Cystic Fibrosis
Resolvin D1 improves airway inflammation and exercise capacity in cystic fibrosis lung disease
FASEB J. 2023 Nov;37(11):e23233. doi: 10.1096/fj.202301495R.
ABSTRACT
Mucus plugging and non-resolving inflammation are inherent features of cystic fibrosis (CF) that may lead to progressive lung disease and exercise intolerance, which are the main causes of morbidity and mortality for people with CF. Therefore, understanding the influence of mucus on basic mechanisms underlying the inflammatory response and identifying strategies to resolve mucus-driven airway inflammation and consequent morbidity in CF are of wide interest. Here, we investigated the effects of the proresolving lipid mediator resolvin (Rv) D1 on mucus-related inflammation as a proof-of-concept to alleviate the burden of lung disease and restore exercise intolerance in CF. We tested the effects of RvD1 on inflammatory responses of human organotypic airways and leukocytes to CF mucus and of humanized mice expressing the epithelial Na + channel (βENaC-Tg) having CF-like mucus obstruction, lung disease, and physical exercise intolerance. RvD1 reduced pathogenic phenotypes of CF-airway supernatant (ASN)-stimulated human neutrophils, including loss of L-selectin shedding and CD16. RNASeq analysis identified select transcripts and pathways regulated by RvD1 in ASN-stimulated CF bronchial epithelial cells that are involved in sugar metabolism, NF-κB activation and inflammation, and response to stress. In in vivo inflammation using βENaC TG mice, RvD1 reduced total leukocytes, PMN, and interstitial Siglec-MΦ when given at 6-8 weeks of age, and in older mice at 10-12 weeks of age, along with the decrease of pro-inflammatory chemokines and increase of anti-inflammatory IL-10. Furthermore, RvD1 treatment promoted the resolution of pulmonary exacerbation caused by Pseudomonas aeruginosa infection and significantly enhanced physical activity and energy expenditure associated with mucus obstruction, which was impaired in βENaC-Tg mice compared with wild-type. These results demonstrate that RvD1 can rectify features of CF and offer proof-of-concept for its therapeutic application in this and other muco-obstructive lung diseases.
PMID:37823221 | DOI:10.1096/fj.202301495R
Medication adherence in Medicare-enrolled older adults with asthma and chronic obstructive pulmonary disease before and during COVID-19 pandemic
Ther Adv Chronic Dis. 2023 Oct 9;14:20406223231205796. doi: 10.1177/20406223231205796. eCollection 2023.
ABSTRACT
BACKGROUND: Medication adherence in Medicare-enrolled older adults with asthma and chronic obstructive pulmonary disease (COPD) before and during the coronavirus disease 2019 (COVID-19) pandemic is unknown.
OBJECTIVES: To evaluate medication adherence and determinants of high adherence before and during the COVID-19 pandemic in this population.
DESIGN: Retrospective cohort study.
METHODS: The proportion of days covered (PDC) reflected medication adherence from January to July 2019 and from January to July 2020. Patients <65 years of age, with COPD or asthma alone, or with cystic fibrosis were excluded. Paired t tests were used to assess adherence changes. Logistic regression explored association of age, sex, diagnosis of depression, number of medications, medication-related problems, prescribers, pharmacies, controller medication classes, albuterol rescue inhaler fills, oral corticosteroid fills, and having a 90-day supply with high adherence (PDC ⩾ 80%).
RESULTS: This analysis included 989 patients. In this cohort, 61.2% of patients received oral corticosteroids. Over 60% of patients had ⩾3 rescue fills in both 2019 and 2020. Medication adherence to controller medications significantly decreased for all controller medications (p < 0.001) in 2020. In 2019 and 2020, number of controller medication classes and having a 90-day supply were associated with high adherence (p < 0.001). In 2019, variables associated with high adherence also included number of medication-related problems and having ⩾3 albuterol rescue inhalers (p < 0.001).
CONCLUSION: Medication adherence to controllers significantly decreased during the pandemic among older adults with asthma and COPD. Patients with multiple controller classes and a 90-day supply were more likely to be highly adherent. A 90-day supply of medications should be used to facilitate access to medication during the pandemic. Healthcare professionals should assess medication adherence, resolve the barriers of adherence and medication-related problems to achieve desired clinical outcomes among older adults with both asthma and COPD.
PMID:37822769 | PMC:PMC10563468 | DOI:10.1177/20406223231205796
Accuracy and impact on quality of life of real-time continuous glucose monitoring in children with hyperinsulinaemic hypoglycaemia
Front Endocrinol (Lausanne). 2023 Sep 26;14:1265076. doi: 10.3389/fendo.2023.1265076. eCollection 2023.
ABSTRACT
OBJECTIVE: Continuous glucose monitoring (CGM) is the standard of care for glucose monitoring in children with diabetes, however there are limited data reporting their use in hyperinsulinaemic hypoglycaemia (HH). Here, we evaluate CGM accuracy and its impact on quality of life in children with HH.
METHODS: Real-time CGM (Dexcom G5 and G6) was used in children with HH aged 0-16years. Data from self-monitoring capillary blood glucose (CBG) and CGM were collected over a period of up to 28days and analysed. Quality of life was assessed by the PedsQL4.0 general module and PedsQL2.0 family impact module, completed by children and their parents/carers before and after CGM insertion. Analysis of accuracy metrics included mean absolute relative difference (MARD) and proportion of CGM values within 15, 20, and 30% or 15, 20, and 30 mg/dL of reference glucose values >100 mg/dL or ≤100 mg/dL, respectively (% 15/15, % 20/20, % 30/30). Clinical reliability was assessed with Clarke error grid (CEG) analyses.
RESULTS: Prospective longitudinal study with data analysed from 40 children. The overall MARD between reference glucose and paired CGM values (n=4,928) was 13.0% (Dexcom G5 12.8%, Dexcom G6 13.1%). The proportion of readings meeting %15/15 and %20/20 were 77.3% and 86.4%, respectively, with CEG analysis demonstrating 97.4% of all values in zones A and B. Within the hypoglycaemia range (<70 mg/dL), the median ARD was 11.4% with a sensitivity and specificity of 64.2% and 91.3%, respectively. Overall PedsQL child report at baseline and endpoint were 57.6 (50.5 - 75.8) and 87.0 (82.9 - 91.2), and for parents were 60.3 (44.8 - 66.0) and 85.3 (83.7 - 91.3), respectively (both p<0.001).
CONCLUSION: Use of CGM for children with HH is feasible, with clinically acceptable accuracy, particularly in the hypoglycaemic range. Quality of life measures demonstrate significant improvement after CGM use. These data are important to explore use of CGM in disease indications, including neonatal and paediatric diabetes, cystic fibrosis and glycogen storage disorders.
PMID:37822600 | PMC:PMC10562688 | DOI:10.3389/fendo.2023.1265076
Transcriptional Response of <em>Burkholderia cenocepacia</em> H111 to Severe Zinc Starvation
Br J Biomed Sci. 2023 Sep 26;80:11597. doi: 10.3389/bjbs.2023.11597. eCollection 2023.
ABSTRACT
Burkholderia cenocepacia is an opportunistic pathogen that is primarily associated with severe respiratory infections in people with cystic fibrosis. These bacteria have significant intrinsic resistance to antimicrobial therapy, and there is a need for more effective treatments. Bacterial zinc uptake and homeostasis systems are attractive targets for new drugs, yet our understanding of how bacteria acquire and utilise zinc remains incomplete. Here we have used RNA-sequencing and differential gene expression analysis to investigate how B. cenocepacia H111 is able to survive in zinc poor environments, such as those expected to be encountered within the host. The data shows that 201 genes are significantly differentially expressed when zinc supply is severely limited. Included in the 85 upregulated genes, are genes encoding a putative ZnuABC high affinity zinc importer, two TonB-dependent outer membrane receptors that may facilitate zinc uptake across the outer cell membrane, and a COG0523 family zinc metallochaperone. Amongst the 116 downregulated genes, are several zinc-dependent enzymes suggesting a mechanism of zinc sparring to reduce the cells demand for zinc when bioavailability is low.
PMID:37822354 | PMC:PMC10563805 | DOI:10.3389/bjbs.2023.11597
Alternative therapies against Mycobacterium abscessus infections
Clin Microbiol Infect. 2023 Oct 9:S1198-743X(23)00486-X. doi: 10.1016/j.cmi.2023.10.001. Online ahead of print.
ABSTRACT
BACKGROUND: Mycobacterium abscessus (Mab) is considered as the most pathogenic rapid-growing mycobacteria (RGM) in humans, causing pulmonary and extra-pulmonary diseases, especially in cystic fibrosis patients. Mab shows intrinsic and acquired resistance to many drugs, leaving limited treatment options that lead to a generally poor prognosis. The standard therapeutic regimen last for more than six months and consists of a drug cocktail that ideally includes a macrolide and amikacin. Yet, toxicity and efficacy are suboptimal due also to the high toxicity. There is a need to introduce innovative and out-of-the-box approaches to improve treatments.
OBJECTIVE: In this narrative review, we summarize the recent research on the alternative strategies proposed and discuss the importance of using appropriate experimental assays to assess their activity.
SOURCES: Included articles were identified by searching PubMed and MEDLINE until June 2023. The search terms were 'mycobacterium abscessus', 'antimicrobial', 'alternative therapies'. Additional relevant references were obtained from articles retrieved from the primary search.
CONTENT: Therapies against Mab including host directed therapies, repurposed drugs, phage therapy, anti-virulence strategies, essential oils, inhalation therapies.
IMPLICATION: Alternative treatments may represent a valid tool to cope the burden of antimicrobial resistance in Mab-caused diseases.
PMID:37820951 | DOI:10.1016/j.cmi.2023.10.001
Emerging In Vitro Models for the Study of Infection and Pathogenesis of Pseudomonas aeruginosa and Testing of Antibacterial Agents
Methods Mol Biol. 2024;2721:233-239. doi: 10.1007/978-1-0716-3473-8_16.
ABSTRACT
Several animal models have been developed to study infection strategies and pathogenesis of Pseudomonas aeruginosa. Some of these models are also used in preclinical and clinical research. However, these models are increasingly showing their limitations, including in recapitulating human diseases such as cystic fibrosis, which is strongly linked to P. aeruginosa infection. The emerging field of human organoids and organs-on-a-chip is expected to provide answers to the need for in vitro modeling of human diseases. Here, we describe the first recent efforts that will hopefully provide the basis for the development of advanced in vitro models for the study of P. aeruginosa infection and pathogenesis and the testing of antibacterial agents.
PMID:37819526 | DOI:10.1007/978-1-0716-3473-8_16
Improving the Predictive Value of Preclinical Mouse Models of Pseudomonas aeruginosa Respiratory Infection to Evaluate Antibiotic Efficacy
Methods Mol Biol. 2024;2721:215-231. doi: 10.1007/978-1-0716-3473-8_15.
ABSTRACT
Disease-specific animal models and treatment regimens are essential to optimize anti-Pseudomonas drug testing. Mouse models of acute and chronic P. aeruginosa infections provide valuable resources that mimic the initial and progressive bronchopulmonary infection typically observed in a wide range of patients - in hospital settings, with cystic fibrosis or chronic obstructive pulmonary disease. In this chapter, we will explain how mice can be treated using different administration routes in disease-specific models of P. aeruginosa respiratory infection. We will also describe methods used to evaluate multiple endpoints, including profiling of bacterial and host responses. The application of these procedures in disease-specific models is essential to optimize the efficacy of anti-P. aeruginosa treatments and provide an enhanced link between preclinical testing and clinical trials.
PMID:37819525 | DOI:10.1007/978-1-0716-3473-8_15
Pseudomonas aeruginosa Soluble Pyocins as Antibacterial Weapons
Methods Mol Biol. 2024;2721:125-136. doi: 10.1007/978-1-0716-3473-8_9.
ABSTRACT
Pseudomonas aeruginosa is an opportunistic pathogen causing nosocomial infections and associated with lung infections in cystic fibrosis (CF) patients (Lyczak et al., Microbes Infect 2:1051-1060, 2000). Multiple drug-resistant P. aeruginosa strains pose a serious problem because of antibiotic treatment failure. There is therefore a need for alternative anti-Pseudomonas molecules. Soluble pyocins (S-pyocins) are bacteriocins produced by P. aeruginosa strains that kill sensitive strains of the same species. These bacteriocins and their immunity gene are easily cloned and expressed in E. coli and their activity spectrum against different P. aeruginosa strains can be tested. In this chapter, we describe the procedures for cloning, expression, and sensitivity testing of two different S-pyocins. We also describe how to identify their receptor binding domain in sensitive strains, how to construct chimeric pyocins with extended activity spectra, and how to identify new pyocins in genomes by multiplex PCR.
PMID:37819519 | DOI:10.1007/978-1-0716-3473-8_9
Effect of malate on the activity of ciprofloxacin against <em>Pseudomonas aeruginosa</em> in different <em>in vivo</em> and <em>in vivo</em>-like infection models
Antimicrob Agents Chemother. 2023 Oct 11:e0068223. doi: 10.1128/aac.00682-23. Online ahead of print.
ABSTRACT
The clinical significance of Pseudomonas aeruginosa infections and the tolerance of this opportunistic pathogen to antibiotic therapy makes the development of novel antimicrobial strategies an urgent need. We previously found that D,L-malic acid potentiates the activity of ciprofloxacin against P. aeruginosa biofilms grown in a synthetic cystic fibrosis sputum medium by increasing metabolic activity and tricarboxylic acid cycle activity. This suggested a potential new strategy to improve antibiotic therapy in P. aeruginosa infections. Considering the importance of the microenvironment on microbial antibiotic susceptibility, the present study aims to further investigate the effect of D,L-malate on ciprofloxacin activity against P. aeruginosa in physiologically relevant infection models, aiming to mimic the infection environment more closely. We used Caenorhabditis elegans nematodes, Galleria mellonella larvae, and a 3-D lung epithelial cell model to assess the effect of D,L-malate on ciprofloxacin activity against P. aeruginosa. D,L-malate was able to significantly enhance ciprofloxacin activity against P. aeruginosa in both G. mellonella larvae and the 3-D lung epithelial cell model. In addition, ciprofloxacin combined with D,L-malate significantly improved the survival of infected 3-D cells compared to ciprofloxacin alone. No significant effect of D,L-malate on ciprofloxacin activity against P. aeruginosa in C. elegans nematodes was observed. Overall, these data indicate that the outcome of the experiment is influenced by the model system used which emphasizes the importance of using models that reflect the in vivo environment as closely as possible. Nevertheless, this study confirms the potential of D,L-malate to enhance ciprofloxacin activity against P. aeruginosa-associated infections.
PMID:37819115 | DOI:10.1128/aac.00682-23
A personalized medicine approach to optimize care for a pediatric cystic fibrosis patient with atypical clinical symptoms
Pediatr Pulmonol. 2023 Oct 11. doi: 10.1002/ppul.26719. Online ahead of print.
NO ABSTRACT
PMID:37818777 | DOI:10.1002/ppul.26719
Comparison of the modified shuttle walk test in children with cystic fibrosis and healthy controls
Physiother Res Int. 2023 Oct 11:e2052. doi: 10.1002/pri.2052. Online ahead of print.
ABSTRACT
OBJECTIVE: To evaluate and compare performance in the modified shuttle walk test (MSWT) with cardiorespiratory parameters and respiratory muscle strength in children with cystic fibrosis (CF) and healthy controls.
METHODS: A cross-sectional study with children divided into the CF group (CFG) and healthy control group (HCG). Two MSWTs were performed and the data from the test with the longest distance walked and its cardiorespiratory parameters (blood pressure, respiratory rate, heart rate (HR), oxygen saturation, and dyspnea sensation) were considered, the last three every 4 levels. Respiratory muscle strength was evaluated using a manometer. The Wilcoxon test was used to compare the parameters before and after the MSWT, and the Mann-Whitney and independent t-tests were applied to compare the data between the groups. The distance walked and its association with the variation in cardiorespiratory parameters and respiratory muscle strength were analyzed by Spearman's correlation.
RESULTS: Sixty-two children (31 in each group) participated, with an average age of 10.2 (2.1) years. Children with CF had poorer performance in the average distance walked (CFG 716.7 (274.3)) when compared to the HCG (948.0 (202.8)). Both groups exhibited an increase in all the cardiorespiratory parameters at the end of the test, but the CFG displayed less variation in some parameters. Children with CF presented a positive correlation between distance walked and respiratory muscle strength, HR variation, and systolic blood pressure.
CONCLUSIONS: There was no difference in respiratory muscle strength between the groups. In the CFG, the greater the respiratory muscle strength, the better the performance in the MSWT. The CFG exhibited less variation in cardiorespiratory parameters than the HCG.
PMID:37818756 | DOI:10.1002/pri.2052
Telemonitoring: An opportunity in cystic fibrosis lung transplant recipients
Heliyon. 2023 Sep 9;9(10):e19931. doi: 10.1016/j.heliyon.2023.e19931. eCollection 2023 Oct.
ABSTRACT
INTRODUCTION: Telemedicine has been successfully employed in a wide range of conditions, such as such as chronic lung disease and COVID-19. This study evaluate the role of telemonitoring for the early diagnosis of acute lung allograft dysfunction in cystic fibrosis adults who underwent lung transplant (LuTx). Quality of life and functional level achieved during a 12 months follow up were assessed.
METHODS: Patients were randomized into two groups; control group received traditional hospital-based follow-up, whereas patients in the intervention group received, on top of standard care, a telemonitoring device, with a pulse oximeter and a spirometer integrated. Telemonitoring data were digitally transmitted to our centre.
RESULTS: Sixteen patients were enrolled in each group. No statistically significant difference was found between the two groups in terms of incidence of allograft dysfunction, time from onset of symptoms to diagnosis and time of occurrence from LuTx. Moreover, both groups achieved similar quality of life and functional level. With reference to the telemonitoring group: 1) hospital reported data were consistent with those being remotely registered; 2) adherence to telemonitoring decreased during the follow up; 3) the majority of patients reported a high degree of satisfaction.
CONCLUSION: The COVID19 pandemic highlighted the necessity to investigate alternative practices to treat chronically ill individuals. Telemonitoring is a valuable tool to improve quality care to LuTx recipients.
PMID:37818011 | PMC:PMC10560782 | DOI:10.1016/j.heliyon.2023.e19931
Editorial: Current omics-based approaches as tools for improving the understanding, diagnosis and management of inflammatory lung disease
Front Med (Lausanne). 2023 Sep 25;10:1280282. doi: 10.3389/fmed.2023.1280282. eCollection 2023.
NO ABSTRACT
PMID:37817810 | PMC:PMC10561216 | DOI:10.3389/fmed.2023.1280282
The effectiveness of CFTR modulators in people with CF and rare mutations: A real-world study
Pediatr Pulmonol. 2023 Oct 11. doi: 10.1002/ppul.26713. Online ahead of print.
NO ABSTRACT
PMID:37817743 | DOI:10.1002/ppul.26713
Adherence to inhaled antibiotics in people with cystic fibrosis: insights from a virtual patient advisory board
Expert Rev Respir Med. 2023 Oct 11:1-3. doi: 10.1080/17476348.2023.2267427. Online ahead of print.
ABSTRACT
BACKGROUND: Chronic airway infection by Pseudomonas aeruginosa significantly impacts the health of people with cystic fibrosis (PwCF), presenting complex treatment challenges.
RESEARCH DESIGN AND METHODS: To gain insights into PwCF's experiences, a virtual European Patient Advisory Board was convened. Board explored inhaled antibiotic usage, treatment adherence, and associated challenges. Additionally, an online survey was conducted among PwCF to further understand real-life experiences and unmet needs, particularly related to CFTR modulators.
RESULTS: The Advisory Board proved instrumental in collecting valuable real-world perspectives, offering potential avenues for reshaping the care model for complex diseases like cystic fibrosis.
CONCLUSIONS: PwCF on CFTR modulators are questioning the necessity of continuing chronic medications and therapies. Physicians are urged to carefully consider the balance between simplifying antibiotic treatment and the risk of clinical deterioration due to bacterial infections when making treatment decisions. Furthermore, the development and global harmonization of diagnostic tools for chronic lung damage and treatment guidelines are crucial to justify the demanding routines that PwCF must endure to manage their condition.The heterogeneity in patient journeys, diagnostic challenges, treatment complexity, and issues related to adherence highlight the need for patient-centric, personalized care that emphasizes improving and maintaining treatment adherence to optimize cystic fibrosis management.
PMID:37817635 | DOI:10.1080/17476348.2023.2267427
Antenatal Screening for CFTR Variants
JAMA. 2023 Oct 10;330(14):1388. doi: 10.1001/jama.2023.14991.
NO ABSTRACT
PMID:37815573 | DOI:10.1001/jama.2023.14991
The accumulation and growth of Pseudomonas aeruginosa on surfaces is modulated by surface mechanics via cyclic-di-GMP signaling
NPJ Biofilms Microbiomes. 2023 Oct 10;9(1):78. doi: 10.1038/s41522-023-00436-x.
ABSTRACT
Attachment of bacteria onto a surface, consequent signaling, and accumulation and growth of the surface-bound bacterial population are key initial steps in the formation of pathogenic biofilms. While recent reports have hinted that surface mechanics may affect the accumulation of bacteria on that surface, the processes that underlie bacterial perception of surface mechanics and modulation of accumulation in response to surface mechanics remain largely unknown. We use thin and thick hydrogels coated on glass to create composite materials with different mechanics (higher elasticity for thin composites; lower elasticity for thick composites) but with the same surface adhesivity and chemistry. The mechanical cue stemming from surface mechanics is elucidated using experiments with the opportunistic human pathogen Pseudomonas aeruginosa combined with finite-element modeling. Adhesion to thin composites results in greater changes in mechanical stress and strain in the bacterial envelope than does adhesion to thick composites with identical surface chemistry. Using quantitative microscopy, we find that adhesion to thin composites also results in higher cyclic-di-GMP levels, which in turn result in lower motility and less detachment, and thus greater accumulation of bacteria on the surface than does adhesion to thick composites. Mechanics-dependent c-di-GMP production is mediated by the cell-surface-exposed protein PilY1. The biofilm lag phase, which is longer for bacterial populations on thin composites than on thick composites, is also mediated by PilY1. This study shows clear evidence that bacteria actively regulate differential accumulation on surfaces of different stiffnesses via perceiving varied mechanical stress and strain upon surface engagement.
PMID:37816780 | DOI:10.1038/s41522-023-00436-x
De Novo Crohn's Disease in Children With Ulcerative Colitis Undergoing Ileal Pouch-Anal Anastomosis: A Multicenter, Retrospective Study From the Pediatric IBD Porto Group of the ESPGHAN
Inflamm Bowel Dis. 2023 Oct 10:izad199. doi: 10.1093/ibd/izad199. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: We sought to define the prevalence and to characterize possible predictive factors of Crohn's disease (CD) occurring in children with ulcerative colitis (UC) after ileal pouch-anal anastomosis (IPAA).
METHODS: This was a multicenter, retrospective study including 15 centers of the Porto IBD group of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition. Children with a confirmed diagnosis of UC undergoing colectomy with IPAA and a minimal follow up of 6 months were identified. The following data were collected: demographic data; endoscopic and histologic data; disease activity; laboratory exams; therapeutic history; indication for surgery, type, and timing; and IPAA functional outcomes and complications. In de novo CD cases, time of diagnosis, phenotype, location, and therapies were gathered.
RESULTS: We identified 111 UC children undergoing IPAA from January 2008 to June 2018 (median age at colectomy: 13 years; age range: 1-18 years; female/male: 59/52). The median time from diagnosis to colectomy was 16 (range, 0-202) months. At the last follow-up, 40 (36%) of 111 children developed pouchitis. The criteria for de novo CD were met in 19(17.1%) of 111 children with a 25-month median (range, 3-61 months). At last follow-up, 12 (63.1%) of 19 were treated with biologics and in 5 (26.3%) of 19 children, the pouch was replaced with definitive ileostomy. In a multivariable logistic regression model, decreased preoperative body mass index z scores (odds ratio, 2.2; 95% confidence interval, 1.1-4.4; P = .01) resulted as the only variable associated with CD development.
CONCLUSIONS: Children with UC undergoing IPAA carry a high risk of developing subsequent CD. De novo CD cases showed decreased preoperative body mass index z scores, identifying a poor nutritional status as a possible predictive factor.
PMID:37816230 | DOI:10.1093/ibd/izad199
Investigation of the effect of vitamin K1 prophylaxis on newborn screenings tests in newborns
J Med Biochem. 2023 Aug 25;42(3):376-382. doi: 10.5937/jomb0-40162.
ABSTRACT
BACKGROUND: Routine screening for hereditary disorders in newborns includes screening for treatable metabolic and endocrine disorders, such as biotidinase deficiency, galactosemia, maple syrup urine disease, hypothyroidism, and cystic fibrosis. Incorrect test results may be encountered due to the use of vitamin K1. To investigate the interference effect of vitamin K1 on neonatal screening tests and to raise awareness of erroneous measurements.
METHODS: Heel blood samples were taken from 25 newborns born in a neonatal intensive care unit. Dry blood C0, C2, C3, C4, C4DC, C5:1, C5OH, C5DC, C6, C6DC, C8, C8:1, C8DC, C10, C10:1, C10DC, C12, C14, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2, C18:OH, methylglutaryl, valine, leucine/isoleucine, methionine, phenylalanine, argininosuccinic acid, aspartate, alanine, arginine, citrulline, glycine, ornithine, and glutamate tests were studied using the tandem mass spectrometry (MS) method. The results of the heel blood samples obtained before and after the application of vitamin K1 (Phyto menadione) were compared.
RESULTS: In two studies conducted with in vitro and in vivo tests, C0, C2, C3, C4, C4DC, C5, C5OH, C6, C8, C10, C10:1, C14, C16, C16:1, C18, C18:1, methylglutaryl, phenylalanine, argininosuccinic acid, tyrosine, aspartate, arginine, citrulline, glycine, and glutamine were all significantly elevated (p < 0.05).
CONCLUSIONS: Heel blood samples may yield false results due to vitamin K1 administration. In the case of doubtful results, a new sample should be taken and the measurement should be repeated.
PMID:37814616 | PMC:PMC10560507 | DOI:10.5937/jomb0-40162
Aromatic pentaamide macrocycles bind anions with high affinity for transport across biomembranes
Nat Chem. 2023 Oct 9. doi: 10.1038/s41557-023-01315-w. Online ahead of print.
ABSTRACT
The convergent positioning of functional groups in biomacromolecules leads to good binding, catalytic and transport capabilities. Synthetic frameworks capable of convergently locking functional groups with minimized conformational uncertainty-leading to similar properties-are highly desirable but rare. Here we report C5-symmetric aromatic pentaamide macrocycles synthesized in one pot from the corresponding monomers. Their crystal structures reveal a star-shaped, fully constrained backbone that causes ten alternating NH/CH hydrogen-bond donors and five large amide dipoles to orient towards the centre of the macrocycle. With a highly electropositive cavity in a high-energy unbound state, the macrocycles bind anions in a 1:1 stoichiometry in solution, with high affinity for halides and very high affinity for oxoanions. We demonstrate that such macrocycles are able to transport anions across lipid bilayers with a high chloride selectivity and restore the depleted airway surface liquid of cystic fibrosis airway cell cultures.
PMID:37814114 | DOI:10.1038/s41557-023-01315-w