six pain intensity conditions (0.5, 1, 2, 3, 4, 5 out of 10) and two pain delivery modes (tonic and phasic). Electrodes were placed over the lateral infrapatellar fat pad and medial tibial condyle to deliver the 10 Hz pure sinusoid via a constant current electrical stimulator. Pain intensity was calibrated prior to each walking bout based on the target intensity and was recorded using an 11-point numerical rating scale. Knee joint angles and moments were recorded over the walking bouts and summarized in waveform and discrete outcomes to be compared with baseline walking. Knee joint angles changed during the swing phase of gait, with higher pain intensities resulting in greater knee flexion angles. Minimal changes in joint moments were observed but there was a consistent pattern of decreasing joint stiffness with increasing pain intensity. Habituation was limited across the 30-90 second walking bouts and the electrical current needed to deliver the target pain intensities showed a positive linear relationship. Experimental knee pain shows subtle biomechanical changes and favourable habituation patterns over short walking bouts. Further exploration of this model is needed in real-world walking conditions and over longer timeframes to quantify motor adaptations.
Topics: Humans; Male; Adult; Biomechanical Phenomena; Female; Knee Joint; Pain; Gait; Locomotion; Walking; Young Adult; Electric Stimulation; Range of Motion, Articular
PubMed: 38941337
DOI: 10.1371/journal.pone.0302752 -
Journal of Integrative Neuroscience May 2024The objective of this study is to compare the differences in effective connectivity within the default mode network (DMN) subsystems between patients with Parkinson's...
OBJECTIVE
The objective of this study is to compare the differences in effective connectivity within the default mode network (DMN) subsystems between patients with Parkinson's disease with mild cognitive impairment (PD-MCI) and patients with Parkinson's disease with normal cognition (PD-CN). The mechanisms underlying DMN dysfunction in PD-MCI patients and its association with clinical cognitive function in PD-MCI are aimed to be investigated.
METHODS
The spectral dynamic causal model (spDCM) was employed to analyze the effective connectivity of functional magnetic resonance imaging (fMRI) data in the resting state for the DMN subsystems, which include the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), left and right angular gyrus (LAG, RAG) in 23 PD-MCI and 22 PD-CN patients, respectively. The effective connectivity values of DMN subsystems in the two groups were statistically analyzed using a two-sample -test. The Spearman correlation analysis was used to test the correlation between the effective connectivity values of the subsystems with significant differences between the two groups and the clinical cognitive function (as measured by Montreal Cognitive Assessment Scale (MoCA) score).
RESULTS
Statistical analysis revealed significant differences in the effective connections of MPFC-LAG and LAG-PCC between the two patient groups (MPFC-LAG: t = -2.993, < 0.05; LAG-PCC: t = 2.174, < 0.05).
CONCLUSIONS
The study findings suggest that abnormal strength and direction of effective connections between DMN subsystems are found in PD-MCI patients.
Topics: Humans; Parkinson Disease; Cognitive Dysfunction; Male; Female; Default Mode Network; Magnetic Resonance Imaging; Aged; Middle Aged; Prefrontal Cortex; Gyrus Cinguli; Connectome; Nerve Net
PubMed: 38940086
DOI: 10.31083/j.jin2306110 -
Case Reports in Otolaryngology 2024Cocaine is the second most consumed drug worldwide, more than 0.4% of the global population, and has become a real public health problem in recent years. Its inhalation...
BACKGROUND
Cocaine is the second most consumed drug worldwide, more than 0.4% of the global population, and has become a real public health problem in recent years. Its inhalation causes significant centrofacial lesions, grouped under the name cocaine-induced midline destructive lesion (CIMDL). These destructions are due to the conjunction of the vasoconstrictor, local prothrombogenic effects, and cytotoxic effects of cocaine. The ischemia produced by this substance is due to vasoconstriction that leads to nasal tissue necrosis and perforation of the nasal septum secondary to chondral necrosis. . A 36-year-old man, previously grappling with cocaine addiction, was hospitalized to undergo comprehensive clinical, microbiological, and radiological examinations because he was suffering from the emergence of crusts and ulceration in the nasal mucosa, accompanied by a palate perforation, a 39°C fever, and chills. Standard bacteriological culture was positive for coagulase-negative staphylococci and , while mycological culture was positive for . The CT scan images of the sinuses confirmed the presence of palatal perforation and total destruction of the nasal septum, cartilaginous portion, maxillary sinus medial wall, lower and middle turbinates, and middle meatus. Nasal endoscopy revealed an exposition of the bony wall and displayed the exposition of the occipital bone's clivus. A diagnosis of CIMDL was confirmed. Antibiotic therapy was decided based on antibiogram results by the consulting microbiologist. Debridement of necrotic tissue was done by nasal endoscopy with local cleaning and was repetitive during the first week to maintain the best cleanliness possible. The patient was discharged with oro-nasal hygiene instructions and referred for prosthetic rehabilation. As for the cocaine addiction, the patient was in follow-up with a psychologist in a specialized centre.
CONCLUSION
The care is multidisciplinary. Psychological help and assistance are essential to guide patients to become cocaine free and to avoid a relapse. Weaning is a prerequisite for surgery. Rehabilitation of speech and swallowing is necessary. Many local flaps or micro-anastomoses are possible.
PubMed: 38939732
DOI: 10.1155/2024/7109261 -
JACC. Advances May 2024
PubMed: 38939635
DOI: 10.1016/j.jacadv.2024.100933 -
JACC. Advances Jun 2024The long-term impact of Kawasaki disease on coronary arteries in vivo is unclear.
BACKGROUND
The long-term impact of Kawasaki disease on coronary arteries in vivo is unclear.
OBJECTIVES
The purpose of this study was to investigate coronary arteries in the late convalescent phase, we followed patients with Kawasaki disease who developed coronary artery aneurysms (CAAs).
METHODS
We followed 24 patients and used optical coherence tomography at a median of 16.6 years after the onset of Kawasaki disease.
RESULTS
Of 72 coronary arteries, optical coherence tomography was performed on 61 arteries: 17 with a persistent CAA, 29 with a regressed CAA, and 15 without a CAA. Between-group comparison was performed by chi-square or Fisher's exact test, and intimal thickening (17 vs 29 vs 15, all 100%, = NA) and medial disruption (17 [100%] vs 29 [100%] vs 14 [93%], = 0.25) were commonly observed in the investigated arteries. Advanced features of atherosclerosis were more frequently seen in arteries with persistent CAAs than in those with regressed CAAs and in those without CAAs: calcification (12 [71%] vs 5 [17%] vs 1 [7%], < 0.001), microvessels (12 [71%] vs 10 [35%] vs 4 [27%], = 0.020), cholesterol crystals (6 [35%] vs 2 [7%] vs 0 [0%], = 0.009), macrophage accumulation (11 [65%] vs 4 [14%] vs 4 [27%], = 0.002), and layered plaque (8 [47%] vs 11 [38%] vs 0 [0%], = 0.004).
CONCLUSIONS
Long after onset of Kawasaki disease, all arteries showed pathological changes. Arteries with persistent CAAs had more advanced features of atherosclerosis than those with regressed CAAs and those without CAAs.
PubMed: 38938853
DOI: 10.1016/j.jacadv.2024.100937 -
JACC. Advances Nov 2023The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features...
BACKGROUND
The prevalence and degree of lower extremity artery disease in hemodialysis (HD) patients is higher than in the general population. However, the pathological features have not yet been evaluated.
OBJECTIVES
The aim of the study was: 1) to compare lesion characteristics of lower extremity artery disease in HD vs non-HD patients; and 2) to determine factors associated with severe medial calcification.
METHODS
Seventy-seven lower limb arteries were assessed from 36 patients (median age 77 years; 23 men; 21 HD and 15 non-HD) who underwent autopsy or lower limb amputation. Arteries were serially cut at 3- to 4-mm intervals creating 2,319 histological sections. Morphometric analysis and calcification measurements were performed using ZEN software. Calcification with a circumferential angle (arc) ≥180° was defined as severe calcification. Multivariable logistic regression was used to identify risk factors for severe medial calcification.
RESULTS
The degree of the medial calcification arc was significantly higher in the HD group compared to the non-HD group ( < 0.0001). In the multivariable analysis, HD was associated with severe medial calcification in below-the-knee lesions (OR: 17.1; = 0.02). The degree of intimal calcification in above-the-knee lesions was also significantly higher in HD patients with a higher prevalence of advanced atherosclerotic plaque ( = 0.02). The prevalence of severe bone formation was more common in the HD patients ( = 0.01).
CONCLUSIONS
Hemodialysis patients demonstrated a higher degree of medial and intimal calcification compared with non-HD patients. The difference was more prominent in the medial calcification of below-the-knee lesions.
PubMed: 38938733
DOI: 10.1016/j.jacadv.2023.100656 -
JACC. Advances Nov 2023
PubMed: 38938703
DOI: 10.1016/j.jacadv.2023.100652