Pathological Patterns Research Articles

Neurocinematic therapy - An interdisciplinary perspective

The present article is a typical perspective paper. It neither substantiates nor confirms theories, nor does it produce robust data-driven outcomes in the context of evidence-based medicine. It rather sheds light on the emerging field of neurocinematic therapy and promotes interdisciplinary discussion. Within the broad realm of neurocinematics, neurocinematic therapy is considered a realm of applied sciences with a particular impact on clinical areas and public health systems. It does not necessarily comply with standardised diagnostic manuals but inspires a multifaceted view of notions referring to pathology. Neuropsychological processing of individual movie experiences plays a crucial role and regards the interplay between psycho-affective phenomena and central-nervous functioning of specific brain areas, network connectivities and neural principles such as brain plasticity. According to the characteristics of meta-syntheses, the article respects all kinds of relevant approaches such as neuroimaging or qualitative empirical research, and harmonises their outcomes from the perspective of scientific epistemology, meta-methodology and theory of science. From a translational medical point of view, such scientific syntheses are designed to impact clinical practice and public health. The present study identifies seven potentially therapeutic features of movie experience which suggest a preliminary scientific framework: i) change of pathological cognitive patterns and compulsive thought, ii) integration of fragmentised identities, iii) intuitive development of self-therapeutic measures, iv) re-balancing of inner calmness and dynamic lifestyles, v) biographical work and episodic exposure training, vi) synchronisation of movie rhythms, life rhythms and inner rhythms, and vii) clinical trance as well as movie-based auto-hypnosis.

Traumatic Brain Injury and Post-Traumatic Stress Disorder and Their Influence on Development and Pattern of Alzheimer's Disease Pathology in Later Life.

Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are potential risk factors for the development of dementia including Alzheimer's disease (AD) in later life. The findings of studies investigating this question are inconsistent though. To investigate if these inconsistencies are caused by the existence of subgroups with different vulnerability for AD pathology and if these subgroups are characterized by atypical tau load/atrophy pattern. The MRI and PET data of 89 subjects with or without previous TBI and/or PTSD from the DoD ADNI database were used to calculate an age-corrected gray matter tau mismatch metric (ageN-T mismatch-score and matrix) for each subject. This metric provides a measure to what degree regional tau accumulation drives regional gray matter atrophy (matrix) and can be used to calculate a summary score (score) reflecting the severity of AD pathology in an individual. The ageN-T mismatch summary score was positively correlated with whole brain beta-amyloid load and general cognitive function but not with PTSD or TBI severity. Hierarchical cluster analysis identified five different spatial patterns of tau-gray matter interactions. These clusters reflected the different stages of the typical AD tau progression pattern. None was exclusively associated with PTSD and/or TBI. These findings suggest that a) although subsets of patients with PTSD and/or TBI develop AD-pathology, a history of TBI or PTSD alone or both is not associated with a significantly higher risk to develop AD pathology in later life. b) remote TBI or PTSD do not modify the typical AD pathology distribution pattern.

Incidence and Pathological Patterns of Nephrotic Syndrome among Infants and Children: A Systematic Review.

Nephrotic syndrome (NS) is known to be a prevalent chronic illness in young patients. Periorbital swelling in children with this condition is a recurring symptom, either with or without generalized edema.The current study aimedto examine the incidence and pattern of nephrotic syndrome in infants and children by thoroughly examining the recently available literature. A thorough search of PubMed, SCOPUS, Web of Science, Science Direct, and Google Scholar was conducted, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, to find pertinent material. The Rayyan software (Qatar Computing Research Institute, Ar-Rayyan, Qatar) was utilized during the whole process. Data from a total of 1418 patients from nine trials were considered in this study. Numerous factors influenced the incidence, mean age, sex dominance, and histological patterns in various sample groups. The current findings conclude that variations in socioeconomic, regional, and genetic factors influence the development and pattern of these diseases. The prevalence of pediatric renal disorders differs throughout countries. Season of occurrence, response to corticosteroid treatment, and histopathologic findings appear to differ amongst the diagnosed cases.

Unlocking the specificity of antimicrobial peptide interactions for membrane-targeted therapies

Antimicrobial peptides (AMPs) are increasingly recognized as potent therapeutic agents, with their selective affinity for pathological membranes, low toxicity profile, and minimal resistance development making them particularly attractive in the pharmaceutical landscape. This study offers a comprehensive analysis of the interaction between specific AMPs, including magainin-2, pleurocidin, CM15, LL37, and clavanin, with lipid bilayer models of very different compositions that have been ordinarily used as biological membrane models of healthy mammal, cancerous, and bacterial cells. Employing unbiased molecular dynamics simulations and metadynamics techniques, we have deciphered the intricate mechanisms by which these peptides recognize pathogenic and pathologic lipid patterns and integrate into lipid assemblies. Our findings reveal that the transverse component of the peptide's hydrophobic dipole moment is critical for membrane interaction, decisively influencing the molecule's orientation and expected therapeutic efficacy. Our approach also provides insight on the kinetic and dynamic dependence on the peptide orientation in the axial and azimuthal angles when coming close to the membrane. The aim is to establish a robust framework for the rational design of peptide-based, membrane-targeted therapies, as well as effective quantitative descriptors that can facilitate the automated design of novel AMPs for these therapies using machine learning methods.

Myoelectric control and virtual reality to enhance motor rehabilitation after stroke.

Effective upper-limb rehabilitation for severely impaired stroke survivors is still missing. Recent studies endorse novel motor rehabilitation approaches such as robotic exoskeletons and virtual reality systems to restore the function of the paretic limb of stroke survivors. However, the optimal way to promote the functional reorganization of the central nervous system after a stroke has yet to be uncovered. Electromyographic (EMG) signals have been employed for prosthetic control, but their application to rehabilitation has been limited. Here we propose a novel approach to promote the reorganization of pathological muscle activation patterns and enhance upper-limb motor recovery in stroke survivors by using an EMG-controlled interface to provide personalized assistance while performing movements in virtual reality (VR). We suggest that altering the visual feedback to improve motor performance in VR, thereby reducing the effect of deviations of the actual, dysfunctional muscle patterns from the functional ones, will actively engage patients in motor learning and facilitate the restoration of functional muscle patterns. An EMG-controlled VR interface may facilitate effective rehabilitation by targeting specific changes in the structure of muscle synergies and in their activations that emerged after a stroke-offering the possibility to provide rehabilitation therapies addressing specific individual impairments.

Identification of congenital valvular murmurs in young patients using deep learning-based attention transformers and phonocardiograms.

One in every four newborns suffers from congenital heart disease (CHD) that causes defects in the heart structure. The current gold-standard assessment technique, echocardiography, causes delays in the diagnosis owing to the need for experts who vary markedly in their ability to detect and interpret pathological patterns. Moreover, echo is still causing cost difficulties for low-and middle-income countries. Here, we developed a deep learning based attention transformer model to automate the detection of heart murmurs caused by CHD at an early stage of life using cost-effective and widely available phonocardiography (PCG). PCG recordings were obtained from 942 young patients at four major auscultation locations, including the aortic valve (AV), mitral valve (MV), pulmonary valve (PV), and tricuspid valve (TV), and they were annotated by experts as absent, present, or unknown murmurs. A transformation to wavelet features was performed to reduce the dimensionality before the deep learning stage for inferring the medical condition. The performance was validated through 10-fold cross-validation and yielded an average accuracy and sensitivity of 90.23% and 72.41%, respectively. The accuracy of discriminating between murmurs' absence and presence reached 76.10% when evaluated on unseen data. The model had accuracies of 70%, 88%, and 86% in predicting murmur presence in infants, children, and adolescents, respectively. The interpretation of the model revealed proper discrimination between the learned attributes, and AV channel was found important (score > 0.75) for the murmur absence predictions while MV and TV were more important for murmur presence predictions. The findings potentiate deep learning as a powerful front-line tool for inferring CHD status in PCG recordings leveraging early detection of heart anomalies in young people. It is suggested as a tool that can be used independently from high-cost machinery or expert assessment. With additional validation on external datasets, more insights on the generalizability of deep learning tools could be obtained before being implemented in real-world clinical settings.

Correlation between Ki-67 or Profilin-1 Expression Levels, Clinicopathological Characteristics and Postoperative Prognosis in Patients with Bladder Cancer.

Bladder cancer is the most common malignancy of the urinary system, and the search for new and reliable biomarkers has important clinical significance for the personalized treatment of bladder cancer. This study aims to explore the correlation between nuclear proliferation antigen (Ki-67) or Profilin-1 (PFN1) levels, clinicopathological characteristics, and postoperative prognosis in patients with bladder cancer. Patients with bladder cancer who underwent transurethral resection of bladder cancer tumor in The Fourth Affiliated Hospital of Soochow University, hospital from January 2019 to January 2021 were selected as the study group (n = 60), and patients with benign lesions of bladder cancer during the same period were selected as the control group (n = 60). The expression of Ki-67 and PFN1 in tumor and bladder tissues of the two groups was analyzed. Ki-67 recorded the patient's pathological parameters and calculated the patient's postoperative prognosis. The correlation between Ki-67 and PFN1 expression levels, pathological parameters, and postoperative prognosis was analyzed. The positive expression rates of Ki-67 and PFN1 in the study group were 63.33% and 73.33%, respectively, which were significantly higher than the positive expression rates in the control group (χ2 = 14.803, 17.757, p < 0.001). The positive expression rates of Ki-67 and PFN1 were related to histological grade, clinical stage, infiltration, and lymph node metastasis, and the differences were statistically significant (p < 0.05). Bladder cancer patients with non muscle-invasive bladder cancer (NMIBC), high-grade histological grade, Ta~T1 clinical stage, invasive, and lymph node metastasis have a higher Ki-67 positive expression rate than bladder cancer patients with muscle-invasive bladder cancer (MIBC), low-grade histological grade, T2~T4, non-invasive, and no lymph node metastasis. The high expression level of Ki-67 has little relationship with gender, age, tumor diameter, and vascular invasion (p > 0.05). The survival time and three-year survival rate of the Ki-67 positive expression group were significantly lower than those of the Ki-67 negative expression group (p < 0.05). The survival time and three-year survival rate of the PFN1 positive expression group were significantly lower than those of the PFN1 negative expression group (p < 0.05). The positive expression rates of Ki-67 and PFN1 in bladder tumor tissue are significantly higher than those in bladder tissue, and pathological pattern, histological grade, clinical stage, infiltration, and lymph node metastasis are related to the positive expression rates of Ki-67 and PFN1, and different genders, ages, tumors diameter and vascular invasion are not related to the positive expression rates of Ki-67 and PFN1. The survival time and three-year survival rates of bladder cancer patients with Ki-67 positive and PFN1 positive expression are shorter.

Pathologic features of brain hemorrhage after radiation treatment: case series with somatic mutation analysis

BackgroundRadiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. MethodsWe retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. ResultsOne lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. ConclusionsDespite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

Structurally constrained and pathology-aware convolutional transformer generative adversarial network for virtual histology staining of human coronary optical coherence tomography images.

There is a significant need for the generation of virtual histological information from coronary optical coherence tomography (OCT) images to better guide the treatment of coronary artery disease (CAD). However, existing methods either require a large pixel-wise paired training dataset or have limited capability to map pathological regions. The aim of this work is to generate virtual histological information from coronary OCT images, without a pixel-wise paired training dataset while capable of providing pathological patterns. We design a structurally constrained, pathology-aware, transformer generative adversarial network, namely structurally constrained pathology-aware convolutional transformer generative adversarial network (SCPAT-GAN), to generate virtual stained H&E histology from OCT images. We quantitatively evaluate the quality of virtual stained histology images by measuring the Fréchet inception distance (FID) and perceptual hash value (PHV). Moreover, we invite experienced pathologists to evaluate the virtual stained images. Furthermore, we visually inspect the virtual stained image generated by SCPAT-GAN. Also, we perform an ablation study to validate the design of the proposed SCPAT-GAN. Finally, we demonstrate 3D virtual stained histology images. Compared to previous research, the proposed SCPAT-GAN achieves better FID and PHV scores. The visual inspection suggests that the virtual histology images generated by SCPAT-GAN resemble both normal and pathological features without artifacts. As confirmed by the pathologists, the virtual stained images have good quality compared to real histology images. The ablation study confirms the effectiveness of the combination of proposed pathological awareness and structural constraining modules. The proposed SCPAT-GAN is the first to demonstrate the feasibility of generating both normal and pathological patterns without pixel-wisely supervised training. We expect the SCPAT-GAN to assist in the clinical evaluation of treating the CAD by providing 2D and 3D histopathological visualizations.

Stress-induced failure of embodied cognition: A general model

We derive the classic, ubiquitous, but enigmatic Yerkes–Dodson effect of applied stress on real-world performance in a highly natural manner from fundamental assumptions on cognition and its dynamics, as constrained by the asymptotic limit theorems of information and control theories. We greatly extend the basic approach by showing how differences in an underlying probability model can affect the dynamics of decision across a broad range of cognitive enterprise. Most particularly, however, this development may help inform our understanding of the different expressions of human psychopathology. A ‘thin tailed’ underlying distribution appears to characterize expression of ‘ordinary’ situational depression/anxiety symptoms of conditions like burnout induced by toxic stress. A ‘fat tailed’ underlying distribution appears to be associated with brain structure and function abnormalities leading to serious mental illness and poor decision making where symptoms are not only emerging in the setting of severe stress but may also appear in a highly punctuated manner at relatively lower levels of stress. A simple hierarchical optimization shows how environmental ‘shadow price’ constraints can buffer or aggravate the effects of stress and arousal. Extension of the underlying theory to other patterns of pathology, like immune disorders and premature aging, seems apt. Applications to the punctuated dynamics of institutional cognition under stress also appear possible. Ultimately, the probability models studied here can be converted to new statistical tools for the analysis of observational and experimental data.

Ankle-foot orthosis in stroke survivors: status of the issue

This paper presents an analysis of information regarding the peculiarity of ankle joint orthosis in cerebral stroke survivors. Gait research methods used to assess gait changes in patients who had suffered a cerebral stroke were briefly reviewed. The three most common patterns of gait impairment after a stroke, namely, stiff-knee gait, “dropped foot,” and gait with knee joint hyperextension, were described. A brief review of the main functional types of ankle joint orthoses, namely, static and dynamic, considering their strengths and weaknesses, was presented. Changes in temporal, spatial, and kinematic parameters of gait in cerebral stroke survivors using orthoses were reported. Changes in gait parameters when using ankle joint orthoses depending on the initial pattern of gait disturbance were assessed. The effect of orthotics on the angles of flexion in the ankle, knee, and hip joints at various gait phases as well as their effect on the speed, rhythm, and length of the step were described. Data on the effect of ankle orthosis on patient’s ability to maintain balance were also presented. The effects of orthosis on gait biomechanics and balance function in stroke survivors are debatable. Thus, our findings in this study allow us to raise the question regarding the optimal timing of the use of ankle joint orthoses during the recovery period of a stroke. Possible reasons for these ambiguous results were considered. The necessity for further research into the effectiveness of ankle–foot orthoses regarding various pathological gait patterns in stroke survivors is justified.

Abstract 153: Noncoding elements of MYCN mRNA are powerful drivers on oncogenicity in neuroblastoma

Abstract Precision in genetic modeling of oncogene-driven cancer is crucial for comprehending disease pathology. Traditionally, models focused on protein expression through open-reading-frame (ORF) transgenes. This approach overlooks post-transcriptional regulation in endogenous mRNAs, which include noncoding elements like 5’ and 3’ UTRs and introns. All patient oncogene mRNAs encompass these elements, and grasping the collective impact of noncoding and protein coding components may revolutionize our comprehension of cancer origins.Neuroblastoma (NB) is the most common extracranial solid tumor in children. Genetic amplification of MYCN (MA) in NB results in very high mRNA levels and drives poor prognosis. MYCN mRNA is targeted by multiple microRNAs, including let-7. We previously demonstrated that in MA disease the 3’ UTR of MYCN can sequester let-7, inhibiting its function. MYCN mRNA thus also influences genetic patterning in NB by relieving the selective pressure to lose chromosome arms harboring let-7 loci, an event frequent in MYCN non-amplified NB but exceedingly rare in MA disease. This work established for the first time that noncoding mRNA elements within an oncogenic mRNA can itself contribute to disease pathology. To further understand the roles of noncoding elements within MYCN mRNA, we generated BALB/c 3T3 fibroblasts and murine Neuro-2a cells that express the following transgenes: 1.MYCN-ORF: expresses only MYCN open reading frame sequence.2.MYCN-GL: intact genetic locus of MYCN, expresses full length MYCN mRNA.3.M/GFP-GL: variant of #2 where MYCN protein coding sequences are replaced by EGFP. All three constructs demonstrated significantly enhanced in vitro proliferation compared to GFP control cells. Notably, cells expressing MYCN-GL exhibited best growth in both cell types, despite possessing an intact 3’UTR. Unexpectedly, M/GFP-GL cells demonstrated comparable growth to MYCN-ORF in 3T3s and significantly outperformed MYCN-ORF in Neuro-2a cells. This observation not only validates our prior research on the oncogenic role of the MYCN 3’ UTR but also extends it by revealing direct contributions to growth advantages, occasionally surpassing even MYCN protein. Syngeneic animal studies mirrored these trends, with MYCN-GL and M/GFP-GL inducing nearly 100% tumor incidence, surpassing the 57% incidence associated with MYCN-ORF. Tumors induced by MYCN-GL and M/GFP-GL were more than twice the size of those induced by MYCN-ORF. These observations underscore that full-length MYCN mRNA, encompassing all noncoding elements, serves as a more potent driver of cellular growth and oncogenicity than only MYCN protein expression. These findings have exciting implications for understating neuroblastoma pathology and genetic patterns, with broader implications for other oncogene-driven cancers. We are currently generating transgenic mouse models based on the above three constructs. Citation Format: Vishwa Patel, Lorraine Rana Benhamou, Dr. John T. Powers. Noncoding elements of MYCN mRNA are powerful drivers on oncogenicity in neuroblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 153.

Pilot study: Effect of Developmental Dysplasia of the Hip on the Gait and Feet Posture

Background: The objective of this pilot study was to assess the effect of Developmental Dysplasia of the Hip (DDH) on gait, in pediatric participants, between the age of one to four years. Few studies are investigating the effect of DDH on the walking pattern within the pediatric rehabilitation practice. From an early age, children are developing a longitudinal foot arch. Constantly changing pediatric foot posture must be assessed. Gait pattern and foot posture are one of the most common parental concerns.&#x0D; Methods: The retrospective review of gait analysis, performed on 410 lower limbs, took place in King Abdullah Specialized Children Hospital (KASCH) in Riyadh, Kingdom of Saudi Arabia, from April 2020 until September 2020. All participants were diagnosed with DDH by pediatric orthopedics physicians in KASCH. Gait analysis was done by a physical therapist twice within three months, using The Wee Glasgow Gait Index (WeeGGI) and foot assessment was done once using Foot Postural Index (FPI-6). The WeeGGI compares eleven gait parameters. Each parameter has a choice of three figures, where each one has a clear explanation and/or value. The FPI-6 evaluates the foot as multi-segmental complex, in double leg support, characterizing pronation with + (plus) and supination with - (minus) numbers. Scoring is 2 (two) points in all six factors it is divided into rearfoot and forefoot assessment in transverse, frontal/transverse, frontal, and sagittal planes.&#x0D; Results: From all gait analyses (n=410). We included only 292 (71%) lower limbs with DDH and had to exclude 60 (15%) after hip surgery, 30 (7%) with another diagnosis, 18 (4%) without conservative treatment of DDH, and 10 (3%) with age above 48 months. According to the scoring of the Wee Glasgow Gait Index within the optimum/normal limits (score 0 - zero), we had 50 (17%), mild deviation (score 1-11) 236 (81%), and gross deviation (score 12-22) had 6 (2%) limbs within first gait analysis. With second gait analysis, 40% of lower limbs were within optimum/normal limits, 60% with mild deviation in gait, and zero within gross deviation. Every limb assessment for gait had the Foot Postural Index as well. Within normal limits (0 till +5) we had 143 (49%) feet, pronation (+6 till +9) was presented in 97 (33%) and high pronation (more then +10) had 52 (18%) pediatric feet. This sample did not present supination (-1 till -4) or high supination (-5 till -12). Limping was observed within 102 (35%) of the legs. The frequency of W-sitting presented in 47% of the results. The first and second gait analysis suggest an effect of DDH on the gait with a small difference between the right and left leg, although the left side was affected more within both gait analyses.&#x0D; Conclusion: Pathological gait pattern with DDH was detected in 83% within the first gait analysis, 60% within the second gait analysis, and Foot Postural Index revealed pronation of 51% feet. Among Saudi participants, a relatively high effect of DDH on gait patterns is reported in this pilot study.&#x0D; Keywords: DDH, gait, FPI-6, physiotherapy, WeeGGI.

Effectiveness of comprehensive rehabilitation of patients with impaired respiratory muscle strength after coronavirus pneumonia

Aim. The study aims to evaluate the effectiveness of a comprehensive rehabilitation program for patients experiencing reduced respiratory muscle strength following coronavirus pneumonia.Materials and methods. This prospective, ran-domized study enrolled 55 individuals (average age 66.1±6.4 years; 21.8% males and 78.2% females) who had recovered from COVID-19. The rehabilitation regimen included 10 sessions of respiratory exercises, 10 chest massage treatments, and 3 sessions of osteopathic adjustment. Assessments of respiratory function and respiratory muscle strength were conducted both before the initiation of rehabilitation and upon its completion.Results. Initial complaints included rapid fatigue, dyspnea under physical strain, vertigo, headaches, chest pain during respiration, and disrupted sleep patterns. Participants were categorized into two groups: males and females. Both groups demonstrated a decrease in expiratory muscle strength by a factor of 1.2 and inspiratory muscle strength by 1.6, compared to normative values. Spirometry indicated impaired lung function across all participants. Post-rehabilitation, a marked improvement in overall health and a reduction in complaint severity were observed. Rehabilitation routing scales showed a decrease in condition severity from 2-3 points to 1-2 points, alongside a statistically significant increase in respiratory muscle strength, enhanced oxygen saturation, and restored lung function.Conclusion. Our proposed comprehensive rehabilitation program, incorporating osteopathic manipulation, respiratory exercises, and massage, successfully shifts the pathological breathing pattern to a physiological one, strengthens respiratory muscles, and reinstates lung function. This leads to improved exercise, reduced anxiety and depression levels, and enhanced quality of life for post-COVID-19 pneumonia patients.

Beyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria.

Sequestration of infected red blood cells (iRBCs) in the microcirculation is a hallmark of cerebral malaria (CM) in post-mortem human brains. It remains controversial how this might be linked to the different disease manifestations, in particular brain swelling leading to brain herniation and death. The main hypotheses focus on iRBC-triggered inflammation and mechanical obstruction of blood flow. Here, we test these hypotheses using murine models of experimental CM (ECM), SPECT-imaging of radiolabeled iRBCs and cerebral perfusion, MR-angiography, q-PCR, and immunohistochemistry. We show that iRBC accumulation and reduced flow precede inflammation. Unexpectedly, we find that iRBCs accumulate not only in the microcirculation but also in large draining veins and sinuses, particularly at the rostral confluence. We identify two parallel venous streams from the superior sagittal sinus that open into the rostral rhinal veins and are partially connected to infected skull bone marrow. The flow in these vessels is reduced early, and the spatial patterns of pathology correspond to venous drainage territories. Our data suggest that venous efflux reductions downstream of the microcirculation are causally linked to ECM pathology, and that the different spatiotemporal patterns of edema development in mice and humans could be related to anatomical differences in venous anatomy.

Psychometric properties of the exercise addiction inventory (EAI) questionnaire among physically active young adults

BackgroundExercise addiction (EA) is a pathological behavior pattern in which a person loses control over his exercise habits and exercises excessively and suffers negative consequences for his health and even his social life. One of the best tools to measure EA is EAI. The aim of this study was to examine the psychometric properties of the EAI among Iranian physically active young adults.MethodsParticipants were randomly selected from sports clubs in Tabriz, Iran. A total of 200 questionnaires were completed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted along with tests of convergent validity. Reliability was assessed using Cronbach’s alpha and test-retest methods.ResultsEFA indicated a one-factor structure explaining 40.43% of variance. CFA confirmed the one-factor model with good fit (Root Mean Square Error of Approximation [RMSEA] = 0.076; Comparative Fit Index [CFI] = 0.968). Internal consistency was acceptable (Cronbach’s alpha = 0.71) and convergent validity was adequate. Test-retest reliability was also adequate (intraclass correlation coefficient [ICC] = 0.71).ConclusionThe results of our study show that the Persian EAI has satisfactory psychometric properties and can be used as a valid tool to assess EA.

Pattern classification of interstitial lung diseases from computed tomography images using a ResNet-based network with a split-transform-merge strategy and split attention.

In patients with interstitial lung disease (ILD), accurate pattern assessment from their computed tomography (CT) images could help track lung abnormalities and evaluate treatment efficacy. Based on excellent image classification performance, convolutional neural networks (CNNs) have been massively investigated for classifying and labeling pathological patterns in the CT images of ILD patients. However, previous studies rarely considered the three-dimensional (3D) structure of the pathological patterns of ILD and used two-dimensional network input. In addition, ResNet-based networks such as SE-ResNet and ResNeXt with high classification performance have not been used for pattern classification of ILD. This study proposed a SE-ResNeXt-SA-18 for classifying pathological patterns of ILD. The SE-ResNeXt-SA-18 integrated the multipath design of the ResNeXt and the feature weighting of the squeeze-and-excitation network with split attention. The classification performance of the SE-ResNeXt-SA-18 was compared with the ResNet-18 and SE-ResNeXt-18. The influence of the input patch size on classification performance was also evaluated. Results show that the classification accuracy was increased with the increase of the patch size. With a 32 × 32 × 16 input, the SE-ResNeXt-SA-18 presented the highest performance with average accuracy, sensitivity, and specificity of 0.991, 0.979, and 0.994. High-weight regions in the class activation maps of the SE-ResNeXt-SA-18 also matched the specific pattern features. In comparison, the performance of the SE-ResNeXt-SA-18 is superior to the previously reported CNNs in classifying the ILD patterns. We concluded that the SE-ResNeXt-SA-18 could help track or monitor the progress of ILD through accuracy pattern classification.

Psychosis in Alzheimer’s disease is associated with specific changes in brain MRI volume, cognition and neuropathology

Psychosis in Alzheimer’s Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy.

Nail involvement in connective tissue diseases: an epidemiological, clinical, and dermoscopic study.

The assessment of nail changes in connective tissue diseases (CTD) has been rarely explored in previous studies. The use of dermoscopy to study vascular changes in nailfolds is an interesting diagnostic technique. The aim of the study was to describe the epidemiological, clinical, and dermoscopic features of nail lesions in CTD. A prospective study was performed at the Dermatology Department of Habib Thameur Hospital (Tunis, Tunisia) in collaboration with the Internal Medicine Department over a period of 15 months, from July 2020 to September 2021, including patients diagnosed with systemic sclerosis (SS), systemic lupus erythematosus (SLE) and dermatomyositis (DM). Our study included 48 patients. Nail involvement was found in 44 cases. Dermoscopic nailfold abnormalities were identified in 37 cases. The most common clinical features were ragged cuticle, nailfold erythema, and onycholysis. Additionally, splinter hemorrhage, longitudinal ridging, lunula abnormalities, melanonychia, trachyonychia, leukonychia, increase in transverse curvature, parrot beak nail, half and half nails, and onychorrhexis were described. Nailfold dermoscopy showed a normal pattern in 10 cases, a nonspecific pattern in nine cases (SLE), and a scleroderma pattern in 29 cases (SS and DM). The scleroderma pattern was further categorized into an early pattern (6), an active pattern (14), and a late pattern (9). Normal pattern was observed solely in patients in remission. The late scleroderma pattern was associated with disease duration and systemic involvement. In SLE, disease activity correlated with onycholysis, nailfold erythema, and pathologic pattern in dermoscopy. However, patients with DM displayed a positive correlation between pulmonary involvement and scleroderma pattern. Nail involvement in CTD includes a diverse range of abnormalities. Despite being nonspecific, it can provide crucial clues for establishing a diagnosis. Nailfold dermoscopy serves as a mirror for microangiopathy, enabling the detection of changes at an initial stage, and thus, it becomes a diagnostic and prognostic tool.

Differing patterns of cortical grey matter pathology identified by multifractal analysis in UMN-predominant ALS patients with and without corticospinal tract hyperintensity

The pathological hallmarks of amyotrophic lateral sclerosis (ALS) are degeneration of the primary motor cortex grey matter (GM) and corticospinal tract (CST) resulting in upper motor neuron (UMN) dysfunction. Conventional brain magnetic resonance imaging (MRI) shows abnormal CST hyperintensity in some UMN-predominant ALS patients (ALS-CST+) but not in others (ALS-CST–). In addition to the CST differences, we aimed to determine whether GM degeneration differs between ALS-CST+ and ALS-CST– patients by cortical thickness (CT), voxel-based morphometry (VBM) and fractal dimension analyses. We hypothesized that MRI multifractal (MF) measures could differentiate between neurologic controls (n = 14) and UMN-predominant ALS patients as well as between patient subgroups (ALS-CST+, n = 21 vs ALS-CST–, n = 27). No significant differences were observed in CT or GM VBM in any brain regions between patients and controls or between ALS subgroups. MF analyses were performed separately on GM of the whole brain, of frontal, parietal, occipital, and temporal lobes as well as of cerebellum. Estimating MF measures D (Q = 0), D (Q = 1), D (Q = 2), Δf, Δα of frontal lobe GM classified neurologic controls, ALS-CST+ and ALS-CST– groups with 98% accuracy and > 95% in F1, recall, precision and specificity scores. Classification accuracy was only 74% when using whole brain MF measures and < 70% for other brain lobes. We demonstrate that MF analysis can distinguish UMN-predominant ALS subgroups based on GM changes, which the more commonly used quantitative approaches of CT and VBM cannot.