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Despite the elucidation of the many processes by which a single eukaryotic cell develops into a complex mature organism, it is still puzzling to some biologists how it is that an unvarying, interconnected set of processes becomes coordinated and insulated from a stochastic universe. This article suggests that electromagnetic processes deriving from the chemistry of an organism may provide such coordination. Specifically, the author develops the pacemaker concept, the periodic, autonomous electrical signal to the entire embryo, the result of which, after each pulse, is to alter or enlarge the transcriptome to produce the next level of complexity and maturity of the organism., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Over the last several decades, substantial treatment advances have improved the quality of life and median predicted survival in people with cystic fibrosis (PwCF). It is critical for CF clinicians to begin to discuss health considerations related to an aging and overall healthier CF population. Such considerations include family planning, reproductive health, and contraception. CF care teams are trusted sources of medical information and therefore often have initial discussions related to contraception for PwCF. The purpose of this article is to review the available pharmacologic contraceptive methods, with a specific focus on the benefits and risks that may be more relevant to PwCF., Competing Interests: Declaration of competing interest All authors declare they have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: As cystic fibrosis (CF) lung disease progresses, the airways become infected with opportunistic pathogens, such as Pseudomonas aeruginosa (PA). In October 2019, the US Food and Drug Administration approved elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective modulator therapy (HEMT), for individuals 12 years and older with 1 copy of the F508del cystic fibrosis transmembrane conductance regulator ( CFTR ) mutation. ETI increases the amount of and function of CFTR in the respiratory epithelium, improving mucociliary clearance and reducing static airway mucus, a major trigger for chronic infection and inflammation., Methods: A retrospective analysis of inhaled tobramycin (iTOB) prescriptions between January 1, 2016, and December 31, 2021, was performed. This captured data before and after ETI approval at Children's Mercy Kansas City (CMKC). The number of individuals with new PA acquisition and individuals considered -chronically infected was analyzed., Results: The number of eradication prescriptions declined in 2020 and 2021, with 15 (7%) and 12 (5%) -individuals prescribed therapy for those years, respectively. A similar pattern was observed for -prescriptions for chronic infection. A reduction was seen in 2020 and 2021, with 28 (13%) and 20 (9%) individuals -prescribed therapy for the respective years., Conclusions: The CMKC experienced a decrease in the number of courses of iTOB prescribed during the last 6 years. The reasons for this are likely multifactorial and may include the implementation of standardized PA surveillance and eradication protocols, the effect of HEMT on mucociliary clearance and airway microbiology, and the poorly understood effects of the SARS-CoV-2 pandemic on the epidemiology of respiratory infections., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

The widespread use of highly effective cystic fibrosis transmembrane-conductance regulator -modulator therapy has dramatically altered the lives of individuals with cystic fibrosis. Clinical trials leading to -modulator approval by the US Food and Drug Administration demonstrated improvements in major -outcome measures including pulmonary function, gastrointestinal symptoms, and quality of life. Subsequent clinical experience has confirmed significant improvement across these domains. Adverse effects reported -during clinical trials included headache and dizziness amongst others including upper respiratory infections, abdominal pain, diarrhea, rash, and elevated serum transaminases. Post marketing clinical experience has suggested that there may be additional central nervous system adverse effects resulting from modulator therapy. Reported events after initiation of cystic fibrosis transmembrane-conductance regulator modulator treatment include headaches and increased prevalence of mental health concerns including anxiety and depression. We report a new tic disorder in a 7-year-old girl with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org.)

Background: Improvement in exocrine pancreatic function in persons with CF (pwCF) on cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been documented in clinical trials using fecal pancreatic elastase-1 (FE-1). Our group endeavored to evaluate real-world data on FE-1 in children on CFTR modulator therapy at three pediatric cystic fibrosis (CF) centers., Methods: Pediatric pwCF were offered FE-1 testing if they were on pancreatic enzyme replacement therapy (PERT) and on CFTR modulator therapy according to their center's guideline. FE-1 data were collected retrospectively. The primary outcome was absolute change in FE-1., Results: 70 pwCF were included for analysis. 53 had baseline and post-modulator FE-1 values. There was a significant increase in FE-1 from median 25 mcg/g (IQR 25-60) at baseline to 57 mcg/g (IQR 20-228) post-modulator (p<0.001 by Wilcoxon matched pairs), with an absolute change in FE-1 of median 28 mcg/g (IQR -5-161) and mean 93.5 ± 146.8 mcg/g. Age was negatively correlated with change in FE-1 (Spearman r=-0.48, p<0.001). 15 pwCF (21%) had post-modulator FE-1 values ≥200 mcg/g, consistent with pancreatic sufficiency (PS). The PS group was significant for younger age at initiation of first CFTR modulator and a higher baseline FE-1., Conclusions: Most pwCF experienced an increase in FE-1 while receiving CFTR modulator treatment and a small percentage demonstrated values reflective of PS. These data suggest that PS may be attained in those that initiated modulator therapy at a younger age or had a higher baseline FE-1. FE-1 testing is suggested for children on any CFTR modulator therapy., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose: Kimberly G. Stephenson, MS, RD, CSP, CACFD Abby J. Lingle, PharmD Kelly A. Baumberger, RD, CSP, CACFD Charles R. Esther Jr., MD, PhD Ellen M. Meier, APRN Christopher M. Oermann, MD Natalie Smith, MS, RD, LD Nicole S. Wimmer, RN, MSN, CPNP |Stephanie R. Duehlmeyer, PharmD, BCPPS, AE-C Charissa W. Kam, PharmD, BCPPS, CPP Margaret O. Poisson, PharmD, BCPPS E. Claire Elson, PharmD, BCPPS, AE-C, (Copyright © 2023. Published by Elsevier B.V.)

Background: Cystic fibrosis (CF) is a multisystem disease that often requires otolaryngology care. Individuals with CF commonly have chronic rhinosinusitis but also present with hearing loss and dysphonia. Given these manifestations of CF, otolaryngologists are frequently involved in the care of patients with CF; however, there is limited consensus on optimal management of sinonasal, otologic, and laryngologic symptoms., Methods: The Cystic Fibrosis Foundation convened a multidisciplinary team of otolaryngologists, pulmonologists, audiologists, pharmacists, a social worker, a nurse coordinator, a respiratory therapist, two adults with CF, and a caregiver of a child with CF to develop consensus recommendations. Workgroups developed draft recommendation statements based on a systematic literature review, and a ≥80% consensus was required for acceptance of each recommendation statement., Results: The committee voted on 25 statements. Eleven statements were adopted recommending a treatment or intervention, while five statements were formulated recommending against a specific treatment or intervention. The committee recommended eight statements as an option for select patients in certain circumstances, and one statement did not reach consensus., Conclusion: These multidisciplinary consensus recommendations will help providers navigate decisions related to otolaryngology consultation, medical and surgical management of CF-CRS, hearing, and voice in individuals with CF. A collaborative and multidisciplinary approach is advocated to best care for our patients with CF. Future clinical research is needed utilizing standardized, validated outcomes with comprehensive reporting of patient outcome, effects of modulator therapies, and genetic characteristics to help continue to advance care, decrease morbidity, and improve the quality of life for individuals with CF., (© 2022 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Background and Objectives: Pediatric patients with immunocompromising or certain chronic medical conditions have an increased risk of acquiring invasive pneumococcal disease (IPD). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients ≥2 years at high risk for IPDs. The aim of this project was to improve PPSV23 vaccination rates for children at high risk for IPD who were seen in 3 specialty clinics from ∼20% to 50% over a 12-month period., Methods: The project team included quality improvement champions from the divisions of rheumatology, infectious diseases, and pulmonology in addition to leaders from our population health management subsidiary. Several initiatives were implemented, starting with review of patient inclusion criteria per the vaccination recommendations, that led to the design and deployment of an automated weekly previsit planning report. Additionally, we implemented a process to stock pneumococcal vaccines and shared best practices among the divisions. We monitored improvement through times series and run charts of PPSV23 vaccination rates., Results: The initial PPSV23 vaccination rate for applicable high-risk patients was ∼20%. There was an increase in vaccination rate to ∼60%. All 3 divisions showed improvements in their individual PPSV23 vaccination rates., Conclusions: Using quality improvement methodology, we increased PPSV23 vaccination rates in 3 pediatric specialty clinics, and this improvement was sustained. We will continue to identify best practices and actively recruit additional divisions because we have the opportunity to reach >9000 high-risk patients., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: Dr Olarte has received a grant from Merck for an investigator-initiated study and has participated as site principal investigator or subinvestigator for pneumococcal vaccine clinical trials for Pfizer and Merck. The other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

This report describes a case of a 15-year-old male with cystic fibrosis caused by N1303K and Q493X cystic fibrosis transmembrane conductance regulator (CFTR) protein variants. In this case, CFTR modulators including tezacaftor-ivacaftor and subsequently elexacaftor-tezacaftor-ivacaftor were used and resulted in clinical stability and improvement., Competing Interests: Disclosures. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all patient information in this report and take responsibility for the integrity and accuracy of the report., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2022.)

Aminoglycoside antibiotics treat respiratory infections in cystic fibrosis (CF). An aminoglycoside induced ototoxicity algorithm (AIOA) was implemented to assess ototoxicity among people with CF treated with intravenous and/or inhaled aminoglycosides. Prior to AIOA implementation, 14 of 52 patients (27%) treated with intravenous aminoglycosides had an audiogram. In the 24 months post AIOA implementation, 43 of 44 patients (98%) treated with intravenous aminoglycosides had an audiogram, with 27 (63%) demonstrating abnormalities. Prior to AIOA development, 18 of 70 patients (26%) who received at least two courses of inhaled aminoglycosides had an audiogram. Post AIOA implementation, 33 patients qualified for an audiogram after receiving inhaled aminoglycosides. Of these, 19 (58%) had an audiogram and 10 (53%) had abnormalities. Overall, we identified 46 (61%) people with CF with hearing abnormalities compared to 2.4% in the CF Foundation Patient Registry. This suggests an urgent need for CF programs to implement AIOAs., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2020. Published by Elsevier B.V.)

Management of infections in patients with cystic fibrosis (CF) presents challenges for healthcare providers, including the eradication of initial acquisition, treatment of acute exacerbations, and chronic infection with suppressive therapy. Inhaled antimicrobial therapy for infections in patients with CF has been used in these capacities, often in an effort to achieve optimal concentrations in sputum for antimicrobial efficacy while mitigating potential toxicities associated with systemic therapy. Unfortunately, there are few commercially available products formulated for inhalation, resulting in the off-label use of other formulations, such as intravenous products, administered via nebulization. This review aims to examine the evidence supporting the efficacy of these off-label formulations for management of acute and chronic infections associated with CF, as well as adverse effects associated with their use., (© 2019 Wiley Periodicals, Inc.)

Patients with cystic fibrosis (CF) develop pulmonary disease secondary to airway infection and dysregulated inflammation. Therapeutic innovations such as nebulized antimicrobial therapy targeting specific pathogens have resulted in improvements in quality of life and life expectancy. Aztreonam lysine for inhalation (AZLI) solution was initially approved to improve respiratory symptoms in CF patients with Pseudomonas aeruginosa (PA) in 2010 by the Food and Drug Administration. Since then, research broadening labeling and clinical application has been developed. In this review, we analyze published and ongoing research regarding AZLI therapy in CF. A search of the Cochrane Database of Systematic Reviews and the PubMed and ClinicalTrials.gov databases was conducted to identify publications about AZLI. Three pre-approval studies were identified and assessed. Two are Phase 3, placebo-controlled trials, assessing a variety of safety and efficacy endpoints, leading to FDA approval. The third is an open-label extension of the two previous trials. An additional seven post-approval, completed trials were identified and are included in this review. They represent a variety of study designs including safety and efficacy in patients with mild lung disease and young patients, an active comparator trial vs inhaled tobramycin, an eradication study, a study among patients with Burkholderia cepacia , and a study assessing continuous alternating antibiotic therapy. Finally, five ongoing clinical trials are discussed. Overall, studies demonstrated that inhaled aztreonam is a safe and effective antimicrobial treatment for the eradication of newly acquired P. aeruginosa and long-term suppressive therapy of chronic endobronchial infection among people with cystic fibrosis., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ECE disclosed she has served on a pharmacist advisory council for Vertex Pharmaceuticals and Gilead Sciences.

Purpose: The incorporation of the multiple mini-interview (MMI) into the postgraduate year 1 (PGY1) pharmacy residency program selection process was evaluated., Methods: Four MMI stations evaluating the highest-rated nonacademic attributes of prospective residents (critical thinking, teamwork, ethical reasoning and integrity, and communication and interpersonal skills) were incorporated into the traditional PGY1 residency interview process at an academic medical center. After completion of the interview, candidates and interviewers were surveyed regarding their perceptions of the refined interview process. Data regarding scores on various components of the applicant profile were also compared for significant correlations. Descriptive statistics were calculated for questionnaire responses and individual components of candidate profiles. Pearson's correlation coefficients were calculated between MMI score, traditional interview score, age, grade point average, application score, college of pharmacy rank, and final candidate rank (subjective score)., Results: A total of 38 candidates were interviewed, 37 of whom completed the postinterview survey. Candidates agreed that the MMI allowed them to convey their abilities effectively; however, they disagreed that it was more effective than traditional interviews. Candidates did not agree that the MMI caused less anxiety than traditional interviews. All 15 interviewers completed the postinterview survey and believed that the MMI effectively evaluated soft skills and that the MMI was more effective than traditional interviews in assessing candidates' abilities, skills, and thought processes., Conclusion: The use of the MMI in a PGY1 pharmacy residency applicant selection process appeared to be well accepted by both candidates and interviewers and likely assesses different attributes than do traditional interview techniques.

There is still not an appealing and testable model to explain how single-celled organisms, usually following fusion of male and female gametes, proceed to grow and evolve into multi-cellular, complexly differentiated systems, a particular species following virtually an invariant and unique growth pattern. An intrinsic electrical oscillator, resembling the cardiac pacemaker, may explain the process. Highly auto-correlated, it could live independently of ordinary thermodynamic processes which mandate increasing disorder, and could coordinate growth and differentiation of organ anlage.

Microwave evoked body movements were studied in mice. A resonant cavity was used to provide head and neck exposure of the mouse to pulsed and gated continuous wave (CW) 1.25 GHz microwaves. No difference in response to pulsed and gated CW stimuli of equal average power was found. The incidence of the microwave evoked body movements increased proportionally with specific absorption (dose) when the whole-body average specific absorption rate was at a constant level (7300 W/kg). Under a constant average specific absorption rate, the response incidence reached a plateau at 0.9 kJ/kg. For doses higher than 0.9 kJ/kg, response incidence was proportional to the specific absorption rate and reached a plateau at 900 W/kg. Body movements could be evoked by a single microwave pulse. The lowest whole-body specific absorption (SA) tested was 0.18 kJ/kg, and the corresponding brain SA was 0.29 kJ/kg. Bulk heating potentials of these SAs were less than 0.1 degree C. For doses higher than 0.9 kJ/kg, the response incidence was also proportional to subcutaneous temperature increment and subcutaneous heating rate. The extrapolated absolute thresholds (0% incidence) were 1.21 degrees C temperature increment and 0.24 degree C/s heating rate. Due to high subcutaneous heating rates, these microwaves must be perceived by the mouse as an intense thermal sensation but not a pain sensation because the temperature increment was well below the threshold for thermal pain. Results of the present study should be considered in promulgation of personnel protection guideline against high peak power but low average power microwaves.

Previously, we demonstrated the requirements for a minimum coherence time of an applied, small amplitude (10 microT) ELF magnetic field if the field were to produce an enhancement of ornithine decarboxylase activity in L929 fibroblasts. Further investigation has revealed a remarkably similar coherence time phenomenon for enhancement of ornithine decarboxylase activity by amplitude-modulated 915 MHz microwaves of large amplitude (SAR 2.5 W/kg). Microwave fields modulated at 55, 60, or 65 Hz approximately doubled ornithine decarboxylase activity after 8 h. Switching modulation frequencies from 55 to 65 Hz at coherence times of 1.0 s or less abolished enhancement, while times of 10 s or longer provided full enhancement. Our results show that the microwave coherence effects are remarkably similar to those observed with ELF fields.

A hypothesis of microwave-induced circulatory under perfusion was tested in ketamine anesthetized rats whose heart rate, mean arterial pressure, pulse pressure, respiration rate, and body temperatures were monitored continuously. Fifty-eight ventral head and neck exposures in a waveguide consisted of sham-exposure and exposure to continuous wave (CW) and pulsed 1.25 GHz microwaves for 5 min. The 0.5 Hz (10 microseconds, 2 W average) and 16 Hz (1 microsecond, 6.4 W average) pulse-modulated microwaves were delivered at 400 kW peak power. The CW microwaves were 2 and 6.4 W. The average specific absorption rate was 4.75 W/kg per watt transmitted in the brain and 17.15 W/kg per watt transmitted in the neck. Respiration rate and mean arterial pressure were not altered. Changes in heart rate and pulse pressure were observed in rats exposed to higher power (16 Hz pulses and 6.4 W CW) but not to the lower average power microwaves (0.5 Hz pulses and 2 W CW). Depression of pulse pressure, an indication of a decrease in stroke volume, and increased (tachycardia) or decreased (bradycardia) heart rate were noted in presence of whole-body hyperthermia. The cardiac output of those animals exposed to higher average power microwaves was considered to be below normal as hypothesized. Decreased cardiac output and normal mean arterial pressure resulted in an increase in the total peripheral resistance which was contrary to the anticipated thermal response of animals.

Normal human lymphocytes were isolated from the peripheral blood of healthy donors. One-ml samples containing (10(6)) cells in chromosome medium 1A were exposed for 5 days to conventional heating or to continuous wave (CW) or pulsed wave (PW) 2450-MHz radiation at non-heating (37 degrees C) and various heating levels (temperature increases of 0.5, 1.0, 1.5, and 2 degrees C). The pulsed exposures involved 1-microsecond pulses at pulse repetition frequencies from 100 to 1,000 pulses per second at the same average SAR levels as the CW exposures. Actual average SARs ranged to 12.3 W/kg. Following termination of the incubation period, spontaneous lymphoblastoid transformation was determined with an image analysis system. The results were compared among each of the experimental conditions and with sham-exposed cultures. At non-heating levels, CW exposure did not affect transformation. At heating levels both conventional and CW heating enhanced transformation to the same extent and correlate with the increases in incubation temperature. PW exposure enhanced transformation at non-heating levels. This finding is significant (P less than .002). At heating levels PW exposure enhanced transformation to a greater extent than did conventional or CW heating. This finding is significant at the .02 level. We conclude that PW 2450-MHz radiation acts differently on the process of lymphoblastoid transformation in vitro compared with CW 2450-MHz radiation at the same average SARs.

The exposure of cells to relatively low-intensity, pulsed, low-frequency electromagnetic fields can result in a transient augmentation of mRNA synthesis. Under certain conditions of irradiation, the augmentation is a function of the strength of the electromagnetic field. A linear, multi-step, chemical-reaction model accounts for many of the principal features that are observed in both the time- and intensity-dependent variations of transcriptional effects. The crucial assumption in the model is that the direct effect of electromagnetic fields on exposed cells is an increase in the rate constant that characterizes one of the intermediate sequential reactions in the synthesis of mRNA.

A waveguide exposure system with automated sample temperature measurement is described. This system provides on-line determination of the temperature profile over time of biological samples in vitro. It allows automated computation of the specific absorption rate determined from heating/cooling curves, uses minimally-perturbing thermometry, is biocompatible and can be used for measurements of both microwave and conventional heating.

Because of the possible carcinogenicity of benzidine, a plasma hemoglobin method that substitutes reagents now used in other methods and poses no similar hazard is presented. It is comparable to the benzidine method in ease and time of accomplishment.