Characterization of Doctor of Pharmacy and Prepharmacy Students' Knowledge, Stigma, and Risk Perceptions Toward Persons Living With HIV/AIDS at a Hispanic-Serving Institution.

OBJECTIVE: To assess the knowledge, stigma, and risk perceptions toward people living with HIV/AIDS in Doctor of Pharmacy and prepharmacy students at a Hispanic-serving institution situated on the United States-Mexico border. METHODS: A cross-sectional survey was administered to prepharmacy and Doctor of Pharmacy students to assess HIV background and knowledge, stigma, and risk perceptions using a self-completed electronic questionnaire. The χ2 and correlational analyses were conducted. RESULTS: Performance on the knowledge assessment was significantly correlated with increases in professional year. Although frequencies of negative stigma were overall low, there were 3 key populations that demonstrated higher rates of negative stigma: people who inject drugs, those who partake in high-risk sexual behavior, and sex workers. Although professional year was associated with knowledge and one's willingness to share food with someone living with HIV/AIDS, professional year was not associated with 8 other risk perception variables. CONCLUSION: The identification of stigma among already stigmatized populations supports the need for targeted educational interventions, especially at Hispanic-serving institutions with colleges and schools of pharmacy. Additional research should be conducted to explore the generalizability of these results and measure the impact of cultural beliefs and practices on stigma and risk perceptions across institutions with predominantly Hispanic/Latinx students.

Developmental screening of full-term infants at 16 to 18 months of age after in-utero exposure to maternal SARS-CoV-2 infection.

OBJECTIVE: To screen for neurodevelopmental delays in a cohort of full-term infants born to mothers with SARS-CoV-2. STUDY DESIGN: This was a prospective, descriptive cohort study of full-term infants born to mothers with SARS-CoV-2 during pregnancy. Subjects underwent neurodevelopmental screening using the Ages and Stages Questionnaires®-Third Edition (ASQ®-3) at 16 to 18 months age. RESULTS: Of 51 subjects, twelve (24%) were below cutoff, and twenty-seven (53%) were either below or close to the cutoff in at least one developmental domain. Communication (29%), fine motor (31%), and problem-solving (24%) were the most affected domains. There were no differences in outcomes between infants born to asymptomatic and mildly symptomatic mothers. CONCLUSION: We observed increased risk of neurodevelopmental delays during screening of infants born at full-term to mothers with SARS-CoV-2 at 16 to 18 months age. These results highlight the urgent need for follow-up studies of infants born to mothers with SARS-CoV-2.

Zoom Objective Structured Clinical Exams: Virtually the Same as the Real Thing?

OBJECTIVE: Objective structured clinical exams (OSCE) are used to train and assess resident foundational family-centered communication skills incorporating key stakeholders. In 2020 encounters were conducted virtually. We sought to compare standardized patient (SP) and family faculty (FF) assessment across OSCE and virtual OSCE (VOSCE) formats. METHODS: The intern classes of 2019 and 2020 completed a live OSCE and VOSCE respectively where they disclosed an error to an SP. The 10 minute encounter was observed by an FF and facilitator followed by a 20 minute debrief. The SP and FF completed a behavioral checklist to evaluate skill mastery. RESULTS: Eighteen (90%) of the 20 interns completed the encounter each year. Total mastery scores were significantly higher for SP assessment than for FF assessment in both OSCE [68% vs 46% (z = -3.005, P < .05)] and VOSCE formats [68% vs 53% (z = -2.105, P < .05)]. Total mastery scores of SPs across OSCE and VOSCE formats did not significantly differ, nor did FF scores based on evaluation format. CONCLUSIONS: Our current experience suggests VOSCEs are a viable alternative to in person sessions given the comparable assessment across the two modalities. The ease of participating in virtual sessions may provide a way to more easily partner with key stakeholders.

Three Years of X + Y Scheduling: Longitudinal Assessment of Resident and Faculty Perceptions.

OBJECTIVE: Five pediatric residency programs implemented true X + Y scheduling in 2018 where residents have continuity clinic in "blocks" rather than half-day per week experiences. We report the impact X + Y scheduling has on pediatric resident and faculty perceptions of patient care and other educational experiences over a 3-year timeframe. METHODS: Electronic surveys were sent to residents and faculty of the participating programs prior to implementing X + Y scheduling and annually thereafter (2018-2021). Survey questions measured resident and faculty perception of continuity clinic schedule satisfaction and the impact of continuity clinic schedules on inpatient and subspecialty rotations. Data were analyzed using z-tests for proportion differences. RESULTS: One hundred and eight six residents were sent the survey preimplementation and 254 to 289 postimplementation with response rates ranging from 47% to 69%. Three hundred and seventy-eight to 395 faculty members were sent the survey with response rates ranging from 26% to 51%. Statistically significant (P < .05) sustained perceived improvements over 3 years with X+Y were seen in outpatient continuity, inpatient workflow, and time for teaching both inpatient and in continuity clinic. CONCLUSIONS: X + Y scheduling can lead to perceived improvements in various aspects of pediatric residency programs. Our study demonstrates these improvements have been sustained over 3 years in the participating programs.

Examining the usability and viability of using a simulated classroom environment to prepare preservice science teachers during and after the COVID-19 pandemic.

Educator preparation programs experienced extreme challenges during the COVID-19 pandemic, as many universities and K-12 schools moved to fully online or hybrid instructional models. These abrupt changes significantly limited preservice teachers' opportunities to engage in classroom-based practice teaching experiences, which are a bedrock of educator preparation programs to support preservice teachers in learning how to teach effectively. In this study, we examined the usability and viability of integrating simulated teaching experiences, which occur in an online, virtual classroom environment consisting of five student avatars, into elementary science method courses during the COVID-19 pandemic to prepare preservice science teachers to engage in one critical science teaching practice: facilitating discussions that engage students in scientific argumentation. This study uses qualitative content analysis of survey data and a focus group interview to identify patterns and themes in how four elementary science teacher educators and 49 of their preservice teachers perceived the use of this tool within elementary science teacher education, particularly the opportunities and challenges this tool afforded during the pandemic and possibilities for use in the post-COVID era. Study findings suggest that these elementary science teacher educators and preservice teachers perceived the simulated teaching experience as valuable for supporting teacher learning, addressing COVID-related challenges, and tackling perennial challenges in science teacher education. They also noted challenges related to implementation and concerns with future access. A discussion of key factors that may support and hinder the use of such tools within elementary science teacher education and implications for leveraging lessons learned post-COVID are included.

The Impact of Hypernatremia in Preterm Infants on Neurodevelopmental Outcome at 18 Months of Corrected Age.

OBJECTIVE: The study objective was to assess the correlation between hypernatremia during the first week of life and neurodevelopmental outcomes at 18 months of corrected age in premature infants. STUDY DESIGN: A retrospective observational study of preterm infants born at less than 32 weeks of gestation who had a neurodevelopmental assessment with the Bayley scales of infant and toddler development III at 18 ± 6 months of corrected age. Serum sodium levels from birth through 7 days of life were collected. The study cohort was divided into two groups: infants with a peak serum sodium of >145 mmol/L (hypernatremia group) and infants with a peak serum sodium level of <145 mmol/L (no hypernatremia group). Prenatal, intrapartum, and postnatal hospital course and neurodevelopmental data at 18 ± 6 months were collected. Logistic regression analysis was used to assess the correlation between neonatal hypernatremia and neurodevelopment with adjustment for selected population characteristics. RESULTS: Eighty-eight preterm infants with complete neurodevelopmental outcome data at 18 ± 6 months of corrected gestational age were included in the study. Thirty-five neonates were in the hypernatremia group and 53 were in the no hypernatremia group. Maternal and neonatal characteristics were similar between the two groups except that the hypernatremia group had a significantly lower average birth weight and gestational age. Comparison of the mean neurodevelopmental scores between the two groups showed that patients in the hypernatremia group as compared with those in the no hypernatremia group had significantly lower neurodevelopmental scaled scores in the fine motor domain (p = 0.01). This difference remained significant (p = 0.03, odds ratio [OR] = 0.8, 95% confidence interval [CI]: 0.6-0.97) when adjusted for birth weight and gestational age. CONCLUSION: Preterm infants born at less than 32 weeks of gestation with hypernatremia in the first week of life have lower fine motor scores at 18 months of corrected age. KEY POINTS: · Hypernatremia is a common electrolyte disturbance in preterm neonates.. · Hypernatremia may be associated with long-term neurodevelopmental outcomes in preterm infants.. · Hypernatremia is a potentially modifiable risk factor..

Teaching and Assessing Communication Skills in Pediatric Residents: How Do Parents Think We Are Doing?

OBJECTIVE: Curricula designed to teach and assess the communication skills of pediatric residents variably integrates the parent perspective. We compared pediatric residents' communication skills in an objective structured clinical exam (OSCE) case as assessed by Family Faculty (FF), parents of pediatric patients, versus standardized patients (SP). METHODS: Residents participated in an OSCE case with a SP acting as a patient's parent. We compared resident performance as assessed by FF and SP with a behaviorally-anchored checklist. Items were rated as not done, partly done or well done, with well-done indicating mastery. The residents evaluated the experience. RESULTS: 42 residents consented to study participation. FF assessed a lower percentage of residents as demonstrating skill mastery as compared to SP in 19 of the 23 behaviors. There was a significant difference between FF and SP for Total Mastery Score and Mastery of the Competency Scores in three domains (Respect and Value, Information Sharing and Participation in Care and Decision Making). The majority of residents evaluated the experience favorably. CONCLUSION: Involving parents of pediatric patients in the instructive and assessment components of a communication curriculum for pediatric residents adds a unique perspective and integrates the true stakeholders in parent-physician communication.

Impact of X+Y Scheduling on Pediatric Resident and Faculty Perceptions of Education and Patient Care.

PURPOSE: Traditional half-day per week continuity clinic experiences can lead to fragmented education in both the inpatient and outpatient arenas. Five pediatric residency programs were granted the ability from the ACGME to create X+Y scheduling where residents have continuity clinic in "blocks" rather than half-day per week experiences. The aim of this study is to assess the impact X+Y scheduling has on pediatric resident and faculty perceptions of patient care and other educational experiences. METHODS: Electronic surveys were sent to residents and faculty of the participating programs both prior to and 12 months after implementing X+Y scheduling. Survey questions measured resident and faculty perception of continuity clinic schedule satisfaction and the impact of continuity clinic schedules on inpatient and subspecialty rotation experiences using a 5-point Likert Scale. Data were analyzed using z-tests for proportion differences for those answering Agree or Strongly Agree between baseline and post-implementation respondents. RESULTS: Hundred and twenty-six out of 186 residents (68%) responded preimplementation and 120 out of 259 residents (47%) responded post-implementation. 384 faculty members were sent the survey with 51% response pre-implementation and 26% response at 12 months. Statistically significant (P < .05) improvements were noted in resident and faculty perceptions of ability to have continuity with patients and inpatient workflow affected by clinic scheduling. CONCLUSIONS: From both resident and faculty perspectives, X+Y scheduling may improve several aspects of patient care and education. X+Y scheduling could be considered as a potential option by pediatric residency programs, especially if validated with more objective data.

Neurodevelopmental outcomes of children with congenital heart disease: A review.

Congenital heart defects are the most common birth anomaly affecting approximately 1% of births. With improved survival in this population, there is enhanced ability to assess long-term morbidities including neurodevelopment. There is a wide range of congenital heart defects, from those with minimal physiologic consequence that do not require medical or surgical intervention, to complex structural anomalies requiring highly specialized medical management and intricate surgical repair or palliation. The impact of congenital heart disease on neurodevelopment is multifactorial. Susceptibility for adverse neurodevelopment increases with advancing severity of the defect with initial risk factors originating during gestation. Complex structural heart anomalies may pre-dispose the fetus to abnormal circulatory patterns in utero that ultimately impact delivery of oxygen rich blood to the fetal brain. Thus, the brain of a neonate born with complex congenital heart disease may be particularly vulnerable from the outset. That vulnerability is compounded during the newborn period and through childhood, as this population endures a myriad of medical and surgical interventions. For each individual patient, these factors are likely cumulative and synergistic with progression from fetal life through childhood. This review discusses the spectrum of risk factors that may impact neurodevelopment in children with congenital heart disease, describes current recommendations and practices for neurodevelopmental follow-up of children with congenital heart disease and reviews important neurodevelopmental trends in this high risk population.

A Qualitative Exploration of Mothers' Experiences Receiving Mental Health Services in a Supermarket Setting.

Objectives Innovative mental health care delivery models have been proposed as a method to address disparities in access and utilization. The aim of this study is to characterize patients' perspectives and experiences of participating in one such innovative delivery model, group cognitive behavioral therapy within a supermarket setting. Methods In this qualitative study, 16 mothers were interviewed to explore their experiences and perspectives of receiving group-based cognitive behavioral therapy in a supermarket setting, as part of their participation in an academic-community research collaborative whose mission is to address mental health needs within low-resourced communities. Data from semi-structured interviews were analyzed using inductive coding. Results Five themes related to receiving mental health services in a supermarket setting emerged from the data: (1) Participants reported a convergence of life stressors and their introduction to supermarket-based services; (2) Participants perceived the supermarket setting as convenient; (3) Participants perceived the supermarket setting as less stigmatizing; (4) Participants perceived services in the supermarket as an acceptable form of mental health treatment; and (5) Participants described the program staff as an influential component of their treatment experience. Conclusions Understanding patient experiences of various service delivery models is critical to improving access to treatment and addressing disparities in mental health service utilization and outcomes. This study supports the use of innovative delivery models to increase access to mental health services in low-resourced communities.

Longitudinal Measurements of Resting Energy Expenditure by Indirect Calorimetry in Healthy Term Infants during the First 2 Months of Life.

OBJECTIVE: To determine longitudinal measurements of resting energy expenditure (REE) by indirect calorimetry (IC) in healthy term infants during the first 2 months of life. STUDY DESIGN: An outpatient prospective pilot study was performed in healthy term infants to estimate REE by measuring expired gas fractions of oxygen (O2) and carbon dioxide (CO2) with IC in a respiratory and metabolic steady state. RESULTS: A total of 30 measurements were performed. Fourteen subjects completed measurements at both 1 and 2 months of life, and two subjects had only measurements made at 1 month of life. Mean REE values were 64.1 ± 12.7 and 58.4 ± 14.3 kcal/kg/d at 1 and 2 months of age, respectively. Mean O2 consumption and CO2 production measurements were 9.3 ± 2.0 and 7.7 ± 1.2 mL/kg/min and 8.1 ± 2.2 and 6.4 ± 1.1 mL/kg/min at 1 and 2 months of age, respectively. CONCLUSION: This pilot study demonstrates longitudinal measurements of REE by IC in healthy term infants during the first 2 months of life. We also demonstrate that, overall, there is consistency in REE values in this population, with a likely decrease in individual longitudinal measurements over the first 2 months of life.

Resting energy expenditure in infants with congenital diaphragmatic hernia without respiratory support at time of neonatal hospital discharge.

BACKGROUND: Infants with congenital diaphragmatic hernia (CDH) are at risk for growth failure because of inadequate caloric intake and high catabolic stress. There is limited data on resting energy expenditure (REE) in infants with CDH. AIMS: To assess REE via indirect calorimetry (IC) in term infants with CDH who are no longer on respiratory support and nearing hospital discharge with advancing post-conceptional age and to assess measured-to-predicted REE using predictive equations. METHODS: A prospective cohort study of term infants with CDH who were no longer on respiratory support and nearing hospital discharge was conducted to assess REE via IC and caloric intake. Baseline characteristics and hospital course data were collected. Three day average caloric intake around time of IC testing was calculated. Change in REE with advancing post-conceptional age and advancing post-natal age was assessed. The average measured-to-predicted REE was calculated for the cohort using predictive equations [22]. RESULTS: Eighteen infants with CDH underwent IC. REE in infants with CDH increased with advancing postconceptional age (r2 = 0.3, p < 0.02). The mean REE for the entire group was 53.2 +/- 10.9 kcal/kg/day while the mean caloric intake was 101.2 +/- 17.4 kcal/kg/day. The mean measured-to-predicted ratio for the cohort was in the normal metabolic range (1.10 +/- 0.17) with 50% of infants considered hypermetabolic and 11% of infants considered hypo-metabolic. CONCLUSIONS: Infant survivors of CDH repair who are without respiratory support at time of neonatal hospital discharge have REE, as measured by indirect calorimetry, that increases with advancing post-conceptional age and that is within the normal metabolic range when compared to predictive equations. LEVEL OF EVIDENCE: III.

Neonatal resuscitation experience curves: simulation based mastery learning booster sessions and skill decay patterns among pediatric residents.

Background Following neonatal resuscitation program (NRP) training, decay in clinical skills can occur. Simulation-based deliberate practice (SBDP) has been shown to maintain NRP skills to a variable extent. Our study objectives were (a) to determine whether a single 30 min simulation-based intervention that incorporates SBDP and mastery learning (ML) can effectively restore skills and prevent skill decay and (b) to compare different timing options. Methods Following NRP certification, pediatric residents were randomly assigned to receive a video-recorded baseline assessment plus SBDP-ML refresher education at between 6 and 9 months (early) or between 9 and 12 months (late). One year following initial certification, participants had repeat skill retention videotaped evaluations. Participants were scored by blinded NRP instructors using validated criteria scoring tools and assigned a global performance rating score (GRS). Results Twenty-seven participants were included. Residents in both early and late groups showed significant skill decay 7 and 10 months after initial NRP. SBDP-ML booster sessions significantly improved participants' immediate NRP performance scores (p<0.001), which persisted for 2 months, but were again lower 4 months later. Conclusions NRP skills may be boosted to mastery levels after a short SBDP-ML intervention and do not appear to significantly decline after 2 months. Brief booster training could potentially serve as a useful supplement to traditional NRP training for pediatric residents.

The Effect of Complete Blood Count Timing on Lumbar Puncture Rates in Asymptomatic Infants Born to Mothers with Chorioamnionitis.

Background Maternal chorioamnionitis is a risk factor for sepsis but, often, these infants are asymptomatic at birth. Different markers for infections, such as the immature to total (I/T) white blood cell (WBC) ratio, are used to help determine which infants require lumbar punctures (LPs), in addition to blood cultures and antibiotics. The timing of when the complete blood count (CBC) is obtained may have some effect on the length of antibiotic treatment. Aims The purpose of this proof-of-concept study was to assess if obtaining a CBC at greater than four hours of life as compared to less than four hours of life has an impact on the incidence of LPs performed in asymptomatic, full-term infants undergoing evaluation for sepsis secondary to maternal chorioamnionitis. Methods We performed a retrospective study of full-term, asymptomatic infants admitted for sepsis evaluation secondary to maternal chorioamnionitis. Subjects were grouped based upon the timing of their initial CBC (early = < four hours of life or late = > four hours of life). The incidence of LPs, duration of antibiotic treatment, and length of hospitalization were compared between the groups. Results A total of 230 subjects were included in the study (early group = 124, late group = 106). Subjects in the late group underwent significantly fewer LPs than subjects in the early group, 5.7% vs. 22.6% (p<0.001). There was no difference in length of treatment or hospitalization. Conclusions Asymptomatic full-term infants undergoing evaluation for sepsis secondary to maternal chorioamnionitis are less likely to undergo an LP if their initial CBC is obtained at greater than four hours of life.

A randomized controlled trial of screening and brief interventions for substance misuse in reproductive health.

BACKGROUND: Screening, brief intervention, and referral to treatment may reduce substance misuse but has received minimal study among women who are treated in reproductive health settings. OBJECTIVE: The purpose of this study was to determine whether "screening, brief intervention and referral to treatment" that is delivered either electronically or by clinician are more effective than enhanced usual care in decreasing days of primary substance use. STUDY DESIGN: Women from 2 reproductive centers who smoked cigarettes or misused alcohol, illicit drugs, or prescription medication were allocated randomly to "screening, brief intervention and referral to treatment" delivered electronically or by clinician or to enhanced usual care. Assessments were completed at baseline and at 1-, 3-, and 6-months after a baseline has been established. Coprimary outcomes were days/months of primary substance use and postintervention treatment use. A sample size of 660 women was planned; randomization was stratified by primary substance use and pregnancy status. "Screening, brief intervention and referral to treatment" groups were compared with enhanced usual care groups with the use of generalized estimation equations, and effect sizes were calculated with the use of Cohen's d. RESULTS: Between September 2011 and January 2015, women were assigned randomly to a group: 143 women (16.8% pregnant) in the electronic-delivered "screening, brief intervention and referral to treatment" group, 145 women (18.6% pregnant) in the clinician-delivered "screening, brief intervention and referral to treatment" group, and 151 women (19.2% pregnant) in the enhanced usual care group; the retention was >84%. Based on the generalized estimating equations model, predicted mean days per month of use at baseline for primary substance were 23.9 days (95% confidence interval, 22.4-25.5) for the electronic-delivered group, 22.8 days (95% confidence interval, 21.4-24.3) for the clinician-delivered group, and 23.5 days (95% confidence interval, 22.2, 24.9) for enhanced usual care, which respectively declined to 20.5 days (95% confidence interval, 19.0-22.2), 19.8 days (95% confidence interval,18.5-21.3), and 21.9 days (95% confidence interval, 20.7-23.1) at 1 month; 16.9 days (95% confidence interval, 15.0-19.0), 16.6 days (95% confidence interval, 14.8-18.6), and 19.5 days (95% confidence interval, 18.1-21.1) at 3 months; and 16.3 days (95% confidence interval, 14.3-18.7), 16.3 days (95% confidence interval, 14.4-18.5), and 17.9 days (95% confidence interval, 16.1-19.9) at 6 months. Estimated declines were greater in the electronic-delivered group (ß [standard error]=-0.090[0.034]; P=.008; Cohen's d, 0.19 at 1 month, 0.30 at 3 months, and 0.17 at 6 months) and the clinician-delivered group (ß [standard error]=-0.078[0.037]; P=.038; Cohen's d, 0.17 at 1 month, 0.22 at 3 months, and 0.06 at 6 months) compared with enhanced usual care. Treatment use did not differ between groups. CONCLUSION: "Screening, brief intervention and referral to treatment" significantly decreased days of primary substance use among women in reproductive healthcare centers; neither resulted in more treatment use than enhanced usual care.

See One, Do One, Order One: a study protocol for cluster randomized controlled trial testing three strategies for implementing motivational interviewing on medical inpatient units.

BACKGROUND: General medical hospitals provide care for a disproportionate share of patients who abuse or are dependent upon substances. This group is among the most costly to treat and has the poorest medical and addiction recovery outcomes. Hospitalization provides a unique opportunity to identify and motivate patients to address their substance use problems in that patients are accessible, have time for an intervention, and are often admitted for complications related to substance use that renders hospitalization a "teachable moment." METHODS/DESIGN: This randomized controlled trial will examine the effectiveness of three different strategies for integrating motivational interviewing (MI) into the practice of providers working within a general medical inpatient hospitalist service: (1) a continuing medical education workshop that provides background and "shows" providers how to conduct MI (See One); (2) an apprenticeship model involving workshop training plus live supervision of bedside practice (Do One); and (3) ordering MI from the psychiatry consultation-liaison (CL) service after learning about it in a workshop (Order One). Thirty providers (physicians, physician assistants, nurses) will be randomized to conditions and then assessed for their provision of MI to 40 study-eligible inpatients. The primary aims of the study are to assess (1) the utilization of MI in each condition; (2) the integrity of MI when providers use it on the medical units; and (3) the relative costs and cost-effectiveness of the three different implementation strategies. DISCUSSION: If implementation of Do One and Order One is successful, the field will have two alternative strategies for supporting medical providers' proficient use of brief behavioral interventions, such as MI, for medical inpatients who use substances problematically. TRIAL REGISTRATION: Clinical Trials.gov ( NCT01825057 ).

Hypercapnia impairs lung neutrophil function and increases mortality in murine pseudomonas pneumonia.

Hypercapnia, an elevation of the level of carbon dioxide (CO2) in blood and tissues, is a marker of poor prognosis in chronic obstructive pulmonary disease and other pulmonary disorders. We previously reported that hypercapnia inhibits the expression of TNF and IL-6 and phagocytosis in macrophages in vitro. In the present study, we determined the effects of normoxic hypercapnia (10% CO2, 21% O2, and 69% N2) on outcomes of Pseudomonas aeruginosa pneumonia in BALB/c mice and on pulmonary neutrophil function. We found that the mortality of P. aeruginosa pneumonia was increased in 10% CO2-exposed compared with air-exposed mice. Hypercapnia increased pneumonia mortality similarly in mice with acute and chronic respiratory acidosis, indicating an effect unrelated to the degree of acidosis. Exposure to 10% CO2 increased the burden of P. aeruginosa in the lungs, spleen, and liver, but did not alter lung injury attributable to pneumonia. Hypercapnia did not reduce pulmonary neutrophil recruitment during infection, but alveolar neutrophils from 10% CO2-exposed mice phagocytosed fewer bacteria and produced less H2O2 than neutrophils from air-exposed mice. Secretion of IL-6 and TNF in the lungs of 10% CO2-exposed mice was decreased 7 hours, but not 15 hours, after the onset of pneumonia, indicating that hypercapnia inhibited the early cytokine response to infection. The increase in pneumonia mortality caused by elevated CO2 was reversible when hypercapnic mice were returned to breathing air before or immediately after infection. These results suggest that hypercapnia may increase the susceptibility to and/or worsen the outcome of lung infections in patients with severe lung disease.

Type III secretion of ExoU is critical during early Pseudomonas aeruginosa pneumonia.

UNLABELLED: The Pseudomonas aeruginosa type III secretion system has been associated with poor outcomes in both animal models and human patients. Despite a large number of studies exploring the regulation of type III secretion in vitro, little is known about the timing of secretion during mammalian infection. Here we demonstrate that the exoU gene, which encodes the highly cytotoxic type III effector ExoU, is induced early during acute P. aeruginosa pneumonia. Immunofluorescence microscopy indicated that the amount of ExoU protein in the lung also increased over time. The importance of early expression was examined using a strain of P. aeruginosa with inducible production of ExoU. Delays in expression as short as 3 h led to reduced bacterial burdens in the lungs of mice and improved survival. Our results demonstrate that early expression of exoU is critical to bacterial survival during pneumonia and suggest that therapeutic interventions that delay ExoU secretion for even short periods of time may be efficacious. IMPORTANCE: Pseudomonas aeruginosa is a major contributor to the large numbers of health care-associated infections occurring annually, particularly for immunocompromised patients. Although this organism possesses many virulence factors, the type III secretion system plays an especially important role in both animal models and humans. This system forms a needle-like apparatus that injects toxins directly into eukaryotic cells. The most toxic protein secreted by this molecular machine is ExoU, which causes rapid cell death. In this study, we demonstrated that exoU was expressed and ExoU was produced early during acute pneumonia in a mouse model. Delaying expression of exoU by as little as 3 h enhanced clearance of bacteria and survival of infected mice. Our findings highlight the importance of understanding the regulation of virulence factor expression during infection when designing therapeutic strategies to inhibit the toxic effects of these proteins.