Cystic Fibrosis

Prevalence and Risk Factors of Functional Gastrointestinal Disorders: A Cross-Sectional Study in Italian Infants and Young Children

Fri, 2023-01-27 06:00

J Pediatr Gastroenterol Nutr. 2023 Feb 1;76(2):e27-e35. doi: 10.1097/MPG.0000000000003653. Epub 2022 Nov 1.

ABSTRACT

OBJECTIVES: Reports of prevalence of functional gastrointestinal disorders (FGIDs) in infants/toddlers are widely variable. Reasons for this variability are not yet fully understood. The objective of this study is to estimate the prevalence of FGIDs according to Rome IV criteria and to evaluate associated factors, in Italian infants and toddlers.

METHODS: Subjects aged 0-48 months were enrolled by general pediatricians from 3 Italian regions. Parents or legal guardians were administered questionnaires including information about the child, the family, and GI symptoms according to Rome IV criteria.

RESULTS: Five hundred eight infants aged 0-12 months [mean age 4.4 ± 3.4 months; females (F) 40.9%], and 268 children aged 13-48 months (mean age 30.8 ± 10.7 months; F 44.4%) were included. In infants, prevalence of FGIDs was 21.1%, and the most prevalent FGID was infant colic (9.3%). In toddlers, prevalence of FGIDs was 19.6%, with functional constipation being the most frequent disorder (16.1%). In infants, multivariable analysis found that being older, being the only child, and living in a rural environment were associated with a lower rate of FGIDs. Prevalence was, in contrast, higher in infants fed with formula.

CONCLUSIONS: One out of 5 Italian infants and young children is affected by at least 1 FGID. The most frequent FGID in infants is infant colic, while in toddlers this is functional constipation. In infants, prevalence of FGIDs is lower if the subject has no siblings, and in children living in a rural environment, while formula feeding represents a risk factor for FGIDs occurrence.

PMID:36705695 | DOI:10.1097/MPG.0000000000003653

Categories: Literature Watch

Australian airway clearance services for adults with chronic lung conditions: A national survey

Fri, 2023-01-27 06:00

Chron Respir Dis. 2023 Jan-Dec;20:14799731221150435. doi: 10.1177/14799731221150435.

ABSTRACT

BACKGROUND: Physiotherapy-led airway clearance interventions are indicated for some people with chronic lung conditions. This study describes Australian clinical models for the provision of adult airway clearance services.

METHODS: This cross-sectional national study recruited public and private health care providers (excluding cystic fibrosis-specific services) identified by a review of websites. Providers were invited to complete an electronic 61-item survey with questions about airway clearance service context, referral demographics, service provision and program metrics. Data were reported descriptively with differences between metropolitan and non-metropolitan services explored with chi-square tests.

RESULTS: Between October-December 2019, the survey was disseminated to 131 providers with 91 responses received (69% response rate; 87 (96%) public (34 metropolitan; 53 non-metropolitan) and 4 (4%) private). Intent (chronic condition self-management) and types of intervention provided (education, breathing techniques, exercise prescription) were common across all services. Geographic location was associated with differences in airway clearance service models (greater use of regular clinics, telephone/telehealth consultations and dedicated cardiorespiratory physiotherapists in metropolitan locations versus clients incurring service and device provision costs in non-metropolitan regions).

CONCLUSIONS: While similarities in airway clearance interventions exist, differences in service models may disadvantage people living with chronic lung conditions, especially in non-metropolitan regions of Australia.

PMID:36704934 | DOI:10.1177/14799731221150435

Categories: Literature Watch

Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function

Fri, 2023-01-27 06:00

Front Immunol. 2023 Jan 10;13:1023553. doi: 10.3389/fimmu.2022.1023553. eCollection 2022.

ABSTRACT

Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis. NETs selectively impact the expression of tight junction genes claudins 4, 8 and 11. Bronchial epithelia exposed to NETs demonstrate visible gaps in E-cadherin staining, a decrease in full-length E-cadherin protein and the appearance of cleaved E-cadherin peptides. Pretreatment of NETs with alpha-1 antitrypsin (A1AT) inhibits NET serine protease activity, limits E-cadherin cleavage, decreases bronchial cell apoptosis and preserves epithelial integrity. In conclusion, NETs disrupt human airway epithelial barrier function through bronchial cell death and degradation of E-cadherin, which are limited by exogenous A1AT.

PMID:36703990 | PMC:PMC9872031 | DOI:10.3389/fimmu.2022.1023553

Categories: Literature Watch

PD-1 expression in transbronchial biopsies of lung transplant recipients is a possible early predictor of rejection

Fri, 2023-01-27 06:00

Front Immunol. 2023 Jan 10;13:1024021. doi: 10.3389/fimmu.2022.1024021. eCollection 2022.

ABSTRACT

INTRODUCTION: Chronic lung allograft dysfunction (CLAD) is the main cause of the reduced survival of lung transplanted (LTx) patients. The possible role of immune checkpoint molecules in establishing tolerance has been scarcely investigated in the setting of lung transplantation.

METHODS: We conducted a retrospective, observational pilot study on a consecutive series of transbronchial cryobiopsies (TCB) obtained from 24 patients during LTx follow-up focusing on PD-1, one of the most investigated immune checkpoint molecules.

RESULTS: Results showed that PD-1-expressing T lymphocytes were present in all TCB with a histological diagnosis of acute rejection (AR; 9/9), but not in most (11/15) of the TCB not resulting in a diagnosis of AR (p=0.0006). Notably, the presence of PD-1-expressing T lymphocytes in TCB resulted in a 10-times higher risk of developing chronic lung allograft dysfunction (CLAD), the main cause of the reduced survival of lung transplanted patients, thus being associated with a clearly worst clinical outcome.

DISCUSSION: Results of this pilot study indicate a central role of PD-1 in the development of AR and its evolution towards CLAD and suggest that the evaluation of PD-1-expressing lymphocytes in TCB could offer a prognostic advantage in monitoring the onset of AR in patients who underwent lung transplantation.

PMID:36703976 | PMC:PMC9871480 | DOI:10.3389/fimmu.2022.1024021

Categories: Literature Watch

Airway clearance therapy in the school environment: Retrospective analysis of a cohort of pediatric patients with cystic fibrosis

Thu, 2023-01-26 06:00

J Cyst Fibros. 2023 Jan 24:S1569-1993(23)00007-3. doi: 10.1016/j.jcf.2023.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: Adherence to airway clearance therapy (ACT) in pediatric cystic fibrosis (CF) patients is reported to be below 50% and inability to sustain daily care is linked to poor health outcomes7,8,9. Through a collaboration between a CF care center and several schools, we hypothesized that ACT completed at school by pediatric CF patients will improve lung function while decreasing pulmonary exacerbations (PEx), days of antibiotics (abx) and hospitalizations.

METHODS: This was a retrospective case-control study at a single CF care center consisting of 50 CF patients age < 18 at time when data was recorded (2012-2020). The case group used high-frequency chest wall oscillation or positive expiratory pressure devices at school for at least 1 year after self-reported or physician identified inadequate use at home. Lung function and measures of healthcare utilization were collected.

RESULTS: In the case group (n = 14), paired t-tests showed that after initiation of ACT at school, there were significant reductions in PEx requiring IV or PO abx (P = 0.010), total days of abx (P = 0.032), and visits to the CF care center (P = 0.037). There was no change in these outcomes in the matched control group (n = 36).

CONCLUSIONS: This is the first known study to highlight an initiative between a CF care center and schools which utilized airway clearance devices at school to ensure pediatric CF patients completed ACT. Through increased adherence, this relationship was associated with improved health outcomes. Use of alternative strategies may help patients with CF sustain adequate airway clearance.

PMID:36702656 | DOI:10.1016/j.jcf.2023.01.006

Categories: Literature Watch

Animated teaching improves student learning of human gastrulation and neurulation

Thu, 2023-01-26 06:00

Ann Anat. 2023 Jan 23:152057. doi: 10.1016/j.aanat.2023.152057. Online ahead of print.

ABSTRACT

Human embryology is a complex topic that brings together core components of anatomy and physiology to describe the developmental process from fertilisation to birth. Embryonic development is a challenging topic of study that is core to the curricula for health science students. There are challenges ingrained in teaching and learning embryology, due to the three-dimensional dynamic processes that occur as the embryo develops. This study aimed to develop and assess two newly developed animations depicting key processes in embryology, namely gastrulation and neurulation, as supplemental learning aids for students. Indeed, animated teaching tools to enhance the learning of gastrulation and neurulation are not widely available. A multi-disciplinary team of physiologists, biochemists, anatomists, and a computer scientist developed the animation sets. A student cohort of 81 first-year health science students were enrolled in this study over a period of three academic years. Both animations are in line with the course content of the first-year health science students undertaking the Human Health and Disease BSc at Trinity College Dublin, who were the study participants. Participants were randomly assigned to a non-animation control group and an animation group. Each set of animated teaching aids was broken down into individual clips which were given identifiable headings to allow the user to interchange between clips to facilitate a more personal learning experience. The animation group had open access to the animations for a three-week period. Questionnaires were designed to assess participants' attitude to the animations and their knowledge of embryology, both at the start of the study and three weeks later following access to the animations. Data presented herein indicate that students incorporated the animated teaching aids into digital home study and that the use of the animations acted as a supplemental tool that increased student knowledge in key areas of human embryology. From a qualitative point of view, students described the animations as enjoyable and helpful in visualising complex processes. This study indicates that the development of gastrulation and neurulation animated learning tools allow for a more engaging learning experience, facilitating student's engagement with academically challenging concepts in human embryology.

PMID:36702366 | DOI:10.1016/j.aanat.2023.152057

Categories: Literature Watch

Antigen specificity and cross-reactivity drive functionally diverse anti-Aspergillus fumigatus T cell responses in cystic fibrosis

Thu, 2023-01-26 06:00

J Clin Invest. 2023 Jan 26:e161593. doi: 10.1172/JCI161593. Online ahead of print.

ABSTRACT

BACKGROUND: The fungus Aspergillus fumigatus causes a variety of clinical phenotypes in patients with cystic fibrosis (pwCF). T-helper (Th) cells orchestrate immune responses against fungi, but the types of A. fumigatus-specific Th-cells in pwCF and their contribution to protective immunity or inflammation remain poorly characterized.

METHODS: We used antigen-reactive T cell enrichment (ARTE) to investigate fungus-reactive Th cells in peripheral blood of pwCF and healthy controls.

RESULTS: We show that clonally expanded, high-avidity A. fumigatus-specific effector Th-cells develop in pwCF, which are absent in healthy donors. Individual patients were characterized by distinct Th1, Th2, or Th17 dominated responses that remained stable over years. These different Th subsets target different A. fumigatus proteins, indicating that differential antigen uptake and presentation directs Th-cell subset development. Patients with allergic bronchopulmonary aspergillosis (ABPA) are characterized by high frequencies of Th2-cells that cross-recognize various filamentous fungi.

CONCLUSION: Our data highlight the development of heterogenous Th responses targeting different protein fractions of a single fungal pathogen and identify the development of multispecies cross-reactive Th2-cells as a potential risk factor for ABPA.

FUNDING: This research was supported by grants from the German Research Foundation (DFG) under Germany's Excellence Strategy - EXC 2167-390884018 "Precision Medicine in Chronic Inflammation", EXC 2051-390713860 "Balance of the Microverse"; the Oskar Helene Heim Stiftung; the Christiane Herzog Stiftung, Stuttgart, Germany; the Mukoviszidose Institut gGmbH, Bonn, the research and development arm of the German Cystic Fibrosis Association Mukoviszidose e.V; the German Federal Ministry of Education and Science (BMBF) InfectControl 2020 Projects AnDiPath, BMBF 03ZZ0838A+B.

PMID:36701198 | DOI:10.1172/JCI161593

Categories: Literature Watch

Correlation between the Brody score and lung function using an ultra-low-dose CT protocol without anesthesia in children with cystic fibrosis

Thu, 2023-01-26 06:00

J Bras Pneumol. 2023 Jan 23;49(1):e20220085. doi: 10.36416/1806-3756/e20220085.

NO ABSTRACT

PMID:36700570 | DOI:10.36416/1806-3756/e20220085

Categories: Literature Watch

Case report: A case of <em>SLC26A4</em> mutations causing pendred syndrome and non-cystic fibrosis bronchiectasis

Thu, 2023-01-26 06:00

Front Pediatr. 2023 Jan 9;10:1077878. doi: 10.3389/fped.2022.1077878. eCollection 2022.

ABSTRACT

The SLC26A4 gene encodes the transmembrane protein pendrin, which is involved in the ion transport of chloride (Cl-), iodide (I-) or bicarbonate (HCO3-). Mutations in the SLC26A4 gene alter the structure and (or) function of pendrin, which are closely related to Pendred syndrome. What's more, researchers have demonstrated in vitro that mutations of SLC26A4 cause acidification of airway surface fluid (ASL), reduce airway defense, and increase the thickness of ASL. In the context of infection, it may lead to chronic inflammation, destruction of airway wall architecture and bronchiectasis. However, there is no case report of bronchiectasis caused by SLC26A4 gene mutations. Here, we describe the first case of Pendred syndrome and non-cystic fibrosis bronchiectasis in a child possibly caused by SLC26A4 mutations. We remind clinicians to pay attention to the possibility of bronchiectasis in patients with SLC26A4 gene mutations.

PMID:36699303 | PMC:PMC9869259 | DOI:10.3389/fped.2022.1077878

Categories: Literature Watch

Using metabolic potential within the airway microbiome as predictors of clinical state in persons with cystic fibrosis

Thu, 2023-01-26 06:00

Front Med (Lausanne). 2023 Jan 9;9:1082125. doi: 10.3389/fmed.2022.1082125. eCollection 2022.

ABSTRACT

INTRODUCTION: Pulmonary exacerbations (PEx) in persons with cystic fibrosis (CF) are primarily related to acute or chronic inflammation associated with bacterial lung infections, which may be caused by several bacteria that activate similar bacterial genes and produce similar by-products. The goal of our study was to perform a stratified functional analysis of bacterial genes at three distinct time points in the treatment of a PEx in order to determine the role that specific airway microbiome community members may play within each clinical state (i.e., PEx, end of antibiotic treatment, and follow-up). Our secondary goal was to compare the change between clinical states with the metabolic activity of specific airway microbiome community members.

METHODS: This was a prospective observational study of persons with CF treated with intravenous antibiotics for PEx between 2016 and 2020 at Children's National Hospital. Demographic and clinical information as well as respiratory samples were collected at hospital admission for PEx, end of antibiotic treatment, and follow-up. Metagenomic sequencing was performed; MetaPhlAn3 and HUMANn3 were used to assign sequences to bacterial species and bacterial metabolic genes, respectively.

RESULTS: Twenty-two persons with CF, with a mean age of 14.5 (range 7-23) years, experienced 45 PEx during the study period. Two-hundred twenty-one bacterial species were identified in the respiratory samples from the study cohort. Ten bacterial species had differential gene abundance across changes in the clinical state including Staphylococcus aureus, Streptococcus salivarius, and Veillonella atypica (all padj < 0.01 and log2FoldChange > |2|). These corresponded to a differential abundance of bacterial genes, with S. aureus accounting for 81% of the genes more abundant in PEx and S. salivarius accounting for 83% of the genes more abundant in follow-up, all compared to the end of treatment. Lastly, 8,653 metabolic pathways were identified across samples, with again S. aureus and S. salivarius contributing to the differential abundance of pathways (106 in PEx vs. 66 in follow-up, respectively). V. atypica was associated with a single metabolic pathway (UDP-N-acetyl-D-glucosamine biosynthesis) increased in follow-up compared to PEx.

DISCUSSION: Taken together, these data suggest that the metabolic potential of bacterial species can provide more insight into changes across clinical states than the relative abundance of the bacteria alone.

PMID:36698799 | PMC:PMC9868313 | DOI:10.3389/fmed.2022.1082125

Categories: Literature Watch

Real-time observation of functional specialization among phosphorylation sites in CFTR

Wed, 2023-01-25 06:00

J Gen Physiol. 2023 Apr 3;155(4):e202213216. doi: 10.1085/jgp.202213216. Epub 2023 Jan 25.

ABSTRACT

Phosphoregulation is ubiquitous in biology. Defining the functional roles of individual phosphorylation sites within a multivalent system remains particularly challenging. We have therefore applied a chemical biology approach to light-control the state of single candidate phosphoserines in the canonical anion channel CFTR while simultaneously measuring channel activity. The data show striking non-equivalency among protein kinase A consensus sites, which vary from <10% to >1,000% changes in channel activity upon phosphorylation. Of note, slow phosphorylation of S813 suggests that this site is rate-limiting to the full activation of CFTR. Further, this approach reveals an unexpected coupling between the phosphorylation of S813 and a nearby site, S795. Overall, these data establish an experimental route to understanding roles of specific phosphoserines within complex phosphoregulatory domains. This strategy may be employed in the study of phosphoregulation of other eukaryotic proteins.

PMID:36695813 | DOI:10.1085/jgp.202213216

Categories: Literature Watch

Pediatric Gastroenterology and Hepatology in Italy before and after the COVID-19: Lessons learned and management changes by SIGENP

Wed, 2023-01-25 06:00

Ital J Pediatr. 2023 Jan 26;49(1):15. doi: 10.1186/s13052-023-01418-7.

ABSTRACT

Around the world, the 2019 Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised serious public health problems and major medical challenges. The Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) published several papers on the impact of COVID-19 on the current management, diagnosis, and treatment of acute and chronic gastrointestinal, hepatic, immune-mediated, and functional disorders. The present article summarizes the most relevant SIGENP reports and consensus during and after the peak of the COVID-19 outbreak, including the diagnosis and treatment of inflammatory bowel disease (IBD), indications and timing of digestive endoscopy, and insights into the novel hepatitis.

PMID:36698148 | DOI:10.1186/s13052-023-01418-7

Categories: Literature Watch

Antisense Oligonucleotide Therapeutics for Cystic Fibrosis: Recent Developments and Perspectives

Wed, 2023-01-25 06:00

Mol Cells. 2023 Jan 31;46(1):10-20. doi: 10.14348/molcells.2023.2172. Epub 2023 Jan 15.

ABSTRACT

Antisense oligonucleotide (ASO) technology has become an attractive therapeutic modality for various diseases, including Mendelian disorders. ASOs can modulate the expression of a target gene by promoting mRNA degradation or changing pre-mRNA splicing, nonsense-mediated mRNA decay, or translation. Advances in medicinal chemistry and a deeper understanding of post-transcriptional mechanisms have led to the approval of several ASO drugs for diseases that had long lacked therapeutic options. For instance, an ASO drug called nusinersen became the first approved drug for spinal muscular atrophy, improving survival and the overall disease course. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF). Although Trikafta and other CFTR-modulation therapies benefit most CF patients, there is a significant unmet therapeutic need for a subset of CF patients. In this review, we introduce ASO therapies and their mechanisms of action, describe the opportunities and challenges for ASO therapeutics for CF, and discuss the current state and prospects of ASO therapies for CF.

PMID:36697233 | DOI:10.14348/molcells.2023.2172

Categories: Literature Watch

A conserved WXXE motif is an apical delivery determinant of ABC transporter C subfamily isoforms

Wed, 2023-01-25 06:00

Cell Struct Funct. 2023 Jan 25. doi: 10.1247/csf.22049. Online ahead of print.

ABSTRACT

ATP-binding cassette transporter isoform C7 (ABCC7), also designated as cystic fibrosis transmembrane conductance regulator (CFTR), is exclusively targeted to the apical plasma membrane of polarized epithelial cells. Although the apical localization of ABCC7 in epithelia is crucial for the Cl- excretion into lumens, the mechanism regulating its apical localization is poorly understood. In the present study, an apical localization determinant was identified in the N-terminal 80-amino acid long cytoplasmic region of ABCC7 (NT80). In HepG2 cells, overexpression of NT80 significantly disturbed the apical expression of ABCC7 in a competitive manner, suggesting the presence of a sorting determinant in this region. Deletion analysis identified a potential sorting information within a 20-amino acid long peptide (aa 41-60) of NT80. Alanine scanning mutagenesis of this region in full-length ABCC7 further narrowed down the apical localization determinant to four amino acids, W57DRE60. This WDRE sequence was conserved among vertebrate ABCC7 orthologs. Site-directed mutagenesis showed that W57 and E60 were critical for the apical expression of ABCC7, confirming a novel apical sorting determinant of ABCC7. Furthermore, a WXXE motif (tryptophan and glutamic acid residues with two-amino acid spacing) was found to be conserved among the N-terminal regions of apically localized ABCC members with 12-TM configuration. The significance of the WXXE motif was demonstrated for proper trafficking of ABCC4 to the apical plasma membrane.Key words: apical plasma membrane, sorting, ATP-binding cassette transporter, CFTR, MRP4.

PMID:36696993 | DOI:10.1247/csf.22049

Categories: Literature Watch

First use of imlifidase desensitization in a highly sensitized lung transplant candidate: a case report

Wed, 2023-01-25 06:00

Am J Transplant. 2022 Dec 29:S1600-6135(22)29297-1. doi: 10.1016/j.ajt.2022.11.025. Online ahead of print.

ABSTRACT

Lung transplant candidates who are highly sensitized against human leucocyte antigen present an ongoing challenge with regards to finding immunologically acceptable donors. Desensitization strategies aimed at reducing preformed donor-specific antibodies have a number of limitations. Imlifidase, an IgG-degrading enzyme derived from Streptococcus pyogenes, is a novel agent that has been used to convert positive crossmatches to negative in kidney transplant candidates, allowing transplantation to occur. We present the first case of imlifidase use for antibody depletion in a highly sensitized lung transplant candidate who went on to undergo a successful bilateral lung transplant.

PMID:36695676 | DOI:10.1016/j.ajt.2022.11.025

Categories: Literature Watch

Transforming the Nutrition Care Model for Infants with Cystic Fibrosis: a qualitative study of clinicians' perspectives

Wed, 2023-01-25 06:00

Pediatr Pulmonol. 2023 Jan 25. doi: 10.1002/ppul.26330. Online ahead of print.

ABSTRACT

Clinician perspectives may inform health service strategies to meet optimal nutrition needs for infants with cystic fibrosis (CF). We conducted a qualitative study with CF-specialized dietitians (RDs) and physicians between July to December 2020 to characterize the current state of infant nutrition care delivery and organize input into a conceptual model to inform CF care program strategies. Among 42 participants, 36 completed survey responses and 6 completed interviews; 93% were RDs. Three global themes emerged in the current care model: nutrition management, family-centered connections, and collaborative care delivery. Within nutrition management clinicians emphasized providing education, setting goals, and maintaining adequate follow-up with families. Under family-centered connections clinicians expressed the need to foster relationships with families and link families to resources for assistance to social stressors such as food insecurity. Collaborative care delivery for clinicians interviewed was defined by sharing expertise from across the interdisciplinary team. Based on the timing of this study, clinicians reported compelling examples for various modes of telehealth and home weight monitoring to facilitate and support these domains of nutrition care, including potential advantages for education, supporting family needs, and communication. We integrate these themes to propose a conceptual model to organize complementary in-person and telehealth activities and enhance quality infant CF nutrition care delivery. Future implementation can refine this model through testing of practical telehealth interventions to optimize nutrition outcomes for infants with CF. This article is protected by copyright. All rights reserved.

PMID:36695543 | DOI:10.1002/ppul.26330

Categories: Literature Watch

A Case of Jejunal Atresia Associated With Heterotrophic Pancreas and Meckel's Diverticulum

Wed, 2023-01-25 06:00

Cureus. 2022 Dec 21;14(12):e32766. doi: 10.7759/cureus.32766. eCollection 2022 Dec.

ABSTRACT

Apart from meconium ileus, amniotic fluid plug syndrome, malrotation of the gut, Hirschprung's disorder, trauma, and other rare causes, bowel atresia is one of the most common causes of bowel obstruction in newborns. Jejunal atresia can affect multiple lengths of the bowel. The higher the level of atresia, the greater the severity. The outcome of bowel atresia related to surgical repair is favorable. In general, both mortality and morbidity are affected by affiliated medical conditions such as preterm birth, cystic fibrosis, and other congenital anomalies; the sophistication of the lesion; and surgical complications. We present the case of a one-day-old baby who had two episodes of bilious vomiting with abdominal distension within 10 minutes of birth. The baby was advised to undergo ultrasonography of the abdomen and pelvis for further evaluation, and the findings were reported.

PMID:36694481 | PMC:PMC9858787 | DOI:10.7759/cureus.32766

Categories: Literature Watch

Molecular dynamics study of Cl<sup>-</sup> permeation through cystic fibrosis transmembrane conductance regulator (CFTR)

Tue, 2023-01-24 06:00

Cell Mol Life Sci. 2023 Jan 24;80(2):51. doi: 10.1007/s00018-022-04621-7.

ABSTRACT

The recent elucidation of atomistic structures of Cl- channel CFTR provides opportunities for understanding the molecular basis of cystic fibrosis. Despite having been activated through phosphorylation and provided with ATP ligands, several near-atomistic cryo-EM structures of CFTR are in a closed state, as inferred from the lack of a continuous passage through a hydrophobic bottleneck region located in the extracellular portion of the pore. Here, we present repeated, microsecond-long molecular dynamics simulations of human CFTR solvated in a lipid bilayer and aqueous NaCl. At equilibrium, Cl- ions enter the channel through a lateral intracellular portal and bind to two distinct cationic sites inside the channel pore but do not traverse the narrow, de-wetted bottleneck. Simulations conducted in the presence of a strong hyperpolarizing electric field led to spontaneous Cl- translocation events through the bottleneck region of the channel, suggesting that the protein relaxed to a functionally open state. Conformational changes of small magnitude involving transmembrane helices 1 and 6 preceded ion permeation through diverging exit routes at the extracellular end of the pore. The pore bottleneck undergoes wetting prior to Cl- translocation, suggesting that it acts as a hydrophobic gate. Although permeating Cl- ions remain mostly hydrated, partial dehydration occurs at the binding sites and in the bottleneck. The observed Cl- pathway is largely consistent with the loci of mutations that alter channel conductance, anion binding, and ion selectivity, supporting the model of the open state of CFTR obtained in the present study.

PMID:36694009 | DOI:10.1007/s00018-022-04621-7

Categories: Literature Watch

Bariatric surgery in a patient with cystic fibrosis and diabetes: A case report

Tue, 2023-01-24 06:00

J Cyst Fibros. 2023 Jan 22:S1569-1993(23)00009-7. doi: 10.1016/j.jcf.2023.01.008. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is incurable and chronic, causing severe multisystemic damage and long-term complications. The most prominent extrapulmonary long-term complication is CF-related diabetes, which is the most reported form of diabetes in individuals with cystic fibrosis. Here we present the first case of an individual with cystic fibrosis who developed type 2 diabetes due to obesity rather than CF-related diabetes. The type 2 diabetes went into remission due to extreme weight loss after gastric bypass surgery. To our knowledge, this case is also the first report describing the effect of bariatric surgery in a patient with CF. This case demonstrates that patients with CF may present with type 2 diabetes instead of CF-related diabetes. Differential diagnosis of these two types of diabetes is essential for optimal treatment and quality of life.

PMID:36693768 | DOI:10.1016/j.jcf.2023.01.008

Categories: Literature Watch

Cystic Fibrosis

Tue, 2023-01-24 06:00

Semin Respir Crit Care Med. 2023 Jan 24. doi: 10.1055/s-0043-1760754. Online ahead of print.

NO ABSTRACT

PMID:36693409 | DOI:10.1055/s-0043-1760754

Categories: Literature Watch

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