Nutr Hosp. 2023 Jan 26. doi: 10.20960/nh.04253. Online ahead of print.

ABSTRACT

INTRODUCTION: cystic fibrosis is a disease that causes inflammation, oxidative stress and metabolic changes that lead to nutrient deficiency, such as vitamin D deficiency. On the other hand, it is suggested that vitamin D has anti-inflammatory and antioxidant actions.

OBJECTIVE: to evaluate the prevalence of hypovitaminosis D and the association between serum 25 hydroxyvitamin D levels with markers of oxidative stress and inflammation in patients with cystic fibrosis.

METHOD: a cross-sectional study was carried out with 48 patients with cystic fibrosis including children, adolescents and adults in the northeast region of Brazil. Blood collection was performed for analysis of 25-hydroxyvitamin D, calcium, parathyroid hormone, inflammatory process (C-reactive protein (CRP) and alpha-1-acid glycoprotein-A1 (A1GPA)) and oxidative stress (malondialdehyde (MDA) and total antioxidant capacity (CAOT)). The statistical analysis was performed using the "Statistical Package for the Social Sciences", adopting a significance level of p < 0.05.

RESULTS: Vitamin D insufficiency/deficiency was found in 64.6 % of patients. After multiple linear regression analysis, MDA showed an inverse association with blood values of 25-Hydroxyvitamin D (p < 0.05) conditioned by the presence of inflammatory process markers. When only oxidative stress was evaluated, this association disappeared.

CONCLUSION: in conclusion, there was a high prevalence of hypovitaminosis D, with 25(OH)D levels associated with greater oxidative stress when combined with inflammatory markers. Improved vitamin D levels may be an alternative to reduce the damage caused by excess oxidative stress and inflammation in CF patients.

PMID:36719006 | DOI:10.20960/nh.04253

Pediatr Pulmonol. 2023 Jan 31. doi: 10.1002/ppul.26334. Online ahead of print.

ABSTRACT

ETI treatment reduces inflammatory markers and positive bacterial cultures on BAL in PwCF. These findings suggest that ETI has a greater impact on chronic infection and inflammation than ivacaftor alone. However, airway inflammation persists in some treated individuals, indicating an ongoing need to optimize other treatments in a subset of patients. This article is protected by copyright. All rights reserved.

PMID:36718851 | DOI:10.1002/ppul.26334

ATS Sch. 2023 Jan 30;4(1):76-86. doi: 10.34197/ats-scholar.2022-0061IN. eCollection 2023 Mar.

ABSTRACT

BACKGROUND: Airway clearance therapies (ACTs) are recommended as an integral part of the management of non-cystic fibrosis bronchiectasis (BE) to prevent inflammation, mucus accumulation, and infection that occur because of ineffective secretion clearance. Adherence to ACTs is low, in part because of perceived burden and a lack of standardization of education and training programs for patients. Poor adherence is associated with more frequent exacerbations, worse health outcomes, and worse quality of life. Structured educational programs increase adherence to ACT among people with cystic fibrosis and may show similar results for people with BE.

OBJECTIVE: This pilot study evaluated the feasibility, clinical utility, sustainability, and expert opinions of this educational program addressing gaps in ACT knowledge and skills in people with BE.

METHODS: The Individual Management of Patient Airway Clearance Therapy- Bronchiectasis (IMPACT BE) was implemented in nine BE centers with 100 patients. Qualitative and quantitative data were collected from patients and providers.

RESULTS: The IMPACT BE program demonstrated good uptake in a clinic setting by multidisciplinary team members, with improvements in medical teams' evaluation of their ability to provide education to patients. All healthcare teams indicated that this program could become a sustainable part of their clinic. Qualitative responses from patients indicated the program was comprehensive and easy to use.

CONCLUSION: In this pilot study, IMPACT BE was found to be useful in teaching airway clearance to people with BE. The open-access toolkit was well received by both patients and a diverse array of providers in a clinic setting.

PMID:37089683 | PMC:PMC10117526 | DOI:10.34197/ats-scholar.2022-0061IN

J Cyst Fibros. 2023 Jan 28:S1569-1993(23)00019-X. doi: 10.1016/j.jcf.2023.01.013. Online ahead of print.

ABSTRACT

BACKGROUND: Adults with cystic fibrosis (CF) are at increased risk for colon cancer. CF patients have reductions in intestinal bacteria that produce short chain fatty acids (SCFAs), although it is unclear whether this corresponds with intestinal SCFA levels and the presence of colonic neoplasia. The aim of this study was to compare gut microbiome and SCFA composition in patients with and without CF, and to assess associations with colonic adenomas.

METHODS: Colonic aspirates were obtained from adults with and without CF undergoing colon cancer screening or surveillance colonoscopy. Microbiome characterization was performed by 16S rRNA V3-V4 sequencing. Targeted profiling of SCFAs and related metabolites was performed by LC-MS.

RESULTS: 42 patients (21 CF, 21 control) were enrolled. CF patients had significantly reduced alpha diversity and decreased relative abundance of many SCFA-producing taxa. There were no significant differences in SCFA levels in CF patients, although there were reduced levels of branched chain fatty acids (BCFAs) and related metabolites. CF patients with adenomas, but not controls with adenomas, had significantly increased relative abundance of Bacteroides fragilis. CF microbiome composition was significantly associated with isovalerate concentration and the presence of adenomas.

CONCLUSIONS: CF patients have marked disturbances in the gut microbiome, and CF patients with adenomas had notably increased relative abundance of B. fragilis, a pathogen known to promote colon cancer. Reductions in BCFAs but not SCFAs were found in CF. Further studies are warranted to evaluate the role of B. fragilis as well the biological significance of reductions in BCFAs in CF.

PMID:36717332 | DOI:10.1016/j.jcf.2023.01.013

Carbohydr Res. 2023 Jan 18;524:108741. doi: 10.1016/j.carres.2023.108741. Online ahead of print.

ABSTRACT

Potential of Mean Force Ramachandran energy maps in aqueous solution have been prepared for all of the glycosidic linkages found in the C1576 exopolysaccharide from the biofilms of the bacterial species Burkholderia multivorans, a member of the Burkholderia cepacian complex that was isolated from a cystic fibrosis patient. C1576 is a rhamnomannan with a tetrasaccharide repeat unit. In general, for the four linkage types in this polymer, hydration did not produce dramatic changes in the Ramachandran energy surfaces, with the 3-methyl-α-d-rhamnopyranose-(1→3)-α-d-rhamnopyranose case exhibiting the greatest hydration change, with the global minimum energy conformation shifting by more than 80° in ψ. However, hydration did reduce the rigidity of all the linkages, increasing the overall flexibility of this polysaccharide.

PMID:36716692 | DOI:10.1016/j.carres.2023.108741

Mol Ecol. 2023 Jan 30. doi: 10.1111/mec.16866. Online ahead of print.

ABSTRACT

The recurrent colonization of freshwater habitats and subsequent loss of diadromy is a major ecological transition that has been reported in many ancestrally diadromous fishes. Such residency is often accompanied by a loss of tolerance to seawater. The amphidromous Galaxias maculatus has repeatedly colonized freshwater streams with evidence that freshwater-resident populations exhibit stark differences in their tolerance to higher salinities. Here, we used transcriptomics to gain insight into the mechanisms contributing to reduced tolerance to higher salinities in freshwater resident populations. We conducted an acute salinity challenge (0 ppt to 23-25 ppt) and measured osmoregulatory ability (muscle water content) over 48 hours in three populations: diadromous, saltwater intolerant resident (Toltén), and saltwater tolerant resident (Valdivia). RNA sequencing of the gills identified genes that were differentially expressed in association with the salinity change and associated with the loss of saltwater tolerance in the Toltén population. Key genes associated with saltwater acclimation were characterized in diadromous G. maculatus individuals, some of which were also expressed in the saltwater tolerant resident population (Valdivia). We found that some of these "saltwater acclimation" genes, including the cystic fibrosis transmembrane conductance regulator gene (CFTR), were not significantly upregulated in the saltwater intolerant resident population (Toltén), suggesting a potential mechanism for the loss of tolerance to higher salinities. As the suite of differentially expressed genes in the diadromous-resident comparison differed between freshwater populations, we hypothesize that diadromy loss results in unique evolutionary trajectories due to drift, so the loss of diadromy does not necessarily lead to a loss in upper salinity tolerance.

PMID:36715263 | DOI:10.1111/mec.16866

ArXiv. 2023 Jan 2:arXiv:2301.00843v1. Preprint.

ABSTRACT

Many natural and engineered systems can be modeled as discrete state Markov processes. Often, only a subset of states are directly observable. Inferring the conditional probability that a system occupies a particular hidden state, given the partial observation, is a problem with broad application. In this paper, we introduce a continuous-time formulation of the sum-product algorithm, which is a well-known discrete-time method for finding the hidden states' conditional probabilities, given a set of finite, discrete-time observations. From our new formulation, we can explicitly solve for the conditional probability of occupying any state, given the transition rates and observations within a finite time window. We apply our algorithm to a realistic model of the cystic fibrosis transmembrane conductance regulator (CFTR) protein for exact inference of the conditional occupancy probability, given a finite time series of partial observations.

PMID:36713255 | PMC:PMC9882579

PNAS Nexus. 2022 Dec 23;2(1):pgac306. doi: 10.1093/pnasnexus/pgac306. eCollection 2023 Jan.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive genetic disease affecting multiple organs. Approximately 30% CF patients develop CF-related liver disease (CFLD), which is the third most common cause of morbidity and mortality of CF. CFLD is progressive, and many of the severe forms eventually need liver transplantation. The mechanistic studies and therapeutic interventions to CFLD are unfortunately very limited. Utilizing the CRISPR/Cas9 technology, we recently generated CF rabbits by introducing mutations to the rabbit CF transmembrane conductance regulator (CFTR) gene. Here we report the liver phenotypes and mechanistic insights into the liver pathogenesis in these animals. CF rabbits develop spontaneous hepatobiliary lesions and abnormal biliary secretion accompanied with altered bile acid profiles. They exhibit nonalcoholic steatohepatitis (NASH)-like phenotypes, characterized by hepatic inflammation, steatosis, and fibrosis, as well as altered lipid profiles and diminished glycogen storage. Mechanistically, our data reveal that multiple stress-induced metabolic regulators involved in hepatic lipid homeostasis were up-regulated in the livers of CF-rabbits, and that endoplasmic reticulum (ER) stress response mediated through IRE1α-XBP1 axis as well as NF-κB- and JNK-mediated inflammatory responses prevail in CF rabbit livers. These findings show that CF rabbits manifest many CFLD-like phenotypes and suggest targeting hepatic ER stress and inflammatory pathways for potential CFLD treatment.

PMID:36712930 | PMC:PMC9832953 | DOI:10.1093/pnasnexus/pgac306

Health Sci Rep. 2023 Jan 25;6(1):e1062. doi: 10.1002/hsr2.1062. eCollection 2023 Jan.

ABSTRACT

BACKGROUND AND AIMS: Labels designed to communicate critical information are paramount for the safe and effective use of over-the-counter medications; in recognition of this, the content and formatting of over the counter (OTC) labels sold in interstate commerce has been regulated for decades. Yet, available studies suggest that consumers frequently rely on limited information during decision making, failing to access the information required in the Drug Facts Label. This is particularly important for older consumers, who are at greater risk for adverse reactions to medicines. In two experiments we objectively evaluate how novel label designs that employ highlighting and a warning label placed on the package's front impact older consumers' attention to, and use of, critical information.

METHODS: In Experiment 1, 68 OTC patients (65+) engaged with a computer-based task answering yes/no scenario-based questions about a drug's appropriateness. In Experiment 2, 63 OTC patients (65+) conducted a forced-choice task where one of two drugs presented on a computer screen was appropriate for a provided scenario while the other was not. Both tasks required participants to access and use critical label information (i.e., warnings or active ingredients) to respond correctly. Dependent variables analyzed were the proportion of correct responses and time to correct response.

RESULTS: Highlighting or placing critical information on the front of the package significantly improved response accuracy and time to correct response in Experiment 1 as compared to responses utilizing the standard label. For Experiment 2, participants were faster and more accurate when critical information was highlighted.

CONCLUSIONS: Results provide direct measures of the efficacy of novel labeling strategies. This information is relevant for regulations which dictate label design in ways that enhance ease and safety of use of medications for older adults.

PMID:36712813 | PMC:PMC9874361 | DOI:10.1002/hsr2.1062

PNAS Nexus. 2022 Nov 10;1(5):pgac145. doi: 10.1093/pnasnexus/pgac145. eCollection 2022 Nov.

ABSTRACT

Nontuberculous mycobacteria (NTM) are frequently present in municipal drinking water and building plumbing, and some are believed to cause respiratory tract infections through inhalation of NTM-containing aerosols generated during showering. However, the present understanding of NTM transfer from water to air is insufficient to develop NTM risk mitigation strategies. This study aimed to characterize the contribution of shower water to the abundance of viable NTM in indoor air. Shower water and indoor air samples were collected, and 16S rRNA and rpoB genes were sequenced. The sequencing results showed that running the shower impacted the bacterial community structure and NTM species composition in indoor air by transferring certain bacteria from water to air. A mass balance model combined with NTM quantification results revealed that on average 1/132 and 1/254 of NTM cells in water were transferred to air during 1 hour of showering using a rain and massage showerhead, respectively. A large fraction of the bacteria transferred from water to air were membrane-damaged, i.e. they had compromised membranes based on analysis by live/dead staining and flow cytometry. However, the damaged NTM in air were recoverable as shown by growth in a culture medium mimicking the respiratory secretions of people with cystic fibrosis, implying a potential infection risk by NTM introduced to indoor air during shower running. Among the recovered NTM, Mycobacterium mucogenicum was the dominant species as determined by rpoB gene sequencing. Overall, this study lays the groundwork for future pathogen risk management and public health protection in the built environment.

PMID:36712351 | PMC:PMC9802317 | DOI:10.1093/pnasnexus/pgac145

bioRxiv. 2023 Jan 22:2023.01.22.525092. doi: 10.1101/2023.01.22.525092. Preprint.

ABSTRACT

Chronic pulmonary bacterial infections and associated inflammation remain a cause of morbidity and mortality in people with cystic fibrosis (PwCF) despite new modulator therapies. Therapies targeting host factors that dampen detrimental inflammation without suppressing immune responses critical for controlling infections remain limited, while the acquisition of antibiotic resistance bacterial infections is an increasing global problem, and a significant challenge in CF. Pharmacological compounds targeting the mammalian MAPK proteins MEK1 and MEK2, referred to as MEK1/2 inhibitor compounds, have potential combined anti-microbial and anti-inflammatory effects. Here we examined the immunomodulatory properties of MEK1/2 inhibitor compounds PD0325901, trametinib, and CI-1040 on CF innate immune cells. Human CF macrophage and neutrophil phagocytic functions were assessed by quantifying phagocytosis of serum opsonized pHrodo red E. coli , Staphylococcus aureus , and zymosan bioparticles. MEK1/2 inhibitor compounds reduced CF macrophage pro-inflammatory cytokine production without impairing CF macrophage or neutrophil phagocytic abilities. Wild-type C57BL6/J and Cftr tm1kth (F508del homozygous) mice were used to evaluate the in vivo therapeutic potential of PD0325901 compared to vehicle treatment in an intranasal methicillin-resistant Staphylococcus aureus (MRSA) infection with the community-acquired MRSA strain USA300. In both wild-type and CF mice, PD0325901 reduced infection related weight loss compared to vehicle treatment groups but did not impair clearance of bacteria in lung, liver, or spleen 1 day after infection. In summary, this study provides the first data evaluating the therapeutic potential of MEK1/2 inhibitor to modulate CF immune cells, and demonstrates that MEK1/2 inhibitors dampen pro-inflammatory responses without impairing host defense mechanisms mediating pathogen clearance.

PMID:36712028 | PMC:PMC9882267 | DOI:10.1101/2023.01.22.525092

bioRxiv. 2023 Jan 18:2023.01.13.523864. doi: 10.1101/2023.01.13.523864. Preprint.

ABSTRACT

The opportunistic bacterium Pseudomonas aeruginosa uses the LasR-I quorum sensing system to increase resistance to the aminioglycoside antibiotic tobramycin. Paradoxically, lasR -null mutants are commonly isolated from chronic human infections treated with tobramycin, suggesting there may be a mechanism allowing the lasR -null mutants to persist under tobramycin selection. We hypothesized that the effects of inactivating lasR on tobramycin resistance might be dependent on the presence or absence of other gene mutations in that strain, a phenomenon known as epistasis. To test this hypothesis, we inactivated lasR in several highly tobramycin-resistant isolates from long-term evolution experiments. We show that the effects of Δ lasR on tobramycin resistance are strain dependent. The effects can be attributed to a point mutation in the gene encoding the translation elongation factor fusA1 (G61A nucleotide substitution), which confers a strong selective advantage to lasR- null PA14 under tobramycin selection. This fusA1 G61A mutation results in increased activity of the MexXY efflux pump and expression of the mexXY regulator ArmZ. The fusA1 mutation can also modulate Δ lasR mutant resistance to two other antibiotics, ciprofloxacin and ceftazidime. Our results demonstrate the importance of epistatic gene interactions on antibiotic susceptibility of Δ lasR mutants. These results support of the idea that gene interactions might play a significant role in the evolution of quorum sensing in P. aeruginosa .

IMPORTANCE: Pseudomonas aeruginosa causes chronic infections in the airways of patients with the genetic disease cystic fibrosis. In these clinical isolates the quorum-sensing regulator LasR frequently becomes mutated, which can affect clinical outcomes. We performed studies of isolates from laboratory evolution experiments to understand the factors that contribute to the emergence of LasR mutants. Under tobramycin selection conditions, mutating lasR was beneficial in some isolates and deleterious in others. This difference was found to be due to a single mutation in the translation elongation factor gene fusA1 . Our results support a model in which the consequence of a lasR- null mutation on tobramycin resistance depends on the genetic background in which it emerges. These results provide a new understanding of the emergence of lasR mutants in infected patients and are relevant to designing strategies to treat P. aeruginosa infections.

PMID:36711731 | PMC:PMC9882136 | DOI:10.1101/2023.01.13.523864

bioRxiv. 2023 Jan 10:2022.12.31.522388. doi: 10.1101/2022.12.31.522388. Preprint.

ABSTRACT

Protein-protein interactions that include recognition of short sequences of amino acids, or peptides, are critical in cellular processes. Protein-peptide interaction surface areas are relatively small and shallow, and there are often overlapping specificities in families of peptide-binding domains. Therefore, dissecting selectivity determinants can be challenging. PDZ domains are an example of a peptide-binding domain located in several intracellular signaling and trafficking pathways, which form interactions critical for the regulation of receptor endocytic trafficking, tight junction formation, organization of supramolecular complexes in neurons, and other biological systems. These domains are also directly targeted by pathogens, and a hallmark of many oncogenic viral proteins is a PDZ-binding motif. However, amidst sequences that target PDZ domains, there is a wide spectrum in relative promiscuity. For example, the viral HPV16 E6 oncoprotein recognizes over double the number of PDZ domain-containing proteins as the cystic fibrosis transmembrane conductance regulator (CFTR) in the cell, despite similar PDZ targeting-sequences and identical motif residues. Here, we determine binding affinities for PDZ domains known to bind either HPV16 E6 alone or both CFTR and HPV16 E6, using peptides matching WT and hybrid sequences. We also use energy minimization to model PDZ-peptide complexes and use sequence analyses to investigate this difference. We find that while the majority of single mutations had a marginal effect on overall affinity, the additive effect on the free energy of binding accurately describes the selectivity observed. Taken together, our results describe how complex and differing PDZ interactomes can be programmed in the cell.

PMID:36711692 | PMC:PMC9881875 | DOI:10.1101/2022.12.31.522388

Heliyon. 2023 Jan 15;9(1):e12960. doi: 10.1016/j.heliyon.2023.e12960. eCollection 2023 Jan.

ABSTRACT

BACKGROUND: Giant cystic meconium peritonitis (MP) is a relatively rare entity. Prompt surgical treatment is required to manage the underlying etiology and reestablish the continuity of the intestines. Despite perinatal and postoperative care improvements, the overall mortality rate is still relatively high. We reported a giant cystic MP that was recognized using antenatal sonography (US). It was successfully treated with primary anastomosis.

CASE PRESENTATION: We presented a female newborn with a chief complaint of abdominal mass. The prenatal sonography showed an intraabdominal cyst at the 28th week of gestation. She was born at the gestational age of 38 weeks via vaginal delivery from a primigravid mother without complications, with a birth weight of 3275 g. Elective surgery was performed at the age of eight days, and a calcified 10 cm cyst was revealed along with severe adhesions. The cyst was found to communicate with the ileum located 30 cm proximal from the ileocecal junction. No malrotation and volvulus were found. The cyst and a portion of the ileum were resected, followed by a primary end-to-end anastomosis. Pathologic examination showed necrotic tissue lined with epithelial tissue with microcalcifications containing bilirubin pigments, consistent with cystic MP. The patient has uneventfully discharged on postoperative day 17. The patient has normal growth and development, except for delayed walking, at the last follow-up of two years of age.

CONCLUSION: Giant cystic MP is a rare disorder that can be detected early using the antenatal US. Our case highlights the importance of early diagnosis for giant cystic MP using the antenatal US leads to prompt surgical treatment and a more favorable prognosis.

PMID:36711283 | PMC:PMC9876943 | DOI:10.1016/j.heliyon.2023.e12960

Can J Respir Ther. 2023 Jan 20;59:1-7. doi: 10.29390/cjrt-2022-046. eCollection 2023.

ABSTRACT

BACKGROUND: Inhaled hypertonic saline (HS) reduces pulmonary exacerbations in patients with cystic fibrosis (CF) aged 6 or more years. However, the effectiveness of HS in improving clinical outcomes in younger children aged 6 or less years is not established. This study examines the efficacy of HS in younger CF patients.

METHODS: Searches were conducted across three databases (Medline, Cochrane Central and EMBASE) from inception through July 2022. Randomized controlled trials assessing the impact of HS in younger CF patients were included. Trials involving only patients greater than 6 years or control group other than isotonic saline (IS) were excluded. Outcomes measured included lung clearance index (LCI), cystic fibrosis questionnaire (CFQ-R) score, spirometry measures, oxygen saturation, respiratory rate, height and weight. Outcomes were reported as mean differences (MDs) with 95% confidence intervals.

RESULTS: Seven studies (n = 390 patients) were included in this review. HS significantly reduced the LCI (MD: -0.67; 95%CI, -1.05 to 0.29, P = 0.0006) compared to IS. In addition, HS was associated with significant improvements in height (MD: 2.23; 95%CI, -0.00 to 4.46, P = 0.05) and CFQ-R (MD: 4.30; 95%CI, 0.65-7.95, P = 0.02), but not in oxygen saturation (MD: -0.15; 95%CI, -0.54 to 0.25, P = 0.47), respiratory rate (MD: -0.21; 95%CI, -2.19 to 1.77, P = 0.83) or weight (MD: 0.70; 95%CI, -0.47 to 1.87, P = 0.24). Furthermore, HS did not significantly improve spirometry measures, including FEV1 (MD: -0.11; 95%CI, -0.21 to 0.43, P = 0.51) and forced vital capacity (MD: 0.27; 95%CI, -0.49 to 1.04, P = 0.48), but significantly improved FEF25-75 (MD: 0.12; 95% CI, 0.05-0.20; P = 0.002).

DISCUSSION: Treatment with HS in younger children with CF improves lung clearance, symptoms and quality of life. FEF25-75 may prove a more sensitive measure for assessing intervention related improvements in pediatric CF trials.

CONCLUSION: The findings support HS as a therapeutic method in CF-affected children.

PMID:36711047 | PMC:PMC9838740 | DOI:10.29390/cjrt-2022-046

Arch Bronconeumol. 2023 Jan 18:S0300-2896(23)00009-1. doi: 10.1016/j.arbres.2023.01.004. Online ahead of print.

NO ABSTRACT

PMID:36710175 | DOI:10.1016/j.arbres.2023.01.004

J Cyst Fibros. 2023 Jan 27:S1569-1993(23)00018-8. doi: 10.1016/j.jcf.2023.01.010. Online ahead of print.

ABSTRACT

BACKGROUND: Individuals with diabetes mellitus (DM) are known to frequently experience gastrointestinal (GI) symptoms. In contrast, the impact of cystic fibrosis-related diabetes (CFRD) on accentuating GI symptoms in people with cystic fibrosis (pwCF) is unknown. We sought to examine this.

METHODS: Abdominal symptoms were measured using the validated CF-specific GI symptom questionnaire - CFAbd-Score© - as part of a multicentre cohort study in pancreatic insufficient adults with CF, not on cystic fibrosis transmembrane conductance regulator (CFTR) modulators. The CFAbd-Score total score (0-100pts), its 5 domains, alongside nine specific GI symptoms associated with DM, were compared between the CFRD and non-CFRD groups.

RESULTS: 27 (31%) and 61 (69%) participants with CF were recruited in the CFRD and non-CFRD groups respectively. Total CFAbd-Score and the two domains: gastroesophageal reflux disease and disorders of appetite were significantly higher in the CFRD group compared to the non-CFRD group (p<0.05), with the mean total CFAbd-Score being 25.4 ± 2.5 and 18.4 ± 1.5 in the CFRD and non-CFRD groups respectively. Among the nine GI symptoms commonly reported as elevated in DM, bloating and nausea were significantly more common in individuals with CFRD compared to those without (p<0.05).

CONCLUSIONS: Individuals with CFRD overall, have a higher GI symptom burden, according to CFAbd-Scores. Specifically, they experience significantly more bloating and nausea. Close monitoring and further research is needed to better understand and manage GI symptoms in this group.

PMID:36710099 | DOI:10.1016/j.jcf.2023.01.010

J Cyst Fibros. 2023 Jan 27:S1569-1993(23)00003-6. doi: 10.1016/j.jcf.2023.01.002. Online ahead of print.

ABSTRACT

BACKGROUND: Advancements in the cystic fibrosis (CF) field have resulted in longer lifespans for individuals with CF. This has led to more responsibility for complex care regimens, frequent health care, and prescription medication utilization that are costly and may not be fully covered by health insurance. There are outstanding questions about unmet medical needs among the U.S. population with CF and how the financial burden of CF is associated with debt, housing instability, and food insecurity.

METHODS: Researchers developed the CF Health Insurance Survey (CF HIS) to survey a convenience sample of people living with CF in the U.S. The sample was weighted to reflect the parameters of the 2019 Cystic Fibrosis Foundation Patient Registry Annual Data Report, and chi-square tests and multiple logistic regression models were conducted.

RESULTS: A total of 1,856 CF patients in the U.S. were included in the study. Of these, 64% faced a financial burden: 55% of respondents faced debt issues, 26% housing issues, and 33% food insecurity issues. A third reported at least one unmet medical need: 24% faced unmet prescription needs, 12% delayed or shortened a hospitalization, and 10% delayed or skipped a care center visit as a result of the cost of care.

CONCLUSIONS: People with CF in the U.S. experience high financial burden, which is associated with unmet medical needs. Income is the biggest risk factor for financial burden for people with CF, with people dually covered by Medicare and Medicaid particularly at risk.

PMID:36710098 | DOI:10.1016/j.jcf.2023.01.002

Lancet. 2023 Jan 28;401(10373):303. doi: 10.1016/S0140-6736(22)02165-1.

NO ABSTRACT

PMID:36709075 | DOI:10.1016/S0140-6736(22)02165-1

Mol Biotechnol. 2023 Jan 27. doi: 10.1007/s12033-023-00668-4. Online ahead of print.

ABSTRACT

Recombinant adeno-associated viruses (rAAVs) may be useful for the development of gene therapy for hereditary diseases. Patient-specific human induced pluripotent stem cells (hiPSCs) can be differentiated into a variety of cells which are difficult or impossible to obtain by biopsy. To date, few research on the efficiency of rAAV transduction of hiPSCs has been published, but the obtained data are very contradictory and do not answer the actual question: how effective are rAAVs for the delivery of transgenes into hiPSCs. In this work, we used rAAV serotypes 5, 6, and 9 carrying the GFP transgene. The transduction efficiency of rAAV2/9-GFP and rAAV2/6-GFP for the immortalized tracheal epithelial cell line derived from a patient with cystic fibrosis (CFTE29o-) was relatively high. At the same time, the efficiency of transduction of iPSCs from a healthy donor and a cystic fibrosis (CF) donor was extremely low. Thus, our results show that the efficiency of hiPSC transduction by rAAV serotypes 5, 6, and 9 is not suitable for the delivery of transgenes.

PMID:36707468 | DOI:10.1007/s12033-023-00668-4