Case Report: Comprehensive evaluation of ECG phenotypes and genotypes in a family with Brugada syndrome carrying SCN5A-R376H.

Background: Brugada syndrome (BrS) is a channelopathy that can lead to sudden cardiac death in the absence of structural heart disease. Patients with BrS can be asymptomatic or present with symptoms secondary to polymorphic ventricular tachycardia or ventricular fibrillation. Even though BrS can exhibit autosomal dominant inheritance, it is not easy to identify the phenotype and genotype in a family thoroughly. Case: We report the case of a 20-year-old man with variants in SCN5A and RyR2 genes who was resuscitated from sudden cardiac death during sleep due to a ventricular fibrillation. The patient did not have underlying diseases. The routine laboratory results, imaging study, coronary angiogram, and echocardiogram (ECG) were normal. A type 1 BrS pattern was identified in one resting ECG. Furthermore, prominent J wave accentuation with PR interval prolongation was identified during therapeutic hypothermia. Therefore, we were easily able to diagnose BrS. For secondary prevention, the patient underwent implantable cardioverter defibrillator implantation. Before discharge, a genetic study was performed using next-generation sequencing. Genotyping was performed in the first-degree relatives, and ECG evaluations of almost all maternal and paternal family members were conducted. The proband and his mother showed SCN5A-R376H and RyR2-D4038Y variants. However, his mother did not show the BrS phenotype on an ECG. One maternal aunt and uncle showed BrS phenotypes. Conclusion: Genetics alone cannotdiagnose BrS. However, genetics could supply evidence or direction for evaluating ECG phenotypes in family groups. This case report shows how family evaluation using ECGs along with a genetic study can be used in BrS diagnosis.

Improving nitrogen content in soil and lemon balm (Melissa officinalis L.) yield by purple nonsulfur bacteria Rhodopseudomonas palustris in two consecutive seasons.

The study was conducted to assess the effects of nitrogen (N)-fixing purple nonsulfur bacteria (PNSB) Rhodopseudomonas palustris TLS06, VNW02, VNW64, and VNS89 on soil fertility, N uptake, essential oil (EO) content, growth, and yield of lemon balm. The experiment followed a completely randomized block design with 9 treatments and 3 replications. The treatments consisted of (i) applying 100% N as the recommended fertilizer rate (RFR), (ii) applying 85% N as RFR, (iii) applying 70% N as RFR, (iv) applying 55% N as RFR, (v) the treatment ii combined with N-PNSB, (vi) the treatment iii combined with N-PNSB, (vii) the treatment iv combined with N-PNSB, (viii) 0% as RFR combined with N-PNSB, and (ix) 0% N as RFR. The results showed that applying N-PNSB increased the plant height, and the number of primary branches in both seasons. In addition, the treatment without N fertilizer combined with N-PNSB increased stem leaf biomass by 41.2 and 50.3% in both seasons as compared with the treatment without neither N fertilizer nor N-PNSB. For soil properties, among treatments without N fertilizer, the treatment with N-PNSB increased concentrations of NH4+, soluble P, and exchangeable K+ by 41.3, 41.4, and 26.8%, respectively, as compared with the treatment without N-PNSB at the end of the second season. Applying 85% N as RFR combined with N-PNSB had a greater yield by 5.78-11.8% as compared with the treatment with 100% N as RFR, and a greater EO content by 23% as compared with the treatment with 85% N as RFR.

Time to be blunt: Substance use in cystic fibrosis.

BACKGROUND: As the population of people with cystic fibrosis (pwCF) continues to age, attention is shifting towards addressing the unique challenges teenagers and adults face, including substance use. Changing attitudes and legality regarding marijuana and cannabidiol (CBD) may influence their use among pwCF, but data on the rate of use, reasons for use, and administration methods are lacking. OBJECTIVE: Investigate marijuana, CBD, e-cigarette, and cigarette usage among pwCF and explore differences in demographics, disease severity, and cystic fibrosis transmembrane receptor (CFTR) modulator use between recent users and nonusers. METHODS: This cross-sectional study used a one-time electronic survey to assess marijuana, CBD, e-cigarette, and cigarette use in pwCF aged >13 years. Demographic and clinical characteristics were compared between recent users and nonusers. The association between recent substance use and CFTR modulator use was analyzed using logistic regressions. RESULTS: Among 226 participants, 29% used marijuana, 22% used CBD, 27% used e-cigarettes, and 22% used cigarettes in the last 12 months. Users of all substances were more likely to be college-educated or aged 29-39 years than nonusers. E-cigarette users were 2.9 times more likely to use CFTR modulators (95% confidence interval [95% CI]: 0.98-11.00, p = .08) and marijuana users were 2.5 times more likely to use CFTR modulators compared to nonusers, adjusted for confounders. CBD, e-cigarettes, and cigarettes users were more likely to have an abnormal mental health screen compared to nonusers. A high proportion of never-users of marijuana and CBD expressed interest in using. CONCLUSION: Substance use is more prevalent among pwCF than previously reported and needs to be addressed by healthcare providers.

The potency of a liquid biofertilizer containing bacterial strains of Rhodopseudomonas spp. on recovery of soil properties damaged by Al3+ and Fe2+ toxins and enhancement of rice yield in acid sulfate soil.

In the Mekong Delta Vietnam, rice is heavily affected by Al3+ and Fe2+ ions appearing in local acid sulfate soils (AAS). Therefore, the current study was carried out to assess the efficacy of a liquid biofertilizer (LB) containing nitrogen-fixing and phosphorus-solubilizing bacterial strains of Rhodopseudomonas spp. on remediation of soil characteristics and improvements of rice uptakes, growth, and yield. The experiment was designed in a randomized block design with nine treatments and four replications in an ASS. The results have shown that the LB application could contribute to the remediation of soil properties, including an increase in concentrations of NH4+ by 12.9%-19.4%, soluble P by 25.7%-42.6%, total N uptake by 40.7-64.0 kg ha-1 and total P uptake by 5.60-12.6 kg ha-1, and a decrease in concentrations of toxins, such as Al3+ by 12.1%-19.7% and Fe2+ by 16.6%-19.0%, compared to the treatment with the farmer-based fertilization. Thereby, grain yield was improved by 31.9%-32.2% with the LB versus the treatments without the bacteria and by 9.5%-11.1% compared to the commercial biofertilizer treatments. The application of LB reduced 25% N and 50% P of the recommendation versus the farmers' fertilization and improved performance of rice growth and yield cultivated on ASS which suffered from Al3+ and Fe2+ ions.

The current study has introduced the potential of the Rhodopseudomonas palustris TLS06, VNW02, VNW64, and VNS89 strains in performance as a bioremediator and a biofertilizer. The strains have shown their ability to recover acid sulfate soils, which had damaged the yield of rice plants due to high concentrations of Al³⁺ and Fe²⁺ ions. The work has delivered a biological approach to improve acid sulfate soil fertility and rice productivity in Vietnam and in other parts of the world, which have similar conditions, to achieve sustainable agriculture and food security.

Evidence for Dicot Plants as Alternative Hosts of Banana Bunchy Top Virus and Its Alphasatellites in South-East Asia.

Banana bunchy top virus is a multicomponent circular ssDNA virus (family Nanoviridae) that causes one of the most devastating diseases of cultivated bananas and plantains (family Musaceae). It is transmitted by the aphids Pentalonia nigronervosa and P. caladii among host plants of Musaceae and some other families of monocots. Our Illumina sequencing reconstruction of virome components of BBTV-infected banana plants and their neighbor non-banana plants sampled in Vietnam and Laos revealed the monocot Commelina sp. (Commelinaceae) and the dicots Bidens pilosa and Chromolaena odorata (both Asteraceae) as hosts of BBTV and circular ssDNA alphasatellites (family Alphasatellitidae). Counting the proportions and relative abundances of Illumina reads representing BBTV genome components and alphasatellites suggested that Chromolaena and Commelina are poor hosts for BBTV and one to three alphasatellite species, whereas Bidens is a permissive host for BBTV and four alphasatellite species representing two genera of Alphasatellitidae. Our findings provide evidence for the dicot plants of family Asteraceae as alternative hosts of BBTV and its alphasatellites, which warrants further investigation of these and other dicots as a potential refuge and source of BBTV and multiple alphasatellites that become associated with this virus and likely affect its replication, transmission, and host range.

Diversity, Equity, and Inclusion in the Pediatric Pulmonary Workforce: An Official American Thoracic Society Workshop Report.

Despite growing recognition of the need for increased diversity among students, trainees, and faculty in health care, the medical workforce still lacks adequate representation from groups historically underrepresented in medicine (URiM). The subspecialty field of pediatric pulmonology is no exception. Although there have been efforts to address issues of diversity, equity, and inclusion (DEI) in our own field, gaps persist. To address these gaps, the members of the Diversity, Equity, and Inclusion Advisory Group (DEI-AG) of the American Thoracic Society Pediatrics Assembly created and distributed a Needs Assessment Survey in the United States and Canada to better understand the racial and ethnic demographics of the pediatric pulmonary workforce and to learn more about successes, gaps, and opportunities to enhance how we recruit, train, and retain a diverse workforce. The DEI-AG leadership cochairs convened a workshop to review the findings of the DEI Needs Assessment Survey and to develop strategies to improve the recruitment and retention of URiM fellows and faculty. This Official ATS Workshop Report aims to identify barriers and opportunities for recruitment, training, and career development within the field of pediatric pulmonology. Additionally, we offer useful strategies and resources to improve the recruitment of URiM residents, the mentorship of trainees and junior faculty, and the career development of URiM faculty in academic centers. This Workshop Report is an important first deliverable by the DEI-AG. We hope that this work, originating from within the Pediatrics Assembly, will serve as a model for other Assemblies, disciplines across the ATS, and other fields in Pediatrics.

Isolation and characterization of novel potassium-solubilizing purple nonsulfur bacteria from acidic paddy soils using culture-dependent and culture-independent techniques.

The current research as aimed (i) to isolate and select the purple nonsulfur bacteria (PNSB) possessing the potassium-solubilizing ability from acid paddy fields and (ii) to evaluate the ability to release the plant growth-promoting substances (PGPS) of selected PNSB. A total of 35 acid sulfate (AS) soil samples were collected in An Giang province, Vietnam. Then, 70 PNSB strains were isolated from the AS soil samples. In the current study, the isolated strains were screened and selected according to their tolerability to acidic conditions, ability to solubilize potassium, and characteristics of a plant growth promoter on basic isolation media with various incubation conditions. Therein, three strains, TT07.4, AN05.1, and AC04.1, presented the highest potassium solubilization under the microaerobic light (11.8-17.7 mg L-1) and aerobic dark (16.4-24.7 mg L-1) conditions and stresses from Al3+, Fe2+, and Mn2+ toxicity. The selected strains were identified as Rhodopseudomonas pentothenatexigens by the 16S rDNA sequence, with 99% similarity. The selected acidic-resistant strains possessed the traits of biofertilizers under both microaerobic light and aerobic dark conditions, with abilities to fix nitrogen (0.17-6.24; 7.93-11.2 mg L-1); solubilize phosphorus from insoluble compounds with 3.22-49.9 and 9.49-11.2 mg L-1 for Al-P, 21.9-25.8 and 20.2-25.1 mg L-1 for Ca-P, and 10.1-29.8 and 18.9-23.2 mg L-1 for Fe-P; produce 5-aminolevulinic acid (0.63-3.01; 1.19-6.39 mg L-1), exopolymeric substances (0.14-0.76; 0.21-0.86 mg L-1), indole-3-acetic acid (12.9-32.6; 13.6-17.8 mg L-1), and siderophores (28.4-30.3; 6.15-10.3%). The selected potassium-solubilizing strains have a great potential to apply in liquid form into rice seed and solid form in AS soils to supply nutrients and PGPS for enhancing rice growth and grain yield.

Ethnic differences in staphylococcus aureus acquisition in cystic fibrosis.

BACKGROUND: Hispanic people with CF (pwCF) have increased morbidity than non-Hispanic White pwCF, including increased risk of Pseudomonas aeruginosa. We aimed to determine if Staphylococcus aureus (S. aureus) acquisition varies between Hispanic and non-Hispanic White pwCF. METHODS: This longitudinal cohort study of pwCF ages 0-25 years in the CF Foundation Patient Registry compared acquisition of methicillin-sensitive S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), persistent MRSA between Hispanic and non-Hispanic White pwCF. Risk of acquisition was assessed by Kaplan-Meier survival curves and its association with ethnicity was evaluated using Cox regressions. Adjusted associations were evaluated using multivariate Cox models adjusting for sex, age of entry into CFFPR, CFTR variant severity, pancreatic insufficiency, CF-related diabetes, maternal education, insurance status. RESULTS: Of 10,640 pwCF, 7.5% were Hispanic and 92.5% were non-Hispanic White. Hispanic pwCF had a 19% higher risk of acquiring MSSA (HR 1.19, 95% CI 1.10-1.28, p<0.001) and 13% higher risk of acquiring MRSA (HR 1.13, 95% CI 1.02-1.26, p = 0.02) than non-Hispanic White pwCF. The difference in persistent MRSA between ethnicities did not reach statistical significance. After adjusting for confounding variables, only the risk of MSSA was significantly associated with ethnicity. Compared to non-Hispanic White pwCF, Hispanic pwCF acquired MSSA and MRSA at younger median ages (4.9 vs. 3.8 years (p<0.001), 22.4 vs. 20.8 years (p = 0.02). CONCLUSION: Hispanic pwCF <25 years of age have an increased risk of acquiring MSSA and acquired MSSA and MRSA at an earlier age. Differences in S. aureus acquisition may contribute to increased morbidity in Hispanic pwCF.

Pediatric Medical Traumatic Stress and Trauma-Informed Care in Pediatric Chronic Illness: A Healthcare Provider Survey.

OBJECTIVE: To inform approaches to pediatric medical traumatic stress (PMTS) by exploring providers' (1) perception of the impact of PMTS on the medical care of patients with pediatric-onset chronic illnesses, (2) self-reported competencies and practices of PMTS prevention, treatment, and counseling, and (3) perception of the barriers influencing the adoption of these practices. STUDY DESIGN: A convenience sample of multidisciplinary healthcare providers was recruited through a multimodal recruitment strategy to participate in an electronic survey adapted from the Trauma-Informed Care Provider Survey. RESULTS: Among participants (n = 304), 99% agreed that PMTS impacts patient health. Participants report altering medical care plans due to PMTS, including deferring or stopping treatments (n = 98 [32%]) and changing medication regimens (n = 88 [29%]). Sixty-eight percent (n = 208) report negative impact of PMTS on patient implementation of medical care plans, including medication nonadherence (n = 153 [50%]) and missed appointments (n = 119 [39%]). Although participants agreed it is their job to decrease patient stress (n = 292 [96%]) and perform PMTS assessments (n = 268 [88%]), few practiced PMTS-focused trauma informed care. Systems-level barriers to practice included insufficient training, absent clinical workflows, and lack of access to mental health experts. CONCLUSIONS: Our findings have helped inform a conceptual framework for understanding the relationship between PMTS and health outcomes. Systems-level opportunities to optimize PMTS-focused trauma-informed care include (1) dissemination of provider training, (2) integrated workflows for PMTS mitigation, and (3) enhanced accessibility to mental health providers. Further work is required to determine if these interventions can improve health outcomes in patients with pediatric-onset chronic illnesses.

Development of Multifunctional Nanoencapsulated trans-Resveratrol/Chitosan Nutraceutical Edible Coating for Strawberry Preservation.

Phytochemical nanoencapsulation for nutrient delivery and edible coatings for perishable food preservation are two emerging technologies. Leveraging the strong antimicrobial function of phytochemical nutrients, we propose convergent research to integrate the two technologies by embedding phytochemical-encapsulated nanoparticles in an edible coating on fresh fruits to achieve multiple functions. In particular, we report the study of an edible coating on strawberries that is composited of trans-resveratrol (R)-encapsulated nanoparticles (RNPs) embedded in a chitosan (CS) matrix. The biodegradable and biocompatible RNPs significantly increased the aqueous solubility of R by 150-fold and bioavailability by 3.5-fold after oral administration. Our results demonstrated the abilities of the RNP-embedded CS edible coating to diminish dehydration, prevent nutrient loss, inhibit microbe growth, increase nutraceutical value, preserve strawberry quality, and extend shelf life during storage at both 22 and 4 °C. Such a phytochemical nanoencapsulation-based edible coating is promising for the dual purposes of enhancing nutrient delivery and preserving perishable foods.

Essential oils of the ginger plants Meistera caudata and Conamomum vietnamense: chemical compositions, antimicrobial, and mosquito larvicidal activities.

The current study describes the chemical identification, antimicrobial, and mosquito larvicidal activities of essential oils from Meistera caudata and Conamomum vietnamense, growing in Vietnam. Essential oils were extracted from the leaves and rhizomes, and characterized by the GC-FID/MS (gas chromatography-flame ionization detection/mass spectrometry) analysis. Monoterpenes (33.1-89.2 %) were the main chemical class found in these oils. ß-Pinene (30.8 %) and α-pinene (23.8 %) were two major compounds in M. caudata leaf oil. C. vietnamense leaf and rhizome essential oils were dominated by 1,8-cineole (47.9-62.0 %) and limonene (10.3-16.2 %). With the same MIC (minimum inhibitory concentration) value of 25 µg/mL, C. vietnamense leaf and rhizome essential oils strongly inhibited the growth of Gram-positive bacteria Staphylococcus aureus ATCC 29213 and Bacillus subtilis ATCC 6501, respectively. For 24 and 48-h treatments, C. vietnamense leaf essential oil strongly controlled the growth of mosquito Aedes aegypti with the respective LC50 values of 7.67 and 6.73 µg/mL, and the respective LC90 values of 13.37 and 10.83 µg/mL. In the same manner, C. vietnamense rhizome essential oil also showed strong mosquito larvicidal activity against Aedes albopictus with the LC50 values of 12.37 and 12.00 µg/mL, and the LC90 values of 20.56 and 18.58 µg/mL, respectively. C. vietnamense essential essential oils containing a high amount of 1,8-cineole are generally better than M. caudata essential essential oils in both two biological assays.

Improvement of Nutrient Uptake, Yield of Black Sesame (Sesamum indicum L.), and Alluvial Soil Fertility in Dyke by Spent Rice Straw from Mushroom Cultivation as Biofertilizer Containing Potent Strains of Rhodopseudomonas palustris.

The aim of the current research was to evaluate the effects of members of purple nonsulfur bacteria (PNSB), Rhodopseudomonas palustris strains of VNW02, TLS06, VNW64, and VNS89, mixed with spent rice straw (SRS) from mushroom cultivation as a carrier on promoting sesame growth and yield, and ameliorating the alluvial soil (AS) fertility in dykes. A 4 × 3 factorial experiment consisting of different levels of the solid PNSB biofertilizer mixture at 0, 3, 4, and 5 t·ha-1 (0, 1.81 × 108, 2.24 × 108, and 2.68 × 108 cells pot-1, respectively), and nitrogen (N) and phosphorus (P) inorganic fertilizer rates (100, 75, and 50 kg·N·ha-1; 60, 45, and 30 kg P2O5·ha-1, respectively) was performed in pots with the sesame variety of ADB1 in the dyked AS. The solid PNSB biofertilizer mixture at at least 3 t·ha-1 significantly enhanced the sesame seed yield by providing higher macronutrients for plants by increasing available N and soluble P concentrations in the soil. The solid PNSB biofertilizer mixture in addition to 75% of the recommended N and P fertilizers produced an equivalent yield in comparison to the utilized 100% of N and P inorganic fertilizers. The solid PNSB biofertilizer mixture in the SRS from the mushroom production reduced at least 25% of N and P chemical fertilizers for gaining the maximal seed yield and enriched soil characteristics for the sustainable black sesame cultivation in the dyked AS.

Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes.

Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but the precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

A qualitative study of people who use methamphetamine during the early COVID-19 pandemic to inform future ED harm reduction strategies.

BACKGROUND: Morbidity and mortality rates related to methamphetamine are on the rise. Simultaneously, social-distancing guidelines were issued in March 2020 to decrease transmission of COVID-19. The aim of this study was to explore concerns regarding methamphetamine use during the COVID-19 pandemic and subsequent harm reduction strategies with patients who use methamphetamine to inform emergency department (ED)-based harm reduction approaches. METHODS: A mixed-methods study of adults residing in Washington with high-risk methamphetamine use and a recent ED visit from April-September 2020 was performed. Participants completed a survey and a semi-structured interview on perceptions and experiences of COVID-19. Descriptive statistics were used for survey responses. Interview transcripts were analyzed and guided by modified grounded theory using an iterative approach to refine the guide and codebook. Interviews were independently coded by 2 investigators and discussed until consensus. RESULTS: Twenty-five participants completed the survey; 20 participants were interviewed (45% recently used heroin, 40% unstably housed). Thirty-five percent was worried about COVID-19 infection. Three themes emerged from the interviews: (1) increase in meth use, (2) interplay of meth obtention and COVID-19, and (3) interactions with healthcare and social services. CONCLUSIONS: People who use methamphetamine noted an increase in use along with the social distancing guidelines put in place for COVID-19 and employed a variety of harm reduction profiles when obtaining methamphetamine. Also, the pandemic brought difficulties in accessing care and amplified mistrust in healthcare instructions and public health messages. Based on these qualitative interviews, further work should consider aligning methamphetamine and COVID-19 harm reduction messages and working with trusted community resources to improve harm reduction strategies for methamphetamine use and COVID-19. IRB: Informed Consent by the University of Washington Human Subjects Division (approval number, STUDY00009277).

"That Line Just Kept Moving": Motivations and Experiences of People Who Use Methamphetamine.

INTRODUCTION: Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency clinicians describe methamphetamine use as a significant problem with high resource utilization and violence against staff, but little is known about the patient's perspective. In this study our objective was to identify the motivations for initiation and continued methamphetamine use among people who use methamphetamine and their experiences in the ED to guide future ED-based approaches. METHODS: This was a qualitative study of adults residing in the state of Washington in 2020, who used methamphetamine in the prior 30 days, met criteria for moderate- to high-risk use, reported recently receiving care in the ED, and had phone access. Twenty individuals were recruited to complete a brief survey and semi-structured interview, which was recorded and transcribed prior to being coded. Modified grounded theory guided the analysis, and the interview guide and codebook were iteratively refined. Three investigators coded the interviews until consensus was reached. Data was collected until thematic saturation. RESULTS: Participants described a shifting line that separates the positive attributes from the negative consequences of using methamphetamine. Many initially used methamphetamine to enhance social interactions, combat boredom, and escape difficult circumstances by numbing the senses. However, continued use regularly led to isolation, ED visits for the medical and psychological sequelae of methamphetamine use, and engagement in increasingly risky behaviors. Because of their overwhelmingly frustrating experiences in the past, interviewees anticipated difficult interactions with healthcare clinicians, leading to combativeness in the ED, avoidance of the ED at all costs, and downstream medical complications. Participants desired a non-judgmental conversation and linkage to outpatient social resources and addiction treatment. CONCLUSION: Methamphetamine use can lead patients to seek care in the ED, where they often feel stigmatized and are provided little assistance. Emergency clinicians should acknowledge addiction as a chronic condition, address acute medical and psychiatric symptoms adequately, and provide positive connections to addiction and medical resources. Future work should incorporate the perspectives of people who use methamphetamine into ED-based programs and interventions.

Medical traumatic stress in cystic fibrosis: A qualitative analysis.

BACKGROUND: People living with cystic fibrosis (PwCF) face a lifetime of potentially traumatic illness-related experiences that can lead to posttraumatic stress symptoms. Existing criteria for this type of posttraumatic stress, called medical traumatic stress (MTS), may not fully capture the CF experience. In this study we aimed to explore: 1) illness-related experiences perceived as traumatic in the setting of CF, 2) perceived MTS symptoms in PwCF, and 3) perceived health-related functional impairments from MTS. METHODS: Informed by our aims, we developed and piloted guides for semi-structured interviews and focus groups with PwCF, family members of PwCF, and CF medical providers. We then conducted a series of interviews and focus groups. The qualitative analytical process followed Deterding and Waters' three stages of flexible coding for in-depth interviews, generating key themes and sub-themes in each domain of study inquiry. RESULTS: We recruited 51 participants, including 24 PwCF, 7 family members of PwCF, and 20 CF care team members. Illness-related experiences perceived as traumatic were often characterized by themes of loss of agency, threats of bodily harm, and shifts in identity. Prominent MTS symptoms included shame, survivor guilt, burden guilt, germaphobia, and symptom panic. Health-related themes of functional impairments perceived to result from MTS included poor adherence and strained relationships between providers and patients/families. CONCLUSIONS: This is the first study to explore the specific experiences of MTS in PwCF. It highlights the need for screening that includes these specific exposure types and symptoms, which may be mitigatable with medical trauma-focused interventions.

Determinants of lung function across childhood in the Severe Asthma Research Program (SARP) 3.

BACKGROUND: Children with asthma are at risk for low lung function extending into adulthood, but understanding of clinical predictors is incomplete. OBJECTIVE: We sought to determine phenotypic factors associated with FEV1 throughout childhood in the Severe Asthma Research Program 3 pediatric cohort. METHODS: Lung function was measured at baseline and annually. Multivariate linear mixed-effects models were constructed to assess the effect of baseline and time-varying predictors of prebronchodilator FEV1 at each assessment for up to 6 years. All models were adjusted for age, predicted FEV1 by Global Lung Function Initiative reference equations, race, sex, and height. Secondary outcomes included postbronchodilator FEV1 and prebronchodilator FEV1/forced vital capacity. RESULTS: A total of 862 spirometry assessments were performed for 188 participants. Factors associated with FEV1 include baseline Feno (B, -49 mL/log2 PPB; 95% CI, -92 to -6), response to a characterizing dose of triamcinolone acetonide (B, -8.4 mL/1% change FEV1 posttriamcinolone; 95% CI, -12.3 to -4.5), and maximal bronchodilator reversibility (B, -27 mL/1% change postbronchodilator FEV1; 95% CI, -37 to -16). Annually assessed time-varying factors of age, obesity, and exacerbation frequency predicted FEV1 over time. Notably, there was a significant age and sex interaction. Among girls, there was no exacerbation effect. For boys, however, moderate (1-2) exacerbation frequency in the previous 12 months was associated with -20 mL (95% CI, -39 to -2) FEV1 at each successive year. High exacerbation frequency (≥3) 12 to 24 months before assessment was associated with -34 mL (95% CI, -61 to -7) FEV1 at each successive year. CONCLUSIONS: In children with severe and nonsevere asthma, several clinically relevant factors predict FEV1 over time. Boys with recurrent exacerbations are at high risk of lower FEV1 through childhood.

Plant-derived nanovesicles: Current understanding and applications for cancer therapy.

Plant-derived vesicles (PDVs) are membranous structures that originate from plant cells and are responsible for multiple physiological and pathological functions. In the last decade, PDVs have gained much attention for their involvement in different biological processes, including intercellular communication and defense response, and recent scientific evidence has opened a new avenue for their applications in cancer treatment. Nevertheless, much remains unknown about these vesicles, and current research remains inconsistent. This review aims to provide a comprehensive introduction to PDVs, from their biological characteristics to purification methods, and to summarize the status of their potential development for cancer therapy.

Changes in the Use of Invasive and Noninvasive Mechanical Ventilation in Pediatric Asthma: 2009-2019.

Rationale: Despite lower overall hospitalization rates for asthma in recent years, there has been an increase in the number of pediatric patients receiving intensive care management in the United States. Objectives: To investigate how the use of invasive and noninvasive mechanical ventilation for asthma has changed in the context of an evolving cohort of critically ill pediatric patients with asthma. Methods: We analyzed children admitted to intensive care units for asthma from 2009 through 2019 in the Virtual Pediatric Systems database. Regression analyses were used to evaluate how respiratory support interventions, mortality, and patient characteristics have changed over time. Odds ratios were calculated to determine how patient characteristics were associated with respiratory support needs. Stratified analyses were performed to determine how changing practice patterns may have differed between patient subgroups. Results: There were 67,614 admissions for 56,727 patients analyzed. Intubation occurred in 4.6% of admissions and decreased from 6.9% to 3.4% over time (P < 0.001), whereas noninvasive ventilation as the maximal respiratory support increased from 8.9% to 20.0% (P < 0.001). Over time, the cohort shifted to include more 2- to 6-year-olds and patients of Asian/Pacific Islander or Hispanic race/ethnicity. Although intubation decreased and noninvasive ventilation increased in all subgroups, the changes were most pronounced in the youngest patients and slightly less pronounced for obese patients. Conclusions: In pediatric asthma, use of intubation has halved, whereas use of noninvasive ventilation has more than doubled. This change in practice appears partially related to a younger patient cohort, although other factors merit exploration.