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Rationale and Objectives To evaluate image quality, radiation dose (phantom study) and tumor volumetry of intraprocedural cone-beam computed tomography (CBCT) compared to postprocedural multidetector computed tomography (MDCT) in patients undergoing hepatic conventional transarterial chemoembolization (cTACE). Materials and Methods One hundred fourteen patients (64/50 female/male; mean age, 57 ± 14 years) who had undergone cTACE including intraprocedural-CBCT and postprocedural-MDCT were retrospectively enrolled. Subjective image quality (IQ) and suitability for assessing Lipiodol distribution were compared using 4-point Likert scales; additionally, lesion to liver contrast (LLC) and contrast-to-noise-ratio (CNR) were compared. Tumor volumes were measured semi-automatically and compared to magnetic resonance imaging (MRI). Effective doses were measured using an anthropomorphic phantom. Results The suitability of CBCT for assessing Lipiodol distribution during cTACE was comparable to MDCT (mean score, 3.2 ± 0.6) and CBCT (3.4 ± 1.0, p = 0.29). Subjective overall IQ was rated with a mean score of 3.2 ± 0.7 (κ = 0.66) in CBCT and 3.1 ± 0.4 (κ = 0.57, p = 0.15) in MDCT. Evaluation of LLC showed significant differences between CBCT and MDCT (mean scores 3.6 ± 1.2 and 2.6 ± 1.5, respectively). CNR analysis demonstrated comparable mean values for CBCT and MDCT (3.5 ± 1.3 vs. 3.4 ± 1.8, p = 0.31). No significant differences were found regarding tumor volumetry (mean volumes: CBCT, 27.0 ± 17.4 mm3; MDCT: 26.8 ± 16.0 mm3; p = 0.66) in comparison to T2-weighted MRI (25.9 ± 17.6 mm3). Effective doses were 3.2 ± 0.6 mSv (CBCT) and 2.5 ± 0.3 mSv (MDCT) (p Conclusion Latest-generation intraprocedural CBCT provides suitable assessment of Lipiodol distribution and similar image quality compared to MDCT while allowing for robust volumetric tumor measurements and immediate complication control by visualizing non-target embolization and hematoma. Therefore, it may improve patient safety and outcome as well as clinical workflow compared to postprocedural MDCT in hepatic cTACE in certain cases.

Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Male Wistar rats (n = 136) underwent sham operation (SH) or aortic banding (AB). Both groups were equally divided into 14 subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME for 4 weeks. HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg

Purpose: To assess and correlate pulmonary involvement and outcome of SARS-CoV-2 pneumonia with the degree of coronary plaque burden based on the CAC-DRS classification (Coronary Artery Calcium Data and Reporting System). Methods: This retrospective study included 142 patients with confirmed SARS-CoV-2 pneumonia (58 ± 16 years; 57 women) who underwent non-contrast CT between January 2020 and August 2021 and were followed up for 129 ± 72 days. One experienced blinded radiologist analyzed CT series for the presence and extent of calcified plaque burden according to the visual and quantitative HU-based CAC-DRS Score. Pulmonary involvement was automatically evaluated with a dedicated software prototype by another two experienced radiologists and expressed as Opacity Score. Results: CAC-DRS Scores derived from visual and quantitative image evaluation correlated well with the Opacity Score (r=0.81, 95% CI 0.76-0.86, and r=0.83, 95% CI 0.77-0.89, respectively; p

BackgroundA large literature demonstrates associations between socioeconomic status (SES) and health, including physiological health and well-being. Moreover, gender differences are often observed among measures of both SES and health. However, relationships between SES and health are sometimes questioned given the lack of true experiments, and the potential biological and SES mechanisms explaining gender differences in health are rarely examined simultaneously.PurposeTo use a national sample of twins to investigate lifetime socioeconomic adversity and a measure of physiological dysregulation separately by sex.MethodsUsing the twin sample in the second wave of the Midlife in the United States survey (MIDUS II), biometric regression analysis was conducted to determine whether the established SES-physiological health association is observed among twins both before and after adjusting for potential familial-level confounds (additive genetic and shared environmental influences that may underly the SES-health link), and whether this association differs among men and women.ResultsAlthough individuals with less socioeconomic adversity over the lifespan exhibited less physiological dysregulation among this sample of twins, this association only persisted among male twins after adjusting for familial influences.ConclusionsFindings from the present study suggest that, particularly for men, links between socioeconomic adversity and health are not spurious or better explained by additive genetic or early shared environmental influences. Furthermore, gender-specific role demands may create differential associations between SES and health.

This paper examines trends and population-level correlates of violent crime rates from 2005 to 2017 in California, including proximity to the U.S./Mexico border and alcohol outlet density. Crime data come from the Crimes and Clearances report compiled by the California Department of Justice. These and U.S. Census data were aggregated at the level of 499 Law Enforcement Reporting Areas (LERA) that contributed to the report. Reported crime rates were related to area characteristics using hierarchical Bayesian Poisson space-time models. Violent crime rates declined 16% from 2005 to 2017. Crime rates were positively related to distance to the border, total alcohol outlet density, percent outlets that are bars and pubs, percent population Black, percent population Hispanic, percent population 30–49 years of age, percent population U.S. born, percent 150% below federal poverty level, percent high school graduate, and percent houses vacant. Violent crimes were negatively related to percent total outlets that are off-premise, percent population male, percent with higher than 2017 adjusted median income, percent owner occupied houses, and lower population density. In conclusion, several population level characteristics including ethnic composition, community socioeconomic stability, and alcohol availability are associated with violent crime rates. Contrary to public perceptions, violent crime rates increase as distance to the Mexico border increases.

BACKGROUND About 30% of all motor vehicle fatalities in the United States are associated with alcohol-impaired motor vehicle crashes. Arrests for drinking and driving (Driving under the influence [DUI]) are 1 of the most important deterrence actions to minimize DUI. This paper examines trends and population-level correlates of drinking driving arrests (DUI) from 2005 to 2017 in California. METHODS Arrest data come from the Monthly Arrest and Citation Register compiled by the California Department of Justice. Sociodemographic and community characteristic data from the U.S. Census, alcohol outlet density, and distance to the U.S.-Mexico border from Law Enforcement Reporting Areas (LERA) centroids were aggregated at the level of 499 LERA contributing to the report. Reported arrest rates were related to area sociodemographic characteristics using hierarchical Bayesian Poisson space-time models. RESULTS Both among men and women rates showed an upward trend until 2008, decreasing after that year. DUI arrest rates were greater among Hispanics than Whites for the 2 younger age groups, 18 to 29 (p

Objective To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19). Methods In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran’s Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity. Results Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52–2.81; p p p p Conclusion A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19 suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.

BACKGROUND Distinguishing the impacts of neighborhood income and off-premise alcohol outlet density on alcohol use has proven difficult, particularly given the conflation of these measures across neighborhood areas. We explicitly test for differential effects related to individual and area income and outlet densities on alcohol use and alcohol use disorders (AUDs) by implementing a stratified microecological sample. METHODS The East Bay Neighborhoods Study included a survey of 984 residents of 72 microenvironments within a geographically contiguous 6-city area in California and Systematic social observations of each site. The sites included 18 areas in each of 4 strata (high/low median household income and off-premise outlet density). We assessed 4 outcomes: 28-day drinking frequency, average quantity of alcohol consumed per drinking occasion, 28-day drinking volume, and Alcohol Use Disorders Identification Test (AUDIT) score. We used zero-inflated negative binomial regression with standard errors adjusted for site clusters to relate drinking measures to individual-level age, race/ethnicity, gender, marital status, education, and income, and neighborhood indicators of site strata, physical disorder, and physical decay. An interaction term was tested representing site-level by individual-level income. RESULTS Living in a high-income site, regardless of off-premise alcohol outlet density, was associated with more frequent drinking and higher alcohol dependence/problems. Both individual-level income and site-level income were related to greater frequencies of use, but lower income drinkers in high-income areas drank more than comparable drinkers in low-income areas. Study participants living in high-density off-premise alcohol outlet sites drank less frequently but did not differ in terms of either AUDIT scores or heavy drinking from participants living in low-density sites. CONCLUSIONS Using a stratified microecological sampling design, we were able to directly assess statistical associations of off-premise outlet density and neighborhood median household income with patterns of drinking and AUDs. Caution should be used interpreting prior study findings linking off-premise outlet densities to drinking.

Background & Aim Under the regulation of various oncogenic pathways, cancer cells undergo adaptive metabolic programming to maintain specific metabolic states that support their uncontrolled proliferation. As it has been difficult to directly and effectively inhibit oncogenic signaling cascades with pharmaceutical compounds, focusing on the downstream metabolic pathways that enable indefinite growth may provide therapeutic opportunities. Thus, we sought to characterize metabolic changes in hepatocellular carcinoma (HCC) development and identify metabolic targets required for tumorigenesis. Methods We compared gene expression profiles of Morris Hepatoma (MH3924a) and DEN (diethylnitrosamine)-induced HCC models to those of liver tissues from normal and rapidly regenerating liver models, and performed gain- and loss-of-function studies of the identified gene targets for their roles in cancer cell proliferation in vitro and in vivo. Results The proline biosynthetic enzyme PYCR1 (pyrroline-5-carboxylate reductase 1) was identified as one of the most upregulated genes in the HCC models. Knockdown of PYCR1 potently reduced cell proliferation of multiple HCC cell lines in vitro and tumor growth in vivo. Conversely, overexpression of PYCR1 enhanced the proliferation of the HCC cell lines. Importantly, PYCR1 expression was not elevated in the regenerating liver, and KD or overexpression of PYCR1 had no effect on proliferation of non-cancerous cells. Besides PYCR1, we found that additional proline biosynthetic enzymes, such as ALDH18A1, were upregulated in HCC models and also regulated HCC cell proliferation. Clinical data demonstrated that PYCR1 expression was increased in HCC, correlated with tumor grade, and was an independent predictor of clinical outcome. Conclusion Enhanced expression of proline biosynthetic enzymes promotes HCC cell proliferation. Inhibition of PYCR1 or ALDH18A1 may be a novel therapeutic strategy to target HCC. Lay summary Even with the recently approved immunotherapies against liver cancer, currently available medications show limited clinical benefits or efficacy in the majority of patients. As such, it remains a top priority to discover new targets for effective liver cancer treatment. Here, we identify a critical role for the proline biosynthetic pathway in liver cancer development, and demonstrate that targeting key proteins in the pathway, namely PYCR1 and ALDH18A1, may be a novel therapeutic strategy for liver cancer.

Background Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting. Methods PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II–III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients’ volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality. Discussion The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients. Trial registration EudraCT 2016-002162-30. ClinicalTrials.govNCT03278548

Background We sought to increase intensive care unit–family meeting (ICU-FM) documentation in the electronic health record in Veterans Affairs (VA) hospitals. Measures Primary outcomes were proportion of VA decedents with ICU-FM and Bereaved Family Survey–Performance Measure (BFS-PM) scores of “excellent.” Intervention Quality improvement (QI) project, clinical champion, and ICU-FM templates were implemented in nine participating VA facilities. ICU-FMs and BFS-PM were determined in decedents between 2011 and 2018. Outcomes ICU-FM increased from 3% to 28% in participating vs. 5% to 6% in nonparticipating facilities over time. Participating facilities were five-fold more likely to have ICU-FMs among ICU decedents (OR = 5.69, [4.45–7.28]). Facility-wide excellent BFS-PM scores increased by 19% in participating vs. nonparticipating facilities at the end of the observation period (OR = 1.19, [1.10–1.30]), but no difference between groups was observed in patients who died in the ICU. Conclusions Increasing ICU-FMs is necessary but not sufficient to improve family-reported satisfaction after an ICU death.

BACKGROUND:Prescription drug monitoring programs (PDMP), by reducing access to prescribed opioids (POs), may contribute to a policy environment in which some people with opioid dependence are at increased risk for transitioning from POs to heroin/other illegal opioids. This study examines how PDMP adoption and changes in the characteristics of PDMPs over time contribute to changes in fatal heroin poisoning in counties within states from 2002 to 2016. METHODS:Latent transition analysis to classify PDMPs into latent classes (Cooperative, Proactive, and Weak) for each state and year, across three intervals (1999-2004, 2005-2009, 2010-2016). We examined the association between probability of PDMP latent class membership and the rate of county-level heroin poisoning death. RESULTS:After adjustment for potential county-level confounders and co-occurring policy changes, adoption of a PDMP was significantly associated with increased heroin poisoning rates (22% increase by third year post-adoption). Findings varied by PDMP type. From 2010-2016, states with Cooperative PDMPs (those more likely to share data with other states, to require more frequent reporting, and include more drug schedules) had 19% higher heroin poisoning rates than states with Weak PDMPs (adjusted rate ratio [ARR]=1.19; 95% CI=1.14, 1.25). States with Proactive PDMPs (those more likely to report outlying prescribing and dispensing and provide broader access to law enforcement) had 6% lower heroin poisoning rates than states with No/Weak PDMPs (ARR=0.94; 95% CI=0.90, 0.98). CONCLUSION:There is a consistent, positive association between state PDMP adoption and heroin poisoning mortality. However, this varies by PDMP type, with Proactive PDMPs associated with a small reduction in heroin poisoning deaths. This raises questions about the potential for PDMPs to support efforts to decrease heroin overdose risk, particularly by using proactive alerts to identify patients in need of treatment for opioid use disorder. Future research on mechanisms explaining the reduction in heroin poisonings after enactment of Proactive PDMPs is merited.

Introduction We sought to understand the association between youthful self-harm and subsequent chronic disease-related healthcare utilization and whether self-harm reflects unique vulnerability in comparison with severe psychiatric disorders. Methods We used a retrospective matched cohort design with statewide, all-payer, individually linked emergency department (ED) data from California, USA. Risk of future ED visits for common chronic conditions in adolescence (headaches, asthma, epilepsy, diabetes, and gastrointestinal disorders, assessed using ICD-9 diagnoses) were compared between three adolescent study groups presenting to an ED in 2010: self-harm patients (n = 5,484), patients with psychiatric complaints but no self-harm (n = 14,235), and patients with other complaints (n = 16,452). Cohort follow-up ended on Sept. 30, 2015. Analyses were adjusted for patients' prior histories of ED utilization for chronic conditions as well as patient- and area-level sociodemographic characteristics. Results Risk of subsequent ED visits was higher among self-harm patients compared to non-psychiatric control patients for subsequent epilepsy- (aRR = 1.77, 95% CI [1.42, 2.21]). Risk of subsequent ED visits was higher among psychiatric patients compared to non-psychiatric control patients for subsequent headache- (aRR = 1.31, 95% CI [1.21, 1.42]), and epilepsy-related problems (aRR = 1.85, 95% CI [1.55, 2.21]). Self-harm patients were at higher risk than psychiatric patients for subsequent gastrointestinal disorder (aRR = 1.76, 95% CI [1.03, 3.01]). Conclusions Findings suggest that self-harm behavior and psychiatric disorders are associated with increased ED utilization for subsequent chronic disease-related ED utilization. Chronic disease among adolescent psychiatric patients should be attended to, potentially involving new models of clinical follow-up care.

BACKGROUND AND AIM To inform the development of effective night-time preventive interventions, our goal was to assess adolescents' residence (i.e. being at) and transitions across contexts during evening hours and risks for drinking and drinking-related problems in relation to contexts and to these transitions. DESIGN Ecological momentary assessment and survey methods. SETTING Twelve mid-sized cities (50 000-500 000 population) in California, USA from December 2014 to September 2015. ANALYTICAL SAMPLE A total of 153 adolescents (mean age = 16.4, 46.2% female). MEASUREMENT Initial conditions (e.g. past-year heavy drinking, gender, best friend's approval of drinking); adolescents' residence (i.e. being at) and transitions between (a) their own homes, (b) others' homes and (c) public spaces (e.g. restaurants, parks, concert venues) at early, middle and late evening hours; drinking in these contexts at early, middle and late evening hours; and drinking-related problems across evening hours. FINDINGS Risks for drinking were 23.5 times greater in others' homes (P

To evaluate the predictive value of volumetric bone mineral density (BMD) assessment of the lumbar spine derived from phantomless dual-energy CT (DECT)-based volumetric material decomposition as an indicator for the 2-year occurrence risk of osteoporosis-associated fractures.L1 of 92 patients (46 men, 46 women; mean age, 64 years, range, 19-103 years) who had undergone third-generation dual-source DECT between 01/2016 and 12/2018 was retrospectively analyzed. For phantomless BMD assessment, dedicated DECT postprocessing software using material decomposition was applied. Digital files of all patients were sighted for 2 years following DECT to obtain the incidence of osteoporotic fractures. Receiver operating characteristic (ROC) analysis was used to calculate cut-off values and logistic regression models were used to determine associations of BMD, sex, and age with the occurrence of osteoporotic fractures.A DECT-derived BMD cut-off of 93.70 mg/cmRetrospective DECT-based volumetric BMD assessment can accurately predict the 2-year risk to sustain an osteoporosis-associated fracture in at-risk patients without requiring a calibration phantom. Lower DECT-based BMD values are strongly associated with an increased risk to sustain fragility fractures.•Dual-energy CT-derived assessment of bone mineral density can identify patients at risk to sustain osteoporosis-associated fractures with a sensitivity of 85.45% and a specificity of 89.19%. •The DECT-derived BMD threshold for identification of at-risk patients lies above the American College of Radiology (ACR) QCT guidelines for the identification of osteoporosis (93.70 mg/cm

Purpose To assess the influence of intravenously injected contrast agent on bone mineral density (BMD) assessment in dual-source dual-energy CT. Methods This retrospective study included 1,031 patients (mean age, 53 ± 7 years; 519 women) who had undergone third-generation dual-source dual-energy CT in context of tumor staging between January 2019 and December 2019. Dedicated postprocessing software based on material decomposition was used for phantomless volumetric BMD assessment of trabecular bone of the lumbar spine. Volumetric trabecular BMD values derived from unenhanced and contrast-enhanced portal venous phase were compared by calculating correlation and agreement analyses using Pearson product-moment correlation, linear regression, and Bland-Altman plots. Results Mean BMD values were 115.53 ± 37.23 and 116.10 ± 37.78 mg/cm3 in unenhanced and contrast-enhanced dual-energy CT series, respectively. Values from contrast-enhanced portal venous phase differed not significantly from those of the unenhanced phase (p = 0.44) and showed high correlation (r = 0.971 [95% CI, 0.969–0.973]) with excellent agreement in Bland-Altman plots. Mean difference of the two phases was 0.61 mg/cm3 (95% limits of agreement, -17.14 and 18.36 mg/cm3). Conclusion Portal venous phase dual-source dual-energy CT allows for accurate opportunistic BMD assessment of trabecular bone of the lumbar spine compared to unenhanced imaging. Therefore, dual-source CT may provide greater flexibility regarding BMD assessment in clinical routine and reduce radiation exposure by avoiding additional osteodensitometry examinations, as contrast-enhanced CT scans in context of tumor staging are increasingly performed in dual-energy mode.

Brain injury induced by acute simian (or human) immunodeficiency virus infection may persist or spontaneously resolve in different brain regions. Identifying the host factor(s) that promotes spontaneous recovery from such injury may reveal targets for therapeutic drug strategies for promoting recovery from acute neuronal injury. The gradual recovery from such injury observed in many, but not all, brain regions in the rhesus macaque model is consistent with the possible existence of a therapeutic window of opportunity for intervening to promote recovery, even in those regions not showing spontaneous recovery. In persons living with human immunodeficiency virus infection, such neuroprotective treatments could ultimately be considered as adjuncts to the initiation of antiretroviral drug therapy., Brain injury occurs within days in simian immunodeficiency virus (SIV) or human immunodeficiency virus (HIV) infection, and some recovery may occur within weeks. Inflammation and oxidative stress associate with such injury, but what drives recovery is unknown. Chronic HIV infection associates with reduced brain frontal cortex expression of the antioxidant/anti-inflammatory enzyme heme oxygenase-1 (HO-1) and increased neuroinflammation in individuals with cognitive impairment. We hypothesized that acute regional brain injury and recovery associate with differences in regional brain HO-1 expression. Using SIV-infected rhesus macaques, we analyzed multiple brain regions through acute and chronic infection (90 days postinfection [dpi]) and quantified viral (SIV gag RNA), synaptic (PSD-95; synaptophysin), axonal (neurofilament/neurofilament light chain [NFL]), inflammatory, and antioxidant (enzymes, including heme oxygenase isoforms [HO-1, HO-2]) markers. PSD-95 was reduced in the brainstem, basal ganglia, neocortex, and cerebellum within 13 dpi, indicating acute synaptic injury throughout the brain. All areas except the brainstem recovered. Unchanged NFL was consistent with no acute axonal injury. SIV RNA expression was highest in the brainstem throughout infection, and it associated with neuroinflammation. Surprisingly, during the synaptic injury and recovery phases, HO-2, and not HO-1, progressively decreased in the brainstem. Thus, acute SIV synaptic injury occurs throughout the brain, with spontaneous recovery in regions other than the brainstem. Within the brainstem, the high SIV load and inflammation, along with reduction of HO-2, may impair recovery. In other brain regions, stable HO-2 expression, with or without increasing HO-1, may promote recovery. Our data support roles for heme oxygenase isoforms in modulating recovery from synaptic injury in SIV infection and suggest their therapeutic targeting for promoting neuronal recovery. IMPORTANCE Brain injury induced by acute simian (or human) immunodeficiency virus infection may persist or spontaneously resolve in different brain regions. Identifying the host factor(s) that promotes spontaneous recovery from such injury may reveal targets for therapeutic drug strategies for promoting recovery from acute neuronal injury. The gradual recovery from such injury observed in many, but not all, brain regions in the rhesus macaque model is consistent with the possible existence of a therapeutic window of opportunity for intervening to promote recovery, even in those regions not showing spontaneous recovery. In persons living with human immunodeficiency virus infection, such neuroprotective treatments could ultimately be considered as adjuncts to the initiation of antiretroviral drug therapy.

Background In morbidly obese patients undergoing laparoscopic bariatric surgery, the combination of obesity-related comorbidities, pneumoperitoneum and extreme posture changes constitutes a high risk of perioperative hemodynamic complications. Thus, an advanced hemodynamic monitoring including continuous cardiac index (CI) assessment is desirable. While invasive catheterization may bear technical difficulties, transesophageal echocardiography is contraindicated due to the surgical procedure. Evidence on the clinical reliability of alternative semi- or non-invasive cardiac monitoring devices is limited. The aim was to compare the non-invasive vascular unloading to a semi-invasive pulse contour analysis reference technique for continuous CI measurements in bariatric surgical patients. Methods This prospective observational study included adult patients scheduled for elective, laparoscopic bariatric surgery after obtained institutional ethics approval and written informed consent. CI measurements were performed using the vascular unloading technique (Nexfin®) and semi-invasive reference method (FloTrac™). At 10 defined measurement time points, the influence of clinically indicated body posture changes, passive leg raising, fluid bolus administration and pneumoperitoneum was evaluated pre- and intraoperatively. Correlation, Bland-Altman and concordance analyses were performed. Results Sixty patients (mean BMI 49.2 kg/m2) were enrolled into the study and data from 54 patients could be entered in the final analysis. Baseline CI was 3.2 ± 0.9 and 3.3 ± 0.8 l/min/m2, respectively. Pooled absolute CI values showed a positive correlation (rs = 0.76, P 92%). Conclusion Non-invasive as compared to semi-invasive CI measurements did not reach criteria of interchangeability for monitoring absolute and trending values of CI in morbidly obese patients undergoing bariatric surgery. Trial registration The study was registered retrospectively on June 12, 2017 with the registration number NCT03184272 .

Previous studies showed that persons living with HIV (PLWH) demonstrate higher brain prefrontal cortex neuroinflammation and immunoproteasome expression compared to HIV-negative individuals; these associate positively with HIV levels. Lower expression of the antioxidant enzyme heme oxygenase 1 (HO-1) was observed in PLWH with HIV-associated neurocognitive impairment (HIV-NCI) compared to neurocognitively normal PLWH. We hypothesized that similar expression patterns occur throughout cortical, subcortical, and brainstem regions in PLWH, and that neuroinflammation and immunoproteasome expression associate with lower expression of neuronal markers. We analyzed autopsied brains (15 regions) from 9 PLWH without HIV-NCI and 7 matched HIV-negative individuals. Using Western blot and RT-qPCR, we quantified synaptic, inflammatory, immunoproteasome, endothelial, and antioxidant biomarkers, including HO-1 and its isoform heme oxygenase 2 (HO-2). In these PLWH without HIV-NCI, we observed higher expression of neuroinflammatory, endothelial, and immunoproteasome markers in multiple cortical and subcortical regions compared to HIV-negative individuals, suggesting a global brain inflammatory response to HIV. Several regions, including posterior cingulate cortex, globus pallidus, and cerebellum, showed a distinct pattern of higher type I interferon (IFN)-stimulated gene and immunoproteasome expression. PLWH without HIV-NCI also had (i) stable or higher HO-1 expression and positive associations between (ii) HO-1 and HIV levels (CSF, plasma) and (iii) HO-1 expression and neuroinflammation, in multiple cortical, subcortical, and brainstem regions. We observed no differences in synaptic marker expression, suggesting little, if any, associated neuronal injury. We speculate that this may reflect a neuroprotective effect of a concurrent HO-1 antioxidant response despite global neuroinflammation, which will require further investigation. Electronic supplementary material The online version of this article (10.1007/s13365-020-00902-8) contains supplementary material, which is available to authorized users.

ObjectiveTo determine whether regulatory variations in the heme oxygenase-1 (HO-1) promoter (GT) n dinucleotide repeat length could identify unique population genetic risks for neurocognitive impairment (NCI) in persons living with HIV (PLWH), we genotyped 528 neurocognitively assessed PLWH of European American and African American descent and linked genotypes to cognitive status.MethodsIn this cross-sectional study of PLWH (the CNS HIV Antiretroviral Therapy Effect Research cohort), we determined HO-1 (GT) n repeat lengths in 276 African Americans and 252 European Americans. Using validated criteria for HIV-associated NCI (HIV NCI), we found associations between allele length genotypes and HIV NCI and between genotypes and plasma markers of monocyte activation and inflammation. For comparison of HO-1 (GT) n allele frequencies with another population of African ancestry, we determined HO-1 (GT) n allele lengths in African PLWH from Botswana (n = 428).ResultsPLWH with short HO-1 (GT) n alleles had a lower risk for HIV NCI (OR = 0.63, 95% CI: 0.42-0.94). People of African ancestry had a lower prevalence of short alleles and higher prevalence of long alleles compared with European Americans, and in subgroup analyses, the protective effect of the short allele was observed in African Americans and not in European Americans.ConclusionsOur study identified the short HO-1 (GT) n allele as partially protective against developing HIV NCI. It further suggests that this clinical protective effect is particularly relevant in persons of African ancestry, where the lower prevalence of short HO-1 (GT) n alleles may limit induction of HO-1 expression in response to inflammation and oxidative stress. Therapeutic strategies that enhance HO-1 expression may decrease HIV-associated neuroinflammation and limit HIV NCI.

BackgroundUnintentional injury, a leading cause of morbidity among adolescents, may also be a risk factor for deliberate self-harm. To inform clinical and public health prevention efforts in adolescent populations, we examined whether distinct subtypes of unintentional injury were differentially associated with deliberate self-harm.MethodsStatewide, all-payer, individually linkable administrative data on adolescent patients presenting to any California emergency department (ED) in 2010 (n=490,071) were used to investigate longitudinal associations between subtypes of unintentional injury and deliberate self-harm. Adolescents aged 10-19years presenting with unintentional drug poisoning, other poisoning, fall, suffocation, or cutting/piercing injuries formed the exposure groups; adolescents presenting with unintentional strike injuries formed the primary referent group. Study patients were followed back in time (2006-2009) to compare the groups' odds of a prior ED visit for deliberate self-harm, as well as forwards in time (2010-2015) to compare their risks of subsequent self-harm.ResultsUnintentional drug-poisoning injury was strongly associated with increased likelihood of ED visits for deliberate self-harm, assessed both retrospectively (adjusted OR=4.52; 95% confidence interval [CI]=3.08, 6.64) and prospectively (adjusted RR=3.74; 95% CI=3.03, 4.60). Positive associations with odds of prior self-harm and/or risk of subsequent self-harm were also observed for patients with unintentional non-drug poisoning, suffocation, and cutting/piercing injuries.ConclusionsCertain subtypes of unintentional injury, particularly drug poisoning, are strongly associated with risk for deliberate self-harm among adolescents, a finding with implications for targeting clinical assessment and intervention in emergency department settings. More research is needed to understand the mechanisms underlying these associations.

Social stratification is an important mechanism of human organization that helps to explain health differences between demographic groups commonly associated with socioeconomic gradients. Individuals, or group of individuals, with similar health profiles may have had different stratification experiences. This is particularly true as social stratification is a significant non-measurable source of systematic unobservable differences in both SES indicators and health statuses of disadvantage. The goal of the present study was to expand the bulk of research that has traditionally treated socioeconomic and demographic characteristics as independent, additive influences on health by examining data from the United States. It is hypothesized that variation in an index of multi-system physiological dysregulation – allostatic load – is associated with social differentiation factors, sorting individuals with similar demographic and socioeconomic characteristics into mutually exclusive econo-demographic classes. The data were from the Longitudinal and Biomarker samples of the national Study of Midlife Development in the US (MIDUS) conducted in 1995 and 2004/2006. Latent class analyses and regression analyses revealed that physiological dysregulation linked to socioeconomic variation among black people, females and older adults are associated with forces of stratification that confound socioeconomic and demographic indicators. In the United States, racial stratification of health is intrinsically related to the degree to which black people in general, and black females in particular, as a group, share an isolated status in society. Findings present evidence that disparities in health emerge from group-differentiation processes to the degree that individuals are distinctly exposed to the ecological, political, social, economic and historical contexts in which social stratification is ingrained. Given that health policies and programmes emanate from said legal and political environments, interventions should target the structural conditions that expose different subgroups to different stress risks in the first place.

Background Survey-based estimates of the prevalence of alcohol abuse, dependence, and disorders in the United States rely upon self-reports of drinking patterns (e.g., binge drinking), social problems (e.g., trouble at work), physiological responses to use (e.g., tolerance), and desistance from use (e.g., withdrawal). Diagnostic criteria derived from these reports enable prevalence estimates of abuse and dependence, but moderating structural relationships among symptom groups may lead some light and moderate drinkers to appear to exhibit an alcohol use disorder (AUD). Methods A dynamic model of drinking and problems predicts that symptoms of dependence will moderate relationships between drinking measures and symptoms of abuse. Wave 1 National Epidemiologic Survey on Alcohol and Related Conditions data on DSM-IV diagnoses of abuse and dependence were used to test predictions from this model and assess whether moderating effects were observed among lighter and heavier drinkers (those who drink 1 to 3 vs. 4 or more drinks on average). A dose-response model that accounts for other known sources of risk heterogeneity related to drinking and problems enabled us to test these predictions. Results As expected from previous work, symptoms of abuse and dependence and dependence criteria were nonlinearly related to drinking patterns; more symptom reports appeared and criteria were met among less frequent drinkers who drank more on each occasion and this pattern of dose-response was substantially moderated among heavier drinkers. Controlling for these effects, relationships between drinking and symptoms of abuse were moderated among respondents who met more dependence criteria. These effects were observed among both lighter and heavier drinkers. Conclusions Moderating relationships observed between measures of drinking, abuse, and dependence criteria among lighter and heavier drinkers suggest that the same etiologic forces are at play among all drinking groups. Greater symptoms of dependence among lighter drinkers may lead to greater reports of symptoms of abuse and an AUD diagnosis.

Objectives The Health and Retirement Study (HRS) was designed as an interdisciplinary study with a strong focus on health, retirement, and socioeconomic environment, to study their dynamic relationships over time in a sample of mid-life adults. The study includes validated self-report measures and individual items that capture the experiences of stressful events (stressor exposures) and subjective assessments of stress (perceived stress) within specific life domains. Methods This article reviews and catalogs the peer-reviewed publications that have used the HRS to examine associations between psychosocial stress measures and psychological, physical health, and economic outcomes. Results We describe the research to date using HRS measures of the following stress types: traumatic and life events, childhood adversity, caregiving and other chronic stressors, discrimination, social strain and loneliness, work stress, and neighborhood disorder. We highlight how to take further advantage of the longitudinal study to test complex biopsychosocial models of healthy aging. Discussion The HRS provides one of the most comprehensive assessments of psychosocial stress in existing population-based studies and offers the potential for a deeper understanding of how psychosocial factors are related to healthy aging trajectories. The next generation of research examining stress and trajectories of aging in the HRS should test complex longitudinal and mediational relationships, include contextual factors in analyses, and include more collaboration between psychologists and population health researchers.

Objective: To describe the barriers and facilitators of end-of-life (EOL) care for Veterans without stable housing (VWSH) as perceived by Veterans at 1 VA medical center and EOL care staff. Design: Qualitative descriptive study. Secondary applied content analysis of data from interviews and focus groups in our parent study. Setting/Participants: VA Puget Sound Health Care System and VWSH. Results: The core emergent theme in the words of Veterans and health-care workers was “meet me where I am,” a statement of what many Veterans want most from their health care. Barriers and facilitators often reflected the presence or absence of important factors such as relationship and trust building, care coordination and flexibility, key individuals and services, and assistance in navigating change. Conclusions: These findings suggest that to improve health care for VWSH, interventions must be multifaceted, including a suite of support services, flexibility and creative problem-solving, and adaptations in communication approaches. The authors offer specific recommendations for improving EOL care for VWSH based on these findings.

Objectives Generativity, or concern with contributing to others, is theorized to be an important goal of mid-to-late life. Greater self-perceptions of generativity are associated with better well-being over time. The aim of this study is to examine how generative self-perceptions and failure to meet generative expectations over time are linked to specific cognitive–affective states (feelings of connectedness, self-worth, and positive affect), and consequently, life satisfaction. Method Analyses used data from Waves 2 and 3 of the National Survey of Midlife Development in the United States (MIDUS). Multiple mediation was utilized to assess whether these cognitive–affective states linked generative failure to decreased life satisfaction. A Johnson–Neyman moderation analysis determined whether these associations vary with age. Results In demographically adjusted regressions, generative contributions and expectations were associated with greater perceived social connectedness, self-worth, and positive effect. Generative failure was associated with lower life satisfaction, a link that was strongest in the middle-aged and young-old and mediated by the cognitive–affective states. Discussion Greater feelings of generativity, and more positive expectations for future contributions, are associated cross-sectionally and over time with better affective well-being. Positive affect, social connectedness, and self-worth may partially explain why generative failure over time is linked to decreased life satisfaction.

Perceptions of neighborhood disorder (trash, vandalism) and cohesion (neighbors trust one another) are related to residents’ health. Affective and behavioral factors have been identified, but often in studies using geographically select samples. We use a nationally representative sample (n = 9032) of United States older adults from the Health and Retirement Study to examine cardiometabolic risk in relation to perceptions of neighborhood cohesion and disorder. Lower cohesion is significantly related to greater cardiometabolic risk in 2006/2008 and predicts greater risk four years later (2010/2012). The longitudinal relation is partially accounted for by anxiety and physical activity.

Background Despite high abstinence rates, American Indians experience elevated rates of many alcohol and other drug problems. American Indians also predominantly reside in poor and rural areas, which may explain some observed health disparities. We investigated whether geographic areas including reservations or large American Indian populations exhibited greater incidence of alcohol- and drug-related hospitalizations. Methods We obtained inpatient hospitalization records for 2 Northern Plain states (Nebraska and South Dakota) for the years 2007 to 2012. We constructed zip code counts for 10 categories of hospitalization with diagnoses or injury causation commonly associated with alcohol or drug use. We related these to community sociodemographic characteristics using Bayesian Poisson space-time regression models and examined associations with and without controls for whether each zip code was located within an American Indian reservation. Results Controlling for other demographic and economic characteristics, zip codes with greater percentage of American Indians exhibited greater incidence for all 10 substance abuse-related health outcomes (9 of 10 well supported); zip code areas within American Indian reservations had greater incidence of self-inflicted injury and drug dependence and abuse, and reduced incidence of alcohol cirrhosis and prescription opioid poisoning. However, the analyses generally demonstrated no well-supported differences in incidence associated with local residence percentages of American Indian versus African American. Conclusions In our analyses, ethnicity or heredity alone did not account for alcohol- and drug-related hospitalizations among Native populations. Aspects of social, economic, and political dimensions of Native lives must be considered in the etiology of alcohol- and drug-related problems for rural-dwelling indigenous peoples.

Purpose Regular physical activity is a key component of healthy aging, but few older adults meet physical activity guidelines. Poor aging expectations can contribute to this lack of activity, since negative stereotypes about the aging process can be internalized and affect physical performance. Although prior cross-sectional studies have shown that physical activity and aging expectations are associated, less is known about this association longitudinally, particularly among traditionally underrepresented groups. It is also unclear whether different domains of aging expectations are differentially associated with physical activity. Design and Methods The number of minutes/week of physical activity in which Baltimore Experience Corps Trial participants (N = 446; 92.6% African American) engaged were measured using the CHAMPS questionnaire, while their aging expectations were measured using the ERA-12 survey. Linear mixed effects models assessed the association between physical activity and aging expectations over 2 years, both in full and sex-stratified samples. Separate models were also fit for different ERA-12 domains. Results We found that higher overall expectations regarding aging are associated with higher engagement in moderate- to high-intensity physical activity over a 2-year period of time for women only. When the ERA-12 domains were examined separately, only the physical domain was associated with physical activity, both in women and overall. Implications Low expectations regarding physical aging may represent a barrier to physical activity for older adults. Given that most older adults do not meet recommended physical activity guidelines, identifying factors that improve aging expectations may be a way to increase physical activity levels in aging populations.