N Engl J Med. 2023 Nov 2;389(18):1693-1707. doi: 10.1056/NEJMra2216474.

NO ABSTRACT

PMID:37913507 | DOI:10.1056/NEJMra2216474

Andes Pediatr. 2023 Jun;94(3):392-400. doi: 10.32641/andespediatr.v94i3.4494.

ABSTRACT

Several studies have supported the positive effect of respiratory rehabilitation (RR) in children and adolescents (CRA) with chronic respiratory diseases (CRD); however, qualitative aspects related to the experiences and perceptions about RR have been scarcely studied.

OBJECTIVE: to analyze the qualitative evidence regarding the perceptions and experiences of patients, families and professionals related to the RR of children and adolescents with CKD.

METHODS: Review of qualitative studies in 5 databases. We used MeSH terms and free English-language terms grouped into three dimensions: patients, intervention, and research design. The study subjects had to be patients, their families, teachers or treating health teams. No restrictions were placed on language or year of publication. The search strategy was configured as follows: ((Cystic fibrosis) OR (Asthma) OR (Neuromuscular diseases)) AND ((Respiratory rehabilitation) OR (Exercise)) AND ((Qualitative research) OR (Phenomenology) OR (Grounded theory) OR (Ethnography)). Two independent authors analyzed atingent titles, abstracts and long texts. Finally, a qualitative description of the results was made.

RESULTS: Twenty-one qualitative studies were selected, all on patients, family members, teachers or professionals treating patients with cystic fibrosis (CF), asthma or neuromuscular diseases (NMD). Perception of benefits, parental influence, enjoyment of the protocols, and time required to engage in physical activity were categories identified in all three groups. Aspects such as perceived safety on school grounds and parental stress were specific categories, highlighted in the context of asthma and CF respectively.

CONCLUSION: Several general and specific factors of a qualitative nature influence the experience of children with CRD during RR. Future studies conducted in our cultural context should be conducted to confirm these results.

PMID:37909943 | DOI:10.32641/andespediatr.v94i3.4494

Infect Immun. 2023 Nov 1:e0041623. doi: 10.1128/iai.00416-23. Online ahead of print.

ABSTRACT

Cystic fibrosis (CF) is a genetic disease affecting epithelial ion transport, resulting in thickened mucus and impaired mucociliary clearance. Persons with CF (pwCF) experience life-long infections of the respiratory mucosa caused by a diverse array of opportunists, which are leading causes of morbidity and mortality. In recent years, there has been increased appreciation for the range and diversity of microbes causing CF-related respiratory infections. The introduction of new therapeutics and improved detection methodology has revealed CF-related opportunists such as Achromobacter xylosoxidans (Ax). Ax is a Gram-negative bacterial species which is widely distributed in environmental sources and has been increasingly observed in sputa and other samples from pwCF, typically in patients in later stages of CF disease. In this study, we characterized CF clinical isolates of Ax and tested colonization and persistence of Ax in respiratory infection using immortalized human CF respiratory epithelial cells and BALB/c mice. Genomic analyses of clinical Ax isolates showed homologs for factors including flagellar synthesis, antibiotic resistance, and toxin secretion systems. Ax isolates adhered to polarized cultures of CFBE41o- human immortalized CF bronchial epithelial cells and caused significant cytotoxicity and depolarization of cell layers. Ax colonized and persisted in mouse lungs for up to 72 h post infection, with inflammatory consequences that include increased neutrophil influx in the lung, lung damage, cytokine production, and mortality. We also identified genes that are differentially expressed in synthetic CF sputum media. Based on these results, we conclude that Ax is an opportunistic pathogen of significance in CF.

PMID:37909751 | DOI:10.1128/iai.00416-23

J Bras Pneumol. 2023 Oct 30;49(5):e20230201. doi: 10.36416/1806-3756/e20230201. eCollection 2023.

ABSTRACT

OBJECTIVE: Mobile health (mHealth) applications are scarce for children and adolescents with chronic pulmonary diseases (CPDs). This study aimed to map and describe the contents of the mHealth apps available for use in children and adolescents with CPDs.

METHODS: We performed a systematic mapping review of published scientific literature in PubMed, Scopus, and Cochrane Library by February of 2023, using relevant keywords. Inclusion criteria were as follows: children aged < 18 years with CPDs; and studies published in English on mHealth apps.

RESULTS: A total number of 353 studies were found, 9 of which met the inclusion criteria. These studies described seven mHealth apps for Android and iOS, designed either for asthma (n = 5) or for cystic fibrosis (n = 2). Five content areas were identified: education/information; pharmacological treatment; emergency; support; and non-pharmacological treatment. The studies (4, 2, and 3, respectively) showed consistent findings using qualitative, quantitative, and mixed methodologies.

CONCLUSIONS: This mapping review provided a guided selection of the most appropriate mHealth apps for use in children and adolescents with CPDs based on the needs of each target population. However, these mHealth apps have limited capabilities to reinforce disease self-management and provide information related to treatment compliance.

PMID:37909552 | DOI:10.36416/1806-3756/e20230201

Heliyon. 2023 Oct 23;9(11):e21469. doi: 10.1016/j.heliyon.2023.e21469. eCollection 2023 Nov.

ABSTRACT

People with cystic fibrosis-related diabetes (CFRD) suffer from chronic infections with Staphylococcus aureus and/or Pseudomonas aeruginosa. In people with CFRD, the concentration of glucose in the airway surface liquid (ASL) was shown to be elevated from 0.4 to 4 mM. The effect of glucose on bacterial growth/interactions in ASL is not well understood and here we studied the relationship between these lung pathogens in artificial sputum medium (ASM), an environment similar to ASL in vivo. S. aureus exhibited more rapid adaptation to growth in ASM than P. aeruginosa. Supplementation of ASM with glucose significantly increased the growth of S. aureus (p < 0.01, n = 5) and P. aeruginosa (p < 0.001, n = 3). ASM conditioned by the presence of S. aureus promoted growth of P. aeruginosa with less lag time compared with non-conditioned ASM, or conditioned medium that had been heated to 121 °C. Stable co-culture of S. aureus and P. aeruginosa could be established in a 50:50 mix of ASM and S. aureus-conditioned supernatant. These data indicate that glucose, in a nutrient depleted environment, can promote the growth of S. aureus and P. aeruginosa. In addition, heat labile factors present in S. aureus pre-conditioned ASM promoted the growth of P. aeruginosa. We suggest that the use of ASM allows investigation of the effects of nutrients such as glucose on common lung pathogens. ASM could be further used to understand the relationship between S. aureus and P. aeruginosa in a co-culture scenario. Our model of stable co-culture could be extrapolated to include other common lung pathogens and could be used to better understand disease progression in vitro.

PMID:37908712 | PMC:PMC10613906 | DOI:10.1016/j.heliyon.2023.e21469

ERJ Open Res. 2023 Oct 30;9(5):00317-2023. doi: 10.1183/23120541.00317-2023. eCollection 2023 Sep.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) lung disease starts in infancy and can be assessed for structural lung abnormalities using computed tomography or magnetic resonance scans, or for lung function impairment using multiple breath washout (MBW). However, in infancy these two methods are not well correlated. Trajectories of CF lung disease assessed by MBW in infants and toddlers remain poorly described, which is why we aimed to 1) describe the trajectory of lung function, 2) explore risk factors for progression and 3) explore the real-life effect of lumacaftor/ivacaftor.

METHODS: This was a nationwide observational cohort study (2018-2021) using data collected as part of the routine clinical surveillance programme (including MBW and monthly endo-laryngeal suction sampling for bacterial pathogens) in children born after implementation of newborn screening for CF (May 2016). Lumacaftor/ivacaftor commenced from age 2 years in children homozygous for F508del. Ventilation distribution efficiency (VDE), recently described to have advantages over lung clearance index (LCI), was reported as the primary MBW outcome after z-score calculations based on published reference data. Mixed effect linear regression models were the main statistical analyses performed in this study.

RESULTS: 59 children, aged 2-45 months, contributed with 211 MBW occasions (median (interquartile range (IQR)) 3 (2-5) MBW occasions per child) with a median (IQR) follow-up time of 10.8 (5.2-22.3) months. An overall mean annual deterioration rate of -0.50 (95% CI -0.78- -0.22) z-VDE was observed, starting from an estimated mean z-VDE of -1.68 (95% CI -2.15- -1.22) at age 0.0 years (intercept). Pseudomonas aeruginosa "ever" (n=14, MBWs 50) had a significantly worse z-VDE trajectory versus P. aeruginosa "never" (mean difference 0.53 (95% CI 0.16-0.89) per year; p=0.0047) and lumacaftor/ivacaftor treatment (n=22, MBWs 46) significantly improved the trajectory of z-VDE (mean difference 1.72 (95% CI 0.79-2.66) per year; p=0.0004), leading to a stable mean z-VDE trajectory after start of treatment.

CONCLUSIONS: Infants and toddlers with CF demonstrated progressive deterioration in z-VDE over the first years of life. P. aeruginosa isolation "ever" was associated with an accelerated deterioration in lung function, while lumacaftor/ivacaftor therapy significantly improved and stabilised the trajectory.

PMID:37908398 | PMC:PMC10613974 | DOI:10.1183/23120541.00317-2023

Pediatric Health Med Ther. 2023 Oct 26;14:361-378. doi: 10.2147/PHMT.S402589. eCollection 2023.

ABSTRACT

Cystic fibrosis (CF) is the leading etiology for exocrine pancreatic insufficiency (EPI) in children, followed by chronic pancreatitis, Shwachman-Diamond syndrome, and other genetic disorders. Management of EPI in children poses several unique challenges such as difficulties in early recognition, lack of widespread availability of diagnostic tests and limited number of pediatric-specific pancreatic centers. Pancreatic enzyme replacement therapy is the cornerstone of EPI management and in young children difficulties in administering pancreatic enzymes are frequently encountered. Patients with EPI also should be screened for fat-soluble vitamin deficiencies and receive appropriate supplementation. Among disorders with EPI in children, CF is the relatively well-studied condition, and most management recommendations for EPI in children come from expert consensus and conventional practice guidelines. The impact of EPI can be greater in children given their high metabolic demands and rapid growth. Early diagnosis and aggressive management of EPI prevent consequences of complications such as malnutrition, fat-soluble vitamin deficiencies, and poor bone health and improve outcomes. Management by multi-disciplinary team is the key to success.

PMID:37908317 | PMC:PMC10615098 | DOI:10.2147/PHMT.S402589

J Ethnopharmacol. 2023 Oct 29:117336. doi: 10.1016/j.jep.2023.117336. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese herbal medicine, rhubarb is said to remove accumulation with purgation, clearing heat, and discharging fire. Modern pharmacology has shown that rhubarb extract has a purgative effect when given to experimental animals in an appropriate dose. However, the active components and their mechanism of action are still not clearly defined.

AIM OF THE STUDY: The current research aimed to evaluate the synergistic stool-softening effects and explore the action mechanism of rhubarb free anthraquinones (RhA) and their monomers on constipation in rats.

MATERIALS AND METHODS: A rat model of water deficit-induced constipation was established to induce constipation, and these rats were treated with RhA and its monomers. ELISA, histopathology, immunohistochemistry, qPCR and Western blotting based on network pharmacology and molecular docking were conducted to explore the possible mechanism of action of RhA and its monomers.

RESULTS: RhA, aloe-emodin, rhein, and chrysophanol showed stool-softening activity, and the combination of aloe-emodin and rhein had the strongest softening effect on faecal pellets. Aloe-emodin, rhein, and chrysophanol significantly increased the serum levels of vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP), upregulated the expression of VIP, cyclase-associated protein 1 (CAP1), protein kinase A (PKA), cystic fibrosis transmembrane conductance regulator (CFTR), aquaporin 3 (AQP3), aquaporin 4 (AQP4), and aquaporin 8 (AQP8), decreased the expression of epithelial sodium channel (ENaC) and Na+/H+ exchanger 3 (NHE3), and reduced the colonic tissue concentration of Na+-K+-ATPase in the constipated rats. Osmolality of colonic fluid in model rats treated by RhA, aloe-emodin, rhein, and chrysophanol was increased.

CONCLUSION: Aloe-emodin, rhein, and chrysophanol were the stool-softening components of the RhA extract, and there were certain drug-interactions between the components. RhA upregulated VIP expression, activated the cyclic adenosine monophosphate protein kinase A (cAMP/PKA) pathway, and further stimulated CFTR expression while inhibiting NHE3 and ENaC expression, resulting in a hypertonic state in the colonic lumen. Water transport could then be driven by an osmotic gradient, which in turn led to the upregulation of AQP3, AQP4, and AQP8 expression. In addition, RhA likely improved gastrointestinal motility by increasing serum VIP, SP, and MTL concentrations, thus promoting faecal excretion.

PMID:37907143 | DOI:10.1016/j.jep.2023.117336

J Cyst Fibros. 2023 Oct 29:S1569-1993(23)01659-4. doi: 10.1016/j.jcf.2023.10.011. Online ahead of print.

ABSTRACT

BACKGROUND: In cystic fibrosis (CF), coughing is associated with a risk of pelvic floor dysfunction. However, data on the prevalence of symptoms (stress urinary incontinence, bladder overactivity, dysuria, and faecal incontinence) are lacking in males and females with CF. The impact of incontinence on adherence to respiratory care has not been studied.

METHODS: We conducted a multicentre study in adults with CF followed in the North-West French CF network. Urinary disorders and their severity were assessed using the Urinary Symptom Profile (USP) self-report questionnaire; the impact of urinary disorders on general quality of life was measured using the SF-Qualiveen questionnaire; faecal incontinence was assessed using the Wexner self-report questionnaire; and the CFQ-R14+ questionnaire was used to assess quality of life. A self-administered questionnaire developed for the study assessed the impact of symptoms on respiratory care.

RESULTS: Of the 178 people with CF included, 34 % reported stress urinary incontinence, with a large female predominance (63.5 % of females vs. 7.5 % of males), 65 % bladder overactivity (including 16 % urge incontinence) and 50 % faecal incontinence, also with a female predominance. Neither urinary nor faecal incontinence were related to the severity of the respiratory impairment (FEV1). Quality of life was particularly affected in women. Stress urinary Incontinence symptoms affected respiratory care in both sexes.

CONCLUSION: The prevalence of functional urinary and faecal disorders was high in adults with CF and impacted on quality of life and respiratory care. Therefore, multidisciplinary teams must have knowledge of symptoms, the diagnostic tools and management strategies to provide specific treatment.

PMID:37907384 | DOI:10.1016/j.jcf.2023.10.011

Andes Pediatr. 2022 Dec;93(6):898-905. doi: 10.32641/andespediatr.v93i6.4361.

ABSTRACT

Recent studies have shown that therapy with Cystic fibrosis transmembrane conductance regulator (CFTR) modulators in Cystic Fibrosis (CF) patients with Elexacaftor-Tezacaftor-Ivacaftor (ETI) decreases exacerbations and improves lung function and quality of life.

OBJECTIVE: to report the clinical response in the first patient in our setting treated with ETI.

CLINICAL CASE: 14-year-old female patient with severe cystic fibrosis phenotype, heterozygous for the Phe508del mutation (Phe508del/1078delT), with moderate pulmonary involvement and pancreatic insufficiency (PI). The patient started ETI therapy after the disease entered a phase of clinical and pulmonary function deterioration. From the second visit (45 days) until the end of the follow-up (365 days), the patient experienced a significant improvement in the quality-of-life domains measured by the CFQ-R 14+ questionnaire. In the pulmonary function study at 45 and 365 days, FVC increased by 21% and 22%, FEV1 by 20% and 27%, and FEF 25-75 by 23% and 37%, respectively. Nutritional assessment para meters in the first six months of follow-up showed an increase in wBMI from 1.6 to 5.6 k. No adverse effects were observed.

CONCLUSION: treatment with ETI in our CF patient showed a remarkable im provement in quality of life, pulmonary function, and nutritional status.

PMID:37906807 | DOI:10.32641/andespediatr.v93i6.4361

Cardiol Young. 2023 Oct 31:1-3. doi: 10.1017/S1047951123003359. Online ahead of print.

ABSTRACT

In utero idiopathic constriction of the arterial duct is a rare condition with only a handful reported cases. Ductal aneurysms with thrombus formations on the other hand are significantly more common. We report a case of a term infant who presented with right heart failure due to premature ductal closure and postnatal severe respiratory distress. Subsequent diagnostics revealed paresis of left laryngeal nerve and obstruction of the left pulmonary artery secondary to a ductal aneurysm. Consequently, surgical intervention was considered necessary. Post-operatively, right ventricular function and hoarseness resolved slowly.

PMID:37905342 | DOI:10.1017/S1047951123003359

Cureus. 2023 Sep 29;15(9):e46228. doi: 10.7759/cureus.46228. eCollection 2023 Sep.

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive disorder of the CF transmembrane conductance regulator (CFTR) gene. CFTR modulators are novel approved therapies, and triple therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is the current gold standard for patients with at least one F508del mutation. CFTR modulators are usually well-tolerated, but some adverse effects may occur, including skin rash. We report a case of a female patient who developed a severe skin rash after initiating treatment with ELX/TEZ/IVA. Modulator therapy and contraception were discontinued, and consequently, there was a drop in lung function and reappearance of respiratory symptoms. After rash resolution, a gradual reintroduction of ELX/TEZ/IVA was started, and this is the protocol the authors have summarized. Triple therapy with CFTR modulators has a significant impact on lung function and the quality of life of CF patients who have at least one F508del mutation, justifying its reintroduction and desensitization even after a severe adverse effect.

PMID:37905296 | PMC:PMC10613531 | DOI:10.7759/cureus.46228

bioRxiv. 2023 Oct 20:2023.10.19.563107. doi: 10.1101/2023.10.19.563107. Preprint.

ABSTRACT

The folding/misfolding and pharmacological rescue of multidomain ATP-binding cassette (ABC) C-subfamily transporters, essential for organismal health, remain incompletely understood. The ABCC transporters core consists of two nucleotide binding domains (NBD1,2) and transmembrane domains (TMD1,2). Using molecular dynamic simulations, biochemical and hydrogen deuterium exchange approaches, we show that the mutational uncoupling or stabilization of NBD1-TMD1/2 interfaces can compromise or facilitate the CFTR(ABCC7)-, MRP1(ABCC1)-, and ABCC6-transporters posttranslational coupled domain-folding in the endoplasmic reticulum. Allosteric or orthosteric binding of VX-809 and/or VX-445 folding correctors to TMD1/2 can rescue kinetically trapped CFTR post-translational folding intermediates of cystic fibrosis (CF) mutants of NBD1 or TMD1 by global rewiring inter-domain allosteric-networks. We propose that dynamic allosteric domain-domain communications not only regulate ABCC-transporters function but are indispensable to tune the folding landscape of their post-translational intermediates. These allosteric networks can be compromised by CF-mutations, and reinstated by correctors, offering a framework for mechanistic understanding of ABCC-transporters (mis)folding.

ONE-SENTENCE SUMMARY: Allosteric interdomain communication and its modulation are critical determinants of ABCC-transporters post-translational conformational biogenesis, misfolding, and pharmacological rescue.

PMID:37905074 | PMC:PMC10614980 | DOI:10.1101/2023.10.19.563107

J Biomol Struct Dyn. 2023 Oct 30:1-19. doi: 10.1080/07391102.2023.2275181. Online ahead of print.

ABSTRACT

Antimicrobial resistance poses a significant challenge to public health, especially in developing countries, due to a substantial rise in bacterial resistance. This situation has become so concerning that we are now at risk of losing the effectiveness of antibiotics altogether. Recent research has firmly established that bacteria engage in a process called quorum sensing (QS). QS regulates various functions, including nutrient scavenging, immune response suppression, increased virulence, biofilm formation and mobility. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, plays a significant role in various medical conditions such as chronic wounds, corneal infections, burn wounds and cystic fibrosis. While antibiotics are effective in killing bacteria, only a few antibiotics, particularly those from the β-lactam group, have been studied for their impact on the quorum sensing of P. aeruginosa. Given the lack of concentrated efforts in this area, we have investigated the role of β-lactam antibiotics on various potential targets of P. aeruginosa. Based on their toxicological profiles and the average binding energy obtained through molecular docking, azlocillin and moxalactam have emerged as lead antibiotics. The binding energy for the docking of azlocillin and moxalactam with LasA was determined to be -8.2 and -8.6 kcal/mol, respectively. Molecular simulation analysis has confirmed the stable interaction of both these ligands with all three target proteins (LasI, LasA and PqsR) under physiological conditions. The results of this research underscore the effectiveness of azlocillin and moxalactam. These two antibiotics may be repurposed to target the quorum sensing of P. aeruginosa.Communicated by Ramaswamy H. Sarma.

PMID:37904338 | DOI:10.1080/07391102.2023.2275181

Sci Rep. 2023 Oct 30;13(1):18573. doi: 10.1038/s41598-023-45201-4.

ABSTRACT

The nasal and bronchial epithelium are unified parts of the respiratory tract that are affected in the monogenic disorder cystic fibrosis (CF). Recent studies have uncovered that nasal and bronchial tissues exhibit intrinsic variability, including differences in mucociliary cell composition and expression of unique transcriptional regulatory proteins which relate to germ layer origin. In the present study, we explored whether intrinsic differences between nasal and bronchial epithelial cells persist in cell cultures and affect epithelial cell functioning in CF. Comparison of air-liquid interface (ALI) differentiated epithelial cells from subjects with CF revealed distinct mucociliary differentiation states of nasal and bronchial cultures. Moreover, using RNA sequencing we identified cell type-specific signature transcription factors in differentiated nasal and bronchial epithelial cells, some of which were already poised for expression in basal progenitor cells as evidenced by ATAC sequencing. Analysis of differentiated nasal and bronchial epithelial 3D organoids revealed distinct capacities for fluid secretion, which was linked to differences in ciliated cell differentiation. In conclusion, we show that unique phenotypical and functional features of nasal and bronchial epithelial cells persist in cell culture models, which can be further used to investigate the effects of tissue-specific features on upper and lower respiratory disease development in CF.

PMID:37903789 | DOI:10.1038/s41598-023-45201-4

Am J Physiol Cell Physiol. 2023 Oct 30. doi: 10.1152/ajpcell.00200.2023. Online ahead of print.

ABSTRACT

Epithelial tissues form selective barriers to ions, nutrients, waste products, and infectious agents throughout the body. Damage to these barriers is associated with conditions such as celiac disease, cystic fibrosis, diabetes, and age-related macular degeneration. Conventional electrophysiology measurements like trans-epithelial resistance can quantify epithelial tissue maturity and barrier integrity but are limited in differentiating between apical, basolateral, and paracellular transport pathways. To overcome this limitation, a combination of mathematical modeling, stem cell biology, and cell physiology led to the development of 3P-EIS, a novel mathematical model and measurement technique. 3P-EIS employs an intracellular pipette and extracellular electrochemical impedance spectroscopy to accurately measure membrane-specific properties of epithelia, without the constraints of prior models. 3P-EIS was validated using electronic circuit models of epithelia with known resistances and capacitances, confirming a median error of 19% (IQR 14%-26%) for paracellular and transcellular resistances and capacitances (n=5). Patient stem cell-derived retinal pigment epithelium tissues were measured using 3P-EIS, successfully isolating the cellular responses to adenosine tri-phosphate. 3P-EIS enhances quality control in epithelial cell therapies and has extensive applicability in drug testing and disease modeling, marking a significant advance in epithelial physiology.

PMID:37899750 | DOI:10.1152/ajpcell.00200.2023

Trials. 2023 Oct 28;24(1):695. doi: 10.1186/s13063-023-07719-w.

ABSTRACT

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by abnormal function of the chloride ion channels and characterized by pancreatic insufficiency and chronic endobronchial airway infection. Pulmonary dysfunction is very common and could lead to a reduction in the quality of life. Airway clearance techniques (ACT) and physical exercises are introduced as one of the main components of treatment. Therefore, it will be of interest to examine the effect of aerobic exercises compared to conventional chest physiotherapy (CPT) on pulmonary function, functional capacity, sputum culture, and quality of life in patients with CF.

METHODS: Thirty patients with CF will participate in a double-blind parallel controlled trial containing 18 sessions of treatment. Group A consists of CPT and placebo aerobic exercise, and group B includes aerobic exercise and placebo CPT. Pulmonary function, functional capacity, sputum culture, and quality of life will be evaluated with a spirometry test, 6-min walk test (6MWT), sputum culture test, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R), respectively, before and after the intervention.

DISCUSSION: We will evaluate and compare the effectiveness of aerobic exercises and conventional chest physiotherapy on pulmonary function, functional capacity, sputum culture, and quality of life. Comparing these two treatment patterns can contribute to a better understanding of the effectiveness. Therefore, if there is a significant difference between the two treatments, the superior treatment will be prioritized clinically.

TRIAL REGISTRATION: https://www.irct.ir , IRCT20210505051181N5. Registered on 19 February 2023.

PMID:37898788 | DOI:10.1186/s13063-023-07719-w

Int J Mol Sci. 2023 Oct 19;24(20):15363. doi: 10.3390/ijms242015363.

ABSTRACT

Advanced reproductive technologies are utilized to identify the genetic mutations that lead to spermatogenic impairment, and allow informed genetic counseling to patients to prevent the transmission of genetic defects to offspring. The purpose of this study was to identify potential single nucleotide polymorphisms (SNPs) associated with male infertility. Genetic variants that may cause infertility are identified by combining the targeted next-generation sequencing (NGS) panel and whole exome sequencing (WES). The validation step of Sanger sequencing adds confidence to the identified variants. Our analysis revealed five distinct affected genes covering seven SNPs based on the targeted NGS panel and WES data: SPATA16 (rs16846616, 1515442, 1515441), CFTR (rs213950), KIF6 (rs2273063), STPG2 (r2903150), and DRC7 (rs3809611). Infertile men have a higher mutation rate than fertile men, especially those with azoospermia. These findings strongly support the hypothesis that the dysfunction of microtubule-related and spermatogenesis-specific genes contributes to idiopathic male infertility. The SPATA16, CFTR, KIF6, STPG2, and DRC7 mutations are associated with male infertility, specifically azoospermia, and a further examination of this genetic function is required.

PMID:37895049 | PMC:PMC10607339 | DOI:10.3390/ijms242015363

Viruses. 2023 Oct 19;15(10):2121. doi: 10.3390/v15102121.

ABSTRACT

Measles has not yet been eradicated; therefore, its outbreaks are still reported throughout the world. Like any infection, measles is dangerous for immunocompromised patients. Levels of anti-measles IgG antibodies were measured in 157 patients aged 17 to 72, who were placed on the lung transplant waiting list. Measurements were undertaken by enzyme-linked immunosorbent assay (ELISA) using the VectoMeasles-IgG kit (Russia). The proportion of patients seronegative for measles was 19% (30/157). Correlation was detected between patients' age and their levels of anti-measles antibodies, with higher proportions of patients having undetectable titers (25.5-28.9%) or low antibody levels (38.3-44.4%) in the young age groups (17-29 and 30-39 years old). There were no differences between male and female patients in levels of anti-measles antibodies or in the proportion of seronegative individuals. Analyses of antibody levels with regard to type of disease revealed the highest rate of seronegative results in cystic fibrosis patients (34.4%, 11/32). Overall, 19% of lung transplant candidates, mostly young people and cystic fibrosis patients, did not have protective immunity against measles.

PMID:37896898 | DOI:10.3390/v15102121

Pharmaceuticals (Basel). 2023 Oct 16;16(10):1467. doi: 10.3390/ph16101467.

ABSTRACT

The rapid emergence of multidrug-resistant (MDR) bacteria in recent times has prompted the search for new and more potent antibiotics. Bacteriophages (commonly known as phages) are viruses that target and infect their bacterial hosts. As such, they are also a potential alternative to antibiotics. These phages can be broadly categorized into monovalent (with a narrow host range spectrum and specific to a single bacterial genus) and polyvalent (with a broad host range and specific to more than two genera). However, there is still much ambiguity in the use of these terms, with researchers often describing their phages differently. There is considerable research on the use of both narrow- and broad-host range phages in the treatment of infections and diseases caused by MDR bacteria, including tuberculosis, cystic fibrosis, and carbapenem-resistant Enterobacterales (CRE) infectious diseases. From this, it is clear that the host range of these phages plays a vital role in determining the effectiveness of any phage therapy, and this factor is usually analyzed based on the advantages and limitations of different host ranges. There have also been efforts to expand phage host ranges via phage cocktail development, phage engineering and combination therapies, in line with current technological advancements. This literature review aims to provide a more in-depth understanding of the role of phage host ranges in the effectiveness of treating MDR-bacterial diseases, by exploring the following: phage biology, the importance of phages in MDR bacteria diseases treatment, the importance of phage host range and its advantages and limitations, current findings and recent developments, and finally, possible future directions for wide host range phages.

PMID:37895938 | DOI:10.3390/ph16101467