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Johanna Heldin,1 Andrei Malinovschi,2 Ane Johannessen,3 Kjell Alving,4 Mathias Holm,5 Karl A Franklin,6 Bertil Forsberg,7 Vivi Schlünssen,8,9 Rain Jögi,10 Thorarinn Gislason,11,12 Bryndis Benediktsdottir,11,12 Cecilie Svanes,3,13 Christer Janson1 1Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 2Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden; 3Centre for International Health, Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 4Department of Women’s and Children’s Health, Paediatric Research, Uppsala University, Uppsala, Sweden; 5Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 6Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden; 7Department of Public Health and Clinical Medicine, Section of Sustainable Health, Umeå University, Umeå, Sweden; 8Department of Public Health, Unit for Environment, Occupation and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark; 9National Research Center for the Working Environment, Copenhagen, Denmark; 10Tartu University Hospital, Lung Clinic, Tartu, Estonia; 11The Medical Faculty, University of Iceland, Reykjavik, Iceland; 12Department of Sleep, Landspitali University Hospital Reykjavik, Reykjavik, Iceland; 13Department of Occupational Medicine, Haukeland University Hospital, Bergen, NorwayCorrespondence: Christer Janson, Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden, Email christer.janson@medsci.uu.seBackground: Although asthma and allergic rhinitis are chronic diseases, some patients experience periods of remission. Information on prognostic factors associated with the remission of asthma and allergic rhinitis is valuable in resource prioritization. This study investigated factors associated with the clinical remission of asthma and allergic rhinitis.Methods: In the Respiratory Health In Northern Europe (RHINE) study, data was collected with questionnaires in stage one (RHINE I, 1989– 1992) and two follow-ups (RHINE II, 1999– 2001 and RHINE III, 2010– 2012) from Sweden, Norway, Denmark, Iceland and Estonia. Clinical remission was defined as having reported asthma or allergic rhinitis in RHINE I or RHINE II but not in RHINE III.Results: Of 13,052 participants, 975 (7.5%) reported asthma in RHINE I or RHINE II, and 3379 (25.9%) allergic rhinitis. Clinical remission of asthma and allergic rhinitis was found in 46.4% and 31.8%, respectively. Living in Estonia (OR (95% CI) 2.44 (1.22– 4.85)) and living in an apartment (1.45 (1.06– 1.98)) were related to remission of asthma, while subjects reporting allergic rhinitis (0.68 (0.51– 0.90)), asthma onset ≤ 12 years of age (0.49 (0.35– 0.68)), receiving treatment with antibiotics for respiratory illness (0.64 (0.47– 0.87)) were less likely to have asthma remission. Factors related to a higher likelihood of remission of allergic rhinitis were no asthma at baseline, age ≥ 58 years in RHINE III, allergic rhinitis onset after 12 years of age, living in rural areas as a child, having only a primary school education and not being pregnant.Conclusion: Clinical remission was found in almost one-half of those with asthma and one-third of persons with allergic rhinitis. Coexisting allergic symptoms were associated with less clinical asthma remission. Age, asthma symptoms and environmental factors in childhood, such as living in a rural area, were found to influence the clinical remission of allergic rhinitis.Keywords: asthma, allergic rhinitis, remission, epidemiology

The impact of active smoking, passive smoking, and obesity on habitual snoring in the population is mainly unknown. We aimed to study the relationship of habitual snoring with active and passive tobacco smoking in a population-based sample. A total of 15,555 of 21,802 (71%) randomly selected men and women aged 25-54 years from Iceland, Estonia, Denmark, Norway, and Sweden answered a postal questionnaire. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was more prevalent among current smokers (24.0%, p < 0.0001) and ex-smokers (20.3%, p < 0.0001) than in never-smokers (13.7%). Snoring was also more prevalent in never-smokers exposed to passive smoking at home on a daily basis than in never-smokers without this exposure (19.8% vs. 13.3%, p < 0.0001). The frequency of habitual snoring increased with the amount of tobacco smoked. Active smoking and passive smoking were related to snoring, independent of obesity, sex, center, and age. Ever smoking accounted for 17.1% of the attributable risk of habitual snoring, obesity (body mass index > or = 30 kg/m(2)) for 4.3%, and passive smoking for 2.2%. Smoking, both current and ex-smoking, is a major contributor to habitual snoring in the general population. Passive smoking is a previously unrecognized risk factor for snoring among adults. [ABSTRACT FROM AUTHOR]

Study Objective: To evaluate the tolerability and to find predictors of treatment success for an individually adjusted, one-piece mandibular advancement device in patients with snoring and obstructive sleep apnea.Design: Prospective study.Setting: Departments of Respiratory Medicine and Orthodontics, Umeå University.Patients: Six hundred nineteen of 630 patients (98%), who consecutively received treatment for sleep apnea and snoring from February 1989 to August 2000, were followed up. They had a mean apnea-hypopnea index of 16 (range, 0.0 to 76) and a mean body mass index of 28 (range, 19 to 42).Measurements: Interviews, questionnaires, and overnight sleep apnea recordings. Patients with an apnea-hypopnea index of >or=10 in the supine and/or lateral position were considered to have obstructive sleep apnea. A lateral apnea-hypopnea index of < 10, together with a supine apnea-hypopnea index of >or= 10, defined supine-dependent sleep apneas.Results: One hundred forty-eight of the 619 patients (24%) discontinued treatment. Female gender predicted treatment success, defined as an apnea-hypopnea index of < 10 in both the supine and lateral positions, with an odds ratio of 2.4 (p = 0.01). In the women, the odds ratios for treatment success were 12 for mild sleep apnea (p = 0.04), and 0.1 for complaints of nasal obstruction (p = 0.03). In the men, the odds ratios for treatment success were 6.0 for supine-dependent sleep apneas (p < 0.001), 2.5 for mild sleep apnea (p = 0.04), 1.3 for each millimeter of mandibular advancement (p = 0.03), and 0.8 for each kilogram of weight increase (p = 0.001).Conclusions: The mandibular advancement device is recommended for women with sleep apnea, for men with supine-dependent sleep apneas defined by a lateral apnea-hypopnea index of < 10, and for snorers without sleep apnea. Men who increase in weight during treatment reduce their chance of treatment success and are advised to be followed up with a new sleep apnea recording with the device. [ABSTRACT FROM AUTHOR]

Objective--Obstructive sleep apnea has been reported to occur in 20-50% of children with Down's syndrome in case series of patients referred for evaluation of suspected sleep apnea. In this population-based controlled study, we aimed to investigate whether sleep apnea is related to Down's syndrome. Material and Methods--Every child aged 2-10 years with Down's syndrome residing in the Umeå healthcare district (n=28) was invited to participate in the study, with their siblings acting as controls. Successful overnight sleep apnea recordings and echocardiography were performed in 17/21 children with Down's syndrome and in 21 controls. Results--Obstructive sleep apnea could not be diagnosed, either in children with Down's syndrome or in the control children. The apnea-hypopnea index in the children with Down's syndrome was 1.2-1.5 and did not differ from that in controls. Snoring and hypertrophy of the tonsils were more common in children with Down's syndrome than in controls. Children with Down's syndrome slept for a shorter time (p<0.001) and changed body position more often (p<0.05) than the control children. Conclusions--Snoring, restless sleep and hypertrophy of the tonsils were common among children with Down's syndrome. Obstructive sleep apnea was, however, not related to Down's syndrome in the present population-based controlled study. [ABSTRACT FROM AUTHOR]

Study Objectives: To evaluate the long-term effects on apneas and sleep and the tolerability of a mandibular advancement device in patients with obstructive sleep apnea.Design: Prospective study.Setting: Department of Respiratory Medicine, University Hospital, Umeå, Sweden.Patients: Thirty-three consecutively treated patients.Interventions: Individually adjusted mandibular advancement devices.Measurements and Results: Polysomnographic sleep recordings on 1 night without the device and 1 night with the device were performed after 0.7 +/- 0.5 years (mean +/- SD) and after 5.2 +/- 0.4 years from the start of treatment. Nineteen of the 33 patients experienced a short-term satisfactory treatment result with an apnea-hypopnea index of < 10 events per hour and a satisfactory reduction in snoring. Fourteen patients were regarded as being insufficiently treated with the device. Seventeen of the short-term satisfactorily treated patients (90%) and 2 of the remaining patients continued treatment on a long-term basis. The apnea-hypopnea index was reduced by the device from 22 +/- 17 to 4.9 +/- 5.1 events per hour (p < 0.001) in these 19 long-term treatment patients, which did not differ from what was found at the short-term follow-up visits in these patients. Patients with their devices replaced or adjusted experienced a better long-term effect than patients still using their original devices (p < 0.05).Conclusions: The long-term effect and tolerability of a mandibular advancement device are good in patients who are recommended the treatment on the basis of a short-term sleep recording, provided that the device is continuously adjusted or replaced with a new one when needed. A short-term follow-up is valuable in the selection of patients who will benefit from long-term treatment with a mandibular advancement device. [ABSTRACT FROM AUTHOR]

Part I. Examines whether the renewed biosynthesis of chlorophyll in regreening senescent leaves is associated with changes in NADPH-protochlorophyllide oxidoreductase levels. Treatments inducing leaf regreening; Effects of light intensity on regreening; Proteins in regreening leaves.

Background: To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life.Methods: A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25-54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%).Results: A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01-1.59), suffering from recurrent otitis as a child (OR = 1.18; 95%CI 1.05-1.33), growing up in a large family (OR = 1.04; 95%CI 1.002-1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI 1.12-1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined.Conclusion: The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood. [ABSTRACT FROM AUTHOR]

Aim: Heritability of cough has not yet been studied. We aimed to evaluate if individuals with cough are more likely to have offspring who develop cough, and if these associations differ by type of cough (productive/nonproductive)., Methods: The RHINESSA Generation Study (Respiratory Health In Northern Europe, Spain and Australia) includes 7155 parents (initially aged 30-54) answering detailed questionnaires in 2000 and 2010, and 8176 offspring ≥20 years answering similar questionnaires in 2012-2019. Chronic cough was categorised as productive or nonproductive (dry) cough. Associations between parental and offspring cough were analysed using mixed-effects logistic regression, adjusting for offspring age, sex, body mass index, smoking history, education level, current asthma, rhinitis, nocturnal gastroesophageal reflux; parent sex and smoking history; centre and family., Results: Among parents with nonproductive cough, 11% of their offspring reported nonproductive cough, compared with 7% of offspring to parents without nonproductive cough, adjusted odds ratio (aOR) 1.59 (95% confidence interval 1.20-2.10). Among parents with productive cough, 14% of their offspring reported productive cough, compared with 11% of offspring to parents without productive cough, aOR 1.34 (1.07-1.67). No associations were found between parent productive cough-offspring nonproductive cough, nor between parent nonproductive cough-offspring productive cough., Conclusions: Parents with chronic cough are more likely to have offspring with chronic cough independent of parental asthma, suggesting cough to be a separate heritable trait. The type of cough is important, as the nonproductive cough in parent associates only with nonproductive cough in offspring, and the same applied for productive cough., Competing Interests: Conflict of interest: Ö.I. Emilsson has participated in advisory boards with MSD Sweden, not related to this manuscript. The other authors have no other competing interests to declare., (Copyright ©The authors 2024.)

Objectives: To investigate the association of early snus use initiation (≤15 years of age) with asthma and asthma symptoms., Design: Cross-sectional analysis of a population-based cohort., Setting: Study centres in Norway, Sweden, Iceland, Denmark and Estonia, from 2016 to 2019., Participants: 9002 male and female participants above 15 years of age of the Respiratory Health in Northern Europe, Spain and Australia study., Main Outcome Measures: Current asthma and asthma symptoms., Results: The median age of study participants was 28 years (range 15-53) and 58% were women. 20% had used snus, 29% men and 14% women. Overall, 26% of males and 14% of females using snus started ≤15 years of age. Early snus use initiation was associated with having three or more asthma symptoms (OR 2.70; 95% CI 1.46 to 5.00) and a higher asthma symptom score (β-coefficient (β) 0.35; 95% CI 0.07 to 0.63) in women. These associations were weak in men (OR 1.23; 95% CI 0.78 to 1.94; β 0.16; 95% CI -0.06 to 0.38, respectively). There was evidence for an association of early snus initiation with current asthma (OR 1.72; 95% CI 0.88 to 3.37 in women; OR 1.31; 95% CI 0.84 to 2.06 in men). A sensitivity analysis among participants without smoking history showed stronger estimates for all three outcomes, in both men and women, statistically significant for three or more asthma symptoms in women (OR 3.28; 95% CI 1.18 to 9.10). Finally, no consistent associations with asthma outcomes were found for starting snus after age 15 years., Conclusions: Snus initiation in puberty was associated with higher likelihood of asthma and asthma symptoms, with the highest estimates in females and those without smoking history. These results raise concerns about the health adversities of early snus initiation and emphasise the need for public health initiatives to protect young people from this tobacco product., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; KAF has received a grant from the Swedish Heart Lung Foundation; no other financial relationships with any organisations might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Cyclic block copolymers ( c BCP) are fundamentally intriguing materials, but their synthetic challenges that demand precision in controlling both the monomer sequence and polymer topology limit access to AB and ABC block architectures. Here, we show that cyclic ABAB tetra-BCPs ( c ABAB) and their linear counterpart ( l ABAB) can be readily obtained at a speed and scale from one-pot (meth)acrylic monomer mixtures, through coupling the Lewis pair polymerization's unique compounded-sequence control with its precision in topology control. This approach achieves fast (<15 min) and quantitative (>99%) conversion to tetra-BCPs of predesignated linear or cyclic topology at scale (40 g) in a one-pot procedure, precluding the needs for repeated chain extensions, stoichiometric addition steps, dilute conditions, and postsynthetic modifications, and/or postsynthetic ring-closure steps. The resulting l ABAB and c ABAB have essentially identical molecular weights ( M n = 165-168 kg mol -1 ) and block degrees/symmetry, allowing for direct behavioral comparisons in solution (hydrodynamic volume, intrinsic viscosity, elution time, and refractive indices), bulk (thermal transitions), and film (thermomechanical and rheometric properties and X-ray scattering patterns) states. To further the morphological characterizations, allylic side-chain functionality is exploited via the thiol-ene click chemistry to install crystalline octadecane side chains and promote phase separation between the A and B blocks, allowing visualization of microdomain formation.

Background: The SF-6D index can be used to calculate quality-adjusted life years in economic evaluations, which is required by reimbursement agencies and national advisory bodies, including the Swedish ones. However, despite that SF-36 has been largely applied among patients undergoing bariatric surgery, almost no study has accessed the short form six-dimensions (SF-6D) after bariatric surgery., Aim: To establish normative values for the SF-6D index among patients undergoing bariatric surgery., Materials and Methods: All patients who received bariatric surgery in Sweden between 2011-01-01 and 2019-03-31 were obtained from the Scandinavian Obesity Surgery Registry (SOReg). Information includes patients' sociodemographic characteristics, details regarding the procedure, and postsurgical conditions. The SF-36 is applied at baseline and at follow-up years 1, 2, and 5. The multiple sequential imputation method was applied to handle missingness on SF-6D items. Based on the UK tariff, the SF-6D preference scores were calculated. The normative values for the mean (SD) SF-6D index were reported by timepoint and surgical complications for men and women, respectively. Multivariate analyses were applied to investigate how the SF-6D index is associated with timepoint, controlling for age, sex, BMI, and comorbidities in a stepwise manner., Results: The SF-6D index increased at 1 year relative to baseline and was roughly maintained at the same level at 2 years. The normative value of the SF-6D index can be used in economic evaluations for bariatric surgery., (© 2024. The Author(s).)

Aim: To study if individuals with nocturnal gastroesophageal reflux (nGER) and habitual snoring are more likely to develop asthma and respiratory symptoms (i.e. wheeze, cough, chest tightness, breathlessness) than those without these conditions, and if these associations are additive., Methods: We used data from the population-based prospective questionnaire study Respiratory Health in Northern Europe (RHINE) (11,024 participants), with data from 1999 and 2011. Participants with heartburn or belching after going to bed, at least 1 night/week, were considered to have nGER. Participants reporting loud snoring at least 3 nights/week were considered to have habitual snoring. Participants were grouped into four groups by their nGER and snoring status: "never"; "former"; "incident"; "persistent". Incident respiratory symptoms were analyzed among participants without respective symptom at baseline., Results: Snoring and nGER were independently associated with incident asthma and respiratory symptoms. The risk of incident wheeze was increased in subjects with incident or persistent snoring (adjusted odds ratio (95 % CI): 1.44 (1.21-1.72)), nGER (2.18 (1.60-2.98)) and in those with both snoring and nGER (2.59 (1.83-3.65)). The risk of developing asthma was increased in subjects with incident or persistent snoring (1.44 (1.15-1.82)), nGER (1.99 (1.35-2.93)) and in those with both snoring and nGER (1.72 (1.06-2.77)). No significant interaction was found between snoring and nGER. A similar pattern was found for the incidence of all other respiratory symptoms studied, with the highest risk among those with both incident or persistent nGER and snoring., Conclusion: The risk of developing asthma and respiratory symptoms is increased among subjects with nGER and habitual snoring. These associations are independent of each other and confounding factors. Snoring and nGER together are additive on respiratory symptoms., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements., Methods: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV 1 , FVC and height at baseline, accounting for personal smoking., Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV 1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV 1 2.6 ml/year; 0.9, 4.4) (FEV 1 /FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV 1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found., Interpretation: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV 1 and FVC later in life comparable to smoking 10 pack-years., Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya., Competing Interests: SCD and CJL have received an investigator-initiated grant from GSK and a partnership grant from AZ for unrelated work. All other authors declare no conflict of interest., (© 2023 The Authors.)

Poly(3-hydroxybutyrate) (P3HB), a biologically produced, biodegradable natural polyester, exhibits excellent thermal and barrier properties but suffers from mechanical brittleness, largely limiting its applications. Here we report a mono-material product design strategy to toughen stereoperfect, brittle bio or synthetic P3HB by blending it with stereomicrostructurally engineered P3HB. Through tacticity ([mm] from 0 to 100 %) and molecular weight (M n to 788 kDa) tuning, high-performance synthetic P3HB materials with tensile strength to ≈30 MPa, fracture strain to ≈800 %, and toughness to 126 MJ m -3 (>110× tougher than bio-P3HB) have been produced. Physical blending of the brittle P3HB with such P3HB in 10 to 90 wt % dramatically enhances its ductility from ≈5 % to 95-450 % and optical clarity from 19 % to 85 % visible light transmittance while maintaining desirably high elastic modulus (>1 GPa), tensile strength (>35 MPa), and melting temperature (160-170 °C). This P3HB-toughening-P3HB methodology departs from the traditional approach of incorporating chemically distinct components to toughen P3HB, which hinders chemical or mechanical recycling, highlighting the potential of the mono-material product design solely based on biodegradable P3HB to deliver P3HB materials with diverse performance properties., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

In 1998, Bill Gray and colleagues showed that warm temperatures trigger arabidopsis hypocotyl elongation in an auxin-dependent manner. This laid the foundation for a vibrant research discipline. With several active members of the 'thermomorphogenesis' community, we here reflect on 25 years of elevated ambient temperature research and look to the future., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Reductions in red to far-red ratio (R:FR) provide plants with an unambiguous signal of vegetational shade and are monitored by phytochrome photoreceptors. Plants integrate this information with other environmental cues to determine the proximity and density of encroaching vegetation. Shade-sensitive species respond to reductions in R:FR by initiating a suite of developmental adaptations termed shade avoidance. These include the elongation of stems to facilitate light foraging. Hypocotyl elongation is driven by increased auxin biosynthesis promoted by PHYTOCHROME INTERACTING FACTORs (PIF) 4, 5 and 7. UV-B perceived by the UV RESISTANCE LOCUS 8 (UVR8) photoreceptor rapidly inhibits shade avoidance, in part by suppressing PIF4/5 transcript accumulation and destabilising PIF4/5 protein. Here, we show that longer-term inhibition of shade avoidance is sustained by ELONGATED HYPOCOTYL 5 (HY5) and HY5 HOMOLOGUE (HYH), which regulate transcriptional reprogramming of genes involved in hormone signalling and cell wall modification. HY5 and HYH are elevated in UV-B and suppress the expression of XYLOGLUCAN ENDOTRANSGLUCOSYLASE/HYDROLASE (XTH) genes involved in cell wall loosening. They additionally increase expression GA2-OXIDASE1 (GA2ox1) and GA2ox2, encoding gibberellin catabolism enzymes that act redundantly to stabilise the PIF-inhibiting DELLA proteins. UVR8 therefore regulates temporally distinct signalling pathways to first rapidly inhibit and subsequently maintain suppression of shade avoidance following UV-B exposure., (© 2023 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

This study aimed to investigate the significance of Hill classification to predict esophagitis, Barrett's esophagus, gastroesophageal reflux disease (GERD) symptomatology, and future prescriptions of proton pump inhibitors in clinical practice. A total of 922 patients (546 women and 376 men; mean age 54.3 [SD 18.4] years) who underwent gastroscopy between 2012 and 2015 were analyzed. Patient questionnaire regarding symptoms were compared with endoscopy findings. A medical chart review was done that focused on the prescription of PPIs, additional gastroscopies, and GERD surgery in a 3-year period before the index gastroscopy and in a 6-year period afterward. In patients naïve to PPI prescriptions (n = 466), Hill grade III was significantly associated with esophagitis (AOR 2.20; 95% CI 1.00-4.84) and > 2 PPI prescriptions 6 year after the index gastroscopy (AOR 1.95; 95% CI 1.01-3.75), whereas Hill grade IV was significantly associated with esophagitis (AOR 4.41; 95% CI 1.92-10.1), with Barrett's esophagus (AOR 12.7; 95% CI 1.45-112), with reported heartburn (AOR 2.28; 95% CI 1.10-4.74), and with >2 PPI prescriptions (AOR 2.16; 95% CI 1.02-4.55). In patients 'non-naïve' to PPI prescription (n = 556), only Hill grade IV was significantly associated with esophagitis, reported heartburn, and with >2 PPI prescriptions. The gastroscopic classification in Hill grades III and IV is important in clinical practice because they are associated with esophagitis, Barrett's esophagus, symptoms of GERD, and prescriptions of PPIs, whereas a differentiation between Hill grades I and II is not., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Asthma and inflammatory bowel disease (IBD) are common inflammatory diseases. The aim of this study was to investigate the associations of IBD with asthma and respiratory symptoms., Methods: This study is based on 13,499 participants from seven northern European countries that filled in a postal questionnaire on asthma, respiratory symptoms, IBD including ulcerative colitis and Crohn's disease and various lifestyle variables., Results: There were 195 participants with IBD. The prevalence of asthma (14.5 vs 8.1%, p = 0.001), different respiratory symptoms (range 11.9-36.8% vs range 6.0-18.6%, p < 0.005), non-infectious rhinitis (52.1 vs. 41.6%, p = 0.004) and chronic rhinosinusitis (11.6 vs 6.0%, p = 0.001) were higher in subjects with IBD than in those without IBD. In multivariable regression analysis, the association between IBD and asthma was statistically significant (OR 1.95 (95% CI 1.28-2.96)) after adjusting for confounders such as sex, BMI, smoking history, educational level and physical activity. There was a significant association between asthma and ulcerative colitis (adjusted OR 2.02 (95% CI 1.27-2.19)), and asthma but not Crohn's disease (adjusted OR 1.66 (95% CI 0.69-3.95)). A significant gender interaction was found with a significant association between IBD and asthma in women but not in men ((OR 2.72 (95% CI 1.67-4.46) vs OR 0.87 (95% CI 0.35-2.19), p = 0.038)., Conclusions: Patients with IBD, particularly those with ulcerative colitis and female, have a higher prevalence of asthma and respiratory symptoms. Our findings indicate that it is important to consider respiratory symptoms and disorders when examining patients with manifest or suspected IBD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Classical homocystinuria (HCU) is a rare inborn error of amino acid metabolism characterized by accumulation of homocysteine, an intermediate product of methionine metabolism, leading to significant systemic toxicities, particularly within the vascular, skeletal, and ocular systems. Most patients require lifelong dietary therapy with severe restriction of natural protein to minimize methionine intake, and many patients still struggle to maintain healthy homocysteine levels. Since eliminating methionine from the diet reduces homocysteine levels, we hypothesized that an enzyme that can degrade methionine within the gastrointestinal (GI) tract could help HCU patients maintain healthy levels while easing natural protein restrictions. We describe the preclinical development of CDX-6512, a methionine gamma lyase (MGL) enzyme that was engineered for stability and activity within the GI tract for oral administration to locally degrade methionine. CDX-6512 is stable to low pH and intestinal proteases, enabling it to survive the harsh GI environment without enteric coating and to degrade methionine freed from dietary protein within the small intestine. Administering CDX-6512 to healthy non-human primates following a high protein meal led to a dose-dependent suppression of plasma methionine. In Tg-I278T Cbs -/- mice, an animal model that recapitulates aspects of HCU disease including highly elevated serum homocysteine levels, oral dosing of CDX-6512 after a high protein meal led to suppression in serum levels of both methionine and homocysteine. When animals received a daily dose of CDX-6512 with a high protein meal for two weeks, the Tg-I278T Cbs -/- mice maintained baseline homocysteine levels, whereas homocysteine levels in untreated animals increased by 39%. These preclinical data demonstrate the potential of CDX-6512 as an oral enzyme therapy for HCU., Competing Interests: Declaration of Competing Interest All work was funded by Codexis, Inc. K.S., V.M., L.T., K.A.F., N.K., C.H.-R., J.H., F.D., S.G., S.G., H.A., N.Z., G.R., M.H.A.I., G.H., K.M., and A.P.S. are employees of Codexis or were employees at the time the work was completed., (Copyright © 2023 Codexis, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether the quality-adjusted life years (QALYs) of the patients who underwent bariatric surgery could be predicted using their baseline information., Materials and Methods: All patients who received bariatric surgery in Sweden between January 1, 2011 and March 31, 2019 were obtained from the Scandinavian Obesity Surgery Registry (SOReg). Baseline information included patients' sociodemographic characteristics, details regarding the procedure, and postsurgical conditions. QALYs were assessed by the SF-6D at follow-up years 1 and 2. The general and regularized linear regression models were used to predict postoperative QALYs., Results: All regression models demonstrated satisfactory and comparable performance in predicting QALYs at follow-up year 1, with R 2 and relative root mean squared error (RRMSE) values of about 0.57 and 9.6%, respectively. The performance of the general linear regression model increased with the number of variables; however, the improvement was ignorable when the number of variables was more than 30 and 50 for follow-up years 1 and 2, respectively. Although minor L1 and L2 regularization provided better prediction ability, the improvement was negligible when the number of variables was more than 20. All the models showed poorer performance for predicting QALYs at follow-up year 2., Conclusions: Patient characteristics before bariatric surgery including health related quality of life, age, sex, BMI, postoperative complications within six weeks, and smoking status, may be adequate in predicting their postoperative QALYs after one year. Understanding these factors can help identify individuals who require more personalized and intensive support before, during, and after surgery., (© 2023. The Author(s).)

The global plastics problem is a trifecta, greatly affecting environment, energy and climate 1-4 . Many innovative closed/open-loop plastics recycling or upcycling strategies have been proposed or developed 5-16 , addressing various aspects of the issues underpinning the achievement of a circular economy 17-19 . In this context, reusing mixed-plastics waste presents a particular challenge with no current effective closed-loop solution 20 . This is because such mixed plastics, especially polar/apolar polymer mixtures, are typically incompatible and phase separate, leading to materials with substantially inferior properties. To address this key barrier, here we introduce a new compatibilization strategy that installs dynamic crosslinkers into several classes of binary, ternary and postconsumer immiscible polymer mixtures in situ. Our combined experimental and modelling studies show that specifically designed classes of dynamic crosslinker can reactivate mixed-plastics chains, represented here by apolar polyolefins and polar polyesters, by compatibilizing them via dynamic formation of graft multiblock copolymers. The resulting in-situ-generated dynamic thermosets exhibit intrinsic reprocessability and enhanced tensile strength and creep resistance relative to virgin plastics. This approach avoids the need for de/reconstruction and thus potentially provides an alternative, facile route towards the recovery of the endowed energy and materials value of individual plastics., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Chloroplasts are a common feature of plant cells and aspects of their metabolism, including photosynthesis, are influenced by low-temperature conditions. Chloroplasts contain a small circular genome that encodes essential components of the photosynthetic apparatus and chloroplast transcription/translation machinery. Here, we show that in Arabidopsis, a nuclear-encoded sigma factor that controls chloroplast transcription (SIGMA FACTOR5) contributes to adaptation to low-temperature conditions. This process involves the regulation of SIGMA FACTOR5 expression in response to cold by the bZIP transcription factors ELONGATED HYPOCOTYL5 and ELONGATED HYPOCOTYL5 HOMOLOG. The response of this pathway to cold is gated by the circadian clock, and it enhances photosynthetic efficiency during long-term cold and freezing exposure. We identify a process that integrates low-temperature and circadian signals, and modulates the response of chloroplasts to low-temperature conditions., (© 2023. The Author(s).)

Background: Obesity Problem Scale (OP) is a widely applied instrument for obesity, however currently calculation of health utility based on OP is not feasible as it is not a preference-based measure. Using data from the Scandinavian Obesity Surgery Registry (SOReg), we sought to develop a mapping algorithm to estimate SF-6D utility from OP. Furthermore, to test whether the mapping algorithm is robust to the effect of surgery., Method: The source data SOReg (n = 36 706) contains both OP and SF-36, collected at pre-surgery and at 1, 2 and 5 years post-surgery. The Ordinary Least Square (OLS), beta-regression and Tobit regression were used to predict the SF-6D utility for different time points respectively. Besides the main effect model, different combinations of patient characteristics (age, sex, Body Mass Index, obesity-related comorbidities) were tested. Both internal validation (split-sample validation) and validation with testing the mapping algorithm on a dataset from other time points were carried out. A multi-stage model selection process was used, accessing model consistency, parsimony, goodness-of-fit and predictive accuracy. Models with the best performance were selected as the final mapping algorithms., Results: The final mapping algorithms were based on OP summary score using OLS models, for pre- and post-surgery respectively. Mapping algorithms with different combinations of patients' characteristics were presented, to satisfy the user with a different need., Conclusion: This study makes available algorithms enabling crosswalk from the Obesity Problem Scale to the SF-6D utility. Different mapping algorithms are recommended for the mapping of pre- and post-operative data., (© 2022. The Author(s).)