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Objective: To examine physical activity and the affinity for food among high school and college students. Methods: A questionnaire designed to assess physical activity, eating frequency, weight status, and psychological affinity for food was administered to high school and college students. Results: As eating-restraint scores increased, weight classification and weight dissatisfaction significantly increased for females. Almost all of the psychological variables were significant among all the groups. Conclusion: Many of the students were discontent with their weight, attempted to avoid food, viewed food as a temptation, and occasionally splurged to produce cheer. [ABSTRACT FROM AUTHOR]

Background: Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limited diagnostic yield of noninvasive infectious tests. In this study, we report an antibiotic prescription pattern informed by bronchoalveolar lavage (BAL) results, where clinicians de-escalate antibiotics based on the combination of quantitative cultures and multiplex PCR rapid diagnostic tests., Methods: We analyzed data from SCRIPT, a single-center prospective cohort study of mechanically ventilated patients who underwent a BAL for suspected pneumonia. We used the novel Narrow Antibiotic Therapy (NAT) score to quantify day-by-day antibiotic prescription pattern for each suspected pneumonia episode etiology (bacterial, viral, mixed bacterial/viral, microbiology-negative, and non-pneumonia control). We also analyzed and compared clinical outcomes for each pneumonia etiology, including unfavorable outcomes (a composite of in-hospital mortality, discharge to hospice, or requiring lung transplantation during hospitalization), duration of ICU stay, and duration of intubation. Clinical outcomes were compared with the Mann-Whitney U test and Fisher's exact test., Results: We included 686 patients with 927 pneumonia episodes. NAT score analysis indicated that an antibiotic de-escalation pattern was evident in all pneumonia etiologies except resistant bacterial pneumonia. Microbiology-negative pneumonia was treated similarly to susceptible bacterial pneumonia in terms of antibiotic spectrum. Over a quarter of the time in viral pneumonia episodes, antibiotics were completely discontinued. Unfavorable outcomes were comparable across all pneumonia etiologies. Patients with viral and mixed bacterial/viral pneumonia had longer durations of ICU stay and intubation., Conclusions: BAL quantitative cultures and multiplex PCR rapid diagnostic tests resulted in prompt antibiotic de-escalation in critically ill pneumonia patients. There was no evidence of increased incidence of unfavorable outcomes., Competing Interests: Declarations of interests: BDS holds US patent 10,905,706, “Compositions and methods to accelerate resolution of acute lung inflammation,” and serves on the scientific advisory board of Zoe Biosciences, in which he holds stock options. Other authors declare no conflicts of interest.

Introduction: Fellows in critical care medicine (CCM) routinely help patients and families navigate complex decisions near the end of life. These "late goals of care" (LGOC) discussions require rigorous skills training and impact patient care. Innovation is needed to ensure that fellow training in leading these discussions is centered on reproducible competency-based standards. The aims of this study were to (1) describe the development of a simulation-based mastery learning (SBML) curriculum for LGOC discussions and (2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners., Innovation: We developed an SBML curriculum for CCM fellows structured around REMAP, a mnemonic outlining foundational components of effective communication around serious illness. A multidisciplinary expert panel iteratively created an LGOC discussion assessment tool. Pilot testing was completed to refine the checklist, set the MPS, and assess skill acquisition., Outcomes: The LGOC discussion assessment tool included an 18-item checklist and 6 scaled items. The tool produced reliable data (k ≥ 0.7 and ICC of ≥ 0.7). Using the Mastery Angoff method, the panel set the MPS at 87%. Ten CCM fellows participated in the pilot study. Performance on the checklist significantly improved from a median score of 52% (IQR 44%-72%) at pretest to 96% (IQR 82%-97%) at post-test (P = 0.005). The number of learners who met the MPS similarly improved from 10% during pre-testing to 70% during post-testing (P = 0.02)., Comment: We describe the development of a LGOC SBML curriculum for CCM fellows which includes a robust communication skills assessment and the delineation of a defensible MPS., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Asynchronous online message boards (OMBs) allow users to write questions or comments and share them with an online group. While the use of OMBs has been associated with positive outcomes in several educational settings, their use has not been studied in pre-clerkship undergraduate medical education (UME)., Methods: This multiyear, observational, longitudinal study examined patterns of OMB use in pre-clerkship UME. Descriptive statistics were used to report the number of students and instructors who logged on and contributed, the number of posts, instructor answers, post views, and the average time to answer. Patterns of use by first- and second-year medical students as well as students undergoing remote versus in-person learning were compared using Wilcoxon signed-rank tests., Results: A total of 9870 posts were made to OMBs, initiated by 3869 student questions. There were 3078 total posts made by instructors and academic support staff and 1024 student answers to student questions. First-year medical students posted significantly more questions (149.83 vs. 83.7, p  < 0.001), which resulted in significantly more instructor answers (125.0 vs. 59.1, p  < 0.001). Modules during the remote learning period received more student questions (152.0 vs. 96.7, p  < 0.001) and produced more instructor answers (123.8 vs. 74.7, p  < 0.001) as compared to modules that took place during in-person learning., Discussion: Online message boards represent a readily available tool to stimulate asynchronous discussion in pre-clerkship UME. First-year medical students and students during remote learning were more active on OMBs., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) under exclusive licence to International Association of Medical Science Educators 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Some culture-negative, PCR-positive BAL samples may represent true infection. A subset of patients with a culture-negative, PCR-positive BAL result will have a subsequent BAL culture positive for the organism initially identified by PCR alone. https://bit.ly/3DWoFPo., Competing Interests: Conflict of interest: The authors declare no conflicts of interest., (Copyright ©The authors 2023.)

Protozoa comprise a major fraction of the microbial biomass in the rumen microbiome, of which the entodiniomorphs (order: Entodiniomorphida) and holotrichs (order: Vestibuliferida) are consistently observed to be dominant across a diverse genetic and geographical range of ruminant hosts. Despite the apparent core role that protozoal species exert, their major biological and metabolic contributions to rumen function remain largely undescribed in vivo. Here, we have leveraged (meta)genome-centric metaproteomes from rumen fluid samples originating from both cattle and goats fed diets with varying inclusion levels of lipids and starch, to detail the specific metabolic niches that protozoa occupy in the context of their microbial co-habitants. Initial proteome estimations via total protein counts and label-free quantification highlight that entodiniomorph species Entodinium and Epidinium as well as the holotrichs Dasytricha and Isotricha comprise an extensive fraction of the total rumen metaproteome. Proteomic detection of protozoal metabolism such as hydrogenases (Dasytricha, Isotricha, Epidinium, Enoploplastron), carbohydrate-active enzymes (Epidinium, Diplodinium, Enoploplastron, Polyplastron), microbial predation (Entodinium) and volatile fatty acid production (Entodinium and Epidinium) was observed at increased levels in high methane-emitting animals. Despite certain protozoal species having well-established reputations for digesting starch, they were unexpectedly less detectable in low methane emitting-animals fed high starch diets, which were instead dominated by propionate/succinate-producing bacterial populations suspected of being resistant to predation irrespective of host. Finally, we reaffirmed our abovementioned observations in geographically independent datasets, thus illuminating the substantial metabolic influence that under-explored eukaryotic populations have in the rumen, with greater implications for both digestion and methane metabolism., (© 2023. The Author(s).)

Background: Clinical end points that constitute successful treatment in severe pneumonia are difficult to ascertain and vulnerable to bias. The utility of a protocolized adjudication procedure to determine meaningful end points in severe pneumonia has not been well described., Methods: This was a single-center prospective cohort study of patients with severe pneumonia admitted to the medical intensive care unit. The objective was to develop an adjudication protocol for severe bacterial and/or viral pneumonia. Each episode of pneumonia was independently reviewed by 2 pulmonary and critical care physicians. If a discrepancy occurred between the 2 adjudicators, a third adjudicator reviewed the case. If a discrepancy remained after all 3 adjudications, consensus was achieved through committee review., Results: Evaluation of 784 pneumonia episodes during 593 hospitalizations achieved only 48.1% interobserver agreement between the first 2 adjudicators and 78.8% when agreement was defined as concordance between 2 of 3 adjudicators. Multiple episodes of pneumonia and presence of bacterial/viral coinfection in the initial pneumonia episode were associated with lower interobserver agreement. For an initial episode of bacterial pneumonia, patients with an adjudicated day 7-8 clinical impression of cure (compared with alternative impressions) were more likely to be discharged alive (odds ratio, 6.3; 95% CI, 3.5-11.6)., Conclusions: A comprehensive adjudication protocol to identify clinical end points in severe pneumonia resulted in only moderate interobserver agreement. An adjudicated end point of clinical cure by day 7-8 was associated with more favorable hospital discharge dispositions, suggesting that clinical cure by day 7-8 may be a valid end point to use in adjudication protocols., Competing Interests: Potential conflicts of interest. B.D.S. holds US patent 10,905,706, “Compositions and methods to accelerate resolution of acute lung inflammation,” and serves on the Scientific Advisory Board of Zoe Biosciences, for which he holds stock options. C.I.P., C.A.G., J.B., J.M.W., J.M.K., H.K.D., A.D., K.C., N.B., and R.G.W. declare no conflicts of interest. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BACKGROUNDDespite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia.METHODSWe performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.RESULTSCarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.CONCLUSIONSUnsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.FUNDINGNational Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.

Abstract: Morgan, B, Mirza, AM, Gimblet, CJ, Ortlip, AT, Ancalmo, J, Kalita, D, Pellinger, TK, Walter, JM, and Werner, TJ. Effect of an 11-week resistance training program on arterial stiffness in young women. J Strength Cond Res 37(2): 315-321, 2023-The current investigation was conducted to determine the effect of 2 resistance training models on indices of arterial stiffness in young, healthy women. Twenty-four women, untrained college students, aged 18-22 years were randomized into 1 of 3 groups: control (CON) group ( n = 8), high-intensity (HI) resistance exercise group ( n = 8), and high-volume (HV) resistance exercise group ( n = 8). Subjects randomized to resistance training groups were required to perform strength training exercises 3-5 days a week for 11 weeks. The exercise regimen consisted of 2-3 sets of 3-8 repetitions (80-90% of 1 repetition maximum [1RM]) for the HI group and 3-4 sets of 10-15 repetitions (50-70% of 1RM) for the HV group. All subjects were instructed to continue their normal diet and avoid cardiovascular exercise during the study. After the intervention, there was a significant increase in carotid femoral pulse wave velocity (PWV) (6.39 ± 0.73 to 8.40 ± 2.31 m·s -1 ; p < 0.05) and carotid radial PWV (9.77 ± 1.74 to 12.58 ± 2.09 m·s -1 ; p < 0.05) in the CON group alone. Both the HI and HV groups increased their maximum squat (36.6 ± 7.9 vs. 41.3 ± 31.8 percent change; p < 0.05), bench press (34.4 ± 12.6 vs. 23.4 ± 11.1 percent change; p < 0.05), and seated row (22.0 ± 12.6 vs. 21.9 ± 12.5 percent change; p < 0.05), respectively. Our findings support the use of resistance training exercise without undue impact on vascular compliance in otherwise healthy women., (Copyright © 2022 National Strength and Conditioning Association.)

Background: Advanced practice providers (APPs) are essential members of intensive care unit (ICU) interprofessional teams and are expected to be competent in performing procedures. There are no published criteria for establishing when APPs can independently perform procedures. Simulation-based mastery learning (SBML) is an effective strategy for improving critical care skills but has not been applied to practicing ICU APPs., Objective: The purpose of this study was to evaluate if an SBML curriculum could improve the critical care skills and procedural self-confidence of ICU APPs., Methods: We performed a pretest-posttest study of central venous catheter (CVC) insertion, thoracentesis, and mechanical ventilation (MV) management skills among ICU APPs who participated in an SBML course at an academic hospital. For each skill, APPs underwent baseline skills assessments (pretests) on a simulator using previously published checklists, followed by didactic sessions and deliberate practice with individualized feedback. Within 2 weeks, participants were required to meet or exceed previously established minimum passing standards (MPS) on simulated skills assessments (posttests) using the same checklists. Further deliberate practice was provided for those unable to meet the MPS until they retested and met this standard. We compared pretest to posttest skills checklist scores and procedural confidence., Results: All 12 eligible ICU APPs participated in internal jugular CVC, subclavian CVC, and MV training. Five APPs participated in thoracentesis training. At baseline, no APPs met the MPS on all skills. At training completion, all APPs achieved the mastery standard. Internal jugular CVC pretest performance improved from a mean of 67.2% (standard deviation [SD], 28.8%) items correct to 97.1% (SD, 3.8%) at posttest ( P  = 0.005). Subclavian CVC pretest performance improved from 29.2% (SD, 32.7%) items correct to 93.1% (SD 3.9%) at posttest ( P  < 0.001). Thoracentesis pretest skill improved from 63.9% (SD, 30.6%) items correct to 99.2% (SD, 1.7%) at posttest ( P  = 0.054). Pretest MV skills improved from 54.8% (SD, 19.7%) items correct to 92.3% (SD, 5.0%) at posttest ( P  < 0.001). APP procedural confidence improved for each skill from pre to posttest., Conclusion: SBML is effective for training APPs to perform ICU skills. Relying on traditional educational methods does not reliably ensure that APPs are adequately prepared to perform skills such as CVC insertion, thoracentesis, and MV management., (Copyright © 2023 by the American Thoracic Society.)

We diagnosed 66 peripheral nerve injuries in 34 patients who survived severe coronavirus disease 2019 (COVID-19). We combine this new data with published case series re-analyzed here (117 nerve injuries; 58 patients) to provide a comprehensive accounting of lesion sites. The most common are ulnar (25.1%), common fibular (15.8%), sciatic (13.1%), median (9.8%), brachial plexus (8.7%) and radial (8.2%) nerves at sites known to be vulnerable to mechanical loading. Protection of peripheral nerves should be prioritized in the care of COVID-19 patients. To this end, we report proof of concept data of the feasibility for a wearable, wireless pressure sensor to provide real time monitoring in the intensive care unit setting., (© 2022. The Author(s).)

Background: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) support is increasingly used in the management of COVID-19-related acute respiratory distress syndrome (ARDS). However, the clinical decision-making to initiate V-V ECMO for severe COVID-19 still remains unclear. In order to determine the optimal timing and patient selection, we investigated the outcomes of both COVID-19 and non-COVID-19 patients undergoing V-V ECMO support., Methods: Overall, 138 patients were included in this study. Patients were stratified into two cohorts: those with COVID-19 and non-COVID-19 ARDS., Results: The survival in patients with COVID-19 was statistically similar to non-COVID-19 patients (p = .16). However, the COVID-19 group demonstrated higher rates of bleeding (p = .03) and thrombotic complications (p < .001). The duration of V-V ECMO support was longer in COVID-19 patients compared to non-COVID-19 patients (29.0 ± 27.5 vs 15.9 ± 19.6 days, p < .01). Most notably, in contrast to the non-COVID-19 group, we found that COVID-19 patients who had been on a ventilator for longer than 7 days prior to ECMO had 100% mortality without a lung transplant., Conclusions: These findings suggest that COVID-19-associated ARDS was not associated with a higher post-ECMO mortality than non-COVID-19-associated ARDS patients, despite longer duration of extracorporeal support. Early initiation of V-V ECMO is important for improved ECMO outcomes in COVID-19 ARDS patients. Since late initiation of ECMO was associated with extremely high mortality related to lack of pulmonary recovery, it should be used judiciously or as a bridge to lung transplantation., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

The diaphragm, the principle muscle of inspiration, is an under-recognized contributor to respiratory disease. Dysfunction of the diaphragm can occur secondary to lung disease, prolonged ventilation, phrenic nerve injury, neuromuscular disease, and central nervous system pathology. In light of the global pandemic of coronavirus disease 2019 (COVID-19), there has been growing interest in the utility of ultrasound for evaluation of respiratory symptoms including lung and diaphragm sonography. Diaphragm ultrasound can be utilized to diagnose diaphragm dysfunction, assess severity of dysfunction, and monitor disease progression. This article reviews diaphragm and phrenic nerve ultrasound and describes clinical applications in the context of COVID-19., (© 2021 American Institute of Ultrasound in Medicine.)

Background: Adult patients with coronavirus disease present primarily with respiratory symptoms, but children and some adults may display a more systemic inflammatory syndrome with rash, fever, mucosal changes, and elevated inflammatory biomarkers., Case Presentation: Here, we report the case of a 29-year-old Hispanic patient presenting with significant rash and multisystem inflammation. We describe his clinical course, review dermatological manifestations of coronavirus disease, and summarize the pathophysiology of coronavirus disease-associated multisystem inflammation., Conclusion: This case should alert physicians to the atypical nature of presenting rash with minimal respiratory symptoms in coronavirus disease., (© 2021. The Author(s).)

Sepsis and acute lung injury (ALI) are linked to mitochondrial dysfunction; however, the underlying mechanism remains elusive. We previously reported that c-Jun N-terminal protein kinase 2 (JNK2) promotes stress-induced mitophagy by targeting small mitochondrial alternative reading frame (smARF) for ubiquitin-mediated proteasomal degradation, thereby preventing mitochondrial dysfunction and restraining inflammasome activation. Here we report that loss of JNK2 exacerbates lung inflammation and injury during sepsis and ALI in mice. JNK2 is downregulated in mice with endotoxic shock or ALI, concomitantly correlated inversely with disease severity. Small RNA sequencing revealed that miR-221-5p, which contains seed sequence matching to JNK2 mRNA 3' untranslated region (3'UTR), is upregulated in response to lipopolysaccharide, with dynamically inverse correlation with JNK2 mRNA levels. miR-221-5p targets the 3'UTR of JNK2 mRNA leading to its downregulation. Accordingly, miR-221-5p exacerbates lung inflammation and injury during sepsis in mice by targeting JNK2. Importantly, in patients with pneumonia in medical intensive care unit, JNK2 mRNA levels in alveolar macrophages flow sorted from non-bronchoscopic broncholaveolar lavage (BAL) fluid were inversely correlated strongly and significantly with the percentage of neutrophils, neutrophil and white blood cell counts in BAL fluid. Our data suggest that miR-221-5p targets JNK2 and thereby aggravates lung inflammation and injury during sepsis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Do-Umehara, Zhang, Wang, Hou, Dong, Perez, Sala, Anekalla, Walter, Liu, Wunderink, Budinger and Liu.)

Many survivors from severe coronavirus disease 2019 (COVID-19) suffer from persistent dyspnea and fatigue long after resolution of the active infection. In a cohort of 21 consecutive severe post-COVID-19 survivors admitted to an inpatient rehabilitation hospital, 16 (76%) of them had at least one sonographic abnormality of diaphragm muscle structure or function. This corresponded to a significant reduction in diaphragm muscle contractility as represented by thickening ratio (muscle thickness at maximal inspiration/end-expiration) for the post-COVID-19 compared to non-COVID-19 cohorts. These findings may shed new light on neuromuscular respiratory dysfunction as a contributor to prolonged functional impairments after hospitalization for post-COVID-19., (© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

The unique combination of depth, salinity, and water masses make the South Atlantic Ocean an ecosystem of special relevance within the global ocean. Yet, the microbiome of this ecosystem has received less attention than other regions of the global Ocean. This has hampered our understanding of the diversity and metabolic potential of the microorganisms that dwell in this habitat. To fill this knowledge gap, we analyzed a collection of 31 metagenomes from the Atlantic Ocean that spanned the epipelagic, mesopelagic and bathypelagic zones (surface to 4000 m). Read-centric and gene-centric analysis revealed the unique taxonomic and functional composition of metagenomes from each depth zone, which was driven by differences in physical and chemical parameters. In parallel, a total of 40 metagenome-assembled genomes were obtained, which recovered one third of the total community. Phylogenomic reconstruction revealed that many of these genomes are derived from poorly characterized taxa of Bacteria and Archaea. Genomes derived from heterotrophic bacteria of the aphotic zone displayed a large apparatus of genes suited for the utilization of recalcitrant organic compounds such as cellulose, chitin and alkanes. In addition, we found genomic evidence suggesting that mixotrophic bacteria from the bathypelagic zone could perform carbon fixation through the Calvin-Benson-Bassham cycle, fueled by sulfur oxidation. Finally, we found that the viral communities shifted throughout the water column regarding their targeted hosts and virus-to-microbe ratio, in response to shifts in the composition and functioning their microbial counterparts. Our findings shed light on the microbial and viral drivers of important biogeochemical processes that take place in the South Atlantic Ocean., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

With surging numbers of patients with coronavirus disease 2019 (COVID-19) throughout the world, neuromuscular complications and rehabilitation concerns are becoming more apparent. Peripheral nerve injury can occur in patients with COVID-19 secondary to postinfectious inflammatory neuropathy, prone positioning-related stretch and/or compression injury, systemic neuropathy, or nerve entrapment from hematoma. Imaging of peripheral nerves in patients with COVID-19 may help to characterize nerve abnormality, to identify site and severity of nerve damage, and to potentially elucidate mechanisms of injury, thereby aiding the medical diagnosis and decision-making process. This review article aims to provide a first comprehensive summary of the current knowledge of COVID-19 and peripheral nerve imaging., (© RSNA, 2021.)

Alveolar macrophages orchestrate the response to viral infections. Age-related changes in these cells may underlie the differential severity of pneumonia in older patients. We performed an integrated analysis of single-cell RNA-Seq data that revealed homogenous age-related changes in the alveolar macrophage transcriptome in humans and mice. Using genetic lineage tracing with sequential injury, heterochronic adoptive transfer, and parabiosis, we found that the lung microenvironment drove an age-related resistance of alveolar macrophages to proliferation that persisted during influenza A viral infection. Ligand-receptor pair analysis localized these changes to the extracellular matrix, where hyaluronan was increased in aged animals and altered the proliferative response of bone marrow-derived macrophages to granulocyte macrophage colony-stimulating factor (GM-CSF). Our findings suggest that strategies targeting the aging lung microenvironment will be necessary to restore alveolar macrophage function in aging.

Some patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop severe pneumonia and acute respiratory distress syndrome 1 (ARDS). Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from that in other types of pneumonia 2 . Here we investigate SARS-CoV-2 pathobiology by characterizing the immune response in the alveoli of patients infected with the virus. We collected bronchoalveolar lavage fluid samples from 88 patients with SARS-CoV-2-induced respiratory failure and 211 patients with known or suspected pneumonia from other pathogens, and analysed them using flow cytometry and bulk transcriptomic profiling. We performed single-cell RNA sequencing on 10 bronchoalveolar lavage fluid samples collected from patients with severe coronavirus disease 2019 (COVID-19) within 48 h of intubation. In the majority of patients with SARS-CoV-2 infection, the alveolar space was persistently enriched in T cells and monocytes. Bulk and single-cell transcriptomic profiling suggested that SARS-CoV-2 infects alveolar macrophages, which in turn respond by producing T cell chemoattractants. These T cells produce interferon-γ to induce inflammatory cytokine release from alveolar macrophages and further promote T cell activation. Collectively, our results suggest that SARS-CoV-2 causes a slowly unfolding, spatially limited alveolitis in which alveolar macrophages containing SARS-CoV-2 and T cells form a positive feedback loop that drives persistent alveolar inflammation.

Background: Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly being used for acute respiratory distress syndrome and as a bridge to lung transplantation. After initiation of venovenous ECMO, systemic anticoagulation therapy is traditionally administered and can cause bleeding diathesis. Here, we investigated whether venovenous ECMO can be administered without continuous systemic anticoagulation administration for patients with acute respiratory distress syndrome., Methods: This is a retrospective review of an institutional ECMO database. We included consecutive patients from January 2015 through February 2019. Overall, 38 patients received low levels of continuous systemic anticoagulation (AC+) whereas the subsequent 36 patients received standard venous thromboprophylaxis (AC-). Published Extracorporeal Life Support Organization guidelines were used for the definition of outcomes and complications., Results: Overall, survival was not different between the two groups (P = .58). However, patients in the AC+ group had higher rates of gastrointestinal bleeding (28.9%, vs AC- group 5.6%; P < .001). The events per patient-day of gastrointestinal bleeding was 0.00025 in the AC- group and 0.00064 in the AC+ group (P < .001). In addition, oxygenator dysfunction was increased in the AC+ group (28.9% and 0.00067 events per patient-day, vs AC- 11.1% and 0.00062 events per patient-day; P = .02). Furthermore, the AC+ group received more transfusions: packed red blood cells, AC+ group 94.7% vs AC- group 55.5% (P < .001); fresh frozen plasma, AC+ 60.5% vs AC- 16.6% (P = .001); and platelets, AC+ 84.2% vs AC- 27.7% (P < .001). There was no circuit thrombosis in either groups throughout the duration of ECMO support., Conclusions: Our results suggest that venovenous ECMO can be safely administered without continuous systemic anticoagulation therapy. This approach may be associated with reduced bleeding diathesis and need for blood transfusions., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Despite the widespread use of antibiotics, bacterial pneumonias in donors strongly predispose to the fatal syndrome of primary graft dysfunction (PGD) following lung transplantation. We report that bacterial endotoxin persists in human donor lungs after pathogen is cleared with antibiotics and is associated with neutrophil infiltration and PGD. In mouse models, depletion of tissue-resident alveolar macrophages (TRAMs) attenuated neutrophil recruitment in response to endotoxin as shown by compartmental staining and intravital imaging. Bone marrow chimeric mice revealed that neutrophils were recruited by TRAM through activation of TLR4 in a MyD88-dependent manner. Intriguingly, low levels of endotoxin, insufficient to cause donor lung injury, promoted TRAM-dependent production of CXCL2, increased neutrophil recruitment, and led to PGD, which was independent of donor NCMs. Reactive oxygen species (ROS) increased in human donor lungs starting from the warm-ischemia phase and were associated with increased transcription and translocation to the plasma membrane of TLR4 in donor TRAMs. Consistently, scavenging ROS or inhibiting their production to prevent TLR4 transcription/translocation or blockade of TLR4 or coreceptor CD14 on donor TRAMs prevented neutrophil recruitment in response to endotoxin and ameliorated PGD. Our studies demonstrate that residual endotoxin after successful treatment of donor bacterial pneumonia promotes PGD through ischemia/reperfusion-primed donor TRAMs.

Turfs are among the major benthic components of reef systems worldwide. The nearly complete genome sequences, basic physiological characteristics, and phylogenomic reconstruction of two phycobiliprotein-rich filamentous cyanobacteria strains isolated from turf assemblages from the Abrolhos Bank (Brazil) are investigated. Both Adonisia turfae CCMR0081 T (= CBAS 745 T ) and CCMR0082 contain approximately 8 Mbp in genome size and experiments identified that both strains exhibit chromatic acclimation. Whereas CCMR0081 T exhibits chromatic acclimation type 3 (CA3) regulating both phycocyanin (PC) and phycoerythrin (PE), CCMR0082 strain exhibits chromatic acclimation type 2 (CA2), in correspondence with genes encoding specific photosensors and regulators for PC and PE. Furthermore, a high number and diversity of secondary metabolite synthesis gene clusters were identified in both genomes, and they were able to grow at high temperatures (28 °C, with scant growth at 30 °C). These characteristics provide insights into their widespread distribution in reef systems.

Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. There is growing appreciation of the burden of noninfluenza viral pathogens in CAP. Due to multiple factors including pneumococcal vaccination programs, declining rates of cigarette smoking, an aging population, and increasingly sensitive diagnostic tests, respiratory viruses are now the most common pathogens detected in CAP, outpacing Streptococcus pneumoniae . Noninfluenza respiratory pathogens are widely accepted as causal pathogens in CAP including in immunocompetent patients. This review provides an overview of five noninfluenza respiratory viral pathogens commonly implicated in CAP pathogenesis: rhinovirus, human metapneumovirus, respiratory syncytial virus, human parainfluenza virus, and human adenoviruses. Nucleic acid amplification testing platforms and their impact on antimicrobial stewardship efforts are also considered., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has emerged as a potential life-saving treatment for patients with acute respiratory failure. Given the accumulating literature supporting the use of VV-ECMO without therapeutic levels of anticoagulation, it might be feasible to use it for planned intubation before surgical procedures. Here, we report consecutive series of patients who underwent planned initiation of VV-ECMO, without anticoagulation, before induction of general anesthesia for anticipated difficult airways or respiratory decompensation. We describe the approach to safely initiate VV-ECMO in an awake patient. We retrospectively identified patients in a prospectively maintained database who underwent planned initiation of VV-ECMO before intubation. Standard statistical methods were used to determine post-procedure outcomes. Patients included were three men and one woman, with a mean age of 34.3 ± 10.4 years. Indications included mediastinal lymphoma, foreign body obstruction, hemoptysis, and tracheo-esophageal fistula. VV-ECMO was initiated electively for all patients, and no anticoagulation was used. The median duration of VV-ECMO support was 2.5 days (1-11 days), the median length of ventilator dependence and intensive care unit stay was 1 day (1-23 days) and 5 days (4-31 days), respectively. The median length of stay was 18.5 days (8-39 days). There were no thrombotic complications and no mortality at 30 days. Initiation of awake VV-ECMO is feasible and is safe before intubation and induction of anesthesia in patients at high risk for respiratory decompensation., (© Copyright 2020 AMSECT.)

We report here the novel species to encompass the isolate A649 T (=CBAS 716 T  = CBRVS P1061 T ) obtained from viscera of the healthy pufferfish Sphoeroides spengleri (Family Tetraodontidae). Genomic taxonomy analysis demonstrates that the novel strain A649 T had < 95% average amino acid identity/average nucleotide identity (AAI/ANI) and < 70% similarity of genome-to-genome distance (GGDH) towards its closest neighbors which places A649 T into a new Enterovibrio species (Enterovibrio baiacu sp nov.). In silico phenotyping disclosed several features that may be used to differentiate related Enterovibrio species. The nearly complete genome assembly of strain A649 T consisted of 5.4 Mbp and 4826 coding genes.

Background: Microorganisms are widespread in all environments, including in and on animal bodies. The gut microbiome has an essential influence on fish health, and is affected by several persistent and harmful organic and inorganic contaminants. Considering the shifts in gut microbiota composition observed in those studies, we hypothesized that certain microbial groups in the gut can serve as indicators of pollution. To test this hypothesis, we explored the possibility of identifying key microbial players that indicate environmental contamination., Methods: Published 16S rRNA gene amplicon sequencing data generated from the gut microbiota of Atlantic cod caught in geographically different Norwegian waters were used for bacterial diversity comparison., Results: Different microbiomes were identified between the northern Norway and southern Norway samples. Several bacterial genera previously identified as polycyclic aromatic hydrocarbon degraders were present only in the samples collected in the southern Norway area, suggesting fish contamination with oil-related compounds., Conclusions: The results contribute to the identification of bacterial taxa present in the Atlantic cod gut that indicate fish exposure to contaminants in the marine environment.

Purpose: In this pilot study, we used shotgun metagenome sequencing (SMS) strategy on bronchoalveolar lavage (BAL) samples from hospitalized patients with suspected ventilate-associated pneumonia (VAP) in order to explore its potential for improving detection of ventilator-associated-pneumonia (VAP) etiology., Methodology: In total, 67BAL samples from patients with VAP were tested with SMS strategy for detection of respiratory pathogens. Results of SMS and routine respiratory culture were compared., Results: SMS detected all pathogens recovered by cultivation approaches. In addition, putative pathogens other than the organisms recovered by culture were detected by SMS in culture-positive samples. In 40 of 45 (89  %) culture-negative samples, a potential pathogen was detected by SMS., Conclusion: This proof-of-concept study demonstrates that SMS is able to detect bacterial, fungal and viral organisms in BAL, including culture-negative cases.

Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.

We report here the novel species Halomonas coralii. The nearly complete genome of strain 362.1 T consisted of 4.4 Mbp (3989 CDS; 66.3% GC). Genomic taxonomy analysis demonstrates that the novel strain has < 83% AAI and < 29% GGDH towards its closest neighbors.