Evaluation of lamin A/C mechanotransduction under different surface topography in LMNA related muscular dystrophy.

Most of the single point mutations of the LMNA gene are associated with distinct muscular dystrophies, marked by heterogenous phenotypes but primarily the loss and symmetric weakness of skeletal muscle tissue. The molecular mechanism and phenotype-genotype relationships in these muscular dystrophies are poorly understood. An effort has been here to delineating the adaptation of mechanical inputs into biological response by mutant cells of lamin A associated muscular dystrophy. In this study, we implement engineered smooth and pattern surfaces of particular young modulus to mimic muscle physiological range. Using fluorescence and atomic force microscopy, we present distinct architecture of the actin filament along with abnormally distorted cell and nuclear shape in mutants, which showed a tendency to deviate from wild type cells. Topographic features of pattern surface antagonize the binding of the cell with it. Correspondingly, from the analysis of genome wide expression data in wild type and mutant cells, we report differential expression of the gene products of the structural components of cell adhesion as well as LINC (linkers of nucleoskeleton and cytoskeleton) protein complexes. This study also reveals mis expressed downstream signaling processes in mutant cells, which could potentially lead to onset of the disease upon the application of engineered materials to substitute the role of conventional cues in instilling cellular behaviors in muscular dystrophies. Collectively, these data support the notion that lamin A is essential for proper cellular mechanotransduction from extracellular environment to the genome and impairment of the muscle cell differentiation in the pathogenic mechanism for lamin A associated muscular dystrophy.

Alterations in Gray Matter Structural Networks in Amnestic Mild Cognitive Impairment: A Source-Based Morphometry Study.

Background: Amnestic mild cognitive impairment (aMCI), considered as the prodromal stage of Alzheimer's disease, is characterized by isolated memory impairment and cerebral gray matter volume (GMV) alterations. Previous structural MRI studies in aMCI have been mainly based on univariate statistics using voxel-based morphometry. Objective: We investigated structural network differences between aMCI patients and cognitively normal older adults by using source-based morphometry, a multivariate approach that considers the relationship between voxels of various parts of the brain. Methods: Ninety-one aMCI patients and 80 cognitively normal controls underwent structural MRI and neuropsychological assessment. Spatially independent components (ICs) that covaried between participants were estimated and a multivariate analysis of covariance was performed with ICs as dependent variables, diagnosis as independent variable, and age, sex, education level, and site as covariates. Results: aMCI patients exhibited reduced GMV in the precentral, temporo-cerebellar, frontal, and temporal network, and increased GMV in the left superior parietal network compared to controls (pFWER < 0.05, Holm-Bonferroni correction). Moreover, we found that diagnosis, more specifically aMCI, moderated the positive relationship between occipital network and Mini-Mental State Examination scores (pFWER < 0.05, Holm-Bonferroni correction). Conclusions: Our results showed GMV alterations in temporo-fronto-parieto-cerebellar networks in aMCI, extending previous results obtained with univariate approaches.

Comparative morphometric analyses of the 2:4 finger ratio and nasal structure in young adults.

The 2:4 finger ratio (2D:4D ratio) refers to the length ratio of the second to the fourth finger of the hand. Studies on the 2D:4D ratio have long established that this ratio tends to be lower in males than in females. Our study aims to investigate the correlation between the 2.4 finger ratio and nasal structure among young adults aged 18-25 through detailed morphometric analysis. The study was conducted on 205 students (Female:127, Male:78) aged between 18 and 25 years studying at Ankara Yildirim Beyazit University Faculty of Medicine. Morphometric measurements of the hand and nose were also measured and recorded by the same researcher. The volunteers were divided into eight groups for age and four groups for BMI. Statistical analysis was performed and p < 0.05 was considered significant. The evaluation revealed significant differences between sexes and the 2D:4D ratio. While no significant relationship was found between age and the 2D:4D ratio, correlations were present with some nasal parameters. A significant relationship was found between the BMI and the right hand 2D:4D ratio (p < 0.05). A positive correlation was observed between the BMI and certain nasal parameters. Furthermore, significant relationships were identified between the 2D:4D ratio and certain nasal parameters (p < 0.05). The data obtained from our study will contribute to the understanding of nasal development, sex determination in forensic medicine, and the diagnosis and treatment of pathologies related to the nose. Additionally, it will assist clinicians involved in planning any nasal operations in describing anatomical points related to this region.

The Feasibility of Condylar Screws for Occipitocervical Fusion in Arabs: Computed Tomography-Based Morphometric Study.

STUDY DESIGN: Retrospective, cross-sectional study. OBJECTIVES: Occipitocervical fusion is indicated for various conditions. Some techniques require placement of screws in the occipital condyle. The objective of this study was to analyze the morphometric features of the occipital condyle among Arabs. METHODS: Computed tomography (CT)-based morphometric analysis of occipital condyles of 200 Arab skeletally mature patients (400 condyles) was done. Axial width of at least 8 mm and coronal height of at least 6.5 mm are the cutoff values for feasibility of condylar screw placement. RESULTS: The mean age of the patients was 48.0 ± 18.3 years. Males were 53.5% (107) of the sample. The mean axial condylar width and length were 8.5 ± 1.5 mm and 20.3 ± 2.6 mm, respectively, while the mean axial screw angle was 35.9° ± 5.5° from midline. The mean sagittal condylar length and height were 16.1 ± 1.9 mm and 8.8 ± 1.5 mm, respectively. The mean condylar coronal height was 8.2 ± 1.4 mm. Based on axial width and coronal height measurements, 150 (37.5%) condyles could safely fit a 3.5 mm condylar screw. One hundred and four (55.9% female condyles) condyles cannot fit a screw in females, while 46 (21.5% male condyles) condyles cannot fit a screw in males. CONCLUSIONS: Condylar screw for occipitocervical fusion is feasible for the majority of Arabs in our sample; however, this applies to slightly less than half of the female condyles. Detailed preoperative radiological planning is critical to avoid complications related to occipital condyle screw placement.

Development and validation of betel-year: a clinical tool for quantifying exposure to betel quid chewing, utilizing nuclear morphometric analysis and validated by cytomorphological analysis.

BACKGROUND: Betel quid chewing, prevalent in Southeast Asia and South Asia, involves components such as betel leaf, areca nut, slaked lime, and sometimes tobacco. This study aims to assess buccal mucosa changes in betel quid chewers, develop a clinical tool for assessing exposure, and investigate its usability in predicting dysplasia. METHODS: After obtaining ethical approval and informed consent, patients were recruited from the Out-Patient Department of Government Medical College, Omandurar, Government Estate, India. A target sample size of 200 was calculated. The data included the history of betel quid chewing, buccal mucosa cells obtained by oral cytology, and the severity of dysplasia of the slides assessed by pathologists. We utilized principal component analysis (PCA) and confirmatory factor analysis (CFA) to validate a new outcome variable reflecting nuclear morphometric parameters (NMPs). Multiplicative regression models were developed for betel years based on betel exposure and additives. Spearman correlation and Kruskal-Wallis test was used to check the association between betel years and dysplasia. RESULTS: Significant differences in NMPs were observed among different betel chewing groups. We derived multiplicative regression models for betel years. In the logarithmic transformation approach, betel year = 0.05×betel-exposure×0.09×slaked-lime use×0.11×tobacco-use. In the original variable approach, betel year = 5.05×betel-exposure^0.00048×slaked-lime-use^0.18133×tobacco-use^1.47513. Spearman correlation and Kruskal-Wallis tests confirmed associations with dysplasia. CONCLUSION: Betel year is a pioneering tool for assessing lifetime betel quid exposure, similar to pack years for smoking. It could aid in risk stratification, targeted interventions and shaping public health policies. Despite limitations, betel year holds promise for revolutionizing oral health risk assessment, and future research can expand its scope globally, considering diverse betel quid compositions.

Morphology and morphometry of the anterior cerebral-anterior communicating artery complex.

PURPOSE: The variations of Cerebral arterial circle (Circle of Willis) are not rare. The study is done to assess the pattern of the component vessels of its anterior part with regard to Right- Left variations and compare with other studies. MATERIAL AND METHOD: 56 formalin fixed cadavers were analyzed. The diameter, length and variations of the following vessels were observed: Anterior Cerebral Artery (proximal A1 segment to distal A2 segment) and anterior communicating artery. Statistical analysis was done by Statistica 14.0.1 software. RESULT: 53.57% had normal anterior cerebral artery- anterior communicating artery complex. Length and diameter were slightly more on left side. Unilateral hypoplasia, Azygos and Tripple Anterior Cerebral Artery was present in 21.43%, 3.57 and 1.78% respectively. Aplastic, double and fenestration type anterior communicating artery were present in 5.3%, 8.92% and 1.78% respectively. CONCLUSION: Anatomical knowledge of variations should be updated regularly for neurosurgeons, radiologists and clinicians to avoid unexpected consequences.

CAT: a computational anatomy toolbox for the analysis of structural MRI data.

A large range of sophisticated brain image analysis tools have been developed by the neuroscience community, greatly advancing the field of human brain mapping. Here we introduce the Computational Anatomy Toolbox (CAT)-a powerful suite of tools for brain morphometric analyses with an intuitive graphical user interface but also usable as a shell script. CAT is suitable for beginners, casual users, experts, and developers alike, providing a comprehensive set of analysis options, workflows, and integrated pipelines. The available analysis streams-illustrated on an example dataset-allow for voxel-based, surface-based, and region-based morphometric analyses. Notably, CAT incorporates multiple quality control options and covers the entire analysis workflow, including the preprocessing of cross-sectional and longitudinal data, statistical analysis, and the visualization of results. The overarching aim of this article is to provide a complete description and evaluation of CAT while offering a citable standard for the neuroscience community.

A Multimodal Meta-Analysis of Structural and Functional Alterations in the Brain of Knee Osteoarthritis Systematic Review.

BACKGROUND: Abnormalities of structural and functional brain regions might influence the persistence of knee pain, the progression, and the response to treatments in knee osteoarthritis (KOA). These complex alterations present a challenge to the understanding of its mechanism. OBJECTIVES: To meta-analyze the concurrence across structural and functional magnetic resonance imaging studies. STUDY DESIGN: Systematic review and meta-analysis. SETTING: This meta-analysis examined all voxel-based morphometric (VBM) and amplitude of low-frequency fluctuation (ALFF) studies involving the whole-brain alterations of KOA. METHODS: VBM and ALFF studies published up to May 7, 2023, were searched in the Web of Science, PubMed, EMBASE, Cochrane Library (CENTRAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database, Chongqing VIP, Wanfang Database. Two independent researchers carried out study screening, quality assessment, clinical data extraction, and neuroimaging data extraction. The whole-brain voxel-based gray matter (GM) and brain activity data of KOA were collected from eligible studies and meta-analyzed using the anisotropic effect size-signed differential mapping (AES-SDM). RESULTS: Fourteen studies were included in this study. In VBM meta-analyses, a total of 481 patients were enrolled in this study (252 KOA and 229 healthy patients). In the ALFF meta-analysis, a total of 518 patients were enrolled in this study (265 KOA and 253 healthy patients). According to the meta-analysis, KOA had increased GM volume in the right inferior frontal gyrus and decreased GM volume in the bilateral superior frontal gyrus, as well as increased brain activity in the left inferior frontal gyrus and inferior temporal gyrus, and decreased brain activity in the left middle occipital gyrus, right supramarginal gyrus, right superior frontal gyrus, and right superior parietal gyrus compared with healthy patients. LIMITATIONS: Most of the ALFF studies included in this meta-analysis were conducted in China. Our findings are exclusively addressed by the VBM and ALFF studies. The meta-regression between the duration of KOA, pain intensity and abnormal gray matter, and functional activity of brain regions in patients with KOA were unable to be analyzed. CONCLUSION: The results of this meta-analysis indicate that patients with KOA present significant abnormalities in GM volume and functional activity. These findings contribute to a better understanding of the structural and functional abnormalities seen in patients with KOA.

Quantitative Morphological Study of Larynx APUD-Cells in Asphyxial Type of Drowning in Fresh Water (Experimental Study).

An additional microscopic diagnostic sign has been identified for verification of asphyxial type of drowning. In white non-linear male rats (age 2 months) subjected to free drowning, significant hyperplasia of argyrophilic and morphofunctional activity of serotonin-containing APUD-cells of the laryngeal mucosa were revealed under conditions of acute anoxia in comparison with the intact control. These changes promote the development of laryngospasm, which prevents water penetration into the airways and lungs in asphyxial type of drowning. The presence of statistically significant hyperplasia of argyrophilic and morphofunctional activity of serotonin-containing APUD-cells of the laryngeal mucosa under conditions of acute anoxia can be used as an additional diagnostic criterion for asphyxial type of drowning in experimental studies.

Quantitative metrics of bone quality determined at the distal radius using photon-counting CT.

OBJECTIVE: To determine the accuracy of photon-counting-detector CT (PCD-CT) at deriving bone morphometric indices and demonstrate utility in vivo in the distal radius. METHODS: Ten cadaver wrists were scanned using PCD-CT and high-resolution peripheral quantitative CT (HRpQCT). Correlation between PCD-CT and HRpQCT morphometric indices was determined. Agreement was assessed by Lin's concordance correlation coefficient (Lin's CCC). Wrist PCD-CTs of patients between 02/2022 and 08/2023 were also evaluated for clinical utility. Morphometric indices of the in vivo distal radii were extracted and compared between patients with or without osteoporosis. RESULTS: In cadavers, strong correlation between PCD-CT and HRpQCT was observed for cortical thickness (Spearman correlation, ρ, 0.85), trabecular spacing (ρ = 0.98), and trabecular bone volume fraction (ρ = 0.68). Moderate negative correlation (ρ = - 0.49) was observed for trabecular thickness. PCD-CT shows good agreement to HRpQCT for cortical thickness, trabecular spacing, and trabecular bone volume fraction (Lin's CCC = 0.80, 0.94, and 0.86, respectively) but poor agreement (Lin's CCC = - 0.1) for trabecular thickness. In forty participants (31 adults and 9 pediatric), bone morphometrics indices for cortical thickness, trabecular thickness, trabecular spacing, and trabecular bone volume fraction were 0.99 mm (IQR, 0.89-1.06), 0.38 mm (IQR, 0.25-0.40), 0.82 mm (IQR, 0.72-1.05), and 0.28 (IQR, 0.25-0.33), respectively. Patients with osteoporosis had statistically significantly larger trabecular spacing (p = 0.025) and lower trabecular volumetric bone mineral density (p = 0.042). CONCLUSION: This study demonstrates the agreement of PCD-CT to HRpQCT in cadavers of most cortical and bone morphometrics examined and provide in vivo quantitative metrics of bone microarchitecture from routine clinical PCD-CT images of the distal radius.

An MRI-based study of the insula in a South African population.

PURPOSE: The insula, a cortical structure buried deep within the sylvian fissure, has long posed a surgical challenge. Comprehensive knowledge of the insular anatomy is therefore integral to preoperative planning and safe interventional procedures. Since magnetic resonance imaging (MRI) is a favoured modality for the identification of cerebral structures, this study aimed to investigate the morphology and morphometry of the insula in a South African population, using MRI scans. METHODS: One-hundred MRI studies of insulae (n = 200 hemispheres) were retrospectively analysed for morphological features and morphometric parameters. RESULTS: The insulae were predominantly trapezoidal in shape (Laterality: Left: 82%; Right: 78%; Sex: Male: 84%, Female: 76%). The central insular sulcus was almost always "well seen" (Laterality: Left: 97%; Right: 99%; Sex: Male: 99%, Female: 97%). The middle short insular gyrus (MSG) was most variable in visibility, especially when compared across the sexes (p = 0.004). Insular gyri widths were comparable in both cerebral hemispheres; the posterior long gyrus (PLG) presented with the smallest mean widths. Anterior lobule (AL) widths were larger than those of the posterior lobule (PL). Widths of the insular gyri and lobules were generally larger in males than in females. The MSG and PLG widths in the left hemisphere, AL width in the right hemisphere, and the PL width in both hemispheres were significantly larger in males than in females (p = 0.001; p = 0.005; p = 0.041; p = 0.001, p = 0.015, respectively). CONCLUSION: MRI scans may be used to accurately interpret insular anatomy. The data obtained may aid neurosurgeons to perform safe insula-related surgical procedures.

Spatial regulation of substrate adhesion directs fibroblast morphotype and phenotype.

The switching of the fibroblast phenotype to myofibroblast is a hallmark of a wide variety of tissue pathologies. This phenotypical switch is known to be influenced not only by humoral factors such as TGF-ß, but also by mechanical and physical cues in the cellular environment, and is accompanied by distinctive changes in cell morphology. However, the causative link between these cues, the concomitant morphological changes, and the resulting phenotypic switch remain elusive. Here, we use protein micropatterning to spatially control dermal fibroblast adhesion without invoking exogenous mechanical changes and demonstrate that varying the spatial configuration of focal adhesions (FAs) is sufficient to direct fibroblast phenotype. We further developed an automated morphometry analysis pipeline, which revealed FA eccentricity as the primary determinant of cell-state positioning along the spectrum of fibroblast phenotype. Moreover, linear fibronectin patterns that constrain the FAs were found to promote a further phenotype transition, characterized by dispersed expression of alpha-smooth muscle actin, pointing to an interesting possibility of controlling fibroblast phenotype beyond the canonical fibroblast-myofibroblast axis. Together, our study reveals that the spatial configuration of adhesion to the cellular microenvironment is a key factor governing fibroblast morphotype and phenotype, shedding new light on fibroblast phenotype regulation.

Associations between brain structures, cognition and dual-task performance in patients with mild cognitive impairment: A study based on voxel-based morphology.

BACKGROUND: This study aimed to explore the associations between brain structures, cognition, and motor control in participants with mild cognitive impairment (MCI), with a focus on dual-task performance. METHODS: Thirty MCI patients and thirty healthy controls were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Structural magnetic resonance imaging data were analyzed using voxel-based morphometry (VBM) to calculate brain parenchyma volume and gray matter volume (GMV). Participants performed single- and dual-task Timed Up and Go (TUG) tests, and the correlations between significant GMV differences and task execution time was analyzed. RESULTS: MCI patients showed significantly lower MoCA scores, particularly in visuospatial/executive, attention, and delayed recall domains (p < 0.05). Dual-task TUG execution time was significantly increased in MCI patients (p < 0.05). The GMV in the right anterior lobe of the cerebellum and both insulae was positively correlated with visuospatial/executive scores (FDR-corrected, p < 0.05). The GMV of the right cerebellar anterior lobe and insula were significantly reduced in MCI patients (p < 0.05). The GMV of the right cerebellar anterior lobe was negatively correlated with dual-task execution time (r = -0.32, p = 0.012). CONCLUSION: Smaller GMV in the right anterior lobe of the cerebellum was associated with impaired dual-task performance, which may provide more evidence for the neural mechanisms of cognitive and motor function impairments in MCI.

Morphometric and functional changes in the kidney of rats induced by inorganic selenium.

Selenium (Se) is an essential trace element. Depending on concentration, Se can manifest both beneficial and harmful effects on the cell and can have both oxidative and antioxidant effects. Because the therapeutic index for Se is very narrow and it can depend on the form of Se used, we aimed to investigate the potential safety and side effects of inorganic Se on kidney function and structure in rats. After 8 days of treatment, no detectable signs of microscopic changes or oxidative stress in kidney tissue were observed. We detected a moderate increase in urea and creatinine levels in the blood as a sign of a slight decrease in kidney function. The most notable changes in our study were morphometric alterations in proximal tubules and glomeruli, both of which were considerably enlarged. The short-term application of inorganic Se to rats in a supratherapeutic dose induced mild functional and ultrastructural changes in the kidneys. The dose of inorganic Se used could be considered relatively safe for short-term application in situations where Se could be beneficial to the organism, such as the usage of known nephrotoxicants or high levels of oxidative stress in the body.

Cortical morphological alterations in cognitively normal Parkinson's disease with severe hyposmia.

Olfactory dysfunction is a common non-motor symptom of Parkinson's disease(PD) and may hold valuable insights into the disease's underlying pathophysiology. This study aimed to investigate cortical morphometry alterations in PD patients with severe hyposmia(PD-SH) and mild hyposmia(PD-MH) using surface-based morphometry(SBM) methods. Participants included 36 PD-SH patients, 38 PD-MH patients, and 40 healthy controls(HCs). SBM analysis revealed distinct patterns of cortical alterations in PD-SH and PD-MH patients. PD-MH patients exhibited reduced cortical thickness in the right supramarginal gyrus, while PD-SH patients showed widespread cortical thinning in regions including the bilateral pericalcarine cortex, bilateral lingual gyrus, left inferior parietal cortex, left lateral occipital cortex, right pars triangularis, right cuneus, and right superior parietal cortex. Moreover, PD-SH patients displayed reduced cortical thickness in the right precuneus compared to PD-MH patients. Fractal dimension analysis indicated increased cortical complexity in PD-MH patients' right superior temporal cortex and right supramarginal gyrus, as well as decreased complexity in the bilateral postcentral cortex, left superior parietal cortex, and right precentral cortex. Similarly, cortical gyrification index and cortical sulcal depth exhibited heterogeneous patterns of changes in PD-SH and PD-MH patients compared to HCs. These findings underscore the multifaceted nature of olfactory impairment in PD, with distinct patterns of cortical morphometry alterations associated with different degrees of hyposmia. The observed discrepancies in brain regions showing alterations reflect the complexity of PD's pathophysiology. These insights contribute to a deeper understanding of olfactory dysfunction in PD and provide potential avenues for early diagnosis and targeted interventions.

Three-dimensional structural and metric characterisation of cardioids.

Exact three-dimensional (3D) structural information of developing organoids is key for optimising organoid generation and for studying experimental outcomes in organoid models. We set up a 3D imaging technique and studied complexly arranged native and experimentally challenged cardioids of two stages of remodelling. The imaging technique we employed is S-HREM (Scanning High Resolution Episcopic Microscopy), a variant of HREM, which captures multiple images of subsequently exposed surfaces of resin blocks and automatically combines them to large sized digital volume data of voxels sizes below 1 µm3. We provide precise volumetric information of the examined specimens and their single components and comparisons between stages in terms of volume and micro- and macroanatomic structure. We describe the 3D arrangement and lining of different types of cavities and their changes between day 10 and day 14 and map the various cell types to their precise spatial and structural environment. Exemplarily, we conducted semiautomatic counts of nuclei. In cryo-injured cardioids, we examined the extension and composition of the injured areas. Our results demonstrate the high quality and the great potential of digital volume data produced with S-HREM. It also provides sound metric and structural information, which assists production of native and experimentally challenged left ventricle cardioids and interpretation of their structural remodelling.

Evaluation of the Vascular Endothelial Growth Factor and Smooth Muscle Actin Expression With Microvessel Density and Morphometric Analysis of Endometrial Vessels in Patients With Abnormal Uterine Bleeding.

BACKGROUND: Abnormal uterine bleeding (AUB) that occurs in a structurally normal uterus with regular menstrual cycles and without other identifiable etiology is often caused by a primary endometrial disorder (AUB-E). Altered vascular morphological changes and expression of markers of angiogenesis have been implicated as an underlying cause in these cases. OBJECTIVES:  The study was conducted to investigate the expression of vascular endothelial growth factor (VEGF) and smooth muscle actin-alpha (SMA-α), and to perform microvessel density (MVD), and morphometric evaluation of endometrial vessels in patients with AUB-E. MATERIAL AND METHODS: Endometrial biopsies and hysterectomy specimens of 40 patients clinically diagnosed with AUB-E were included in the study with 40 age-matched controls. Immunohistochemistry (IHC) with VEGF and SMA-α was performed, and the expression and staining pattern was recorded as the number of positive vessels per 10 high power fields and intensity scores. Morphometric analysis was performed on CD34 stained sections using Leica Application Suite, version 4.4.0 software (Leica Microsystems, Wetzlar, Germany). MVD was calculated by the vascular hotspot method. RESULTS: A statistically significant increase in VEGF vessel count (p-value<0.001) and a decline in SMA-α expression (p-value=0.23) was seen in cases as compared to the control group. There was a statistically significant increase in microvessel caliber (p-value=0.01) and MVD (p-value <0.001) in cases as compared to controls. CONCLUSION: These findings support aberrant vascular proliferation and impaired vessel maturation, contributing to the pathology of AUB-E. Alterations in angiogenesis in these patients reveal potential therapeutic targets for AUB.

Biomarkers of neural integrity and immunoglobulin genes influence neurodegeneration in Alzheimer's disease.

Compelling evidence has been presented in favor of herpes simplex virus type 1 (HSV1) being one of the causative agents of Alzheimer's disease (AD). The success of HSV1 as a pathogen relates to its sophisticated strategies to evade host immunosurveillance. One strategy involves encoding a decoy Fcγ receptor (FcγR) that thwarts the Fcγ-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), a potent host immunosurveillance mechanism against virally infected cells. The decoy FcγR binds to antibodies of all IgG subclasses, except IgG3; therefore, IgG3 would be expected to play an important role in viral clearance by neutralization and ADCC, and thus contribute to protection from HSV1-spurred diseases. Previous studies have shown significant association between anti-HSV1 IgG3 antibodies and cortical thinning of the areas of the brain typically altered in AD and also targeted by HSV1. The aim of the present investigation was to determine whether GM (γ marker) 5 and GM 21 allotypes, hereditary allelic determinants expressed on IgG3, together with brain biomarkers of neural integrity, contributed to neurodegeneration-as measured by mini-mental state examination (MMSE) score-in patients with AD. Multiple regression analyses showed that the homozygous GM 5/5 genotype, preserved right hippocampus, and right insula thickness were associated with higher MMSE scores (p < 0.001), whereas the opposite pattern and GM 5/21 genotype were associated with worse clinical profiles. Influence of GM 5/21-expressing IgG3 antibodies on the ADCC of HSV1-infected neurons could, at least partially, explain these results.

Developmental changes in brain structure and function following exposure to oral LSD during adolescence.

LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90-120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90-120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.

The study of the number and localization of the nutrient foramen on the clavicle and its relationship with other clavicle parameters.

BACKGROUND: Nutrient foramen (NF) is a hole on the long bones that allows the passage of the nutrient artery. The vasculature of the bone is very important for fracture healing and vascularized bone grafting. Therefore, information about the location and number of NFs is important for surgical and clinical practice. The clavicle is the most commonly fractured bone. The aim of this study was to analyze the relationship between the location and number of NFs on the clavicle and other clavicle parameters. MATERIALS AND METHODS: This study was performed on 86 dry clavicles of contemporary adult individuals without age and gender records. Some clavicle parameters and NF parameters were measured and the relationship between them was analyzed. Measurements were performed using a digital caliper. RESULTS: Most of the clavicles had a single NF. There was a positive correlation between DFant/DFpost (distance between NF and anterior border/distance between NF and posterior border) and vertical thickness of sternal end (VTs), vertical thickness of thinnest point (VTt) and clavicular thinnest point index (CIt) in all cases (p < 0.05). Sagittal thickness of acromial end (STa), vertical thickness of clavicle (VTc), sagittal thickness of clavicle (STc) and sagittal thickness of thinnest point (STt) were associated with NF counts. The most common localization of NFs was type 2. The NFs were mostly located in the inferior position. CONCLUSIONS: Relationships between the number and morphometric characteristics of NFs and some clavicle parameters were determined. It was suggested that the knowledge of the number and morphometric characteristics of NFs is important for the protection of the nutrient artery in orthopedic surgery applications.