Fecal calprotection in the pediatric population: a 2020 update.

Minerva Pediatr. 2020 Jul 29;:

Authors: Cisaró F, Pizzol A, Rigazio C, Calvo PL

Abstract
INTRODUCTION: Calprotectin is a calcium and zinc-binding protein, formed by a hetero complex of S100A8 and S100A9 proteins, which belong to the S-100 protein family consisting in more than 20 different proteins with a tissue-specific expression pattern. This protein is secreted extracellularly from stimulated neutrophils or released by cell disruption or death. The presence of calprotectin in feces quantitatively relates to neutrophil migration toward the GI tract; thus, it represents a useful marker of intestinal inflammation.
EVIDENCE ACQUISITION: Fecal calprotectin (FC) has been proven largely useful for etermining the inflammatory origin of GI symptoms differentiating between organic and non-organic diseases. Indeed, increased FC levels are also seen in gastroenteritis, microscopic colitis, polyps, malignancies and cystic fibrosis.
EVIDENCE SYNTHESIS: To date, there are many evidences regarding usefulness in the detection of fecal calprotectin (FC) for the management of gastrointestinal (GI) disorders, both in children and adults but, especially in the pediatric population, still clear indications for its use are lacking. Its incorporation in primary care reduces the risk of missing an organic disease, and facilitates the indication for expensive and invasive investigations as colonoscopy.
CONCLUSIONS: We herein review and discuss the last evidences on the usefulness of FC in children, with its current indications and future prospective.

PMID: 32731735 [PubMed - as supplied by publisher]

Pseudomonas Aeruginosa Induced Cell Death in Acute Lung Injury and Acute Respiratory Distress Syndrome.

Int J Mol Sci. 2020 Jul 28;21(15):

Authors: Deshpande R, Zou C

Abstract
Pseudomonas aeruginosa is an important opportunistic pathogen responsible for the cause of acute lung injury and acute respiratory distress syndrome. P. aeruginosa isthe leading species isolated from patients with nosocomial infection and is detected in almost all the patients with long term ventilation in critical care units. P. aeruginosa infection is also the leading cause of deleterious chronic lung infections in patients suffering from cystic fibrosis as well as the major reason for morbidity in people with chronic obstructive pulmonary disease. P. aeruginosa infections are linked to diseases with high mortality rates and are challenging for treatment, for which no effective remedies have been developed. Massive lung epithelial cell death is a hallmark of severe acute lung injury and acute respiratory distress syndrome caused by P. aeruginosa infection. Lung epithelial cell death poses serious challenges to air barrier and structural integrity that may lead to edema, cytokine secretion, inflammatory infiltration, and hypoxia. Here we review different types of cell death caused by P. aeruginosa serving as a starting point for the diseases it is responsible for causing. We also review the different mechanisms of cell death and potential therapeutics in countering the serious challenges presented by this deadly bacterium.

PMID: 32731491 [PubMed - in process]

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Aspergillus Is Inhibited by Pseudomonas aeruginosa Volatiles.

J Fungi (Basel). 2020 Jul 25;6(3):

Authors: Nazik H, Sass G, Déziel E, Stevens DA

Abstract
BACKGROUND: Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) compete with each other for nutrients and survival in natural environments, and have been extensively studied because of their intermicrobial interactions in the human microbiome. These are the principal microbes infecting immunocompromised patients and persons with cystic fibrosis, particularly the airways. These intermicrobial studies have largely been conducted in liquid medium or on agar, and thus focus on soluble or diffusible microbial products. Several key inhibitory molecules were defined in such studies.
METHODS: in the present report, we examine several methodologies which can be conveniently used to study the interaction of microbial volatiles, including capture methods and kinetics.
RESULTS: Pa volatiles inhibit Af, and the inhibitory mechanism appears to be the incorporation of the inhibitory molecules into the substrate nourishing the Af, rather than directly onto Af structures. We define by mass spectroscopy some specific volatile Pa products that can inhibit Af. Some of these molecules are selected for interest by the study of gene deletion mutants, producing a few Pa strains that were impaired in inhibition. We presumed the volatiles of these latter strains could be excluded from the search for inhibitors.
CONCLUSION: the Pa inhibition of Af via a gaseous phase could be critical components in their competition, particularly in airways, where more direct contact may not be extensive.

PMID: 32722412 [PubMed]

Association of Inhaled Antibiotics in Addition to Standard IV Therapy and Outcomes of Pediatric Inpatient Pulmonary Exacerbations.

Ann Am Thorac Soc. 2020 Jul 29;:

Authors: Cogen JD, Faino AV, Onchiri F, Hoffman LR, Kronman MP, Nelson M, Nichols DP, Rosenfeld M, VanDevanter DR, Gibson RL

Abstract
RATIONALE: Considerable morbidity and disease progression in people with cystic fibrosis (CF) result from pulmonary exacerbations (PEx). PEx guidelines note insufficient evidence to recommend for or against the concomitant use of inhaled and IV antibiotics.
OBJECTIVES: We hypothesize that the addition of inhaled antibiotics for PEx therapy is associated with improvements in lung function and a longer time to next PEx compared with standard IV antibiotics alone.
METHODS: Retrospective cohort study using the CF Foundation Patient Registry-Pediatric Health Information System linked dataset. People with CF were included if hospitalized for PEx from 2006-2016 and 6-21 years of age. Lung function outcomes were assessed by linear mixed effect modeling and generalized estimating equations. Time to next PEx was assessed by Cox proportional hazards regression. To estimate independent causal effects while accounting for indication bias and other confounders, inverse probabilities of treatment weights were calculated based on covariates thought to influence the likelihood of inhaled antibiotic use during PEx treatment.
RESULTS: 3,253 children and adolescents contributed 9,040 PEx events for analysis. Inhaled antibiotics were used in 23% of PEx events but were not associated with better pre- to post-PEx ppFEV1 responses (mean difference -1.11%, [95% CI -1.83, -0.38]; p=0.003), higher odds of returning to lung function baseline (odds ratio 0.94, [0.82, 1.07]; p=0.34), or longer time to next PEx (hazard ratio 1.05, [0.99, 1.12]; p=0.098).
CONCLUSIONS: The addition of inhaled antibiotics to standard IV antibiotic PEx treatment was not associated with improved lung function outcomes or a longer time to next PEx.

PMID: 32726564 [PubMed - as supplied by publisher]

Gut microbiome a promising target for management of respiratory diseases.

Biochem J. 2020 Jul 31;477(14):2679-2696

Authors: Trivedi R, Barve K

Abstract
The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut-lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut-lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.

PMID: 32726437 [PubMed - as supplied by publisher]

Identification of flucloxacillin-haptenated HLA-B*57:01 ligands: evidence of antigen processing and presentation.

Toxicol Sci. 2020 Jul 29;:

Authors: Waddington JC, Meng X, Illing PT, Tailor A, Adair K, Whitaker P, Hamlett J, Jenkins RE, Farrell J, Berry N, Purcell AW, Naisbitt DJ, Park BK

Abstract
Flucloxacillin is a β-lactam antibiotic associated with a high incidence of drug-induced liver reactions. Although expression of HLA-B*57:01 increases susceptibility, little is known of the pathological mechanisms involved in the induction of the clinical phenotype. Irreversible protein modification is suspected to drive the reaction through the modification of peptides that are presented by the risk allele. In this study, the binding of flucloxacillin to immune cells was characterized and the nature of the peptides presented by human leukocyte antigen HLA-B*57:01 was analyzed using mass spectrometric based immunopeptidomics methods. Flucloxacillin modification of multiple proteins was observed, providing a potential source of neo-antigens for HLA presentation. Of the peptides eluted from flucloxacillin-treated C1R-B*57:01 cells, 6 putative peptides were annotated as flucloxacillin-modified HLA-B*57:01 peptide ligands (Data are available via ProteomeXchange with identifier PXD020137). To conclude, we have characterized naturally processed drug-haptenated HLA ligands presented on the surface of antigen presenting cells that may drive drug-specific CD8+ T-cell responses.

PMID: 32726429 [PubMed - as supplied by publisher]

Cellular Mechanism Underlying Oxytocin-Stimulated Cl- Secretion in Rat Cauda Epididymal Epithelium.

Am J Physiol Cell Physiol. 2020 Jul 29;:

Authors: Gao DD, Wang LL, Xu JW, Qiu ZE, Zhu YX, Zhang YL, Zhou WL

Abstract
The neurohypophyseal hormone oxytocin (OT) plays critical roles in lactation and parturition, whilst its function in male reproduction system is largely unknown. This study aims to investigate the effect of OT on regulating transepithelial ion transport in rat cauda epididymal epithelium. Using RT-PCR, western blot and immunohistochemical analysis, we found that OT receptor (OTR) was expressed and localized at the basal membrane of rat cauda epididymal epithelium. The short-circuit current (ISC) measurement showed that basolateral application of OT to the primary cultured rat cauda epididymal epithelial cells elicited an increase in ISC, which was abrogated by pretreating the epithelial cells with CFTRinh-172, a blocker of cystic fibrosis transmembrane conductance regulator (CFTR). Pretreatment with the prostaglandin H synthase (PGHS) inhibitors indomethacin and piroxicam, or the non-selective antagonists of PGE2 receptor EP2 or EP4, AH-6809 and AH-23848, significantly attenuated OT-stimulated ISC response. Furthermore, the generation of prostaglandin E2 (PGE2) was measured using enzyme-linked immunosorbent assay, demonstrating that OT induced a substantial increase in PGE2 release from primary cultured rat cauda epididymal epithelial cells. In conclusion, activation of OTR by OT triggered PGE2 release, resulting in CFTR-dependent Cl- secretion through paracrine/autocrine pathways in rat cauda epididymal epithelium.

PMID: 32726160 [PubMed - as supplied by publisher]

Azithromycin and ciprofloxacin inhibit interleukin-8 secretion without disrupting human sinonasal epithelial integrity in vitro.

Int Forum Allergy Rhinol. 2020 Jul 28;:

Authors: Lim DJ, Thompson HM, Walz CR, Ayinala S, Skinner D, Zhang S, Grayson JW, Cho DY, Woodworth BA

Abstract
BACKGROUND: We recently developed a ciprofloxacin and azithromycin sinus stent (CASS) to target recalcitrant infections in chronic rhinosinusitis (CRS). The objective of this study was to evaluate the anti-inflammatory activity of azithromycin released from the CASS and assess the impact on the integrity and function of primary human sinonasal epithelial cells (HSNECs).
METHODS: Pseudomonas aeruginosa lipopolysaccharide (LPS)-stimulated HSNECs were treated with azithromycin and/or ciprofloxacin at concentrations attainable from CASS release. Interleukin-8 (IL-8) secretion was quantified by enzyme-linked immunosorbent assay (ELISA). Epithelial integrity (transepithelial resistance [TEER], paracellular permeability [fluorescein isothiocyanate-labeled dextran], lactate dehydrogenase [LDH] assays) and function (ciliary beat frequency [CBF]) were also evaluated.
RESULTS: Azithromycin significantly reduced secreted IL-8 from P. aeruginosa LPS-stimulated HSNECs at all concentrations tested (mean ± standard deviation; control = 5.77 ± 0.39 ng/mL, azithromycin [6 μg/mL] = 4.58 ± 0.40 ng/mL, azithromycin [60 µg/mL] = 4.31 ± 0.06, azithromycin [180 µg/mL] = 4.27 ± 0.26 ng/mL, p < 0.05). Co-incubation with azithromycin (6 µg/mL) and ciprofloxacin (2.4 µg/mL) in LPS-stimulated HSNECs also displayed a significant reduction in secreted IL-8 when compared to P. aeruginosa LPS alone (co-treatment = 4.61 ± 0.29 ng/mL, P. aeruginosa LPS = 7.35 ± 0.89 ng/mL, p < 0.01). The drugs did not negatively impact TEER, paracellular permeability, LDH release, or CBF, indicating retention of cell integrity and function.
CONCLUSION: Azithromycin decreased P. aeruginosa LPS IL-8 production in HSNECs at drug concentrations attainable with sustained release of azithromycin from the CASS. In addition to antibacterial activity, anti-inflammatory properties of the CASS should provide further benefit for patients with recalcitrant CRS.

PMID: 32725797 [PubMed - as supplied by publisher]

Key role of pediatricians and disease for influenza vaccination in children with high-risk chronic diseases.

Eur J Pediatr. 2020 Jul 28;:

Authors: Alauzet P, Morand A, Mazenq J, Gaudart J, Bosdure E, Dubus JC

Abstract
Annual influenza vaccination is recommended for children with chronic diseases. Studies on influenza vaccines, following controversies related to the 2009 H1N1 influenza, are scarce in Europe. Our aim was to evaluate the influenza vaccination coverage in such children in a French tertiary hospital. Secondary objectives were the evaluation of the influenza vaccination coverage trend and the identification of factors influencing the vaccination status. A prospective and descriptive study by questionnaire was performed at the end of 2017 in 402 French hospital outpatients with various underlying chronic diseases eligible to the influenza vaccination. The 2016-2017 vaccination coverage was 46.5%. Figures of 75% or greater were only found in patients with cystic fibrosis and sickle cell disease. CART analysis identified vaccination in the previous year, medical recommendation for vaccination, and maternal influenza vaccination as a child's decisive factors for being vaccinated.Conclusion: Influenza vaccination coverage remains insufficient in children receiving hospital follow-up for chronic diseases. Its implementation clearly depends on pediatricians' recommendation to vaccinate and on the type of chronic disease. What is Known: • Despite health policy recommendations, the rate of annual influenza vaccination in children with chronic diseases is low What is New: • Influenza vaccination coverage depends on the type of chronic disease and on the pediatricians' counseling to vaccine.

PMID: 32725288 [PubMed - as supplied by publisher]

Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases.

Theranostics. 2020;10(18):7993-8017

Authors: Li Y, Liu R, Wu J, Li X

Abstract
Fibrosis occurs in most human organs including the liver, lung, heart and kidney, and is crucial for the progression of most chronic diseases. As an indispensable catabolic process for intracellular quality control and homeostasis, autophagy occurs in most mammalian cells and is implicated in many biological processes including fibrogenesis. Although advances have been made in understanding autophagy process, the potential role of autophagy in fibrotic diseases remains controversial and has recently attracted a great deal of attention. In the current review, we summarize the commonalities of autophagy affecting different types of fibrosis in different organs, including the liver, lung, heart, and kidney as well as in cystic fibrosis, systematically outline the contradictory results and highlight the distinct role of autophagy during the various stages of fibrosis. In summary, the exact role autophagy plays in fibrogenesis depends on specific cell types and different stimuli, and identifying and evaluating the pathogenic contribution of autophagy in fibrogenesis will promote the discovery of novel therapeutic strategies for the clinical management of these fibrotic diseases.

PMID: 32724454 [PubMed - as supplied by publisher]

Cigarette smoke induces endoplasmic reticulum stress and suppresses efferocytosis through the activation of RhoA.

Sci Rep. 2020 Jul 28;10(1):12620

Authors: Ito H, Yamashita Y, Tanaka T, Takaki M, Le MN, Yoshida LM, Morimoto K

Abstract
Impaired efferocytosis is a key mechanism of inflammatory lung diseases, including chronic obstructive pulmonary disease and cystic fibrosis. Cigarette smoking activates RhoA and impairs efferocytosis in alveolar macrophages, but the mechanism has not been fully elucidated. We investigated the role of endoplasmic reticulum (ER) stress induced by cigarette smoking in the disruption of efferocytosis. Both tunicamycin (10 μg/ml) and thapsigargin (0.1 and 1 μM), which are ER stress inducers, suppressed efferocytosis in J774 cells, and a Rho-associated coiled-coil-forming kinase (ROCK) inhibitor (Y27632) reversed this effect. We validated the effect of tunicamycin on efferocytosis in experiments using RAW264.7 cells. Then, we investigated the role of the unfolded protein response (UPR) in efferocytosis impaired by ER stress. A PERK inhibitor (GSK2606414) restored the efferocytosis that had been impaired by TM, and an eIF2α dephosphorylation inhibitor (salubrinal) suppressed efferocytosis. Cigarette smoke extract (CSE) induced ER stress in J774 macrophages and RhoA activation in J774 cells, and the CSE-induced ROCK activity was successfully reversed by GSK2606414 and tauroursodeoxycholic acid. Finally, we confirmed that ER stress suppresses efferocytosis in murine alveolar macrophages and that GSK2606414 could rescue this process. These data suggest that cigarette smoke-induced ER stress and the UPR play crucial roles in RhoA activation and suppression of efferocytosis in the lung.

PMID: 32724133 [PubMed - as supplied by publisher]

External and Genetic Conditions Determining Male Infertility.

Int J Mol Sci. 2020 Jul 24;21(15):

Authors: Kamiński P, Baszyński J, Jerzak I, Kavanagh BP, Nowacka-Chiari E, Polanin M, Szymański M, Woźniak A, Kozera W

Abstract
We explain environmental and genetic factors determining male genetic conditions and infertility and evaluate the significance of environmental stressors in shaping defensive responses, which is used in the diagnosis and treatment of male infertility. This is done through the impact of external and internal stressors and their instability on sperm parameters and their contribution to immunogenetic disorders and hazardous DNA mutations. As chemical compounds and physical factors play an important role in the induction of immunogenetic disorders and affect the activity of enzymatic and non-enzymatic responses, causing oxidative stress, and leading to apoptosis, they downgrade semen quality. These factors are closely connected with male reproductive potential since genetic polymorphisms and mutations in chromosomes 7, X, and Y critically impact on spermatogenesis. Microdeletions in the Azoospermic Factor AZF region directly cause defective sperm production. Among mutations in chromosome 7, impairments in the cystic fibrosis transmembrane conductance regulator CFTR gene are destructive for fertility in cystic fibrosis, when spermatic ducts undergo complete obstruction. This problem was not previously analyzed in such a form. Alongside karyotype abnormalities AZF microdeletions are the reason of spermatogenic failure. Amongst AZF genes, the deleted in azoospermia DAZ gene family is reported as most frequently deleted AZF. Screening of AZF microdeletions is useful in explaining idiopathic cases of male infertility as well as in genetic consulting prior to assisted reproduction. Based on the current state of research we answer the following questions: (1) How do environmental stressors lessen the quality of sperm and reduce male fertility; (2) which chemical elements induce oxidative stress and immunogenetic changes in the male reproductive system; (3) how do polymorphisms correlate with changes in reproductive potential and pro-antioxidative mechanisms as markers of pathophysiological disturbances of the male reproductive condition; (4) how do environmental stressors of immunogenetic disorders accompany male infertility and responses; and (5) what is the distribution and prevalence of environmental and genetic risk factors.

PMID: 32722328 [PubMed - in process]

Spelunking in Sputum: Single Cell RNA Sequencing Sheds New Insights into Cystic Fibrosis.

Am J Respir Crit Care Med. 2020 Jul 28;:

Authors: Iwanaga N, Kolls JK

PMID: 32721178 [PubMed - as supplied by publisher]

Expanding access to CFTR modulators for rare mutations: The utility of n-of-1 trials.

J Cyst Fibros. 2020 01;19(1):1-2

Authors: Magaret AS, Mayer-Hamblett N, VanDevanter D

PMID: 31831338 [PubMed - indexed for MEDLINE]

Diagnosis and treatment of biofilm infections in children.

Curr Opin Infect Dis. 2019 10;32(5):505-509

Authors: Munro APS, Highmore CJ, Webb JS, Faust SN

Abstract
PURPOSE OF REVIEW: Biofilm-associated infections cause difficulties in the management of childhood chronic infections and other diseases, due to the invasive nature of interventions which are often necessary for definitive management. Despite their importance, there are challenges in diagnosing biofilm infections and gaps in clinicians' understanding regarding the significance of biofilms.
RECENT FINDINGS: Many chronic infections associated with biofilms remain difficult or impossible to eradicate with conventional therapy. Surgical intervention, implant removal or long-term intermittent or suppressive antimicrobial therapy may be required. There are still significant challenges in detecting biofilms which presents a barrier in clinical practice and research. Novel therapies to disrupt biofilms are currently under investigation, which may help reduce the impact of antimicrobial resistance.
SUMMARY: Biofilm-associated infection should be considered wherever there is clinical concern for an infection affecting prosthetic material, where there is a predisposing condition such as suppurative lung disease; or in the setting of chronic or relapsing infections which may be culture negative. New diagnostic methods for detecting biofilms are a research priority for both clinical diagnosis and the ability to conduct high quality clinical trials of novel antibiofilm interventions.

PMID: 31335442 [PubMed - indexed for MEDLINE]

Early pathogenesis of cystic fibrosis gallbladder disease in a porcine model.

Lab Invest. 2020 Jul 27;:

Authors: Zarei K, Stroik MR, Gansemer ND, Thurman AL, Ostedgaard LS, Ernst SE, Thornell IM, Powers LS, Pezzulo AA, Meyerholz DK, Stoltz DA

Abstract
Hepatobiliary disease causes significant morbidity in people with cystic fibrosis (CF), yet this problem remains understudied. We previously found that newborn CF pigs have microgallbladders with significant luminal obstruction in the absence of infection and consistent inflammation. In this study, we sought to better understand the early pathogenesis of CF pig gallbladder disease. We hypothesized that loss of CFTR would impair gallbladder epithelium anion/liquid secretion and increase mucin production. CFTR was expressed apically in non-CF pig gallbladder epithelium but was absent in CF. CF pig gallbladders lacked cAMP-stimulated anion transport. Using a novel gallbladder epithelial organoid model, we found that Cl- or HCO3- was sufficient for non-CF organoid swelling. This response was absent for non-CF organoids in Cl-/HCO3--free conditions and in CF. Single-cell RNA-sequencing revealed a single epithelial cell type in non-CF gallbladders that coexpressed CFTR, MUC5AC, and MUC5B. Despite CF gallbladders having increased luminal MUC5AC and MUC5B accumulation, there was no significant difference in the epithelial expression of gel-forming mucins between non-CF and CF pig gallbladders. In conclusion, these data suggest that loss of CFTR-mediated anion transport and fluid secretion contribute to microgallbladder development and luminal mucus accumulation in CF.

PMID: 32719544 [PubMed - as supplied by publisher]

Allergic bronchopulmonary aspergillosis.

Indian J Med Res. 2020 Jun;151(6):529-549

Authors: Agarwal R, Sehgal IS, Dhooria S, Muthu V, Prasad KT, Bal A, Aggarwal AN, Chakrabarti A

Abstract
Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by immunologic reactions initiated against Aspergillus fumigatus colonizing the airways of patients with asthma and cystic fibrosis. The common manifestations include treatment-resistant asthma, transient and fleeting pulmonary opacities and bronchiectasis. It is believed that globally there are about five million cases of ABPA, with India alone accounting for about 1.4 million cases. The occurrence of ABPA among asthmatic patients in special clinics may be as high as 13 per cent. Thus, a high degree of suspicion for ABPA should be entertained while treating a patient with bronchial asthma, particularly in specialized clinics. Early diagnosis and appropriate treatment can delay (or even prevent) the onset of bronchiectasis, which suggests that all patients of bronchial asthma should be screened for ABPA, especially in chest clinics. The current review summarizes the recent advances in the pathogenesis, diagnosis and management of ABPA.

PMID: 32719226 [PubMed - in process]

Noninvasive wearable electroactive pharmaceutical monitoring for personalized therapeutics.

Proc Natl Acad Sci U S A. 2020 Jul 27;:

Authors: Lin S, Yu W, Wang B, Zhao Y, En K, Zhu J, Cheng X, Zhou C, Lin H, Wang Z, Hojaiji H, Yeung C, Milla C, Davis RW, Emaminejad S

Abstract
To achieve the mission of personalized medicine, centering on delivering the right drug to the right patient at the right dose, therapeutic drug monitoring solutions are necessary. In that regard, wearable biosensing technologies, capable of tracking drug pharmacokinetics in noninvasively retrievable biofluids (e.g., sweat), play a critical role, because they can be deployed at a large scale to monitor the individuals' drug transcourse profiles (semi)continuously and longitudinally. To this end, voltammetry-based sensing modalities are suitable, as in principle they can detect and quantify electroactive drugs on the basis of the target's redox signature. However, the target's redox signature in complex biofluid matrices can be confounded by the immediate biofouling effects and distorted/buried by the interfering voltammetric responses of endogenous electroactive species. Here, we devise a wearable voltammetric sensor development strategy-centering on engineering the molecule-surface interactions-to simultaneously mitigate biofouling and create an "undistorted potential window" within which the target drug's voltammetric response is dominant and interference is eliminated. To inform its clinical utility, our strategy was adopted to track the temporal profile of circulating acetaminophen (a widely used analgesic and antipyretic) in saliva and sweat, using a surface-modified boron-doped diamond sensing interface (cross-validated with laboratory-based assays, R 2 ∼ 0.94). Through integration of the engineered sensing interface within a custom-developed smartwatch, and augmentation with a dedicated analytical framework (for redox peak extraction), we realized a wearable solution to seamlessly render drug readouts with minute-level temporal resolution. Leveraging this solution, we demonstrated the pharmacokinetic correlation and significance of sweat readings.

PMID: 32719130 [PubMed - as supplied by publisher]

Palliative care and advances in cystic fibrosis: where now?

BMJ Support Palliat Care. 2020 Jul 27;:

Authors: Johnson B, Lee S, Ezmigna D

PMID: 32718954 [PubMed - as supplied by publisher]