The University of Texas Health Science Center at Houston
Recent publications
Pain is a multifactorial debilitating condition associated with some psychiatric comorbidities such as generalized anxiety and depression. Concerning pharmacological treatment, which is often inefficient or associated with intense side effects, the physical and social context may be fundamental for patient's health improvement. In this sense, we sought to assess the impact of an enriched environment (EE) on neuropathic pain (NP) and depression comorbid. For this purpose, mice exposed to EE or non-enriched conditions for three weeks were submitted to either a chronic constriction injury (CCI) of the ischiadicus nervus or a sham procedure. After three weeks of EE or non-enriched exposition, allodynia (recorded by von Frey and acetone tests), hyperalgesia (recorded by hot plate test), despair behavioral response (recorded by tail suspension test), and apathy (recorded by sucrose spray test) were evaluated. Mice submitted to CCI procedure showed increased rates of hyperalgesia and allodynia, as well as depression-like behaviors compared to the sham procedure-submitted mice. Exposure to EE significantly increased pain thresholds and significantly diminished depression-related behaviors. These findings suggest that the sensory, physical, and social context can be an extra tool for controlling not only sensory-discriminative pain but also emotional pain-related psychiatric comorbidities, such as depression.
Background Rapid Whole Genome Sequencing (rWGS) is increasingly being used in neonatal intensive care units, as there is growing evidence that rare singe gene disorders present in the neonatal period and early identification can change management. While the diagnostic utility is increased with this broad testing, the possibility of unexpected findings also increases significantly. Here, we present a patient found to have three distinct genetic conditions through rWGS testing, with significant psychosocial and health consequences. Methods and Results This case report describes a patient who was identified with a form of chondrodysplasia punctata, as well as incidental findings of MECP2‐related disorder and Jacobs' syndrome. To our knowledge, this is one of the first documented cases of triple genetic diagnoses in the literature, underscoring the expanding clinical utility of rWGS. Conclusion Our patient represents a unique example of the utility of rWGS in the NICU setting. As two of the three conditions were unexpected results, his case is an important reminder of the possibility of unexpected findings for both providers and families. His case demonstrates the importance of pretest counseling and consenting processes, particularly in an acute setting. It also will add to our understanding of MECP2 variant presentations in males in the future.
Prior research suggests that technical assistance which includes one-on-one, individualized support, guidance, and assistance is necessary to promote high-quality implementation of evidence-based interventions. However, this area lacks measures. This paper uses a mixed methods and community-engaged approach to develop and then evaluate a standardized measure of the collaborative working relationship between technical assistance providers and coalitions/coalition leaders. For measure development, researchers interviewed eight coalition leaders and eight coalition technical assistance providers about their experience providing or receiving technical assistance, using a human-centered design approach. A heat-mapping technique used with the interview data identified 11 themes related to the provision of high-quality technical assistance. Researchers then created survey items through an iterative process. After multiple rounds of revision and feedback with coalition leaders and coalition and technical assistance researchers, the reliability of seven of the constructs was piloted with 52 coalition leaders. The seven constructs included the following: competence and autonomy support, responsiveness, authentic and meaningful participation, co-creation, trust and rapport, compliance, and negative interactions. Researchers used Cronbach’s Alphas and correlational analyses to further refine the scales. Empirical results mapped well onto prior theoretical work and suggested that the collaborative working relationship is a multi-dimensional construct. This research moves prevention research methods and measurement development into a more community-engaged, stakeholder-involved approach.
Background Stapled and hand-sewn techniques dominate gastrointestinal anastomotic procedures. These techniques are effective but not without flaws. Retained foreign bodies, pathways from mucosa to serosa, and increased scar tissue are some of the drawbacks, and can lead to postoperative complications. The GI Windows Flexagon™ system utilizes self-forming magnets (SFM’s) to create anastomoses by compression, sealing serosa to serosa, leaving no foreign bodies. Combining the Flexagon™ SFM with the OTOLoc™ device (implant with a central lumen which provides radial support to the enterotomies), enables immediate flow through the anastomosis and facilitates creation of enteral bypass procedures unique to this technology. We sought to compare the safety and efficacy of the GI Windows Flexagon™ and OTOLoc™ technologies against conventional stapling. Methods A preclinical study was conducted on 14 Yorkshire swine to compare laparoscopic magnetic and stapled duodenoileostomies and jejunojejunostomies. Study endpoints included: adverse or serious adverse events, anastomotic burst pressure, adhesions, histopathology, and bacterial ingress. A Likert scale was used to assess the usability of the devices. Results All procedures were successfully completed via laparoscopic approach; no adverse or serious adverse events were observed at the 42-day endpoint. All SFM’s were expelled in less than 20 days. Average anastomotic burst pressure was 129.2 mmHg for SFM compared to 79.4 mmHg in stapled controls. Adhesion scores were similar between groups. Histopathology revealed that magnetic anastomoses have less intestinal wall distortion, fewer signs of chronic inflammation, and no bacterial ingress. The usability of all devices was reported as “Easy” or “Very Easy.” Conclusion GI Windows magnetic compression anastomoses creation in this porcine model revealed an overall ease of use, all while demonstrating procedural feasibility, safety, and clinical effectiveness. Surprisingly, in nearly all results assessed, SFM anastomoses were found to be comparable to the control stapled anastomoses in regard to structural, physiological, and histological endpoints.
Structural information on channelrhodopsins’ mechanism of light-gated ion conductance is scarce, limiting its engineering as optogenetic tools. Here, we use single-particle cryo-electron microscopy of peptidisc-incorporated protein samples to determine the structures of the slow-cycling mutant C110A of kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) in the dark and upon laser flash excitation. Upon photoisomerization of the retinal chromophore, the retinylidene Schiff base NH-bond reorients from the extracellular to the cytoplasmic side. This switch triggers a series of side chain reorientations and merges intramolecular cavities into a transmembrane K⁺ conduction pathway. Molecular dynamics simulations confirm K⁺ flux through the illuminated state but not through the resting state. The overall displacement between the closed and the open structure is small, involving mainly side chain rearrangements. Asp105 and Asp116 play a key role in K⁺ conductance. Structure-guided mutagenesis and patch-clamp analysis reveal the roles of the pathway-forming residues in channel gating and selectivity.
Social constructivists have significantly advanced our understanding of how digital technologies give rise to different forms of organizing between organizations but less is known about similar dynamics within the organizations. Therefore, we investigated the implementation of telehealth within an academic health center during the COVID-19 pandemic. We developed a grounded model of the integration of work with technology based on 54 interviews with 27 healthcare professionals. The model comprises two moments. During the moment of enactment, four connected themes—material affordances, material constraints, embodiment, and relationality—emerged. In the subsequent moment of variation, two themes—stabilization and closure—determined the bifurcation into technology-adjacent and technology-distant organizing. Technology-adjacent organizing involves a telemedicine team continuing to treat patients with serious mental illness admitted to remote state hospitals. Technology-distant organizing entails the redeployment of telehealth in the focal psychiatric hospital for future disasters. The model contributes to scholarship at the intersection of institutional theory and information studies.
Schizophrenia is a chronic psychiatric disorder characterized by a variety of symptoms broadly categorized into positive, negative, and cognitive domains. Its etiology is multifactorial, involving a complex interplay of genetic, neurobiological, and environmental factors, and its neurobiology is associated with abnormalities in different neurotransmitter systems. Due to this multifactorial etiology and neurobiology, leading to a wide heterogeneity of symptoms and clinical presentations, current antipsychotic treatments face challenges, underscoring the need for novel therapeutic approaches. Recent studies have revealed differences in the gut microbiome of individuals with schizophrenia compared to healthy controls, establishing an intricate link between this disorder and gastrointestinal health, and suggesting that microbiota-targeted interventions could help alleviate clinical symptoms. Therefore, this meta-analysis investigates whether gut microbiota manipulation can ameliorate psychotic outcomes in patients with schizophrenia receiving pharmacological treatment. Nine studies (n=417 participants) were selected from 81 records, comprising seven randomized controlled trials and two open-label studies, all with a low risk of bias, included in this systematic review and meta-analysis. The overall combined effect size indicated significant symptom improvement following microbiota treatment (Hedges' g = 0.48, 95% CI = 0.09 to 0.88, p = 0.004, I2 = 62.35%). However, according to Hedges' g criteria, the effect size was small (approaching moderate), and study heterogeneity was moderate based on I2 criteria. This review also discusses clinical and preclinical studies to elucidate the neural, immune, and metabolic pathways by which microbiota manipulation, particularly with Lactobacillus and Bifidobacterium genera, may exert beneficial effects on schizophrenia symptoms via the gut-brain axis. Finally, we address the main confounding factors identified in our systematic review, highlight key limitations, and offer recommendations to guide future high-quality trials with larger participant cohorts to explore microbiome-based therapies as a primary or adjunctive treatment for schizophrenia.
831 Background: Systemic treatment of metastatic appendiceal adenocarcinoma (AA) has been challenging due to a lack of well-established AA chemotherapy regimens and historical reliance on colorectal cancer (CRC) protocols. In the United States, but less commonly in Europe, bevacizumab is frequently incorporated in treatment of AA given its approved use for CRC. However, previously there have been no studies evaluating if there is a survival benefit attributable to bevacizumab in patients with AA. Methods: The Palantir Foundry system was used to extract data from the MD Anderson Cancer Center (MDA) electronic medical record for patients with biopsy-proven AA who received chemotherapy at MDA from 2015 to 2024. Only patients with complete staging and histopathology data were included in the analysis. Results: We identified 203 patients with AA who received chemotherapy at MDA and had complete tumor data. Of these, 43% (n=87) received bevacizumab at some point in their treatment. Patients who received bevacizumab were demographically similar to patients who received non-bevacizumab chemotherapy in terms of age at diagnosis, race, and sex; mucinous histology was more frequent in the bevacizumab cohort (52%, n=45 vs. 39%, n=45 in non-bevacizumab cohort). The 87 patients who received bevacizumab were treated with 1-6 lines of therapy per patient (mean = 1.57). The most frequently used bevacizumab-containing regimens were FOLFOX + bevacizumab (34%, n=46), FOLRIRI + bevacizumab (29%, n=40), 5-FU + bevacizumab (15%, n=21), and atezolizumab + bevacizumab (11%, n=15), with less common irinotecan + bevacizumab, TAS-102 + bevacizumab, and FOLFOXIRI + bevacizumab. Three regimens containing bevacizumab were discontinued due to complications: one instance of hand-foot syndrome attributed to xeloda, one instance of cardiomyopathy attributed to immunotherapy, and one bowel perforation with abdominal wall abscess attributed to bevacizumab. To determine if bevacizumab was associated with overall survival (OS) benefit we performed Kaplan-Meier analysis, with OS calculated from start of first line chemotherapy to death, in patients with metastatic AA who received either 5-FU doublet therapy alone or 5-FU doublet therapy with bevacizumab. Patients who received bevacizumab trended toward better OS (median 52 vs 25 months for doublet therapy alone, HR: 0.53, p= 0.059). The effect of bevacizumab was particularly notable in patients with signet ring cell histology; where bevacizumab use was associated with significantly longer OS (median OS 50 vs 14 months for doublet therapy alone, HR: 0.24, p= 0.034). Conclusions: Bevacizumab is frequently added to cytotoxic chemotherapy in the treatment of AA. These retrospective data suggest an OS benefit to adding bevacizumab to doublet chemotherapy, particularly in the case of signet ring cell histology.
90 Background: Appendiceal adenocarcinoma incidence rates are increasing across all age groups, sexes and histological subtypes in the United States. Birth cohort patterns of appendiceal adenocarcinomas can provide us with new, etiologic clues into these rising rates but have not been examined for this rare malignant tumor type. We estimated appendiceal adenocarcinoma incidence rates across birth cohorts in the United States. Methods: Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program data from eight population-based cancer registries, we identified a total of 4,858 persons aged 20+ years when diagnosed with a pathologically-confirmed primary appendiceal adenocarcinoma (non-mucinous, mucinous, goblet cell, signet ring cell carcinoma) between 1975 and 2019. Birth cohorts (1900-1904 to 1990-1994) were created using five-year age groups and time periods. The ratio of age-specific incidence rates was estimated in each birth cohort relative to the 1945-1949 birth cohort and reported as incidence rate ratios (IRRs) with 95% confidence intervals (CI). Results: Compared to persons born in 1945-1949, appendiceal adenocarcinoma incidence rates more than tripled among persons born in 1980-1984 (IRR 3.41, 95%CI 2.54-4.56) and quadrupled among persons born in 1985-1989 (IRR 4.62, 95%CI 3.12-6.82). For all tumor histological types, age-specific appendiceal adenocarcinoma incidence rates increased across successive birth cohorts after 1945-1949—although to varying degrees reported across histological types (e.g., 1980-1984: mucinous adenocarcinoma: IRR 2.71, 95% CI 1.73-4.26; non-mucinous adenocarcinoma: IRR 2.60, 95% CI 1.46-4.63; goblet cell adenocarcinoma: IRR 4.95, 95% CI 2.77-8.85). Conclusions: There are strong, yet distinct birth cohort effects for appendiceal adenocarcinomas across histological subtypes that remain unexplained. These patterns signal that recent exposure changes may be influencing this increasing disease risk for Generation X and Millennials now entering mid-adulthood. With the trend toward more non-operative management of appendicitis, another significant consideration for providers is to keep occult appendiceal tumors in the differential diagnosis of patients who present in this way. The current absence of appendiceal cancer prevention and screening modalities emphasizes the importance of efforts to support earlier detection in a rare malignancy where clinical trials have been historically very limited. Moreover, as similar trends have been reported in other gastrointestinal cancers, this is also suggestive of potential shared exposures contributing to this rising cancer burden across generations.
819 Background: Incidence rates of rare appendiceal cancers are increasing across the United States. Although this is suggestive of a growing population of appendiceal cancer survivors over time, the risk of second primary cancers specific to patients with a first primary appendiceal adenocarcinoma remains unknown. Methods: We conducted a population-based study of adults (age ≥18 years) diagnosed with a first primary appendiceal adenocarcinoma from 1992 to 2021, using data from the Surveillance, Epidemiology, and End Results (SEER) Program. We estimated cumulative incidence of second primary cancer, defined as any primary cancer diagnosed at least 3 months after appendiceal adenocarcinoma, with Fine and Gray methods to account for the competing risk of death. For comparison to the general population, we also estimated standardized incidence ratios [SIRs], or the observed number of second cancers relative to the expected number based on age-, sex-, and race-specific incidence rates. Results: A total of 5,827 adults diagnosed with a first primary appendiceal adenocarcinoma (mean age 58.0 years; 51.8% female; 68.5% non-Hispanic White) were identified during the study period, of whom 418 developed a second primary cancer. The most common types of second primary cancer were prostate (17.7%), colorectal (14.4%), female breast (10.5%), lung (8.4%), and melanoma (6.0%). At 10 and 20 years after appendiceal adenocarcinoma diagnosis, the cumulative incidence of second primary cancer was 7.5% (95%CI 6.8%-8.4%) and 11.7% (95%CI 10.5%-12.9%), respectively. Cumulative incidence significantly differed by sex (p<0.01) and age at appendiceal adenocarcinoma diagnosis (early-onset [age<50] vs late-onset; p<0.01). For example, at 10 years post-diagnosis, the cumulative incidence of second primary cancer was 6.4% (95%CI 5.4%-7.4%) for females and 8.8% (95%CI 7.6%-10.1%) for males. The overall SIR for any second primary cancer was 1.12 (95%CI, 1.02-1.23)—corresponding to 14.8 excess cancers per 10,000 person-years. SIRs for common types of second primary cancers were: 1.07 (95%CI 0.84-1.35) for prostate, 2.12 (95%CI 1.63-2.70) for colorectal, 0.91 (95%CI 0.68-1.19) for female breast, 0.81 (95%CI 0.58-1.09) for lung, and 1.20 (95%CI 0.79-1.73) for melanoma. Conclusions: Approximately one in every 13 adults diagnosed with a first primary appendiceal adenocarcinoma in the United States will be diagnosed with a second primary cancer within 10 years. After diagnosis of an appendiceal adenocarcinoma, patients have a 12% excess incidence in second primary cancers and double the excess incidence in second primary colorectal cancers compared to the general population. Implementation of cancer prevention and early detection strategies (e.g., colonoscopy screening, genetic testing) for patients with an appendiceal adenocarcinoma is a clinical priority.
Introduction: The prevalence of social isolation (SI) increases with aging and contributes to poor health outcomes and increased risk of cognitive impairment, especially in Aβ-related diseases. Cerebral amyloid angiopathy (CAA) is characterized by amyloid β (Aβ) deposition in the cortical and leptomeningeal vessels, and is a leading cause of hemorrhagic stroke and age-related cognitive impairment. How social isolation affects vascular amyloid deposition, cognitive decline and social behavior in CAA is unknown. Methods: TgSwDI mice carrying Swedish, Dutch, and Iowa mutations of human amyloid precursor protein were used as a CAA model. Male and female C57BL/6 wildtype (WT) and CAA mice were randomly assigned to pair housing (PH) or SI at 3 months of age. Affective and social behaviors were assessed at baseline and every 3 months thereafter using the tail suspension test (TST) and three-chamber social interaction test. At 9 months post-SI, cognitive behaviors and general well-being were measured using fear conditioning (FC) and the nesting test, respectively. Body weights were recorded, and white adipocyte size was measured using immunostaining. Results: SI led to increased immobility in the TST at 3- and 6-months post-SI in both male and female WT and CAA mice, suggesting depressive-like behavior (n=5-8/grp, p<0.05). Isolated CAA mice displayed greater cognitive deficits in FC, while only male WT SI mice showed impaired cognition (n=5-12/grp, p<0.005). Sex differences in social behavior were observed in isolated CAA mice. Specifically, at 6 months post-SI, female CAA mice displayed deficits in sociability and social novelty (n=4-9/grp, p<0.05), which was not seen in male CAA mice. SI negatively impacts the general well-being in both male WT and CAA SI animals (n=5-12/grp, p<0.005). Preliminary findings showed increased white adipocyte size in male WT SI mice with a similar trend in male CAA SI animals, pointing to potential metabolic effects of isolation. Conclusion: SI induced cognitive decline in both male and female CAA mice. Behavioral differences between sexes were noted in CAA mice including nesting ability, sociability, and depressive-like behaviors. Further research is needed to determine the cellular and molecular mechanism underlying SI-induced metabolic changes in CAA.
Introduction: Randomized clinical trials have demonstrated efficacy and safety of endovascular thrombectomy (EVT) among patients presenting up to 24 hours of last known well (LKW). Recent reports have suggested EVT could result in better functional outcomes with acceptable risk profile even in patients presenting beyond 24 hours of LKW, but exploration of the role of EVT in elderly patients presenting beyond 24 hours is limited. Methods: We aimed to evaluate functional and safety outcomes for EVT in patients with age ≥80y with a large vessel occlusion (LVO) beyond 24 hours of LKW, from a pooled, international cohort (17 centers across US, Spain, Australia and New Zealand) between 7/2012 and 12/2021. Primary outcome was a shift on modified Rankin Scale score at 90-day follow-up. Results: Of 301 included, 88 (53 EVT, 35 medical management MM) were aged ≥80y, with 57 females and 21 nonagenarians. Median(IQR) NIHSS - 17.5 (11-22),CT ASPECTS - 7(4-9), ischemic core 5.5 (0-26) ml. Overall, as age increased, clinical outcomes worsened (acOR: 0.64, 95% CI: 0.55-0.74, p<0.001 per 10 year increment). However, EVT was associated with a shift towards better functional outcome among patients with age≥80y (acOR: 8.31, 95% CI:2.80-24.68, p<0.001) and among patients with age<80y (acOR: 2.11, 95% CI: 1.22-3.66, p=0.008), with a significant interaction (p-int:0.047 – fig1) suggesting higher improvement within octogenarians. Estimates of Functional independence (EVT: 27% vs MM: 6%, aOR: 11.86, 95% CI: 1.75-80.28, p=0.011) and mortality (EVT: 42% vs MM: 71%, aOR: 0.16, 95% CI: 0.05-0.52, p=0.003) also favored EVT, with similar results obtained using inverse probability of treatment weights [Table 1]. 4 patients within EVT arm and no patients within MM arm developed symptomatic ICH. Among octogenarians receiving EVT, lower presentation NIHSS (aOR: 0.77, 95% CI: 0.64-0.92, p=0.003 per point increment) and presence of M2 occlusion (aOR: 11.01, 95% CI: 1.15-105.36, p=0.037 were independently associated with functional independence at 90-day follow-up), but not time to procedure (aOR: 0.99, 95% CI: 0.96-1.02, p=0.64, fig2). Conclusions: In a pooled international cohort of octogenarians who presented beyond 24 hours with an LVO, EVT was associated with better functional outcomes, higher functional independence and lower mortality. Lower stroke severity and presence of M2 occlusion were independently associated with functional independence at 90-day after EVT.
Background: Obtaining timely informed consent is a key barrier in acute ischemic stroke (AIS) clinical trial recruitment. Electronic consent (eConsent) allows electronic delivery and documentation of the informed consent process which may optimize recruitment. eConsent utilization in AIS clinical trials, however, is limited and understudied. We report eConsent adoption in MOST, a Phase III AIS clinical trial, and studied the impact on recruitment. Methods: Study databases were reviewed to determine informed consent modality for each participant: paper-in person, paper-remote, eConsent-in person, eConsent-remote (remote consent occurred when the study team and participant/legally authorized representative were in different physical locations). eConsent adoption trends, participant demographics, and diversity were reported using descriptive statistics. We utilized chi-square and Kruskal Wallis tests to compare individual site enrollment, remote consent utilization, baseline-neuroimaging-to-randomization times, data clarification requests (DCRs), and reportable unanticipated events (UEs), across consent modalities. Results: eConsent was utilized for 173 (33.7%) out of 514 participants. 32 of 57 sites (56.1%) utilized eConsent at least once: those sites had higher median enrollment than non-eConsent sites (7.5 [IQR 5-17] vs 3 [IQR 2-4], p<0.001). eConsent was completed remotely more frequently than paper consent (46.2% vs 1.2%, p<0.001). Participant diversity and baseline-neuroimaging-to-randomization times were similar between eConsent-in person and paper-in person consent (median 58.5 min [IQR 46.5-72.5] vs median 55 min [IQR 39-70]). Consent documentation adherence was superior with eConsent-in person compared to paper-in person including decreased DCRs (44 vs 81 per 100 participants, p<0.001) and reportable UEs (6 vs 25 per 100 participants, p<0.001). Conclusion: eConsent in MOST was associated with higher individual site enrollment, higher remote consent rates, and improved consent documentation adherence over paper consent. Our study outlines the potential advantages of eConsent adoption in future AIS clinical trials and stroke research networks.
Introduction: VWF is an endothelial protein with known roles in hemostasis and thrombosis. We previously demonstrated abnormal deposition of VWF in the mural layer of leptomeningeal collateral arterioles (LMCs) during flow-induced outward remodeling. Additionally, LMC remodeling was attenuated in VWF KO mice, suggesting a modulating role for VWF. We now test the hypothesis that intramural VWF potentiates LMC remodeling in response to sustained increased luminal flow. Methods: VWF protein was infused into the cisterna magna (CM) of WT and VWF KO C57BL/6 mice (3-7 mos females) to deliver VWF to the perivascular space around the leptomeningeal arteries (2.5 mg/ml at 1 ul/min; 5-7ul total). To confirm successful delivery of VWF to the wall of the leptomeningeal vessels, brain surface preparations containing the cortical leptomeningeal vessels were “planed off” and evaluated for VWF and smooth muscle actin (SMA) immunofluorescence at one hour after VWF infusion (cohort 1). In a subsequent experiment, right common carotid artery ligation (rCCAL) was performed on VWF KO and WT mice to induce increased flow in collateral vessels supplying the right MCA territory (cohort 2). VWF or vehicle was injected via CM at 16 hours after the rCCAL. At 3 days post-rCCAL, the intact leptomeningeal vessel preparations were evaluated by immunofluorescence (Ki67&SMA) and morphometric analyses. Results: [Cohort 1] WT and VWF KO mice demonstrated exogenous VWF protein surrounding the leptomeningeal vessels and within the mural layer. VWF KO mice were used to distinguish between endogenous and exogenous VWF. [Cohort 2] At 3 days, rCCAL induced endothelial cell proliferation (Ki67+) and outward vascular remodeling of collateral vessels supplying rescue flow following carotid ligation. In the VWF infusion group, there was a significant increase in Ki67+ ECs, 14.1 ± 3.1 vs. 5.4 ± 1.2 per mm of vessel of the control group ( p = 0.042). In VWF KO mice, VWF infusion also increased the number of Ki67+ ECs, showing 18.3 ± 3.2 vs. 6.1 ± 2.8 per mm of vessel in the control group ( p < 0.0001). In both WT and VWF KO mice, VWF infusion promoted non-uniform LMC remodeling. Conclusions: Our study demonstrates that VWF in the vascular wall of LMCs potentiates the adaptive response to increased luminal flow, albeit with irregular resulting vascular morphology. These finding suggest that the presence of intramural VWF may contribute to abnormal vascular remodeling in the brain.
Stroke is the leading cause of serious long-term disability in the United States. Stroke recovery is greatly varied since the long term effect is determined by the site and size of the initial lesion. Specifically, post stroke motor impairments occur due to damage to the corticospinal tract and maladaptive upregulation of the cortico-reticulospinal tract. Transcranial direct current stimulation (tDCS) may be an effective treatment for stroke rehabilitation. However, conventional tDCS is limited by spatial resolution to precisely target a specific brain region. To improve its spatial resolution, this study used targeted high-definition tDCS (HD-tDCS) navigated by paired-pulse transcranial magnetic stimulation. In a double-blind randomized crossover study, stroke participants (n=12) had three visits 1) anodal HD-tDCS stimulation of the arm region of the primary motor cortex (M1) to improve function of the corticospinal tract in the lesioned hemisphere, 2) cathodal stimulation of the arm region of the dorsal premotor (PM) cortex to inhibit maladaptive use of the cortico-reticulospinal tract in the contralesional hemisphere, and 3) sham. The effect was measured by quantitative electroencephalogram (qEEG) metrics delta alpha ratio (DAR) and delta theta alpha beta ratio (DTABR), calculated from a pre and post 3-minute EEG. Acute changes in brain activity of these power bands have been associated with the severity of motor impairment post stroke. The results demonstrate that anodal (p=0.026) and cathodal (p=0.0108) stimulation significantly decreased the DAR compared to the sham. The reducation of DAR value is associated with the improvement of Fugl-Meyer Upper Extremity score. However, there were no significant differences found in the DTABR. These results indicate that both anodal and cathodal HD-tDCS may improve brain function following stimulation. However, future work is required on the use of qEEG metrics and its use as a marker of stroke recovery. This work is important as qEEG could be used as a more objective method, compared to clinical assessments, to track stroke rehabilitation.
Introduction: Complete reperfusion (TICI 2c/3) with the fewest number of passes remains the target for EVT techniques, but at present, rates remain relatively low. Prior studies have demonstrated that switching techniques between passes may improve rates of reperfusion. Here we assess the efficacy of technique switching after the first pass failed reperfusion in a large multi-center cohort. Methods: All consecutive patients treated with EVT from 12 centers across the US were prospectively collected between 10/2018 – 12/2021 (SVIN Registry). Patients were included if they underwent EVT for occlusion of the M1 or ICA-T. Exclusion criteria included incomplete data. EVT technique was categorized as Stent-Retriever (SR), Contact Aspiration (CA), or a Combined Technique (CT). The primary outcome was the likelihood of achieving TICI 2c/3 with or without switching the thrombectomy technique and was determined using multivariable logistic regression adjusted for the use of balloon guide catheter, occlusion location, age, and co-morbid medical conditions. Results: Among 2,891 patients in the SVIN registry included in this analysis, the median age was 69 years [IQR, 58-80], 49.9% were female and median NIHSS was 17 [IQR, 12-22]. Occlusion location was ICA-T in 18.4% and M1 in 81.6%. As shown in Figure 1a, for patients with ICA-T occlusions, first-pass TICI 2c/3 occurred in 32.7% with SR, 23% with CA, and 31.2% with CT. As shown in Figure 1b, for patients with M1 occlusions, first-pass TICI 2c/3 occurred in 37.7% with SR, 35.9% with CA, and 35.4% with CT. Switching from CA to SR or CT for the 2nd pass was associated with increased point estimates of 2nd pass TICI 2c/3 for patients with ICA-T occlusions (27% vs 12%, second pass SR vs. second pass CA, p=0.06). In multivariable logistic regression, odds of TICI 2c/3 were significantly greater (OR 3.7, CI 95% [1.1 – 12.4]) after switching to SR or CT after a failed first pass with CA in patients with ICA-T occlusion. Conclusions: Switching from CA to SR-based techniques was associated with improvement in TICI 2c/3 reperfusion rates among patients with Internal Carotid Artery Terminus occlusions.
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4,863 members
Dean Forrest Sittig
  • School of Biomedical Informatics
Anne Marie Krachler
  • Department of Microbiology and Molecular Genetics
David Morton Low
  • Division of Management, Policy and Community Health
Benson Mwangi
  • Department of Psychiatry and Behavioral Sciences
Leomar Y Ballester
  • Department of Pathology and Laboratory Medicine
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Houston, United States
Head of institution
Giuseppe N. Colasurdo, M.D.