Laboratory biomarkers for lung disease severity and progression in cystic fibrosis.

Clin Chim Acta. 2020 May 16;:

Authors: Bene Z, Fejes Z, Macek M, Amaral MD, Balogh I, Nagy B

Abstract
Although the clinical outcomes of cystic fibrosis (CF) have been markedly improved through the recent implementation of novel CF transmembrane conductance regulator (CFTR) modulator drugs, robust and reliable biomarkers are still demanded for the early detection of CF lung disease progression, monitoring treatment efficacy and predicting life-threatening clinical complications. Thus, there is an unmet need to identify and validate novel, ideally blood based biomarkers with strong correlations to the severity of CF lung disease, which represents a major contribution to overall CF morbidity and mortality. In this review, we aim to summarize the utility of thus far studied blood-, sputum- and bronchoalveolar lavage (BAL)-based biomarkers to evaluate inflammatory conditions in the lung and to follow treatment efficacy in CF. Measurements of sweat chloride concentrations and the spirometric parameter FEV1 are currently utilized to monitor CFTR function and the effect of various CF therapies. Nonetheless, both have inherent pitfalls and limitations, thus routinely analyzed biomarkers in blood, sputum or BAL samples are required as surrogates for lung disorders. Recent discovery of new protein (e.g. HE4) and RNA-based biomarkers (e.g. microRNAs) may offer a higher efficacy, which in aggregate may be valuable to evaluate disease prognosis and to substantiate CF drug efficacy.

PMID: 32428503 [PubMed - as supplied by publisher]

Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium.

Nat Commun. 2020 May 19;11(1):2485

Authors: Goldfarbmuren KC, Jackson ND, Sajuthi SP, Dyjack N, Li KS, Rios CL, Plender EG, Montgomery MT, Everman JL, Bratcher PE, Vladar EK, Seibold MA

Abstract
Cigarette smoke first interacts with the lung through the cellularly diverse airway epithelium and goes on to drive development of most chronic lung diseases. Here, through single cell RNA-sequencing analysis of the tracheal epithelium from smokers and non-smokers, we generate a comprehensive atlas of epithelial cell types and states, connect these into lineages, and define cell-specific responses to smoking. Our analysis infers multi-state lineages that develop into surface mucus secretory and ciliated cells and then contrasts these to the unique specification of submucosal gland (SMG) cells. Accompanying knockout studies reveal that tuft-like cells are the likely progenitor of both pulmonary neuroendocrine cells and CFTR-rich ionocytes. Our smoking analysis finds that all cell types, including protected stem and SMG populations, are affected by smoking through both pan-epithelial smoking response networks and hundreds of cell-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.

PMID: 32427931 [PubMed - in process]

Small Molecule Channels Harness Membrane Potential to Concentrate Potassium in trk1Δtrk2Δ Yeast.

ACS Chem Biol. 2020 May 19;:

Authors: Hou J, Daniels PN, Burke MD

Abstract
Many protein ion channels harness membrane potential to move ions in opposition to their chemical gradient. Deficiencies of such proteins cause several human diseases, including cystic fibrosis, Bartter Syndrome, and proximal renal tubular acidosis. Using yeast as a eukaryotic model system, we asked whether, in the context of a protein ion channel deficiency in vivo, small molecule channels could similarly harness membrane potential to concentrate ions. Trk potassium transporters use membrane potential to move potassium from a relatively low concentration outside cells (~15mM) to one of >10X higher inside (150-500mM); trk1Δtrk2Δ are unable to concentrate potassium or grow in standard media. Here we show that potassium permeable, but not potassium selective, small molecule ion channels formed by amphotericin B can harness membrane potential to concentrate potassium and thereby restore trk1Δtrk2Δ growth. This finding expands the list of potential human channelopathies that might be addressed by a molecular prosthetics approach.

PMID: 32427463 [PubMed - as supplied by publisher]

Changes in Mucociliary Clearance Over Time in Children with Cystic Fibrosis.

Pediatr Pulmonol. 2020 May 19;:

Authors: Laube BL, Carson KA, Evans CM, Richardson VL, Sharpless G, Zeitlin PL, Mogayzel PJ

Abstract
OBJECTIVES: (1) To quantify changes in mucociliary clearance (MCC) over time in children with cystic fibrosis (CF) and the relationship between MCC and rate of infection with Pseudomonas aeruginosa (PA); (2) to determine the impact of MCC on the evolution of CF lung disease; and (3) to explore the role of mucus composition as a determinant of MCC.
METHODS: Children with CF, who had previously undergone an MCC measurement (Visit 1), underwent the following tests 3-10 years later: (1) second MCC measurement (Visit 2); (2) multiple breath washout to assess ventilation inhomogeneity, expressed as lung clearance index (LCI); (3) high resolution computed tomography lung scan (HRCT); and (4) induced sputum test. Number of PA+ cultures/year between visits was documented and mucus dry weight was quantified in the children and adult controls.
RESULTS: Nineteen children completed both visits. Median time between visits was 4.6 years. Clearance declined 30% between visits. Lower MCC on Visit 2 was associated with more PA+ cultures/year between visits. Lower MCC values on Visit 1 were associated with higher LCI values and higher HRCT scores on Visit 2. Mucus dry weight was significantly higher in children with CF compared to controls. Higher dry weights were associated with lower MCC.
CONCLUSIONS: Mucociliary clearance declines significantly over time in children with CF. The decline is associated with PA infection rate and is affected by mucus composition. Children with early slowing of MCC appear to be at risk for developing ventilation inhomogeneity and parenchymal lung damage when they are older. This article is protected by copyright. All rights reserved.

PMID: 32427408 [PubMed - as supplied by publisher]

Cystic Fibrosis Patients Infected With Epidemic Pseudomonas aeruginosa Strains Have Unique Microbial Communities.

Front Cell Infect Microbiol. 2020;10:173

Authors: Acosta N, Waddell B, Heirali A, Somayaji R, Surette MG, Workentine ML, Rabin HR, Parkins MD

Abstract
Pseudomonas aeruginosa is the archetypal cystic fibrosis (CF) pathogen. However, the clinical course experienced by infected individuals varies markedly. Understanding these differences is imperative if further improvements in outcomes are to be achieved. Multiple studies have found that patients infected with epidemic P. aeruginosa (ePA) strains may have a worse clinical prognosis than those infected with unique, non-clonal strains. Additionally, the traditionally uncultured CF lung bacterial community (i.e., CF microbiome) may further influence the outcome. We sought to identify if these two important variables, not identified through routine culture, associate and together may contribute to disease pathogenesis. Patients were classified as being infected with Prairie Epidemic ePA (PES) or a non-clonal strain, unique PA strains (uPA), through a retrospective assessment of a comprehensive strain biobank using a combination of PFGE and PES-specific PCR. Patients were matched to age, sex, time-period controls and sputum samples from equivalent time periods were identified from a sputum biobank. Bacterial 16S rRNA gene profiling and Pseudomonas qPCR was used to characterize the respiratory microbiome. We identified 31 patients infected with PES and matched them with uPA controls. Patients infected with PES at baseline have lower microbial diversity (P = 0.02) and higher P. aeruginosa relative abundance (P < 0.005). Microbial community structure was found to cluster by PA strain type, although it was not the main determinant of community structure as additional factors were also found to be drivers of CF community structure. Communities from PES infected individuals were enriched with Pseudomonas, Streptococcus and Prevotella OTUs. The disproportionate disease experienced by ePA infected CF patients may be mediated through a combination of pathogen-pathogen factors as opposed to strictly enhanced virulence of infecting P. aeruginosa strains.

PMID: 32426295 [PubMed - in process]

Spatial mapping of polymicrobial communities reveals a precise biogeography associated with human dental caries.

Proc Natl Acad Sci U S A. 2020 May 18;:

Authors: Kim D, Barraza JP, Arthur RA, Hara A, Lewis K, Liu Y, Scisci EL, Hajishengallis E, Whiteley M, Koo H

Abstract
Tooth decay (dental caries) is a widespread human disease caused by microbial biofilms. Streptococcus mutans, a biofilm-former, has been consistently associated with severe childhood caries; however, how this bacterium is spatially organized with other microorganisms in the oral cavity to promote disease remains unknown. Using intact biofilms formed on teeth of toddlers affected by caries, we discovered a unique 3D rotund-shaped architecture composed of multiple species precisely arranged in a corona-like structure with an inner core of S. mutans encompassed by outer layers of other bacteria. This architecture creates localized regions of acidic pH and acute enamel demineralization (caries) in a mixed-species biofilm model on human teeth, suggesting this highly ordered community as the causative agent. Notably, the construction of this architecture was found to be an active process initiated by production of an extracellular scaffold by S. mutans that assembles the corona cell arrangement, encapsulating the pathogen core. In addition, this spatial patterning creates a protective barrier against antimicrobials while increasing bacterial acid fitness associated with the disease-causing state. Our data reveal a precise biogeography in a polymicrobial community associated with human caries that can modulate the pathogen positioning and virulence potential in situ, indicating that micron-scale spatial structure of the microbiome may mediate the function and outcome of host-pathogen interactions.

PMID: 32424080 [PubMed - as supplied by publisher]

A novel combination of CYP51A mutations confers pan-azole resistance in Aspergillus fumigatus.

Antimicrob Agents Chemother. 2020 May 18;:

Authors: Macedo D, Brito Devoto T, Pola S, Finquelievich JL, Cuestas ML, García-Effron G

Abstract
The treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide.The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype of three Aspergillus fumigatus clinical strains isolated from an Argentinian cystic fibrosis patient under long-term triazole treatment.Strain susceptibilities were assessed and CYP51A gene sequences were analyzed. Two of the studied Aspergillus fumigatus strains harbored the TR34-L98H allele. These strains showed high MIC values for all tested triazole (>16.00 μg/ml, 1.00 μg/ml, 1.00 μg/ml and 2.00 μg/ml for itraconazole, isavuconazole, posaconazole and voriconazole, respectively). The third one showed a novel amino acid change (R65K) combined with the TR34-L98H mutations. This new mutation combination induces a pan-azole MIC augment when compared with TR34-L98H mutants (>16 μg/ml, 4.00 μg/ml, 4.00 μg/ml and 8.00 μg/ml for itraconazole, isavuconazole, posaconazole and voriconazole, respectively). The strain harboring the TR34-R65K-L98H allele showed no inhibition halo when voriconazole susceptibility was evaluated by disk diffusion. The effect of these mutations in the azole-resistant phenotype was confirmed by gene replacement experiments. Transformants harboring the TR34-L98H and TR34-R65K-L98H alleles mimicked the azole-resistance phenotype of the clinical isolates while the incorporation of the TR34-R65K and R65K alleles did not significantly increase azole MIC values.This is the first report of the TR34-L98H allele in Argentina. Moreover, a novel CYP51A allele (TR34-R65K-L98H) that induce a panazole MIC augment is described.

PMID: 32423948 [PubMed - as supplied by publisher]

Mycobacterium abscessus clearance by neutrophils is independent of autophagy.

Infect Immun. 2020 May 18;:

Authors: Pohl K, Grimm XA, Caceres SM, Poch KR, Rysavy N, Saavedra M, Nick JA, Malcolm KC

Abstract
Mycobacterium abscessus, a rapidly growing nontuberculous mycobacteria, is increasingly prevalent in chronic lung disease, including cystic fibrosis, and infections are characterized by neutrophil-dominated environments. However, mechanisms of immune control are poorly understood. Azithromycin, a macrolide antibiotic with immunomodulatory effects, is used to treat M. abscessus infections. Recently, inhibition of macrophage bactericidal autophagy was described for azithromycin, which could be detrimental to the host. Therefore, we explored the role of autophagy in mycobactericidal in neutrophils. Azithromycin did not affect M. abscessus-induced neutrophil reactive oxygen species formation, phagocytosis, or cytokine secretion, and neutrophils treated with azithromycin killed M. abscessus equally well as untreated neutrophils from either healthy or cystic fibrosis subjects. One clinical isolate was killed more effectively in azithromycin-treated neutrophils, suggesting that pathogen-specific factors may interact with an azithromycin-sensitive pathway. Chloroquine and rapamycin, an inhibitor and an activator of autophagy, respectively, also failed to affect mycobactericidal activity, suggesting that autophagy was not involved. However, wortmannin, an inhibitor of intracellular trafficking, inhibited mycobactericidal activity, but as a result of inhibiting phagocytosis. The effects of these autophagy-modifying agents and azithromycin in neutrophils from healthy subjects were similar between the smooth and rough morphotypes of M. abscessus However, in cystic fibrosis neutrophils wortmannin inhibited killing of a rough clinical isolate and not a smooth isolate, suggesting that unique host-pathogen interactions exist in cystic fibrosis. These studies increase our understanding of M. abscessus virulence and of neutrophil mycobactericidal mechanisms. Insight into the immune control of M. abscessus may provide novel targets of therapy.

PMID: 32423916 [PubMed - as supplied by publisher]

Identification of FDA-approved antivirulence drugs targeting the Pseudomonas aeruginosa quorum sensing effector protein PqsE.

Virulence. 2020 May 18;:

Authors: Baldelli V, D'Angelo F, Pavoncello V, Fiscarelli EV, Visca P, Rampioni G, Leoni L

Abstract
The ability of the bacterial pathogen Pseudomonas aeruginosa to cause both chronic and acute infections mainly relies on its capacity to finely modulate the expression of virulence factors through a complex network of regulatory circuits, including the pqs quorum sensing (QS) system. While in most QS systems the signal molecule/receptor complexes act as global regulators that modulate the expression QS-controlled genes, the main effector protein of the pqs system is PqsE. This protein is involved in the synthesis of the QS signal molecules 2-alkyl-4(1H)-quinolones (AQs), but it also modulates the expression of genes involved in virulence factors production and biofilm formation via AQ-independent pathway(s). P. aeruginosa pqsE mutants disclose attenuated virulence in plant and animal infection models, hence PqsE is considered a good target for the development of antivirulence drugs against P. aeruginosa.In this study, the negative regulation exerted by PqsE on its own transcription has been exploited to develop a screening system for the identification of PqsE inhibitors in a library of FDA-approved drugs. This led to the identification of nitrofurazone and erythromycin estolate, two antibiotic compounds that reduce the expression of PqsE-dependent virulence traits and biofilm formation in the model strain P. aeruginosa PAO1 at concentrations far below those affecting the bacterial growth rate. Notably, both drugs reduce the production of the PqsE-controlled virulence factor pyocyanin also in P. aeruginosa strains isolated from cystic fibrosis patients, and do not antagonize the activity of antibiotics commonly used to treat P. aeruginosa infection.

PMID: 32423284 [PubMed - as supplied by publisher]

Pulmonary fibrosis secondary to COVID-19: a call to arms?

Lancet Respir Med. 2020 May 15;:

Authors: Spagnolo P, Balestro E, Aliberti S, Cocconcelli E, Biondini D, Casa GD, Sverzellati N, Maher TM

PMID: 32422177 [PubMed - as supplied by publisher]

Plasma pharmacokinetics of ceftolozane/tazobactam in pediatric patients with cystic fibrosis.

Pediatr Pulmonol. 2020 May 18;:

Authors: Arrieta AC, Ang JY, Zhang Z, Larson KB, Yu B, Johnson MG, Rhee EG, Feng EH, Rizk ML

Abstract
BACKGROUND: The antipseudomonal cephalosporin/β-lactamase inhibitor combination ceftolozane/tazobactam could be a potential treatment option for cystic fibrosis (CF) pulmonary exacerbations. The pharmacokinetics (PK) of ceftolozane/tazobactam in children with CF merits further evaluation.
METHODS: This is a retrospective subgroup analysis of a phase 1, noncomparative trial that characterized PK, safety, and tolerability of single intravenous doses of ceftolozane/tazobactam in pediatric patients. This analysis compares ceftolozane and tazobactam plasma PK parameters, estimated from a population PK model, between patients with and without CF enrolled in that trial. Individual attainment of PK/pharmacodynamic (PD) targets of ceftolozane and tazobactam (free ceftolozane concentration >4 µg/mL for >30% and free tazobactam concentration >1 µg/mL for 20% of the dosing interval) in patients with and without CF were evaluated.
RESULTS: The study enrolled 18 patients aged greater than or equal to 2 to less than 18 years old, which included 9 with CF. Weight-normalized ceftolozane PK parameters were similar between patients with CF (clearance: 0.16 L/h/kg, half-life: 1.54 hours, volume of distribution: 0.26 L/kg) and without CF (clearance: 0.15 L/h/kg, half-life: 1.62 hours, volume of distribution: 0.26 L/kg), as were most weight-normalized tazobactam PK parameters. Weight-normalized tazobactam clearance was higher in patients with CF (0.73 L/h/kg) than patients without CF (0.42 L/h/kg). All patients achieved the prespecified PK/PD targets for ceftolozane and tazobactam.
CONCLUSIONS: This retrospective analysis demonstrated generally similar weight-normalized plasma PK parameters for ceftolozane and tazobactam among children with and without CF; thus, projected doses for treatment of pediatric hospital-acquired/ventilator-associated pneumonia, which are higher than the pediatric complicated urinary tract infection/intra-abdominal infection doses, may be appropriate for treatment of CF pulmonary exacerbation.

PMID: 32421928 [PubMed - as supplied by publisher]

Prospective evaluation of vascular changes in acute respiratory infections in children with cystic fibrosis.

Turk J Med Sci. 2020 May 18;:

Authors: Kartal Öztürk G, Eşki A, Çelebi Çelik F, Conkar S, Gülen F, Demir E, Keskinoğlu A

Abstract
BACKGROUND/AIM: Acute exacerbations and chronic inflammation are risk factors for cardiovascular disease (CVD) in cystic fibrosis (CF) patients. The aim of this study was to investigate the effects of acute exacerbation therapy on arterial stiffness in children with CF.
MATERIALS AND METHODS: Augmentation index (Aix) and pulse wave velocity (PWV) were measured before and after treatment and one month after the end of treatment in patients with acute exacerbation. The relationship between hemodynamic measurements and c-reactive protein (CRP) and pulmonary function tests (PFTs) was investigated.
RESULTS: Measurements before and after treatment were evaluated in 27 patients and were repeated in 21 patients who were clinically stable one month following acute exacerbation. There was a significant decrease in CRP and an increase in spirometry parameters after treatment. While no significant difference was found between PWV (p=0.33), a significant difference for Aix before (41.95 ± 12.96%) and after (30.95 ± 11.47%) treatment and before treatment and stable clinical condition (34.19 ± 14.36%) was obtained (p=0.00, and p=0.01, respectively). No significant difference in heart rate and other hemodynamic measurements was found. Pre-treatment Aix is associated with poor clinical condition (PFTs, BMI, and clinical score) and systemic inflammation (CRP) (p<0.05).
CONCLUSION: The decrease of arterial stiffness (Aix) with acute exacerbation treatment in children with CF has been demonstrated. This result shows that systemic inflammation in CF may cause an increase in arterial stiffness and recurrent exacerbations may increase the risk of CVD. Prevention and treatment of acute exacerbations in childhood may reduce the risk of CVD in patients.

PMID: 32421279 [PubMed - as supplied by publisher]

Cystic fibrosis-associated liver disease in children.

Minerva Pediatr. 2020 May 15;:

Authors: Wasuwanich P, Karnsakul W

Abstract
INTRODUCTION: As improvements in nutritional and pulmonary care increase the life expectancy of cystic fibrosis (CF) patients, CF-associated liver disease (CFLD) is emerging as a cause of mortality. CFLD is the third leading cause of death in CF patients.
EVIDENCE ACQUISITION: We performed a search on PubMed and Google Scholar for published articles on CFLD.
EVIDENCE SYNTHESIS: We reviewed the articles found in the literature search and gave priority to recent publications and studies with larger sample sizes.
CONCLUSIONS: The prevalence of CFLD in the CF population is around 23% with a range of 2-62% and that prevalence increases linearly with age from 3.7% at age 5 to 32.2% at age 30. CFLD can present clinically in various ways such as hepatomegaly, variceal hemorrhage, persistent elevation of liver enzymes, and microgallbladder. Due to the focal nature of fibrosis in majority cases of CFLD, liver biopsies are sparsely performed for diagnosis or the marker of liver fibrosis. Although the mechanism of CFLD development is still unknown, many potential factors are reported. Some mutations of CFTR such as having a homozygous F508del mutation has been reported to increase the risk of developing CFLD and its severity. Having the SERPINA1 Z allele, a history of pancreatic insufficiency, a history meconium ileus, CF-related diabetes, or being male increases the risk of developing CFLD. Environmental factors do not appear to have significant effect on modulating CFLD development. Ursodeoxycholic acid is commonly used to treat or prevent CFLD, but the efficacy of this treatment is questionable.

PMID: 32418413 [PubMed - as supplied by publisher]

Colectomy and health-related quality of life in children with ulcerative colitis.

Minerva Pediatr. 2020 May 15;:

Authors: Dipasquale V, Catena MA, Paiano L, Trimarchi G, Romeo C, Navarra G, Mattioli G, Romano C

Abstract
BACKGROUND: Restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) is the recommended elective surgery for children with ulcerative colitis (UC). The aim of this study was to evaluate functional and long-term health-related quality of life (HRQoL) outcomes of surgery in paediatric patients with UC.
METHODS: We reviewed the hospital records of all paediatric patients who had undergone surgery for UC between January 2009 and December 2016 in the Units of Paediatric Gastroenterology and Surgery, of both the University Hospital of Messina, and the Gaslini Children's Hospital of Genoa. Surgical treatment was represented by restorative proctocolectomy and laparoscopic IPAA. Patients and parents were interviewed by telephone before and after surgery and responded to the modified IMPACT III questionnaire about health outcomes and HRQoL. The questionnaire was scored on a five-point scale with higher scores indicating a better HRQoL. The total score ranged from 35 (worst HRQoL) to 175 (best HRQoL).
RESULTS: Data were obtained in 30 patients (16 males), with a median age of 12 (range 3- 16). The median amount of time elapsed after the operation was 3 years (range 1-4.5). Preoperative scores were very low in all 4 domains of the questionnaire. Postoperatively, HRQoL measures improved significantly (p<0.05), on symptoms, school attendance, social activities, and emotional aspects. Overall, nearly all were completely satisfied with the outcome of surgery.
CONCLUSIONS: Our data confirmed that surgical treatment improves the overall HRQoL in paediatric patients with UC.

PMID: 32418405 [PubMed - as supplied by publisher]

Inhaled therapies for NTM disease - The way forward?

J Cyst Fibros. 2019 09;18(5):581-583

Authors: Thomson R

PMID: 31500810 [PubMed - indexed for MEDLINE]

Soy Isoflavones and Gastrointestinal Health.

Curr Nutr Rep. 2020 May 16;:

Authors: Al-Nakkash L, Kubinski A

Abstract
PURPOSE OF REVIEW: Soy isoflavones are known to have beneficial effects on several aspects of gastrointestinal physiological functions (contractility or motility, secretion, morphology, and barrier function). In this review, we discuss the effects of soy isoflavones on the overall gut function and inflammation and assess how these effects might be implicated in the treatment of several gut-related diseases.
RECENT FINDINGS: Soy isoflavones influence several key aspects of gastrointestinal health: improve basal intestinal secretion, alleviate inflammation, limit intestinal morphological damage, and improve epithelial barrier function in several clinically relevant murine models of gastrointestinal diseases. Dietary supplementation with isoflavones proves to be a key means to improve the overall gut function and health. Future mechanistic studies with isoflavone interventions will help treat clinically related diseases such as cystic fibrosis and inflammatory-related gut problems such as colitis and diabetes.

PMID: 32418173 [PubMed - as supplied by publisher]

A Pilot Study of Mindfulness-Based Cognitive Therapy to Improve Well-Being for Health Professionals Providing Chronic Disease Care.

J Pediatr. 2020 May 13;:

Authors: Hente E, Sears R, Cotton S, Pallerla H, Siracusa C, Filigno SS, Boat T

Abstract
OBJECTIVE: To assess the efficacy of mindfulness-based cognitive therapy delivered onsite during work hours in reducing stress and improving well-being in an interdisciplinary chronic care health care team.
STUDY DESIGN: A longitudinal, mixed methods, observational pilot study using a survey created from validated assessment tools to measure effectiveness of training. Surveys were completed before training, and 1 and 15 months after training. Twenty-four professionals in the cystic fibrosis Centers at Cincinnati Children's Hospital and the University of Cincinnati participated in 6 mindfulness-based cognitive therapy training sessions. Sessions incorporated mindfulness, cognitive therapy, and experiential exercises for processing feelings related to stress and burnout.
RESULTS: The presurvey and 1-month postsurvey responses revealed statistically significant improvements for empathy, perceived stress, depersonalization, anxiety, perspective taking, resilience, and negative affect. Sustained effects were seen at 15 months for empathy, perspective taking, and depressive symptoms. The 1-month post-training surveys reported a quarter of respondents (25%) practiced skills at least 5 times in between sessions; at 15 months, 35% reported practicing at the same frequency. Participants reported using mindfulness skills for personal stressful events (74%), work-related general stress (65%), patient-related stress (30%), sleep or general relaxation (22%), and wellness (13%).
CONCLUSIONS: Group mindfulness-based cognitive therapy training was feasible and effective in decreasing stress for interdisciplinary cystic fibrosis care team members who elected to participate. Further investigation is needed to determine optimal dose of training, durability of perceived benefits, and generalizability to health care professionals working with other chronic disorders.

PMID: 32417086 [PubMed - as supplied by publisher]

Theranostic Nanoparticles for Pancreatic Cancer Treatment.

Endocr Metab Immune Disord Drug Targets. 2020 May 16;:

Authors: Jaidev LR, Chede LS, Kandikattu HK

Abstract
Pancreatic cancer is one of the low vascular permeable tumors with a high mortality rate. The five-year survival period is ~5%. The field of drug delivery is at its pace in developing unique drug delivery carriers to treat high mortality rate cancers such as pancreatic cancer. Theranostic nanoparticles are the new novel delivery carriers where the carrier is loaded with both diagnostic and therapeutic agents. The present review discusses various therapeutic and theranostic nanocarriers for pancreatic cancer.

PMID: 32416712 [PubMed - as supplied by publisher]

Nocardia Infections: Ten Years Experience from a Tertiary Health Care Center in North India (2007-2016).

Infect Disord Drug Targets. 2020 May 16;:

Authors: Bansal Y, Singla N, Butta H, Aggarwal D, Gulati N, Chander J

Abstract
BACKGROUND: Nocardia species are important cause of infections in humans but are underreported due to missed diagnosis as well as misdiagnosis. Majority of the literature on these infections consists of case reports or series with few articles describing high number of cases.
OBJECTIVE: To study the epidemiology of Nocardia infections in a tertiary care center.
MATERIALS AND METHODS: This retrospective observational study was done in a tertiary care centre of North India over a period of 10 years (2007-2016). The detection of Nocardia spp. from clinical specimens was done by conventional methods viz. direct microscopy (Gram's stain, modified Ziehl-Neelsen stain [1%], KOH examination) and culture.
RESULTS: A total of 25 cases of nocardiosis were diagnosed during the study period. The mean age of the patients was 50.9 years (range 30-72 years) with a male:female ratio of 3:2. The site of disease in these patients included pulmonary (n=18), cutaneous (n=4), perinephric abscess (n=1), ocular (n=1) and bone (n=1). Risk factors associated were underlying lung disease (n=11), smoking (n=7), diabetes (n=5) and steroid therapy (n=4) in pulmonary nocardiosis, iatrogenic (n=1) and leprosy (n=1) in cutaneous nocardiosis, diabetes in perinephric abscess and cataract surgery in ocular nocardiosis. Culture was positive in 12/25 (48%) patients for Nocardia spp. Direct microscopy was positive in 22 patients. We wish to highlight that meticulous observation of KOH wet mount examination helped in clinching the diagnosis of Nocardiosis in 3 cases which were earlier missed by other methods.
CONCLUSIONS: Good communication with the clinician alongside a meticulous effort in the laboratory is essential for appropriate diagnosis and management of these cases.

PMID: 32416708 [PubMed - as supplied by publisher]

A broad-spectrum antibacterial natural product from the cystic fibrosis isolate, Pantoea agglomerans Tx10.

Microbiol Res. 2020 Apr 24;237:126479

Authors: Robinson LJ, Verrett JN, Sorout N, Stavrinides J

Abstract
The prevalence of antibiotic-resistant Gram-positive and Gram-negative pathogens has prompted considerable efforts to identify new antibacterials. Here we show that Pantoea agglomerans Tx10-an isolate from the sputum sample of a cystic fibrosis patient-is a strong competitor that inhibits the growth of a wide range of Gram-positive and Gram-negative bacteria through the production of a secreted compound. A genetic screen to identify the genes involved in the production of this compound resulted in the delineation of a 6-gene biosynthetic cluster. We called this compound Pantoea Natural Product 2 (PNP-2). Assays with mutants deficient in PNP-2 production revealed they were still able to inhibit Erwinia amylovora, suggesting the production of a second antibiotic, which we identified as Pantocin A. We generated Pantocin A knockouts, and a PNP-2/Pantocin A double knockout and used these to evaluate the spectrum of activity of both natural products. We show that strains of Enterobacter, E. coli, Klebsiella, Kosakonia, Pseudocitrobacter, Salmonella, Staphylococcus, and Streptococcus as well as the majority of Pantoea strains assayed are susceptible to PNP-2, indicating a broad spectrum of activity, and potential for therapeutic development.

PMID: 32416447 [PubMed - as supplied by publisher]