Abstract only Background: We evaluated the cerebrovascular and neurological disease (CVND) burden among patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and ...leukoencephalopathy (CADASIL). Methods: Harmonized electronic medical record data from a global research network were utilized to identify diagnosed CADASIL patients. We compared demographics, risk factors, co-existing conditions, and outcomes for CADASIL patients with and without stroke sub-types (ischemic stroke IS, intracerebral hemorrhage ICH, subarachnoid hemorrhage SAH and transient ischemic attack TIA). Likelihood of stroke incidence and overall mortality associated with sex were computed. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: Between 2018 and 2020, 914 CADASIL patients were identified (Median (IQR) age: 60 (50 - 69) years, 61.3% females); of whom 596 (65.2%) had a stroke diagnosis. Among all CADASIL-Stroke patients, 89.4% had IS, which co-existed with TIAs in 27.7% and ICH / SAH in 6.2% (Figure). Among 30% and 71% of CADASIL-Stroke patients, the initial stroke event occurred before 50 and 65 years of age, respectively. In addition to a higher burden of hypertension, atrial fibrillation, hyperlipidemia, and diabetes; a higher proportion of CADASIL-Stroke patients (vs CADASIL-non-Stroke) had other co-existing neurological conditions, including migraines (36.7% vs 29.9%), cognitive impairment (38.8% vs 24.2%), epilepsy / seizures (18.6% vs 11.6%), and mood disorders (52.9% vs 40.9%). Adjusted for age and commodities, males had a higher risk of stroke (OR, CI: 1.37, 1.01 - 1.86) and also demonstrated higher overall mortality in a separate model additionally adjusted for stroke diagnoses (OR, CI: 2.72, 1.53 - 4.84). Conclusion: Given the high CVND burden; early genetic screening and targeted preventive strategies are warranted among patients with suspected CADASIL and other hereditary cerebral small vessel diseases.
Abstract only Background: The evidence of association between Intracerebral Hemorrhage (ICH) outcomes and hypercholesterolemia (HC) is equivocal. We provide nationwide estimates of ICH in-hospital ...mortality (IHM) among patients with HC, across race/ethnicity subgroups. Methods: In a pooled cross-sectional analysis of adult (≥ 18 years) primary ICH patients in the National Inpatient Sample (2004 - 2018), we used ICD 9 / 10 codes to identify patients with HC. We fit survey design multivariable logistic regression models to provide nationwide estimates of the association between IHM and HC as adjusted odds ratio (aOR) and 95% confidence interval (CI). Results: Among a total of 803,230 ICH hospitalizations, we identified 56,635 HC ICH patients. HC patients, compared to patients with no hypercholesterolemia (NHC), were older (72.3 vs. 68.7 years), had higher proportional (%) burden of diabetes (35.8 vs. 26.4), hypertension (90.0 vs. 80.9), obesity (9.2 vs. 8.0), atrial fibrillation (22.1 vs. 19.3) and past / current use of anticoagulation (11.9 vs. 9.8). However, HC patients (vs. NHC) were less likely to have extreme loss of function (21.4 vs. 28.7) or receive invasive treatment, including extra-ventricular drain (5.2 vs. 7.6), invasive ventilation (5.7 vs. 7.9), tracheostomy (2.4 vs. 4.2) and gastric tube placement (6.0 vs. 8.5). Overall, and non-Hispanic whites (NHW), non-Hispanic black and Hispanic, HC patients (vs. NHC) had lower IHM (aOR, CI for overall effect: 0.85, 0.81 - 0.90) (Figure 1). The HC - IHM association was significantly modified by age among NHW, whereby the likelihood of IHM among HC (vs. NHC) significantly increased with advancing age (aOR, CI: 1.01, 1.00 - 1.02) (Figure 2). Conclusion: HC is associated with lower ICH severity and IHM, albeit with significant race/ethnic variations. Further evaluation of potential role of genetic, environmental and treatment factors, across race/ethnicity sub-groups, in the relationship between HC and ICH outcomes is warranted.
Abstract only Background: Relationships between neighborhood socioeconomic deprivation (NSD) and Intracerebral hemorrhage (ICH) outcomes are not well characterized. We sought to evaluate the impact ...of NSD on ICH outcomes and assessed mediating pathways for association between NSD and poor outcomes. Methods: Clinical data were extracted from the electronic medical records and 90-day modified Rankin Scale (mRS) scores were obtained from a prospectively collected stroke registry at a large healthcare system. Presentation NIHSS score was used to assess ICH severity. Exact patient addresses were geocoded, and state-level Area Deprivation Index (ADI) was calculated, with high NSD (H-NSD) categorized as top 15% of ADI scores. The outcome was severe disability or death (SDD) (mRS ≥ 4). Age-adjusted logistic regression models were fitted, and mediation analyses were performed utilizing structured equation modeling. Odds ratios (OR) and 95% Confidence Intervals (CI) are reported. Results: Final analyses included 486 patients with complete data (mean age: 65.6 years, 45.9 % female, 28.8% non-Hispanic Black, 20.2% Hispanic, median presentation NIHSS: 10, and median 90-day mRS 4). In separate age-adjusted models, both high NIHSS scores (OR, CI: 1.24, 1.20 - 1.29) and H-NSD (OR, CI: 1.59, 1.02 - 2.46) were associated with SDD. In a mediation analysis, H-NSD significantly contributed to higher NIHSS scores (OR, CI: 14.30, 1.44 - 141.61) and in turn higher NIHSS scores were significantly associated with SDD (OR, CI: 1.03, 1.03 - 1.04). In this analysis, H-NSD did not retain a significant direct effect on SDD (OR, CI: 1.38, 0.96 - 1.12) and was instead fully mediated by high NIHSS scores (Figure 1). Discussion: Our analyses uniquely identify higher stroke severity as a potential causal pathway between NSD and poor ICH outcomes. These findings warrant comprehensive understanding of factors that may predispose the disadvantaged to experience higher ICH severity and greater neurological deficit.
Abstract only Background: Impact of socioeconomic disadvantage on outcomes among acute ischemic stroke (AIS) patients has not been well characterized. Methods: Clinical data on AIS patients were ...extracted from electronic medical records and 90-day modified Rankin Scale (mRS) scores were collected as a part of prospective stroke registry. Exact patient addresses were geocoded, and state-level Area Deprivation Index (ADI) ranks were categorized as low, medium, high. Patients with a 90-day mRS score ≥ 4 were categorized as severe disability or death (SDD). Logistic regression models (adjusted for treatment with intravenous tissue plasminogen activator or mechanical thrombectomy, age, sex, race/ethnicity, insurance, prior stroke, vascular risk factors) were fitted to compute odds ratios (OR) and 95% confidence intervals (CI) for total effect of high ADI on SDD. Structural equation modeling was used to assess mediation effects of stroke severity as measured by National Institutes of Health Stroke Scale (NIHSS). Results: Between May 2016 and Apr 2021, a total of 2,900 AIS patients (mean age: 68.5 years; 50.1% male; 28.4% non-Hispanic Black; 12.9% Hispanic) with complete outcomes data were included. In an adjusted model, high ADI was significantly associated with SDD (OR, CI: 1.14, 1.02-1.28). In the mediation analysis, patients in higher ADI neighborhoods had a 28% increased likelihood of having higher NIHSS (OR: 1.28, CI: 1.15-1.44). Likewise, higher NIHSS was associated with SDD (OR: 7.10, CI: 5.96-8.51). The effect of neighborhood disadvantage on SDD was fully mediated by NIHSS (average causal mediation effect of ADI on SDD: P=0.002), with 77% of the total effect pathway mediated through NIHSS. The proportions of 90-day mRS by ADI categories are reported (Figure). Conclusion: Neighborhood disadvantage leads to poor stroke outcomes mediated via stroke severity. Tracking social determinants of health may identify opportunities for reducing stroke related disability.
Abstract only Background: Delirium in-hospital (DIH) results in poor in-patient outcomes. However, it’s longer-term effects among intracerebral hemorrhage (ICH) patients are not well characterized. ...We sought to evaluate the association between DIH and 90-day readmission (RA) among primary ICH patients. Method: Clinical, imaging and outcomes data, from May 2016 to June 2021, were obtained from the Neurological Outcomes Registry for ICH (NEURO-RICH) ; an informatics pipeline across 7 comprehensive and primary stroke centers which implement protocolized delirium assessments via 4AT / CAM-ICU scales. Demographic (age, sex, race, ethnicity, marital status), Glasgow Coma Scale (GCS), systolic and diastolic blood pressure (S/DBP), sepsis, systemic inflammatory response syndrome, and comorbidity data were analyzed. Survival analysis for time-to-90-Day RA was performed with death modeled as a competing risk. Sub hazard ratios (SHR) and 95% confidence intervals (CI) are reported. Subgroup with imaging data (ICH score and cerebral small vessel disease) was analyzed. Results: Final analyses included 1,434 ICH patients (mean age: 66.0 years, 47.2% female, 24.8% non-Hispanic Black, 19.9% Hispanic, median GCS: 13.2, SBP: 163 mmHg). In the fully adjusted model, DIH was significantly associated with higher rates of 90-Day RA (SHR, CI: 2.24, 1.04 - 4.81) (Figure 1A). Anticoagulant therapy (1.36, 1.03 - 1.80), hypertension (1.95, 1.38 - 2.74), diabetes (1.13, 1.09 - 1.17), and Charlson Comorbidity Index (1.08, 1.04 - 1.13) were also independently associated with 90-Day RA (SHR, CI reported). In the imaging subgroup of 523 patients, DIH retained independent association with 90-Day RA (SHR: 3.94 1.37 - 11.36) (Figure 1B). Discussion: In addition to traditional predictors of poor outcomes among ICH patients, DIH demonstrated strong and independent association with 90-day RA. Screening, identification, and active management of DIH is critical to reduce long-term disease burden of ICH.
Commissioning observations with the Apache Point Observatory Galactic Evolution Experiment (APOGEE), part of the Sloan Digital Sky Survey III, have produced radial velocities (RVs) for ~4700 ...K/M-giant stars in the Milky Way (MW) bulge. These high-resolution (R ~ 22,500), high-S/N (>100 per resolution element), near-infrared (NIR; 1.51-1.70 mu m) spectra provide accurate RVs ( epsilon sub(v) ~ 0.2 km s super(-1)) for the sample of stars in 18 Galactic bulge fields spanning -1degrees < l < 20degrees, b < 20degrees, and delta > -32degrees. This represents the largest NIR high-resolution spectroscopic sample of giant stars ever assembled in this region of the Galaxy. A cold (sigma sub(v) ~ 30 km s super(-1)), high-velocity peak (V sub(GSR) asymptotically = +200 km s super(-1)) is found to comprise a significant fraction (~10%) of stars in many of these fields. These high RVs have not been detected in previous MW surveys and are not expected for a simple, circularly rotating disk. Preliminary distance estimates rule out an origin from the background Sagittarius tidal stream or a new stream in the MW disk. Comparison to various Galactic models suggests that these high RVs are best explained by stars in orbits of the Galactic bar potential, although some observational features remain unexplained.
The synthetic steroid mifepristone blocks the growth of ovarian cancer cells, yet the mechanism driving such effect is not entirely understood. Unbiased genomic and proteomic screenings using ovarian ...cancer cell lines of different genetic backgrounds and sensitivities to platinum led to the identification of two key genes upregulated by mifepristone and involved in the unfolded protein response (UPR): the master chaperone of the endoplasmic reticulum (ER), glucose regulated protein (GRP) of 78 kDa, and the CCAAT/enhancer binding protein homologous transcription factor (CHOP). GRP78 and CHOP were upregulated by mifepristone in ovarian cancer cells regardless of p53 status and platinum sensitivity. Further studies revealed that the three UPR-associated pathways, PERK, IRE1α, and ATF6, were activated by mifepristone. Also, the synthetic steroid acutely increased mRNA translation rate, which, if prevented, abrogated the splicing of XBP1 mRNA, a non-translatable readout of IRE1α activation. Moreover, mifepristone increased LC3-II levels due to increased autophagic flux. When the autophagic–lysosomal pathway was inhibited with chloroquine, mifepristone was lethal to the cells. Lastly, doses of proteasome inhibitors that are inadequate to block the activity of the proteasomes, caused cell death when combined with mifepristone; this phenotype was accompanied by accumulation of poly-ubiquitinated proteins denoting proteasome inhibition. The stimulation by mifepristone of ER stress and autophagic flux offers a therapeutic opportunity for utilizing this compound to sensitize ovarian cancer cells to proteasome or lysosome inhibitors.
•Mifepristone triggers the unfolded protein response (UPR) in ovarian cancer cells.•Mifepristone-induced UPR is mediated by increased mRNA translation rate.•Mifepristone increases autophagic flux in ovarian cancer cells.•Mifepristone is lethal to ovarian cancer cells when combined with chloroquine.•Mifepristone kills ovarian cancer cells in combination with proteasome inhibitors.
The adhesion of human epidermal keratinocytes to the implant surface is one of the most critical steps during the patient's recovery from implantation of transcutaneous prosthesis. To improve the ...success rate of transcutaneous prosthetic implants, we explored a new “top-down” approach to promoting this dynamic adhering process through modulation of upstream cell signaling pathways. To examine the feasibility of this novel approach, we first established an in vitro platform that is capable of providing a non-invasive, real-time, quantitative characterization of the keratinocyte-implant interaction. This platform is based on the dissipation monitoring function of the quartz crystal microbalance with dissipation monitoring (QCM-D) in conjunction with the open-module setup of the QCM-D. We then employed this platform to assess the effects of various pathways-specific modulators on the adhering process of keratinocytes. We demonstrated that this “top-down” approach is as effective in enhancing the adhesion of keratinocytes as the conventional “bottom-up” approach that relies on modifying the substrate surface with the adhesion protein such as fibronectin. We envision that this new “top-down” approach combined with the QCM-D-based in vitro platform will help facilitate the future development of new therapies for enhancing osseointegration and promoting wound healing.
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•Modulation of cell signaling pathways enhances the keratinocyte-implant adhesion.•Modulation of cell signaling pathways can be as effective as fibronectin coating.•The QCM-D-based in vitro platform is effective in examining cell adhering process.•The ΔD-response is a better measure of cell adhesion than the Δf-response.
Improving utilization of antenatal care is a critical strategy for achieving China's Millennium Development Goal of decreasing the maternal mortality ratio (MMR). While overall utilization has ...increased recently in China, an urban vs. rural disparity in access remains. Here we aim to assess utilization of antenatal care in rural-to-urban migrant women and identify its risk and protective factors.
Migrant women who had been living in Shanghai for more than six months, delivered in one of the two study hospitals between August 2009 and February 2010, and provided written consent were interviewed using a structured questionnaire.
Of 767 women, 90.1% (691) made at least one antenatal care visit, while 49.7% (381) had adequately utilized antenatal care (i.e., made five or more antenatal care visits). Only 19.7% of women visited an antenatal care center during the first trimester (12 weeks). Women between the ages of 25 and 30 and women older than 30 were more likely than younger women to have adequately utilized antenatal care (AOR=2.2 and 1.9, 95%CI=1.4-3.5 and 1.1-3.2, respectively). Women whose husbands held Shanghai residency status (AOR=4.9, 95%CI=2.2-10.9) or who had more than 10 years of education (AOR=1.8, 95%CI=1.2-2.9), previously experienced a miscarriage or abortion (AOR=2.2, 95%CI=1.3-3.8), had higher household income (AOR=1.6, 95%CI=1.0-2.5) were more likely to have adequately utilized antenatal care. Women from high-income households were also more likely to receive antenatal care during the first 12 weeks (AOR=3.5, 95%CI=1.7-5.5).
Many migrant women in Shanghai did not receive adequate antenatal care and initiated antenatal care later than the optimal first 12 weeks of pregnancy. Poor antenatal care utilization was associated with low socioeconomic status, education, and certain demographic factors. Tailored health education for both migrant women and their husbands should be strengthened to improve maternal health. Financing supports should be provided to improve the utilization of antenatal care.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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