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Background: Lower cerebral blood flow (CBF) and excessive brain atrophy are linked to Alzheimer’s disease (AD). It is still undetermined whether reduced CBF precedes or follows brain tissue loss. Objective: We compared total CBF (tCBF), global cerebral perfusion (GCP), and volumes of AD-prone regions between cognitively normal (CN) and early amnestic mild cognitive impairment (aMCI) and tested their associations with cognitive performance to assess their predictive value for differentiation between CN and early aMCI. Methods: A total of 74 participants (mean age 69.9±6.2 years, 47 females) were classified into two groups: 50 CN and 24 aMCI, of whom 88% were early aMCI. tCBF, GCP, and global and regional brain volumetry were measured using phase-contrast and T1-weighted MRI. Neuropsychological tests tapping global cognition and four cognitive domains (memory, executive function, language, and visuospatial) were administered. Comparisons and associations were investigated using analyses of covariance (ANCOVA) and linear regression analyses, respectively. Results: Women had significantly higher GCP than men. Both, tCBF and GCP were significantly reduced in aMCI compared with CN, while differences in volumes of cerebral gray matter, white matter, and AD-prone regions were not significant. tCBF and GCP were significantly associated with global cognition (standardized beta (stβ) = 0.324 and stβ= 0.326) and with memory scores (stβ≥0.297 and stβ≥0.264) across all participants. Associations of tCBF and GCP with memory scores were also significant in CN (stβ= 0.327 and stβ= 0.284) and in aMCI (stβ= 0.627 and stβ= 0.485). Conclusion: Reduced tCBF and GCP are sensitive biomarkers of early aMCI that likely precede brain tissue loss.

Objective To identify spine patients' barriers to appropriate postoperative opioid use, comfort with naloxone, knowledge of safe opioid disposal practices, and associated factors. Methods We preoperatively surveyed 174 spine patients about psychobehavioral barriers to appropriate opioid use, comfort with naloxone, and knowledge about opioid disposal. Multivariable logistic regression identified factors associated with barriers and knowledge (α = 0.05). Results Common barriers were fear of addiction (71%) and concern about disease progression (43%). Most patients (78%) had neutral/low confidence in the ability of nonopioid medications to control pain; most (57%) felt neutral or uncomfortable with using naloxone; and most (86%) were familiar with safe disposal. Anxiety was associated with fear of distracting the physician (adjusted odds ratio [aOR], 3.8; 95% confidence interval [CI], 1.1–14) and with lower odds of knowing safe disposal methods (aOR, 0.18; 95% CI, 0.04–0.72). Opioid use during the preceding month was associated with comfort with naloxone (aOR, 4.9; 95% CI, 2.1–12). Patients with a higher educational level had lower odds of reporting fear of distracting the physician (aOR, 0.30; 95% CI, 0.09–0.97), and those with previous postoperative opioid use had lower odds of concern about disease progression (aOR, 0.25; 95% CI, 0.09–0.63) and with a belief in tolerating pain (aOR, 0.34; 95% CI, 0.12–0.95). Conclusions Many spine patients report barriers to appropriate postoperative opioid use and are neutral or uncomfortable with naloxone. Some are unfamiliar with safe disposal. Associated factors include anxiety, lack of recent opioid use, and no previous postoperative use.

Rats commonly undergo surgery for research purposes. However, the effects of different methods of hair removal on wound healing and surgical site infections (SSI) in rats has not been evaluated. The current study evaluated 2 hair removal methods, clipping with an electric clipper and using a depilatory agent, and their effect on wound healing and SSI. Swabs for bacterial culture were obtained on Day 0 just after hair removal, after aseptic skin preparation, and on Days 1 and 3 before conducting skin biopsies to assess bacterial load and recolonization. Full-thickness punch biopsies were taken for histopathologic evaluation on Days 0, 1, 3, 7, and 10. The surgical incisions were assigned an ASEPSIS score on Days 1 and 3. The data revealed that the bacterial load was significantly higher with the depilatory method as compared with the clipper method, but only on Day 1. The histopathologic evaluation found no significant difference in wound healing between the 2 methods. Although the ASEPSIS score was significantly higher for the clipping method than for the depilatory method on Day 1, both techniques were equivalent by Day 3. We conclude that both hair removal methods are safe and efficacious components of aseptic technique in rats.

Study design Retrospective review of prospectively collected data OBJECTIVE:: To assess the association between preoperative and postoperative mental health status with postoperative satisfaction in lumbar degenerative surgery patients. Summary of background data Poor preoperative mental health has been shown to negatively affect postoperative satisfaction among spine surgery patients, but there is limited evidence on the impact of postoperative mental health on satisfaction. Materials and methods Adult patients undergoing surgery for lumbar degenerative conditions at a single institution were included. Mental health was assessed preoperatively and 12 months postoperatively using Patient-Reported Outcomes Measurement Information System Depression and Anxiety scores. Satisfaction was assessed 12 months postoperatively using North American Spine Society Patient Satisfaction Index. The authors evaluated associations between mental health and satisfaction with univariate and multivariable logistic regression to adjust for confounders. Preoperative depression/anxiety level was corrected for postoperative depression/anxiety level, and vice versa. Statistical significance was assessed at α=0.05. Results A total of 183 patients (47% male individuals; avg. age, 62 y) were included. Depression was present in 27% preoperatively and 29% postoperatively, and anxiety in 50% preoperatively and 31% postoperatively. Ninteen percent reported postoperative dissatisfaction using the North American Spine Society Patient Satisfaction Index. Univariate analysis identified race, family income, relationship status, current smoking status, change in pain interference, and change in physical function as potential confounders. In adjusted analysis, odds of dissatisfaction were increased in those with mild postoperative depression (adjusted odds ratio=6.1; 95% confidence interval, 1.2-32; P=0.03) and moderate or severe postoperative depression (adjusted odds ratio=7.5; 95% confidence interval, 1.3-52; P=0.03). Preoperative and postoperative anxiety and preoperative depression were not associated with postoperative satisfaction. Conclusions Following lumbar degenerative surgery, patients with postoperative depression, irrespective of preoperative depression status, have significantly higher odds of dissatisfaction. These results emphasize the importance of postoperative screening and treatment of depression in spine patients with dissatisfaction. Level of evidence Level III-nonrandomized cohort study.

OBJECTIVE The aim of this study was to compare all-cause reoperation rates and costs in nonelderly patients treated with anterior cervical discectomy and fusion (ACDF) with structural allograft versus synthetic cages for degenerative pathology. METHODS We queried a private claims database to identify adult patients ( ≤ 65 years) who underwent single-level ACDF in a hospital setting using either structural allograft or a synthetic cage (polyetheretherketone, metal, or hybrid device), from 2010 to 2016. The rate of all-cause reoperations at 2 years were compared between the 2 groups. Index hospitalization costs and 90-day complication rates were also compared. Significance was set at p < 0.05. RESULTS A total of 26,754 patients were included in the study. 11,514 patients (43%) underwent ACDF with structural allograft and 15,240 (57%) underwent ACDF with a synthetic cage. The patients in the allograft group were younger and more likely to be male. There was no significant difference between the 2 groups with respect to 90-day complications including: wound dehiscence, dysphagia, dysphonia, and hematoma/seroma. In the 2-year postoperative period, the synthetic cage group had a significantly higher rate of allcause reoperation compared to the allograft group (9.1% vs. 8.0%, p = 0.002). Index hospitalization costs were significantly higher in the synthetic cage group compared to those in the allograft group ($23,475 vs. $20,836, p < 0.001). CONCLUSION Structural allograft is associated with lower all-cause reoperation rates and lower index costs in nonelderly patients undergoing ACDF surgery for degenerative pathology. It is important to understand this data as we transition toward value-based care.

Bacterial quorum quenching (QQ), whose mechanism involves the degradation of quorum-sensing signal molecules, is an effective strategy for controlling biofouling in membrane bioreactors (MBRs). However, MBRs operated at low temperatures, either due to cold climates or seasonal variations, exhibit severe deterioration in QQ efficiency. In this study, a modified culture method for

Objective Fatigue is among the most common complaints in community-dwelling older adults, yet its etiology is poorly understood. Based on models implicating frontostriatal pathways in fatigue pathogenesis, we hypothesized that smaller basal ganglia volume would be associated with higher levels of subjective fatigue and reduced set-shifting in middle-aged and older adults without dementia or other neurologic conditions. Methods Forty-eight non-demented middle-aged and older adults ( Mage = 68.1, SD = 9.4; MMMSE = 27.3, SD = 1.9) completed the Fatigue Symptom Inventory, set-shifting measures, and structural MRI as part of a clinical evaluation for subjective cognitive complaints. Associations were examined cross-sectionally. Results Linear regression analyses showed that smaller normalized basal ganglia volumes were associated with more severe fatigue (β = −.29, P = .041) and poorer Trail Making Test B-A (TMT B-A) performance (β = .30, P = .033) controlling for depression, sleep quality, vascular risk factors, and global cognitive status. Putamen emerged as a key structure linked with both fatigue ( r = −.43, P = .003) and TMT B-A (β = .35, P = .021). The link between total basal ganglia volume and reduced TMT B-A was particularly strong in clinically fatigued patients. Conclusion This study is among the first to show that reduced basal ganglia volume is an important neurostructural correlate of subjective fatigue in physically able middle-aged and older adults without neurological conditions. Findings suggest that fatigue and rapid set-shifting deficits may share common neural underpinnings involving the basal ganglia, and provide a framework for studying the neuropathogenesis and treatment of subjective fatigue.

High dimensional neuroimaging datasets and machine learning have been used to estimate and predict domain-specific cognition, but comparisons with simpler models composed of easy-to-measure variables are limited. Regularization methods in particular may help identify regions-of-interest related to domain-specific cognition. Using data from the Northern Manhattan Study, a cohort study of mostly Hispanic older adults, we compared three models estimating domain-specific cognitive performance: sociodemographics and APOE ε4 allele status (basic model), the basic model and MRI markers, and a model with only MRI markers. We used several machine learning methods to fit our regression models: elastic net, support vector regression, random forest, and principal components regression. Model performance was assessed with the RMSE, MAE, and R(2) statistics using 5-fold cross-validation. To assess whether prediction models with imaging biomarkers were more predictive than prediction models built with randomly generated biomarkers, we repeated our prediction analyses using 1000 datasets with random biomarkers and compared the distribution of the RMSE and R(2) in models using these random biomarkers to the RMSE and R(2) from observed models. Basic models explained ~30–41% of the variance in domain-specific cognition. Addition of MRI markers did not improve estimation. However, elastic net models with only MRI markers performed significantly better than random MRI markers (one-sided P

Background How cerebrovascular disease and neurodegeneration affect each other to impact cognition is not yet known. We aimed to test whether Alzheimer’s disease-signature (AD) cortical thickness mediates the association between cholinergic white matter lesion load and change in domain-specific cognition. Methods Clinically stroke-free participants from the Northern Manhattan Study with both regional white matter hyperintensity volume (WMHV) and gray matter measurements were included (N = 894). Tract-specific WMHVs were quantified through FSL using the Johns Hopkins University white matter tract atlas. We used Freesurfer 5.1 to estimate regional cortical thickness. We fit structural equation models, including multiple indicator latent change score models, to examine associations between white matter hyperintensity volume (WMHV) in cholinergic tracts, AD-signature region cortical thickness (CT), and domain-specific cognition. Results Our sample (N = 894) had a mean (SD) age = 70 (9) years, years of education = 10 (5), 63% women, and 67% Hispanics/Latinos. Greater cholinergic WMHV was significantly related to worse processing speed at baseline (standardized β = −0.17, SE = 0.05, p = .001) and over time (standardized β = −0.28, SE = 0.09, p = .003), with a significant indirect effect of AD-signature region CT (baseline: standardized β = −0.02, SE = 0.01, p = .023; change: standardized β = −0.03, SE = 0.02, p = .040). Conclusions Cholinergic tract WMHV is associated with worse processing speed, both directly and indirectly through its effect on AD-signature region CT.

Although prescribing opioid medication on a limited basis for postoperative pain control is common practice, few studies have focused on chronic opioid use following anterior cervical discectomy and fusion (ACDF).To determine the prevalence of and risk factors for chronic opioid use following one and two-level ACDF for degenerative cervical pathology.Retrospective cohort.Using an insurance claims database, we identified patients aged 18-64 who underwent one or two-level primary ACDF from 2010 to 2015 for degenerative cervical pathology.Opioid prescription strength at various timepoints pre- and postoperatively and development of chronic postoperative opioid use.Prescription opioid use was examined during the following periods: 90 days before 7 days preceding surgery (preoperative), 6 days preceding surgery to 90 days following surgery (perioperative) and from 91 to 365 days following surgery (postoperative). The primary outcome was chronic postoperative opioid use, defined as ≥120 days' supply of opioid prescriptions filled or ≥10 opioid prescriptions between 3 and 12 months postoperatively. Secondary outcomes were high-dose (90 morphine milligram equivalents [MME]/day) and very high-dose (200 MME/day) opioid prescriptions. A multivariate logistic model (area under the ROC curve 0.75, p.001) was built to predict long-term opioid use.Among 28,813 patients who underwent ACDF, most were female (55%) and underwent single-level ACDF (68%), with mean age of 50±8.0 years. Fifty-two percent of patients filled an opioid prescription in the preoperative period, 95% of patients filled a prescription in the perioperative period, and 39% of patients filled a prescription in the postoperative period. High-dose and very high-dose opioid prescriptions in the perioperative period were identified in 45% and 24% of patients, respectively, whereas 17% met criteria for chronic postoperative opioid use. The odds of chronic opioid use were highest in the Western US (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.3, 1.6). Duration of opioids prescribed was also highest in the Western US (median 111 days, interquartile range 11-336), p.001. Factors associated with the highest risk for chronic opioid use were preoperative opioid use (OR 5.7, 95% CI 5.3, 56.2), drug abuse (OR 3.5, 95% CI 2.6, 4.5), depression (OR 1.7, 95% CI 1.6, 1.9), anxiety (OR 1.5, 95% CI 1.4, 1.6), and surgery in the western region of the United States (OR 1.5, 95% CI 1.3, 1.6).Patients undergoing ACDF commonly receive high-dose opioid prescriptions after surgery, and certain patient factors increase risk for chronic opioid use following ACDF. Intervention focusing on patients with these factors is essential to reduce long-term use of prescription opioids and postoperative care.

Poor sleep quality is a known risk factor for Alzheimer's disease. This longitudinal imaging study aimed to determine the acceleration in the rates of tissue loss in cognitively critical brain regions due to poor sleep in healthy elderly individuals. Cognitively-normal healthy individuals, aged ≥60 years, reported Pittsburgh Sleep Quality Index (PSQI) and underwent baseline and 2-year follow-up magnetic resonance imaging brain scans. The links between self-reported sleep quality, rates of tissue loss in cognitively-critical brain regions, and white matter hyperintensity load were assessed. A total of 48 subjects were classified into normal (n = 23; PSQI score5) and poor sleepers (n = 25; PSQI score ≥5). The two groups were not significantly different in terms of age, gender, years of education, ethnicity, handedness, body mass index, and cognitive performance. Compared to normal sleepers, poor sleepers exhibited much faster rates of volume loss, over threefold in the right hippocampus and fivefold in the right posterior cingulate over 2 years. In contrast, there were no significant differences in the rates of volume loss in the cerebral and cerebellar grey and white matter between the two groups. Rates of volume loss in the right posterior cingulate were negatively associated with global PSQI scores. Poor sleep significantly accelerates volume loss in the right hippocampus and the right posterior cingulate cortex. These findings demonstrate that self-reported sleep quality explains inter-individual differences in the rates of volume loss in cognitively-critical brain regions in healthy older adults and provide a strong impetus to offer sleep interventions to cognitively normal older adults who are poor sleepers.

Pulmonary artery (PA) pressure increases during lung growth after unilateral pneumonectomy (PNX). Mechanosensitive transcriptional co-activator, yes-associated protein (YAP1), in endothelial cells (ECs) is necessary for angiogenesis during post-PNX lung growth. We investigate whether increases in PA pressure following PNX control-angiogenesis through YAP1. When hydrostatic pressure is applied to human pulmonary arterial ECs (HPAECs), the expression of YAP1, transcription factor TEAD1, and angiogenic factor receptor Tie2 increases, while these effects are inhibited when HPAECs are treated with YAP1 siRNA or YAP1S94A mutant that fails to bind to TEAD1. Hydrostatic pressure also stimulates DNA synthesis, cell migration, and EC sprouting in HPAECs, while YAP1 knockdown or YAP1S94A mutant inhibits the effects. Gene enrichment analysis reveals that the levels of genes involved in extracellular matrix (ECM), cell adhesion, regeneration, or angiogenesis are altered in post-PNX mouse lung ECs, which interact with YAP1. Exosomes are known to promote tissue regeneration. Proteomics analysis reveals that exosomes isolated from conditioned media of post-PNX mouse lung ECs contain the higher levels of ECM and cell-adhesion proteins compared to those from sham-operated mouse lung ECs. Recruitment of host lung ECs and blood vessel formation are stimulated in the fibrin gel containing exosomes isolated from post-PNX mouse lung ECs or pressurized ECs, while YAP1 knockdown inhibits the effects. These results suggest that increases in PA pressure stimulate angiogenesis through YAP1 during regenerative lung growth.

S-SCAM/MAGI-2 gene duplication is associated with schizophrenia (SCZ). S-SCAM overexpression in the forebrain induces SCZ-like phenotypes in a transgenic (Tg) mouse model. Interestingly, S-SCAM Tg mice show male-specific impairments in synaptic plasticity and working memory. However, mechanisms underlying the sex-specific deficits remain unknown. Here we report that S-SCAM Tg mice have male-specific deficits in synaptic GSK3β functions, as shown by reduced synaptic protein levels and increased inhibitory phosphorylation of GSK3β. This GSK3β hyper-phosphorylation was associated with increased CaMKII activities. Notably, synaptic levels of Axin1, to which GSK3β binds in competition with S-SCAM, were also reduced in male S-SCAM Tg mice. We demonstrated that Axin-binding is required for the S-SCAM overexpression-induced synaptic GSK3β reduction. Axin stabilization using XAV939 rescued the GSK3β deficits and restored the temporal activation of GSK3β during long-term depression in S-SCAM overexpressing neurons. Interestingly, synaptic Axin2 levels were increased in female S-SCAM Tg mice. Female sex hormone 17β-estradiol increased Axin2 expression and increased synaptic GSK3β levels in S-SCAM overexpressing neurons. These results reveal the role of S-SCAM in controlling Axin-dependent synaptic localization of GSK3β. Moreover, our studies point out the pathological relevance of GSK3β hypofunction found in humans and contribute to understanding the molecular underpinnings of sex differences in SCZ.

We aim to determine the sleep correlates of age-related brain loss in a sample of middle-aged to older males with obstructive sleep apnea (OSA). We recruited consecutive treatment naïve male patients with moderate to severe OSA from January to November of 2019. We excluded participants if they had dementia, stroke or heart disease. We collected demographic variables and vascular risk factors. We also obtained the insomnia severity index, the Epworth sleepiness scale and the Pittsburgh sleep quality index. We also obtained computerized neurocognitive testing with the go-no-go response inhibition test, Stroop interference test, catch game test, staged information processing speed test, verbal memory test and non-verbal memory test. We derived age and education adjusted domain-specific Z-scores for global cognition, memory, attention, processing speed and executive function. We used brain MRI T1-weighted images to derive total hippocampal and gray matter volumes. Partial correlations evaluated associations between variables from sleep questionnaires (e.g., insomnia severity index score), and polysomnographic variables (the apnea-hypopnea index, average oxygen levels during sleep) with cognitive domains and brain volumes. We examined 16 participants with an age range of 40–76 years, 73% Hispanic/Latino. The mean apnea-hypopnea index was 48.9 ± 25.5 and average oxygen saturation during sleep was 91.4% ± 6.9%. Hypertension was seen in 66% and diabetes mellitus in 27%. We found that the insomnia severity index score and average oxygen levels during sleep had the strongest correlations with brain volumes and cognition. These preliminary findings may aid in developing future strategies to improve age-related brain loss in patients with OSA.

Recent studies demonstrated reduced hippocampal volumes in elderly healthy individuals who are cognitively normal but poor sleepers. The association between sleep quality and the pattern of volume loss across hippocampal subfields (HSs) is not well known. Thus, it is the focus of the present study. Sleep quality was self-assessed using the Pittsburgh Sleep Quality Index (PSQI). The HS volumes were measured using sub-millimetre in-plane resolution T2-weighted magnetic resonance imaging data. A total of 67 cognitively normal elderly individuals aged 60-83 years were classified into 30 normal sleepers with a PSQI

Rats commonly undergo surgery for research purposes. However, the effects of different methods of hair removal on wound healing and surgical site infections (SSI) in rats has not been evaluated. The current study evaluated 2 hair removal methods, clipping with an electric clipper and using a depilatory agent, and their effect on wound healing and SSI. Swabs for bacterial culture were obtained on Day 0 just after hair removal, after aseptic skin preparation, and on Days 1 and 3 before conducting skin biopsies to assess bacterial load and recolonization. Full-thickness punch biopsies were taken for histopathologic evaluation on Days 0, 1, 3, 7, and 10. The surgical incisions were assigned an ASEPSIS score on Days 1 and 3. The data revealed that the bacterial load was significantly higher with the depilatory method as compared with the clipper method, but only on Day 1. The histopathologic evaluation found no significant difference in wound healing between the 2 methods. Although the ASEPSIS score was significantly higher for the clipping method than for the depilatory method on Day 1, both techniques were equivalent by Day 3. We conclude that both hair removal methods are safe and efficacious components of aseptic technique in rats.

Mechanical compliance of a compartment is defined by the change in its volume with respect to a change in the inside pressure. The compliance of the spinal canal regulates the intracranial pressure (ICP) under postural changes. Understanding how gravity affects ICP is beneficial for poorly understood cerebrospinal fluid (CSF)-related disorders. The aim of this study was to evaluate postural effects on cranial hemo- and hydrodynamics. This was a prospective study, which included 10 healthy volunteers (three males, seven females, mean ± standard deviation age: 29 ± 7 years). Cine gradient-echo phase-contrast sequence acquired at 0.5 T, "GE double-doughnut" scanner was used. Spinal contribution to overall craniospinal compliance (CSC), craniospinal CSF stroke volume (SV), magnetic resonance (MR)-derived ICP (MR-ICP), and total cerebral blood flow (TCBF) were measured in supine and upright postures using automated blood and CSF flows quantification. Statistical tests performed were two-sided Student's t-test, Cohen's d, and Pearson correlation coefficient. MR-ICP and the craniospinal CSF SV were significantly correlated with the spinal contribution to the overall CSC (r = 0.83, p < 0.05) and (r = 0.62, p < 0.05), respectively. Cranial contribution to CSC increased from 44.5% ± 16% in supine to 74.9% ± 8.4% in upright posture. The average MR-ICP dropped from 9.9 ± 3.4 mmHg in supine to -3.5 ± 1.5 mmHg. The CSF SV was over 2.5 times higher in the supine position (0.55 ± 0.14 ml) than in the upright position (0.21 ± 0.13 ml). In contrast, TCBF was slightly higher in the supine posture (822 ± 152 ml/min) than in the upright posture (761 ± 139 ml/min), although not statistically significant (p = 0.16). The spinal-canal compliance contribution to CSC is larger than the cranial contribution in the supine posture and smaller in the upright posture. Thereby, the spinal canal plays a role in modulating ICP upon postural changes. The lower pressure craniospinal CSF system was more affected by postural changes than the higher-pressure cerebral vascular system. Craniospinal hydrodynamics is affected by gravity and is likely to be altered by its absence in space. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) infection may result in severe acute respiratory disease syndrome (ARDS) and death For COVID-19 patients failing mechanical ventilation, extra corporeal membrane oxygenation (ECMO) has been used with varying efficacy in academic medical centers and quaternary referral centers METHODS: During the three-month study period, 70 patients with COVID-19 were admitted to the ICU at Regional Medical Center of San Jose From this cohort, 57 (81%) developed acute respiratory failure requiring mechanical ventilation Seven (12%) of the mechanically ventilated patients developed progressive ARDS and met criteria for initiation of ECMO All patients receiving VV ECMO were younger than 70 years of age with a median age of 57 years Four of the seven patients were women and three were men The median body mass index (BMI) was 36 kg/ m2 and two of the seven patients met the criteria for morbid obesity with a BMI greater than 40 kg/m2 The median duration of VV ECMO was eleven days with a minimum of six days and a maximum of 37 days The median duration of mechanical ventilation pre-ECMO was five days and post-ECMO eight days Five of the seven (71%) VV ECMO patients survived to discharge Two of the seven patients were discharged home, two to long-term ambulatory care (LTAC) facilities and one transferred to another hospital due to third-party payer request Two patients died, one during ECMO cannulation with perforation of the right ventricle Another patient died after six days of VV ECMO following cardiopulmonary arrest that resulted in severe cerebral anoxia For the mechanically ventilated patients in our ICU who did not receive VV ECMO, 34 of 50 patients (68%) survived to discharge With VV-ECMO rescue treatment the overall mortality rate for all mechanically ventilated COVID-19 patients decreased from 40 3% to 31 5% RESULTS: We report the successful use of veno-venous (VV) ECMO to treat refractory ARDS due to COVID-19 in a community hospital setting with survival to discharge rate of 71% over a three-month period In a community hospital with adequate resources, VV ECMO can be an effective rescue therapy for selected COVID-19 patients who fail all other available treatments

Background and Purpose— Few studies have examined the separate contributions of systolic blood pressure and diastolic blood pressures (DBP) on subclinical cerebrovascular disease, especially using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines. Furthermore, associations with region-specific white matter hyperintensity volume (WMHV) are underexplored. Methods— Using data from the NOMAS (Northern Manhattan Study), a prospective cohort study of stroke risk and cognitive aging, we examined associations between systolic blood pressure and DBP, defined by the 2017 American College of Cardiology/American Heart Association guidelines, with regional WMHV. We used a linear mixed model approach to account for the correlated nature of regional brain measures. Results— The analytic sample (N=1205; mean age 64±8 years) consisted of 61% women and 66% Hispanics/Latinos. DBP levels were significantly related to WMHV differentially across regions ( P for interactiont tests showed that estimates for periventricular WMHV were significantly different from estimates for temporal WMHV (Holms stepdown–adjusted P Conclusions— Lower DBP levels, defined by the 2017 American College of Cardiology/American Heart Association guidelines, were related to lower white matter lesion load, especially in the periventricular regions relative to the temporal region.

To compare the efficacy of a dedicated eyelid cleanser and diluted baby shampoo in the management of blepharitis.Forty-three participants with clinical blepharitis signs were enrolled in a prospective, randomized, double-masked, paired-eye trial. A dedicated eyelid cleanser (TheraTearsBaseline measurements did not differ between treatments (all p 0.05). The eyelid cleanser was preferred over baby shampoo by the majority of participants (p 0.001). Improvements in the tear lipid layer, inferior lid wiper epitheliopathy (LWE), cylindrical collarettes, and MMP-9 expression were limited to the dedicated eyelid cleanser (all p 0.05), and a greater decrease in SANDE symptoms score was also observed (p = 0.04). Meibomian gland capping and MUC5AC expression worsened with baby shampoo treatment (both p 0.05). SPEED symptoms score, superior LWE, seborrhoeic lash crusting, and trichiasis decreased significantly following application of both treatments (all p 0.05), but did not differ between treatments (all p 0.05).Clinical improvements in blepharitis occurred with both treatments. However, only the dedicated eyelid cleanser proved effective in reducing ocular surface inflammation, and was the preferred therapy. Long term impact of decreased goblet cell function secondary to baby shampoo treatment requires further exploration.

Hippocampal volumes are smaller in psychiatric disorder patients and lower levels of hippocampal neurogenesis are the hypothesized cause. Understanding which molecular processes regulate hippocampal progenitor differentiation might aid in the identification of novel drug targets that can promote larger hippocampal volumes. Here we use a unique human cell line to assay genome-wide expression changes when hippocampal progenitor cells differentiate. RNA was extracted from proliferating cells versus differentiated neural cells and applied to Illumina Human HT-12 v4 Expression BeadChips. Linear regressions were used to determine the effect of differentiation on probe expression and we assessed enrichment for gene ontology (GO) terms. Genetic pathway analysis (MAGMA) was used to evaluate the relationship between hippocampal progenitor cell differentiation and adult hippocampal volume, using results from the imaging genomics consortium, ENIGMA. Downregulated transcripts were enriched for mitotic processes and upregulated transcripts were enriched for cell differentiation. Upregulated (differentiation) transcripts specifically, were also predictive of adult hippocampal volume; with Early growth response protein 2 identified as a hub transcription factor within the top GO term, and a potential drug target. Our results suggest that genes governing differentiation, rather than mitosis, have an impact on adult hippocampal volume and that these genes represent important drug targets.

Objective:To assess the effect of weightlessness and the respective roles of CSF and vascular fluid on changes in white matter hyperintensity (WMH) burden in astronauts.Methods:We analyzed prespaceflight and postspaceflight brain MRI scans from 17 astronauts, 10 who flew a long-duration mission on the International Space Station (ISS) and 7 who flew a short-duration mission on the Space Shuttle. Automated analysis methods were used to determine preflight to postflight changes in periventricular and deep WMH, CSF, and brain tissue volumes in fluid-attenuated inversion recovery and high-resolution 3-dimensional T1-weighted imaging. Differences between cohorts and associations between individual measures were assessed. The short-term reversibility of the identified preflight to postflight changes was tested in a subcohort of 5 long-duration astronauts who had a second postflight MRI scan 1 month after the first postflight scan.Results:Significant preflight to postflight changes were measured only in the long-duration cohort and included only the periventricular WMH and ventricular CSF volumes. Changes in deep WMH and brain tissue volumes were not significant in either cohort. The increase in periventricular WMH volume was significantly associated with an increase in ventricular CSF volume (ρ = 0.63, p = 0.008). A partial reversal of these increases was observed in the long-duration subcohort with a 1-month follow-up scan.Conclusions:Long-duration exposure to microgravity is associated with an increase in periventricular WMH in astronauts. This increase was linked to an increase in ventricular CSF volume documented in ISS astronauts. There was no associated change in or abnormal levels of WMH volumes in deep white matter as reported in U-2 high-altitude pilots.

In an effort to reduce exposure to secondhand smoke, many governments have enacted smoke-free laws in public spaces. To the extent that smoke-free laws change perceptions, norms, and attitudes abou...

The Disrupted-in-Schizophrenia 1 (DISC1) protein has been implicated in a range of biological mechanisms underlying chronic mental disorders such as schizophrenia. Schizophrenia is associated with abnormal striatal dopamine signalling, and all antipsychotic drugs block striatal dopamine 2/3 receptors (D(2/3)Rs). Importantly, the DISC1 protein directly interacts and forms a protein complex with the dopamine D(2) receptor (D(2)R) that inhibits agonist-induced D(2)R internalization. Moreover, animal studies have found large striatal increases in the proportion of D(2)R receptors in a high affinity state (D(2)(high)R) in DISC1 rodent models. Here, we investigated the relationship between the three most common polymorphisms altering the amino-acid sequence of the DISC1 protein (Ser704Cys (rs821616), Leu607Phe (rs6675281) and Arg264Gln (rs3738401)) and striatal D(2/3)R availability in 41 healthy human volunteers, using [(11)C]-(+)-PHNO positron emission tomography. We found no association between DISC1 polymorphisms and D(2/3)R availability in the striatum and D(2)R availability in the caudate and putamen. Therefore, despite a direct interaction between DISC1 and the D(2)R, none of its main functional polymorphisms impact striatal D(2/3)R binding potential, suggesting DISC1 variants act through other mechanisms.

STUDY OBJECTIVES: This study aims to evaluate the extent to which sleep quality impacts amnestic mild cognitive impairment (aMCI)-related brain regions in a cognitively normal cohort of individuals. METHODS: Seventy-four participants were rigorously evaluated using a battery of cognitive tests and a detailed clinical assessment to verify normal cognitive status. We then screened for sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and depressive symptoms using the Geriatric Depression Scale (GDS). Five subjects were excluded due to mild depression. Overall 38 individuals with mean age 70.7 ± 7 were classified as poor sleepers and 31 with mean age of 69.6 ± 6 years as normal sleepers. Structural MRI and Freesurfer brain parcellation were used to measure aMCI-related brain regions. RESULTS: Relative to normal sleepers, poor sleepers exhibited significant reductions in cortical and subcortical volumes bilaterally in the hippocampi, as well as in the superior parietal lobules and left amygdala. The effects were strongest in the left superior parietal lobule (p < .015), followed by the hippocampi. Diffuse patterns of cortical thinning were observed in the frontal lobes, but significant effects were concentrated in the right mesial frontal cortex. Lower sleep duration was most correlated with cortical volume and thickness reductions among all subjects. CONCLUSIONS: Atrophy related to poor sleep quality impacted a number of regions implicated in aMCI and Alzheimer’s disease (AD). As such, interventions targeted towards improving sleep quality amongst the elderly may prove an effective tool for modulating the course of aMCI and AD.

Background The distribution of cranio-spinal compliance (CSC) in the brain and spinal cord is a fundamental question, as it would determine the overall role of the compartments in modulating ICP in healthy and diseased states. Invasive methods for measurement of CSC using infusion-based techniques provide overall CSC estimate, but not the individual sub-compartmental contribution. Additionally, the outcome of the infusion-based method depends on the infusion site and dynamics. This article presents a method to determine compliance distribution between the cranium and spinal canal non-invasively using data obtained from patients. We hypothesize that this CSC distribution is indicative of the ICP. Methods We propose a lumped-parameter model representing the hydro and hemodynamics of the cranio-spinal system. The input and output to the model are phase-contrast MRI derived volumetric transcranial blood flow measured in vivo, and CSF flow at the spinal cervical level, respectively. The novelty of the method lies in the model mathematics that predicts CSC distribution (that obeys the physical laws) from the system dc gain of the discrete-domain transfer function. 104 healthy individuals (48 males, 56 females, age 25.4 ± 14.9 years, range 3–60 years) without any history of neurological diseases, were used in the study. Non-invasive MR assisted estimate of ICP was calculated and compared with the cranial compliance to prove our hypothesis. Results A significant negative correlation was found between model-predicted cranial contribution to CSC and MR-ICP. The spinal canal provided majority of the compliance in all the age groups up to 40 years. However, no single sub-compartment provided majority of the compliance in 41–60 years age group. The cranial contribution to CSC and MR-ICP were significantly correlated with age, with gender not affecting the compliance distribution. Spinal contribution to CSC significantly positively correlated with CSF stroke volume. Conclusions This paper describes MRI-based non-invasive way to determine the cranio-spinal compliance distribution in the brain and spinal canal sub-compartments. The proposed mathematics makes the model always stable and within the physiological range. The model-derived cranial compliance was strongly negatively correlated to non-invasive MR-ICP data from 104 patients, indicating that compliance distribution plays a major role in modulating ICP.

Genetic factors are considered to be important in the pathogenesis of diabetic nephropathy (DN). Despite several genome-wide association studies (GWASs) demonstrating that specific polymorphisms of candidate genes were associated with DN, there were some limitations in previous studies. We conducted a GWAS using customized DNA chips to identify novel susceptibility loci for DN in Korean. We analyzed a total of 414 DN cases and 474 normoalbuminuric diabetic hyper-controls across two stages using customized DNA chips containing 98 667 single nucleotide polymorphisms (SNPs). We explored the associations between SNPs and DN in samples from 87 DN cases, mostly confirmed by renal biopsy, and 104 diabetic hyper-controls, and replicated these associations in independent cohort samples with 327 DN cases and 370 diabetic hyper-controls. The top significant SNPs from the discovery samples were selected for replication in the independent cohort. rs3765156 in PIK3C2B was significantly associated with DN in the replication cohort after multiple test. The SNPs identified in our study provide new insights into the pathogenesis of DN in the Korean population. Additional studies are needed to determine biological effects and clinical utility of our findings.