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-β, 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.

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.
OBJECTIVE:  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.
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.
CONCLUSIONS: 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.

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.

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.

Brain atrophy and cortical thinning are typically observed in people with Alzheimer\'s disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle-aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non-carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross-sectional study, we investigated textural properties of T1-weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT-Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel-based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non-carriers. Textural maps were generated and were subsequently harmonised using voxel-wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non-carriers at midlife and have established associations of textural features with ageing and sex.

The exploration of heterocyclic compounds and their fused analogs, featuring key pharmacophore fragments like pyridine, thiophene, pyrimidine, and triazine rings, is pivotal in medicinal chemistry. These compounds possess a wide array of biological activities, making them an intriguing area of study. The quest for new neurotropic drugs among derivatives of these heterocycles with pharmacophore groups remains a significant research challenge. The aim of this research work was to develop a synthesis method for new heterocyclic compounds, evaluate their neurotropic and neuroprotective activities, study histological changes, and perform docking analysis. Classical organic synthesis methods were used in the creation of novel heterocyclic systems containing pharmacophore rings. To evaluate the neurotropic activity of these synthesized compounds, a range of biological assays were employed. Docking analysis was conducted using various software packages and methodologies. The neuroprotective activity of compound 13 was tested in seizures with and without pentylenetetrazole (PTZ) administration. Histopathological examinations were performed in different experimental groups in the hippocampus and the entorhinal cortex. As a result of chemical reactions, 16 new, tetra- and pentacyclic heterocyclic compounds were obtained. The biologically studied compounds exhibited protection against PTZ seizures as well as some psychotropic effects. The biological assays evidenced that 13 of the 16 studied compounds showed a high anticonvulsant activity by antagonism with PTZ. The toxicity of the compounds was low. According to the results of the study of psychotropic activity, it was found that the selected compounds have a sedative effect, except compound 13, which exhibited activating behavior and antianxiety effects (especially compound 13). The studied compounds exhibited antidepressant effects, especially compound 13, which is similar to diazepam. Histopathological examination showed that compound 13 produced moderate changes in the brain and exhibited neuroprotective effects in the entorhinal cortex against PTZ-induced damage, reducing gliosis and neuronal loss. Docking studies revealed that out of 16 compounds, 3 compounds bound to the γ-aminobutyric acid type A (GABAA) receptor. Thus, the selected compounds demonstrated anticonvulsant, sedative, and activating behavior, and at the same time exhibited antianxiety and antidepressant effects. Compound 13 bound to the GABAA receptor and exhibited antianxiety, antidepressant, and neuroprotective effects in the entorhinal cortex against PTZ-induced changes.

Background: The Coronal Plane Alignment of the Knee (CPAK) classification system has been developed as a comprehensive framework delineating nine coronal plane phenotypes, based on arithmetic hip-knee angle (aHKA) and joint line obliquity (JLO). Our study aimed to assess the prevalence of knee phenotypes in the Romanian population using the CPAK classification, encompassing both osteoarthritic and healthy cohorts. Methods: We conducted an observational cross-sectional study, analyzing data from 500 knees with osteoarthritis and 500 healthy knees that met the inclusion criteria. Demographic data were collected, and radiological parameters including lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), aHKA, and JLO were measured. Knee phenotypes were categorized using the CPAK classification. Results: In the osteoarthritic cohort, the most prevalent CPAK phenotype was type I (42.4%), characterized by varus alignment and an apex distal joint. Conversely, in the healthy population, CPAK type II, indicating neutral alignment and an apex distal joint, was the most prevalent phenotype (39.0%). CPAK types VII, VIII, and IX were rare. Conclusions: Our findings demonstrate similarities in knee phenotypes compared to other populations, with some minor differences and particularities. The CPAK classification proves to be a valuable tool in assessing knee tyalignment.

This study aimed to reveal the morphological characteristics of pure Holstein and Simmental skulls and to obtain reference values for morphometric analysis. Moreover, 54 skulls from 12- to 14-month-old male Holstein (n = 25) and Simmental (n = 29) cattle were collected from Turkey\'s Southeastern Anatolia Region between 2023 and 2024. Linear measurements indicated that Holsteins had longer skulls compared to Simmentals. Holsteins exhibited significantly higher values for the greatest length of nasals and the shortest skull length. The facial breadth was wider in Holsteins and statistically distinctive between the breeds. Holsteins had a more oval orbital bony roof, while Simmentals exhibited a wider orbital structure. The orbital index was higher in Holsteins, distinguishing between the two breeds. It was observed that Simmental cattle had a wider occipital region. This difference is likely due to the larger lateral appearance of the Simmental skull, which has more body weight and provides a larger surface area for muscle attachment. These differences not only aid in breed identification but also offer insights into the functional adaptations of each breed. Future research should explore the genetic and environmental factors contributing to these morphological traits, further enriching our knowledge of cattle morphology and its implications for breeding and conservation efforts.

Background The human placenta is a remarkable organ that develops during pregnancy and is crucial in supporting fetal growth and development. The placenta supplies oxygen and nutrients to the fetus and removes waste products from the fetal bloodstream. It also produces hormones that support pregnancy, such as human chorionic gonadotropin, progesterone, and estrogen. Placental insufficiency occurs when the placenta cannot deliver adequate nutrients and oxygen to the fetus. This can result in intrauterine fetal death (IUFD), stillbirth, intrauterine growth restriction, low birth weight, and premature birth. It can also be associated with developmental delays or long-term health issues for the baby. This study aimed to assess the morphologic, morphometric, and histologic changes in the placenta associated with IUFD and compare it with the placenta of live births. Methodology This study was conducted at the Department of Anatomy in collaboration with the Department of Obstetrics and Gynaecology, Integral Institute of Medical Sciences and Research and King George\'s Medical University Lucknow, where 60 placentas were studied. Placentas were further categorized into the following two groups: Group A, the study group in which placentas from IUFD were taken (n = 30), and Group B, the control group where placentas from live births were taken (n = 30). Morphological and morphometric features of both groups were recorded and compared. Histological features of placentas from IUFD (Group A) were examined after hematoxylin and eosin staining. Results A total of 60 placentas were observed (Group A and Group B). In Group A (IUFD) and Group B (control group), most pregnancies were multigravidas. Round-shaped placentas were the most common type in both groups (Group A = 46.67%, Group B = 66.67%). The average thickness of placentas from Group A (IUFD) cases was significantly reduced (mean thickness = 1.17 ± 0.07 cm) compared to controls in Group B (mean thickness = 2.04 ± 0.93 cm). The p-value obtained was significant at 0.0001. There was a notable reduction in the average placental diameter in Group A (mean diameter = 241.73 ± 65.54 cm) compared to Group B (mean diameter = 263.72 ± 162.67 cm). The p-value obtained was not significant at 0.49. On histopathological examination of the placentas of Group A (IUFD), perivillous fibrin deposition and high-grade calcification were seen in a significantly high number of placentas (70% and 60%, respectively). Conclusions The knowledge of the placenta\'s morphologic, morphometric, and histologic changes can be utilized to establish the cause of fetal death. In instances of fetal growth limitation and fetal demise that are clinically inexplicable, they can also explain the causes.

UNASSIGNED: The goal was to measure the piriform sinus, epiglottis, and thyroid cartilage in our sample population.
UNASSIGNED: This study included 22 adult embalmed cadavers available in the Department of Anatomy. Dimensions were measured using a digital Vernier caliper.
UNASSIGNED: The mean height of the thyroid laminae was 27 ± 1.4 mm at the right side and 25.5 ± 1.4 mm at the left side. Mean width of the thyroid lamina was 27.1 ± 1.3 mm at the right side and 27.4 ± 0.9 mm at the left side. The mean thickness of thyroid cartilage was found to be 4.4 ± 0.4 mm and 3.9 ± 0.5 mm over the right and left sides. The mean length, width and thickness of the epiglottis were 29.1 ± 0.5 mm, 22.2 ± 0.6 mm and 2.6 ± 0.3 mm correspondingly. The height, width and thickness of the right piriform sinus were 25 ± 0.5 mm, 14.2 ± 0.5 mm and 12.6 ± 0.5 mm, the same parameters were 25.3 ± 1.3 mm, 15.1 ± 0.7 mm and 13.3 ± 0.4 mm for the left side.
UNASSIGNED: The height and thickness of the thyroid cartilage were greater on the right side than on the left side (p<0.05). It was statistically observed that the width and thickness were greater on the left side than on the right side (p < 0.05). The data about the height, width and thickness of the thyroid cartilage, epiglottis and piriform sinus are essential during the laryngeal and other neck surgeries. They guide in the preoperative positioning, predicting the difficulty of intraoperative exposure and retractor pulling.