Vitamin C Supplementation Among Pregnant Smokers and Airway Function Trajectory in Offspring: A Secondary Analysis of a Randomized Clinical Trial.

This secondary analysis of a randomized clinical trial analyzes the association of vitamin C supplementation in women who smoked during pregnancy with airway function trajectory in their offspring at 4 to 6 years of age.

A Matched Comparative Analysis of Type-2 Diabetes Mellitus Remission Between Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

OBJECTIVE: Multiple scores validate long-term type-2 diabetes mellitus (T2DM) remission after metabolic and bariatric surgery (MBS). However, studies comparing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) have not adequately controlled for certain parameters, which may influence procedure selection. METHODS: We conducted a multicenter retrospective review of patients with T2DM who underwent RYGB or SG between 2008 and 2017. Data on demographics, clinical, laboratory, and metabolic values were collected annually for up to 14 years. Each eligible RYGB patient was individually matched to an eligible SG patient based on diabetes severity, weight loss, and follow-up duration. RESULTS: Among 1149 T2DM patients, 467 were eligible for matching. We found 97 matched pairs who underwent RYGB or SG. RYGB showed significantly higher T2DM remission rates (46.4%) compared to SG (33.0%) after matching. SG patients had higher insulin usage (35.1%) than RYGB patients (20.6%). RYGB patients also experienced greater decreases in HbA1c levels and diabetes medication usage than SG patients. CONCLUSIONS: RYGB demonstrates higher efficacy for T2DM remission compared to SG, regardless of baseline characteristics, T2DM severity, weight loss, and follow-up duration. Further studies are needed to understand the long-term metabolic effects of MBS and the underlying pathophysiology of T2DM remission after MBS.

Type 2 diabetes remission after Roux-en-Y gastric bypass: a multicentered experience with long-term follow-up.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is associated with short- and mid-term type 2 diabetes (T2D) remission. Long-term outcomes and predictive parameters associated with remission following RYGB have not been well elucidated. OBJECTIVE: Determining the overall long-term T2D remission rates following RYGB and identifying predictive variables associated with remission. SETTING: Multicentered study including patients who underwent RYGB at 3 tertiary referral centers for bariatric surgery. METHODS: We performed a retrospective cohort study between 2008-2017 to allow a minimum of 5 years of follow-up. We evaluated long-term T2D remission rates and annual T2D clinical and metabolic parameters up to 14 years after surgery. Predictors of remission were assessed using multivariate logistic regression. Patients were divided into 4 groups based on quartiles of total body weight loss percentage (%TBWL) to compare remission rates between groups. RESULTS: A total of 815 patients were included (68.9% female, age 52.1 ± 11.5 yr; body mass index 45.1 ± 7.7 kg/m2) with a follow-up of 7.3 ± 3.8 years. Remission was demonstrated in 51% of patients. Predictors of remission included pre-operative duration of diabetes, baseline HbA1C, insulin use prior to surgery, number of antidiabetic medications and %TBWL (all P < .01). Remission rates were proportionally associated with %TBWL quartile (Q1, 40.9%; Q2, 52.7%; Q3, 53.1%; Q4, 56.1%) (P = .02). CONCLUSIONS: Longer duration and higher severity of T2D were negatively associated with remission while higher %TBWL had a positive association. A significant proportion of patients in all quartiles experienced long-term remission after RYGB with a greater likelihood of remission correlated with greater weight loss.

Reconstruction of Noma Sequelae: A Surgical Treatment Algorithm Developed from Lessons from 210 Cases in Ethiopia.

Noma is an infectious disease affecting mostly children aged 0-10. Although it has almost completely disappeared from the Western world, it is still prevalent in many developing regions, mainly Africa's Sahel region. The infection behaves like a necrotizing fasciitis of the face, originating from the gums and progressively expanding into the cheek, nose, or eye regions. In an estimated 90% of cases, the disease is lethal as a result of systemic sepsis. For survivors, typical results are extensive defects of the cheek, nose, and periorbital and perioral regions. Due to the defects, extensive scarring is common, which leads to secondary problems such as growth alterations in an infant's skeleton due to inhibition and restraint of growth resulting typically in cicatricial skeletal hypoplasia. Other sequelae include trismus, partially caused by scarring or complete fusion between maxilla/zygomatic arch and mandible. The resulting overall disfiguring facial appearance results in patients being disabled and socially isolated. Methods: Facing Africa is a UK-based non-governmental organization that treats the secondary problems of Ethiopian noma survivors. Operations are performed in Addis Ababa by a visiting expert team. Postoperatively, patients are seen annually for years after the surgery. Results: This article discusses basic principles, goals, and a practical surgical algorithm for operating on lip, cheek, and oral defects, based on 210 noma patients who were operated on in Ethiopia over a period of 11 years. Conclusions: The suggested algorithm has proven to work for the Facing Africa team members and is considered shareware for all surgeons to use and benefit from.

Neighborhood environmental vulnerability and pediatric asthma morbidity in US metropolitan areas.

BACKGROUND: Research suggests demographic, economic, residential, and health-related factors influence vulnerability to environmental exposures. Greater environmental vulnerability may exacerbate environmentally related health outcomes. We developed a neighborhood environmental vulnerability index (NEVI) to operationalize environmental vulnerability on a neighborhood level. OBJECTIVE: We explored the relationship between NEVI and pediatric asthma emergency department (ED) visits (2014-19) in 3 US metropolitan areas: Los Angeles County, Calif; Fulton County, Ga; and New York City, NY. METHODS: We performed separate linear regression analyses examining the association between overall NEVI score and domain-specific NEVI scores (demographic, economic, residential, health status) with pediatric asthma ED visits (per 10,000) across each area. RESULTS: Linear regression analyses suggest that higher overall and domain-specific NEVI scores were associated with higher annual pediatric asthma ED visits. Adjusted R2 values suggest that overall NEVI scores explained at least 40% of the variance in pediatric asthma ED visits. Overall NEVI scores explained more of the variance in pediatric asthma ED visits in Fulton County. NEVI scores for the demographic, economic, and health status domains explained more of the variance in pediatric asthma ED visits in each area compared to the NEVI score for the residential domain. CONCLUSION: Greater neighborhood environmental vulnerability was associated with greater pediatric asthma ED visits in each area. The relationship differed in effect size and variance explained across the areas. Future studies can use NEVI to identify populations in need of greater resources to mitigate the severity of environmentally related outcomes, such as pediatric asthma.

Effect of Vitamin C Supplementation for Pregnant Smokers on Offspring Airway Function and Wheeze at Age 5 Years: Follow-up of a Randomized Clinical Trial.

Importance: Vitamin C supplementation (500 mg/d) for pregnant smokers has been reported to increase offspring airway function as measured by forced expiratory flow (FEF) through age 12 months; however, its effects on airway function at age 5 years remain to be assessed. Objective: To assess whether vitamin C supplementation in pregnant smokers is associated with increased and/or improved airway function in their offspring at age 5 years and whether vitamin C decreases the occurrence of wheeze. Design, Setting, and Participants: This study followed up the Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) double-blind, placebo-controlled randomized clinical trial conducted at 3 centers in the US (in Oregon, Washington, and Indiana) between 2012 and 2016. Investigators and participants remain unaware of the treatment assignments. Forced expiratory flow measurements at age 5 years were completed from 2018 to 2021. Interventions: Pregnant smokers were randomized to vitamin C (500 mg/d) or placebo treatment. Main Outcomes and Measures: The primary outcome was the prespecified measurement of FEF between 25% and 75% expired volume (FEF25-75) by spirometry at age 5 years. Secondary outcomes included FEF measurements at 50% and 75% of expiration (FEF50 and FEF75), forced expiratory volume in 1 second (FEV1), and occurrence of wheeze. Results: Of the 251 pregnant smokers included in this study, 125 (49.8%) were randomized to vitamin C and 126 (50.2%) were randomized to placebo. Of 213 children from the VCSIP trial who were reconsented into this follow-up study, 192 (90.1%) had successful FEF measurements at age 5 years; 212 (99.5%) were included in the analysis of wheeze. Analysis of covariance demonstrated that offspring of pregnant smokers allocated to vitamin C compared with placebo had 17.2% significantly higher mean (SE) measurements of FEF25-75 at age 5 years (1.45 [0.04] vs 1.24 [0.04] L/s; adjusted mean difference, 0.21 [95% CI, 0.13-0.30]; P < .001). Mean (SE) measurements were also significantly increased by 14.1% for FEF50 (1.59 [0.04] vs 1.39 [0.04] L/s; adjusted mean difference, 0.20 [95% CI, 0.11-0.30]; P < .001), 25.9% for FEF75 (0.79 [0.02] vs 0.63 [0.02] L/s; 0.16 [95% CI, 0.11-0.22]; P < .001), and 4.4% for FEV1 (1.13 [0.02] vs 1.09 [0.02] L; 0.05 [95% CI, 0.01-0.09]; P = .02). In addition, offspring of pregnant smokers randomized to vitamin C had significantly decreased wheeze (28.3% vs 47.2%; estimated odds ratio, 0.41 [95% CI, 0.23-0.74]; P = .003). Conclusions and Relevance: In this follow-up study of offspring of pregnant smokers randomized to vitamin C vs placebo, vitamin C supplementation during pregnancy resulted in significantly increased airway function of offspring at age 5 years and significantly decreased the occurrence of wheeze. These findings suggest that vitamin C supplementation for pregnant smokers may decrease the effects of smoking in pregnancy on childhood airway function and respiratory health. Trial Registration: ClinicalTrials.gov Identifier: NCT03203603.

Engineering Lipid Nanoparticles for Enhanced Intracellular Delivery of mRNA through Inhalation.

Despite lipid nanoparticles' (LNPs) success in the effective and safe delivery of mRNA vaccines, an inhalation-based mRNA therapy for lung diseases remains challenging. LNPs tend to disintegrate due to shear stress during aerosolization, leading to ineffective delivery. Therefore, LNPs need to remain stable through the process of nebulization and mucus penetration, yet labile enough for endosomal escape. To meet these opposing needs, we utilized PEG lipid to enhance the surficial stability of LNPs with the inclusion of a cholesterol analog, ß-sitosterol, to improve endosomal escape. Increased PEG concentrations in LNPs enhanced the shear resistance and mucus penetration, while ß-sitosterol provided LNPs with a polyhedral shape, facilitating endosomal escape. The optimized LNPs exhibited a uniform particle distribution, a polyhedral morphology, and a rapid mucosal diffusion with enhanced gene transfection. Inhaled LNPs led to localized protein production in the mouse lung without pulmonary or systemic toxicity. Repeated administration of these LNPs led to sustained protein production in the lungs. Lastly, mRNA encoding the cystic fibrosis transmembrane conductance regulator (CFTR) was delivered after nebulization to a CFTR-deficient animal model, resulting in the pulmonary expression of this therapeutic protein. This study demonstrated the rational design approach for clinical translation of inhalable LNP-based mRNA therapies.

Study Protocol: Interactive Dynamics of Coral Reef Fisheries and the Nutrition Transition in Kiribati.

The Kiribati 2019 Integrated Household Income and Expenditure Survey (Integrated HIES) embeds novel ecological and human health research into an ongoing social and economic survey infrastructure implemented by the Pacific Community in partnership with national governments. This study seeks to describe the health status of a large, nationally representative sample of a geographically and socially diverse I-Kiribati population through multiple clinical measurements and detailed socio-economic surveys, while also conducting supporting food systems research on ecological, social, and institutional drivers of change. The specific hypotheses within this research relate to access to seafood and the potential nutritional and health benefits of these foods. We conducted this research in 21 of the 23 inhabited islands of Kiribati, excluding the two inhabited islands-Kanton Islands in the Phoenix Islands group with a population of 41 persons (2020 census) and Banaba Island in the Gilbert Islands group with a population of 333 persons (2020 census)-and focusing exclusively on the remaining islands in the Gilbert and Line Islands groups. Within this sample, we focused our intensive human health and ecological research in 10 of the 21 selected islands to examine the relationship between ecological conditions, resource governance, food system dynamics, and dietary patterns. Ultimately, this research has created a baseline for future Integrated HIES assessments to simultaneously monitor change in ecological, social, economic, and human health conditions and how they co-vary over time.

Functional evaluation of the cystic fibrosis transmembrane conductance regulator in the endocervix†.

The cystic fibrosis transmembrane conductance regulator (CFTR) is an apical membrane chloride/bicarbonate ion channel in epithelial cells. Mutations in CFTR cause cystic fibrosis, a disease characterized by thickened mucus secretions and is associated with subfertility and infertility. CFTR function has been well characterized in vitro and in vivo in airway and other epithelia studies. However, little is known about CFTR function in the cervix in health and its contribution to cyclic regulation of fertility from endocervical mucus changes. Contributing to this research gap is the lack of information on the effect of sex steroid hormones on CFTR expression in cervical epithelial cells across the menstrual cycle. Herein, we demonstrate the hormonal regulation of CFTR expression in endocervical cells both in vitro and in vivo, and that conditionally reprogrammed endocervical epithelial cells can be used to interrogate CFTR ion channel function. CFTR activity was demonstrated in vitro using electrophysiological methods and functionally inhibited by the CFTR-specific inhibitors inh-172 and GlyH-101. We also report that CFTR expression is increased by estradiol in the macaque cervix both in vitro and in vivo in Rhesus macaques treated with artificial menstrual cycles. Estrogen upregulation of CFTR is blocked in vivo by cotreatment with progesterone. Our findings provide the most comprehensive evidence to date that steroid hormones drive changes in CFTR expression. These data are integral to understanding the role of CFTR as a fertility regulator in the endocervix.

Rights and representation support justice across aquatic food systems.

Injustices are prevalent in food systems, where the accumulation of vast wealth is possible for a few, yet one in ten people remain hungry. Here, for 194 countries we combine aquatic food production, distribution and consumption data with corresponding national policy documents and, drawing on theories of social justice, explore whether barriers to participation explain unequal distributions of benefits. Using Bayesian models, we find economic and political barriers are associated with lower wealth-based benefits; countries produce and consume less when wealth, formal education and voice and accountability are lacking. In contrast, social barriers are associated with lower welfare-based benefits; aquatic foods are less affordable where gender inequality is greater. Our analyses of policy documents reveal a frequent failure to address political and gender-based barriers. However, policies linked to more just food system outcomes centre principles of human rights, specify inclusive decision-making processes and identify and challenge drivers of injustice.

Environmental performance of blue foods.

Fish and other aquatic foods (blue foods) present an opportunity for more sustainable diets1,2. Yet comprehensive comparison has been limited due to sparse inclusion of blue foods in environmental impact studies3,4 relative to the vast diversity of production5. Here we provide standardized estimates of greenhouse gas, nitrogen, phosphorus, freshwater and land stressors for species groups covering nearly three quarters of global production. We find that across all blue foods, farmed bivalves and seaweeds generate the lowest stressors. Capture fisheries predominantly generate greenhouse gas emissions, with small pelagic fishes generating lower emissions than all fed aquaculture, but flatfish and crustaceans generating the highest. Among farmed finfish and crustaceans, silver and bighead carps have the lowest greenhouse gas, nitrogen and phosphorus emissions, but highest water use, while farmed salmon and trout use the least land and water. Finally, we model intervention scenarios and find improving feed conversion ratios reduces stressors across all fed groups, increasing fish yield reduces land and water use by up to half, and optimizing gears reduces capture fishery emissions by more than half for some groups. Collectively, our analysis identifies high-performing blue foods, highlights opportunities to improve environmental performance, advances data-poor environmental assessments, and informs sustainable diets.

Barrett's Oesophagus and Bariatric/Metabolic Surgery-IFSO 2020 Position Statement.

The International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) has been playing an integral role in educating both the metabolic surgical and the medical community at large about the importance of surgical and/or endoscopic interventions in treating adiposity-based chronic diseases. The occurrence of chronic conditions following bariatric/metabolic surgery (BMS), such as gastro-oesophageal reflux disease (GERD) and columnar (intestinal) epithelial metaplasia of the distal oesophagus (also known as Barrett's oesophagus (BE)), has long been discussed in the metabolic surgical and medical community. Equally, the risk of neoplastic progression of Barrett's oesophagus to oesophageal adenocarcinoma (EAC) and the resulting requirement for surgery are the source of some concern for many involved in the care of these patients, as the surgical alteration of the gastrointestinal tract may lead to impaired reconstructive options. As such, there is a requirement for guidance of the community.The IFSO commissioned a task force to elucidate three aspects of the presenting problem: First, to determine what the estimated incidence of Barrett's oesophagus is in patients presenting for BMS; second, to determine the frequency at which Barrett's oesophagus may develop following BMS (with a particular focus on the laparoscopic sleeve gastrectomy (LSG)); and third, to determine if regression of Barrett's oesophagus may occur following BMS given the close relationship of obesity and the development of BE/EAC. Based on these findings, a position statement regarding the management of this pathology in the context of BMS was developed. The following position statement is issued by the IFSO Barrett's Oesophagus task force andapproved by the IFSO Scientific Committee and Executive Board. This statement is based on current clinical knowledge, expert opinion and published peer-reviewed scientific evidence. It will be reviewed regularly.

Evaluation of rescue oral glucocorticoid therapy during inpatient cystic fibrosis exacerbations.

An acute pulmonary exacerbation (APE) in cystic fibrosis (CF) is characterized by increased pulmonary symptoms attributed to bacterial colonization, neutrophil recruitment, and inflammation. Antimicrobials, airway clearance, and nutrition are the mainstay of therapy. However, when patients fail to improve, corticosteroids have been added to therapy. We retrospectively examined the use of rescue steroids in a children's hospital from 2013 to 2017 during CF APE treatment following at least 1 week of inpatient therapy without expected clinical improvement. In total, 106 encounters of 53 unique patients, aged 6-20 years, who had FEV1 percent predicted (FEV1pp) data at baseline, admission, midpoint, and discharge, and had admission duration of at least 12 days were studied. Encounters treated with steroids had less improvement at midpoint percent change from admission in FEV1pp (4.9 ± 11.3) than nonsteroid group change in FEV1pp (20.1 ± 24.6; p < .001). Failure to improve as expected was the rationale for steroid use. At discharge, there was no difference in mean FEV1pp (p = .76). Delays in steroid therapy by waiting until the end of the second week increased the total length of stay (LOS). Propensity matching, comparing outcomes in patients without midpoint improvement in FEV1pp, was also evaluated. There was no difference in admission or discharge FEV1pp between groups. Equally, no difference in FEV1pp at follow-up visit or in time until the next APE was detected. Secondary analysis for associations including gender, genotype, fungal colonization, or inhaled antimicrobials was nonsignificant. These data suggest rescue use of corticosteroids during APE does not predictably impact important outcome measures during CF APE treatment.

Engineered mutant α-ENaC subunit mRNA delivered by lipid nanoparticles reduces amiloride currents in cystic fibrosis-based cell and mice models.

Cystic fibrosis (CF) results from mutations in the chloride-conducting CF transmembrane conductance regulator (CFTR) gene. Airway dehydration and impaired mucociliary clearance in CF is proposed to result in tonic epithelial sodium channel (ENaC) activity, which drives amiloride-sensitive electrogenic sodium absorption. Decreasing sodium absorption by inhibiting ENaC can reverse airway surface liquid dehydration. Here, we inhibit endogenous heterotrimeric ENaC channels by introducing inactivating mutant ENaC α mRNA (αmutENaC). Lipid nanoparticles carrying αmutENaC were transfected in CF-based airway cells in vitro and in vivo. We observed a significant decrease in macroscopic as well as amiloride-sensitive ENaC currents and an increase in airway surface liquid height in CF airway cells. Similarly, intranasal transfection of αmutENaC mRNA decreased amiloride-sensitive nasal potential difference in CFTRKO mice. These data suggest that mRNA-based ENaC inhibition is a powerful strategy for reducing mucus dehydration and has therapeutic potential for treating CF in all patients, independent of genotype.

In Vitro Efficacy for Chlorpyrifos Degradation by Novel Isolate Tistrella sp. AUC10 Isolated from Chlorpyrifos Contaminated Field.

Chlorpyrifos, an organophosphate (OP) pesticide, possess broad-spectrum insecticidal activity against Lepidoptera, Diptera, Homoptera, Coleoptera, Orthoptera, Hymenoptera, and Hemiptera. Organophosphate pesticides have acute neurotoxicity because they suppress acetylcholine esterase (AChE) which regulates the enzyme of neurotransmitters by reducing acetylcholine concentration at synaptic junctions. On exposure to OP, AChE is inactivated and leads to accumulation of acetylcholine in the junction. Moreover, due to their persistence nature they biomagnify at different food chain levels. In the present study, a newly isolated indigenous bacterial strain Tistrella sp. AUC10 was exploited for its ability to degrade chlorpyrifos pesticide. The isolate completely degrades (99.86%) chlorpyrifos. The degraded metabolites of chlorpyrifos by Tistrella sp. AUC10 were identified by GC-MS analysis. Based on the GC-MS analysis, a putative pathway of degradation of chlorpyrifos by Tistrella sp. AUC10 has been proposed. It emulsified various hydrocarbons and also confirms biosurfactant production on CTAB agar. This study is the first report on elucidation of the mechanism of degradation of chlorpyrifos by Tistrella sp. Furthermore, phytotoxicity studies of the parent compound and the biodegraded chlorpyrifos products revealed drastic reduction in the toxicity of metabolites as compared to the parent chlorpyrifos. This implies that the biodegraded metabolites of chlorpyrifos are of non-toxic nature. This study thus indicates the efficacy of Tistrella sp. AUC10 for the treatment of chlorpyrifos contaminated agricultural fields.

The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial.

OBJECTIVE: To compare changes in lung volumes, as measured by functional residual capacity (FRC), through to discharge in stable infants randomized to 2 weeks of extended continuous positive airway pressure CPAP (eCPAP) vs CPAP discontinuation (dCPAP). STUDY DESIGN: Infants born at ≤32 weeks of gestation requiring ≥24 hours of CPAP were randomized to 2 weeks of eCPAP vs dCPAP when meeting CPAP stability criteria. FRC was measured with the nitrogen washout technique. Infants were stratified by gestational age (<28 and ≥ 28 weeks) and twin gestation. A linear mixed-effects model was used to evaluate the change in FRC between the 2 groups. Data were analyzed blinded to treatment group allocation. RESULTS: Fifty infants were randomized with 6 excluded, for a total of 44 infants. Baseline characteristics were similar in the 2 groups. The infants randomized to eCPAP vs dCPAP had a greater increase in FRC from randomization through 2 weeks (12.6 mL vs 6.4 mL; adjusted 95% CI, 0.78-13.47; P = .03) and from randomization through discharge (27.2 mL vs 17.1 mL; adjusted 95% CI, 2.61-17.59; P = .01). CONCLUSIONS: Premature infants randomized to eCPAP had a significantly greater increase in FRC through discharge compared with those randomized to dCPAP. An increased change in FRC may lead to improved respiratory health. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02249143.

Duodenal switch in revisional bariatric surgery: conclusions from an expert consensus panel.

BACKGROUND: Duodenal switch (BPD/DS) is gaining popularity as a secondary procedure for inadequate weight loss after an initial operation. OBJECTIVES: We aimed to generate expert consensus points on the appropriate use of BPD/DS in the revisional bariatric surgical setting. SETTING: Data were gathered at an international conference with attendees from a variety of different institutions and settings. METHODS: Sixteen lines of questioning regarding revisional BPD/DS were presented to an expert panel of 29 bariatric surgeons. Current available literature was reviewed extensively for each topic and proposed to the panel before polling. Responses were collected and topics defined as achieving consensus (≥70% agreement) or no consensus (<70% agreement). RESULTS: Consensus was present in 10 of 16 lines of questioning, with several key points most prominent. CONCLUSIONS: As a second-stage procedure, BPD/DS is most appropriate after sleeve gastrectomy (SG) for the treatment of super morbid obesity (96.7% agree) or as a subsequent operation for a reliable patient with insufficient weight loss after SG (88.5%). In a patient with weight regain and reflux and/or enlarged fundus after SG, Roux-en-Y gastric bypass is preferable and BPD/DS should be avoided (90%). BPD/DS should not be used prophylactically in patients with a history of jejunoileal bypass who are otherwise doing well (80.8%). Applicability of BPD/DS is limited by technical difficulty; 86.2% of experts would routinely recommend or consider the procedure if it were more technically feasible after failed bypass. No consensus was found on approaches to revision of BPD/DS for protein malnutrition.

Lipid Nanoparticle-Delivered Chemically Modified mRNA Restores Chloride Secretion in Cystic Fibrosis.

The promise of gene therapy for the treatment of cystic fibrosis has yet to be fully clinically realized despite years of effort toward correcting the underlying genetic defect in the cystic fibrosis transmembrane conductance regulator (CFTR). mRNA therapy via nanoparticle delivery represents a powerful technology for the transfer of genetic material to cells with large, widespread populations, such as airway epithelia. We deployed a clinically relevant lipid-based nanoparticle (LNP) for packaging and delivery of large chemically modified CFTR mRNA (cmCFTR) to patient-derived bronchial epithelial cells, resulting in an increase in membrane-localized CFTR and rescue of its primary function as a chloride channel. Furthermore, nasal application of LNP-cmCFTR restored CFTR-mediated chloride secretion to conductive airway epithelia in CFTR knockout mice for at least 14 days. On day 3 post-transfection, CFTR activity peaked, recovering up to 55% of the net chloride efflux characteristic of healthy mice. This magnitude of response is superior to liposomal CFTR DNA delivery and is comparable with outcomes observed in the currently approved drug ivacaftor. LNP-cmRNA-based systems represent a powerful platform technology for correction of cystic fibrosis and other monogenic disorders.

Cost effectiveness of vitamin c supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma.

OBJECTIVE: To determine the implications of supplemental vitamin C for pregnant tobacco smokers and its effects on the prevalence of pediatric asthma, asthma-related mortality, and associated costs. STUDY DESIGN: A decision-analytic model built via TreeAge compared the outcome of asthma in a theoretical annual cohort of 480,000 children born to pregnant smokers through 18 years of life. Vitamin C supplementation (500 mg/day) with a standard prenatal vitamin was compared to a prenatal vitamin (60 mg/day). Model inputs were derived from the literature. Deterministic and probabilistic sensitivity analyses assessed the impact of assumptions. RESULT: Additional vitamin C during pregnancy would prevent 1637 cases of asthma at the age of 18 per birth cohort of pregnant smokers. Vitamin C would reduce asthma-related childhood deaths and save $31,420,800 in societal costs over 18 years per birth cohort. CONCLUSION: Vitamin C supplementation in pregnant smokers is a safe and inexpensive intervention that may reduce the economic burden of pediatric asthma.