Now showing items 21-40 of 14133

    • Effects of neuroactive metabolites of the tryptophan pathway on working memory and cortical thickness in schizophrenia

      Huang, Junchao; Tong, Jinghui; Zhang, Ping; Zhou, Yanfang; Cui, Yimin; Tan, Shuping; Wang, Zhiren; Yang, Fude; Kochunov, Peter; Chiappelli, Joshua; et al. (Springer Nature, 2021-04-01)
      A number of tryptophan metabolites known to be neuroactive have been examined for their potential associations with cognitive deficits in schizophrenia. Among these metabolites, kynurenic acid (KYNA), 5-hydroxyindole (5-HI), and quinolinic acid (QUIN) are documented in their diverse effects on α-7 nicotinic acetylcholine receptor (α7nAChR) and/or N-methyl-D-aspartate receptor (NMDAR), two of the receptor types thought to contribute to cognitive impairment in schizophrenia. In this study, serum levels of KYNA, 5-HI, and QUIN were measured in 195 patients with schizophrenia and in 70 healthy controls using liquid chromatography-tandem mass spectrometry; cognitive performance in MATRICS Consensus Cognitive Battery and cortical thickness measured by magnetic resonance imaging were obtained. Patients with schizophrenia had significantly lower serum KYNA (p < 0.001) and QUIN (p = 0.02) levels, and increased 5-HI/KYNA (p < 0.001) and QUIN/KYNA ratios (p < 0.001) compared with healthy controls. Multiple linear regression showed that working memory was positively correlated with serum 5-HI levels (t = 2.10, p = 0.04), but inversely correlated with KYNA concentrations (t = -2.01, p = 0.05) in patients. Patients with high 5-HI and low KYNA had better working memory than other subgroups (p = 0.01). Higher 5-HI levels were associated with thicker left lateral orbitofrontal cortex (t = 3.71, p = 2.94 × 10-4) in patients. The different effects of 5-HI and KYNA on working memory may appear consistent with their opposite receptor level mechanisms. Our findings appear to provide a new insight into the dynamic roles of tryptophan pathway metabolites on cognition, which may benefit novel therapeutic development that targets cognitive impairment in schizophrenia.
    • Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

      Natarajan, Pradeep; Pampana, Akhil; Graham, Sarah E; Ruotsalainen, Sanni E; Perry, James A; de Vries, Paul S; Broome, Jai G; Pirruccello, James P; Honigberg, Michael C; Aragam, Krishna; et al. (Springer Nature, 2021-04-12)
      Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10-72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10-4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10-5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
    • TELEmedicine for Patients With Inflammatory Bowel Disease (TELE-IBD) Does Not Improve Depressive Symptoms or General Quality of Life Compared With Standard Care at Tertiary Referral Centers

      Schliep, Matthew; Chudy-Onwugaje, Kenechukwu; Abutaleb, Ameer; Langenberg, Patricia; Regueiro, Miguel; Schwartz, David A; Tracy, J Kathleen; Ghazi, Leyla; Patil, Seema A; Quezada, Sandra; et al. (Oxford University Press, 2020-01-31)
      A total of 217 participants were included in this analysis. After 1 year, there was no significant difference in the change in MHI-5 (TELE-IBD W +3.0 vs TELE-IBD EOW +0.7 vs standard care +3.4; P = 0.70), MCS (TELE-IBD W +1.4 vs TELE-IBD EOW +1.0 vs standard care +2.5; P = 0.89), and PCS scores (TELE-IBD W +0.4 vs TELE-IBD EOW +0.6 vs standard care +3.7; P = 0.06) between the groups.
    • Proactive Drug Monitoring Is Associated With Higher Persistence to Infliximab and Adalimumab Treatment and Lower Healthcare Utilization Compared With Reactive and Clinical Monitoring

      Syed, Nauroz; Tolaymat, Mazen; Brown, Sara A; Sivasailam, Barathi; Cross, Raymond K (Oxford University Press, 2020-06-05)
      Background: Serum drug-level assays for infliximab (IFX) and adalimumab (ADA) are widely available and are most often obtained reactively, to determine the next steps in patients with loss of response. Studies done thus far on the use of these assays proactively, or during symptom remission, have had mixed results. Here we investigate persistence on therapy and healthcare utilization in patients on 3 drug-level monitoring strategies. Methods: We conducted a retrospective chart review of 235 patients treated for both Crohn disease and ulcerative colitis on either IFX or ADA. Monitoring strategy was defined as proactive if patients underwent testing at predefined time points regardless of symptoms or signs of disease, reactive if done during relapse, or control if no drug levels were obtained. Groups were compared on persistence on original therapeutic at 1 and 2 years as well as on various measures of healthcare utilization during the 2-year follow-up period. Results: Proactive drug monitoring was associated with a higher likelihood of persistence on therapy at 1 year when compared with the control (odds ratio [OR] = 4.76, 95% confidence interval [CI] = 1.65, 13.67) and reactive groups (OR = 6.10, CI = 2.19, 17.02). Similarly, at 2 years, proactive monitoring was superior to the control (OR = 5.41, CI = 2.26, 12.94) and reactive groups (OR = 4.51, CI = 1.88, 10.80). Proactive monitoring was also associated with lower healthcare utilization across almost all measures related to inflammatory bowel disease. Conclusions: Proactive drug monitoring increases persistence on IFX and ADA in patients with ulcerative colitis or Crohn disease and decreases overall healthcare utilization in these patients. Lay Summary Proactive drug monitoring of infliximab and adalimumab in Crohn disease and ulcerative colitis was associated with a higher likelihood of staying on the original therapeutic at 1 and 2 years, as well as lower healthcare utilization. © 2020 Crohn’s & Colitis Foundation.
    • Commentary: We need to know more about erythropoietin

      D'Ambra, Michael N. (Elsevier BV, 2020-07-31)
    • Uncultivated Viral Populations Dominate Estuarine Viromes on the Spatiotemporal Scale

      Sun, Mengqi; Zhan, Yuanchao; Marsan, David; Páez-Espino, David; Cai, Lanlan; Chen, Feng (American Society for Microbiology, 2021-03-16)
      Viruses are ubiquitous and abundant in the oceans, and viral metagenomes (viromes) have been investigated extensively via several large-scale ocean sequencing projects. However, there have not been any systematic viromic studies in estuaries. Here, we investigated the viromes of the Delaware Bay and Chesapeake Bay, two Mid-Atlantic estuaries. Deep sequencing generated a total of 48,190 assembled viral sequences (>5 kb) and 26,487 viral populations (9,204 virus clusters and 17,845 singletons), including 319 circular viral contigs between 7.5 kb and 161.8 kb. Unknown viruses represented the vast majority of the dominant populations, while the composition of known viruses, such as pelagiphage and cyanophage, appeared to be relatively consistent across a wide range of salinity gradients and in different seasons. A difference between estuarine and ocean viromes was reflected by the proportions of Myoviridae, Podoviridae, Siphoviridae, Phycodnaviridae, and a few well-studied virus representatives. The difference in viral community between the Delaware Bay and Chesapeake Bay is significantly more pronounced than the difference caused by temperature or salinity, indicating strong local profiles caused by the unique ecology of each estuary. Interestingly, a viral contig similar to phages infecting Acinetobacter baumannii ("Iraqibacter") was found to be highly abundant in the Delaware Bay but not in the Chesapeake Bay, the source of which is yet to be identified. Highly abundant viruses in both estuaries have close hits to viral sequences derived from the marine single-cell genomes or long-read single-molecule sequencing, suggesting that important viruses are still waiting to be discovered in the estuarine environment.IMPORTANCE This is the first systematic study about spatial and temporal variation of virioplankton communities in estuaries using deep metagenomics sequencing. It is among the highest-quality viromic data sets to date, showing remarkably consistent sequencing depth and quality across samples. Our results indicate that there exists a large pool of abundant and diverse viruses in estuaries that have not yet been cultivated, their genomes only available thanks to single-cell genomics or single-molecule sequencing, demonstrating the importance of these methods for viral discovery. The spatiotemporal pattern of these abundant uncultivated viruses is more variable than that of cultured viruses. Despite strong environmental gradients, season and location had surprisingly little impact on the viral community within an estuary, but we saw a significant distinction between the two estuaries and also between estuarine and open ocean viromes.
    • Predicting tissue-specific gene expression from whole blood transcriptome.

      Basu, Mahashweta; Wang, Kun; Ruppin, Eytan; Hannenhalli, Sridhar (American Association for the Advancement of Science, 2021-04-02)
      Complex diseases are mediated via transcriptional dysregulation in multiple tissues. Thus, knowing an individual’s tissue-specific gene expression can provide critical information about her health. Unfortunately, for most tissues, the transcriptome cannot be obtained without invasive procedures. Could we, however, infer an individual’s tissue-specific expression from her whole blood transcriptome? Here, we rigorously address this question. We find that an individual’s whole blood transcriptome can significantly predict tissue-specific expression levels for ~60% of the genes on average across 32 tissues, with up to 81% of the genes in skeletal muscle. The tissue-specific expression inferred from the blood transcriptome is almost as good as the actual measured tissue expression in predicting disease state for six different complex disorders, including hypertension and type 2 diabetes, substantially surpassing the blood transcriptome. The code for tissue-specific gene expression prediction, TEEBoT, is provided, enabling others to study its potential translational value in other indications. Copyright © 2021 The Authors, some rights reserved.
    • Collaboration and decision-making on trauma teams: A survey assessment

      Sethuraman, Kinjal N.; Chang, Wan Tsu W.; Zhou, Amy L.; Xia, Boyan; Gingold, Daniel B.; McCunn, Maureen (eScholarship, 2021-01-11)
      Introduction: Leadership, communication, and collaboration are important in well-managed trauma resuscitations. We surveyed resuscitation team members (attendings, fellows, residents, and nurses) in a large urban trauma center regarding their impressions of collaboration among team members and their satisfaction with patient care decisions. Methods: The Collaboration and Satisfaction About Care Decisions in Trauma (CSACD.T) survey was administered to members of ad hoc trauma teams immediately after resuscitations. Survey respondents self-reported their demographic characteristics; the CSACD.T scores were then compared by gender, occupation, self-identified leader role, and level of training. Results: The study population consisted of 281 respondents from 52 teams; 111 (39.5%) were female, 207 (73.7%) were self-reported White, 78 (27.8%) were nurses, and 140 (49.8%) were physicians. Of the 140 physician respondents, 38 (27.1%) were female, representing 13.5% of the total surveyed population. Nine of the 52 teams had a female leader. Men, physicians (vs nurses), fellows (vs attendings), and self-identified leaders trended toward higher satisfaction across all questions of the CSACD.T. In addition to the comparison groups mentioned, women and general team members (vs non-leaders) gave lower scores. Conclusion: Female residents, nurses, general team members, and attendings gave lower CSACD.T scores in this study. Identification of nuances and underlying causes of lower scores from female members of trauma teams is an important next step. Gender-specific training may be necessary to change negative team dynamics in ad hoc trauma teams.
    • Effect of blood pressure variability on outcomes in emergency patients with intracranial hemorrhage

      Tran, Quincy K.; Najafali, Daniel; Tiffany, Laura; Tanveer, Safura; Andersen, Brooke; Dawson, Michelle; Hausladen, Rachel; Jackson, Matthew; Matta, Ann; Mitchell, Jordan; et al. (eScholarship, 2021-01-12)
      Introduction: Patients with spontaneous intracranial hemorrhage (sICH) have high mortality and morbidity, which are associated with blood pressure variability. Additionally, blood pressure variability is associated with acute kidney injury (AKI) in critically ill patients, but its association with sICH patients in emergency departments (ED) is unclear. Our study investigated the association between blood pressure variability in the ED and the risk of developing AKI during sICH patients' hospital stay. Methods: We retrospectively analyzed patients with sICH, including those with subarachnoid and intraparenchymal hemorrhage, who were admitted from any ED and who received an external ventricular drain at our academic center. Patients were identified by the International Classification of Diseases, Ninth Revision (ICD-9). Outcomes were the development of AKI, mortality, and being discharged home. We performed multivariable logistic regressions to measure the association of clinical factors and interventions with outcomes. Results: We analyzed the records of 259 patients: 71 (27%) patients developed AKI, and 59 (23%) patients died. Mean age (± standard deviation [SD]) was 58 (14) years, and 150 (58%) were female. Patients with AKI had significantly higher blood pressure variability than patients without AKI. Each millimeter of mercury increment in one component of blood pressure variability, SD in systolic blood pressure (SBPSD), was significantly associated with 2% increased likelihood of developing AKI (odds ratio [OR] 1.02, 95% confidence interval [CI], 1.005-1.03, p = 0.007). Initiating nicardipine infusion in the ED (OR 0.35, 95% CI, 0.15-0.77, p = 0.01) was associated with lower odds of in-hospital mortality. No ED interventions or blood pressure variability components were associated with patients' likelihood to be discharged home. Conclusion: Our study suggests that greater SBPSD during patients' ED stay is associated with higher likelihood of AKI, while starting nicardipine infusion is associated with lower odds of in-hospital mortality. Further studies about interventions and outcomes of patients with sICH in the ED are needed to confirm our observations. © 2021 Tran et al.
    • Transfer of patients with spontaneous intracranial hemorrhage who need external ventricular drain: Does admission location matter?

      Tran, Quincy K.; Dave, Sagar; Haase, Daniel J.; Tiffany, Laura; Gaasch, Shannon; Chang, Wan Tsu W.; Jones, Kevin; Kole, Matthew J.; Wessell, Aaron; Schwartzbauer, Gary; et al. (eScholarship, 2021-01-12)
      Introduction: Patients with spontaneous intracranial hemorrhage (sICH) are associated with high mortality and require early neurosurgical interventions. At our academic referral center, the neurocritical care unit (NCCU) receives patients directly from referring facilities. However, when no NCCU bed is immediately available, patients are initially admitted to the critical care resuscitation unit (CCRU). We hypothesized that the CCRU expedites transfer of sICH patients and facilitates timely external ventricular drain (EVD) placement comparable to the NCCU. Methods: This is a pre-post study of adult patients transferred with sICH and EVD placement. Patients admitted between January 2011-July 2013 (2011 Control) were compared with patients admitted either to the CCRU or the NCCU (2013 Control) between August 2013-September 2015. The primary outcome was time interval from arrival at any intensive care units (ICU) to time of EVD placement (ARR-EVD). Secondary outcomes included time interval from emergency department transfer request to arrival, and in-hospital mortality. We assessed clinical association by multivariable logistic regressions. Results: We analyzed 259 sICH patients who received EVDs: 123 (48%) CCRU; 81 (31%) 2011 Control; and 55 (21%) in the 2013 Control. The groups had similar characteristics, age, disease severity, and mortality. Median ARR-EVD time was 170 minutes [106-311] for CCRU patients; 241 minutes [152-490] (p < 0.01) for 2011 Control; and 210 minutes [139-574], p = 0.28) for 2013 Control. Median transfer request-arrival time for CCRU patients was significantly less than both control groups. Multivariable logistic regression showed each minute delay in ARR-EVD was associated with 0.03% increased likelihood of death (odds ratio 1.0003, 95% confidence interval, 1.0001-1.006, p = 0.043). Conclusion: Patients admitted to the CCRU had shorter transfer times when compared to patients admitted directly to other ICUs. Compared to the specialty NCCU, the CCRU had similar time interval from arrival to EVD placement. A resuscitation unit like the CCRU can complement the specialty unit NCCU in caring for patients with sICH who require EVDs.
    • Baseline cardiometabolic profiles and SARS-CoV-2 infection in the UK Biobank

      Scalsky, Ryan J; Chen, Yi-Ju; Desai, Karan; O'Connell, Jeffery R; Perry, James A; Hong, Charles C (Public Library of Science, 2021-04-01)
      Background SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. Objective This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. Methods We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. Results Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. Conclusion Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular. © 2021 Scalsky et al.
    • Virtual Face to Face with Dr. Bruce Jarrell: Redefining Aging

      Jarrell, Bruce E.; Brandt, Nicole; Magaziner, Jay S.; Martin, Diane, Ph.D.; Likowski, Alex (2021-04-06)
    • Rotavirus disease burden pre-vaccine introduction in young children in Rural Southern Mozambique, an area of high HIV prevalence

      Acácio, Sozinho; Nhampossa, Tacilta; Quintò, Llorenç; Vubil, Delfino; Garrine, Marcelino; Bassat, Quique; Farag, Tamer; Panchalingam, Sandra; Nataro, James P; Kotloff, Karen L; et al. (Public Library of Science, 2021-04-08)
      Background: Rotavirus vaccines have been adopted in African countries since 2009, including Mozambique (2015). Disease burden data are needed to evaluate the impact of rotavirus vaccine. We report the burden of rotavirus-associated diarrhea in Mozambique from the Global Enteric Multicenter Study (GEMS) before vaccine introduction. Methods: A case-control study (GEMS), was conducted in Manhiça district, recruiting children aged 0-59 months with moderate-to-severe diarrhea (MSD) and less-severe-diarrhea (LSD) between December 2007 and November 2012; including 1-3 matched (age, sex and neighborhood) healthy community controls. Clinical and epidemiological data and stool samples (for laboratory investigation) were collected. Association of rotavirus with MSD or LSD was determined by conditional logistic regression and adjusted attributable fractions (AF) calculated, and risk factors for rotavirus diarrhea assessed. Results: Overall 915 cases and 1,977 controls for MSD, and 431 cases and 430 controls for LSD were enrolled. Rotavirus positivity was 44% (217/495) for cases and 15% (160/1046) of controls, with AF = 34.9% (95% CI: 32.85-37.06) and adjusted Odds Ratio (aOR) of 6.4 p< 0.0001 in infants with MSD compared to 30% (46/155) in cases and 14% (22/154) in controls yielding AF = 18.7%, (95% CI: 12.02-25.39) and aOR = 2.8, p = 0.0011 in infants with LSD. The proportion of children with rotavirus was 32% (21/66) among HIV-positive children and 23% (128/566) among HIV-negative ones for MSD. Presence of animals in the compound (OR = 1.9; p = 0.0151) and giving stored water to the child (OR = 2.0, p = 0.0483) were risk factors for MSD; while animals in the compound (OR = 2.37, p = 0.007); not having routine access to water on a daily basis (OR = 1.53, p = 0.015) and washing hands before cooking (OR = 1.76, p = 0.0197) were risk factors for LSD. Conclusion: The implementation of vaccination against rotavirus may likely result in a significant reduction of rotavirus-associated diarrhea, suggesting the need for monitoring of vaccine impact.
    • Inactivating histone deacetylase HDA promotes longevity by mobilizing trehalose metabolism

      Yu, Ruofan; Cao, Xiaohua; Sun, Luyang; Zhu, Jun-Yi; Wasko, Brian M; Liu, Wei; Crutcher, Emeline; Liu, Haiying; Jo, Myeong Chan; Qin, Lidong; et al. (Nature Publishing Group, 2021-03-31)
      Histone acetylations are important epigenetic markers for transcriptional activation in response to metabolic changes and various stresses. Using the high-throughput SEquencing-Based Yeast replicative Lifespan screen method and the yeast knockout collection, we demonstrate that the HDA complex, a class-II histone deacetylase (HDAC), regulates aging through its target of acetylated H3K18 at storage carbohydrate genes. We find that, in addition to longer lifespan, disruption of HDA results in resistance to DNA damage and osmotic stresses. We show that these effects are due to increased promoter H3K18 acetylation and transcriptional activation in the trehalose metabolic pathway in the absence of HDA. Furthermore, we determine that the longevity effect of HDA is independent of the Cyc8-Tup1 repressor complex known to interact with HDA and coordinate transcriptional repression. Silencing the HDA homologs in C. elegans and Drosophila increases their lifespan and delays aging-associated physical declines in adult flies. Hence, we demonstrate that this HDAC controls an evolutionarily conserved longevity pathway.
    • Implantable cardiac devices in geriatric patients: a primer for primary and geriatric physicians

      Wani, Farah; Amir, Rawan; Aljadah, Michael; Albosta, Michael; Guidi, Jean Claude; Singh, Jagmeet; Kanjwal, Khalil; Kichloo, Asim (MedReviews, 2021-03-30)
      In the next 20 years, the percentage of people older than 65 years of age in the United States is expected to double. Heart disease is the leading cause of mortality in developed nations, including the United States. Due to the increased incidence of cardiac disease in elderly patients, the need for special treatment considerations, including cardiac devices, may be necessary to reduce morbidity and mortality in this patient population. The purpose of this review is to provide a primer of the common cardiac devices used in the management of cardiac disorders in the geriatric patient population. In order to do this, we have performed a literature review for articles related to cardiac devices published between 2000 and 2020, in addition to reviewing guidelines and recommendations from relevant professional societies. We provide readers with an overview of several cardiac devices including implantable loop recorders, pacemakers, cardiac resynchronization therapy, automated implantable cardiac defibrillators, watchman devices, and ventricular assist devices. Indications, contraindications, clinical trial data, and general considerations in the geriatric population were included. Due to the aging population and increased incidence of cardiac disease, clinicians should be aware of the indications and contraindications of cardiac device therapy in the management of various cardiac conditions that afflict the geriatric population. © 2021 The Authors.
    • Perceptions of Resident Autonomy in Internal Medicine, Pediatrics, and Internal Medicine-Pediatrics

      Mieczkowski, Alexandra E; Gonzaga, Alda Maria R; Kraemer, Kevin; Habicht, Robert; Friedland, Allen R; Rubio, Doris; Van Deusen, Reed (Springer Nature, 2021-03-10)
      Of 489 eligible respondents, 215 (44%) responded. Internal medicine-pediatrics residents were more likely than categorical pediatrics residents and pediatrics faculty to disagree that they received an appropriate level of autonomy while on inpatient pediatrics general wards (mean = 2.7 relative to 4.0 and 4.3, categorical residents and faculty; 5-point Likert scale; P < .001). On a 5-point Likert scale, the internal medicine-pediatrics residents were more likely to agree that they received too much oversight on pediatrics general ward rotations (mean, 3.9) compared to internal medicine general ward rotations (mean, 1.9) with a P-value between rotations of <.001. Combined internal medicine-pediatrics perceptions of too much oversight while on pediatric general ward rotations were significantly different from their categorical pediatrics peers (pediatrics mean 2.0, P < .001).
    • Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition.

      Li, Shuaizhang; Zhao, Jinghua; Huang, Ruili; Travers, Jameson; Klumpp-Thomas, Carleen; Yu, Wenbo; MacKerell, Alexander D; Sakamuru, Srilatha; Ooka, Masato; Xue, Fengtian; et al. (National Institute of Environmental Health Sciences, 2021-04-12)
      Background: Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents). Objectives: The objective of the current study was to identify environmental chemicals that inhibit AChE activity using in vitro and in silico models. Methods: To identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively. Results: A group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds. Conclusions: Our tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity.
    • Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review

      Wieland, L Susan; Piechotta, Vanessa; Feinberg, Termeh; Ludeman, Emilie; Hutton, Brian; Kanji, Salmaan; Seely, Dugald; Garritty, Chantelle (Springer Nature, 2021-04-07)
      Background: Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. Methods: We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. Results: We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. Conclusions: Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.
    • Long-term Risk of Hypertension After Surgical Repair of Congenital Heart Disease in Children

      Greenberg, Jason H; McArthur, Eric; Thiessen-Philbrook, Heather; Zappitelli, Michael; Wald, Ron; Kaushal, Sunjay; Ng, Derek K; Everett, Allen D; Chanchlani, Rahul; Garg, Amit X; et al. (American Medical Association, 2021-04-08)
      IMPORTANCE: The long-term risk of hypertension in children after surgery for congenital heart disease (CHD) is unclear. OBJECTIVE: To assess the incidence of hypertension after cardiac surgery in children with CHD. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective matched cohort study was conducted in Ontario, Canada, using administrative databases. A total of 3600 children with surgical repair of CHD were matched to 10 children (n = 36 000) from the general population without CHD on age, sex, index date, rurality, and neighborhood income. MAIN OUTCOMES AND MEASURES: Diagnosis of hypertension over a median follow-up time of 9.8 years (interquartile range, 6.8-12.9 years) after surgery. The last follow-up was March 31, 2019. RESULTS: Overall, in 3600 children with surgical repair of CHD, the median age at first surgery was 150 days (interquartile range, 40-252 days) and 2005 (55.7%) were boys. During follow-up, 445 (12.4%) children with surgical repair of CHD developed hypertension compared with 398 (1.1%) in the matched control group. The incidence rate of hypertension in children who received surgery for CHD was 141.3 (95% CI, 128.8-155.1) per 10 000 person-years compared with children in the matched control group, who had a rate of 11.1 (95% CI, 10.1-12.3) per 10 000 person-years. The risk of hypertension was higher in children with index surgical dates at an age of less 150 days compared with those who had surgical dates at an age of 150 days or older (P = .006 for interaction). The risk of hypertension was increased in children with more complex surgery, particularly children with hypoplastic left heart syndrome (49 of 140 [35.0%]), and in children who received dialysis (22 of 126 [17.5%]; hazard ratio, 1.67; 95% CI, 1.09-2.56) during the index cardiac surgery hospitalization. CONCLUSIONS AND RELEVANCE: The incidence of long-term hypertension in this study was 12 times higher in children with surgical repair of CHD compared with children in the matched control group. The findings suggest that interventions aimed at reducing the long-term risk of hypertension after cardiac surgery in this population are needed.