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BackgroundPredictors of worse outcomes (rebleeding, surgery and death) of peptic ulcer bleeds (PUBs) are essential indicators because of significant morbidity and mortality rates of PUBs. However those have been infrequently reported since changes in medical therapy (PPI, proton pump inhibitors) and application of newer endoscopic haemostatic technique.AimsTo determine: (i) independent risk factors for 30-day rebleeding, surgery, and death and (ii) whether ulcer size is an independent predictor of major outcomes in patients with severe PUB after successful endoscopic haemostasis and treatment with optimal medical (high dose IV PPI) vs. prior treatment (high dose IV histamine 2 antagonists - H2RAs).MethodsA large prospectively followed population of patients hospitalised with severe PUBs between 1993 and 2011 at two US tertiary care academic medical centres, stratified by stigmata of recent haemorrhage (SRH) was studied. Using multivariable logistic regression analyses, independent risk factors for each outcome (rebleeding, surgery and death) up to 30 days were analysed. Effects for medical treatment (H2RA patients 1993-2005 vs. PPIs 2006-2011) were also analysed.ResultsA total of 1264 patients were included. For ulcers ≥10 mm, the odds of 30-day rebleeding increased 6% per each 10% increase in ulcer size (OR 1.06, 95% CI 1.02-1.10, P = 0.0053). Other risk factors for 30-day rebleeding were major SRH, in-patient start of bleeding, and prior GI bleeding. Major SRH and ulcer size≥10 mm were predictors of 30-day surgery. Risk factors for 30-day death were major SRH, in-patient bleeding, and any initial platelet transfusion or fresh frozen plasma transfusion ≥2 units. Among patients with major SRH and out-patient start of bleeding, larger ulcer size was also a risk factor for death (OR 1.08 per 10% increase in ulcer size, 95% CI 1.02-1.14, P = 0.0095). Ulcer size was a significant independent variable for both time periods.ConclusionsUlcer size is a risk factor for worse outcomes after PUB and should be carefully recorded at initial endoscopy to improve patient triage and management.

Asthma and gestational diabetes mellitus are prevalent during pregnancy and associated with adverse perinatal outcomes. The risk of gestational diabetes mellitus is increased with asthma, and more severe asthma; yet, the underlying mechanisms are unknown. This review examines existing literature to explore possible links. Asthma and gestational diabetes mellitus are associated with obesity, excess gestational weight gain, altered adipokine levels and low vitamin D levels; yet, it's unclear if these underpin the gestational diabetes mellitus–asthma association. Active antenatal asthma management reportedly mitigates asthma-associated gestational diabetes mellitus risk. However, mechanistic studies are lacking. Existing research suggests asthma management during pregnancy influences gestational diabetes mellitus risk; this may have important implications for future antenatal strategies to improve maternal-fetal outcomes by addressing both conditions. Addressing shared risk factors, as part of antenatal care, may also improve outcomes. Finally, mechanistic studies, to establish the underlying pathophysiology linking asthma and gestational diabetes mellitus, could uncover new treatment approaches to optimise maternal and child health outcomes. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the clinical performance of Concept indirect posterior heat- and pressure-polymerized restorative material and compare it to the performance of cast gold. Method and materials: Inlays and onlays placed in a standardized manner as part of a clinical study were evaluated at 7 years. Eighteen patients (45%) who had received 36 Concept restorations returned and were evaluated using the US Public Health Service criteria. Restorations were evaluated in seven categories as the percentage receiving Alfa (ideal), Bravo (clinically acceptable), or Charlie (clinically unacceptable) scores or as restoration no longer present. Fourteen of the restorations were cemented with Heliobond bonding resin and 13 were cemented with Special Bond bonding resin. Each patient also received a cast-gold restoration for comparison. Results: Concept restorations received scores of Alfa at the following rates: color match, 64%; interfacial staining, 47%; secondary caries, 75%; wear, 58%; marginal integrity, 64%; surface texture, 72%; and axial contour, 58% (in 14% this category was not applicable because they were Class 1 restorations). Nine Concept restorations (25%) were no longer present. Fifteen of 18 gold restorations were present at this recall. Statistical analysis indicated no significant differences in any categories between the two bonding resins used with Concept restorative material and the gold restorations. Conclusion: At 7 years in vivo, the Concept indirect posterior restorative system yields clinically acceptable restorations, particularly in premolars. [ABSTRACT FROM AUTHOR]

Abstract Background In animal studies tumor size is used to assess responses to anticancer therapy. Current standard for volumetric measurement of xenografted tumors is by external caliper, a method often affected by error. The aim of the present study was to evaluate if microCT gives more accurate and reproducible measures of tumor size in mice compared with caliper measurements. Furthermore, we evaluated the accuracy of tumor volume determined from 18F-fluorodeoxyglucose (18F-FDG) PET. Methods Subcutaneously implanted human breast adenocarcinoma cells in NMRI nude mice served as tumor model. Tumor volume (n = 20) was determined in vivo by external caliper, microCT and 18F-FDG-PET and subsequently reference volume was determined ex vivo. Intra-observer reproducibility of the microCT and caliper methods were determined by acquiring 10 repeated volume measurements. Volumes of a group of tumors (n = 10) were determined independently by two observers to assess inter-observer variation. Results Tumor volume measured by microCT, PET and caliper all correlated with reference volume. No significant bias of microCT measurements compared with the reference was found, whereas both PET and caliper had systematic bias compared to reference volume. Coefficients of variation for intra-observer variation were 7% and 14% for microCT and caliper measurements, respectively. Regression coefficients between observers were 0.97 for microCT and 0.91 for caliper measurements. Conclusion MicroCT was more accurate than both caliper and 18F-FDG-PET for in vivo volumetric measurements of subcutaneous tumors in mice.18F-FDG-PET was considered unsuitable for determination of tumor size. External caliper were inaccurate and encumbered with a significant and size dependent bias. MicroCT was also the most reproducible of the methods.

Abstract Background Mycobacterium avium is an environmental mycobacterium that can be divided into the subspecies avium, hominissuis, paratuberculosis and silvaticum. Some M. avium subspecies are opportunistic pathogens for animals and humans. They are ubiquitous in nature and can be isolated from natural sources of water, soil, plants and bedding material. Isolates of M. avium originating from humans (n = 37), pigs (n = 51) and wild birds (n = 10) in Norway were examined by IS1245 and IS1311 RFLP using new and specific probes and for the presence of IS901 and ISMpa1 by PCR. Analysis and generation of a dendrogram were performed with the software BioNumerics. Results IS1311 RFLP provided clear results that were easy to interpret, while IS1245 RFLP generated more complex patterns with a higher discriminatory power. The combination of the two methods gave additional discrimination between isolates. All avian isolates except one were M. avium subsp. avium with two copies of IS1311 and one copy of IS1245, while the isolates of human and porcine origin belonged to M. avium subsp.hominissuis. The isolates from human patients were distributed randomly among the clusters of porcine isolates. There were few identical isolates. However, one isolate from a human patient was identical to a porcine isolate. Regional differences were detected among the porcine isolates, while there was no clustering of human isolates according to type of clinical symptoms or geographical location of the patient's home addresses. Conclusion The results demonstrate that a wide range of M. avium subsp.hominissuis are present in pigs and humans in Norway, and that some of these isolates are very similar. It remains to be determined whether humans are infected from pigs or if they are infected from common environmental sources.

Background: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma., Objective: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes., Search Strategy: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*)., Selection Criteria: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma., Data Collection and Analysis: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined., Main Results: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance., Conclusions: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Introduction: The natural history of patients with well-documented presumptive diverticular hemorrhage (TICH) is unknown. Our aims are to report (i) rebleeding rates and clinical outcomes of presumptive TICH patients with and without rebleeding, (ii) conversion to definitive TICH during long-term follow-up (F/U), and (iii) risk factors of presumptive diverticular (TIC) rebleeding., Methods: This was a retrospective cohort study of prospectively collected results of presumptive TICH patients from 1994 to 2023. Presumptive TICH was diagnosed for patients with TICs without stigmata of recent hemorrhage and no other cause of bleeding found on anoscopy, enteroscopy, capsule endoscopy, computed tomography angiography, or tagged red blood cell scan. Patients with ≤6 months of F/U were excluded., Results: Of 139 patients with presumptive TICH, 104 were male and 35 female. The median age was 76 years. There were no significant differences in baseline demographics of rebleeders and non-rebleeders. During long-term median F/U of 73 months, 24.5% (34/139) rebled. A total of 56% (19/34) of rebleeders were diagnosed as definitive TICH, and they had significantly higher rates of readmission ( P < 0.001), reintervention ( P < 0.001), and surgery ( P < 0.001). During F/U, there were significantly higher rates of newly diagnosed hypertension and/or atherosclerotic cardiovascular disease in rebleeders ( P = 0.033 from a logistic model). All-cause mortality was 42.8%, but none was from TICH., Discussion: For presumptive TICH during long-term F/U, (i) 75.5% did not rebleed and 24.5% rebled. (ii) 56% of rebleeders were diagnosed as definitive TICH. (iii) New development of hypertension and atherosclerotic cardiovascular disease were risk factors of TIC rebleeding., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Millions of people are exposed to landscape fire smoke (LFS) globally, and inhalation of LFS particulate matter (PM) is associated with poor respiratory and cardiovascular outcomes. However, how LFS affects respiratory and cardiovascular function is less well understood., Objective: We aimed to characterize the pathophysiologic effects of representative LFS airway exposure on respiratory and cardiac function and on asthma outcomes., Methods: LFS was generated using a customized combustion chamber. In 8-week-old female BALB/c mice, low (25 μg/m 3 , 24-hour equivalent) or moderate (100 μg/m 3 , 24-hour equivalent) concentrations of LFS PM (10 μm and below [PM 10 ]) were administered daily for 3 (short-term) and 14 (long-term) days in the presence and absence of experimental asthma. Lung inflammation, gene expression, structural changes, and lung function were assessed. In 8-week-old male C57BL/6 mice, low concentrations of LFS PM 10 were administered for 3 days. Cardiac function and gene expression were assessed., Results: Short- and long-term LFS PM 10 airway exposure increased airway hyperresponsiveness and induced steroid insensitivity in experimental asthma, independent of significant changes in airway inflammation. Long-term LFS PM 10 airway exposure also decreased gas diffusion. Short-term LFS PM 10 airway exposure decreased cardiac function and expression of gene changes relating to oxidative stress and cardiovascular pathologies., Conclusions: We characterized significant detrimental effects of physiologically relevant concentrations and durations of LFS PM 10 airway exposure on lung and heart function. Our study provides a platform for assessment of mechanisms that underpin LFS PM 10 airway exposure on respiratory and cardiovascular disease outcomes., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Landscape fire smoke (LFS) contains several hazardous air pollutants that are known to be detrimental to human health. People with asthma are more vulnerable to the health impact of LFS than general populations. The aim of this review is to investigate the effectiveness of personal strategies to reduce the effect of LFS on asthma-related outcomes., Methods and Analysis: We will electronically search databases such as Medline, Embase, CINAHL and Cochrane Clinical Trials Register to identify eligible articles for the review. Screening of search results and data extraction from included studies will be completed by two independent reviewers. The risk of bias (RoB 2) will be assessed using the Risk of Bias Assessment Tool for Non-Randomised Studies for observational studies, the Cochrane Collaboration tool for assessing the RoB 2 for randomised controlled trials (RCTs) and the Risk Of Bias In Nonrandomized Studies of Interventions tool for non-RCTs. A random-effect meta-analysis will be performed to determine the pooled summary of findings of the included studies. If meta-analysis is not possible, we will conduct a narrative synthesis. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Ethics and Dissemination: This study will synthesise the available evidence obtained from published studies and as such, no ethical approval is required. The review will be disseminated through peer-reviewed publications and conference presentations., Prospero Registration Number: CRD42022341120., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are few reports of clinical outcomes or the natural history of definitive diverticular hemorrhage (DDH)., Aims: To describe 1-year clinical outcomes of patients with documented DDH treated with colonoscopic hemostasis, angioembolization, surgery, or medical treatment., Methods: DDH was diagnosed when active bleeding or other stigmata of hemorrhage were found in a colonic diverticulum during urgent colonoscopy or extravasation on angiography or red blood cell (RBC) scanning. This was a retrospective analysis of prospectively collected data of DDH patients from two referral centers between 1993 and 2022. Outcomes were compared for the four treatment groups. The Kaplan-Meier analysis was for time-to-first diverticular rebleed., Results: 162 patients with DDH were stratified based on their final treatment before discharge-104 colonoscopic hemostasis, 24 medical treatment alone, 19 colon surgery, and 15 angioembolization. There were no differences in baseline characteristics, except for a higher Glasgow-Blatchford score in the angioembolization group vs. the colonoscopic group. Post-treatment, the colonoscopic hemostasis group had the lowest rate of RBC transfusions and fewer hospital and ICU days compared to surgical and embolization groups. The medical group had significantly higher rates of rebleeding and reintervention. The surgical group had the highest postoperative complications., Conclusions: Medically treated DDH patients had significantly higher 1-year rebleed and reintervention rates than the three other treatments. Those with colonoscopic hemostasis had significantly better clinical outcomes during the index hospitalization. Surgery and embolization are recommended as salvage therapies in case of failure of colonoscopic and medical treatments., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Individuals with asthma experienced severe and prolonged symptoms after the Australian 2019 to 2020 landscape fire. Many of these symptoms, such as throat irritation, occur in the upper airway. This suggests that laryngeal hypersensitivity contributes to persistent symptoms after smoke exposure., Objective: This study examined the relationship between laryngeal hypersensitivity and symptoms, asthma control, and health impacts on individuals exposed to landscape fire smoke., Method: The study was a cross-sectional survey of 240 participants in asthma registries who were exposed to smoke during the 2019 to 2020 Australian fire. The survey, completed between March and May 2020, included questions about symptoms, asthma control, and health care use, as well as the Laryngeal Hypersensitivity Questionnaire. Daily concentration levels of particulate matter less than or equal to 2.5 μm in diameter were measured over the 152-day study period., Results: The 49 participants with laryngeal hypersensitivity (20%) had significantly more asthma symptoms (96% vs 79%; P = .003), cough (78% vs 22%; P < .001), and throat irritation (71% vs 38%; P < .001) during the fire period compared with those without laryngeal hypersensitivity. Participants with laryngeal hypersensitivity had greater health care use (P ≤ .02), more time off work (P = .004), and a reduced capacity to participate in usual activities (P < .001) during the fire period, as well as poorer asthma control during the follow-up (P = .001)., Conclusions: Laryngeal hypersensitivity is associated with persistent symptoms, reports of lower asthma control, and increased health care use in adults with asthma who were exposed to landscape fire smoke. Management of laryngeal hypersensitivity before, during, or immediately after landscape fire smoke exposure might reduce the symptom burden and health impact., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Objective: Discontinuation of, and non-adherence to, inhaled corticosteroids (ICS) for asthma treatment is a significant issue in pregnancy. This study characterized beliefs about medicines in pregnant women with asthma and investigated associations with ICS adherence., Methods: Pregnant women with relatively mild asthma ( n  = 302) were grouped according to ICS use and self-reported adherence (≥80% doses taken). They completed questions about dislike of asthma medications and the validated Beliefs about Medicines Questionnaire (BMQ), which consists of ten questions about asthma medicines ("necessity" questions about maintaining health, or "concern" questions about adverse effects), and eight general medicine questions, scored on five-point Likert scales. The Necessity Concerns differential (N-C) was calculated, with positive scores indicating that the patient perceives the benefits of medicines to outweigh the risks., Results: ICS was used by 87 (29%) women, with 49 (56%) self-reporting adherence. Of the 22% who disliked taking asthma medications during pregnancy, 20% had the belief that the medication was unsafe. ICS users had a significantly higher BMQ necessity score and higher necessity-concern differential score than nonusers; when adjusted for covariates, ICS non-adherence was associated with a lower necessity score ( p  = 0.015). Women adherent to ICS were more likely to agree to "my health at present depends on my asthma medication" compared to non-adherent ICS users., Conclusions: ICS non-adherence was not associated with having relatively more concerns about asthma medicines; however, ICS users were more likely to perceive that the benefits of medication use outweighed any risks. Interventions to improve asthma medication adherence in pregnancy are needed.

Background: The 2019/2020 Australian landscape fires (bushfires) resulted in prolonged extreme air pollution; little is known about the effects on breastfeeding women and their infants. This study aimed to examine the impact of prolonged landscape fires on infant feeding methods and assess the concentration of polycyclic aromatic hydrocarbons (PAHs) and elements in breast milk samples., Methods: From May - December 2020, women with asthma, who were feeding their infants during the fires, were recruited from an existing cohort. Data on infant feeding and maternal concern during the fires were retrospectively collected. Breast milk samples were collected from a sample of women during the fire period and compared with samples collected outside of the fire period for levels of 16 PAHs (gas chromatography coupled with mass spectrometry), and 20 elements (inductively coupled plasma-mass spectrometry)., Results: One-hundred-and-two women who were feeding infants completed the survey, and 77 provided 92 breast milk samples. Two women reported concern about the impact of fire events on their infant feeding method, while four reported the events influenced their decision. PAHs were detected in 34% of samples collected during, versus no samples collected outside, the fire period (cross-sectional analysis); specifically, fluoranthene (median concentration 0.015 mg/kg) and pyrene (median concentration 0.008 mg/kg) were detected. Women whose samples contained fluoranthene and pyrene were exposed to higher levels of fire-related fine particulate matter and more fire days, versus women whose samples had no detectable fluoranthene and pyrene. Calcium, potassium, magnesium, sodium, sulphur, and copper were detected in all samples. No samples contained chromium, lead, nickel, barium, or aluminium. No statistically significant difference was observed in the concentration of elements between samples collected during the fire period versus outside the fire period., Conclusions: Few women had concerns about the impact of fire events on infant feeding. Detection of fluoranthene and pyrene in breast milk samples was more likely during the 2019/2020 Australian fire period; however, levels detected were much lower than levels expected to be related to adverse health outcomes., (© 2023. Crown.)

Physiologic changes during pregnancy have implications for both upper and lower airway function. Upper airway resistance increases, and total lung capacity decreases. Upper airway symptoms increase; some women develop pregnancy-induced rhinitis and there is an increased prevalence of sleep-disordered breathing compared to prepregnancy. Longitudinal studies examining changes in upper and lower airway function parameters are limited, particularly in women with asthma. Some studies have observed reduced lung function with advancing gestation; however, changes are small and unlikely to be of major clinical significance. Spirometry is therefore a useful tool for clinical assessment of women with asthma during pregnancy., Competing Interests: Disclosure Both authors have no conflicts of interest to declare. Dr V.E. Murphy is funded by a fellowship from the Medical Research Future Fund (Investigator Grant Application ID 1196252). Dr M.E. Jensen is funded by the Peggy Lang Early Career Fellowship from the Hunter Children’s Research Foundation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Infections, including sepsis, are leading causes of death and fluid administration is part of the treatment. The optimal fluid therapy remains controversial. If the patient is transported by Emergency Medical Services (EMS), fluids can be initiated during transportation, which may result in increased overall fluid administration and fluid overload, which may be harmful. The aim of the study was to investigate the effect of EMS transportation on 24-h fluid administration in patients with suspected infection., Methods: This is a post hoc study of a prospective, multicenter, observational study, conducted in three Danish Emergency Departments (EDs), 20 January-2 March 2020, aiming at describing fluid administration in patients with suspected infection. Patients were stratified into the groups: simple infection or sepsis, in accordance with SEPSIS-3-guidelines. The primary outcome of the current study was 24-h total fluid volume (oral and intravenous) stratified by transportation mode to the EDs., Main Results: Total 24-h fluids were registered for 734 patients. Patients with simple infection or sepsis arriving by EMS ( n = 388, 54%) received mean 3,774 ml (standard deviation [SD]: 1900) and non-EMS received 3,627 ml (SD: 1568); mean difference (MD) was 303 ml [95% CI: 32; 573] adjusted for age, site, and total SOFA-score. Patients brought in by EMS received more intravenous fluids (MD: 621 ml [95% CI: 378; 864]) and less oral fluids (MD: -474 ml [95% CI: -616; -333]) than non-EMS patients., Conclusion: Patients transported by EMS received more intravenous fluids and less oral fluids but overall, more fluid in total in the first 24-h than non-EMS after adjusting for age, site and SOFA-score., 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 © 2022 Jensen, Kølsen-Petersen, Kirkegaard and Jessen.)

Background: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant., Methods: Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants' primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM 2.5 )., Results: The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 μg/m 3 PM 2.5 and 105 μg/m 3 peak PM 2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13); p < 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy., Conclusion: Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma., (© 2022. Crown.)

Introduction: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide ( F ENO )-based asthma management improves perinatal outcomes compared to usual care., Methods: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat)., Results: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05)., Conclusion: F ENO -guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (Copyright ©The authors 2022.)

Thermogenic brown or beige adipocytes dissipate energy in the form of heat and thereby counteract obesity and related metabolic complications. The miRNA cluster miR-130b/301b is highly expressed in adipose tissues and has been implicated in metabolic diseases as a posttranscriptional regulator of mitochondrial biogenesis and lipid metabolism. We investigated the roles of miR-130b/301b in regulating beige adipogenesis in vivo and in vitro. miR-130b/301b declined in adipose progenitor cells during beige adipogenesis, while forced overexpression of miR-130b-3p or miR-301b-3p suppressed uncoupling protein 1 (UCP1) and mitochondrial respiration, suggesting that a decline in miR-130b-3p or miR-301b-3p is required for adipocyte precursors to develop the beige phenotype. Mechanistically, miR-130b/301b directly targeted AMP-activated protein kinase (AMPKα1) and suppressed peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α), key regulators of brown adipogenesis and mitochondrial biogenesis. Mice lacking the miR-130b/301b miRNA cluster showed reduced visceral adiposity and less weight gain. miR-130b/301b null mice exhibited improved glucose tolerance, increased UCP1 and AMPK activation in subcutaneous fat (inguinal white adipose tissue [iWAT]), and increased response to cold-induced energy expenditure. Together, these data identify the miR-130b/301b cluster as a new regulator that suppresses beige adipogenesis involving PGC-1α and AMPK signaling in iWAT and is therefore a potential therapeutic target against obesity and related metabolic disorders., (© 2022 by the American Diabetes Association.)

Abdominal obesity associates with cardiometabolic disease and an accumulation of lipids in the visceral adipose depot, whereas lipid accumulation in the subcutaneous depot is more benign. We aimed to further investigate whether the adipogenic properties where cell-intrinsic, or dependent on a depot-specific or obesity-produced microenvironment. We obtained visceral and subcutaneous biopsies from non-obese women ( n = 14) or women living with morbid obesity ( n = 14) and isolated adipose stem and progenitor cells (ASPCs) from the stromal vascular fraction of non-obese ( n = 13) and obese ( n = 13). Following in vitro differentiation into mature adipocytes, we observed a contrasting pattern with a lower gene expression of adipogenic markers and a higher gene expression of immunogenic markers in the visceral compared to the subcutaneous adipocytes. We identified the immunogenic factor BST2 as a marker for visceral ASPCs. The effect of obesity and insulin resistance on adipogenic and immunogenic markers in the in vitro differentiated cells was minor. In contrast, differentiation with exogenous Tumor necrosis factor resulted in increased immunogenic signatures, including increased expression of BST2 , and decreased adipogenic signatures in cells from both depots. Our data, from 26 women, underscore the intrinsic differences between human visceral and subcutaneous adipose stem and progenitor cells, suggest that dysregulation of adipocytes in obesity mainly occurs at a post-progenitor stage, and highlight an inflammatory microenvironment as a major constraint of human adipogenesis., 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 © 2022 Mathur, Severinsen, Jensen, Naver, Schrölkamp, Laye, Watt, Nielsen, Krogh-Madsen, Pedersen and Scheele.)

Introduction: Alcohol use disorder is a difficult-to-treat psychiatric disorder and a major burden on public health. Existing treatment efficacy is moderate, and relapse rates are high. Preliminary findings suggest that psilocybin, a psychedelic compound, can safely and reliably occasion highly meaningful experiences that may spur a positive change in drinking behaviour when administered in a therapeutic context. However, the efficacy of a single psilocybin administration and its potential neurobiological underpinnings still remain unknown., Methods and Analysis: To establish efficacy, we will investigate the effects of psilocybin-assisted therapy versus placebo in a randomised, double-blinded, placebo-controlled 12-week clinical trial. Ninety treatment-seeking patients, aged 20-70 years, diagnosed with alcohol use disorder will be recruited from the community via advertisement and referrals from general practitioners or specialised treatment units. The psilocybin or placebo will be administered in accordance with a protocol for psychological support before, during and after the dosing. Outcome assessments will be carried out 1, 4, 8 and 12 weeks postdosing. The primary outcome is reduction in the percentage of heavy drinking days from baseline to follow-up at 12 weeks. Key secondary outcomes are as follows: (1) total alcohol consumption, (2) phosphatidyl-ethanol, an objective biomarker for alcohol, (3) plasma psilocin, the active metabolite, to establish a possible therapeutic range, (4) the acute subjective drug experience as a possible predictor of treatment outcome and (5) neuronal response to alcohol cues and cognitive flexibility within corticostriatal pathways by use of functional MR brain imaging 1-week postdosing., Ethics and Dissemination: Ethical approval has been obtained from the Committee on Health Research Ethics of the Capital Region of Denmark (H-20043832). All patients will be provided oral and written information about the trial before screening. The study results will be disseminated by peer-review publications and conference presentations., Trial Registration Number: EudraCT 2020-000829-55 and NCT05416229., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Genetic associations with macroscopic brain structure can provide insights into brain function and disease. However, specific associations with measures of local brain folding are largely under-explored. Here, we conducted large-scale genome- and exome-wide associations of regional cortical sulcal measures derived from magnetic resonance imaging scans of 40,169 individuals in UK Biobank. We discovered 388 regional brain folding associations across 77 genetic loci, with genes in associated loci enriched for expression in the cerebral cortex, neuronal development processes, and differential regulation during early brain development. We integrated brain eQTLs to refine genes for various loci, implicated several genes involved in neurodevelopmental disorders, and highlighted global genetic correlations with neuropsychiatric phenotypes. We provide an interactive 3D visualisation of our summary associations, emphasising added resolution of regional analyses. Our results offer new insights into the genetic architecture of brain folding and provide a resource for future studies of sulcal morphology in health and disease., (© 2022. The Author(s).)

BackgroundAlcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown.MethodsIn a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and single-photon emission CT (SPECT) brain scans.ResultsA total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal.ConclusionThis randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.Trial registrationEudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).FundingNovavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

Background: Asthma is one of the most common chronic health conditions experienced during pregnancy and is associated with numerous adverse maternal and perinatal outcomes., Aims: To better understand the confidence, evidence-based knowledge and guideline use among healthcare professionals around Australia commonly involved in providing antenatal care for women with asthma., Materials and Methods: An online, cross-sectional survey was developed and distributed to maternity carers (obstetricians and midwives), primary carers (general practitioners and general practice nurses) and respiratory specialists (respiratory physicians and respiratory nurses). Self-reported confidence and use of clinical guidelines were recorded. Evidence-based knowledge was assessed with 13 questions relating to four clinical scenarios that covered recommendations from national and international guidelines., Results: Primary carers and respiratory specialists were more confident in providing antenatal asthma care, more likely to use clinical guidelines and scored significantly higher in evidence-based knowledge of antenatal asthma management than maternity carers (P < 0.01 and P < 0.001, respectively). There was no significant difference in evidence-based knowledge among healthcare professionals from metropolitan, regional and rural backgrounds. However, healthcare professionals who used clinical guidelines scored significantly higher than those who did not (P < 0.0001)., Conclusion: Greater utilisation of clinical guidelines could improve the evidence-based knowledge of maternity carers. However, the absence of antenatal asthma management in obstetric- and maternity-specific guidelines poses a potential barrier that needs to be addressed. Furthermore, the development of multidisciplinary antenatal clinics, staffed by respiratory nurses and/or physicians, could improve outcomes for pregnant women with asthma who are not undertaking shared care., (© 2022 Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Children with asthma are at risk of acute exacerbations triggered mainly by viral infections. A diet high in fruit and vegetables (F&V), a rich source of carotenoids, may improve innate immune responses in children with asthma. Children with asthma (3−11 years) with a history of exacerbations and low F&V intake (≤3 serves/d) were randomly assigned to a high F&V diet or control (usual diet) for 6 months. Outcomes included respiratory-related adverse events and in-vitro cytokine production in peripheral blood mononuclear cells (PBMCs), treated with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS). During the trial, there were fewer subjects with ≥2 asthma exacerbations in the high F&V diet group (n = 22) compared to the control group (n = 25) (63.6% vs. 88.0%, p = 0.049). Duration and severity of exacerbations were similar between groups. LPS-induced interferon (IFN)-γ and IFN-λ production showed a small but significant increase in the high F&V group after 3 months compared to baseline (p < 0.05). Additionally, RV1B-induced IFN-λ production in PBMCs was positively associated with the change in plasma lycopene at 6 months (rs = 0.35, p = 0.015). A high F&V diet reduced asthma-related illness and modulated in vitro PBMC cytokine production in young children with asthma. Improving diet quality by increasing F&V intake could be an effective non-pharmacological strategy for preventing asthma-related illness by enhancing children’s innate immune responses.

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM 2.5 ) was estimated by geolocation and validated modelling. Respondents ( n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM 2.5 exposure (mean PM 2.5 32.5 μg/m 3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM 2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

Background: Conflicting literature exists regarding the risk factors for exacerbations among pregnant women with asthma. This systematic review and meta-analysis aimed to determine risk factors for asthma exacerbations during pregnancy., Methods: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*) and (exacerb* or flare up or morbidit* or attack*).All studies published between 2000 and 24 August 2021 were considered for inclusion if they reported at least one potential risk factor of asthma exacerbations in pregnant women with asthma. Of the 3337 references considered, 35 publications involving 429 583 pregnant women with asthma were included. Meta-analyses were conducted to determine mean difference in risk factor between exacerbation groups, or the relative risks of exacerbation with certain risk factors. Good study quality was found through the Newcastle-Ottawa Scale (median score 8, interquartile range 7-9)., Results: Increased maternal age (mean difference 0.62, 95% CI 0.11-1.13), obesity (relative risk 1.25, 95% CI 1.15-1.37), smoking (relative risk 1.35, 95% CI 1.04-1.75), black ethnicity (relative risk 1.62, 95% CI 1.52-1.73), multiparity (relative risk 1.31, 95% CI 1.01-1.68), depression/anxiety (relative risk 1.42, 95% CI 1.27-1.59), moderate-severe asthma (relative risk 3.44, 95% CI 2.03-5.83, versus mild) and severe asthma (relative risk 2.70, 95% CI 1.85-3.95, versus mild-moderate) were associated with an increased risk of asthma exacerbations during pregnancy., Conclusions: Future interventions aimed at reducing exacerbations in pregnancy could address the modifiable factors, such as smoking and depression/anxiety, and introduce more regular monitoring for those with nonmodifiable risk factors such as obesity and more severe asthma., Competing Interests: Conflict of interest: M.P. Bokern reports support for the present manuscript from Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology and Economics, University of Groningen, Groningen, the Netherlands and Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK. M.P. Bokern reports grants or contracts from GlaxoSmithKline (GSK PhD scholarship at London School of Hygiene and Tropical Medicine), outside the submitted work. V.E. Murphy reports support for the present manuscript from Medical Research Future Fund Investigator Grant (paid to her institution). The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: Asthma is the most common medical condition to affect pregnancy. Asthma exacerbations occur in up to 45% of pregnant women and have been associated with adverse perinatal and infant outcomes. Conflicting literature exists regarding the risk factors for exacerbations, and no synthesis of the literature currently exists. Therefore, this systematic review and meta-analysis aims to determine risk factors for asthma exacerbations during pregnancy among pregnant women with asthma., Methods: This protocol has been reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis protocols checklist. A systematic search will be conducted in the electronic MEDLINE, Embase, CINAHL and Cochrane Clinical Trials Register databases (from January 2000 onwards). Eligibility of each publication will be determined based on predefined selection criteria. Prospective cohort studies, retrospective cohort studies, case-control studies and randomised controlled trials (RCTs) will be included. Quality of included studies will be determined using the Newcastle Ottawa Scale and the Cochrane Risk of Bias tool. Pooled relative risk will be computed using random-effects meta-analyses. Heterogeneity will be assessed using the chi-squared test and the I 2 parameter. Publication bias will be assessed by inspecting a funnel plot for asymmetry and with the Egger's test of analyses including ten studies or more., Discussion: The results of this systematic review and meta-analysis will discuss the potential risk factors for asthma exacerbations during pregnancy. This may aid healthcare professionals in early identification of pregnant women with asthma at risk of poor outcomes, providing the opportunity to implement early interventions in order to avoid deterioration of asthma symptoms during pregnancy., Systematic Review Registration: PROSPERO CRD42020196190., (© 2022. The Author(s).)

Background: Treatment with antipsychotics is associated with an increased risk of type 2 diabetes mellitus (T2D), and increased levels of inflammatory biomarkers are present in patients with T2D. We previously demonstrated that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduced glucometabolic disturbances and body weight in prediabetic, overweight/obese schizophrenia-spectrum disorder patients treated with clozapine or olanzapine. This study aims to assess the involvement of cytokines in the therapeutic effects of liraglutide., Methods: Serum concentrations of 10 cytokines (interferon-γ [IFN-γ], tumor necrosis factor-α, interleukin 1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, and IL-13) from fasting prediabetic and normal glucose-tolerant (NGT) patients with schizophrenia-spectrum disorders were measured using multiplexed immunoassays. Prediabetic patients were randomized to 16 weeks of treatment with liraglutide or placebo, and cytokines were measured again at the end of the treatment., Results: IFN-γ (1.98 vs 1.17 pg/ml, P = .001), IL-4 (0.02 vs 0.01 pg/ml, P < .001), and IL-6 (0.73 vs 0.46 pg/ml, P < .001) were significantly higher in prediabetic (n = 77) vs NGT patients (n = 31). No significant changes in cytokine levels following treatment with liraglutide (n = 37) vs placebo (n = 40) were found., Conclusion: Prediabetic vs NGT patients with schizophrenia treated with clozapine or olanzapine had increased serum levels of several proinflammatory cytokines, further substantiating the link between inflammation and T2D. Treatment with liraglutide did not affect the investigated cytokines. Further testing of these findings in larger numbers of individuals is needed.

Purpose: To compare short- and long-term outcomes of hospitalized patients with ischemic colitis (IC) presenting with severe hematochezia and treated medically or colectomy and also those with inpatient vs. outpatient start of hematochezia., Methods: A retrospective analysis of prospectively collected data for IC patients hospitalized for severe hematochezia from two teaching hospitals was done from 1994 to 2020, with the diagnosis of IC made colonoscopically and confirmed histologically., Results: Ninety-seven patients initially all had medical management for IC. Seventy-two (74.2%) were stable and had no further bleeding; 17 (17.5%) had colon resection; and 8 were critically ill and not surgical candidates. Surgical patients and non-surgical candidate had higher comorbidity scores; received more red blood cell (RBC) transfusion (median (IQR) 5 (3-10) vs. 4.5 (3-6.5) vs. 1 (0-4) units, p < 0.001); had significantly longer hospital and ICU days; had higher severe complication rates (35.3% vs. 100%. vs. 5.6%, p < 0.001); and had higher 30-day all-cause mortality rates (23.5% vs. 87.5% vs. 0, p < 0.001). Inpatients developing IC hemorrhage had more RBC transfusions, more complications, longer hospital stays, and higher mortality than patients whose IC bleeding started as outpatients., Conclusions: The majority of IC patients hospitalized for severe hematochezia were successfully treated medically. Patients who were not surgical candidate had the highest rates of severe complications and mortality. Surgical patients and those who were not surgical candidate had worse outcomes than the medical group. Patients with inpatient start of bleeding from IC had significantly worse outcomes than those with outpatient start of bleeding., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Fluid therapy in patients with suspected infection is controversial, and it is not known whether fluid treatment administered in the prehospital setting is beneficial. In the absence of evidence-based guidelines for prehospital fluid therapy for patients with suspected infection, Emergency Medical Services (EMS) personnel are challenged on when and how to initiate such therapy. This study aimed to assess EMS personnel's decision-making in prehospital fluid therapy, including triggers for initiating fluid and fluid volumes, as well as the need for education and evidence-based guidelines on prehospital fluid therapy in patients with suspected infection., Methods: An online survey concerning fluid administration in prehospital patients with suspected infection was distributed to all EMS personnel in the Central Denmark Region, including ambulance clinicians and prehospital critical care anaesthesiologists (PCCA). The survey consisted of sections concerning academic knowledge, statements about fluid administration, triggers to evaluate patient needs for intravenous fluid, and clinical scenarios., Results: In total, 468/807 (58%) ambulance clinicians and 106/151 (70%) PCCA responded to the survey. Of the respondents, 73% (n = 341) of the ambulance clinicians and 100% (n = 106) of the PCCA felt confident about administering fluids to prehospital patients with infections. However, both groups primarily based their fluid-related decisions on "clinical intuition". Ambulance clinicians named the most frequently faced challenges in fluid therapy as "Unsure whether the patient needs fluid" and "Unsure about the volume of fluid the patient needs". The five most frequently used triggers for evaluating fluid needs were blood pressure, history taking, skin turgor, capillary refill time, and shock index, the last of which only applied to ambulance clinicians. In the scenarios, the majority administered 500 ml to a normotensive woman with suspected sepsis and 1000 ml to a woman with suspected sepsis-related hypotension. Moreover, 97% (n = 250) of the ambulance clinicians strongly agreed or agreed that they were interested in more education about fluid therapy in patients with suspected infection., Conclusion: The majority of ambulance clinicians and PCCA based their fluid administration on "clinical intuition". They faced challenges deciding on fluid volumes and individual fluid needs. Thus, they were eager to learn more and requested research and evidence-based guidelines., (© 2022. The Author(s).)

Background and Aims: Soluble adhesion molecules are associated with cardiovascular disease and increased in individuals with diabetes. This study assesses the impact of diabetes exposure in utero on the abundance of circulating adhesion molecules in cord serum and soluble adhesion molecules released from human umbilical vein endothelial cells (HUVEC) exposed to high glucose concentrations., Methods and Results: Women with and without diabetes were recruited. DM was diagnosed based on the American Diabetes Association criteria. Primary cultures of HUVEC were cultured in 5 mM and 25 mM glucose with 25 mM mannitol osmotic control. The soluble adhesion molecules, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM) and E-selectin were measured by ELISA in the cord blood serum and conditioned HUVEC media. The mothers with DM were older with higher BMI (p = 0.027 and 0.008, respectively). In a fully adjusted model, VCAM was significantly increased in the cord serum of infants born to mothers with diabetes (p = 0.046), but ICAM and E-selectin were not different. ICAM was also significantly correlated with maternal HbA1c (r 2  = 0.16, p = 0.004) and cord serum non-esterified fatty acids (r 2  = 0.08, p = 0.013). From the HUVEC media, the abundance of adhesion molecules was not different based on DM or high glucose exposure; however, VCAM abundance in the HUVEC supernatant was significantly correlated with ICAM (r 2  = 0.27, p = 0.010) and cord serum c-peptide (R 2  = 0.19, p = 0.043)., Conclusions: Alterations in soluble adhesion molecule abundance in infants exposed to the diabetic milieu of pregnancy may reflect early alterations in vascular function predicting future cardiovascular disease., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objective: Guidelines for asthma management contain a consensus recommendation that inhaled corticosteroid (ICS) dose should not be stepped down in pregnancy. However, this is not consistent with consumer preferences and pharmacological principles to minimize medication exposure during pregnancy. We investigated exacerbations after changes to ICS and long acting beta agonist (LABA) therapy in pregnant women with asthma., Methods: Pregnant women ( n  = 220) were recruited to a randomized controlled trial (RCT) where maintenance treatment was adjusted monthly based on either symptoms (control group), or fractional exhaled nitric oxide (FeNO, to alter ICS) and symptoms (to alter LABA, FeNO group). Exacerbations were monitored prospectively., Results: ICS were used by 137 (62.3%) women at some time during pregnancy. ICS dose remained unchanged in 16 women (11.7%, 95% confidence interval [CI] 7-18%), increased in 37 women (27%, 95%CI 20-35%), decreased in 34 women (24.8%, 95%CI 18%-33%), or both increased and decreased in 50 women (36.5%, 95%CI 29-45%). Exacerbations occurred within 14 days of ICS step-down in 11 women (13%, 95%CI 7.5%-22%). This was not significantly different from exacerbations occurring within 14 days of step-up, in 7 women (8.1%, 95%CI 4%-16%, P  = 0.294). There were no differences between management groups. Exacerbations occurred within 14 days of step-down in 14.7% (95%CI 7%-30%) of women in the control group, and in 12% (95%CI 6%-24%) of women in the FENO group., Conclusions: ICS step-down could be considered when eosinophilic inflammation or symptoms are low, and may be a useful management approach for women, doctors, and midwives wishing to minimize ICS exposure during pregnancy.

Background: There are few reports about reflux esophagitis (RE) as a cause of severe upper gastrointestinal bleeding (UGIB)., Aims: This study aims to evaluate (1) changes in its prevalence over the last three decades and (2) clinical and endoscopic characteristics and 30-day outcomes among RE patients with and without focal esophageal ulcers (EUs) and stigmata of recent hemorrhage (SRH)., Methods: A retrospective study of prospectively collected data of esophagitis patients hospitalized with severe UGIB between 1992 and 2020. Descriptive analysis and statistical comparisons were performed., Results: Of 114 RE patients, the mean age was 61.1 years and 76.3% were males. 38.6% had prior gastroesophageal reflux disease (GERD) symptoms; overall 36% were on acid suppressants. Over three consecutive decades, the prevalence of RE as a cause of severe UGIB increased significantly from 3.8 to 16.7%. 30-day rebleeding and all-cause mortality rates were 11.4% and 6.1%. RE patients with focal EUs and SRH (n = 23) had worse esophagitis than those with diffuse RE (n = 91) (p = 0.012). There were no differences in 30-day outcomes between RE patients with and without EUs and SRH., Conclusions: For patients with severe UGIB caused by RE, (1) the prevalence has increased significantly over the past three decades, (2) the reasons for this increase and preventive strategies warrant further study, (3) most patients lacked GERD symptoms and did not take acid suppressants, and (4) those with focal ulcers and SRH had more severe esophagitis and were treated endoscopically., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Maternal iron deficiency occurs in 40-50% of all pregnancies and is associated with an increased risk of respiratory disease and asthma in children. We used murine models to examine the effects of lower iron status during pregnancy on lung function, inflammation and structure, as well as its contribution to increased severity of asthma in the offspring. A low iron diet during pregnancy impairs lung function, increases airway inflammation, and alters lung structure in the absence and presence of experimental asthma. A low iron diet during pregnancy further increases these major disease features in offspring with experimental asthma. Importantly, a low iron diet increases neutrophilic inflammation, which is indicative of more severe disease, in asthma. Together, our data demonstrate that lower dietary iron and systemic deficiency during pregnancy can lead to physiological, immunological and anatomical changes in the lungs and airways of offspring that predispose to greater susceptibility to respiratory disease. These findings suggest that correcting iron deficiency in pregnancy using iron supplements may play an important role in preventing or reducing the severity of respiratory disease in offspring. They also highlight the utility of experimental models for understanding how iron status in pregnancy affects disease outcomes in offspring and provide a means for testing the efficacy of different iron supplements for preventing disease.

Background: Asthma exacerbations during pregnancy are associated with adverse pregnancy outcomes., Objective: The aim of this study was to establish factors associated with asthma exacerbations during pregnancy., Methods: We obtained data from three cohorts of pregnant women with asthma recruited in eastern Australia (2004-2019; n = 1461). Severe exacerbations were defined as episodes of asthma requiring hospitalization, an emergency department visit, or prescription of oral corticosteroids after enrollment. Baseline information on potential risk factors included demographic characteristics, asthma characteristics (eg, lung function, asthma triggers, asthma control, medication use), pregnancy factors (eg, fetal sex, parity, antenatal care type), and other maternal factors (body mass index, smoking status, mental health). Backward stepwise logistic regression and Akaike information criterion were used to determine the best-fitting model., Results: A total of 135 participants experienced a severe exacerbation during pregnancy (9.2%). Medium to high ICS dose was most strongly associated with severe asthma exacerbations (adjusted odds ratio = 3.20; 95% confidence interval, 1.85-5.53). Worse asthma control, possession of a written action plan, and a history of asthma exacerbations in the year preceding pregnancy were associated with an increased rate of exacerbations., Conclusions: Asthma exacerbations before pregnancy and more severe asthma at the beginning of pregnancy were associated with an increased rate of exacerbations during pregnancy. Despite Global Initiative for Asthma step 3 and 4 treatment and optimal management including a written asthma action plan, there is still a significant asthma burden in a group of women at high risk for severe exacerbations in pregnancy., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), and their ratio (FEV 1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV 1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood., (© 2021 World Obesity Federation.)