Improved treatments for cystic fibrosis (CF)-related lung disease have resulted in increased longevity, but also increased prevalence and severity of extrapulmonary manifestations of CF, ...treatment-related complications, age-related conditions, and psychosocial effects of longstanding chronic disease. Likewise, the recognition of mild CF phenotypes has changed the landscape of CF disease. This review outlines our current understanding of the common extrapulmonary complications of CF, as well as the changing landscape and future directions of the extrapulmonary complications experienced by patients with CF.
Improved clinical care has led to a dramatic increase in life expectancy for people with cystic fibrosis (CF). As they live longer, people with CF are therefore developing secondary complications. ...Cystic fibrosis-related diabetes (CFRD) is the commonest extrapulmonary complication of CF. Insulin deficiency is the primary defect in CFRD, but insulin resistance and impairment of the enteroinsular axis play contributory roles. CFRD affects 9% of people with CF aged 5 to 9 years, 26% aged 10 to 20 years, and up to 50% by the age of 30. The presence of CFRD is associated with accelerated decline in pulmonary function, poorer growth and nutritional status, and increased mortality. The need for early detection of abnormal glucose handling in CF is clear since it is linked with clinical decline. Patients with CFRD may be asymptomatic for many years, so it is recommended that screening be commenced at 10 years of age. Although oral glucose tolerance test is recommended, it is well recognized that early glucose handling abnormalities will not be detected and the chance to intervene early may be missed. Many centers are therefore using continuous glucose monitoring to refine the diagnosis and investigate real-life glycemic control. Future research will hopefully widen our understanding of the pathophysiology of CFRD and therefore the treatment options available. There are clearly some promising results suggesting the use of oral agents may prove beneficial in treating CFRD but insulin should remain the mainstay of treatment until these are further evaluated.
This article reviews the significance of nutritional status in patients with cystic fibrosis (CF), and sheds light on the reasons behind the intense focus placed on perpetual weight gain and ...increased caloric intake by CF patients and their providers. The manuscript explores the potential mechanisms by which aberrant CFTR may contribute to increased resting energy expenditure (REE), and how correcting and potentiating its activity, possibly by reducing REE, among other intended and off-target effects, can contribute to weight gain in this patient population. The commentary also examines what is currently known about metabolic and vascular complications of obesity in patients with CF, and presents dietary, nutritional, pharmacologic and surgical approaches that may help obese patients with CF lose weight and build more lean body mass.
•Overnutrition and obesity are incresing in patients with CF•Known effects of weight on FEV1, mortality, comorbidities and graft function post lung transplant are summarized.•Individualized caloric targets should be assessed at every visit to optimize weight and decrease risk of over-nutrition.•More prospective studies are needed to explore effects of obesity on health outcomes in this patient population.
Passive sampling to quantify net partitioning of hydrophobic organic contaminants between the porewater and solid phase has advanced risk management for contaminated sediments. Direct porewater (C ...free) measures represent the best way to predict adverse effects to biota. However, when the need arises to convert between solid-phase concentration (C total) and C free, a wide variation in observed sediment-porewater partition coefficients (K TOC) is observed due to intractable complexities in binding phases. We propose a stochastic framework in which a given C total is mapped to an estimated range of C free through variability in passive sampling-derived K TOC relationships. This mapping can be used to pair estimated C free with biological effects data or inversely to translate a measured or assumed C free to an estimated C total. We apply the framework to both an effects threshold for polycyclic aromatic hydrocarbon (PAH) toxicity and an aggregate adverse impact on an assemblage of species. The stochastic framework is based on a “bioavailability ratio” (BR), which reflects the extent to which potency-weighted, aggregate PAH partitioning to the solid-phase is greater than that predicted by default, K OW-based K TOC values. Along a continuum of C total, we use the BR to derive an estimate for the probability that C free will exceed a threshold. By explicitly describing the variability of KTOC and BR, estimates of risk posed by sediment-associated contaminants can be more transparent and nuanced.
Cystic Fibrosis Related Diabetes Mellitus (CFRD) drives excess pulmonary morbidity and mortality in patients with cystic fibrosis (CF). The recommended treatment is insulin therapy. Insulin therapy ...in CF should be customized to the specific patient. CF patients typically require intensive insulin regimens such as multiple daily injections or insulin pump therapy, but frequently require lower doses than in type 1 diabetes mellitus. Patients with CF may also need insulin to cover intravenous or enteral feedings. Pre-diabetic glycaemic abnormalities are also associated with clinical decline in cystic fibrosis prior to the diagnosis of CFRD, however, whether and how this should be treated is not fully determined. There is also interest, but inadequate data regarding other treatments besides insulin (i.e., oral medications) for treatment of pre-diabetes or CFRD. CFTR potentiator and corrector therapy has yet to demonstrate an effect on the rate of CFRD, but may improve insulin secretion. There is great opportunity for further research to better understand when and how best to treat glycaemic abnormalities in cystic fibrosis.
•Cystic Fibrosis Related Diabetes Mellitus (CFRD) drives excess morbidity in CF.•Insulin therapy is the only recommended treatment for CFRD at this time.•Insulin is typically given in a basal-bolus format via injection or insulin pump.•Carbohydrate restriction is not a recommended treatment for CFRD.•Currently, there is inadequate systematic data for non-insulin therapies for CFRD.
Pyrethroids and fipronil insecticides partition to sediment and organic matter in aquatic systems and may pose a risk to organisms that use these matrices. It has been suggested that bioavailability ...of sediment‐sorbed pesticides is reduced, but data on toxicity of sediment‐associated pesticides for pyrethroids and fipronil are limited. In the current study, 10‐d sediment exposures were conducted with larval Chironomus tentans for bifenthrin, lambda‐cyhalothrin, permethrin, fipronil, fipronil‐sulfide, and fipronilsulfone, the last two being common fipronil metabolites. Sublethal endpoints included immobilization, instantaneous growth rate (IGR), body condition index, and growth estimated by ash‐free dry mass (AFDM). Pyrethroid lethal concentrations to 50% of the population (LC50s) were 6.2, 2.8, and 24.5 μg/g of organic carbon (OC) for bifenthrin, lambda‐cyhalothrin, and permethrin, respectively; with the former two lower than previously published estimates. Fipronil, fipronil‐sulfide, and fipronilsulfone LC50 values were 0.13, 0.16, and 0.12 μg/g of OC, respectively. Ratios of LC50s to sublethal endpoints (immobilization, IGR, and AFDM) ranged from 0.90 to 9.03. The effects on growth observed in the present study are important because of the unique dipteran life cycle involving pupation and emergence events. Growth inhibition would likely lead to ecological impacts similar to mortality (no emergence and thus not reproductively viable) but at concentrations up to 4.3 times lower than the LC50 for some compounds. In addition, C. tentans was highly sensitive to fipronil and metabolites, suggesting that dipterans may be important for estimating risk and understanding effects of phenylpyrazole‐class insecticides on benthic macroinvertebrate communities.
New anatomical and physiological knowledge is combined with eastern energy techniques and traditional actor training methods as the basis for this pioneering approach to actor training. Practical ...exercises extend understanding of the somatic systems and how to create flexible bodies for truthful performances.
Thyroperoxidase (TPO) is an enzyme essential for thyroid hormone (TH) synthesis and a target site for a number of xenobiotics that disrupt TH homeostasis. An in vitro high-throughput screening assay ...for TPO inhibition, the Amplex UltraRed-TPO (AUR-TPO), has been used to screen the ToxCast chemical libraries for this action. Output from this assay would be most useful if it could be readily translated into an in vivo response, namely a reduction of TH in serum. To this end, the relationship between TPO inhibition in vitro and serum TH decreases was examined in rats exposed to 2 classic TPO inhibitors, propylthiouracil (PTU) and methimazole (MMI). Serum and gland PTU, MMI, and TH levels were quantified using tandem liquid chromatography mass spectrometry. Thyroperoxidase activity was determined in thyroid gland microsomes treated with PTU or MMI in vitro and ex vivo from thyroid gland microsomes prepared from exposed animals. A quantitative model was constructed by contrasting in vitro and ex vivo AUR-TPO results and the in vivo time-course and dose-response analysis. In vitro:ex vivo correlations of AUR-TPO outputs indicated that less than 30% inhibition of TPO in vitro was sufficient to reduce serum T4 by 20%, a degree of regulatory significance. Although further testing of model estimates using other TPO inhibitors is essential for verification of these initial findings, the results of this study provide a means to translate in vitro screening assay results into predictions of in vivo serum T4 changes to inform risk assessment.
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