Second-Line Uterotonics for Uterine Atony: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the comparative efficacy of two of the most commonly used second-line uterotonics-methylergonovine maleate and carboprost tromethamine. METHODS: We conducted a double-blind randomized trial at two large academic perinatal centers in patients undergoing nonemergency cesarean delivery with uterine atony refractory to oxytocin, as diagnosed by the operating obstetrician. The intervention included administration of a single dose of intramuscular methylergonovine or carboprost intraoperatively at diagnosis. The primary outcome, uterine tone on a 0-10 numeric rating scale 10 minutes after study drug administration, was rated by operating obstetricians blinded to the drug administered. Secondary outcomes included uterine tone score at 5 minutes, administration of additional uterotonic agents, other interventions for uterine atony or hemorrhage, quantitative blood loss, urine output, postpartum change in serum hematocrit, transfusion, length of hospital stay, adverse drug or transfusion reactions, and postpartum hemorrhage complications. A sample size of 50 participants per group was planned to detect a 1-point difference (with estimated within-group SD of 1.5) in the mean primary outcome with 80% power at a two-sided α level of 0.05 while accounting for potential protocol violations. RESULTS: A total of 1,040 participants were enrolled, with 100 randomized to receive one of the study interventions. Mean±SD 10-minute uterine tone scores were 7.3±1.7 after methylergonovine and 7.6±2.1 after carboprost, with an adjusted difference in means of -0.1 (95% CI, -0.8 to 0.6, P=.76). Additional second-line uterotonics were required in 30.0% of the methylergonovine arm and 34.0% in the carboprost arm (adjusted odds ratio 0.72, 95% CI, 0.27-1.89, P=.505), and geometric mean quantitative blood loss was 756 mL (95% CI, 636-898) and 708 mL (95% CI, 619-810) (adjusted ratio of geometric means 1.06, 95% CI, 0.86-1.31, P=.588), respectively. No differences were detected in the occurrence of other interventions for uterine atony or postpartum hemorrhage. CONCLUSION: No difference was detected in uterine tone scores 10 minutes after administration of either methylergonovine or carboprost for refractory uterine atony, indicating that either agent is acceptable. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03584854.

Atrial fibrillation after cardiac surgery: identifying candidate predictors through a Delphi process.

OBJECTIVES: This study was undertaken to identify potential predictors of atrial fibrillation after cardiac surgery (AFACS) through a modified Delphi process and expert consensus. These will supplement predictors identified through a systematic review and cohort study to inform the development of two AFACS prediction models as part of the PARADISE project (NCT05255224). Atrial fibrillation is a common complication after cardiac surgery. It is associated with worse postoperative outcomes. Reliable prediction of AFACS would enable risk stratification and targeted prevention. Systematic identification of candidate predictors is important to improve validity of AFACS prediction tools. DESIGN: This study is a Delphi consensus exercise. SETTING: This study was undertaken through remote participation. PARTICIPANTS: The participants are an international multidisciplinary panel of experts selected through national research networks. INTERVENTIONS: This is a two-stage consensus exercise consisting of generating a long list of variables, followed by refinement by voting and retaining variables selected by at least 40% of panel members. RESULTS: The panel comprised 15 experts who participated in both stages, comprising cardiac intensive care physicians (n=3), cardiac anaesthetists (n=2), cardiac surgeons (n=1), cardiologists (n=4), cardiac pharmacists (n=1), critical care nurses (n=1), cardiac nurses (n=1) and patient representatives (n=2). Our Delphi process highlighted candidate AFACS predictors, including both patient factors and those related to the surgical intervention. We generated a final list of 72 candidate predictors. The final list comprised 3 demographic, 29 comorbidity, 4 vital sign, 13 intraoperative, 10 postoperative investigation and 13 postoperative intervention predictors. CONCLUSIONS: A Delphi consensus exercise has the potential to highlight predictors beyond the scope of existing literature. This method proved effective in identifying a range of candidate AFACS predictors. Our findings will inform the development of future AFACS prediction tools as part of the larger PARADISE project. TRIAL REGISTRATION NUMBER: NCT05255224.

Conference proceedings: Inaugural meeting of the consortium for autism, genetic neurodevelopmental disorders, and digestive diseases.

OBJECTIVES: Individuals with neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), often experience a higher prevalence of gastrointestinal (GI) symptoms but have complex medical and behavioral comorbidities that make diagnosis and treatment difficult. A multi-stakeholder conference was convened to (a) determine patient and family experiences related to GI symptoms in NDDs, (b) review the clinicians' and researchers' perspectives, and (c) determine actionable steps for future research. METHODS: The Consortium for Autism, Neurodevelopmental Disorders and Digestive Diseases (CANDID; www.candidgi.com) virtually over 2 days in 2022 and consisted of four key activities: (1) an electronic family survey to assess underlying NDDs and GI symptoms, (2) a session focused on family perspectives, (3) review current clinical care and research, and (4) discussion to identify key next steps. Survey results were obtained electronically via the REDCap platform, and descriptive statistics were generated. The sessions were recorded, and themes were identified. RESULTS: The pre-conference survey ran for ~2 months and 739 families provided responses, with 634 completing all items. 83% had a child with an NDD under age 18, and most patients were White (85%) and non-Hispanic (87%). Constipation (80%), GI reflux disease (51%), and bloating (49%) were the most frequently reported symptoms. Families gave unstructured feedback that the measures used in the surveys were often difficult to answer for patients with NDDs or who were nonspeaking. Family and clinical/scientific sessions identified several common themes, including (1) the need for less invasive diagnostic modalities, (2) the need to validate or adapt existing diagnostic measures (e.g., the Rome IV criteria) and outcome assessments, and (3) the need for enhanced attention to parent and caregiver input in treatment plans. CONCLUSIONS: Those providing care to children with NDDs, especially those with communication and cognitive challenges, should be aware of the differing needs in this community and consider family perspectives in managing, treating, and measuring GI issues. Future research should focus on adapting or creating diagnostic and research measures for those with NDDs, developing new diagnostic methods to account for diversity in neurodevelopment and communication, and improving methods for family and caregiver engagement in the care of GI disorders.

Neonatal intestinal colonization of Streptococcus agalactiae and the multiple modes of protection limiting translocation.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a predominant pathogen of neonatal sepsis, commonly associated with early-onset neonatal sepsis. GBS has also been associated with cases of late-onset sepsis potentially originating from the intestine. Previous findings have shown GBS can colonize the infant intestinal tract as part of the neonatal microbiota. To better understand GBS colonization dynamics in the neonatal intestine, we collected stool and milk samples from prematurely born neonates for identification of potential pathogens in the neonatal intestinal microbiota. GBS was present in approximately 10% of the cohort, and this colonization was not associated with maternal GBS status, delivery route, or gestational weight. Interestingly, we observed the relative abundance of GBS in the infant stool negatively correlated with maternal IgA concentration in matched maternal milk samples. Using a preclinical murine model of GBS infection, we report that both vertical transmission and direct oral introduction resulted in intestinal colonization of GBS; however, translocation beyond the intestine was limited. Finally, vaccination of dams prior to breeding induced strong immunoglobulin responses, including IgA responses, which were associated with reduced mortality and GBS intestinal colonization. Taken together, we show that maternal IgA may contribute to infant immunity by limiting the colonization of GBS in the intestine.

Replication protein A dynamically re-organizes on primer/template junctions to permit DNA polymerase δ holoenzyme assembly and initiation of DNA synthesis.

DNA polymerase δ (pol δ) holoenzymes, comprised of pol δ and the processivity sliding clamp, PCNA, carry out DNA synthesis during lagging strand replication, initiation of leading strand replication, and the major DNA damage repair and tolerance pathways. Pol δ holoenzymes are assembled at primer/template (P/T) junctions and initiate DNA synthesis in a stepwise process involving the major single strand DNA (ssDNA)-binding protein complex, RPA, the processivity sliding clamp loader, RFC, PCNA and pol δ. During this process, the interactions of RPA, RFC and pol δ with a P/T junction all significantly overlap. A burning issue that has yet to be resolved is how these overlapping interactions are accommodated during this process. To address this, we design and utilize novel, ensemble FRET assays that continuously monitor the interactions of RPA, RFC, PCNA and pol δ with DNA as pol δ holoenzymes are assembled and initiate DNA synthesis. Results from the present study reveal that RPA remains engaged with P/T junctions throughout this process and the RPA•DNA complexes dynamically re-organize to allow successive binding of RFC and pol δ. These results have broad implications as they highlight and distinguish the functional consequences of dynamic RPA•DNA interactions in RPA-dependent DNA metabolic processes.

Replication of [AT/TA]25 Microsatellite Sequences by Human DNA Polymerase δ Holoenzymes Is Dependent on dNTP and RPA Levels.

Fragile sites are unstable genomic regions that are prone to breakage during stressed DNA replication. Several common fragile sites (CFS) contain A+T-rich regions including perfect [AT/TA] microsatellite repeats that may collapse into hairpins when in single-stranded DNA (ssDNA) form and coincide with chromosomal hotspots for breakage and rearrangements. While many factors contribute to CFS instability, evidence exists for replication stalling within [AT/TA] microsatellite repeats. Currently, it is unknown how stress causes replication stalling within [AT/TA] microsatellite repeats. To investigate this, we utilized FRET to characterize the structures of [AT/TA]25 sequences and also reconstituted lagging strand replication to characterize the progression of pol δ holoenzymes through A+T-rich sequences. The results indicate that [AT/TA]25 sequences adopt hairpins that are unwound by the major ssDNA-binding complex, RPA, and the progression of pol δ holoenzymes through A+T-rich sequences saturated with RPA is dependent on the template sequence and dNTP concentration. Importantly, the effects of RPA on the replication of [AT/TA]25 sequences are dependent on dNTP concentration, whereas the effects of RPA on the replication of A+T-rich, nonstructure-forming sequences are independent of dNTP concentration. Collectively, these results reveal complexities in lagging strand replication and provide novel insights into how [AT/TA] microsatellite repeats contribute to genome instability.

Streptococcus agalactiae and Escherichia coli induce distinct effector γδ T cell responses during neonatal sepsis.

Neonates born prematurely are vulnerable to life-threatening conditions such as bacterial sepsis. Streptococcus agalactiae (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, however, it remains unclear if these pathogens induce differential immune responses. We find that γδ T cells rapidly respond to single-organism GBS and E. coli bloodstream infections in neonatal mice. Furthermore, GBS and E. coli induce distinct cytokine production from IFN-γ and IL-17 producing γδ T cells, respectively. We also find that IL-17 production during E. coli infection is driven by γδTCR signaling, whereas IFN-γ production during GBS infection occurs independently of γδTCR signaling. The divergent effector responses of γδ T cells during GBS and E. coli infections impart distinctive neuroinflammatory phenotypes on the neonatal brain. Thus, the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.

Shifts in Students' Attitudes Towards Pain Patients, Pain, and Opioid Management Following a Dedicated Medical School Pain Curriculum.

Objective: To examine the immediate effects of a comprehensive pain course on medical students' pre-existing perceptions and attitudes toward pain patients and opioid management. Methods: First-year medical students at a major academic medical center enrolled in a required pre-clerkship pain course in June 2020 and completed pre- and post-course online surveys with Likert-scale questions about their attitudes toward pain management and opioid-related issues. Additionally, the surveys included a free-text question where the students listed the first five words that came to mind when hearing the word "opioids". These words were categorized as "professional" or "lay" words and further as having "positive", "negative", or "neutral" connotations. Data analyses included descriptive statistics, as well as non-parametric and parametric tests. Results: Fifty-four of the 119 students responded to pretest and posttest surveys and were included in paired analyses. There was a significant difference between the number of professional words used before (M=1.21, SD=0.97) and after the course (M=2.40 SD=1.33); t(52)=-6.39, P<0.001. Students also used more lay-positive words after the course (M=0.81, SD=0.63) than they used pre-course (M=0.23, SD=0.43); t(51)=-5.98, P<0.001. Students' post-course responses to several key Likert-scale questions showed significant shifts toward more positive attitudes about caring for patients with pain. For example, students acknowledged greater comfort in providing opioids for chronic pain (P<0.001) where appropriate, and enhanced interest in handling complex pain cases (P<0.001). Conclusion: Results showed that a comprehensive, multi-disciplinary pain course could greatly enhance first-year medical students' attitudes toward pain management, chronic pain patients, and the complex issues surrounding opioids.

Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires.

BACKGROUND: Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models. METHODS: In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery. RESULTS: A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain. CONCLUSIONS: The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

Postoperative and postdischarge nausea and vomiting following ambulatory eye, head, and neck surgeries: a retrospective cohort study comparing incidence and associated factors.

BACKGROUND: Ambulatory surgery is often followed by the development of nausea and/or vomiting (N/V). Although risk factors for postoperative nausea and vomiting (PONV) are frequently discussed, the distinction between PONV and postdischarge nausea and vomiting (PDNV) is unclear. This is especially troublesome given the potential consequences of postdischarge nausea and vomiting (PDNV), which include major discomfort and hospital readmission. METHODS: In this retrospective cohort study, data from 10,231 adult patients undergoing ambulatory ophthalmology or otolaryngology procedures with general anesthesia were collected and analyzed. Binary and multinomial logistic regression was used to assess the association between patient and anesthetic characteristics (including age, body mass index (BMI), American Society of Anesthesiologists Physical Status (ASA P/S) classification, current smoker status, and intra- and postoperative opioid usage) and the odds ratios of experiencing only PDNV, only PONV, or both PONV and PDNV, as compared to not experiencing N/V at all. RESULTS: We found that 17.8% of all patients developed N/V (PONV and/or PDNV). Patients who experienced PONV had a 2.79 (95% confidence interval 2.24-3.46) times greater risk of reporting PDNV. Binary logistic regression found that younger age, opioid use, and female sex were associated with an increased likelihood of experiencing any N/V. Increased use of nitrous oxide and a higher ASA P/S class was associated with elevated likelihood of PONV, but not PDNV or PONV plus PDNV. CONCLUSIONS: Patients experiencing N/V in the PACU are observed to develop PDNV disproportionately by a factor of 2.79. The patients have distinct predictors, indicating important opportunities for care improvements beyond current guidelines.

Serotonin Strengthens a Developing Glutamatergic Synapse through a PI3K-Dependent Mechanism.

It is well established that, during neural circuit development, glutamatergic synapses become strengthened via NMDA receptor (NMDAR)-dependent upregulation of AMPA receptor (AMPAR)-mediated currents. In addition, however, it is known that the neuromodulator serotonin is present throughout most regions of the vertebrate brain while synapses are forming and being shaped by activity-dependent processes. This suggests that serotonin may modulate or contribute to these processes. Here, we investigate the role of serotonin in the developing retinotectal projection of the Xenopus tadpole. We altered endogenous serotonin transmission in stage 48/49 (∼10-21 days postfertilization) Xenopus tadpoles and then carried out a set of whole-cell electrophysiological recordings from tectal neurons to assess retinotectal synaptic transmission. Because tadpole sex is indeterminate at these early stages of development, experimental groups were composed of randomly chosen tadpoles. We found that pharmacologically enhancing and reducing serotonin transmission for 24 h up- and downregulates, respectively, AMPAR-mediated currents at individual retinotectal synapses. Inhibiting 5-HT2 receptors also significantly weakened AMPAR-mediated currents and abolished the synapse strengthening effect seen with enhanced serotonin transmission, indicating a 5-HT2 receptor-dependent effect. We also determine that the serotonin-dependent upregulation of synaptic AMPAR currents was mediated via an NMDAR-independent, PI3K-dependent mechanism. Altogether, these findings indicate that serotonin regulates AMPAR currents at developing synapses independent of NMDA transmission, which may explain its role as an enabler of activity-dependent plasticity.

Streptococcus agalactiae and Escherichia coli Induce Distinct Effector γδ T Cell Responses During Neonatal Sepsis.

Neonates born prematurely are highly vulnerable to life-threatening conditions such as bacterial sepsis. Streptococcus agalactiae, also known as group B Streptococcus (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, however, it remains unclear if distinct sepsis pathogens induce differential adaptive immune responses. In the present study, we find that γδ T cells in neonatal mice rapidly respond to single-organism GBS and E. coli bloodstream infections and that these pathogens induce distinct activation and cytokine production from IFN-γ and IL-17 producing γδ T cells, respectively. We also report differential reliance on γδTCR signaling to elicit effector cytokine responses during neonatal sepsis, with IL-17 production during E. coli infection being driven by γδTCR signaling, and IFN-γ production during GBS infection occurring independently of γδTCR signaling. Furthermore, we report that the divergent effector responses of γδ T cells during GBS and E. coli infections impart distinctive neuroinflammatory phenotypes on the neonatal brain. The present study reveals that the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.

The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: a large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL).

ABSTRACT: A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL-Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. We assessed pain among those reaching the end of the VITAL intervention phase using questions from the 2012 National Health Interview Survey. We used ordinal logistic regression to test the effect of vitamin D and omega-3 fatty acids on the odds ratio (OR) and 95% confidence interval [CI] of reporting higher pain prevalence or severity. Overall, 19,611 participants provided complete pain information at the end of the VITAL trial. The ORs for higher pain prevalence or severity for vitamin D and omega-3 supplementation vs placebo were 0.99 ([CI] 0.94-1.05) and 0.99 ([CI] 0.94-1.04), respectively. There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U.S. adults.

Replication of [AT/TA]25 microsatellite sequences by human DNA polymerase δ holoenzymes is dependent on dNTP and RPA levels.

Difficult-to-Replicate Sequences (DiToRS) are natural impediments in the human genome that inhibit DNA replication under endogenous replication. Some of the most widely-studied DiToRS are A+T-rich, high "flexibility regions," including long stretches of perfect [AT/TA] microsatellite repeats that have the potential to collapse into hairpin structures when in single-stranded DNA (ssDNA) form and are sites of recurrent structural variation and double-stranded DNA (dsDNA) breaks. Currently, it is unclear how these flexibility regions impact DNA replication, greatly limiting our fundamental understanding of human genome stability. To investigate replication through flexibility regions, we utilized FRET to characterize the effects of the major ssDNA-binding complex, RPA, on the structure of perfect [AT/TA]25 microsatellite repeats and also re-constituted human lagging strand replication to quantitatively characterize initial encounters of pol δ holoenzymes with A+T-rich DNA template sequences. The results indicate that [AT/TA]25 sequences adopt hairpin structures that are unwound by RPA and pol δ holoenzymes support dNTP incorporation through the [AT/TA]25 sequences as well as an A+T-rich, non-structure forming sequence. Furthermore, the extent of dNTP incorporation is dependent on the sequence of the DNA template and the concentration of dNTPs. Importantly, the effects of RPA on the replication of [AT/TA]25 sequences are dependent on the concentration of dNTPs, whereas the effects of RPA on the replication of an A+T-rich, non-structure forming sequence are independent of dNTP concentration. Collectively, these results reveal complexities in lagging strand replication and provide novel insights into how flexibility regions contribute to genome instability.

Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine.

BACKGROUND: The dural puncture epidural (DPE) technique has a faster onset, better sacral spread, and improved bilateral coverage when compared to the conventional epidural (EPL) technique. Whether these qualities translate into a lower bupivacaine dose to provide initial analgesia is unknown. We sought to determine the effective dose of bupivacaine to achieve initial (first 30 minutes) labor analgesia in 90% of patients (ED90) with the DPE and EPL techniques, using a biased-coin, sequential allocation method. METHODS: A total of 100 women of mixed parity with term, singleton gestation at ≤5 cm dilation with no major comorbidities were randomized to receive a DPE or an EPL technique. An experienced anesthesiologist performed these techniques and administered an allocated dose of plain bupivacaine diluted with isotonic sterile 0.9% saline to a total volume of 20 mL via the EPL catheter. Bupivacaine doses for each subject were determined by the response of the previous subject, using a biased-coin sequential allocation method, with success defined by a numeric rating scale (NRS) < 3 at 30 minutes. Outcome assessments were performed by an investigator blinded to the technique and bupivacaine dose. Sensory and motor blockade and maternal or fetal side effects were recorded every 5 minutes for the first 30 minutes. The ED90 of bupivacaine with each technique was estimated using centered isotonic regression. RESULTS: A total of 95 women were included in the final analysis. The ED90 of bupivacaine was estimated at 29.30 mg (90% confidence interval [CI], 28.55-31.56) with a DPE technique and 45.25 mg (90% CI, 42.80-52.03) with an EPL technique. CONCLUSIONS: Using a biased-coin, sequential allocation method, the DPE technique requires less bupivacaine to achieve effective initial analgesia (ED90) when compared to the EPL technique.

Does the Association Between Psychosocial Factors and Opioid Use After Elective Spine Surgery Differ by Sex in Older Adults?

Purpose: Psychosocial disorders have been linked to chronic postoperative opioid use and the development of postoperative pain. The potential interaction between sex and psychosocial factors with respect to opioid use after elective spine surgery in the elderly has not yet been evaluated. Our aim was to assess whether any observed association of anxiety or depression indicators with opioid consumption in the first 72 hours after elective spine surgery varies by sex in adults ≥65 years. Patients and Methods: Secondary analysis of a retrospective cohort of 647 elective spine surgeries performed at Brigham and Women's Hospital, July 1, 2015-March 15, 2017, in patients ≥65. Linear mixed-effects models were used to test whether history of anxiety, anxiolytic use, history of depression, and antidepressant use were associated with opioid consumption 0-24, 24-48, and 48-72 post surgery, and whether these potential associations differed by sex. Results: History of anxiety, anxiolytic use, history of depression, and antidepressant use were more common among women (51.3% of the sample). During the first 24 hours after surgery, men with a preoperative history of anxiety consumed an adjusted mean of 19.5 morphine milligram equivalents (MME) (99.6% CI: 8.1, 31.0) more than men without a history of anxiety; women with a history of anxiety only consumed an adjusted mean 2.9 MME (99.6% CI: -3.1, 8.9) more than women without a history of anxiety (P value for interaction between sex and history of anxiety <0.001). No other interactions were detected between sex and psychosocial factors with respect to opioid use after surgery. Conclusion: Secondary analysis of this retrospective cohort study found minimal evidence that the association between psychosocial factors and opioid consumption after elective spine surgery differs by sex in adults ≥65.

Comparison of chest radiograph and lung ultrasound in children with acute respiratory failure.

PURPOSE: Chest x-ray (CXR) is the standard imaging used to evaluate children in acute respiratory distress and failure. Our objective was to compare the lung-imaging techniques of CXR and lung ultrasound (LUS) in the evaluation of children with acute respiratory failure (ARF) to quantify agreement and to determine which technique identified a higher frequency of pulmonary abnormalities. METHODS: This was a secondary analysis of a prospective observational study evaluating the sensitivity and specificity of LUS in children with ARF from 12/2018 to 02/2020 completed at the University of Wisconsin-Madison (USA). Children > 37.0 weeks corrected gestational age and ≤ 18 years of age admitted to the PICU with ARF were evaluated with LUS. We compared CXR and LUS completed within 6 h of each other. Kappa statistics (k) adjusted for maximum attainable agreement (k/kmax) were used to quantify agreement between imaging techniques and descriptive statistics were used to describe the frequency of abnormalities. RESULTS: Eighty-eight children had LUS completed, 32 with concomitant imaging completed within 6 h are included. There was fair agreement between LUS and CXR derived diagnoses with 58% agreement (k/kmax = 0.36). Evaluation of imaging patterns included: normal, 57% agreement (k = 0.032); interstitial pattern, 47% agreement (k = 0.003); and consolidation, 65% agreement (k = 0.29). CXR identified more imaging abnormalities than LUS. CONCLUSIONS: There is fair agreement between CXR and LUS-derived diagnoses in children with ARF. Given this, clinicians should consider the benefits and limitations of specific imaging modalities when evaluating children with ARF. Additional studies are necessary to further define the role of LUS in pediatric ARF given the small sample size of our study.

Short-term dietary changes can result in mucosal and systemic immune depression.

Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time, but the health consequences of this short-term consumption of energy-dense nutrients are unclear. Here, we show that short-term reiterative switching to 'feast diets', mimicking our social eating behavior, breaches the potential buffering effect of the intestinal microbiota and reorganizes the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic immunity, leading to higher susceptibility to Salmonella enterica serovar Typhimurium and Listeria monocytogenes infections. The ability to respond to antigenic challenges with a model antigen was also impaired. These observations could be explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to reduced microbial provision of fiber metabolites. Reintroducing dietary fiber rewired T cell metabolism and restored mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention with human volunteers confirmed the effect of short-term dietary switches on human CD4+ T cell functionality. Therefore, short-term nutritional changes cause a transient depression of mucosal and systemic immunity, creating a window of opportunity for pathogenic infection.

Protocol for measuring visual preferences of freely swimming Xenopus laevis tadpoles.

Xenopus tadpoles display innate visually guided behaviors which are thought to promote survival by guiding them toward sources of food and away from predators. Experimentally, studying these behaviors can provide insight into the formation and function of the neural circuits which underlie them. Here, we present a protocol for measuring visual preferences of freely swimming tadpoles. We describe steps to create the visual stimuli, carry out the experiments, and analyze the resulting data. For complete details on the use and execution of this protocol, please refer to Hunt et al.1 and Bruno et al.2.