Fractal dimension to characterize interactions between blood and lymphatic endothelial cells.

Spatial patterning of different cell types is crucial for tissue engineering and is characterized by the formation of sharp boundary between segregated groups of cells of different lineages. The cell-cell boundary layers, depending on the relative adhesion forces, can result in kinks in the border, similar to fingering patterns between two viscous partially miscible fluids which can be characterized by its fractal dimension. This suggests that mathematical models used to analyze the fingering patterns can be applied to cell migration data as a metric for intercellular adhesion forces. In this study, we develop a novel computational analysis method to characterize the interactions between blood endothelial cells (BECs) and lymphatic endothelial cells (LECs), which form segregated vasculature by recognizing each other through podoplanin. We observed indiscriminate mixing with LEC-LEC and BEC-BEC pairs and a sharp boundary between LEC-BEC pair, and fingering-like patterns with pseudo-LEC-BEC pairs. We found that the box counting method yields fractal dimension between 1 for sharp boundaries and 1.3 for indiscriminate mixing, and intermediate values for fingering-like boundaries. We further verify that these results are due to differential affinity by performing random walk simulations with differential attraction to nearby cells and generate similar migration pattern, confirming that higher differential attraction between different cell types result in lower fractal dimensions. We estimate the characteristic velocity and interfacial tension for our simulated and experimental data to show that the fractal dimension negatively correlates with capillary number (Ca), further indicating that the mathematical models used to study viscous fingering pattern can be used to characterize cell-cell mixing. Taken together, these results indicate that the fractal analysis of segregation boundaries can be used as a simple metric to estimate relative cell-cell adhesion forces between different cell types.

Highly Oxidized Ecdysteroids from a Commercial Cyanotis arachnoidea Root Extract as Potent Blood-Brain Barrier Protective Agents.

Ecdysteroid-containing herbal extracts, commonly prepared from the roots of Cyanotis arachnoidea, are marketed worldwide as a "green" anabolic food supplement. Herein are reported the isolation and complete 1H and 13C NMR signal assignments of three new minor ecdysteroids (compounds 2-4) from this extract. Compound 4 was identified as a possible artifact that gradually forms through the autoxidation of calonysterone. The compounds tested demonstrated a significant protective effect on the blood-brain barrier endothelial cells against oxidative stress or inflammation at a concentration of 1 µM. Based on these results, minor ecdysteroids present in food supplements may offer health benefits in various neurodegenerative disease states.

What happens after the kidney biopsy? The findings nephrologists should know.

BACKGROUND: Percutaneous kidney biopsies are important tools for the diagnosis of kidney diseases. Nephrologists must be familiar with the expected complications of the procedure to provide an adequate informed consent. Here, we present a quality improvement analysis that reviews the complication rate of percutaneous kidney biopsies performed over a 2-year period by nephrologists at a single center, and that tabulates the nature and timing of these events. METHODS: From a single center cohort, pre- and post-biopsy anthropomorphic and clinical measurements were collected. Post-biopsy complications were tracked and sorted into either major or minor complications. Statistical tests were used to analyze complication incidence across the pre- and post-biopsy measurements obtained. RESULTS: Of the 154 nephrologist-performed percutaneous native kidney biopsies, 2 biopsies (1.3%) were found to result in a major complication. Both major complications were detected within 4 hours of the biopsy. Analysis of the pre-biopsy and post-biopsy measurements found that the proportion of complications was higher in patients with hematuria prior to biopsy. It was also found that patients with complications were statistically younger and had fewer comorbidities. Under univariable analysis, older age was associated with a lower incidence rate ratio for complications. However, no pre-or-post biopsy measurement or characteristic had a statistically significant change in incidence rate ratio under multivariable analysis. CONCLUSIONS: Percutaneous kidney biopsies were found to be low risk when performed by nephrologists in this single center cohort. Consistent with past literature, life threatening major complications rarely occurred and were reliably identified within 4 hours of biopsy, suggesting that centers can consider reduced observation times without compromising patient safety. Minor complications, such as pain, were more likely to occur in younger, healthier patients, and in those with hematuria prior to biopsy. This extensive tabulation of all biopsy adverse events is the first of its kind and will be beneficial for nephrologists to inform discussions with patients about expectations and risk-benefit of this procedure.

Preoperative antithrombotic treatment in acutely symptomatic carotid artery stenosis.

OBJECTIVES: Early recurrence of cerebral ischemia in acutely symptomatic carotid artery stenosis can precede revascularization. The optimal antithrombotic regimen for this high-risk population is not well established. Although antiplatelet agents are commonly used, there is limited evidence for the use of anticoagulants. We sought to understand the safety and efficacy of short-term preoperative anticoagulants in secondary prevention of recurrent cerebral ischemic events from acutely symptomatic carotid stenosis in patients awaiting carotid endarterectomy (CEA). MATERIALS AND METHODS: A retrospective query of a prospective single institution registry of carotid revascularization was performed. Patients who presented with acute ischemic stroke or transient ischemic attack (TIA) attributable to an ipsilateral internal carotid artery stenosis (ICA) were included. Antiplatelet (AP) only and anticoagulation (AC) treatment arms were compared. The primary outcome was a composite of preoperative recurrent ischemic stroke or TIA. The primary safety outcome was symptomatic intracranial hemorrhage. RESULTS: Out of 443 CEA patients, 342 were in the AC group and 101 in the AP group. Baseline characteristics between groups (AC vs AP) were similar apart from age (71±10.5 vs 73±9.5, p=0.04), premorbid modified Rankin scale (mRS) score (1.0±1.2 vs 1.4±1.3, p=0.03) and stroke as presenting symptom (65.8 vs 53.5%, p=0.02). Patients in the AC group had a lower incidence of recurrent stroke/TIA (3.8 vs 10.9%, p=0.006). One patient had symptomatic intracranial hemorrhage in the AC group, and none in the AP group. In multivariate analysis controlling for age, premorbid mRS, stroke severity, degree of stenosis, presence of intraluminal thrombus (ILT) and time to surgery, AC was protective (OR 0.30, p=0.007). This effect persisted in the cohort exclusively without ILT (OR 0.23, p=0.002). CONCLUSIONS: Short term preoperative anticoagulation in patients with acutely symptomatic carotid stenosis appears safe and effective compared to antiplatelet agents alone in the prevention of recurrent cerebral ischemic events while awaiting CEA.

Cardiovascular Risk Factors Affect Specific Segments of the Intracranial Vasculature in High-Resolution (HR) Vessel Wall Imaging (VWI).

OBJECTIVES: Luminal-based imaging have identified different risk factors for extracranial and intracranial atherosclerosis (ICAS), but these techniques are known to underestimate the true extent of the disease. High-resolution (HR) vessel wall imaging (VWI) has recently gained recognition as a valuable tool in the assessment of ICAS. The aim of this study is to determine the association between cardiovascular risk factors and specific intracranial vessel segment involvement using HR-VWI. MATERIALS AND METHODS: From January 2017 to January 2020, consecutive patients ≥ 18 years-old undergoing HR-VWI of the brain were identified. Patients with history of primary or secondary vasculitis, reversible cerebral vasoconstriction syndrome, or moya-moya were excluded. The presence of vessel wall thickening and enhancement were assessed in the perpendicular plane for each vessel segment by two neuroradiologists. Univariate and multivariate analyses were performed to assess associations between imaging findings and cardiovascular risk factors. Interrater reliability was calculated. RESULTS: Seventy-one patients (39 men; mean age: 55.9 years) were included. Vessel wall enhancement was seen in 39/71 (55%). A total number of 105 vessel segments demonstrated abnormal enhancement and 79/105 (75%) had an eccentric pattern. Eccentric vessel wall enhancement was independently associated with age >65 years-old in the ICA (OR 9.0, CI 2.1 - 38.2, p < 0.01) and proximal MCA (OR 4.0, CI 1.2 - 13.2, p = 0.02), and with hyperlipidemia in the posterior circulation (OR 44.0, CI2.9-661.0, p<0.01). CONCLUSION: There is a significant association between eccentric vessel wall enhancement of the ICA and proximal MCA in patients with age > 65; and of the proximal posterior circulation (basilar - PCA1) with hyperlipidemia.

Accuracy of MRI T2*-weighted sequences (GRE-EPI) compared to CTA for detection of anterior circulation large vessel thrombus.

PURPOSE: Rapid detection of vessel occlusion is pivotal to the management of patients with acute stroke. Magnetic resonance (MR) T2*-weighted (W) sequence has proven its capability to detect intravascular thrombi, but its diagnostic value compared to computed tomography angiography (CTA) is not well established. We aimed to determine the diagnostic performance of fast 1.5-T MR T2*W sequences compared to CTA for the detection of intra-arterial thrombi in patients with acute stroke. METHODS: About 71 consecutive patients with known middle cerebral artery (MCA) territory stroke were identified. Patients with CTA and MR imaging within 12 h of symptom onset were included in the study. Two investigators reviewed the DWI and T2*W sequences for the presence of infarction and susceptibility vessel sign (SVS). A comparison to the corresponding internal carotid artery (ICA) and M1 and M2 segments of the MCA findings on CTA was made. RESULTS: Of the 51 patients included in our study, CTA thrombi were identified 84% patients (43/51). Of these, 77% (33/43) presented a corresponding SVS on T2*W. A total of 29 CTA thrombi were identified in the M1 segment, and of these, 22 patients had a corresponding SVS. Of the patients without M1 thrombus on CTA, no M1-SVS was detected on T2*W sequences. We found an accuracy of 92%, sensitivity of 85%, specificity of 100%, PPV 100%, and NPV of 86% for M1 occlusion. The Kappa coefficient was 0.79. CONCLUSION: Fast T2*W sequences demonstrated very good diagnostic performance and inter-reader agreement for detecting SVS in the M1 segment in patients with acute ischemic stroke.

Multivariable analysis on factors associated with aneurysm rupture in patients with multiple intracranial aneurysms.

PURPOSE: Multiple intracranial aneurysms (MIA) occur in one-third of patients with intracranial aneurysms (IA), and have been previously associated with an overall worse prognosis. Risk factors for IA formation and rupture in patients with a single IA are well-known. However, risk factors associated with rupture in patients with MIA have been less studied. METHODS: We performed a retrospective search of patients with MIA identified by computed tomography angiography (CTA) within a 10-year period. Patients with > 1 saccular aneurysm with size ≥ 2.0 mm were included. The location, size, number, and rupture status of the aneurysms were recorded. Patient demographics and cerebrovascular risk factors were obtained from electronic medical records. The primary endpoint of this study was to determine the association of these factors with aneurysmal rupture. The case-fatality rate was evaluated as a secondary outcome. RESULTS: Of the 2957 patients with IA in our CTA database, 425 patients were diagnosed with MIA and were therefore included in our study. A total of 1082 aneurysms were identified. Predictors of increased risk of aneurysmal rupture were age (OR 0.98, 95% CI, 0.96-0.99), size ≥ 5 mm (OR 4.4, 95% CI 2.76-7.0); and location in the anterior communicating artery complex (AcomC) (OR 2.62, 95% CI, 1.46-4.72) or posterior communicating artery (PCOM) (OR 2.66, 95% CI, 1.45-4.87). CONCLUSIONS: Younger age, aneurysm size ≥ 5 mm, and location in the AcomC and PCOM were independently associated with aneurysmal rupture in patients with MIA. Identifying these features could help recognize patients who might benefit from early intervention.

The Impact of Osteoarthritis on the Functioning and Health Status of a Low-Income Population: An Example of a Disability Paradox.

OBJECTIVE: The aim of this study was to measure the impact of osteoarthritis on the functioning and health status of individuals living in a low-income urban community in Mexico. METHODS: We conducted a cross-sectional, community-based study from December 2014 to November 2015, using the Community Oriented Program for Control of Rheumatic Diseases methodology to identify cases of musculoskeletal disease in a sample of adults older than 18 years in Pueblo Nuevo, Apodaca, Mexico. Two rheumatologists confirmed all cases of osteoarthritis (OA) using predefined criteria. Functioning was evaluated through (a) self-report of difficulty doing personal care, work, and leisure activities; (b) the modified Stanford Health Assessment Questionnaire-Disability Index; and (c) the Timed Up and Go test. Health status was evaluated using the EuroQoL 5 Dimensions. Statistical analyses were performed using χ tests and logistic regression models. RESULTS: Four hundred thirty-nine individuals with a mean age of 45.2 years were included, and 83 cases of OA were confirmed. The presence of OA was not significantly associated with having difficulties to do personal care, work, or leisure activities, but it was significantly associated with a higher Health Assessment Questionnaire-Disability Index score, longer time to complete the Timed Up and Go, and lower health status. CONCLUSIONS: Osteoarthritis is associated with having higher disability and worse health status in the community studied. A disability paradox was detected as some individuals perceived disability for doing standard activities but did not present disability performing their real-life activities. This underlies the importance of addressing the mental dimension during the management of this population.

Randomized controlled trial of the use of a large-pore polypropylene mesh to prevent incisional hernia in colorectal surgery.

OBJECTIVE: To reduce the incidence of incisional hernia (IH) in colorectal surgery by implanting a mesh on the overlay position. BACKGROUND: The incidence of IH in colorectal surgery may be as high as 40%. IH causes severe health and cosmetic problems, and its repair increases health care costs. MATERIAL AND METHODS: Randomized, controlled, prospective trial. Patients undergoing any colorectal procedure (both elective and emergency) through a midline laparotomy were divided into 2 groups. The abdomen was closed with an identical technique in both groups, except for the implantation of an overlay large-pore polypropylene mesh in the study group. Patients were followed up clinically and radiologically for 24 months. RESULTS: A total of 107 patients were included: 53 in the study group and 54 in the control group. Both groups were homogeneous, except for a higher incidence of diabetes in the mesh group. There were 20 emergency procedures in the study group and 17 in the control group. There were no statistical differences in surgical site infections, seromas, or mortality between the groups (33.3%, 13.8%, and 3.7% in the control group and 18.9%, 13.2%, and 3.8% in the study group). No mesh rejection was reported. The incidence of IH was 17 of 54 (31.5%) in the control group and 6 of 53 (11.3%) in the study group (P = 0.011). CONCLUSIONS: The incidence of IH is high in patients undergoing elective or emergency surgery for colorectal diseases. The addition of a prophylactic large-pore polypropylene mesh on the overlay position decreases the incidence of IH without adding morbidity.

Intestinal helminths in wild Peruvian red uakari monkeys (Cacajao calvus ucayalii) in the northeastern Peruvian Amazon.

Parasites are important in the management of the health of primate populations. We examined 36 fecal samples from Peruvian red uakari monkeys (Cacajao calvus ucayalii) collected from wild animals in the northeastern Peruvian Amazon. Samples were positive for helminth infection. Nematodes egg: Strongyloididae, Trypanoxyuris sp., Spirurid, and a cestode egg were identified.

Multiplicative Impact of Adverse Social Determinants of Health on Outcomes in Lupus Nephritis: A Meta-analysis and Systematic Review.

OBJECTIVE: Social determinants of health (SDoH) likely contribute to outcome disparities in lupus nephritis (LN). Understanding the overall burden and contribution of each domain could guide future health equity-focused interventions to improve outcomes and reduce disparities in LN. Objectives of this meta-analysis were to 1) determine the association of overall SDoH and specific SDoH domains on LN outcomes and 2) develop a framework for the multidimensional impact of SDoH on LN outcomes. METHODS: We performed a comprehensive search of studies measuring associations between SDoH and LN outcomes. We examined pooled odds of poor LN outcomes including death, end-stage kidney disease, or cardiovascular disease in patients with and without adverse SDoH. Additionally, we calculated the pooled odds ratios of outcomes by four SDoH domains: individual (eg, insurance), health care (eg, fragmented care), community (eg, neighborhood socioeconomic status), and health behaviors (eg, smoking). RESULTS: Among 531 screened studies, 31 meeting inclusion criteria and 13 with raw data were included in meta-analysis. Pooled odds of poor outcomes were 1.47-fold higher in patients with any adverse SDoH. Patients with adverse SDoH in individual and health care domains had 1.64-fold and 1.77-fold higher odds of poor outcomes. We found a multiplicative impact of having two or more adverse SDoH on LN outcomes. Black patients with public insurance and fragmented care had 12-fold higher odds of poor LN outcomes. CONCLUSION: Adverse SDoH is associated with poor LN outcomes. Having two or more adverse SDoH, specifically in different SDoH domains, had a multiplicative impact leading to worse LN outcomes, widening disparities.

Focused review: Clinico-neuropathological aspects of late onset epilepsies: Pathogenesis.

The aim of the present study was to review the current knowledge on the neuropathological spectrum of late onset epilepsies. Several terms including 'neuropathology*' AND 'late onset epilepsy' (LOE) combined with distinct neuropathological diagnostic terms were used to search PubMed until November 15, 2023. We report on the relevance of definitional aspects of LOE with implications for the diagnostic spectrum of epilepsies. The neuropathological spectrum in patients with LOE is described and includes vascular lesions, low-grade neuroepithelial neoplasms and focal cortical dysplasias (FCD). Among the latter, the frequency of the FCD subtypes appears to differ between LOE patients and those with seizure onset at a younger age. Neurodegenerative neuropathological changes in the seizure foci of LOE patients require careful interdisciplinary interpretation with respect to the differential diagnosis of primary neurodegenerative changes or epilepsy-related changes. Innate and adaptive neuroinflammation represents an important cause of LOE with intriguing therapeutic options.

A phased genome assembly of a Colombian Trypanosoma cruzi TcI strain and the evolution of gene families.

Chagas is an endemic disease in tropical regions of Latin America, caused by the parasite Trypanosoma cruzi. High intraspecies variability and genome complexity have been challenges to assemble high quality genomes needed for studies in evolution, population genomics, diagnosis and drug development. Here we present a chromosome-level phased assembly of a TcI T. cruzi strain (Dm25). While 29 chromosomes show a large collinearity with the assembly of the Brazil A4 strain, three chromosomes show both large heterozygosity and large divergence, compared to previous assemblies of TcI T. cruzi strains. Nucleotide and protein evolution statistics indicate that T. cruzi Marinkellei separated before the diversification of T. cruzi in the known DTUs. Interchromosomal paralogs of dispersed gene families and histones appeared before but at the same time have a more strict purifying selection, compared to other repeat families. Previously unreported large tandem arrays of protein kinases and histones were identified in this assembly. Over one million variants obtained from Illumina reads aligned to the primary assembly clearly separate the main DTUs. We expect that this new assembly will be a valuable resource for further studies on evolution and functional genomics of Trypanosomatids.

Comparative proteomic analysis of the hemolymph and salivary glands of Rhodnius prolixus and R. colombiensis reveals candidates associated with differential lytic activity against Trypanosoma cruzi Dm28c and T. cruzi Y.

BACKGROUND: Immune response of triatomines plays an important role in the success or failure of transmission of T. cruzi. Studies on parasite-vector interaction have shown the presence of trypanolytic factors and have been observed to be differentially expressed among triatomines, which affects the transmission of some T. cruzi strains or DTUs (Discrete Typing Units). METHODOLOGY/PRINCIPAL FINDINGS: Trypanolytic factors were detected in the hemolymph and saliva of R. prolixus against epimastigotes and trypomastigotes of the Y strain (T. cruzi II). To identify the components of the immune response that could be involved in this lytic activity, a comparative proteomic analysis was carried out, detecting 120 proteins in the hemolymph of R. prolixus and 107 in R. colombiensis. In salivary glands, 1103 proteins were detected in R. prolixus and 853 in R. colombiensis. A higher relative abundance of lysozyme, prolixin, nitrophorins, and serpin as immune response proteins was detected in the hemolymph of R. prolixus. Among the R. prolixus salivary proteins, a higher relative abundance of nitrophorins, lipocalins, and triabins was detected. The higher relative abundance of these immune factors in R. prolixus supports their participation in the lytic activity on Y strain (T. cruzi II), but not on Dm28c (T. cruzi I), which is resistant to lysis by hemolymph and salivary proteins of R. prolixus due to mechanisms of evading oxidative stress caused by immune factors. CONCLUSIONS/SIGNIFICANCE: The lysis resistance observed in the Dm28c strain would be occurring at the DTU I level. T. cruzi I is the DTU with the greatest geographic distribution, from the south of the United States to central Chile and Argentina, a distribution that could be related to resistance to oxidative stress from vectors. Likewise, we can say that lysis against strain Y could occur at the level of DTU II and could be a determinant of the vector inability of these species to transmit T. cruzi II. Future proteomic and transcriptomic studies on vectors and the interactions of the intestinal microbiota with parasites will help to confirm the determinants of successful or failed vector transmission of T. cruzi DTUs in different parts of the Western Hemisphere.

Improvement in Cutaneous Lupus Erythematosus After Twenty Weeks of Belimumab Use: A Systematic Review and Meta-Analysis.

OBJECTIVE: Cutaneous lupus erythematosus (CLE), with or without systemic lupus erythematosus (SLE), can be debilitating and cause psychological distress. Belimumab, a monoclonal antibody that inhibits B cell activation, is a Federal Drug Administration-approved SLE medication, but less is known on its use in CLE. Moreover, the time to response after starting belimumab in CLE is unknown, which may lead to premature discontinuation in the absence of early perceivable benefits. Thus, the objectives of this meta-analysis were to examine the efficacy of belimumab, as well as the time to response after starting belimumab in patients with CLE with or without SLE. METHODS: A comprehensive literature search was performed to include studies that examined clinical response in patients with CLE with or without SLE receiving belimumab. A clinical response at 52 weeks in belimumab users versus nonusers was summarized in a random-effects model. Additionally, we calculated the pooled odds ratio (OR) for each consecutive 4-week observation interval to identify time to a clinical response in CLE with or without SLE after starting belimumab. RESULTS: Among 747 screened studies, 14 were included. The pooled odds of clinical response at 52 weeks in belimumab users were 44% higher compared to nonusers (OR 1.44 [95% confidence interval (95% CI) 1.20-1.74], I2  = 0%). A clinical response was first noted after 20 weeks of starting belimumab (OR 1.35 [95% CI 1.01-1.81], I2  = 0%), with a sustained clinical response through 1 year. CONCLUSION: The findings support belimumab as an effective therapy for CLE with SLE. Likewise, the findings inform patient counseling regarding estimates of 20 weeks to achieve a response.

Utilisation of cardiovascular preventive services in a rheumatoid arthritis population-based cohort.

OBJECTIVES: The objective is to examine utilisation of cardiovascular preventive services in patients with rheumatoid arthritis (RA), compared with a non-RA population, and to examine cardiovascular disease (CVD) screening rates among RA patients without diabetes mellitus (DM), hypertension or hyperlipidaemia to non-RA patients with one of these diagnoses. METHODS: All ≥18-year-old patients with an RA diagnosis living in one of eight Minnesota counties on 1 January 2015 were included and matched (1:1) by sex, age and county to non-RA comparators. Rates of screening for CVD risk factors, including DM (ie, glucose), hypertension (ie, blood pressure) and hyperlipidaemia (ie, lipids), were compared between groups using Cox models. RESULTS: The study included 1614 patients with RA and 1599 non-RA comparators. DM screening was more common among patients with RA (HR: 1.10, 95% CI: 1.01 to 1.19), as was hypertension screening (HR: 1.37, 95% CI: 1.24 to 1.52). Hyperlipidaemia screening in RA was similar to comparators (HR: 0.99, 95% CI: 0.89 to 1.10). Conversely, patients with RA and no CVD risk factors had a lower probability of undergoing diabetes (HR: 0.67, 95% CI: 0.57 to 0.78) and hyperlipidaemia screening (HR: 0.65, 95% CI: 0.54 to 0.79) than non-RA patients with only one CVD risk factor diagnosis. Hypertension screening was similar between both groups. CONCLUSIONS: RA patients undergo CVD preventive screening at rates at least comparable to the general population. However, patients with RA as their sole CVD risk factor were less likely to undergo screenings, despite an equivalent-to-higher risk as the traditional CVD risk factors. These findings demonstrate opportunities for improvement of RA patient care.

Highly dynamic inflammatory and excitability transcriptional profiles in hippocampal CA1 following status epilepticus.

Transient brain insults including status epilepticus (SE) can initiate a process termed 'epileptogenesis' that results in chronic temporal lobe epilepsy. As a consequence, the entire tri-synaptic circuit of the hippocampus is fundamentally impaired. A key role in epileptogenesis has been attributed to the CA1 region as the last relay station in the hippocampal circuit and as site of aberrant plasticity, e.g. mediated by acquired channelopathies. The transcriptional profiles of the distinct hippocampal neurons are highly dynamic during epileptogenesis. Here, we aimed to elucidate the early SE-elicited mRNA signature changes and the respective upstream regulatory cascades in CA1. RNA sequencing of CA1 was performed in the mouse pilocarpine-induced SE model at multiple time points ranging from 6 to 72 h after the initial insult. Bioinformatics was used to decipher altered gene expression, signalling cascades and their corresponding cell type profiles. Robust transcriptomic changes were detected at 6 h after SE and at subsequent time points during early epileptogenesis. Major differentially expressed mRNAs encoded primarily immediate early and excitability-related gene products, as well as genes encoding immune signalling factors. Binding sites for the transcription factors Nfkb1, Spi1, Irf8, and two Runx family members, were enriched within promoters of differentially expressed genes related to major inflammatory processes, whereas the transcriptional repressors Suz12, Nfe2l2 and Rest were associated with hyperexcitability and GABA / glutamate receptor activity. CA1 quickly responds to SE by inducing transcription of genes linked to inflammation and excitation stress. Transcription factors mediating this transcriptomic switch represent targets for new highly selected, cell type and time window-specific anti-epileptogenic strategies.

Venous thrombosis, thromboembolism, biomarkers of inflammation, and coagulation in coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with abnormal inflammatory and coagulation markers, potentially mediating thrombotic events. Our objective was to investigate the incidence, time course, laboratory features, and in-hospital outcomes of COVID-19 patients with suspected venous thromboembolism (VTE). METHODS: A retrospective observational cohort study was conducted of patients hospitalized with COVID-19 who had undergone ultrasound imaging for suspected VTE from March 13 to May 18, 2020. The medical records of the included patients were reviewed for D-dimer, fibrinogen, prothrombin time, partial thromboplastin time, platelet count, C-reactive protein (CRP), and high-sensitivity troponin T at admission and at up to seven time points before and after ultrasound examination. The clinical outcomes included superficial venous thrombosis, deep vein thrombosis, pulmonary embolism, intubation, and death. Mixed effects logistic, linear, and Cox proportional hazards methods were used to evaluate the relationships between the laboratory markers and VTE and other in-hospital outcomes. RESULTS: Of 138 patients who had undergone imaging studies, 44 (31.9%) had evidence of VTE. On univariable analysis, an elevated admission CRP (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.09; P = .02; per 10-U increase in CRP), platelet count (OR, 1.48; 95% CI, 1.04-2.12; P = .03; per 1000-U increase in platelet count), and male sex (OR, 2.64; 95% CI, 1.19-5.84; P = .02), were associated with VTE. However only male sex remained significant on multivariable analysis (OR, 2.37; 95% CI, 1.01-5.56; P = .048). The independent predictors of death included older age (hazard ratio [HR], 1.04; 95% CI, 1.00-1.07; P = .04), active malignancy (HR, 4.39; 95% CI, 1.39-13.91; P = .01), elevated admission D-dimer (HR, 1.016; 95% CI, 1.003-1.029; P = .02), and evidence of disseminated intravascular coagulation (HR, 4.81; 95% CI, 1.76-13.10; P = .002). CONCLUSIONS: Male sex, elevated CRP, and elevated platelet count at admission were associated with VTE on univariable analysis. However, only male sex remained significant on multivariable analysis. Older age, active malignancy, disseminated intravascular coagulation, and elevated D-dimer at admission were independently associated with death for patients hospitalized with COVID-19.