Capillary Changes Research Articles

6912 Nail Fold Capillary Findings In Patients With Somatic EPAS1 Pathogenic Variants

Abstract Disclosure: H. Alkaissi: None. B. Turturice: None. J.S. Rosenblum: None. A.S. Alzahrani: None. S. Talvacchio: None. A. Derkyi: None. M. Nazari: None. H. Wang: None. I. Pinal Fernandez: None. Z. Zhuang: None. K. Pacak: None. We recently discovered a new syndrome characterized by a triad of pheochromocytoma/paraganglioma, polycythemia, and somatostatinoma (so called Pacak-Zhuang syndrome) caused by somatic gain-of-function pathogenic variants in the EPAS1 gene, encoding hypoxia-inducible factor 2α (HIF-2α). Recently, we have described additional features of this syndrome, including systemic developmental vascular malformations in patients and the mouse model [1]. Here we evaluated vascular changes in the nailfold capillaries by using video capillaroscopy in four patients, three of whom were female and carried the same pathogenic somatic EPAS1 variant allele (EPAS1A530V). The first patient is an 18-year-old female with a history of ventricular septal defect since birth, acrocyanosis, abdominal paraganglioma, left adrenal pheochromocytoma, and polycythemia. The second patient is a 64-year-old female who presented with paraganglioma without polycythemia, in whom we found the EPAS1A530V variant from hair sample, and an additional variant (EPAS1P53[1]A) in a resected paraganglioma, confirming the diagnosis. The third patient is a 33-year-old female had polycythemia, right adrenal pheochromocytoma, abdominal paragangliomas and duodenal somatostatinoma. The fourth patient is a 25-year-old male with PZS bearing a somatic EPAS1M535V pathogenic variant and an additional D536_L542 deletion, with hypoplastic left ventricle and metastatic paraganglioma who never developed polycythemia due to concomitant sickle cell-thalassemia traits. Despite the notable differences in genotype between the first three patients compared to the fourth patient, whose genotype is more complex, nailfold video capillaroscopy of all these patients showed similar phenotype—abnormal capillary structure marked by widespread dilations, megacapillaries, sporadic capillary hemorrhages, and regions with diminished capillary density. While polycythemia has been implicated in megacapillaries phenotype, two of our patients did not have polycythemia at the time of evaluation, further supporting the role of HIF-2a in angiogenesis. In conclusion, we describe nailfold capillary changes on video capillaroscopy as a non-invasive clinical sign in patients with EPAS1 pathogenic variants. Whether this finding is due to circulating angiogenic factors secreted by the tissues harboring HIF-2α mutation, or a direct effect of HIF-2α on angiogenesis remains to be determined.

Peripheral Superficial Retina Vascular Density and Area of Radial Peripapillary Capillaries Changes in Myopic Individuals: A Wide-Field OCT Angiography Study.

Using swept-source optical coherence tomography (SS-OCT) to explore the effect of high myopia on superficial retina vascular density (SVD) of the peripheral region and the area of radial peripapillary capillaries (RPCs). In this cross-sectional study, a total of 91 volunteers (34 male subjects and 57 female subjects) were recruited and 34 individuals in the high myopic group (group A) and 57 individuals in the low myopic group (group B). Using the wide-field OCT-angiography (OCTA; 24 × 20 mm, 120 degrees angular field) compared the peripheral SVD and the area of RPC between the two groups and investigated its correlation with ocular axial length and diopter. Peripheral SVD of group B around the supratemporal (SVD1), supranasal (SVD2), infratemporal (SVD3), and infranasal (SVD4) directions were significantly higher than those of group A (all P < 0.05). The RPC area of group B around the supranasal (RPC2) and infranasal (RPC4) were significantly larger than that of group A (all P < 0.01). Ocular axial length and diopter were significantly correlated with SVD2 and SVD4 (all P < 0.05), and they also have a significant correlation with the supratemporal (RPC1), RPC2, and RPC4 (all P < 0.05). Peripheral SVD was decreased and the RPC area was mainly reduced on the nasal side in the high myopic group. Peripheral SVD and area of RPC are significantly correlated with ocular axial length and diopter. The wide-field OCTA can be used for new detection of myopia's impact on the retinal peripheral SVD and area of peripapillary RPC, offering new insights into the progression of myopia.

Nailfold capillaroscopy for diagnosis of onychodystrophies: A prospective cross-sectional study

Nail diseases are often associated with significant physical and psychosocial burden, but diagnosis is challenging due to non-specific clinical and histological findings. Nail fold capillaroscopy has been studied for diagnosis of systemic diseases, but studies on nail diseases are lacking. Our objectives were to characterize and compare capillary changes in a set of nail conditions vs. controls, between nail groups, and based on demographic/clinical criteria. This was a prospective cross-sectional study of patients with nail psoriasis, onychomycosis, idiopathic onycholysis, brittle nail syndrome, nail lichen planus, retronychia, other nail conditions, and no nail findings (controls) undergoing capillaroscopy imaging/analysis. Nail psoriasis vs. control patients demonstrated decreased capillary length/density and increased abnormal capillaries, with higher frequency in older, male patients. Onychomycosis was associated with increased meandering capillaries compared to controls, nail psoriasis, and nail lichen planus. Retronychia is associated with increased disorganized polymorphic capillaries compared to controls and onychomycosis. Limitations include small sample size for certain nail conditions and small numbers of nail psoriasis patient with psoriatic arthritis. Our findings highlight nailfold capillaroscopy as a potentially quick, cost-effective, and non-invasive imaging modality, as an adjunct for diagnosis and treatment initiation for patients with onychodystrophies.

Nailfold Capillary Changes in Adult Bangladeshi Patients with Systemic Lupus Erythematosus: Correlation with Disease Activity

Nailfold Capillary Changes in Adult Bangladeshi Patients with Systemic Lupus Erythematosus: Correlation with Disease Activity

YOLOv8-Based System for Nail Capillary Detection on a Single-Board Computer.

Nail capillaroscopic examination is an inexpensive and easily applicable method to identify capillary morphological changes in patients with conditions such as systemic sclerosis and Raynaud's. The detection of changes in capillaries makes an important contribution to diagnosing these diseases. Capillary morphology is important in the symptoms of these diseases, and capillary diameter, visibility, distribution, length, microbleeds, blood flow, and density are important indicators in capillaroscopic evaluation. Manual examination to determine these parameters is subjective, causes inconsistent results, and is labor-intensive and time-consuming. To overcome these problems, a YOLOv8s-based system was proposed in this paper to detect the number, thickness, and density of capillaries in the nail bed. The system's components include database systems that store the analysis results, artificial intelligence-based software that runs on the SBC (Single-Board Computer), and recorded microscope images. mAP and F1_score parameters were used to evaluate the system's performance, and values of 0.882 and 0.83 were obtained. The proposed system is promising in improving the diagnosis process of diseases such as systemic sclerosis and Raynaud's by providing objective measurements and the early diagnosis and monitoring of diseases.

Oscillation of a Liquid Column in an Eccentric Annulus

The velocity distribution of flow in an eccentric cylindrical annulus is determined in an attempt to investigate the vertical capillary rise in the channel. The critical values of the radii ratio and the eccentricity at which the capillary rise changes from oscillatory to monotone or vice versa are determined. For a particular aspect ratio, the rise becomes monotonic as the eccentricity increases. The oscillations are also dampened as the annulus becomes thinner. These critical values depend on Galileo and Bond numbers as well as the contact angle. The results reduce to the limiting cases of concentric and fully eccentric annuli. The critical values are also calculated for the special arrangements when the radii ratios are 1 and 0. The latter limit is in perfect agreement with the conditions found in the literature for the classical circular channel.

Differential Capillary and Large Vessel Analysis Improves OCTA Classification of Diabetic Retinopathy.

This study aimed to investigate the impact of distinctive capillary-large vessel (CLV) analysis in optical coherence tomography angiography (OCTA) on the classification performance of diabetic retinopathy (DR). This multicenter study analyzed 212 OCTA images from 146 patients, including 28 controls, 36 diabetic patients without DR (NoDR), 31 with mild non-proliferative DR (NPDR), 28 with moderate NPDR, and 23 with severe NPDR. Quantitative features were derived from the whole image as well as the parafovea and perifovea regions. A support vector machine classifier was employed for DR classification. The accuracy and area under the receiver operating characteristic curve were used to evaluate the classification performance, utilizing features derived from the whole image and specific regions, both before and after CLV analysis. Differential CLV analysis significantly improved OCTA classification of DR. In binary classifications, accuracy improved by 11.81%, rising from 77.45% to 89.26%, when utilizing whole image features. For multiclass classifications, accuracy increased by 7.55%, from 78.68% to 86.23%. Incorporating features from the whole image, parafovea, and perifovea further improved binary classification accuracy from 83.07% to 93.80%, and multiclass accuracy from 82.64% to 87.92%. This study demonstrated that feature changes in capillaries are more sensitive during DR progression, and CLV analysis can significantly improve DR classification performance by extracting features that are specific to large vessels and capillaries in OCTA. Incorporating regional features further improves DR classification accuracy. Differential CLV analysis promises better disease screening, diagnosis, and treatment outcome assessment.

Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain.

Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.

Lymphatic Capillarization in Different Fiber Types of Rat Skeletal Muscles With Growth and Age.

To clarify the effect of growth and advancing age on lymphatic capillarization in rat skeletal muscles, we examined the histological and biochemical changes of lymphatic capillaries in different fiber types of skeletal muscles across juvenile, young, and middle-aged generations. We collected the tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) muscles. Immunohistochemical staining using LYVE-1 and CD31 markers was used for lymphatic and blood capillaries, respectively. Real-time PCR was used to analyze mRNA expression of lymphangiogenic factors. The density of LYVE-1-positive lymphatic capillaries in the muscles peaked during the juvenile period and subsequently decreased with increasing age. In contrast to blood capillaries, fast-twitch dominant muscles (i.e., TA and EDL) exhibited an age-related decrease in lymphatic capillaries. Similar to blood capillaries, lymphatic capillaries were abundant in SOL, a slow-twitch dominant muscle, which showed less susceptibility to age-related lymphatic decline. The mRNA expression of lymphangiogenic factors was significantly upregulated in SOL and decreased in all muscles of middle-aged rats. The age-related decrease of lymphatic capillaries in fast-twitch muscles might be associated with age-related muscle atrophy.

Nailfold Capillaroscopy: A Comprehensive Review on Its Usefulness in Both Clinical Diagnosis and Improving Unhealthy Dietary Lifestyles.

Since the 1970s, the utility of nailfold capillaroscopy (NFC) in diagnosing rheumatological disorders such as systemic sclerosis has been well established. Further studies have also shown that NFC can detect non-rheumatic diseases such as diabetes, glaucoma, dermatitis, and Alzheimer disease. In the past decade, nailfold capillary morphological changes have also been reported as symptoms of unhealthy lifestyle habits such as poor diet, smoking, sleep deprivation, and even psychological stress, all of which contribute to slow blood flow. Therefore, studying the relationships between the morphology of nailfold capillaries and lifestyle habits has a high potential to indicate unhealthy states or even pre-disease conditions. Simple, inexpensive, and non-invasive methods such as NFC are important and useful for routine medical examinations. The present study began with a systematic literature search of the PubMed database followed by a summary of studies reporting the assessment of morphological changes detected by NFC, and a comprehensive review of NFC's utility in clinical diagnosis and improving unhealthy dietary lifestyles. It culminates in a summary of dietary and lifestyle health promotion strategy, assessed based on NFC and other related measurements that indicate healthy microvascular blood flow and endothelial function.

Long-Term Data on Efficacy and Safety of Selexipag for Digital Systemic Sclerosis Vasculopathy.

Raynaud phenomenon (RP) and digital ulcers (DUs) are the main signs of digital vasculopathy in systemic sclerosis (SSc). Selexipag is an oral prostacyclin agonist approved for SSc-related pulmonary arterial hypertension. Following our previous preliminary short-course report, we herein present long-term data on selexipag safety and efficacy in the treatment of SSc digital vasculopathy. Selexipag was administered to patients with SSc with severe digital vasculopathy refractory or with contraindication to all other vasoactive therapies. Each subject was assessed at baseline and after 3, 6, and 12 months. Clinical outcomes related to RP and DUs were evaluated along with modified Rodnan skin score of the fingers. Digital perfusion was assessed by laser speckle contrast analysis (LASCA). Nailfold videocapillaroscopy (NVC) was also performed. Eight patients with SSc (63% female, mean age 50.1 years) received selexipag. After 12 months of treatment, RP was reported to significantly decrease in the number of daily episodes and mean duration (P < 0.001 and P = 0.01, respectively). All patients achieved a complete healing of their DUs (P = 0.03) within 6 months. A progressive reduction of fingers skin score was observed (P = 0.03). No structural changes of capillaries were noted on NVC. Conversely, LASCA revealed an important increase in total digital perfusion (P = 0.004) despite seasonal variability. The safety profile was consistent with that reported in the literature. We observed a sustained efficacy of selexipag on SSc digital vasculopathy during 1 year of administration. Our promising results encourage the design of a new randomized controlled trial to evaluate the effect of selexipag on SSc digital vasculopathy.

Cutaneous manifestations of anti‐synthetase syndrome: Case series and literature review

AbstractBackgroundAnti‐synthetase syndrome (ASyS) is a rare inflammatory myopathy associated with anti‐aminoacyl transfer RNA synthetase antibodies, and is characterized by a triad of interstitial lung disease, arthritis, and myopathy. ASyS has been considered to represent a subtype of dermatomyositis (DM), however it is not clear whether cutaneous findings overlap in both diseases.ObjectivesWe aimed to characterize mucocutaneous features which should raise suspicion of ASyS and prompt early diagnostic testing.MethodsWe reviewed 28 cases of ASyS in our institution, and retrieved data from 43 articles reporting clinical features of ASyS in the literature.ResultsDermatologic manifestations of ASyS can be categorized as: specific cutaneous signs strongly associated with ASyS (‘Mechanic's hands’, ‘Hiker's feet’); mucocutaneous signs overlapping with other collagenoses; nailfold changes (resembling those of DM and systemic sclerosis); and mucocutaneous signs of undetermined significance. Only 20% had pathognomonic DM signs.ConclusionsDermatologic manifestations of ASyS are heterogeneous and do not always reproduce the pattern seen in DM. Presence of palmar hyperkeratosis (‘Mechanic's hands’), cuticular overgrowth, skin ulcerations and nailfold capillary changes should prompt further diagnostic workup of ASyS. Limitations of our study include inconsistent reporting of dermatologic findings within our series between virtual and in‐person visits. Not all patients were seen in dermatology consultation.

Skeletal muscle myosin heavy chain expression and 3D capillary network changes in streptozotocin-induced diabetic female mice.

It is not well-understood how type 1 diabetes (T1DM) affects skeletal muscle histological phenotype, particularly capillarisation. This study aimed to analyze skeletal muscle myosin heavy chain (MyHC) fibre type changes and 3D capillary network characteristics in experimental T1DM mice. Female C57BL/6J-OlaHsd mice were categorized into streptozotocin (STZ)-induced diabetic (n = 12) and age-matched non-diabetic controls (n =12). The muscle fibre phenotype of the soleus, gluteus maximus, and gastrocnemius muscles were characterized based on the expression of MyHC isoforms, while capillaries of the gluteus maximus were assessed with immunofluorescence staining, confocal laser microscopy and 3D image analysis. STZ-induced diabetic mice exhibited elevated glucose levels, reduced body weight, and prolonged thermal latency, verifying the T1DM phenotype. In both T1DM and non-diabetic mice, the gluteus maximus and gastrocnemius muscles predominantly expressed fast-twitch type 2b fibers, with no significant differences noted. However, the soleus muscle in non-diabetic mice had a greater proportion of type 2a fibers and comparable type 1 fiber densities (26.2 ± 14.6% vs 21.9 ± 13.5%) relative to diabetic mice. T1DM mice showed reduced fiber diameters (P = 0.026), and the 3D capillary network analysis indicated a higher capillary length per muscle volume in the gluteus maximus of diabetic mice compared to controls (P < 0.05). Overall, T1DM induced significant changes in the skeletal muscle, including shifts in MyHC fibre types, decreased fibre diameters, and increased relative capillarisation, possibly due to muscle fibre atrophy. Our findings emphasize the superior detail provided by the 3D analytical method for characterizing skeletal muscle capillary architecture, highlighting caution in interpreting 2D data for capillary changes in T1DM.

Rate of Initial Optic Nerve Head Capillary Density Loss and Risk of Visual Field Progression

Rapid initial optic nerve head capillary density loss may be used to assess the risk of glaucoma visual field progression. To investigate the association between the rate of initial optic nerve head capillary density loss from optical coherence tomography angiography (OCTA) and visual field progression. This was a retrospective study of a longitudinal cohort at a glaucoma referral center. A total of 167 eyes (96 with primary open-angle glaucoma and 71 with glaucoma suspect) of 109 patients were monitored for a mean (SD) of 5.7 (1.4) years from January 2015 to December 2022. Data analysis was undertaken in April 2023. The rates of initial capillary density and average retinal nerve fiber layer loss were calculated from the first 3 optic nerve head OCTA and OCT scans, respectively, during the initial follow-up (mean [SD], 2.0 [1.0] years). Based on the median rate, eyes were categorized into fast and slow progressor groups. The association between initial capillary density change or retinal nerve fiber layer thinning and visual field progression was evaluated using linear-mixed and time-varying Cox models. A total of 167 eyes of 109 patients (mean [SD] age, 69.0 [11.1] years; 56 [51.4%] female and 53 [48.6%] male) were assessed. Eighty-three eyes were slow OCTA progressors, while 84 eyes were fast with mean capillary density loss of -0.45% per year and -1.17% per year, respectively (mean difference, -0.72%/year; 95% CI,-0.84 to -0.60; P < .001). Similarly, 83 eyes were slow OCT progressors, while 84 eyes were fast with mean retinal nerve fiber layer thinning of -0.09 μm per year and -0.60 μm per year, respectively (mean difference, -0.51 μm/year; 95% CI,-0.59 to -0.43; P < .001). The fast OCTA and OCT progressors were associated with more rapid visual field loss (mean difference, -0.18 dB/year; 95% CI,-0.30 to -0.06; P = .004 and -0.17 dB/year; 95% CI,-0.29 to -0.06; P = .002, respectively). Fast OCTA progressing eyes were more likely to have visual field progression (hazard ratio, 1.96; 95% CI, 1.04-3.69; P = .04). Seventeen of 52 eyes (32.7%; 95% CI, 32.5-32.8) with fast OCTA and OCT progression developed subsequent visual field likely progression. Rapid initial optic nerve head capillary density loss from OCTA was associated with a faster rate of visual field progression and a doubling of the risk of developing event progression in this study. These findings may support clinical use of OCTA and OCT optic nerve head measurements for risk assessment of glaucoma progression.

Neutralization of Interleukin 1-beta is associated with preservation of thalamic capillaries after experimental traumatic brain injury.

Traumatic brain injury to thalamo-cortical pathways is associated with posttraumatic morbidity. Diffuse mechanical forces to white matter tracts and deep grey matter regions induce an inflammatory response and vascular damage resulting in progressive neurodegeneration. Pro-inflammatory cytokines, including interleukin-1β (IL-1β), may contribute to the link between inflammation and the injured capillary network after TBI. This study investigates whether IL-1β is a key contributor to capillary alterations and changes in pericyte coverage in the thalamus and cortex after TBI. Animals were subjected to central fluid percussion injury (cFPI), a model of TBI causing widespread axonal and vascular pathology, or sham injury and randomized to receive a neutralizing anti-IL-1β or a control, anti-cyclosporin A antibody, at 30 min post-injury. Capillary length and pericyte coverage of cortex and thalamus were analyzed by immunohistochemistry at 2- and 7-days post-injury. Our results show that early post-injury attenuation of IL-1β dependent inflammatory signaling prevents capillary damage by increasing pericyte coverage in the thalamus.

Study of Macular Capillary network changes after branch retinal vein occlusion (BRVO) on optical coherence tomography angiography (OCT-A).

Study of Macular Capillary network changes after branch retinal vein occlusion (BRVO) on optical coherence tomography angiography (OCT-A).

Optical Coherence Tomography Angiography Assessment of the Optic Nerve Head in Patients Hospitalized Due to COVID-19 Bilateral Pneumonia.

Background and objectives: We aimed to investigate changes in the radial peripapillary capillary (RPC) network using optical coherence tomography angiography (OCTA) in patients who recovered from coronavirus disease 2019 (COVID-19). Materials and Methods: This was a prospective study of patients hospitalized due to COVID-19 bilateral pneumonia between March and May 2021. The control group included healthy individuals matched for age and sex. Two months after discharge, the patients underwent ophthalmological examination, including optical coherence tomography (OCT) imaging. The RPC network and retinal nerve fiber layer (RNFL) of the optic disc (RNFL optic disc) were automatically evaluated and compared between the study groups. Additionally, the RPC parameters were compared between the men and women in the COVID-19 group, and correlations between the RPC and RNFL optic disc parameters were assessed. Results: A total of 63 patients (120 eyes) with bilateral pneumonia caused by severe acute respiratory syndrome coronavirus 2 infection were examined. No ophthalmic symptoms were reported by the patients. No significant differences were observed in the RPC parameters between the patients from the COVID-19 group and the 43 healthy controls. Moreover, the RPC parameters did not differ between the men and women in the COVID-19 group. A positive correlation was found between the RPC and RNFL optic disc parameters in the COVID-19 patients (p < 0.001). Conclusions: No changes in the RPC network were observed among the patients with COVID-19 bilateral pneumonia in the early period after hospital discharge. However, a longer follow-up is needed to monitor COVID-19-related changes in the microvasculature of the optic nerve head.

Correlation of light and electron microscopic morphometric parameters of glomerular capillaries with serum creatinine and proteinuria

ABSTRACT Waste products in the bloodstream are filtered by the glomerular capillaries in the kidneys and excreted into the urine. When making a differential diagnosis of kidney diseases, structural assessment of glomeruli using histological, ultrastructural, and immunological studies is crucial. This study assessed the microscopic and ultrastructural morphometric parameters of glomerular capillaries and examined their correlation with serum creatinine and proteinuria. A total of 60 kidney biopsy cases received by the transmission electron microscope (TEM) laboratory for diagnosis were included in the study. Toluidine blue stained 300 nm thick sections of TEM tissue blocks were scanned for glomerular morphometry by a whole slide imaging system, and the estimation of Bowman’s capsule (BC) area, glomerular capillary lumen diameter (GCLD), glomerular capillary density (GCD), glomerular capillary surface area density (GCSA), and percentage of glomerular capillary lumen space (%GCLS) was performed with QuPath software. TEM images of 70 nm thick sections were used for the evaluation of endothelial fenestration diameter (EFD), glomerular basement membrane (GBM) thickness, and podocyte foot process (PFP) effacement. Proteinuria and serum creatinine showed positive correlations with GBM thickness and PFP effacement. Negative correlations of serum creatinine were observed with EFD, %GCLS, and GCSA. Hence, glomerular filtration is greatly affected by the total area of the glomerular capillary surface and structural changes of GBM. Reduction of glomerulus filtration due to foot process effacement and thickening of GBM results in damage to the filtration barrier leading to the leakage of plasma protein into urine.

Disease-associated immune cell endotypes in anti-MDA5-positive dermatomyositis using unbiased hierarchical clustering.

Clinical and prognostic features of Anti-MDA5-Positive Dermatomyositis (MDA5+ DM) are diverse. This study aimed to examine the peripheral immune cell profiles of patients with MDA5+ DM, identify disease endotypes related to the heterogeneous manifestations and prognosis, and guide individualized therapy regimen. This inpatient cohort included 123 patients with MDA5+ DM. Unsupervised hierarchical clustering analysis was used to derive disease endotypes from the circulating immune cell profiles on admission. Clinical symptoms, laboratory test results, inpatient treatments, and disease outcomes were then analyzed among the identified endotypes. Three disease endotypes in MDA5+ DM were identified from peripheral immune cell profiles. Endotype1 had the highest percentages of CD4+ T cells and monocytes, and the lowest percentage of neutrophils; Endotype2 had the highest percentage of B cells; Endotype3 had the highest percentage of CD8+ T cells and NK cells. Clinical and prognostic heterogeneity of the endotypes were revealed. Endotype1 had the lowest 3-month mortality with the high incidence of periungual capillary changes. Endotype2 and Endotype3 had higher prevalence of rapidly progressive interstitial lung disease (RPILD) and mortality at 3 months than Endotype1. Meanwhile, Endotype3 had higher pneumocystis jiroveci and CMV viremia cases with significantly elevated of activated CD8+ T cells and multiple cytokines than Endotype1. Clustering analysis of peripheral immune cell profiles identified three different endotypes in MDA5+ dermatomyositis. Endotpye2 and 3 showed higher RPILD, 3-month mortality, pneumocystis jiroveci and CMV viremia.

Unsteady wetting of soft solids

HypothesisSpreading of liquids on soft solids often occurs intermittently, i.e., the liquid's wetting front switches between sticking and slipping. Studies of this so-called stick-slip wetting on soft solids mostly are confined within quasi-static or forced spreading conditions. In these situations, because the sticking duration is set much larger than the viscoelastic relaxation time of the solid, a ridge is persistently and fully developed at the wetting front as the soft solid yields to the liquid's surface tension. The sticking duration and spreading velocity, therefore, were shown to have little impact to the contact angle change required for stick-to-slip transitions. For unsteady wetting of soft solids, a commonly encountered but largely unexplored situation, we hypothesize that the stick-to-slip transition is controlled not only by a combination of sticking duration and the spreading velocity, but also by an increasing depinning threshold caused by the growing ridge at the wetting front. ExperimentWe performed unsteady wetting experiment on soft solids by letting water droplets spread freely on soft solid surfaces of various stiffness. We capture both the stick-slip spreading behavior and growing wetting ridges using synchronous high-speed imaging and high-speed interferometry. Recorded data of liquid spreading and solid deforming at the wetting front were analyzed to shed light on the relation between stick-slip characteristics and the growing wetting ridge. FindingsWe find that intermittent wetting on a soft solid surface results from a competition between three key factors: liquid inertia, capillary force change during sticking, and growing pinning force caused by the solid's viscoelastic response. We theoretically formulate their quantitative contributions to predict how stick-to-slip transitions occur, i.e., how the contact angle change and sticking duration depend on the liquid's spreading velocity and the solid's viscoelastic characteristics. This provides a mechanistic understanding and methods to control unsteady wetting phenomena in diverse applications, from tissue engineering and fabrication of flexible electronics to biomedicine.