Patchy Pattern Research Articles

COVID-19-Induced Changes in the Fibrin Network of Pulmonary and Renal Microthrombi

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes coagulation disorders that affect highly vascularized organs, such as the lungs and kidneys. Objective The objective of this study was to report the histopathological findings of variations in the fibrin pattern of pulmonary and renal microthrombi in patients who died from SARS-CoV-2 infection. Methods Minimally invasive autopsies were performed on 40 patients to collect lung (n=40) and kidney (n=16) tissue samples. Histochemical and immunohistochemical staining techniques were used for histopathological analyses. Premortem laboratory data were obtained from the patients' electronic medical records. Results The lung tissue showed a patchy pattern, characterized by areas of both minimal and severe damage. The most significant histopathological finding was the detection of thrombi with fibrin structures organized into discrete star-shaped units, which were more frequently observed in areas with severe lung injury than in those with minimal lung injury (p = 0.012). Star-shaped fibrin structures were also observed in the renal glomerular capillaries. Immunohistochemical staining revealed the presence of platelets and the procoagulant proteins von Willebrand factor (VWF) and Factor VIII within the star-shaped fibrin thrombi. Patients with star-shaped fibrin thrombi had higher levels of the systemic inflammatory indicators C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR). Conclusion Our observations suggest that the inflammatory microenvironment resulting from SARS-CoV-2 infection may contribute to the formation of star-shaped fibrin units in the pulmonary and renal microthrombi.

Granulomatous cheilitis: a rare case report

Granulomatous cheilitis is a rare granulomatous disorder characterized by a recurrent firm swelling of one or both lips. This is called the cheilitis granulomatosa of Miescher (CGM) when it occurs in isolation. It is called Melkersson-Rosenthal syndrome (MRS) if the classical triad of recurrent or persistent orofacial edema, plicated or fissured tongue (lingua plicata), and relapsing peripheral facial nerve paralysis is present. A 40-year-old female patient came to the Dermatology Department with persistent painless swelling of both lips and perioral area for the last one year. On histopathological examination there was a nodular tuberculoid granulomatous inflammation in patchy pattern present throughout the submucosa. The granuloma consists of lymphocytes, histiocytes and occasional plasma cells. AFB stain and PAS stain were negative. Diagnosis of granulomatous cheilitis was made and patient was put on tab clofazimine and intralesional corticosteroids. The case is being reported due to its rarity and the role of dermatopathologist to make a diagnosis.

Potential biodiversity maps of Geadephaga (Coleoptera) from subantarctic forests: Relating diversity patterns and conservation hotspots with forest integrity

Abstract Potential biodiversity maps (PBMs) allow the identification of areas with different potential for conservation, to support political decisions about the management and protection of biodiversity. As these maps are seldom constructed for inconspicuous species, we proposed to develop PBMs for species belonging to the Geadephaga (Coleoptera), which is a group of beetles that contributes as predators for pest suppression and other ecosystem services in forest ecosystems. Given that human activities are reducing forest integrity, we consider that it is crucial to recognize how diversity patterns of Geadephaga are related to degraded forests. We developed these maps for the Geadephaga associated with subantarctic forests considering diversity measures of species richness, specificity, and rarity to establish spatial relationships between each diversity measure and different levels of forest integrity, and to identify potential hotspots and suggest conservation priorities. Results showed a latitudinal pattern of decrease in scores on richness and specificity from north to south, but a patchy pattern of species rarity across the region. Outcomes also show that areas with high scores of diversity measures are overlapped with degraded forest, and that hotspots have a low spatial overlap between them. In this work, we provide for the first time regional PBMs at a relatively high spatial resolution of three different diversity measures for Geadephaga that inhabit subantarctic forest. These maps constitute tools that allow not only to recognize potential diversity patterns of these insects, but also to offer valuable information to be used in conservation decision‐making.

Morphogenic Modeling of Corrosion Reveals Complex Effects of Intermetallic Particles.

Corrosion processes are often discussed as stochastic events. Here, it is shown that some of these seemingly random processes are not driven by nanoscopic fluctuations but rather by the spatial distribution of micrometer-scale heterogeneities that trigger fast reactions associated with corrosion. Using a novel excitable reaction-diffusion model, corrosion waves traveling over the metal surface and the associated material loss are described. This resulting nonuniform corrosion penetration, seen as a height loss in modeling, exposes buried intermetallic particles, which depending on the local electrochemical state of the surface trigger or block new waves. Informed by quantitative experimental data for the Mg-Al-Zn alloy AZ31B, wave speeds, wave widths, and average material loss are accurately captured. Morphogenic mitigation based on wave-breaking microparticles is also simulated. While AZ31B corrosion is identified as a process driven by rare-wave events, this study predicts several other corrosion regimes that proceed via spots or patchy patterns, opening the door for new protection, design, and prediction strategies.

Characterization of brain transduction capability of a BBB-penetrant AAV vector in mice, rats and macaques reveals differences in expression profiles

Different screening methods are being developed to generate adeno-associated viral vectors (AAV) with the ability to bypass the blood-brain barrier (BBB) upon intravenous administration. Recently, the AAV9P31 stood out as the most efficient version among a library of peptide-displaying capsids selected in C57BL/6 mice using RNA-driven biopanning. In this work we have characterized in detail its biodistribution in different mouse strains (C57BL/6 and Balb/c), as well as in Sprague Dawley rats and non-human primates (Macaca fascicularis). Using GFP and NanoLuc reporter genes, we confirmed homogeneous infection and transgene expression across the CNS of mice injected intravenously with AAV9P31. A more restricted pattern was observed upon either intracerebroventricular or intraparenchymal injection. Following intravenous delivery, region- and cell-specific differential patterns of transduction were observed in the mouse brain, including a preferential transduction of astrocytes and neurons in the cerebral cortex and striatum, whereas neurons were the only transduced cell type in subcortical locations across the hippocampus, thalamus, hypothalamus, mesencephalon, brainstem and cerebellum. Furthermore, transduced microglial cells were never found in any CNS location. Peripheral organs transduced upon intravenous administration included lung, liver, peritoneum, heart and skeletal muscle. However, a comparable performance of AAV9P31 to bypass the BBB in rats and macaques was not observed, although a more limited neuronal transduction was found in the brainstem of rats upon intravenous delivery. Finally, intracerebroventricular delivery in macaques resulted in neuronal transduction in cortical, subcortical structures and cerebellum following a patchy pattern. In conclusion, the widespread CNS transduction obtained in mice upon intravenous delivery of AAV9P31 represents a powerful tool for modeling a wide variety of neurological disorders as well as an appealing choice for the evaluation of gene therapy-based therapeutics.

P-wave velocity evolution and interpretation of seepage mechanisms during CO2 hydrate formation in quartz sands: Perspective of hydrate pore habits

The hydrate-based CO2 storage (HBCS) is a promising technology for controlling CO2 emissions. A comprehensive understanding of the hydrate pore habits and seepage mechanism of hydrate-bearing sediments (HBSs) could provide a theoretical basis for HBCS. In the study, the hydrate occurrence characteristics, water migration and P-wave velocity response during hydrate formation in quartz sands are investigated. In addition, a new theoretical equation that relates P-wave velocity to permeability is presented. The digital core of porous media containing hydrate is also established, and the seepage characteristics during hydrate formation are revealed by numerical simulation. The results show that hydrates are preferentially generated in large pores and initially appear in a non-cementing pore-filling pattern, while an annular flow path for water is formed in quartz sands during hydrate formation. The hydrate morphology is changed from a pore-filling pattern to a patchy pattern at a critical hydrate saturation of around 3–7% for quartz sands with various particle diameters. The formation sites and spatial heterogeneity of hydrates can be depicted by the evolution pattern of streamlines. The results of the experiments indicate that the new semiempirical model is effective for estimating the permeability from the P-wave velocity of HBSs. These findings offer significant theoretical and practical insights for HBCS in porous media.

Adhesion of Candida albicanson PTFE membranes used in guided bone regeneration.

Guided bone regeneration (GBR) is a core procedure used to regenerate bone defects. The aim of the study was to investigate the adherence of Candida albicans on six commercially available polytetrafluoroethylene (PTFE) membranes used in GBR procedures and the subsequent clinical consequences. Six commercially available PTFE membranes were tested. Two of the membranes had a textured surface and the other four a plane, nontextured one. C. albicans (ATCC 24433) was cultured for 24 h, and its cell surface hydrophobicity was assessed using a modified method. C. albicans adhesion to membrane discs was studied by scanning electron microscopy (SEM) and real-timepolymerase chain reaction (PCR). C. albicans was found to be hydrophobic (77.25%). SEM analysis showed that C. albicans adherence to all membranes examined was characterized by patchy, scattered, and small clustered patterns except for one nontextured membrane with a most rough surface in which a thick biofilm was observed. Real-timePCR quantification revealed significantly greater adhesion of C. albicans cells to PTFE membranes than the control membrane (p ≤ .001) with the membranes having a textured surface exhibiting the highestcount of 2680 × 104 cells/ml compared to the count of 707 × 104 cells/mL on those with a nontextured one (p ≤ .001). One membrane with nontextured surface, but with most rough surface was found to exhibit the highest count of 3010 × 104 cells/ml (p ≤ .05). The results of this study indicate that C. albicans adhesion on membranes' surfaces depends on the degree of surface roughness and/or on the presence of a texture. Textured PTFE membranes and/or membranes high roughness showed significantly more adhered C. albicans cells. These findings can impact the surgeon's choice of GBR membrane and postoperative maintenance.

Dissimilarity of megabenthic community structure between deep-water seamounts with cobalt-rich crusts: Case study in the northwestern Pacific Ocean

As anthropogenic disturbance on deep-sea seamount ecosystems grows, there is an urgent need for a better understanding of the biodiversity and community structure in benthic ecosystems, which can vary at local and regional scales. A survey of the benthic megafauna on two adjacent deep-water seamounts in the northwestern Pacific Ocean was conducted, which are covered by cobalt-rich crusts, to assess the biodiversity patterns and dissimilarity of assemblage composition. Based on a multidisciplinary dataset generated from video recordings, multibeam bathymetry data, and near-bottom currents, environmental and spatial factors impacting the megabenthic communities were explored. Results showed that these two deep-water seamounts were dominated by hexactinellids, crinoids, and octocorals. The seamounts were able to support diverse and moderately abundant megafauna, with a total of 6436 individuals classified into 94 morphospecies. The survey covered a distance of 52.2 km across a depth range of 1421–3335 m, revealing multiple distinct megabenthic assemblages. The megabenthic communities of the two deep-water seamounts, with comparable environmental conditions, exhibited similarities in overall density, richness, and faunal lists, while dissimilarities in the relative abundance of taxa and assemblage composition. No gradual depth-related change in terms of abundance, richness, or species turnover was observed across the two seamounts, despite the statistical significance of depth in structuring the overall communities. The spatial distribution of megabenthic communities displayed a discontinuous and patchy pattern throughout the two deep-water seamounts. This patchiness was driven by the interactive effects of multiple environmental factors. Near-bottom currents and microhabitat features were the primary drivers influencing their dissimilarities in megabenthic community structure. This case study on the megabenthic community structure of two adjacent seamounts with cobalt-rich crusts can serve as an environmental baseline, providing a reference status for the conservation and management of seamount ecosystems, particularly valuable for areas being considered for deep-sea mining.

Confined placental mosaicism: Distribution of chromosomally abnormal cells over the term placenta

ObjectiveNon-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta. MethodsFour chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array. ResultsThe chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy. DiscussionCytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS.

Short-Term l-arginine Treatment Mitigates Early Damage of Dermal Collagen Induced by Diabetes.

Changes in the structural properties of the skin due to collagen alterations are an important factor in diabetic skin complications. Using a combination of photonic methods as an optic diagnostic tool, we investigated the structural alteration in rat dermal collagen I in diabetes, and after short-term l-arginine treatment. The multiplex approach shows that in the early phase of diabetes, collagen fibers are partially damaged, resulting in the heterogeneity of fibers, e.g., "patchy patterns" of highly ordered/disordered fibers, while l-arginine treatment counteracts to some extent the conformational changes in collagen-induced by diabetes and mitigates the damage. Raman spectroscopy shows intense collagen conformational changes via amides I and II in diabetes, suggesting that diabetes-induced structural changes in collagen originate predominantly from individual collagen molecules rather than supramolecular structures. There is a clear increase in the amounts of newly synthesized proline and hydroxyproline after treatment with l-arginine, reflecting the changed collagen content. This suggests that it might be useful for treating and stopping collagen damage early on in diabetic skin. Our results demonstrate that l-arginine attenuates the early collagen I alteration caused by diabetes and that it could be used to treat and prevent collagen damage in diabetic skin at a very early stage.

Patchy FDG uptake on FDG PET/CT in a patient with vasculitic neuropathy in restricted lower‐limb vasculitis

AbstractA 54‐year‐old man with diabetes mellitus presented with fever, pain, muscle weakness, and sensory disturbances in the lower limbs. His serum C‐reactive protein level was markedly increased; However, no autoantibodies, other than anti‐glutamic acid decarboxylase antibody, were detected. Nerve conduction studies revealed axonal polyneuropathy. 18F‐fluorodeoxyglucose positron emission tomography/computed tomography revealed patchy uptake patterns specific to restricted lower‐limb vasculitis. The muscle and nerve biopsy specimens suggested vasculitic neuropathy. Treatment with oral prednisolone and cyclophosphamide pulse therapy markedly improved his lower‐limb weakness and paresthesia. Clinicians should consider the involvement of vasculitic neuropathy, as well as myopathy, in patients with restricted lower‐limb vasculitis.

Cardiac magnetic resonance imaging in heart transplant recipients with biopsy-negative graft dysfunction.

Graft dysfunction (GD) after heart transplantation (HTx) can develop without evidence of cell- or antibody-mediated rejection. Cardiac magnetic resonance imaging (CMR) has an evolving role in detecting rejection; however, its role in biopsy-negative GD has not been described. This study examines CMR findings, evaluates outcomes based on CMR results, and seeks to identify the possibility of rejection missed through endomyocardial biopsy by using CMR in HTx recipients with biopsy-negative GD. HTx recipients with GD [defined as a decrease in left ventricular ejection fraction (LVEF) by >5% and LVEF<50%] in the absence of rejection by biopsy or allograft vasculopathy and who underwent CMR were included in the study. The primary outcome was a composite of all-cause mortality, re-transplantation, or persistent LVEF<50%. Overall, 34 HTx recipients developed biopsy-negative GD and underwent CMR. Left ventricular late gadolinium enhancement (LGE) on CMR was observed in 16 patients with two distinct patterns: diffuse epicardial (n=13) and patchy (n=3) patterns. Patients with LGE developed GD later after HTx [4 (1.4-6.8) vs. 0.8 (0.3-1.2) years, P<0.001], were more often symptomatic (88% vs. 56%, P=0.06), and had greater haemodynamic derangement (pulmonary capillary wedge pressure: 19±7 vs. 13±3mmHg, P=0.002) as compared with those without LGE. No significant difference was observed in the primary composite outcome between patients with LGE and those without LGE (50% vs. 38% of patients with events, P=0.515). During a median follow-up of 3.8years, mean LVEF improved similarly in the LGE-negative (37-55%) and LGE-positive groups (32-55%) (P=0.16). Biopsy-negative GD occurs with and without LGE when assessed by CMR, indicative of possible rejection/inflammation occurring only in a subset of patients. Irrespective of LGE, LVEF improvement occurs in most GD patients, suggesting that other neurohormonal or immunomodulatory mechanisms may also contribute to GD development.

The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.

We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p < 0.001 vs. CF controls). Selenium deficiency (Se < 60 µg/L) was associated with more severe LV dysfunction, higher prevalence of CF CMP, higher NTproBNP levels, and more severe pulmonary and digestive involvement. 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients.

DOP38 A rare KRT17+ population emerges from the epithelium in the inflamed intestinal mucosa of patients with Ulcerative Colitis

Abstract Background KRT17 is an epithelial "alarmin" that contributes to the early host innate immune response to insults. We previously found that KRT17 transcription, not detectable in the healthy colon, is up-regulated in the intestinal mucosa of patients with active ulcerative colitis (UC). Here, we aimed to characterize the epithelial cells expressing KRT17 in UC mucosa and explore the contribution of the intestinal environment in promoting the emergence of this cell population. Methods We conducted single-cell RNAseq (scRNA-seq) on the epithelial compartment of intestinal biopsies from a cohort of non-inflammatory bowel disease (IBD) controls and patients with active UC. Analysis was performed using our own-curated pipeline in Seurat1. Spatial protein localization was analysed by immunofluorescence on fixed intestinal samples. To measure the modulation of KRT17 and associated markers, ex vivo air-liquid interface (ALI) epithelial cultures derived from human non-IBD organoids were used. The signatures of UC-derived organoids2 were mapped onto the scRNA-seq dataset. Results ScRNA-seq analysis identified a rare KRT17+ epithelial cell population emerging in active UC characterized by the expression of KRT17 (Fig. 1A) and other alarmins (KRT6A, KRT16, S100A8), metalloproteinases (MMP1, MMP10), and inflammatory markers (SAA1, DUOX2…). KRT17 protein, absent in non-IBD colon, was expressed in the epithelium of the inflamed UC mucosa exhibiting a patchy pattern, and marked epithelial clusters with both columnar and squamous-like morphology (Fig. 1B). The ALI culture closely recapitulated the differentiated intestinal epithelium in homeostasis by showing a columnar aspect, high expression of differentiation markers, and low or undetectable expression of stem/proliferation or KRT17+-cell markers. Exposure of the ALI culture to hypoxic stress (by re-submersion in expansion medium) induced the expression of KRT17+ cell-specific and inflammation markers (Fig. 1C), and the acquisition of a squamous morphology (Fig. 1D). IBD-related IFN-ɣ and IL-22 cytokines could not fully replicate this phenotype (Fig. 1E). Lastly, we observed that genes up-regulated in UC, compared to non-IBD organoids, were predominantly expressed within the KRT17+ population (Fig. 1F). Conclusion Our results suggest that a novel KRT17+ epithelial population may arise from the intestinal cells of inflamed UC mucosa under the influence of specific environmental factors. This population could contribute to the persistence of the disease over time.

Modelling the habitat preferences of the NE-Atlantic Sea cucumber Holothuria forskali: Demographics and abundance

Sea cucumbers' historical demand, together with the depletion of several traditional species in the market, has popularized new target species from new fishing grounds. Holothuria forskali is one of those emergent species in the trade market. However, it is a species for which there is no relevant information to allow sustainable stock management. Fundamental knowledge of the populations' structure and habitat preferences are key elements without which any measure is inconsequent. This work aims to fill that gap by modelling temporal and spatial patterns of abundance and demographic structure of this species in a NE-Atlantic area, as a function of environmental features.For a period of 15 months, nine regular sampling campaigns collected data on density, individual length, individual conditions of occurrence (e.g. sheltered, on sand, on algae cover) and environmental parameters (water column, sediment, substrate cover and type), using random transects throughout a costal rocky-reef, considering habitat heterogeneity and substrate types. To determine the species' habitat preferences Generalized Linear Models were used to model density and demographic structure of the species as a function of environmental conditions. The models revealed that the main drivers shaping the distribution of H. forskali are neither abiotic nor biotic parameters of the water column, but physical stressors, like current intensity and depth, and substrate type in a patchy distribution pattern. Estuarine conditions are generally avoided, although with a size-dependent opportunistic strategy. Larger individuals show temporal and spatial displacement patterns towards suitable reproductive conditions (pre-breeding aggregation) and favourable feeding grounds and smaller size-classes tend to aggregate in higher numbers in more stable environments.Sustainable sources for market supply, like aquaculture, are still a long way from commercial production. So, these results are fundamental to support effective conservation measures for stock management of H. forskali.

Clinicohistopathological Features and Immunohistochemical Expression Patterns of p53 in Epithelial Ovarian Tumours: A Cross-sectional Study

Introduction: Ovarian tumours represent 3% of female malignancies, with epithelial tumours constituting more than 90% of all ovarian cancers. Tumour suppressor gene 53 (TP53) mutations play an important role in the prognosis and treatment of ovarian cancer. The tumour suppressor gene Tumour Protein 53 (p53), located on the short arm of chromosome 17, acts by suppressing abnormal cell growth at the beginning of the Synthesis phase (S-phase) of the cell cycle. Previous studies have shown a correlation between p53 mutation or overexpression and patient prognosis in various types of tumours, including breast cancer, rectal cancer, intestinal cancer, lung cancer, and ovarian cancer. Aim: To investigate the clinicohistopathological features and immunohistochemical expression of p53 in Epithelial Ovarian Tumours (EOT). Materials and Methods: A cross-sectional study was conducted in the Department of Pathology at Hind Institute of Medical Sciences, Barabanki, Uttar Pradesh, India. The duration of the study was one year and two months, from September 2021 to November 2022. A total of 80 cases of EOT were included and histopathological diagnosis was performed, and immunohistochemical expression of p53 was evaluated in all cases. The Chi-square test was used to compare categorical data (the number of benign, borderline, and malignant EOT) and determine whether the difference in p53 expression (positive or negative) was statistically significant, using Statistical Package for the Social Sciences (SPSS) version 26.0. Results: The total of 80 cases of EOT in the present study comprised 56 (70%) benign, 5 (6.25%) borderline, and 19 (23.75%) malignant tumours. The p53 expression was statistically significant. Immunohistochemistry (IHC) for p53 showed diffuse strong positive nuclear staining (&gt;60%) of the tumour cells in 14 cases, all of which were malignant epithelial tumours. Focally weak and patchy positive nuclear staining patterns (5%-60%) were observed in 64 cases, including 56 benign cases, four borderline cases, and four cases of malignant epithelial tumours, respectively. p53 positivity (&lt;5% staining of tumour cells) was seen in two cases, one each of borderline and malignant epithelial tumour, respectively. Conclusion: The IHC marker p53 serves as a surrogate marker for p53 gene mutation, and its positivity is observed in serous EOT. Understanding p53 staining patterns can be used in conjunction with a panel of other antibodies to correctly classify morphologically confusing EOT. This can aid in assessing prognosis and understanding the biological behaviour of the tumour, which can be helpful in modifying the treatment plan.

Relationship between hyperintensity on MRI-T1WI and hemorrhagic transformation after cerebral infarction and its influencing factors

This study aims to investigate the correlation between hyperintensity on Magnetic Resonance Imaging-T1 weighted imaging (MRI-T1WI) and post-infarction hemorrhagic transformation (HT) after cerebral infarction (CI) and analyze the influencing factors. This retrospective study comprised 115 patients diagnosed with cerebral infarction at our hospital. Their clinical data were collected, and they were then divided into a hyperintensity and a non-hyperintensity group based on their T1WI image characteristics. Comparative analysis was performed and the diagnostic value of T1WI hyperintensity for HT and influencing factors were assessed. Lesions in the 115 cerebral infarction patients were distributed as follows: 52 in the cerebral cortex, 37 in the basal ganglia, 14 in the cerebellum, 7 in the thalamus, and 5 in the subcortex. Hyperintensity on T1WI was observed in 4 cases before treatment, which increased to 27 cases after treatment, including 16 affecting the cerebral cortex. These hyperintense signals manifested as spotty, patchy or linear patterns along the gyri. In the basal ganglia, 10 cases exhibited spotty or patchy signals, surrounded by an annular hypointense shadow. Additionally, 3 cases involved the cerebellum, 1 the thalamus, and 1 the subcortex, all with spotty or patchy hyperintensities. HT occurred in 17 out of 115 patients (14.78%) one month after treatment. The diagnostic performance of T1WI hyperintensity for HT showed sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 94.12%, 84.69%, 86.09%, 51.61% and 98.81%, respectively, with a Kappa value of 0.588. Multivariate logistic regression analysis revealed that age, atherosclerosis, and infarct size were significant risk factors for T1WI hyperintensity in cerebral infarction (p &lt; 0.05). Hyperintensity on T1WI in cerebral infarction primarily correlates with HT and could be a valuable diagnostic marker for HT, with age, atherosclerosis and infarct size identified as potential influencing factors.

Force adaptation through the intravenous route in naïve mice

Aim of the study: Force adaptation is a process whereby the contractile capacity of the airway smooth muscle increases during a sustained contraction (aka tone). Tone also increases the response to a nebulized challenge with methacholine in vivo, presumably through force adaptation. Yet, due to its patchy pattern of deposition, nebulized methacholine often spurs small airway narrowing heterogeneity and closure, two important enhancers of the methacholine response. This raises the possibility that the potentiating effect of tone on the methacholine response is not due to force adaptation but by furthering heterogeneity and closure. Herein, methacholine was delivered homogenously through the intravenous (i.v.) route. Materials and Methods: Female and male BALB/c mice were subjected to one of two i.v. methacholine challenges, each of the same cumulative dose but starting by a 20-min period either with or without tone induced by serial i.v. boluses. Changes in respiratory mechanics were monitored throughout by oscillometry, and the response after the final dose was compared between the two challenges to assess the effect of tone. Results: For the elastance of the respiratory system (Ers), tone potentiated the methacholine response by 64 and 405% in females (37.4 ± 10.7 vs. 61.5 ± 15.1 cmH2O/mL; p = 0.01) and males (33.0 ± 14.3 vs. 166.7 ± 60.6 cmH2O/mL; p = 0.0004), respectively. For the resistance of the respiratory system (Rrs), tone potentiated the methacholine response by 129 and 225% in females (9.7 ± 3.5 vs. 22.2 ± 4.3 cmH2O·s/mL; p = 0.0003) and males (10.7 ± 3.1 vs. 34.7 ± 7.9 cmH2O·s/mL; p < 0.0001), respectively. Conclusions: As previously reported with nebulized challenges, tone increases the response to i.v. methacholine in both sexes; albeit sexual dimorphisms were obvious regarding the relative resistive versus elastic nature of this potentiation. This represents further support that tone increases the lung response to methacholine through force adaptation.

Optimizing the sodium iodate model: Effects of dose, gender, and age

Sodium iodate (NaIO3) is a commonly used model for age-related macular degeneration (AMD), but its rapid and severe induction of retinal pigment epithelial (RPE) and photoreceptor degeneration can lead to the premature dismissal of potentially effective therapeutics. Additionally, little is known about how sex and age affect the retinal response to NaIO3. This study aims to establish a less severe yet reproducible regimen by testing low doses of NaIO3 while considering age- and sex-related effects, enabling a broader range of therapeutic evaluations. In this study, young (3–5 months) and old (18–24 months) male and female C57Bl/6J mice were given an intraperitoneal (IP) injection of 15, 20, or 25 mg/kg NaIO3. Damage assessment one week post-injection included in vivo imaging, histological examination, and qRT-PCR analysis. The results revealed that young mice showed no damage at 15 mg/kg IP NaIO3, with varying degrees of damage observed at 20 mg/kg. At 25 mg/kg, most young mice displayed widespread retinal damage, with females exhibiting less retinal thinning than males. In contrast, older mice at 20 and 25 mg/kg displayed a more patchy degeneration pattern, outer retinal undulations, and greater variability in degeneration than the young mice. The most effective model for minimizing damage while maintaining consistency utilizes young female mice injected with 25 mg/kg NaIO3. The observed sex- and age-related differences underscore the importance of considering these variables in research, aligning with the National Institutes of Health's guidance. While the model does not fully replicate the complexity of AMD, these findings enhance its utility as a valuable tool for testing RPE/photoreceptor protective or replacement therapies.

Abstract 15046: Atrial Sarcomeric Dysfunction in Ttntv Mice Indicates a Causal Relationship Between Rare Variation in TTN and Early Onset Atrial Fibrillation in Patients

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia with a substantial genetic component. Rare variation in TTN and other sarcomeric genes have been associated with AF, in particular in early-onset disease. Aim: To describe the burden of rare, functional variants in a Norwegian early-onset AF population and to perform functional characterization in a Ttn truncating variant ( Ttntv ) mouse model. Methods: We performed whole-genome sequencing in 90 individuals with onset of AF before age 50 years and calculated the burden of rare, functional variation for all genes. Variant frequencies and gene burden from gnomAD 3.1.2 NFE were used as controls. The burden was defined as the sum of allele counts for rare (MAF&lt;1%) and damaging variants (high and moderate impact) for each gene, and differences in burden was assessed using Fisher’s exact test. Functional characterization, including echocardiography, electron microscopy and mRNA expression analyses, was performed in atria from haploinsufficient Ttntv mice. Results: We identified an increased burden of rare, functional variation in 57 genes, including the sarcomeric genes TTN , MYH6 and OBSL1 , but also in the cell adhesion gene DCHS2 , in individuals with early-onset AF. Ttntv mice had normal cardiac function assessed by echocardiography, but electron microscopy revealed structural remodeling of the atria, with a patchy pattern of unorganized sarcomeres with focal fibrosis and lipid droplet accumulation. Molecular profiling of atria using RNA sequencing showed differential expression of genes related to cellular stress, sarcomeric structure and fibrosis, including increased levels of Anp , Malat1 and Kcna1 . Dchs2 displayed decreased expression in Ttntv atria. Conclusion: We identified an increased burden of rare, functional variation in genes associated with sarcomeric function in early-onset AF. Atrial myopathy with sarcomeric lesions, focal fibrosis, lipid droplet accumulation and altered gene expression of Anp , Malat1 and Kcna1 was found in atria of mice with Ttntv , suggesting a causal, pathophysiological relationship between TTN variants and AF. Interestingly, DCHS2 displayed both increased burden of rare variation in early-onset AF and decreased expression in Ttntv mouse atria.