The anatomy of transcriptionally active chromatin loops in Drosophila primary spermatocytes using super-resolution microscopy.

While the biochemistry of gene transcription has been well studied, our understanding of how this process is organised in 3D within the intact nucleus is less well understood. Here we investigate the structure of actively transcribed chromatin and the architecture of its interaction with active RNA polymerase. For this analysis, we have used super-resolution microscopy to image the Drosophila melanogaster Y loops which represent huge, several megabases long, single transcription units. The Y loops provide a particularly amenable model system for transcriptionally active chromatin. We find that, although these transcribed loops are decondensed they are not organised as extended 10nm fibres, but rather they largely consist of chains of nucleosome clusters. The average width of each cluster is around 50nm. We find that foci of active RNA polymerase are generally located off the main fibre axis on the periphery of the nucleosome clusters. Foci of RNA polymerase and nascent transcripts are distributed around the Y loops rather than being clustered in individual transcription factories. However, as the RNA polymerase foci are considerably less prevalent than the nucleosome clusters, the organisation of this active chromatin into chains of nucleosome clusters is unlikely to be determined by the activity of the polymerases transcribing the Y loops. These results provide a foundation for understanding the topological relationship between chromatin and the process of gene transcription.

Target-enriched nanopore sequencing and de novo assembly reveals co-occurrences of complex on-target genomic rearrangements induced by CRISPR-Cas9 in human cells.

The CRISPR-Cas9 system is widely used to permanently delete genomic regions via dual guide RNAs. Genomic rearrangements induced by CRISPR-Cas9 can occur, but continuous technical developments make it possible to characterize complex on-target effects. We combined an innovative droplet-based target enrichment approach with long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving the allelic co-occurrence of a genomic duplication and inversion of the target region, as well as integrations of exogenous DNA and clustered interchromosomal DNA fragment rearrangements. Furthermore, we found that these genomic alterations led to functional aberrant DNA fragments and can alter cell proliferation. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations, and introduce a data-driven workflow enabling detailed dissection of the on-target sequence content with superior resolution.

Dopamine Modulates Effective Connectivity in Frontal Cortex.

There is increasing evidence that the left lateral frontal cortex is hierarchically organized such that higher-order regions have an asymmetric top-down influence over lower order regions. However, questions remain about the underlying neuroarchitecture of this hierarchical control organization. Within the frontal cortex, dopamine plays an important role in cognitive control functions, and we hypothesized that dopamine may preferentially influence top-down connections within the lateral frontal hierarchy. Using a randomized, double-blind, within-subject design, we analyzed resting-state fMRI data of 66 healthy young participants who were scanned once each after administration of bromocriptine (a dopamine agonist with preferential affinity for D2 receptor), tolcapone (an inhibitor of catechol-O-methyltransferase), and placebo, to determine whether dopaminergic stimulation modulated effective functional connectivity between hierarchically organized frontal regions in the left hemisphere. We found that dopaminergic drugs modulated connections from the caudal middle frontal gyrus and the inferior frontal sulcus to both rostral and caudal frontal areas. In dorsal frontal regions, effectivity connectivity strength was increased, whereas in ventral frontal regions, effective connectivity strength was decreased. These findings suggest that connections within frontal cortex are differentially modulated by dopamine, which may bias the influence that frontal regions exert over each other.

Striatal dopamine synthesis and cognitive flexibility differ between hormonal contraceptive users and nonusers.

In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women's hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women's health.

Variability in Practice and Implementation of Oxygen Target Saturation Policies in United States' Neonatal Intensive Care Units.

OBJECTIVE: This study aimed to describe target oxygen saturation (SpO2) ranges used for premature infants in United States' neonatal intensive care units (NICUs) and to describe if these target SpO2 ranges have changed in recent years. STUDY DESIGN: A 29-question survey focused on target SpO2 practices and policies was distributed via the NICU medical directors listservs for the American Academy of Pediatrics Section of Neonatal-Perinatal Medicine and Pediatrix Medical Group between August and October of 2021. Results were collected via Research Electronic Data Capture (REDCap). RESULTS: We received responses representing 170 unique, levels 2, 3, and 4 NICUs from 36 states. Most NICUs (130, 78%) have recently changed their SpO2 targets in response to target SpO2 clinical trials. Over time, the most commonly reported target SpO2 range has shifted from 88-92% to 90-95%. Of NICUs that changed limits, the most common lower SpO2 limits increased from 88 to 90% and the upper SpO2 limits changed from 92 to 95%. The interquartile range for lower SpO2 limit shifted from 85-88% to 88-90% and the IQR for upper SpO2 limit decreased from 92-95% to 94-95%. Most NICUs had designated conditions that would allow for deviations from standard target SpO2 ranges. These most commonly include pulmonary hypertension (152, 95%), severe bronchopulmonary dysplasia (81, 51%), and retinopathy of prematurity (51, 32%). CONCLUSION: Oxygen saturation limits have changed over time with an overall increase in targeted SpO2. However, there remains considerable interunit variation in SpO2 policies. There is a need to achieve consensus to optimize clinical outcomes. KEY POINTS: · What are the SpO2 ranges in United States' NICUs?. · There is a shift in SpO2 ranges for preterm infants in NICUs across United States.. · Variability still persists in SpO2 ranges for preterm infants in United States' NICUs..

Epstein-Barr Virus Genome Deletions in Epstein-Barr Virus-Positive T/NK Cell Lymphoproliferative Diseases.

The main target cells for Epstein-Barr virus (EBV) infection and persistence are B lymphocytes, although T and NK cells can also become infected. In this paper, we characterize the EBV present in 21 pediatric and adult patients who were treated in France for a range of diseases that involve infection of T or NK cells. Of these 21 cases, 5 pediatric patients (21%) and 11 adult patients (52%) were of Caucasian origin. In about 30% of the cases, some of the EBV genomes contain a large deletion. The deletions are different in every patient but tend to cluster near the BART region of the viral genome. Detailed investigation of a family in which several members have persistent T or NK cell infection by EBV indicates that the virus genome deletions arise or are selected independently in each individual patient. Genome sequence polymorphisms in the EBV in these T or NK cell diseases reflect the geographic origin of the patient and not a distinct type of EBV (the 21 cases studied included examples of both type 1 and type 2 EBV infection). Using virus produced from type 1 or type 2 EBV genomes cloned in bacterial artificial chromosome (BAC) vectors, we demonstrate infection of T cells in cord blood from healthy donors. Our results are consistent with transient infection of some T cells being part of normal asymptomatic infection by EBV in young children. IMPORTANCE EBV contributes to several types of human cancer. Some cancers and nonmalignant lymphoproliferative diseases involving T or NK cells contain EBV. These diseases are relatively frequent in Japan and China and have been shown sometimes to have deletions in the EBV genome in the disease cells. We identify further examples of deletions within the EBV genome associated with T or NK cell diseases, and we provide evidence that the virus genomes with these deletions are most likely selected in the individual cases, rather than being transmitted between people during infection. We demonstrate EBV infection of cord blood T cells by highly characterized, cloned EBV genomes and suggest that transient infection of T cells may be part of normal asymptomatic infection by EBV in young children.

Antiemetic Administration and Its Association with Race: A Retrospective Cohort Study.

BACKGROUND: Anesthesiologists' contribution to perioperative healthcare disparities remains unclear because patient and surgeon preferences can influence care choices. Postoperative nausea and vomiting is a patient- centered outcome measure and a main driver of unplanned admissions. Antiemetic administration is under the sole domain of anesthesiologists. In a U.S. sample, Medicaid insured versus commercially insured patients and those with lower versus higher median income had reduced antiemetic administration, but not all risk factors were controlled for. This study examined whether a patient's race is associated with perioperative antiemetic administration and hypothesized that Black versus White race is associated with reduced receipt of antiemetics. METHODS: An analysis was performed of 2004 to 2018 Multicenter Perioperative Outcomes Group data. The primary outcome of interest was administration of either ondansetron or dexamethasone; secondary outcomes were administration of each drug individually or both drugs together. The confounder-adjusted analysis included relevant patient demographics (Apfel postoperative nausea and vomiting risk factors: sex, smoking history, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use; as well as age) and included institutions as random effects. RESULTS: The Multicenter Perioperative Outcomes Group data contained 5.1 million anesthetic cases from 39 institutions located in the United States and The Netherlands. Multivariable regression demonstrates that Black patients were less likely to receive antiemetic administration with either ondansetron or dexamethasone than White patients (290,208 of 496,456 [58.5%] vs. 2.24 million of 3.49 million [64.1%]; adjusted odds ratio, 0.82; 95% CI, 0.81 to 0.82; P < 0.001). Black as compared to White patients were less likely to receive any dexamethasone (140,642 of 496,456 [28.3%] vs. 1.29 million of 3.49 million [37.0%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.78; P < 0.001), any ondansetron (262,086 of 496,456 [52.8%] vs. 1.96 million of 3.49 million [56.1%]; adjusted odds ratio, 0.84; 95% CI, 0.84 to 0.85; P < 0.001), and dexamethasone and ondansetron together (112,520 of 496,456 [22.7%] vs. 1.0 million of 3.49 million [28.9%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.79; P < 0.001). CONCLUSIONS: In a perioperative registry data set, Black versus White patient race was associated with less antiemetic administration, after controlling for all accepted postoperative nausea and vomiting risk factors.

Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation.

Characteristics of transformed and tumor cells include increased levels of protein synthesis and elevated expression of RNA polymerase (pol) III products, such as tRNAs and 5S rRNA. However, whether deregulated pol III transcription contributes to transformation has been unclear. Generating cell lines expressing an inducible pol III-specific transcription factor, Brf1, allowed us to raise tRNA and 5S rRNA levels specifically. Brf1 induction caused an increase in cell proliferation and oncogenic transformation, whereas depletion of Brf1 impeded transformation. Among the gene products induced by Brf1 is the tRNA(iMet) that initiates polypeptide synthesis. Overexpression of tRNA(iMet) is sufficient to stimulate cell proliferation and allow immortalized fibroblasts to form foci in culture and tumors in mice. The data indicate that elevated tRNA synthesis can promote cellular transformation.

Biofuel blending reduces particle emissions from aircraft engines at cruise conditions.

Aviation-related aerosol emissions contribute to the formation of contrail cirrus clouds that can alter upper tropospheric radiation and water budgets, and therefore climate. The magnitude of air-traffic-related aerosol-cloud interactions and the ways in which these interactions might change in the future remain uncertain. Modelling studies of the present and future effects of aviation on climate require detailed information about the number of aerosol particles emitted per kilogram of fuel burned and the microphysical properties of those aerosols that are relevant for cloud formation. However, previous observational data at cruise altitudes are sparse for engines burning conventional fuels, and no data have previously been reported for biofuel use in-flight. Here we report observations from research aircraft that sampled the exhaust of engines onboard a NASA DC-8 aircraft as they burned conventional Jet A fuel and a 50:50 (by volume) blend of Jet A fuel and a biofuel derived from Camelina oil. We show that, compared to using conventional fuels, biofuel blending reduces particle number and mass emissions immediately behind the aircraft by 50 to 70 per cent. Our observations quantify the impact of biofuel blending on aerosol emissions at cruise conditions and provide key microphysical parameters, which will be useful to assess the potential of biofuel use in aviation as a viable strategy to mitigate climate change.

Sex Differences in In-Hospital Mortality After Open Cardiac Valve Surgery.

BACKGROUND: Cardiac valvular disease affects millions of people worldwide and is a major cause of morbidity and mortality. Female patients have been shown to experience inferior clinical outcomes after nonvalvular cardiac surgery, but recent data are limited regarding open valve surgical cohorts. The primary objective of our study was to assess whether female sex is associated with increased in-hospital mortality after open cardiac valve operations. METHODS: Utilizing the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID), we conducted a retrospective cohort study of patients who underwent open cardiac valve surgery from 2007 to 2018 in Washington, Maryland, Kentucky, and Florida; from 2007 to 2011 in California; and from 2007 to 2016 in New York. The primary objective of this study was to estimate the confounder-adjusted association between sex and in-hospital mortality (as recorded and coded by SID HCUP) after open cardiac valve surgery. We used multilevel multivariable models to account for potential confounders, including intrahospital practice patterns. RESULTS: A total of 272,954 patients (108,443 women; 39.73% of sample population with mean age of 67.6 ± 14.3 years) were included in our analysis. The overall mortality rates were 3.8% for male patients and 5.1% for female patients. The confounder-adjusted odds ratio (OR) for in-hospital mortality for female patients compared to male patients was 1.41 (95% confidence interval [CI], 1.35-1.47; P < .001). When stratifying by surgical type, female patients were also at increased odds of in-hospital mortality ( P < .001) in populations undergoing aortic valve replacement (adjusted OR [aOR], 1.38; 95% CI, 1.25-1.52); multiple valve surgery (aOR, 1.38; 95% CI, 1.22-1.57); mitral valve replacement (aOR, 1.22; 95% CI, 1.12 - 1.34); and valve surgery with coronary artery bypass grafting (aOR, 1.64; 95% CI, 1.54 - 1.74; all P < .001). Female patients did not have increased odds of in-hospital mortality in populations undergoing mitral valve repair (aOR, 1.26; 95% CI, 0.98 - 1.64; P = .075); aortic valve repair (aOR, 0.87; 95% CI, 0.67 - 1.14; P = .32); or any other single valve repair (aOR, 1.10; 95% CI, 0.82 - 1.46; P = .53). CONCLUSIONS: We found an association between female patients and increased confounder-adjusted odds of in-hospital mortality after open cardiac valve surgery. More research is needed to better understand and categorize these important outcome differences. Future research should include observational analysis containing granular and complete patient- and surgery-specific data.

Patient care in rapid-expansion intensive care units during the COVID-19 pandemic crisis.

BACKGROUND: The coronavirus-2019 (COVID-19) pandemic highlighted the unfortunate reality that many hospitals have insufficient intensive care unit (ICU) capacity to meet massive, unanticipated increases in demand. To drastically increase ICU capacity, NewYork-Presbyterian/Weill Cornell Medical Center modified its existing operating rooms and post-anaesthesia care units during the initial expansion phase to accommodate the surge of critically ill patients. METHODS: This retrospective chart review examined patient care in non-standard Expansion ICUs as compared to standard ICUs. We compared clinical data between the two settings to determine whether the expeditious development and deployment of critical care resources during an evolving medical crisis could provide appropriate care. RESULTS: Sixty-six patients were admitted to Expansion ICUs from March 1st to April 30th, 2020 and 343 were admitted to standard ICUs. Most patients were male (70%), White (30%), 45-64 years old (35%), non-smokers (73%), had hypertension (58%), and were hospitalized for a median of 40 days. For patients that died, there was no difference in treatment management, but the Expansion cohort had a higher median ICU length of stay (q = 0.037) and ventilatory length (q = 0.015). The cohorts had similar rates of discharge to home, but the Expansion ICU cohort had higher rates of discharge to a rehabilitation facility and overall lower mortality. CONCLUSIONS: We found no significantly worse outcomes for the Expansion ICU cohort compared to the standard ICU cohort at our institution during the COVID-19 pandemic, which demonstrates the feasibility of providing safe and effective care for patients in an Expansion ICU.

Non-White Race/Ethnicity and Female Sex Are Associated with Increased Allogeneic Red Blood Cell Transfusion in Cardiac Surgery Patients: 2007-2018.

OBJECTIVE: To evaluate racial and/or ethnic and sex disparities in allogeneic and autologous red blood cell (RBC) transfusions in cardiac surgery. DESIGN: A retrospective observational study. SETTING: 2007 to 2018 data from FL, MD, KY, WA, NY, and CA from the State Inpatient Databases (SID), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. PARTICIPANTS: A total of 710,296 inpatients who underwent elective or emergency coronary artery bypass grafting (CABG), cardiac valve surgery,or combination CABG and/or valve surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were cohorted by race and/or ethnicity and sex, as defined by SID-HCUP. Demographic characteristics and comorbidities were compared. Rates and risk-adjusted odds ratios (aOR) were calculated for allogeneic and autologous RBC transfusion (primary outcomes). Additional secondary analyses were conducted for in-hospital mortality, 30-day readmission, 90-day readmission, hospital length of stay, and total charges to examine the effect of RBC transfusion status. Effect modification between race and sex was assessed. When controlling for patient demographics, comorbidities, and hospital characteristics, non-White patients were more likely to receive an allogeneic RBC transfusion during cardiac surgery than White patients (Black: aOR 1.17, 99% CI 1.13-1.20, p < 0.001, Hispanic: aOR 1.22, 99% CI 1.19-1.22, p < 0.001). Women were more likely to receive allogeneic RBC than men (aOR 1.69, 99% CI 1.66-1.72, p < 0.001). In interaction models, non-White women had the highest odds of allogeneic blood transfusion as compared to White men (reference category; Black women: aOR 2.04, 99% CI 1.91-2.17, p < 0.001, Hispanic women: aOR 2.03, 99% CI 1.90-2.16, p < 0.001). CONCLUSION: These findings highlighted the differences in the rates of allogeneic RBC transfusion for non-White and female patients undergoing cardiac surgery, which is a well-established marker of poorer outcomes.

Medicare and Medicaid insurance status is associated with increased allogeneic red blood cell transfusion in cardiac surgery patients: 2007-2018.

BACKGROUND AND AIM: Allogeneic red blood cell (RBC) transfusion and health insurance status are independently associated with perioperative morbidity. The aim of this study was to evaluate the effect of insurance status on allogeneic and autologous transfusion risk in cardiac surgery patients. METHODS: We conducted a retrospective observational study of data spanning 2007-2018 from six states from the State Inpatient Databases. Patients were cohorted by medical insurance type. Rates and risk-adjusted odds ratios (aOR) were calculated for allogenic and autologous RBC transfusions. Interactions between insurance and race/ethnicity were assessed. RESULTS: A total of 710,296 cardiac surgery patients were included. Allogeneic infusions occurred in 34.7% of Medicare patients, 31.9% of Medicaid patients, 24.7% of privately insured patients, and 26.1% of uninsured patients. Autologous rates were 2.3%, 2.5%, 3.4%, and 2.6% for Medicare, Medicaid, privately insured, and uninsured patients, respectively. Medicare and Medicaid patients were more likely to receive allogeneic RBC than privately insured patients (Medicare: aOR: 1.42, 99% confidence interval [CI]: 1.40-1.44, p < .001, Medicaid: aOR: 1.18, 99% CI: 1.14-1.21, p < .001). Nonwhite Medicare patients showed higher odds of allogeneic transfusion compared with White patients with private insurance (Black Medicare: aOR 1.74, 99% CI: 1.65-1.83, p < .001, Hispanic Medicare: aOR 1.92, 99% CI: 1.84-2.00, p < .001). CONCLUSION: Cardiac surgery patients with Medicare and Medicaid insurance demonstrate increased risk of allogeneic RBC transfusion; nonwhite patient groups are particularly vulnerable. Further research is needed to understand the causes and implications of these disparities, and to help ensure equitable care across patient groups.

Disparities in Obstetric Readmissions: A Multistate Analysis, 2007-2014.

OBJECTIVE: Hospital readmissions are generally higher among racial-ethnic minorities and patients of lower socioeconomic status. However, this has not been widely studied in obstetrics. The aim of the study is to determine 30-day postpartum readmission rates by patient-level social determinants of health: race ethnicity, primary insurance payer, and median income, independently and as effect modifiers. STUDY DESIGN: Using state inpatient databases from the health care cost and utilization project from 2007 to 2014, we queried all deliveries. To produce accurate estimates of the effects of parturients' social determinants of health on readmission odds while controlling for confounders, generalized linear mixed models (GLMMs) were used. Additional models were generated with interaction terms to highlight any associations and their effect on the outcome. Adjusted odds ratios (aOR) with 95% confidence intervals are reported. RESULTS: There were 5,129,867 deliveries with 79,260 (1.5%) 30-day readmissions. Of these, 947 (1.2%) were missing race ethnicity. Black and Hispanic patients were more likely to be readmitted within 30 days of delivery, as compared with White patients (p < 0.001 and p < 0.05, respectively). Patients with government insurance were more likely to be readmitted than those with private insurance (p < 0.001). Patients living in the second quartile of median income were also more likely to be readmitted than those living in other quartiles (p < 0.05). Using GLMMs, we observed that Black patients with Medicare were significantly more likely to get readmitted as compared with White patients with private insurance (aOR 2.78, 95% CI 2.50-3.09, p < 0.001). Similarly, Black patients living in the fourth (richest) quartile of median income were more likely to get readmitted, even when compared with White patients living in the first (poorest) quartile of median income (aOR 1.48, 95% CI 1.40-1.57, p < 0.001). CONCLUSION: Significant racial-ethnic disparities in obstetric readmissions were observed, particularly in Black patients with government insurance and even in Black patients living in the richest quartile of median income. KEY POINTS: · Using generalized linear mixed models, we observed significant interactions.. · Government-insured Black patients were 2.78X more likely to be readmitted.. · The wealthiest Black patients were still 1.48X more likely to be readmitted..

Enhanced Recovery after Surgery for Cesarean Delivery: A Quality Improvement Initiative.

OBJECTIVE: Enhanced recovery after surgery (ERAS) was developed as a way to standardize clinical care pathways and communication across multidisciplinary teams to improve patient recovery and reduce hospital length of stay (LOS). Our objective was to implement an ERAS protocol for cesarean delivery (ERAS-CD) and evaluate its efficacy in reducing LOS. STUDY DESIGN: An ERAS-CD program was implemented at our institution in October 2018. Patients undergoing scheduled and unscheduled CD were maintained on an ERAS pathway of care, which included preoperative hydration, standardized intraoperative protocols, and postoperative analgesic regimens as well as early feeding, urinary catheter removal, and ambulation. We compared LOS after delivery (calculated from time of delivery to discharge), readmission rates, health care disparities and postoperative opioid prescribing practices before (October 2017-September 2018) and after (November 2018-October 2019) ERAS implementation. We excluded any outliers, defined as a LOS >25 days. Continuous data are expressed as mean ± standard deviation. Student's t-test and Chi-square were used for statistical comparison with p <0.05 considered statistically significant. RESULTS: There were 1,729 patients who had a CD in the pre-ERAS group with a mean LOS after delivery of 3.32 ± 6.19 days. In the post-ERAS group, 1,753 women underwent CD with a mean LOS after delivery of 2.85 ± 5.79 days, a statistically significant difference from the pre-ERAS group (p <0.001). There was no difference in readmission rates between pre- and post-ERAS implementation groups (1.9 vs. 2.2%, p = 0.53). There was a reduction in health care disparities in postoperative LOS, when stratifying by race-ethnicity, and a reduction in opioid prescribing practices after the implementation of the program. CONCLUSION: With the implementation of an ERAS-CD program, we achieved a reduced LOS, without increasing readmission rates, and saw a reduction in health care disparities and opioid dispensing. A shorter LOS could offer an enhanced patient experience, as well as improved and equitable perioperative outcomes. KEY POINTS: · ERAS-CD is associated with a reduction in postoperative hospital length of stay.. · A reduction in health care disparities by race-ethnicity was observed with the implementation of ERAS-CD.. · A reduction in opioid dispensing was observed with the implementation of ERAS-CD..

Postattenuation neurologic signs after surgical attenuation of congenital portosystemic shunts in dogs: A review.

The development of postattenuation neurologic signs (PANS) is a poorly understood and potentially devastating complication after surgical attenuation of congenital portosystemic shunts in dogs. Postattenuation neurologic signs include seizures but also more subtle neurologic signs such as depression, behavioral changes, tremors, and twitching. They most commonly occur within 7 days postoperatively and are typically unrelated to hyperammonemia, hypoglycemia, or electrolyte disturbances. This narrative review summarizes the findings of 50 publications from 1988-2020 that report occurrence of PANS. While most published reports included only dogs affected by postattenuation seizures (PAS), others included dogs with any form of PANS. Overall, PANS (including PAS) affected 1.6%-27.3% of dogs, whereas incidence of PAS ranged from 0%-18.2%. The etiology of PANS remains unknown; however, several theories have been proposed. Risk factors include preoperative hepatic encephalopathy, increasing age, and possibly certain breeds and extrahepatic shunt morphology. There is increasing evidence that prophylactic antiepileptic drugs do not prevent PANS. Treatment is centered around controlling neurologic signs with antiepileptic drugs and providing supportive intensive care. The 30-day survival rate in studies that included a minimum of four dogs affected by PANS was 0%-100% (median, 50.0%) and 0%-75.0% (median, 37.5%) for those with PAS. Mortality associated with PANS was typically related to occurrence of generalized seizure activity. Prognostic factors positively associated with short-term survival included having a history of preoperative seizures and development of focal seizures only. If affected dogs survived to discharge, survival for several years was possible, and the majority of neurologic signs manifested as part of the phenomenon of PANS appeared to resolve.

Obstetric and perinatal racial and ethnic disparities.

PURPOSE OF REVIEW: Healthcare disparities are health differences that adversely affect disadvantaged populations. In the United States, research shows that women of color, in particular Black and Hispanic women and their offspring, experience disproportionately higher mortality, severe maternal morbidity, and neonatal morbidity and mortality. This review highlights recent population health sciences and comparative effectiveness research that discuss racial and ethnic disparities in maternal and perinatal outcomes. RECENT FINDINGS: Epidemiological research confirms the presence of maternal and neonatal disparities in national and multistate database analysis. These disparities are associated with geographical variations, hospital characteristics and practice patterns, and patient demographics and comorbidities. Proposed solutions include expanded perinatal insurance coverage, increased maternal healthcare public funding, and quality improvement initiatives/efforts that promote healthcare protocols and practice standardization. SUMMARY: Obstetrical healthcare disparities are persistent, prevalent, and complex and are associated with systemic racism and social determinants of health. Some of the excess disparity gap can be explained through community-, hospital-, provider-, and patient-level factors. Providers and healthcare organizations should be mindful of these disparities and strive to promote healthcare justice and patient equity. Several solutions provide promise in closing this gap, but much effort remains.

Enhancing dopamine tone modulates global and local cortical perfusion as a function of COMT val158met genotype.

The cognitive effects of pharmacologically enhancing cortical dopamine (DA) tone are variable across healthy human adults. It has been postulated that individual differences in drug responses are linked to baseline cortical DA activity according to an inverted-U-shaped function. To better understand the effect of divergent starting points along this curve on DA drug responses, researchers have leveraged a common polymorphism (rs4680) in the gene encoding the enzyme catechol-O-methyltransferase (COMT) that gives rise to greater (Met allele) or lesser (Val allele) extracellular levels of cortical DA. Here we examined the extent to which changes in resting cortical perfusion following the administration of two mechanistically-distinct dopaminergic drugs vary by COMT genotype, and thereby track predictions of the inverted-U model. Using arterial spin labeling (ASL) and a double-blind, within-subject design, perfusion was measured in 75 healthy, genotyped participants once each after administration of tolcapone (a COMT inhibitor), bromocriptine (a DA D2/3 agonist), and placebo. COMT genotype and drug interacted such that COMT Val homozygotes exhibited increased prefusion in response to both drugs, whereas Met homozygotes did not. Additionally, tolcapone-related perfusion changes in the right inferior frontal gyrus correlated with altered performance on a task of executive function. No comparable effects were found for a genetic polymorphism (rs1800497) affecting striatal DA system function. Together, these results indicate that both the directionality and magnitude of drug-induced perfusion change provide meaningful information about individual differences in response to enhanced cortical DA tone.

Correction: Epstein-Barr virus nuclear antigen EBNA-LP is essential for transforming naïve B cells, and facilitates recruitment of transcription factors to the viral genome.

[This corrects the article DOI: 10.1371/journal.ppat.1006890.].