Plasma per- and polyfluoroalkyl substance mixtures during pregnancy and duration of breastfeeding in the New Hampshire birth cohort study.

BACKGROUND: Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse. METHODS: We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010-2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively. RESULTS: PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months. CONCLUSIONS: In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding.

Respiratory Exposure to Highly Fluorinated Chemicals via Application of Ski Wax and Related Health Effects.

PURPOSE: Waxes containing per- and polyfluoroalkyl substances (PFAS) are applied to the base of skis and snowboards ("skis") to reduce friction with the snow surface and improve glide. PFAS exposure can adversely impact cardiometabolic, thyroid, liver, kidney, reproductive, and immune health and are associated with increased risk of certain cancers. In the present review, we summarize the state of the science on PFAS exposure from fluorinated ski wax use, including acute respiratory health effects and PFAS concentrations in biological and environmental media collected from ski waxing settings. RECENT FINDINGS: Perfluoroalkyl carboxylic acid (PFCA) concentrations in serum and air collected from professional wax technicians and the rooms where waxes are applied are among the highest of any occupation investigated to date, including the fluorochemical industry. High airborne concentrations of fluorotelomer alcohols contribute to high body burdens of certain PFCAs among ski waxers. Fluorinated ski waxes are a significant source of PFAS exposure for people waxing skis and/or spending time in areas where waxing occurs. We highlight recommendations for future research, policy, and technologies needed to address PFAS exposures from fluorinated wax use.

Predictors of Breastfeeding Duration in the New Hampshire Birth Cohort Study.

INTRODUCTION: Breastfeeding has significant health benefits for infants and birthing persons, including reduced risk of chronic disease. The American Academy of Pediatrics recommends exclusively breastfeeding infants for 6 months and recently extended its recommendation for continuing to breastfeed with supplementation of solid foods from one to two years. Studies consistently identify lower breastfeeding rates among US infants, with regional and demographic variability. We examined breastfeeding in birthing person-infant pairs among healthy, term pregnancies enrolled in the New Hampshire Birth Cohort Study between 2010 and 2017 (n = 1176). METHODS: Birthing persons 18-45 years old were enrolled during prenatal care visits at ~ 24-28 weeks gestation and have been followed since enrollment. Breastfeeding status was obtained from postpartum questionnaires. Birthing person and infant health and sociodemographic information was abstracted from medical records and prenatal and postpartum questionnaires. We evaluated the effects of birthing person age, education, relationship status, pre-pregnancy body mass index, gestational weight gain (GWG), smoking and parity, and infant sex, ponderal index, gestational age and delivery mode on breastfeeding initiation and duration using modified Poisson and multivariable linear regression. RESULTS: Among healthy, term pregnancies, 96% of infants were breastfed at least once. Only 29% and 28% were exclusively breastfed at 6-months or received any breastmilk at 12-months, respectively. Higher birthing person age, education, and parity, being married, excessive GWG, and older gestational age at delivery were associated with better breastfeeding outcomes. Smoking, obesity, and cesarean delivery were negatively associated with breastfeeding outcomes. CONCLUSIONS: Given the public health importance of breastfeeding for infants and birthing persons, interventions are needed to support birthing persons to extend their breastfeeding duration.

Evaluation of hearing protection device effectiveness for musicians.

OBJECTIVE: To evaluate musicians' personal attenuation and perceptions of three types of hearing protection devices (HPDs): formable foam earplugs and both non-custom and custom versions of uniform attenuation earplugs (UAEs) marketed to musicians. DESIGN: A mixed-methods approach was used to evaluate the HPDs. Audiometric testing obtained hearing levels at baseline and with each HPD across frequencies (125-8000 Hz) to determine personal attenuation ratings and uniformity of attenuation. Participants completed surveys over six months regarding how often they used the HPDs and their perceptions about wearing them. STUDY SAMPLE: Twenty-four musicians were recruited to participate. RESULTS: Substantial variability was observed in the attenuation achieved among participants for each HPD type, but custom UAEs provided the most consistent attenuation across frequencies. Participants' HPD preferences were influenced by multiple factors including personal instrument and specific activity. Custom UAEs were most frequently used but usage rates continually decreased over the 6-month period. CONCLUSIONS: Fit-testing is important to determine fit and sizing. Combining information on the effectiveness of HPDs with musicians' opinions about wearing them can inform recommendations for which types may be the most effective and feasible options for reducing sound exposures.

The impact of coronavirus disease 2019 (COVID-19) response on hospital infection prevention programs and practices in the southeastern United States.

Initial assessments of coronavirus disease 2019 (COVID-19) preparedness revealed resource shortages and variations in infection prevention policies across US hospitals. Our follow-up survey revealed improvement in resource availability, increase in testing capacity, and uniformity in infection prevention policies. Most importantly, the survey highlighted an increase in staffing shortages and use of travel nursing.

Early recognition and response to increases in surgical site infections using optimised statistical process control charts-The early 2RIS trial: A multicentre stepped wedge cluster randomised controlled trial.

Background: Traditional approaches for surgical site infection (SSI) surveillance have deficiencies that delay detection of SSI outbreaks and other clinically important increases in SSI rates. We investigated whether use of optimised statistical process control (SPC) methods and feedback for SSI surveillance would decrease rates of SSI in a network of US community hospitals. Methods: We conducted a stepped wedge cluster randomised trial of patients who underwent any of 13 types of common surgical procedures across 29 community hospitals in the Southeastern United States. We divided the 13 procedures into six clusters; a cluster of procedures at a single hospital was the unit of randomisation and analysis. In total, 105 clusters were randomised to 12 groups of 8-10 clusters. All participating clusters began the trial in a 12-month baseline period of control or "traditional" SSI surveillance, including prospective analysis of SSI rates and consultative support for SSI outbreaks and investigations. Thereafter, a group of clusters transitioned from control to intervention surveillance every three months until all clusters received the intervention. Electronic randomisation by the study statistician determined the sequence by which clusters crossed over from control to intervention surveillance. The intervention was the addition of weekly application of optimised SPC methods and feedback to existing traditional SSI surveillance methods. Epidemiologists were blinded to hospital identity and randomisation status while adjudicating SPC signals of increased SSI rates, but blinding was not possible during SSI investigations. The primary outcome was the overall SSI prevalence rate (PR=SSIs/100 procedures), evaluated via generalised estimating equations with a Poisson regression model. Secondary outcomes compared traditional and optimised SPC signals that identified SSI rate increases, including the number of formal SSI investigations generated and deficiencies identified in best practices for SSI prevention. This trial was registered at ClinicalTrials.gov, NCT03075813. Findings: Between Mar 1, 2016, and Feb 29, 2020, 204,233 unique patients underwent 237,704 surgical procedures. 148,365 procedures received traditional SSI surveillance and feedback alone, and 89,339 procedures additionally received the intervention of optimised SPC surveillance. The primary outcome of SSI was assessed for all procedures performed within participating clusters. SSIs occurred after 1171 procedures assigned control surveillance (prevalence rate [PR] 0.79 per 100 procedures), compared to 781 procedures that received the intervention (PR 0·87 per 100 procedures; model-based PR ratio 1.10, 95% CI 0.94-1.30, p=0.25). Traditional surveillance generated 24 formal SSI investigations that identified 120 SSIs with deficiencies in two or more perioperative best practices for SSI prevention. In comparison, optimised SPC surveillance generated 74 formal investigations that identified 458 SSIs with multiple best practice deficiencies. Interpretation: The addition of optimised SPC methods and feedback to traditional methods for SSI surveillance led to greater detection of important SSI rate increases and best practice deficiencies but did not decrease SSI rates. Additional research is needed to determine how to best utilise SPC methods and feedback to improve adherence to SSI quality measures and prevent SSIs. Funding: Agency for Healthcare Research and Quality.

Waxing activity as a potential source of exposure to per- and polyfluoroalkyl substances (PFAS) and other environmental contaminants among the US ski and snowboard community.

BACKGROUND: Skiers and snowboarders apply waxes and solvents to their equipment to enhance glide across the snow. Waxing results in exposures to per- and polyfluoroalkyl substances (PFAS) and particulate matter, which have been associated with adverse health effects among professional wax technicians in Scandinavia. However, little is known about exposure among people who participate at other levels of sport, including recreationally, in other regions. OBJECTIVE: We sought to characterize wax-related exposures among US skiers and snowboarders who participate across numerous levels of sport to expand scientific understanding of environmental health risks among this population. METHODS: We used an anonymous electronic survey to evaluate wax-related exposures among US cross-country and downhill skiers and snowboarders. Specifically, we assessed (Fang et al., 2020): duration of time involved with each sport in any role (Freberg et al., 2013), intensity of wax-related exposures based on time spent in waxing areas, wax use, and wax type (Rogowski et al., 2007), frequency of fluorinated wax application, and (Freberg et al., 2010) use of exposure interventions. RESULTS: Participants tended to be long-term winter sports enthusiasts (e.g., median downhill skiing duration: 31 years). Nearly all (92%) participants personally applied some wax to their skis/snowboards and most applied waxes containing PFAS (67%) and solvents (62%). Ski professionals waxed the most pairs of skis with fluorinated waxes annually (median (IQR): 20 (1, 100)), though individuals participating recreationally also applied fluorinated waxes regularly. Exposure interventions were not widely used. SIGNIFICANCE: Waxing activities may pose significant risk of exposure to PFAS and other environmental contaminants among the US ski and snowboard community. Efforts are needed to reduce these exposures through changes to wax use patterns and broader adoption of exposure reduction strategies.

The NIOSH Agricultural Centers' YouTube Channel: Time Series Modeling of Viewership of Agricultural Health and Safety Videos.

We sought to understand the mechanism underlying the growth trajectory in the United States Agricultural Safety and Health Centers YouTube channel. We also explored the benefits and limitations of using YouTube analytics to evaluate the impacts of public health interventions involving YouTube. Time series analysis of total views, total watch hours, average duration of watch time, and number of subscribers were assessed to determine the monthly patterns of non-seasonal and seasonal components in the data from 2013 to 2020. Health, safety, and animal handling video views were summarized descriptively across time and season. Lastly, time series regressions were used to determine the type of video that best predicted growth in the channel viewership metrics. The time series were not random but could be explained by autoregressive and moving average correlation structures. Health videos were the strongest predictors of future growth but were not the most watched type of video. Strong seasonality components indicated that videos were most watched during periods of high agricultural activity, but less so during the winter months. Generally, growth in YouTube viewership metrics was explained by past month viewership predicting future viewership. Outreach and media content may produce spikes of increased interest, but in order to sustainably grow the channel over time, Ag Centers and other agricultural stakeholders should continue to focus on the value of particular content to potential viewers, how and when content is released, and strategic promotion of the channel and its videos.

Comparison of Recreational Fish Consumption Advisories Across the USA.

PURPOSE OF REVIEW: Our comparative analysis sought to understand the factors which drive differences in fish consumption advisories across the USA - including exposure scenarios (acute and chronic health risk, non-cancer and cancer health endpoints), toxicity values (reference dose, cancer slope factor, acute tolerance level), and meal size and bodyweight assumptions. RECENT FINDINGS: Fish consumption provides essential nutrients but also results in exposure to contaminants such as PCBs and methylmercury. To protect consumers from the risks of fish contaminants, fish consumption advisories are established, most often by state jurisdictions, to estimate the amount of a certain fish species a person could consume throughout their lifetime without harm. However, inconsistencies in advisories across the USA confuse consumers and undermine the public health goals of fish advisory programs. To date, no rigorous comparison of state and national fish consumption advisories has been reported. Our work identifies discrepancies in key assumptions used to derive risk-based advisories between US states, reflecting differences in the interpretation of toxicity science. We also address the implications for these differences by reviewing advisories issued by contiguous states bordering two waterbodies: Lake Michigan and the Lower Mississippi River. Our findings highlight the importance of regional collaboration when issuing advisories, so that consumers of self-caught fish are equipped with clear knowledge to make decisions to protect their health.

Assessment of occupational personal sound exposures for music instructors.

Daily activities performed by music instructors generate high sound levels that could potentially lead to overexposure. Adverse outcomes associated with high-exposure to sound, such as hearing loss and tinnitus, can be especially devastating to music instructors as hearing is essential to both job performance and career reward. The primary objective of this study was to compare sound exposures of music instructors to recommended exposure limits. Secondary objectives were to identify high-exposure activities and to evaluate potential similar exposure groups by examining between- and within-worker exposure variability. Personal sound exposure measurements from music instructors were collected using dosimeters during full workdays for up to 4 weeks over multiple semesters at a university's school of music. Study participants completed an activity log to record work-related activities throughout each day of sampling. Dosimeters logged 1-sec sound equivalent levels in A-weighted decibels. These data were used to calculate 8-hr time-weighted averages, daily dose, and activity-specific contributions to that dose to determine if daily exposures exceeded the recommended limit of 85 dBA and to identify high-exposure activities that could be targeted for future intervention. Seventeen participants were sampled for a total of 200 days. Approximately one-third of daily exposures exceeded recommended limits. The groups with the highest exposures were brass and conducting instructors. Conductors experienced the highest between-day variability in daily exposures. Activities that contributed the most to daily dose included group rehearsals, personal practice sessions, and performances, while classes and administrative work did not substantially contribute to daily dose. Daily exposures were highly variable, ranging from 60-95 dBA (mean = 81 dBA, sd = 8 dBA), and were influenced by instructional area and musical activity. Future exposure assessments for music instructors should include sampling for multiple days, and those above-recommended limits should be placed into hearing conservation programs.

Assessing severe acute respiratory coronavirus virus 2 (SARS-CoV-2) preparedness in US community hospitals: A forgotten entity.

We performed a cross-sectional survey of infection preventionists in 60 US community hospitals between April 22 and May 8, 2020. Several differences in hospital preparedness for SARS-CoV-2 emerged with respect to personal protective equipment conservation strategies, protocols related to testing, universal masking, and restarting elective procedures.

Endocrine-disrupting chemicals and breastfeeding duration: a review.

PURPOSE OF REVIEW: The purpose of this review is to describe epidemiologic and toxicological literature investigating how endocrine-disrupting chemicals (EDCs) affect mammary gland development and function, thereby impacting lactation duration. RECENT FINDINGS: Perfluoroalkyl and polyfluoroalkyl substances appear to reduce breastfeeding duration through impaired mammary gland development, lactogenesis, and suppressed endocrine signaling. Halogenated aromatic hydrocarbons have differing associations with lactation duration, likely because of the variety of signaling pathways that they affect, pointing to the importance of complex mixtures in epidemiologic studies. Although epidemiologic literature suggests that pesticides and fungicides decrease or have no effect on lactation duration, toxicology literature suggests enhanced mammary gland development through estrogenic and/or antiandrogenic pathways. Toxicological studies suggest that phthalates may affect mammary gland development via estrogenic pathways but no association with lactation duration has been observed. Bisphenol A was associated with decreased duration of breastfeeding, likely through direct and indirect action on estrogenic pathways. SUMMARY: EDCs play a role in mammary gland development, function, and lactogenesis, which can affect breastfeeding duration. Further research should explore direct mechanisms of EDCs on lactation, the significance of toxicant mixtures, and transgenerational effects of EDCs on lactation.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.

BACKGROUND: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. METHODS: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. RESULTS: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (ß = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (ß = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (ß = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (ß = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (ß = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (ß = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (ß = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (ß = 0.14 mm, 95%CI = 0.002, 0.28). CONCLUSIONS: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Human health risks due to airborne polychlorinated biphenyls are highest in New Bedford Harbor communities living closest to the harbor.

In response to concerns raised by communities surrounding the New Bedford Harbor Superfund site, we completed a field and modeling study that concluded the harbor is the primary source of polychlorinated biphenyls (PCBs) in air around the harbor. The follow-up question from residents was whether the PCBs measured in air pose a risk to their health. The US Environmental Protection Agency focuses their site-specific, risk-based decisions for site clean-up on cancers. We focused our assessment on the non-cancer effects on the thyroid based on the congener specific patterns and concentrations of PCBs measured in air near and distant to the harbor. Human and animal studies of PCB-induced effects on the thyroid provide evidence to support our analysis. Drawing from the published toxicological data, we used a Margin of Exposure (MOE) approach to derive a human-equivalent concentration in air associated with human health effects on the thyroid. Based on the MOEs calculated herein, evaluation of the MOE indicates that changes in thyroid hormone levels are possible among people living adjacent to the Harbor. Changes in thyroid hormone levels are more likely among people who live near the harbor compared to residents living in areas distant from the harbor. This risk assessment documents potential health risks associated with proximity to a marine Superfund Site using site-specific ambient air PCB congener data.

Altered lipid homeostasis in a PCB-resistant Atlantic killifish (Fundulus heteroclitus) population from New Bedford Harbor, MA, U.S.A.

Sentinel species such as the Atlantic killifish (Fundulus heteroclitus) living in urban waterways can be used as toxicological models to understand impacts of environmental metabolism disrupting compound (MDC) exposure on both wildlife and humans. Exposure to MDCs is associated with increased risk of metabolic syndrome, including impaired lipid and glucose homeostasis, adipogenesis, appetite control, and basal metabolism. MDCs are ubiquitous in the environment, including in aquatic environments. New Bedford Harbor (NBH), Massachusetts is polluted with polychlorinated biphenyls (PCBs), and, as we show for the first time, tin (Sn). PCBs and organotins are ligands for two receptor systems known to regulate lipid homeostasis, the aryl hydrocarbon receptor (AHR) and the peroxisome proliferator-activated receptors (PPARs), respectively. In the current study, we compared lipid homeostasis in laboratory-reared killifish from NBH (F2) and a reference location (Scorton Creek, Massachusetts; F1 and F2) to evaluate how adaptation to local conditions may influence responses to MDCs. Adult killifish from each population were exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126, dioxin-like), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153, non-dioxin-like), or tributyltin (TBT, a PPARγ ligand) by a single intraperitoneal injection and analyzed after 3 days. AHR activation was assessed by measuring cyp1a mRNA expression. Lipid homeostasis was evaluated phenotypically by measuring liver triglycerides and organosomatic indices, and at the molecular level by measuring the mRNA expression of pparg and ppara and a target gene for each receptor. Acute MDC exposure did not affect phenotypic outcomes. However, overall NBH killifish had higher liver triglycerides and adiposomatic indices than SC killifish. Both season and population were significant predictors of the lipid phenotype. Acute MDC exposure altered hepatic gene expression only in male killifish from SC. PCB126 exposure induced cyp1a and pparg, whereas PCB153 exposure induced ppara. TBT exposure did not induce ppar-dependent pathways. Comparison of lipid homeostasis in two killifish populations extends our understanding of how MDCs act on fish and provides a basis to infer adaptive benefits of these differences in the wild.

Identifying determinants of noise in a medical intensive care unit.

Continuous and intermittent exposure to noise elevates stress, increases blood pressure, and disrupts sleep among patients in hospital intensive care units. The purpose of this study was to determine the effectiveness of a behavior-based intervention to reduce noise and to identify determinants of noise in a medical intensive care unit. Staff were trained for 6 weeks to reduce noise during their activities in an effort to keep noise levels below 55 dBA during the day and below 50 dBA at night. One-min noise levels were logged continuously in patient rooms 8 weeks before and after the intervention. Noise levels were compared by room position, occupancy status, and time of day. Noise levels from flagged days (>60 dBA for >10 hr) were correlated with activity logs. The intervention was ineffective, with noise frequently exceeding project goals during the day and night. Noise levels were higher in rooms with the oldest heating, ventilation, and air-conditioning system, even when patient rooms were unoccupied. Of the flagged days, the odds of noise over 60 dBA occurring was 5.3 dBA higher when high-flow respiratory support devices were in use compared to times with low-flow devices in use (OR = 5.3, 95% CI = 5.0-5.5). General sources, like the heating, ventilation, and air-conditioning system, contribute to high baseline noise and high-volume (>10 L/min) respiratory-support devices generate additional high noise (>60 dBA) in Intensive Care Unit patient rooms. This work suggests that engineering controls (e.g., ventilation changes or equipment shielding) may be more effective in reducing noise in hospital intensive care units than behavior modification alone.

Theratyping in cystic fibrosis.

PURPOSE OF REVIEW: The treatment of cystic fibrosis (CF) with CF transmembrane conductance regulator (CFTR) modulators continues to develop at a fast pace. These compounds are potentially disease modifying but are only available to certain patient subsets based on genotype. This review discusses the role of theratyping in CF and the potential to assess all patients' response to current and emerging therapies. RECENT FINDINGS: There are limitations to treatment determined by mutation, as variable clinical response to CFTR modulators has been observed within the same genotype. Patients with rare mutations not currently licensed for CFTR modulator therapy have demonstrated response to these medications. Patient-specific cellular models called organoids can be used to demonstrate response to different CFTR modulators in vitro prior to their clinical application and represent a method of theratyping. SUMMARY: Theratyping charts patients' clinical response to different treatments on an individual basis. This overcomes the limitations of genotype being used to predict response to individual therapies and includes all patients regardless of mutation. The use of organoids in high throughput screening allows numerous compounds to be tested on patient-specific tissue preclinically. This could lead to the extension of theratyping beyond CFTR modulators.

Rapid Analysis of the Size Distribution of Metal-Containing Aerosol.

Conventional methods to measure the metallic content of particles by size are time consuming and expensive, requiring collection of particles with a cascade impactor and subsequent metals analysis by inductively coupled plasma mass spectrometry (ICP-MS). In this work, we describe a rapid way to measure the size distribution of metal-containing particles from 10 nm to 20 µm, using a nano micro-orifice uniform-deposit impactor (nano-MOUDI) to size-selective and collect particles that are then analyzed with a field portable X-ray fluorescence (FP-XRF) to determine metal composition and concentration. The nano-MOUDI was used to sample a stainless-steel aerosol produced by a spark discharge system. The particle-laden substrates were then analyzed directly with FP-XRF and then with ICP-MS. Results from FP-XRF were linearly correlated with results from ICP-MS (R2 = 0.91 for Fe and R2 = 0.84 for Cr). Although the FP-XRF was unable to detect Fe particles at mass per substrate loadings less than 2.5 µg effectively, it produced results similar to those using the ICP-MS at a mass per substrate loading greater than 2.5 µg.

Synthesis and characterization of pullulan-polycaprolactone core-shell nanospheres encapsulated with ciprofloxacin.

Nanosphere-encapsulated drugs offer a means to overcome many drug delivery limitations by localizing the site of delivery and providing controlled release. This research details the synthesis and encapsulation of ciprofloxacin in pullulan-polycaprolactone (PCL) core shell nanospheres and the characterization of these materials by 1H-NMR, UV spectroscopy, dynamic light scattering (DLS) and scanning electron microscopy (SEM).1H-NMR results confirm that the pullulan-PCL grafted copolymer was successfully synthesized. UV spectroscopy showed that the ciprofloxacin loaded nanospheres contain 35-40% ciprofloxacin by weight. DLS and SEM results indicate that the loaded nanospheres are spherical in shape and approximately 142+/-12 nm in size. Under in vitro test conditions, approximately 20% of the ciprofloxacin is released in the first 4 hours, with additional release over 10 days. The nanoparticles demonstrate bioactivity against Escheria coli and do not affect the proliferation of two human cell lines. These results demonstrate the potential of pullulan-PCL core-shell nanospheres as delivery vehicles of hydrophobic drugs, including antibiotics for localized treatments applicable to a wide-range of human bacterial infections.