Morphological Correlates Research Articles

Atrial functional and ventricular functional mitral regurgitation: definitions, epidemiology, and prognostic implications

Abstract Background Severe functional mitral regurgitation (fMR) can be divided into two subgroups: fMR of atrial (AfMR) and fMR of ventricular origin (VfMR). Studies on AfMR are scarce and inconsistent, lacking a uniform definition of AfMR. Hence, little is known about its epidemiology, morphological features, associated risk profiles, and prognostic implications. Purpose The objective of this study was to develop and test a uniform definition of fMR based on the morphological correlate and to describe demographic characteristics, detail entity-specific morphological features and to investigate the associated prognostic impact. Methods 13052 patients with severe fMR and those at risk of severe fMR (comprising mild and moderate fMR)were included. Based on the ratio of left atrial volume (LA) to left ventricular end-diastolic volume (LVEDV), those with severe fMR (n=1163) were divided into AfMR and VfMR. The median of this ratio was used for allocation. Therefore, a LA/LVEDV ratio ≤ 0.56 indicated predominantly ventricular eccentric remodelling, whereas a ratio > 0.56 indicated predominantly atrial remodelling. Results AfMR was more frequently observed in female patients and peak age was a decade later, compared to VfMR. AfMR was the predominant fMR subtype in patients with heart failure with preserved (76%) and mildly reduced ejection fraction (61%), but a significant proportion could be observed even in patients with heart failure with reduced ejection fraction (32%). Severe fMR was associated with excess mortality for both entities: VfMR HR 1.31 [95% CI: 1.14-1.50], p<0.001, with a more pronounced impact in patients with AfMR HR 1.68 [95% CI: 1.47-1.91], p<0.001; AfMR vs. VfMR: HR 1.27 [95% CI: 1.06-1.54], p=0.011. The association between fMR and excess mortality persisted even after multivariate adjustment. In both entities, ischaemic heart disease was common and resulted in a significant increase of mortality (VfMR: HR 1.67 [95% CI: 1.40-1.98], p for interaction<0.001; AfMR: HR 2.10 [95% CI: 1.75-2.52], p for interaction=0.006). Conclusion Based on the entity-specific morphological correlate, severe fMR can be classified into AfMR and VfMR. AfMR occurs across the entire HF spectrum, is more frequently observed in elderly and female patients, and exhibits a worse prognosis than VfMR. The presence of ischaemic heart disease is associated with a near doubling of mortality in both subgroups of severe fMR.Prevalence of fMRKaplan-Meier analysis

A retrospective longitudinal study of 52 Finnish patients with X-linked retinoschisis.

To describe clinical characteristics in Finnish patients with X-linked retinoschisis (XLRS) longitudinally with emphasis on retinal morphology and genotype-phenotype correlations. A retrospective cohort study reviewed medical records from patients with genetically confirmed XLRS from the Department of Ophthalmology, Helsinki University Hospital. Best-corrected visual acuity (BCVA), refraction, colour fundus photography, spectral-domain optical coherence tomography and genetic information were collected. Fifty-two males were diagnosed at the median age of 7 years (range 1-57) and followed for a median of 8 years (range, 1-49). Baseline findings included macular retinoschisis in 92(89%), macular atrophy in 25 (24%) and peripheral retinoschisis in 22 (21%) eyes. Vitreous haemorrhage occurred in 10 (10%) eyes, more frequently with peripheral schisis (p < 0.001). Nearly half of the patients, 22 (42%) were classified as visually impaired according to WHO. Median central retinal thickness was similar between initial (355 μm) and latest visits (360 μm) (p = 0.781). Low BCVA was associated with macular atrophy (p < 0.001), ellipsoid zone disruption (p = 0.007) and peripheral retinoschisis (p = 0.006). The three Finnish founder mutations c.214G >A, c.221G >T, and c.325G >C in exon 4 of retinoschisin 1 (RS1) were identified in 40 patients (77%). No associations were found between the genotypes and phenotypes. Three-fourths of the patients carried the Finnish founder mutations in RS1, but we did not detect any genotype-phenotype association. Macular atrophy was associated with the poorest visual acuity. Ocular compilations were associated with peripheral retinoschisis, suggesting that these patients should be followed more frequently.

Morphological correlates of anxiety-related experiences during a ketamine infusion

Objectives: Ketamine exerts rapid antidepressant effects by enhancing neuroplasticity, particularly in the amygdala and hippocampus—regions involved in fear processing and learning. While the role of ketamine’s dissociative effects in its antidepressant response is debated, anxiety experienced during infusion has been negatively correlated with treatment outcomes. Methods: In this single-blind, placebo-controlled study, a subset of 17 healthy volunteers (6 males, 23.12 ± 1.9 years) received intravenously a placebo in the first and 0.5 mg/kg racemic ketamine in the second session. Anxiety-related experiences were assessed by the 5D-ASC score obtained post-infusion, structural magnetic resonance imaging scans were acquired 4 h post-infusion. An anxiety-score was obtained from the 5D-ASC. Relation between post-placebo amygdala volume, hippocampal volume, and its subfields with the anxiety-score were assessed using linear regression models. Results: Results showed a statistically significant negative relation between hippocampal head volume and the anxiety score (β = −0.733, p = 0.006), with trending negative association for each subfield’s head and the score. Conclusion: These findings suggest that anxiety-related experiences during ketamine infusion may be mediated by the hippocampus, with smaller hippocampal volumes leading to more anxiety-related experiences. Thus, hippocampal subfield volumes may be used as a predictor for anxiety-related events during ketamine use and might predict treatment outcome in future approaches.

The mitochondrial function of peripheral blood mononuclear cells in frail older patients

BackgroundFrailty increases the incidence of geriatric syndromes and even the risk of death in old adults. However, the diagnostic criteria for frailty are inconsistent because of complex pathological processes and diverse clinical manifestations. To determine the effective biomarker and recognize frail status early, we investigated the correlation of mitochondrial morphology and function of human peripheral blood mononuclear cells (PBMCs) with frailty status in older adults. MethodsThis Cross-sectional study followed 393 participants (aged 25–100 years, female 31.04 %) from the First Affiliated Hospital of Nanjing Medical University. The frailty status of subjects was assessed by the physical frailty phenotype (PFP) scale. We analyzed mitochondria functions including mitochondria copy number (mtDNAcn), the mRNA expressions of mitochondrial dynamics-related genes mitofusin 1(MFN1), mitofusin 2(MFN2), optic atrophy protein-1(OPA1), fission protein-1(FIS1) and dynamin-related protein 1(DRP1), mitochondrial oxidative respiration and reactive oxygen species(ROS) levels in PBMCs. Mitochondria morphology, size, and number were observed by transmission electron microscopy (TEM). ResultsAfter adjustment for sex and BMI, mtDNAcn, the mRNA expression of FIS1, mitochondrial respiratory function (proton leak, maximum oxygen consumption, and respiratory reserve) and ROS level were significantly correlated with age (P = 0.031, 0.030, 0.042, 0.003, 0.002, 0.022, respectively). After correcting for age, sex, and BMI, mtDNAcn and the mRNA expression of OPA1 were correlated with 4 m gait speed respectively (P = 0.003, 0.028, respectively). Compared with non-frail people, mtDNAcn, the mRNA expression of MFN1, mitochondrial basal respiration, proton leak, maximum oxygen consumption, ATP production and space capacity were significantly decreased in frail older adults (P = 0.013, 0.036, 0.026, 0.024, 0.012, 0.032, 0.020, respectively). ROS levels were significantly increased in the frail group (P = 0.016). Compared with non-frail people, the number, length, and perimeter, area of mitochondria were reduced in frail group under TEM (all P < 0.001). ConclusionMitochondrial dysfunctions (decreased mtDNAcn, impaired mitochondrial morphology, imbalanced mitochondrial dynamic, impaired mitochondrial respiratory function, and increased ROS levels) were significantly correlated with frail status.

The correlation of muscle morphology with variations of 10-repetition maximum bench press strength in resistance-trained subjects

The relationship between muscle mass and strength is complex as it can be influenced by several neurological factors. Variations in the type of training and its mechanisms involved, such as strength- or hypertrophy-oriented training, may influence this relationship in different ways (Carvalho et al., 2022). In addition, the relationship between muscle stiffness and strength remains unclear (Akagi et al., 2016; Mannarino et al., 2019). Thus, this research aimed to investigate the potential correlation between the strength levels, measured by the 10-repetition maximum (10RM), across different ranges of motion (ROM) in the barbell bench press exercise (BP) to the cross-sectional area (CSA) and shear modulus (= indication for stiffness) of the muscles primarily engaged in the exercise. Twenty-one resistance-trained participants (age 27.1 ± 3.4 years) volunteered in this study. The CSA and muscle shear modulus were assessed in a resting position with ultrasound imaging using an ultrasound system (Supersonic Imaging, Aix-en-Provence, France). CSA ultrasound images were captured with panoramic mode for the pectoralis major and the triceps brachii long head. Muscle shear modulus was measured for the pectoralis major, the anterior deltoid, and the triceps brachii long head using shear wave elastography (SWE). Additionally, participants were assessed for their 10RMs of the three types of BP variations, a full ROM and two partial ROMs, the upper half and lower half of the full movement. Data analyses revealed significant correlations between all BP variations and the medial and lateral CSA of the pectoralis major with correlations ranging from r = 0.775 to r = 0.832 (p = 0.001). Significant correlations were also found for the proximal CSA of the triceps brachii long head with the strength values of all tested BP variations with correlations ranging from ρ = 0.492 to ρ = 0.494 (p = 0.028 to p = 0.027). The distal CSA of the triceps brachii did only correlate significantly with the lower ROM BP (r = 0.484, p = 0.026). No significant correlations were found between the SWE of the measured muscles and the bench press variations tested. Additionally, no differences were observed in the correlations between the BP variations. Correlations between 10RM strength levels and the CSA of the pectoralis, and to a lesser extent, the triceps muscle, show the significance of muscle mass for strength in resistance-trained individuals. This finding aligns with a previous training study that examined the hypertrophic effects of bench press exercises on various muscles (Ogasawara et al., 2012). The study revealed that although both the pectoralis and triceps muscles increased in size, the triceps tended to plateau earlier. This suggests that the pectoralis muscle has a greater capacity for muscle volume growth and, consequently, a higher potential for force production. Finally, SWE measurements revealed no significant correlation with BP variations, implying that muscle stiffness may not play as critical a role in 10RM performance as muscle CSA does. This conclusion aligns with other studies that could not find significant changes in muscle stiffness using SWE following resistance training interventions (Dankel &amp; Razzano, 2020). References Akagi, R., Shikiba, T., Tanaka, J., &amp; Takahashi, H. (2016). A six-week resistance training program does not change shear modulus of the triceps brachii. Journal of Applied Biomechanics, 32(4), 373–378. https://doi.org/10.1123/jab.2015-0290 Carvalho, L., Junior, R. M., Barreira, J., Schoenfeld, B. J., Orazem, J., &amp; Barroso, R. (2022). Muscle hypertrophy and strength gains after resistance training with different volume-matched loads: A systematic review and meta-analysis. Applied Physiology, Nutrition, and Metabolism, 47(4), 357–368. https://doi.org/10.1139/apnm-2021-0515 Dankel, S. J., &amp; Razzano, B. M. (2020). The impact of acute and chronic resistance exercise on muscle stiffness: A systematic review and meta-analysis. Journal of Ultrasound, 23(4), 473–480. https://doi.org/10.1007/s40477-020-00486-3 Mannarino, P., Matta, T. T. D., &amp; Oliveira, L. F. D. (2019). An 8-week resistance training protocol is effective in adapting quadriceps but not patellar tendon shear modulus measured by Shear Wave Elastography. PLoS ONE, 14(4), Article e0205782. https://doi.org/10.1371/journal.pone.0205782 Ogasawara, R., Thiebaud, R. S., Loenneke, J. P., Loftin, M., &amp; Abe, T. (2012). Time course for arm and chest muscle thickness changes following bench press training. Interventional Medicine and Applied Science, 4(4), 217–220. https://doi.org/10.1556/imas.4.2012.4.7

Highly efficient Dy3+ activated Sr9Al6O18 nanophosphors for W-LEDs, optical thermometry and deep learning-based intelligent system for personal identification applications

A novel single-phase Dy3+ activated Sr9Al6O18 nanophosphors (NPs) was synthesized using a solution combustion method with urea as the fuel. When phosphors are excited at 350 nm, their photoluminescence (PL) spectra exhibit strong emissions at 484 and 574 nm, which are associated with the 4F9/2→6H15/2 and 4F9/2→6H13/2 transitions. These emissions are attributed to magnetic and electric dipole allowed transitions, correspondingly. It is found that dipole–dipole interactions are the main source of concentration quenching and energy transfer among the activator ions. The prepared NPs show thermal stability up to 480 K having an activation energy (Ea) of 0.2437 eV, as determined by temperature-dependent photoluminescence (TDPL). With a remarkable internal quantum efficiency (IQE) of 66.14 %, the optimized phosphor achieves notable relative sensitivity (Sr) and absolute sensitivity (Sa), estimated to be 2.65 % K−1 and 1.38×10−3 K−1 at 300 K, respectively. Thus, Sr9Al6O18:Dy3+ is a promising material for non-contact optical thermometry applications. Latent fingerprints (LFPs) and latent lip prints (LLPs) can be efficiently produced on a variety of surfaces by using the optimized NPs with the simple powder dusting technique. The prints are made visible under UV light with a 365 nm wavelength. The You Only Look Once version 8 (YOLOv8x) approach analyzes the overall morphological correlations of different minutiae to identify essential minutiae that indicate the identities of people from FPs. Splitting and matching multi-scale fingerprints (FPs) features improves the validity of the authenticating findings. The results show that the recommended method, which improves the entire FP authentication process, offers exceptional accuracy, resilience and speed. The findings provide strong support for the implementation of the optimized NPs in photonic devices, optical thermometers, and advanced forensic applications.

Correlations of temporomandibular joint morphology and position using cone-beam computed tomography and dynamic functional analysis in orthodontic patients: A cross-sectional study.

To correlate temporomandibular joint (TMJ) morphology and position with cone-beam computed tomography (CBCT) images, Joint Vibration Analysis (JVA), and Jaw Tracker (JT) to develop a radiation-free, dynamic method for screening and monitoring the TMJ in orthodontic patients. A total of 236 orthodontic patients without symptoms of TMJ disorders who had undergone CBCT were selected for the JVA and JT tests in this cross-sectional study. TMJ position and morphology were measured using a three-dimensional analysis software. JT measurements involved six opening-closing cycles, and JVA measurements were performed using a metronome to guide the mouth opening-closing movements of the patients. The correlations among the three measuring devices were evaluated. Abnormalities in condylar surface morphology affected the mandibular range of motion. The cut-off value results show that when various measurement groups are within a certain range, abnormalities may be observed in morphology (area under the curve, 0.81; P < 0.001). A 300/< 300 Hz ratio ≥ 0.09 suggested abnormal morphology (P < 0.05). Correlations were observed among the maximum opening velocity, maximum vertical opening position, and joint spaces in the JT measurements. Correlations were also observed between the > 300/< 300 Hz ratio, median frequency, total integral, integral < 300 Hz, and peak frequency with joint spaces in the JVA measurements. JT and JVA may serve as rapid, non-invasive, and radiation-free dynamic diagnostic tools for monitoring and screening TMJ abnormalities before and during orthodontic treatment.

Morphological and Productive Correlations of Cutting Pennisetum Varieties Under Conditions of Peruvian Humid Tropics

Morphological and Productive Correlations of Cutting Pennisetum Varieties Under Conditions of Peruvian Humid Tropics

Correlation of Morphological Appearance of Peritoneal Lesions at Laparotomy and Disease at Pathological Assessment in Patients Undergoing Cytoreductive Surgery for Peritoneal Malignancy: Results of Phase I of the PRECINCT Study in 707 Patients.

The PRECINCT (Pattern of peritoneal dissemination and REsponse to systemic Chemotherapy IN Common and uncommon peritoneal Tumors) is a prospective, multicenter, observational study. This report from phase I of PRECINCT outlines variations in recording the surgical peritoneal cancer index (sPCI) at experienced peritoneal malignancy centers and the incidence of pathologically confirmed disease in morphologically different peritoneal lesions (PL). The sPCI was recorded in a prespecified format that included the morphological appearance of PL. Six prespecified morphological terms were provided. The surgical and pathological findings were compared. From September 2020 to December 2021, 707 patients were enrolled at 10 centers. The morphological details are routinely recorded at two centers, structure bearing the largest nodule, and exact size of the largest tumor deposit in each region at four centers each. The most common morphological terms used were normal peritoneum in 3091 (45.3%), tumor nodules in 2607 (38.2%) and confluent disease in 786 (11.5%) regions. The incidence of pathologically confirmed disease was significantly higher in 'tumor nodules' with a lesion score of 2/3 compared with a lesion score of 1 (63.1% vs. 31.5%; p<0.001). In patients receiving neoadjuvant chemotherapy, the incidence of pathologically confirmed disease did not differ significantly from those undergoing upfront surgery [751 (47.7%) and 532 (51.4%) respectively; p=0.069]. The sPCI was recorded with heterogeneity at different centers. The incidence of pathologically confirmed disease was 49.2% in 'tumor nodules'. Frozen section could be used more liberally for these lesions to aid clinical decisions. A large-scale study involving pictorial depiction of different morphological appearances and correlation with pathological findings is indicated.

Selective disruption of synaptic NMDA receptors of the hippocampal trisynaptic circuit in Aβ pathology

Synaptic dysfunction is an early feature in Alzheimer’s disease (AD) pathogenesis and a major morphological correlate of memory deficits. Given the main synaptic location of N-methyl-D-aspartate receptors (NMDARs), their dysregulation has been implicated in these pathological effects. Here, to detect possible alterations in the expression and synaptic localisation of the GluN1 subunit in the brain of amyloidogenic APP/PS1 mice, we employed histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques. Histoblots showed that GluN1 expression was significantly reduced in the hippocampus in a layer-dependent manner, in the cortex and the caudate putamen of APP/PS1 transgenic mice at 12 months of age but was unaltered at 1 and 6 months. Using quantitative SDS-FRL, we unravelled the molecular organisation of GluN1 in seven excitatory synapse populations at a high spatial resolution in the CA1 and CA3 fields and the DG of the hippocampus in 12-month-old APP/PS1 mice. In the CA1 field, the labelling density for GluN1 in the excitatory synapses established on spines and interneurons, was significantly reduced in APP/PS1 mice compared to age-matched wild-type mice in the stratum lacunosum-moleculare but unaltered in the stratum radiatum. In the CA3 field, synaptic GluN1 was reduced in mossy fibre-CA3 pyramidal cell synapses but unaltered in the A/C-CA3 pyramidal cell synapses. In the DG, the density of GluN1 in granule cell-perforant pathway synapses was reduced in APP/PS1 mice. Altogether, our findings provide evidence of specific alterations of synaptic GluN1 in the trisynaptic circuit of the hippocampus in Aβ pathology. This differential vulnerability in the disruption of NMDARs may be involved in the mechanisms causing abnormal network activity of the hippocampal circuit and cognitive impairment characteristic of APP/PS1 mice.

Morphological correlates of synaptic protein turnover in the mouse brain.

Synaptic proteins need to be replaced regularly, to maintain function and to prevent damage. It is unclear whether this process, known as protein turnover, relates to synaptic morphology. To test this, we relied on nanoscale secondary ion mass spectrometry, to detect newly synthesized synaptic components in the brains of young adult (6 mo old) and aged mice (24 mo old), and on transmission electron microscopy, to reveal synapse morphology. Several parameters correlated to turnover, including pre- and postsynaptic size, the number of synaptic vesicles and the presence of a postsynaptic nascent zone. In aged mice, the turnover of all brain compartments was reduced by ∼20%. The turnover rates of the pre- and postsynapses correlated well in aged mice, suggesting that they are subject to common regulatory mechanisms. This correlation was poorer in young adult mice, in line with their higher synaptic dynamics. We conclude that synapse turnover is reflected by synaptic morphology.

Multi-generational benefits of genetic rescue

Genetic rescue—an increase in population fitness following the introduction of new alleles—has been proven to ameliorate inbreeding depression in small, isolated populations, yet is rarely applied as a conservation tool. A lingering question regarding genetic rescue in wildlife conservation is how long beneficial effects persist in admixed populations. Using data collected over 40 years from 1192 endangered Florida panthers (Puma concolor coryi) across nine generations, we show that the experimental genetic rescue implemented in 1995—via the release of eight female pumas from Texas—alleviated morphological, genetic, and demographic correlates of inbreeding depression, subsequently preventing extirpation of the population. We present unequivocal evidence, for the first time in any terrestrial vertebrate, that genetic and phenotypic benefits of genetic rescue remain in this population after five generations of admixture, which helped increase panther abundance (> fivefold) and genetic effective population size (> 20-fold). Additionally, even with extensive admixture, microsatellite allele frequencies in the population continue to support the distinctness of Florida panthers from other North American puma populations, including Texas. Although threats including habitat loss, human-wildlife conflict, and infectious diseases are challenges to many imperiled populations, our results suggest genetic rescue can serve as an effective, multi-generational tool for conservation of small, isolated populations facing extinction from inbreeding.

AI-driven Discovery of Morphomolecular Signatures in Toxicology.

Early identification of drug toxicity is essential yet challenging in drug development. At the preclinical stage, toxicity is assessed with histopathological examination of tissue sections from animal models to detect morphological lesions. To complement this analysis, toxicogenomics is increasingly employed to understand the mechanism of action of the compound and ultimately identify lesion-specific safety biomarkers for which in vitro assays can be designed. However, existing works that aim to identify morphological correlates of expression changes rely on qualitative or semi-quantitative morphological characterization and remain limited in scale or morphological diversity. Artificial intelligence (AI) offers a promising approach for quantitatively modeling this relationship at an unprecedented scale. Here, we introduce GEESE, an AI model designed to impute morphomolecular signatures in toxicology data. Our model was trained to predict 1,536 gene targets on a cohort of 8,231 hematoxylin and eosin-stained liver sections from Rattus norvegicus across 127 preclinical toxicity studies. The model, evaluated on 2,002 tissue sections from 29 held-out studies, can yield pseudo-spatially resolved gene expression maps, which we correlate with six key drug-induced liver injuries (DILI). From the resulting 25 million lesion-expression pairs, we established quantitative relations between up and downregulated genes and lesions. Validation of these signatures against toxicogenomic databases, pathway enrichment analyses, and human hepatocyte cell lines asserted their relevance. Overall, our study introduces new methods for characterizing toxicity at an unprecedented scale and granularity, paving the way for AI-driven discovery of toxicity biomarkers.

3D U-Net Neural Network Architecture-Assisted LDCT to Acquire Vertebral Morphology Parameters: A Vertebral Morphology Comprehensive Analysis in a Chinese Population.

To evaluate the feasibility of acquiring vertebral height from chest low-dose computed tomography (LDCT) images using an artificial intelligence (AI) system based on 3D U-Net vertebral segmentation technology and the correlation and features of vertebral morphology with sex and age of the Chinese population. Patients who underwent chest LDCT between September 2020 and April 2023 were enrolled. The Altman and Pearson's correlation analyses were used to compare the correlation and consistency between the AI software and manual measurement of vertebral height. The anterior height (Ha), middle height (Hm), posterior height (Hp), and vertebral height ratios (VHRs) (Ha/Hp and Hm/Hp) were measured from T1 to L2 using an AI system. The VHR is the ratio of Ha to Hp or the ratio of Hm to Hp of the vertebrae, which can reflect the shape of the anterior wedge and biconcave vertebrae. Changes in these parameters, particularly the VHR, were analysed at different vertebral levels in different age and sex groups. The results of the AI methods were highly consistent and correlated with manual measurements. The Pearson's correlation coefficients were 0.855, 0.919, and 0.846, respectively. The trend of VHRs showed troughs at T7 and T11 and a peak at T9; however, Hm/Hp showed slight fluctuations. Regarding the VHR, significant sex differences were found at L1 and L2 in all age bands. This innovative study focuses on vertebral morphology for opportunistic analysis in the mainland Chinese population and the distribution tendency of vertebral morphology with ageing using a chest LDCT aided by an AI system based on 3D U-Net vertebral segmentation technology. The AI system demonstrates the potential to automatically perform opportunistic vertebral morphology analyses using LDCT scans obtained during lung cancer screening. We advocate the use of age-, sex-, and vertebral level-specific criteria for the morphometric evaluation of vertebral osteoporotic fractures for a more accurate diagnosis of vertebral fractures and spinal pathologies.

Biomechanical and biochemical changes in murine skin during development and aging

Aging leads to biochemical and biomechanical changes in skin, with biological and functional consequences. Despite extensive literature on skin aging, there is a lack of studies which investigate the maturation of the tissue and connect the microscopic changes in the skin to its macroscopic biomechanical behavior as it evolves over time. The present work addresses this knowledge gap using multiscale characterization of skin in a murine model considering newborn, adult and aged mice. Monotonic uniaxial loading, tension relaxation with change of bath, and loading to failure tests were performed on murine skin samples from different age groups, complemented by inflation experiments and atomic force microscopy indentation measurements. In parallel, skin samples were characterized using histological and biochemical techniques to assess tissue morphology, collagen organization, as well as collagen content and cross-linking. We show that 1-week-old skin differs across nearly all measured parameters from adult skin, showing reduced strain stiffening and tensile strength, a thinner dermis, lower collagen content and altered crosslinking patterns. Surprisingly, adult and aged skin were similar across most biomechanical parameters in the physiologic loading range, while aged skin had lower tensile strength and lower stiffening behavior at large force values. This correlates with altered collagen content and cross-links. Based on a computational model, differences in mechanocoupled stimuli in the skin of the different age groups were calculated, pointing to a potential biological significance of the age-induced biomechanical changes in regulating the local biophysical environment of dermal cells. Statement of significanceSkin microstructure and the emerging mechanical properties change with age, leading to biological, functional and health-related consequences. Despite extensive literature on skin aging, only very limited quantitative data are available on microstructural changes and the corresponding macroscopic biomechanical behavior as they evolve over time. This work provides a wide-range multiscale mechanical characterization of skin of newborn, adult and aged mice, and quantifies microstructural correlations in tissue morphology, collagen content, organization and cross-linking. Remarkably, aged skin retained normal hydration and normal biomechanical function in the physiological loading range but showed significantly reduced properties at super-physiological loading. Our data show that age-related microstructural differences have a profound effect not only on tissue-level properties but also on the cell-level biophysical environment.

Clinical and morphological correlations in patients with lupus nephritis: a retrospective study

To analyze associations between clinical and morphological features of kidney involvement in patients with systemic lupus erythematosus. In the retrospective cohort study, we enrolled adult (≥18 years) patients with morphologically proven lupus nephritis (LN) stratified according to the ISN/RPS classification. Systemic lupus erythematosus was classified in accordance with ACR/EULAR classification criteria (2019). Antiphospholipid syndrome was diagnosed according to the 2006 classification criteria. Disease activity was assessed with SELENA-SLEDAI score. We enrolled 62 patients with LN, among them 84% were females. Median age of SLE onset was 23 (16,3; 30,8) years. In all cases kidney involvement was accompanied by extrarenal manifestations, among which joint (82%), skin (57%) and hematological involvement (68%) was the most common. LN class I was proven in one patient, class II - in three patients, class III - in 24, including III+V in seven, class IV - in 18, including IV+V in two, class V - in 13, class VI - in three patients. APS nephropathy was diagnosed in 4 (6.5%) of patients with LN. The most common clinical manifestation was proteinuria (85%), however its prevalence, level and the frequency of nephrotic syndrome showed no significant differences between the LN classes. LN III/IV±V was characterized by the highest levels of serum creatinine (and the lowest eGFR) at the time of biopsy. LN is characterized by the high heterogeneity of the clinical and morphological manifestations, which makes LN class prediction impossible without kidney biopsy.

Assessment and Correlation of Dentofacial Morphology and Lateral Cephalometric Parameters with Smile Characteristics in Lateral and Oblique View: Short Study

Aim: This study evaluated and established correlations between the dentofacial morphology of Angle’s Cl II and Cl I malocclusions, lateral cephalometric parameters, and smile characteristics assessed through lateral and oblique smile views. Methods: A sample of 20 random patients (&gt;15 years, with prior orthodontic treatment) were selected for this study according to their arrival at the department. The selected individuals were grouped according to Angle’s classification of malocclusion, i.e., Angle’s Cl I and Angle’s Cl II malocclusion. Pretreatment records were taken for the study, including lateral cephalogram and extra-oral smile photographs (one lateral smiling and one oblique smiling). In the lateral cephalogram, skeletal, dental, and facial parameters were recorded, and in lateral and oblique smile views, lateral smile index, commissure angle, and incisal displays were recorded. Results: The results showed no significant difference in most cephalometric parameters except for UFH/LFH, which was higher in Angle’s Cl II. Additionally, smile analysis revealed significant differences between the two groups. In addition, significant differences were found in the incisal display, which was greater in Angle’s Cl II malocclusion. Conclusion: Smile characteristics differ between Angle Cl I and Cl II malocclusions. There was a significant difference in lateral and oblique smile parameters when Angle’s malocclusions classified as Cl I and Cl II were evaluated. Lateral and oblique smile index decreased from Cl I to Cl II malocclusion, whereas lateral and oblique smile commissure angle and lateral smile incisor display increased in Cl II malocclusion.

Correlations of pathomorphological parameters between lesions at the invasive front and lymph node metastases in colorectal cancer: a retrospective clinical study

BackgroundLymph node (LN) metastasis is one of the most important indicators to evaluate stage, choose treatment strategy, and predict outcome of colorectal cancer (CRC). The morphological correlation between primary tumors and LN metastases can help predict the incidence of LN metastasis in CRC more accurately and assist with more individualized risk-stratification management decisions.MethodsA retrospective study was devised with paired tissue specimens from the invasive front of primary tumors and LN metastases in 426 patients after a radial surgery for CRC. According to the presence (N +) or absence (N-) of regional LN metastasis and the number of LN metastases (pN1a/1b/1c/2a/2b), comparisons were performed regarding tumor budding (TB) and poorly-differentiated clusters (PDC). In addition, their correlation with the incidence of LN metastasis and the extent were explored.ResultsThe TB and PDC in the invasive front of primary tumors presented significant correlations with the incidence of LN metastasis and the number of LN metastases in CRC (P < 0.001). TB2/3 led to a risk of LN metastasis 6.68-fold higher than TB1, while PDC2/3 resulted in a risk of LN metastasis 8.46-fold higher than PDC1. Additionally, the risk of developing 4 or more LN metastases was 3.08-fold and 2.86-fold higher upon TB2/3 and PDC2/3 than that with TB1 and PDC1, respectively. Moderate positive correlations were found between the invasive front of primary tumors and LN metastases in terms of TB and PDC, respectively.ConclusionsTB and PDC, at the invasive tumor front are important morphological markers to evaluate LN metastasis in CRC, and they can be employed as reference indicators to assess or predict the potential of LN metastasis in CRC in clinical practice.

Happy people are always similar: The evidence from brain morphological and functional inter-subject correlations

A fundamental question in the study of happiness is whether there is neural evidence to support a well-known hypothesis that happy people are always similar while unfortunate people have their own misfortunes. To investigate this, we employed several happiness-related questionnaires to identify potential components of happiness, and further investigated and confirmed their associations with personality, mood, aggressive behaviors, and amygdala reactivity to fearful faces within a substantial sample size of college students (n = 570). Additionally, we examined the functional and morphological similarities and differences among happy individuals using the inter-subject representational similarity analysis (IS-RSA). IS-RSA emphasizes the geometric properties in a high-dimensional space constructed by brain or behavioral patterns and focuses on individual subjects. Our behavioral findings unveiled two factors of happiness: individual and social, both of which mediated the effect of personality traits on individual aggression. Subsequently, mood mediated the impact of happiness on aggressive behaviors across two subgroup splits. Functional imaging data revealed that individuals with higher levels of happiness exhibited reduced amygdala reactivity to fearful faces, as evidenced by a conventional face-matching task (n = 104). Moreover, IS-RSA demonstrated that these participants manifested similar neural activation patterns when processing fearful faces within the visual pathway, but not within the emotional network (e.g., amygdala). Morphological observations (n = 425) indicated that individuals with similar high happiness levels exhibited comparable gray matter volume patterns within several networks, including the default mode network, fronto-parietal network, visual network, and attention network. Collectively, these findings offer early neural evidence supporting the proposition that happy individuals may share common neural characteristics.

Correlations of Corneal Endothelial Morphology and Corneal Thickness With Anterior Segment Parameters in Healthy Individuals.

The purpose of this study was to investigate the associations between central corneal endothelial cell density (ECD), endothelial morphology, and corneal thickness (central corneal thickness) with the anterior chamber depth, corneal volume (CV), white-to-white (WTW) distance, mean anterior chamber angle (CAmean), and gender in healthy individuals. This observational study included 136 healthy volunteers. The ECD, coefficient of variation of cell area, and hexagonal cell appearance ratio (%Hex) were measured by means of specular microscopy. The central corneal thickness, anterior chamber depth, CV, WTW distance, and the angle width of 12 points were taken by the Pentacam HR Scheimpflug anterior segment imaging. The arithmetical mean of the 12 points was considered as the CAmean. We used mixed effect linear regression model for the statistical analysis of the data. ECD was positively correlated with CV ( P = 0.028), while after adjusting for age, it was negatively correlated with age ( P < 0.001). Coefficient of variation of cell area was positively correlated with CAmean ( P = 0.036), while after adjusting for age, it was positively correlated with age ( P < 0.001) and CAmean ( P = 0.005). Hex was negatively correlated with WTW ( P = 0.023) and CAmean ( P = 0.025), and after adjusting for age, this correlation remained the same ( P = 0.029 when correlated with WTW and P = 0.035 with CAmean). There were significant changes in the morphology of the corneal endothelial cells in eyes with wider anterior chamber angle. Greater pleomorphism and polymegethism of the corneal endothelium was observed in healthy patients with wider CAmean. Deepening of the anterior chamber as myopia progresses could render the corneal endothelium more fragile and susceptible to mechanical stress, which is an area worthy of further study.