UNASSIGNED: Changes in land use and climate change have been reported to reduce biodiversity of both the environment and human microbiota. These reductions in biodiversity may lead to inadequate and unbalanced stimulation of immunoregulatory circuits and, ultimately, to clinical diseases, such as asthma and allergies.
UNASSIGNED: We summarized available empirical evidence on the role of inner (gut, skin, and airways) and outer (air, soil, natural waters, plants, and animals) layers of biodiversity in the development of asthma, wheezing, and allergic sensitization.
UNASSIGNED: We conducted a systematic search in SciVerse Scopus, PubMed MEDLINE, and Web of Science up to 5 March 2024 to identify relevant human studies assessing the relationships between inner and outer layers of biodiversity and the risk of asthma, wheezing, or allergic sensitization. The protocol was registered in PROSPERO (CRD42022381725).
UNASSIGNED: A total of 2,419 studies were screened and, after exclusions and a full-text review of 447 studies, 82 studies were included in the comprehensive, final review. Twenty-nine studies reported a protective effect of outer layer biodiversity in the development of asthma, wheezing, or allergic sensitization. There were also 16 studies suggesting an effect of outer layer biodiversity on increasing asthma, wheezing, or allergic sensitization. However, there was no clear evidence on the role of inner layer biodiversity in the development of asthma, wheezing, and allergic sensitization (13 studies reported a protective effect and 15 reported evidence of an increased risk).
UNASSIGNED: Based on the reviewed literature, a future systematic review could focus more specifically on outer layer biodiversity and asthma. It is unlikely that association with inner layer biodiversity would have enough evidence for systematic review. Based on this comprehensive review, there is a need for population-based longitudinal studies to identify critical periods of exposure in the life course into adulthood and to better understand mechanisms linking environmental exposures and changes in microbiome composition, diversity, and/or function to development of asthma and allergic sensitization. https://doi.org/10.1289/EHP13948.

UNASSIGNED: The overutilization of antibiotics in very preterm infants (VPIs) at low risk of early-onset sepsis (EOS) is associated with increased mortality and morbidities. Nevertheless, the association of early antibiotic exposure with bronchopulmonary dysplasia (BPD) remains equivocal.
UNASSIGNED: To evaluate the association of varying durations and types of early antibiotic exposure with the incidence of BPD in VPIs at low risk of EOS.
UNASSIGNED: This national multicenter cohort study utilized data from the Chinese Neonatal Network (CHNN) which prospectively collected data from January 1, 2019, to December 31, 2021. VPIs less than 32 weeks\' gestational age or with birth weight less than 1500 g at low risk of EOS, defined as those born via cesarean delivery, without labor or rupture of membranes, and no clinical evidence of chorioamnionitis, were included. Data analysis was conducted from October 2022 to December 2023.
UNASSIGNED: Early antibiotic exposure was defined as the total number of calendar days antibiotics were administered within the first week of life, which were further categorized as no exposure, 1 to 4 days of exposure, and 5 to 7 days of exposure.
UNASSIGNED: The primary outcome was the composite of moderate to severe BPD or mortality at 36 weeks\' post menstrual age (PMA). Logistic regression was employed to assess factors associated with BPD or mortality using 2 different models.
UNASSIGNED: Of the 27 176 VPIs included in the CHNN during the study period (14 874 male [54.7%] and 12 302 female [45.3%]), 6510 (23.9%; 3373 male [51.8%] and 3137 female [48.2.%]) were categorized as low risk for EOS. Among them, 1324 (20.3%) had no antibiotic exposure, 1134 (17.4%) received 1 to 4 days of antibiotics treatment, and 4052 (62.2%) received 5 to 7 days of antibiotics treatment. Of the 5186 VPIs who received antibiotics, 4098 (79.0%) received broad-spectrum antibiotics, 888 (17.1%) received narrow-spectrum antibiotics, and 200 (3.9%) received antifungals or other antibiotics. Prolonged exposure (5-7 days) was associated with increased likelihood of moderate to severe BPD or death (adjusted odds ratio [aOR], 1.23; 95% CI, 1.01-1.50). The use of broad-spectrum antibiotics (1-7 days) was also associated with a higher risk of moderate to severe BPD or death (aOR, 1.27; 95% CI, 1.04-1.55).
UNASSIGNED: In this cohort study of VPIs at low risk for EOS, exposure to prolonged or broad-spectrum antibiotics was associated with increased risk of developing moderate to severe BPD or mortality. These findings suggest that VPIs exposed to prolonged or broad-spectrum antibiotics early in life should be monitored for adverse outcomes.

UNASSIGNED: Little is known about the degree to which suspected sepsis drives broad-spectrum antibiotic use in hospitals, what proportion of antibiotic courses are unnecessarily broad in retrospect, and whether these patterns are changing over time.
UNASSIGNED: To describe trends in empiric broad-spectrum antibiotic use for suspected community-onset sepsis.
UNASSIGNED: This cross-sectional study used clinical data from adults admitted to 241 US hospitals in the PINC AI Healthcare Database. Eligible participants were aged 18 years or more and were admitted between 2017 and 2021 with suspected community-onset sepsis, defined by a blood culture draw, lactate measurement, and intravenous antibiotic administration on admission.
UNASSIGNED: Empiric anti-methicillin-resistant Staphylococcus aureus (MRSA) and/or antipseudomonal β-lactam agent use.
UNASSIGNED: Annual rates of empiric anti-MRSA and/or antipseudomonal β-lactam agent use and the proportion that were likely unnecessary in retrospect based on the absence of β-lactam resistant gram-positive or ceftriaxone-resistant gram-negative pathogens from clinical cultures obtained through hospital day 4. Annual trends were calculated using mixed-effects logistic regression models, adjusting for patient and hospital characteristics.
UNASSIGNED: Among 6 272 538 hospitalizations (median [IQR] age, 66 [53-78] years; 443 465 male [49.6%]; 106 095 Black [11.9%], 65 763 Hispanic [7.4%], 653 907 White [73.1%]), 894 724 (14.3%) had suspected community-onset sepsis, of whom 582 585 (65.1%) received either empiric anti-MRSA (379 987 [42.5%]) or antipseudomonal β-lactam therapy (513 811 [57.4%]); 311 213 (34.8%) received both. Patients with suspected community-onset sepsis accounted for 1 573 673 of 3 141 300 (50.1%) of total inpatient anti-MRSA antibiotic days and 2 569 518 of 5 211 745 (49.3%) of total antipseudomonal β-lactam days. Between 2017 and 2021, the proportion of patients with suspected sepsis administered anti-MRSA or antipseudomonal therapy increased from 63.0% (82 731 of 131 275 patients) to 66.7% (101 003 of 151 435 patients) (adjusted OR [aOR] per year, 1.03; 95% CI, 1.03-1.04). However, resistant organisms were isolated in only 65 434 cases (7.3%) (30 617 gram-positive [3.4%], 38 844 gram-negative [4.3%]) and the proportion of patients who had any resistant organism decreased from 9.6% to 7.3% (aOR per year, 0.87; 95% CI, 0.87-0.88). Most patients with suspected sepsis treated with empiric anti-MRSA and/or antipseudomonal therapy had no resistant organisms (527 356 of 582 585 patients [90.5%]); this proportion increased from 88.0% in 2017 to 91.6% in 2021 (aOR per year, 1.12; 95% CI, 1.11-1.13).
UNASSIGNED: In this cross-sectional study of adults admitted to 241 US hospitals, empiric broad-spectrum antibiotic use for suspected community-onset sepsis accounted for half of all anti-MRSA or antipseudomonal therapy; the use of these types of antibiotics increased between 2017 and 2021 despite resistant organisms being isolated in less than 10% of patients treated with broad-spectrum agents.

BACKGROUND: The situation in France is unique, having a legal framework for continuous and deep sedation (CDS). However, its use in intensive care units (ICU), combined with the withdrawal of life-sustaining therapies, still raises ethical issues, particularly its potential to hasten death. The legalization of assistance in dying, i.e., assisted suicide or euthanasia at the patient\'s request, is currently under discussion in France. The objectives of this national survey were first, to assess whether ICU professionals perceive CDS administered to ICU patients as a practice that hastens death, in addition to relieving unbearable suffering, and second, to assess ICU professionals\' perceptions of assistance in dying.
METHODS: A national survey with online questionnaires for ICU physicians and nursesaddressed through the French Society of Anesthesiology and Critical Care Medicine.
RESULTS: A total of 956 ICU professionals responded to the survey (38% physicians and 62% nurses). Of these, 22% of physicians and 12% of nurses (p < 0.001) felt that the purpose of CDS was to hasten death. For 20% of physicians, CDS combined with terminal extubation was considered an assistance in dying. For 52% of ICU professionals, the current framework did not sufficiently cover the range of situations that occur in the ICU. A favorable opinion on the potential legalization of assistance in dying was observed in 83% of nurses and 71% of physicians (p < 0.001), with no preference between assisted suicide and euthanasia.
CONCLUSIONS: Our findings highlight the tension between CDS and assisted suicide/euthanasia in the specific context of intensive care and suggest that ICU professionals would be supportive of a legislative evolution.

BACKGROUND: Women are known to be disadvantaged compared with men in the early links of the Chain of Survival, receiving fewer bystander interventions. We aimed to describe sex-based disparities in emergency medical service resuscitation quality and processes of care for out-of-hospital cardiac arrest.
RESULTS: We conducted a retrospective analysis of patients who were nontraumatic with out-of-hospital cardiac arrest aged ≥16 years where resuscitation was attempted between March 2019 and June 2023. We investigated 18 routinely captured performance metrics and performed adjusted logistic and quantile regression analyses to assess sex-based differences in these metrics. During the study period, 10 161 patients with out-of-hospital cardiac arrest met the eligibility criteria, of whom 3216 (32%) were women. There were no clinically relevant sex-based differences observed in regard to external cardiac compressions; however, women were 34% less likely to achieve a systolic blood pressure >100 mm Hg on arrival at the hospital (adjusted odds ratio [AOR], 0.66 [95% CI, 0.47-0.92]). Furthermore, women had a longer time to 12-lead ECG acquisition after return of spontaneous circulation (median adjusted difference, 1.00 minute [95% CI, 0.38-1.62]) and 33% reduced odds of being transported to a 24-hour percutaneous coronary intervention-capable facility (AOR, 0.67 [95% CI, 0.49-0.91]). Resuscitation was also terminated sooner for women compared with men (median adjusted difference, -4.82 minutes [95% CI, -6.77 to -2.87]).
CONCLUSIONS: Although external cardiac compression quality did not vary by sex, significant sex-based disparities were seen in emergency medical services processes of care following out-of-hospital cardiac arrest. Further investigation is required to elucidate the underlying causes of these differences and examine their influence on patient outcomes.

OBJECTIVE: Comparative assessment of the level of differentiating growth factor 15 (GDF 15 ) against the background of a 6-month course of respiratory support in the mode of automatic positive pressure in the airways therapy (aPAP therapy) in patients with obstructive sleep apnea syndrome (OSA).
METHODS: 59 men participated in the study, the average age was 51.9±2.4 years. The main group (MG1) consisted of 30 patients with a verified diagnosis of moderate OSA. 29 men of comparable age and body weight made up the control group (CG) without an objectively confirmed diagnosis of OSA. After the stage of introduction into the study, the type of respiratory support with individual pressure settings was selected for patients with MG1. After 6 months of aPAP therapy with high compliance (at least 85%), the same patients who made up MG2 after treatment underwent repeated polysomnography (PSG) and the GDF 15 content was evaluated. Methods: questionnaire, examination, polysomnography, enzyme immunoassay of blood serum to determine the content of GDF 15.
RESULTS: A 6-month course of aPAP therapy with a high degree of compliance significantly improved the sleep structure and breathing pattern: the representation of NREM 3 increased from 79.2±15.6 to 102.6±21.6 minutes and the REM phase from 56.9± 13.6 to 115.6±26.8. Episodes of apnea were eliminated - apnea-hypopnea index decreased from 21.1 [17.3; 39.1] to 2.5 [1.8; 4.6] and the average values of SaO2 increased from 85.9% to 91.5%. At the same time, a statistically significant excess of GDF 15 was revealed in MG1 - 20.4 [14.16; 31.71] and MG2 - 17.2 [13.63; 24.44]) in comparison with CG - 13.65 [10.7; 17.09]. Despite the lack of statistical significance, a change in the level of GDF 15 was revealed in the form of a decrease in its concentration after a 6-month course of aPAP therapy.
CONCLUSIONS: A 6-month course of aPAP therapy made it possible to eliminate intermittent nocturnal hypoxia and improve sleep structure in patients with OSA, as well as reduce the content of GDF 15 protein in blood serum in patients with OSA. However, the tendency to decrease the content of this protein, despite the lack of statistical reliability, confirms the effectiveness of OSA therapy and the possibility of preventing early and pathological aging from the standpoint of somnology and molecular biogerontology.
UNASSIGNED: Сравнительная оценка уровня дифференцировочного фактора роста 15 (GDF 15) на фоне 6-месячного курса респираторной поддержки в режиме автоматического создания положительного давления в дыхательных путях (automatic Positive Airway Pressure — aPAP-терапия) у пациентов с синдромом обструктивного апноэ сна (СОАС).
UNASSIGNED: В исследовании участвовали 59 мужчин, средний возраст 51,9±2,4 года. Основную группу (ОГ1) составили 30 пациентов с верифицированным диагнозом СОАС средней степени тяжести. Контрольную группу (КГ) составили 29 мужчин, сопоставимых по возрасту и массе тела, без объективно подтвержденного диагноза СОАС. После этапа введения в исследование пациентам ОГ1 был подобран тип респираторной поддержки с индивидуальными настройками давления. Через 6 мес aPAP-терапии с высоким комплаенсом (не менее 85%) этим же пациентам, которые составили после лечения ОГ2, была проведена повторная полисомнография (ПСГ) и оценено содержание GDF 15. Методы: анкетирование, осмотр, ПСГ, иммуноферментный анализ сыворотки крови для определения содержания GDF 15.
UNASSIGNED: Шестимесячный курс aPAP-терапии с высокой степенью комплаентности позволил значимо улучшить структуру сна и паттерн дыхания: увеличились представленность фазы медленного сна 3 (NREM 3) с 79,2±15,6 до 102,6±21,6 мин и фазы сна с быстрыми движениями глаз (REM) с 56,9±13,6 до 115,6±26,8. Устранены эпизоды апноэ — индекс апноэ-гипопноэ уменьшился с 21,1 [17,3; 39,1] до 2,5 [1,8; 4,6], увеличились средние значения сатурации крови кислородом (SaO2) с 85,9 до 91,5%. При этом выявлено статистически достоверное превышение GDF 15 в ОГ1 — 20,4 [14,16; 31,71] и ОГ2 — 17,2 [13,63; 24,44]) в сравнении с КГ — 13,65 [10,7; 17,09] пг/мл. Несмотря на отсутствие статистической значимости, выявлено изменение уровня GDF 15 в виде уменьшения его концентрации после 6-месячного курса aPAP-терапии.
UNASSIGNED: Шестимесячный курс aPAP-терапии позволил устранить интермиттирующую ночную гипоксию и улучшить структуру сна у пациентов с СОАС, а также снизить содержание белка GDF 15 в сыворотке крови у пациентов с СОАС. Однако тенденция к снижению содержания данного белка, несмотря на отсутствие статистической достоверности, является подтверждением эффективности терапии СОАС и возможности профилактики раннего и патологического старения с позиции сомнологии и молекулярной биогеронтологии.

OBJECTIVE: Analysis of factors affecting adherence to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea (OSA).
METHODS: The literature search was carried out using the databases PubMED, Google Scholar, E-library, Cyberleninka for the period 2013-2023 and included reviews and original articles.
RESULTS: The main groups of factors affecting adherence to CPAP therapy in patients with OSA have been established. These include sociodemographic and socioeconomic factors, the severity of OSA and the severity of clinical symptoms, and psychosocial factors. Strategies that can improve adherence were identified (educational technologies for patients, telemedicine technologies, behavioral therapy, modern technical interventions).
CONCLUSIONS: Factors that improve adherence to CPAP therapy are high levels of education and income, more severe OSA forms accompanied by daytime sleepiness, support from the patient\'s spouse and social support. Factors such as low levels of education and income, smoking, symptoms of depression and hypochondria, as well as side-effects worsen adherence to CPAP therapy, including refusal to continue treatment. It should be noted that all the identified factors are very closely associated with each other, so it is necessary to evaluate them comprehensively in each patient with OSA.
UNASSIGNED: Анализ факторов, оказывающих влияние на приверженность неинвазивной вентиляции постоянным положительным давлением воздушного потока во время сна (CPAP-терапия) пациентов с СОАС.
UNASSIGNED: Поиск литературы проводился с помощью поисковых систем PubMed, Google Scholar, eLIBRARY, Киберленинка за период 2013—2023 гг. и включал обзорные и оригинальные статьи.
UNASSIGNED: Установлены основные группы факторов, оказывающих влияние на приверженность CPAP-терапии пациентов с СОАС. К ним относятся социально-демографические и социально-экономические факторы, степень тяжести СОАС и выраженность клинических симптомов, психосоциальные факторы. Выявлены мероприятия, направленные на улучшение приверженности (обучающие технологии для пациентов, телемедицинские технологии, поведенческая терапия, современные технические решения).
UNASSIGNED: Исходя из вышеизложенного, факторами, улучшающими приверженность CPAP-терапии, являются высокие уровни образованности и доходов пациентов, более тяжелые формы СОАС, сопровождающиеся дневной сонливостью, поддержка супруга пациента и социальная поддержка. А такие факторы, как низкие уровни образования и доходов, курение, наличие симптомов депрессии и ипохондрии, а также возникающие побочные эффекты, ухудшают приверженность CPAP-терапии вплоть до отказа от продолжения лечения. Следует отметить, что все выявленные факторы очень тесно взаимосвязаны друг с другом, поэтому необходимо оценивать их комплексно у каждого пациента с СОАС.

Type III interferon signaling contributes to the pathogenesis of the important human pathogen Staphylococcus aureus in the airway. Little is known of the cellular factors important in this response. Using Ifnl2-green fluorescent protein reporter mice combined with flow cytometry and cellular depletion strategies, we demonstrate that the alveolar macrophage is the primary producer of interferon lambda (IFN-λ) in response to S. aureus in the airway. Bone marrow chimeras showed reduced bacterial burden in IFN-λ receptor (IFNLR1)-deficient recipient mice, indicative that non-hematopoietic cells were important for pathogenesis, in addition to significant reductions in pulmonary inflammation. These observations were confirmed through the use of an airway epithelial-specific IFNLR knockout mouse. Our data suggest that upon entry to the airway, S. aureus activates alveolar macrophages to produce type III IFN that is subsequently sensed by the airway epithelium. Future steps will determine how signaling from the epithelium then exerts its influence on bacterial clearance. These results highlight the important, yet sometimes detrimental, role of type III IFN signaling during infection and the impact the airway epithelium plays during host-pathogen interactions.IMPORTANCEThe contribution of type III interferon signaling to the control of bacterial infections is largely unknown. We have previously demonstrated that it contributes to the pathogenesis of acute Staphylococcus aureus respiratory infection. In this report, we document the importance of two cell types that underpin this pathogenesis. We demonstrate that the alveolar macrophage is the cell that is responsible for the production of type III interferon and that this molecule is sensed by airway epithelial cells, which impacts both bacterial clearance and induction of inflammation. This work sheds light on the first two aspects of this important pathogenic cascade.

Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., Pseudomonas), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.

BACKGROUND: Particulate β-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown.
METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF).
RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF.
CONCLUSIONS: These results highlight OAW\'s robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.