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Keywords = anatomical plausibility

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20 pages, 2786 KiB  
Article
Inverse Kinematics-Augmented Sign Language: A Simulation-Based Framework for Scalable Deep Gesture Recognition
by Binghao Wang, Lei Jing and Xiang Li
Algorithms 2025, 18(8), 463; https://doi.org/10.3390/a18080463 - 24 Jul 2025
Viewed by 239
Abstract
In this work, we introduce IK-AUG, a unified algorithmic framework for kinematics-driven data augmentation tailored to sign language recognition (SLR). Departing from traditional augmentation techniques that operate at the pixel or feature level, our method integrates inverse kinematics (IK) and virtual simulation to [...] Read more.
In this work, we introduce IK-AUG, a unified algorithmic framework for kinematics-driven data augmentation tailored to sign language recognition (SLR). Departing from traditional augmentation techniques that operate at the pixel or feature level, our method integrates inverse kinematics (IK) and virtual simulation to synthesize anatomically valid gesture sequences within a structured 3D environment. The proposed system begins with sparse 3D keypoints extracted via a pose estimator and projects them into a virtual coordinate space. A differentiable IK solver based on forward-and-backward constrained optimization is then employed to reconstruct biomechanically plausible joint trajectories. To emulate natural signer variability and enhance data richness, we define a set of parametric perturbation operators spanning spatial displacement, depth modulation, and solver sensitivity control. These operators are embedded into a generative loop that transforms each original gesture sample into a diverse sequence cluster, forming a high-fidelity augmentation corpus. We benchmark our method across five deep sequence models (CNN3D, TCN, Transformer, Informer, and Sparse Transformer) and observe consistent improvements in accuracy and convergence. Notably, Informer achieves 94.1% validation accuracy with IK-AUG enhanced training, underscoring the framework’s efficacy. These results suggest that algorithmic augmentation via kinematic modeling offers a scalable, annotation free pathway for improving SLR systems and lays the foundation for future integration with multi-sensor inputs in hybrid recognition pipelines. Full article
(This article belongs to the Section Algorithms for Multidisciplinary Applications)
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23 pages, 900 KiB  
Review
Perspectives on the Parathyroid–Thymus Interconnection—A Literature Review
by Maria-Paula Comănescu, Otilia Boișteanu, Delia Hînganu, Marius Valeriu Hînganu, Roxana Grigorovici and Alexandru Grigorovici
Int. J. Mol. Sci. 2025, 26(13), 6000; https://doi.org/10.3390/ijms26136000 - 23 Jun 2025
Viewed by 383
Abstract
The parathyroid and thymus glands are key components of the endocrine and immune systems, respectively, with intriguing developmental, anatomical, and functional interrelationships. This study starts from the hypothesis that, given their shared embryological origin, it is plausible that the thymus and parathyroid glands [...] Read more.
The parathyroid and thymus glands are key components of the endocrine and immune systems, respectively, with intriguing developmental, anatomical, and functional interrelationships. This study starts from the hypothesis that, given their shared embryological origin, it is plausible that the thymus and parathyroid glands interact functionally and may share pathological pathways. The present study explores the developmental pathways, spatial proximity, and potential cross-talk between these glands. Recent studies suggest that parathyroid hormone (PTH) may influence thymic function, including T-cell maturation and immune regulation, while thymic signaling molecules could impact calcium homeostasis and parathyroid activity. Understanding the functional and etiopathogenical relations between these endocrine glands offers new insights into endocrine–immunological crosstalk, and therapeutic approaches targeting disorders such as hypoparathyroidism, thymomas, myasthenia gravis and thymic hypoplasia. Perspectives and conclusion: Future research is essential to discover the molecular mechanisms underpinning this dynamic interrelation and its broader implications for health and disease. Because there is still very little data on this interaction, in-depth studies are necessary on large groups of patients. This research proposes a cross-study of the receptors for the main substances secreted by the two categories of endocrine glands. At the same time, it is essential to carry out an in-depth study on the cervico-pericardial ligaments through the lens of this glandular interaction. These ligaments could contain the main blood and nerve communication pathway between the parathyroids and the glands. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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26 pages, 15080 KiB  
Article
Mesopancreas—Anatomical Insights and Its Implications for Diagnosis and Clinical and Surgical Practice
by Florin-Mihail Filipoiu, Georgian-Theodor Badea, Mihaly Enyedi, Ștefan Oprea, Zoran-Florin Filipoiu and Daniela-Elena Gheoca Mutu
Diagnostics 2025, 15(7), 914; https://doi.org/10.3390/diagnostics15070914 - 2 Apr 2025
Cited by 1 | Viewed by 926
Abstract
Background: The concept of mesopancreas is frequently discussed in the surgical literature as the neural pathway for metastatic spread in pancreatic head cancer. It generally refers to a retro-pancreatic plane that should be resected to reduce the incidence of regional metastases. However, this [...] Read more.
Background: The concept of mesopancreas is frequently discussed in the surgical literature as the neural pathway for metastatic spread in pancreatic head cancer. It generally refers to a retro-pancreatic plane that should be resected to reduce the incidence of regional metastases. However, this concept remains poorly defined, both embryologically and anatomically. Our objective was to establish a clear embryological and anatomical definition of the mesopancreas, making anatomical data more applicable in surgical practice. Methods: We examined seven cadavers (5 males, 2 females, aged 62–71) with no medical or surgical history, preserved in 9% formalin at Carol Davila University’s Anatomy Department. Regional dissections were performed in successive planes, highlighting the celiac ganglia and the associated network of neural connections that comprise the mesopancreas. Results: Our study defines the “mesopancreas” as remnants of primordial mesenteries that coalesced into the Treitz fascia. We identified its functional components as nerve fibers linking the celiac ganglia and superior mesenteric plexus to the pancreas, along with vascular structures, lymphatics, and connective and adipose tissue. These components likely contribute to regional metastasis in pancreatic head cancer. While resection of the mesopancreas could help prevent metastasis, its complex anatomy and proximity to major vessels pose significant surgical challenges. Conclusions: Based on our findings, we propose a plausible definition for the term “mesopancreas”. It encompasses the structures that originated as part of the primordial mesenteries, which subsequently coalesced, resulting in the formation of the Treitz fascia. In essence, the mesopancreas is the functional content of a former mesentery. Full article
(This article belongs to the Special Issue Abdominal Diseases: Diagnosis, Treatment and Management)
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15 pages, 3628 KiB  
Article
Anatomical Plausibility in Deformable Image Registration Using Bayesian Optimization for Brain MRI Analysis
by Mauricio Castaño-Aguirre, Hernán Felipe García, David Cárdenas-Peña, Gloria Liliana Porras-Hurtado and Álvaro Ángel Orozco-Gutiérrez
Appl. Sci. 2024, 14(23), 10890; https://doi.org/10.3390/app142310890 - 24 Nov 2024
Viewed by 1175
Abstract
Deformable image registration plays a crucial role in medical imaging by aligning anatomical structures across multiple datasets, which is essential for accurate diagnosis and treatment planning. However, existing deep learning-based deformable registration models often face challenges in ensuring anatomical plausibility, leading to unnatural [...] Read more.
Deformable image registration plays a crucial role in medical imaging by aligning anatomical structures across multiple datasets, which is essential for accurate diagnosis and treatment planning. However, existing deep learning-based deformable registration models often face challenges in ensuring anatomical plausibility, leading to unnatural deformations in critical brain structures. This paper proposes a novel framework that uses Bayesian optimization to address these challenges, focusing on registering 3D point clouds that represent brain structures. Our method uses probabilistic modeling to optimize non-rigid transformations, providing smooth and interpretable deformations that align with anatomical constraints. The proposed framework is validated using MRI data from patients diagnosed with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia. These datasets include brain scans taken at multiple time points, enabling the modeling of structural changes over time. By incorporating Bayesian optimization, we enhance the accuracy of the registration process while maintaining anatomical fidelity. Our results demonstrate that the approach provides interpretable, anatomically plausible deformations, outperforming conventional methods in terms of accuracy and reliability. This work offers an improved tool for brain MRI analysis, aiding healthcare professionals in better understanding disease progression and guiding therapeutic interventions. Full article
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17 pages, 2260 KiB  
Article
From Phantoms to Patients: Improved Fusion and Voxel-Wise Analysis of Diffusion-Weighted Imaging and FDG-Positron Emission Tomography in Positron Emission Tomography/Magnetic Resonance Imaging for Combined Metabolic–Diffusivity Index (cDMI)
by Katharina Deininger, Patrick Korf, Leonard Lauber, Robert Grimm, Ralph Strecker, Jochen Steinacker, Catharina S. Lisson, Bernd M. Mühling, Gerlinde Schmidtke-Schrezenmeier, Volker Rasche, Tobias Speidel, Gerhard Glatting, Meinrad Beer, Ambros J. Beer and Wolfgang Thaiss
Diagnostics 2024, 14(16), 1787; https://doi.org/10.3390/diagnostics14161787 - 16 Aug 2024
Viewed by 1490
Abstract
Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially [...] Read more.
Hybrid positron emission tomography/magnetic resonance imaging (PET/MR) opens new possibilities in multimodal multiparametric (m2p) image analyses. But even the simultaneous acquisition of positron emission tomography (PET) and magnetic resonance imaging (MRI) does not guarantee perfect voxel-by-voxel co-registration due to organs and distortions, especially in diffusion-weighted imaging (DWI), which would be, however, crucial to derive biologically meaningful information. Thus, our aim was to optimize fusion and voxel-wise analyses of DWI and standardized uptake values (SUVs) using a novel software for m2p analyses. Using research software, we evaluated the precision of image co-registration and voxel-wise analyses including the rigid and elastic 3D registration of DWI and [18F]-Fluorodeoxyglucose (FDG)-PET from an integrated PET/MR system. We analyzed DWI distortions with a volume-preserving constraint in three different 3D-printed phantom models. A total of 12 PET/MR-DWI clinical datasets (bronchial carcinoma patients) were referenced to the T1 weighted-DIXON sequence. Back mapping of scatterplots and voxel-wise registration was performed and compared to the non-optimized datasets. Fusion was rated using a 5-point Likert scale. Using the 3D-elastic co-registration algorithm, geometric shapes were restored in phantom measurements; the measured ADC values did not change significantly (F = 1.12, p = 0.34). Reader assessment showed a significant improvement in fusion precision for DWI and morphological landmarks in the 3D-registered datasets (4.3 ± 0.2 vs. 4.6 ± 0.2, p = 0.009). Most pronounced differences were noted for the chest wall (p = 0.006), tumor (p = 0.007), and skin contour (p = 0.014). Co-registration increased the number of plausible ADC and SUV combinations by 25%. The volume-preserving elastic 3D registration of DWI significantly improved the precision of fusion with anatomical sequences in phantom and clinical datasets. The research software allowed for a voxel-wise analysis and visualization of [18F]FDG-PET/MR data as a “combined diffusivity–metabolic index” (cDMI). The clinical value of the optimized PET/MR biomarker can thus be tested in future PET/MR studies. Full article
(This article belongs to the Special Issue New Trends and Advances of MRI and PET Hybrid Imaging in Diagnostics)
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20 pages, 16701 KiB  
Article
A Multistage Rigid-Affine-Deformable Network for Three-Dimensional Multimodal Medical Image Registration
by Anika Strittmatter, Anna Caroli and Frank G. Zöllner
Appl. Sci. 2023, 13(24), 13298; https://doi.org/10.3390/app132413298 - 16 Dec 2023
Cited by 5 | Viewed by 2861
Abstract
Multimodal image registration is an important component of medical image processing, allowing the integration of complementary information from various imaging modalities to improve clinical applications like diagnosis and treatment planning. We proposed a novel multistage neural network for three-dimensional multimodal medical image registration, [...] Read more.
Multimodal image registration is an important component of medical image processing, allowing the integration of complementary information from various imaging modalities to improve clinical applications like diagnosis and treatment planning. We proposed a novel multistage neural network for three-dimensional multimodal medical image registration, which addresses the challenge of larger rigid deformations commonly present in medical images due to variations in patient positioning in different scanners and rigid anatomical structures. This multistage network combines rigid, affine and deformable transformations in three stages. The network was trained unsupervised with Mutual Information and Gradient L2 loss. We compared the results of our proposed multistage network with a rigid-affine-deformable registration with the classical registration method NiftyReg as a baseline and a multistage network, which combines affine and deformable transformation, as a benchmark. To evaluate the performance of the proposed multistage network, we used four three-dimensional multimodal in vivo datasets: three renal MR datasets consisting of T1-weighted and T2-weighted MR scans and one liver dataset containing CT and T1-weighted MR scans. Experimental results showed that combining rigid, affine and deformable transformations in a multistage network leads to registration results with a high structural similarity, overlap of the corresponding structures (Dice: 76.7 ± 12.5, 61.1 ± 14.0, 64.8 ± 16.2, 68.1 ± 24.6 for the four datasets) and a low level of image folding (|J| ≤ 0: less than or equal to 1.1%), resulting in a medical plausible registration result. Full article
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22 pages, 998 KiB  
Review
Neuroinflammation in Alzheimer’s Disease: A Potential Role of Nose-Picking in Pathogen Entry via the Olfactory System?
by Xian Zhou, Paayal Kumar, Deep J. Bhuyan, Slade O. Jensen, Tara L. Roberts and Gerald W. Münch
Biomolecules 2023, 13(11), 1568; https://doi.org/10.3390/biom13111568 - 24 Oct 2023
Cited by 8 | Viewed by 54480
Abstract
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide and tau deposition, but more recent evidence suggests that neuroinflammation may also play an—at [...] Read more.
Alzheimer’s disease (AD) is a complex neurodegenerative disorder characterized by progressive cognitive decline and memory impairment. Many possible factors might contribute to the development of AD, including amyloid peptide and tau deposition, but more recent evidence suggests that neuroinflammation may also play an—at least partial—role in its pathogenesis. In recent years, emerging research has explored the possible involvement of external, invading pathogens in starting or accelerating the neuroinflammatory processes in AD. In this narrative review, we advance the hypothesis that neuroinflammation in AD might be partially caused by viral, bacterial, and fungal pathogens entering the brain through the nose and the olfactory system. The olfactory system represents a plausible route for pathogen entry, given its direct anatomical connection to the brain and its involvement in the early stages of AD. We discuss the potential mechanisms through which pathogens may exploit the olfactory pathway to initiate neuroinflammation, one of them being accidental exposure of the olfactory mucosa to hands contaminated with soil and feces when picking one’s nose. Full article
(This article belongs to the Special Issue From Biomarkers to Therapy to Puzzle Out Alzheimer’s Disease)
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18 pages, 1239 KiB  
Article
Comparison of T1/2 Tongue Carcinoma with or without Radial Forearm Flap Reconstruction Regarding Post-Therapeutic Function, Survival, and Gender
by Katharina El-Shabrawi, Katharina Storck, Jochen Weitz, Klaus-Dietrich Wolff and Andreas Knopf
Cancers 2023, 15(6), 1885; https://doi.org/10.3390/cancers15061885 - 21 Mar 2023
Cited by 2 | Viewed by 2119
Abstract
Background: Flap reconstruction is commonly used in advanced tongue carcinoma in order to compensate for the loss of tongue tissue and function. Surprisingly, a large number of reconstructed early-stage tongue cancer can be found. Survival or functional benefits in these cases remain unclear. [...] Read more.
Background: Flap reconstruction is commonly used in advanced tongue carcinoma in order to compensate for the loss of tongue tissue and function. Surprisingly, a large number of reconstructed early-stage tongue cancer can be found. Survival or functional benefits in these cases remain unclear. Methods: A retrospective data analysis of 384 surgically treated tongue carcinoma patients was conducted aiming to find epidemiologic and survival differences between patients with (n = 158) or without flap reconstruction (n = 226). A prospective functional analysis was performed on 55 early-stage tongue cancer patients, 33 without and 22 with radial-forearm flap reconstruction, focusing on post-therapeutic swallowing function as the primary endpoint, speech as the secondary endpoint, xerostomia, quality of life, and mouth opening. Results: Consistent with the current literature, we demonstrated the significantly more frequent use of flap grafts in advanced tongue carcinomas. For the first time, we depicted a higher female ratio in the reconstructed group (p = 0.02). There were no significant differences in survival or functional outcomes between the groups. The none-reconstructed group showed more frequent use of adjuvant C/RT despite presenting fewer N+ stages. Conclusions: The higher female ratio in the reconstruction group is plausible due to the anatomically smaller oral cavity and relatively larger carcinoma in women. A higher presence of close margins in the none-reconstruction group may explain the more frequent use of adjuvant C/RT. Since we found no survival or functional differences between the groups, we propose a critical approach toward flap reconstruction in T1/2 tongue carcinoma. At the same time, proportional aspects and adequate resection margins should be taken into account. Full article
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11 pages, 14227 KiB  
Case Report
Discordance between Invasive and Non-Invasive Coronary Angiography: An In-Depth Functional and Anatomical Analysis
by Shigetaka Kageyama, Kaoru Tanaka, Shinichiro Masuda, Momoko Kageyama, Scot Garg, Adam Updegrove, Johan De Mey, Mark La Meir, Yoshinobu Onuma and Patrick W. Serruys
Biomedicines 2023, 11(3), 913; https://doi.org/10.3390/biomedicines11030913 - 15 Mar 2023
Cited by 1 | Viewed by 2906
Abstract
A 79-year-old male with chronic coronary syndrome with complex coronary artery disease was included in the first-in-man trial of surgical revascularization guided solely by coronary computed tomography angiography (CCTA) and fractional flow reserve derived from CCTA (FFRCT). In CCTA analysis, the [...] Read more.
A 79-year-old male with chronic coronary syndrome with complex coronary artery disease was included in the first-in-man trial of surgical revascularization guided solely by coronary computed tomography angiography (CCTA) and fractional flow reserve derived from CCTA (FFRCT). In CCTA analysis, the patient had calcified three-vessel disease, with a global anatomical SYNTAX score of 27. In contrast, in the initial FFRCT, only the ramus intermediate stenosis was physiologically significant, with no other vessels having an FFRCT ≤ 0.80 (functional SYNTAX score of 2). Discordance between the results of the CCTA and FFRCT necessitated an in-depth analysis by using both invasive and non-invasive coronary angiography. Angiography-derived fractional flow reserve (FFR) confirmed that the stenosis in the proximal left anterior descending artery (LAD) was physiologically significant, while it remained functionally negative in the second assessment of FFRCT. Extensive calcification is the most plausible explanation for the underestimation of the stenosis of proximal LAD in CCTA-derived FFR technology. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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9 pages, 618 KiB  
Opinion
Arousal Regulation by the External Globus Pallidus: A New Node for the Mesocircuit Hypothesis
by Zhong Sheng Zheng, Nicco Reggente and Martin M. Monti
Brain Sci. 2023, 13(1), 146; https://doi.org/10.3390/brainsci13010146 - 14 Jan 2023
Cited by 5 | Viewed by 4035
Abstract
In the decade since its debut, the Mesocircuit Hypothesis (MH) has provided researchers a scaffolding for interpreting their findings by associating subcortical-cortical dysfunction with the loss and recovery of consciousness following severe brain injury. Here, we leverage new findings from human and rodent [...] Read more.
In the decade since its debut, the Mesocircuit Hypothesis (MH) has provided researchers a scaffolding for interpreting their findings by associating subcortical-cortical dysfunction with the loss and recovery of consciousness following severe brain injury. Here, we leverage new findings from human and rodent lesions, as well as chemo/optogenetic, tractography, and stimulation studies to propose the external segment of the globus pallidus (GPe) as an additional node in the MH, in hopes of increasing its explanatory power. Specifically, we discuss the anatomical and molecular mechanisms involving the GPe in sleep-wake control and propose a plausible mechanistic model explaining how the GPe can modulate cortical activity through its direct connections with the prefrontal cortex and thalamic reticular nucleus to initiate and maintain sleep. The inclusion of the GPe in the arousal circuitry has implications for understanding a range of phenomena, such as the effects of the adenosine (A2A) and dopamine (D2) receptors on sleep-wake cycles, the paradoxical effects of zolpidem in disorders of consciousness, and sleep disturbances in conditions such as Parkinson’s Disease. Full article
(This article belongs to the Special Issue Women in Brain Science: Achievements, Challenges and Perspectives)
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28 pages, 913 KiB  
Article
Self-Calibrating Magnetometer-Free Inertial Motion Tracking of 2-DoF Joints
by Daniel Laidig, Ive Weygers and Thomas Seel
Sensors 2022, 22(24), 9850; https://doi.org/10.3390/s22249850 - 15 Dec 2022
Cited by 11 | Viewed by 4103
Abstract
Human motion analysis using inertial measurement units (IMUs) has recently been shown to provide accuracy similar to the gold standard, optical motion capture, but at lower costs and while being less restrictive and time-consuming. However, IMU-based motion analysis requires precise knowledge of the [...] Read more.
Human motion analysis using inertial measurement units (IMUs) has recently been shown to provide accuracy similar to the gold standard, optical motion capture, but at lower costs and while being less restrictive and time-consuming. However, IMU-based motion analysis requires precise knowledge of the orientations in which the sensors are attached to the body segments. This knowledge is commonly obtained via time-consuming and error-prone anatomical calibration based on precisely defined poses or motions. In the present work, we propose a self-calibrating approach for magnetometer-free joint angle tracking that is suitable for joints with two degrees of freedom (DoF), such as the elbow, ankle, and metacarpophalangeal finger joints. The proposed methods exploit kinematic constraints in the angular rates and the relative orientations to simultaneously identify the joint axes and the heading offset. The experimental evaluation shows that the proposed methods are able to estimate plausible and consistent joint axes from just ten seconds of arbitrary elbow joint motion. Comparison with optical motion capture shows that the proposed methods yield joint angles with similar accuracy as a conventional IMU-based method while being much less restrictive. Therefore, the proposed methods improve the practical usability of IMU-based motion tracking in many clinical and biomedical applications. Full article
(This article belongs to the Collection Sensors for Gait, Human Movement Analysis, and Health Monitoring)
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11 pages, 699 KiB  
Review
The Mechanistic Pathways of Periodontal Pathogens Entering the Brain: The Potential Role of Treponema denticola in Tracing Alzheimer’s Disease Pathology
by Flavio Pisani, Valerio Pisani, Francesca Arcangeli, Alice Harding and Simarjit Kaur Singhrao
Int. J. Environ. Res. Public Health 2022, 19(15), 9386; https://doi.org/10.3390/ijerph19159386 - 31 Jul 2022
Cited by 27 | Viewed by 4409
Abstract
Alzheimer’s Disease (AD) is a complex neurodegenerative disease and remains the most common form of dementia. The pathological features include amyloid (Aβ) accumulation, neurofibrillary tangles (NFTs), neural and synaptic loss, microglial cell activation, and an increased blood–brain barrier permeability. One longstanding hypothesis suggests [...] Read more.
Alzheimer’s Disease (AD) is a complex neurodegenerative disease and remains the most common form of dementia. The pathological features include amyloid (Aβ) accumulation, neurofibrillary tangles (NFTs), neural and synaptic loss, microglial cell activation, and an increased blood–brain barrier permeability. One longstanding hypothesis suggests that a microbial etiology is key to AD initiation. Among the various periodontal microorganisms, Porphyromonas gingivalis has been considered the keystone agent to potentially correlate with AD, due to its influence on systemic inflammation. P. gingivalis together with Treponema denticola and Tannerella forsythia belong to the red complex consortium of bacteria advocated to sustain periodontitis within a local dysbiosis and a host response alteration. Since the implication of P. gingivalis in the pathogenesis of AD, evidence has emerged of T. denticola clusters in some AD brain tissue sections. This narrative review explored the potential mode of spirochetes entry into the AD brain for tracing pathology. Spirochetes are slow-growing bacteria, which can hide within ganglia for many years. It is this feature in combination with the ability of these bacteria to evade the hosts’ immune responses that may account for a long lag phase between infection and plausible AD disease symptoms. As the locus coeruleus has direct connection between the trigeminal nuclei to periodontal free nerve endings and proprioceptors with the central nervous system, it is plausible that they could initiate AD pathology from this anatomical region. Full article
(This article belongs to the Special Issue Basics of Hygiene in Public Health and Health Promotion)
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23 pages, 4634 KiB  
Article
Targeted Disruption of the Inhibitor of DNA Binding 4 (Id4) Gene Alters Photic Entrainment of the Circadian Clock
by Giles E. Duffield, Maricela Robles-Murguia, Tim Y. Hou and Kathleen A. McDonald
Int. J. Mol. Sci. 2021, 22(17), 9632; https://doi.org/10.3390/ijms22179632 - 6 Sep 2021
Cited by 3 | Viewed by 2738
Abstract
Inhibitor of DNA binding (Id) genes comprise a family of four helix–loop–helix (HLH) transcriptional inhibitors. Our earlier studies revealed a role for ID2 within the circadian system, contributing to input, output, and core clock function through its interaction with CLOCK and [...] Read more.
Inhibitor of DNA binding (Id) genes comprise a family of four helix–loop–helix (HLH) transcriptional inhibitors. Our earlier studies revealed a role for ID2 within the circadian system, contributing to input, output, and core clock function through its interaction with CLOCK and BMAL1. Here, we explore the contribution of ID4 to the circadian system using a targeted disruption of the Id4 gene. Attributes of the circadian clock were assessed by monitoring the locomotor activity of Id4−/− mice, and they revealed disturbances in its operation. Id4-mutant mice expressed a shorter circadian period length, attenuated phase shifts in responses to continuous and discrete photic cues, and an advanced phase angle of entrainment under a 12:12 light:dark cycle and under short and long photoperiods. To understand the basis for these properties, suprachiasmatic nucleus (SCN) and retinal structures were examined. Anatomical analysis reveals a smaller Id4−/− SCN in the width dimension, which is a finding consistent with its smaller brain. As a result of this feature, anterograde tracing in Id4−/− mice revealed retinal afferents innovate a disproportionally larger SCN area. The Id4−/− photic entrainment responses are unlikely to be due to an impaired function of the retinal pathways since Id4−/− retinal anatomy and function tested by pupillometry were similar to wild-type mice. Furthermore, these circadian characteristics are opposite to those exhibited by the Id2−/− mouse, suggesting an opposing influence of the ID4 protein within the circadian system; or, the absence of ID4 results in changes in the expression or activity of other members of the Id gene family. Expression analysis of the Id genes within the Id4−/− SCN revealed a time-of-day specific elevated Id1. It is plausible that the increased Id1 and/or absence of ID4 result in changes in interactions with bHLH canonical clock components or with targets upstream and/or downstream of the clock, thereby resulting in abnormal properties of the circadian clock and its entrainment. Full article
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24 pages, 1950 KiB  
Review
Aberrant Neurogliovascular Unit Dynamics in Cerebral Small Vessel Disease: A Rheological Clue to Vascular Parkinsonism
by Che Mohd Nasril Che Mohd Nassir, Thenmoly Damodaran, Siti R. Yusof, Anwar Norazit, Geetha Chilla, Isaac Huen, Bhanu Prakash K. N., Norlinah Mohamed Ibrahim and Muzaimi Mustapha
Pharmaceutics 2021, 13(8), 1207; https://doi.org/10.3390/pharmaceutics13081207 - 5 Aug 2021
Cited by 12 | Viewed by 7036
Abstract
The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood–brain barrier permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the glymphatic system that manages the flow of interstitial solutes, [...] Read more.
The distinctive anatomical assemble and functionally discrete multicellular cerebrovasculature dynamics confer varying rheological and blood–brain barrier permeabilities to preserve the integrity of cerebral white matter and its neural microenvironment. This homeostasis intricately involves the glymphatic system that manages the flow of interstitial solutes, metabolic waste, and clearance through the venous circulation. As a physiologically integrated neurogliovascular unit (NGVU) serving a particularly vulnerable cerebral white matter (from hypoxia, metabolic insults, infection, and inflammation), a likely insidious process over a lifetime could inflict microenvironment damages that may lead to pathological conditions. Two such conditions, cerebral small vessel disease (CSVD) and vascular parkinsonism (VaP), with poorly understood pathomechanisms, are frequently linked to this brain-wide NGVU. VaP is widely regarded as an atypical parkinsonism, described by cardinal motor manifestations and the presence of cerebrovascular disease, particularly white matter hyperintensities (WMHs) in the basal ganglia and subcortical region. WMHs, in turn, are a recognised imaging spectrum of CSVD manifestations, and in relation to disrupted NGVU, also include enlarged perivascular spaces. Here, in this narrative review, we present and discuss on recent findings that argue for plausible clues between CSVD and VaP by focusing on aberrant multicellular dynamics of a unique integrated NGVU—a crossroad of the immune–vascular–nervous system—which may also extend fresher insights into the elusive interplay between cerebral microvasculature and neurodegeneration, and the potential therapeutic targets. Full article
(This article belongs to the Special Issue Biological Barriers in Health and Disease)
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24 pages, 4125 KiB  
Review
Vulvar Lichen Sclerosus from Pathophysiology to Therapeutic Approaches: Evidence and Prospects
by Monica Corazza, Natale Schettini, Pierantonia Zedde and Alessandro Borghi
Biomedicines 2021, 9(8), 950; https://doi.org/10.3390/biomedicines9080950 - 3 Aug 2021
Cited by 66 | Viewed by 20648
Abstract
Vulvar lichen sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. Treatment goals are relieving symptoms, reversing signs and preventing anatomical changes. Despite the availability of numerous therapeutic options, treatment outcome may not be entirely satisfactory [...] Read more.
Vulvar lichen sclerosus (VLS) is a chronic, distressing, inflammatory disease with an enormous impact on quality of life. Treatment goals are relieving symptoms, reversing signs and preventing anatomical changes. Despite the availability of numerous therapeutic options, treatment outcome may not be entirely satisfactory and a definitive cure does not exist. This may be due to the fact that the exact VLS etiopathogenesis remains unknown. The objectives of this paper were to review the most up-to-date knowledge on VLS etiopathogenesis and to consider the available therapies through the lens of a plausible pathogenetic model. An electronic search on both VLS etiopathogenesis and its treatment was performed using the National Library of Medicine PubMed database. Based on current knowledge, it is conceivable that various, heterogeneous environmental factors acting on a genetic background trigger an autoimmune, Th-1 response, which leads to a chronic inflammatory state. This, in turn, can determine both tissue and micro-vascular injury and activation of signaling pathways involved in fibroblast and collagen metabolism. This pathogenetic sequence may explain the effectiveness of anti-inflammatory treatments, mostly topical corticosteroids, in improving VLS clinical-pathological changes. Further deepening of the disease pathways will presumably allow key mediators to become new therapeutic targets and optimize the available treatments. Full article
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