Valley Networks and the Record of Glaciation on Ancient Mars.

The lack of evidence for large-scale glacial landscapes on Mars has led to the belief that ancient glaciations had to be frozen to the ground. Here we propose that the fingerprints of Martian wet-based glaciation should be the remnants of the ice sheet drainage system instead of landforms generally associated with terrestrial ice sheets. We use the terrestrial glacial hydrology framework to interrogate how the Martian surface gravity affects glacial hydrology, ice sliding, and glacial erosion. Taking as reference the ancient southern circumpolar ice sheet that deposited the Dorsa Argentea formation, we compare the theoretical behavior of identical ice sheets on Mars and Earth and show that, whereas on Earth glacial drainage is predominantly inefficient, enhancing ice sliding and erosion, on Mars the lower gravity favors the formation of efficient subglacial drainage. The apparent lack of large-scale glacial fingerprints on Mars, such as drumlins or lineations, is to be expected.

The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation.

BACKGROUND: Barrier dysfunction is an important feature of atopic dermatitis (AD) in which IL-4 and IL-13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL-4 or IL-13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL-13 signal. METHODS: We systematically identified periostin-dependent expression profile using DNA microarrays. We then investigated whether IL-24 downregulates filaggrin expression downstream of the IL-13 signals and whether IL-13-induced IL-24 expression and IL-24-induced downregulation of filaggrin expression are dependent on the JAK/STAT pathway. To build on the significance of in vitro findings, we investigated expression of IL-24 and activation of STAT3 in mite-treated mice and in AD patients. RESULTS: We identified IL-24 as an IL-13-induced molecule in a periostin-dependent manner. Keratinocytes are the main IL-24-producing tissue-resident cells stimulated by IL-13 in a periostin-dependent manner via STAT6. IL-24 significantly downregulated filaggrin expression via STAT3, contributing to barrier dysfunction downstream of the IL-13/periostin pathway. Wild-type mite-treated mice showed significantly enhanced expression of IL-24 and activation of STAT3 in the epidermis, which disappeared in both STAT6-deficient and periostin-deficient mice, suggesting that these events are downstream of both STAT6 and periostin. Moreover, IL-24 expression was enhanced in the epidermis of skin tissues taken from AD patients. CONCLUSIONS: The IL-13/periostin pathway induces IL-24 production in keratinocytes, playing an important role in barrier dysfunction in AD.

Assessing the influence of working hours on general health by migrant status and family structure: the case of Ecuadorian-, Colombian-, and Spanish-born workers in Spain.

OBJECTIVES: The purpose of this study was to analyze the relationship between working hours (WHs) and the likelihood of poor self-reported general health (SRGH) in the first data wave from a cohort of immigrant and native workers in Spain. STUDY DESIGN: Cross-sectional analyses from a prospective cohort study. METHODS: Data were drawn from the first wave of the Platform of Longitudinal Studies on Immigrant Families. The selected sample was composed of 217 immigrant workers and 89 native-born workers. We explored differences by immigrant status and family structure, assessing prevalences and Poisson regression models; an additional analysis explored statistically optimized work hour cut points. RESULTS: Highest prevalence of poor SRGH (72.7%) was reported by immigrant, single-parent workers working >40 WH/week. Immigrant single-parent families were more likely to report poor SRGH for three WH categories: ≤20 WH/week (prevalence ratio [PR] = 3.3, 95% confidence interval [CI] 1.6-7.2), >30-≤40 WH/week (PR = 2.8, 95% CI 1.3-6.4), and >40 WH/week (PR = 4.2, 95% CI 1.8-10.1). In two-parent families, immigrants working standard hours (i.e. >30-≤40) and native-born workers in the highest and lowest categories of WHs (i.e. ≤20 and >40) had similar PRs for poor SRGH compared with native-born workers working standard hours. Findings suggested that native-born workers residing in two-parent families were able to work more than 10 h longer per week than immigrant workers before reporting equivalent prevalences of poor SRGH. CONCLUSIONS: Differences in the association of WHs and poor SRGH among immigrants in Spain seem to be explained by family structure, which suggests that the influence of WHs on health differentially affects vulnerable groups, such as immigrant workers residing in single-parent families.

"Neurophobia": More Nurture than Nature?

AIM: "Neurophobia" is the fear of neurology experienced by medical students. The aim of this study was to investigate if neurology now has a stigma attached to it causing a preconceived negative perception of neurology by students. METHODS: An online questionnaire was distributed to medical students via social media and email. Questions focused on students' perceptions of neurology before and after exposure to the subject. RESULTS: There were one hundred and thirty-seven responses. Twenty percent of preclinical students, twenty-six percent of early clinical students and fifty-six percent of clinical students said that they would not consider neurology as a speciality in the future. Neurophysiology and neuroanatomy were considered to be the most difficult aspects of neurology. Integration of preclinical academic training with clinical training was highlighted as a point of difficulty for students. DISCUSSION: Contrary to our initial hypothesis, "neurophobia" does not appear to be innate in medical students but is acquired during the course of their medical training.

A single centre service evaluation of patients' experiences participating in radiotherapy clinical trials during and post COVID-19 in Northern Ireland, UK.

INTRODUCTION: Radiotherapy (RT) clinical trials allow patients to access cutting-edge innovative cancer treatments. Clinical Research Therapy Radiographers (CRRs) play an important role in the management and care of RT trial patients. The COVID-19 pandemic caused major disruption to RT trial delivery. Measures to mitigate COVID-19 risk continue to have an effect on patient contact and communication within cancer centres in the United Kingdom (UK). This study aimed to explore patient perspectives regarding their recent RT trial experience in Northern Ireland (NI), UK. METHODS: A single centre service evaluation was conducted in NI. Patients who were recruited into a RT clinical trial from January 2020 to January 2023 were invited to participate. Surveys were posted to 50 participants in April 2023. Quantitative and qualitative data was captured and analysed using descriptive statistics and Braun and Clarke's six-step thematic analysis framework respectively. Ethical approval was obtained through Ulster University and the NHS Trust. RESULTS: Forty-three of the 50 invited participants responded (86%). Forty-two respondents (79%) had a prostate cancer diagnosis. Forty-one (98%) participants indicated that CRRs were always approachable, polite and courteous and would recommend taking part in a RT trial to friends and family. Identified areas for improvement included aspects regarding consent and participant decision-making. CONCLUSION: This study suggests that despite the implemented measures to suspend research and mitigate COVID-19 risk, patients remained highly satisfied with the quality of care that they received through their participation in RT trials. IMPLICATIONS FOR PRACTICE: The results of this service evaluation will facilitate maintenance and improvement of patient focused delivery of cancer trials within the host centre. This study builds on evidence highlighting the importance of the CRR role and role development for radiographers.

Impact of a cleaner-burning cookstove intervention on blood pressure in Nicaraguan women.

Few studies have evaluated the cardiovascular-related effects of indoor biomass burning or the role of characteristics such as age and obesity status, in this relationship. We examined the impact of a cleaner-burning cookstove intervention on blood pressure among Nicaraguan women using an open fire at baseline; we also evaluated heterogeneity of the impact by subgroups of the population. We evaluated changes in systolic and diastolic blood pressure from baseline to post-intervention (range: 273-383 days) among 74 female cooks. We measured indoor fine particulate matter (PM(2.5); N = 25), indoor carbon monoxide (CO; N = 32), and personal CO (N = 30) concentrations. Large mean reductions in pollutant concentrations were observed for all pollutants; for example, indoor PM(2.5) was reduced 77% following the intervention. However, pollution distributions (baseline and post-intervention) were wide and overlapping. Although substantial reductions in blood pressure were not observed among the entire population, a 5.9 mmHg reduction [95% confidence interval (CI): -11.3, -0.4] in systolic blood pressure was observed among women aged 40 or more years and a 4.6 mmHg reduction (95% CI: -10.0, 0.8) was observed among obese women. Results from this study provide an indication that certain subgroups may be more likely to experience improvements in blood pressure following a cookstove intervention.

A protective role for periostin and TGF-ß in IgE-mediated allergy and airway hyperresponsiveness.

BACKGROUND: The pathophysiology of asthma involves allergic inflammation and remodelling in the airway and airway hyperresponsiveness (AHR) to cholinergic stimuli, but many details of the specific underlying cellular and molecular mechanisms remain unknown. Periostin is a matricellular protein with roles in tissue repair following injury in both the skin and heart. It has recently been shown to be up-regulated in the airway epithelium of asthmatics and to increase active TGF-ß. Though one might expect periostin to play a deleterious role in asthma pathogenesis, to date its biological role in the airway is unknown. OBJECTIVE: To determine the effect of periostin deficiency on airway responses to inhaled allergen. METHODS: In vivo measures of airway responsiveness, inflammation, and remodelling were made in periostin deficient mice and wild-type controls following repeated intranasal challenge with Aspergillus fumigatus antigen. In vitro studies of the effects of epithelial cell-derived periostin on murine T cells were also performed. RESULTS: Surprisingly, compared with wild-type controls, periostin deficient mice developed increased AHR and serum IgE levels following allergen challenge without differences in two outcomes of airway remodelling (mucus metaplasia and peribronchial fibrosis). These changes were associated with decreased expression of TGF-ß1 and Foxp3 in the lungs of periostin deficient mice. Airway epithelial cell-derived periostin-induced conversion of CD4(+) CD25(-) cells into CD25(+) , Foxp3(+) T cells in vitro in a TGF-ß dependent manner. CONCLUSIONS AND CLINICAL RELEVANCE: Allergen-induced increases in serum IgE and bronchial hyperresponsiveness are exaggerated in periostin deficient mice challenged with inhaled aeroallergen. The mechanism of periostin's effect as a brake on allergen-induced responses may involve augmentation of TGF-ß-induced T regulatory cell differentiation.

Fluvial Depositional Systems of the African Humid Period: An Analog for an Early, Wet Mars in the Eastern Sahara.

A widely hypothesized but complex transition from widespread fluvial activity to predominantly aeolian processes is inferred on Mars based on remote sensing data observations of ancient landforms. However, the lack of analysis of in situ martian fluvial deposits hinders our understanding of the flow regime nature and sustainability of the martian fluvial activity and the hunt for ancient life. Studying analogs from arid zones on Earth is fundamental to quantitatively understanding geomorphic processes and climate drivers that might have dominated during early Mars. Here we investigate the formation and preservation of fluvial depositional systems in the eastern Sahara, where the largest arid region on Earth hosts important repositories of past climatic changes. The fluvial systems are composed of well-preserved single-thread sinuous to branching ridges and fan-shaped deposits interpreted as deltas. The systems' configuration and sedimentary content suggest that ephemeral rivers carved these landforms by sequential intermittent episodes of erosion and deposition active for 10-100s years over ∼10,000 years during the late Quaternary. Subsequently, these landforms were sculpted by a marginal role of rainfall and aeolian processes with minimum erosion rates of 1.1 ± 0.2 mm/yr, supplying ∼96 ± 24 × 1010 m3 of disaggregated sediment to adjacent aeolian dunes. Our results imply that similar martian fluvial systems preserving single-thread, short distance source-to-sink courses may have formed due to transient drainage networks active over short durations. Altogether, this study adds to the growing recognition of the complexity of interpreting climate history from orbital images of landforms.

Isolation of the fungus Geosmithia argillacea in sputum of people with cystic fibrosis.

We report the repeated isolation of the fungus Geosmithia argillacea from sputum samples of people with cystic fibrosis. Identification was based on morphology and DNA sequence analysis. Isolation of G. argillacea did not appear to be associated with clinical deterioration. The pathogenic potential of G. argillacea is discussed.

Does the reproductive cycle influence sleep patterns in women with sleep complaints?

OBJECTIVE: The aim of the present study was to investigate how prominent gynecological factors (regular/irregular menstrual cycle, premenstrual complaints, or menopause) can influence both subjective and objective sleep data. METHODS: A total of 931 women who sought clinical assistance because of a sleep complaint were included in the investigation. All subjects filled out a sleep and gynecological questionnaire prior to undergoing a polysomnography (PSG) recording. RESULTS: Premenopausal women with an irregular menstrual cycle were more likely to report sleep difficulties (related to falling sleep and insomnia symptoms) than those with a regular cycle (odds ratio 2.1; 95% confidence interval 1.2-3.5). These women showed increased light sleep stages and awakenings. Premenstrual complaints were reported by a higher percentage of women with periodic leg movement, lower time in saturation under 90%, and higher sleep efficiency. A lower percentage of women who took hormonal contraceptives reported snoring, had fewer arousals and longer REM latency compared to those not taking hormonal contraceptives. Menopausal women with hot flushes had more restless leg complaints. Awake time was shorter in hormone therapy users compared with non-users. Women with menopause are more likely to have an apnea-hypoapnea index greater than 5/h. CONCLUSION: The present findings suggest that gynecological status is associated with subjective sleep quality and objective sleep parameters in women with sleep complaints.

Depicting corrosion-born defects in pipelines with combined neutron/γ ray backscatter: a biomimetic approach.

The identification of corrosion, cracks and defects in pipelines used for transporting oil and gas can reduce the possibility of leaks, and consequently, it can limit the extent of an environmental disaster, public hazard and the associated financial impact of such events. Typically, corrosion in oil pipelines is measured with non-destructive ultrasonic or electromagnetic techniques, on the basis that corrosion and defects are often manifest as a change of thickness in the steel from which pipelines are made. However, such approaches are not practical for underground pipelines and their deployment can be complicated for the case of pipelines covered by insulation. In this paper, we present an innovative, non-destructive testing technique, which exploits the backscatter of a combination of fast-neutron and γ radiation from steel samples of a variety of thicknesses consistent with changes that might arise due to corrosion of a pipe wall. Our research demonstrates the potential to measure and characterise different steel thicknesses by detecting both the elastic, fast-neutron backscatter and the Compton-scattered γ radiations, simultaneously. Further, we demonstrate that the presence of insulation yields a consistent and separable influence on the experimental, wall-thickness measurements. The data from experimental measurements are supported by a comprehensive Monte Carlo computer simulation study.

Prevention of allogeneic fetal rejection by tryptophan catabolism.

In 1953 Medawar pointed out that survival of the genetically disparate (allogeneic) mammalian conceptus contradicts the laws of tissue transplantation. Rapid T cell-induced rejection of all allogeneic concepti occurred when pregnant mice were treated with a pharmacologic inhibitor of indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme expressed by trophoblasts and macrophages. Thus, by catabolizing tryptophan, the mammalian conceptus suppresses T cell activity and defends itself against rejection.

Initiation and Flow Conditions of Contemporary Flows in Martian Gullies.

Understanding the initial and flow conditions of contemporary flows in Martian gullies, generally believed to be triggered and fluidized by CO2 sublimation, is crucial for deciphering climate conditions needed to trigger and sustain them. We employ the RAMMS (RApid Mass Movement Simulation) debris flow and avalanche model to back calculate initial and flow conditions of recent flows in three gullies in Hale crater. We infer minimum release depths of 1.0-1.5 m and initial release volumes of 100-200 m3. Entrainment leads to final flow volumes that are ∼2.5-5.5 times larger than initially released, and entrainment is found necessary to match the observed flow deposits. Simulated mean cross-channel flow velocities decrease from 3-4 m/s to ∼1 m/s from release area to flow terminus, while flow depths generally decrease from 0.5-1 to 0.1-0.2 m. The mean cross-channel erosion depth and deposition thicknesses are ∼0.1-0.3 m. Back-calculated dry-Coulomb friction ranges from 0.1 to 0.25 and viscous-turbulent friction between 100 and 200 m/s2, which are values similar to those of granular debris flows on Earth. These results suggest that recent flows in gullies are fluidized to a similar degree as are granular debris flows on Earth. Using a novel model for mass flow fluidization by CO2 sublimation we are able to show that under Martian atmospheric conditions very small volumetric fractions of CO2 of ≪1% within mass flows may indeed yield sufficiently large gas fluxes to cause fluidization and enhance flow mobility.

Atmospheric implications of large C2-C5 alkane emissions from the U.S. oil and gas industry.

Emissions of C2-C5 alkanes from the U.S. oil and gas sector have changed rapidly over the last decade. We use a nested GEOS-Chem simulation driven by updated 2011NEI emissions with aircraft, surface and column observations to 1) examine spatial patterns in the emissions and observed atmospheric abundances of C2-C5 alkanes over the U.S., and 2) estimate the contribution of emissions from the U.S. oil and gas industry to these patterns. The oil and gas sector in the updated 2011NEI contributes over 80% of the total U.S. emissions of ethane (C2H6) and propane (C3H8), and emissions of these species are largest in the central U.S. Observed mixing ratios of C2-C5 alkanes show enhancements over the central U.S. below 2 km. A nested GEOS-Chem simulation underpredicts observed C3H8 mixing ratios in the boundary layer over several U.S. regions and the relative underprediction is not consistent, suggesting C3H8 emissions should receive more attention moving forward. Our decision to consider only C4-C5 alkane emissions as a single lumped species produces a geographic distribution similar to observations. Due to the increasing importance of oil and gas emissions in the U.S., we recommend continued support of existing long-term measurements of C2-C5 alkanes. We suggest additional monitoring of C2-C5 alkanes downwind of northeastern Colorado, Wyoming and western North Dakota to capture changes in these regions. The atmospheric chemistry modeling community should also evaluate whether chemical mechanisms that lump larger alkanes are sufficient to understand air quality issues in regions with large emissions of these species.

The 2018 rift eruption and summit collapse of Kilauea Volcano.

In 2018, Kilauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'O'o vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (M w) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to M w 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kilauea enabled successful forecasting of hazardous events.

Exercise during childhood and adolescence: a prophylaxis against cystic fibrosis-related low bone mineral density? Exercise for bone health in children with cystic fibrosis.

Inadequate bone mineral accrual during growth and accelerated bone demineralisation in adulthood are recognised as additional and serious complications for patients with cystic fibrosis (CF). However, little attention has been given to preventative strategies for this population. Inadequate bone accrual during childhood and adolescence, and premature bone loss, lead to a failure to attain an optimal peak bone mass, osteoporosis and fracture in patients with CF. Pharmaceutical treatments may assist in the improvement of bone in patients with CF, but these are usually not preferable for use in children. Evidence indicates that regular, weight-bearing exercise significantly enhances bone accrual in healthy children. This paper reviews the literature concerning the potential for weight-bearing exercise to improve bone mineral accrual in children with CF. All relevant literature since 1979 was obtained and reviewed from the Medline, PubMed, Cochrane and PEDro data base. Evidence concerning the efficacy of exercise for bone health in CF is lacking. There have been no controlled trials investigating the value of weight-bearing exercise for bone accrual in children with CF. As exercise may offer an effective and enjoyable strategy to improve the bone development in children who have CF, exercise should be a high priority for randomised controlled trials in this population.

Enteral tube feeding for cystic fibrosis.

BACKGROUND: Enteral tube feeding is routinely used in many cystic fibrosis centres when weight for height percentage is less than 85%, when there has been weight loss for longer than a two-month period or when there has been no weight gain for two to three months (under five years old) or for six months (over five years old). OBJECTIVES: To examine the evidence that in people with cystic fibrosis supplemental enteral tube feeding improves nutritional status, respiratory function, and quality of life without significant adverse effects. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also contacted the companies that market enteral feeds and reviewed their databases. Date of the most recent search of the Group's Cystic Fibrosis Trials Register: November 2007. SELECTION CRITERIA: All randomised controlled trials comparing supplemental enteral tube feeding for one month or longer with no specific intervention in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Thirteen trials were identified by the search; however, none were eligible for inclusion in this review. MAIN RESULTS: There are no trials included in this review. AUTHORS' CONCLUSIONS: Supplemental enteral tube feeding is widely used throughout the world to improve nutritional status in people with cystic fibrosis. The methods mostly used, nasogastric or gastrostomy feeding, are invasive, expensive, and may have a negative effect on self-esteem and body image. Reported use of enteral tube feeding suggests that it results in nutritional and respiratory improvement and it is disappointing that their efficacy has not been fully assessed by randomised controlled trials. With the more frequent recommendations to use enteral tube feeding as an early rather than a late intervention, this systematic review identifies the need for a multicentre, randomised controlled trial assessing both efficacy and possible adverse effects of enteral tube feeding in cystic fibrosis. There are no trials included in the review and we have not identified any relevant trials up to November 2007. We therefore do not plan to update this review until new trials are published.

Periostin is essential for the integrity and function of the periodontal ligament during occlusal loading in mice.

BACKGROUND: The ability of the periodontal ligament (PDL) to absorb and distribute forces is necessary for periodontal homeostasis. This adaptive response may be determined, in part, by a key molecule, periostin, which maintains the integrity of the PDL during occlusal function and inflammation. Periostin is primarily expressed in the PDL and is highly homologous to betaig-H3 (transforming growth factor-beta [TGF-beta] inducible gene). Cementum, alveolar bone, and the PDL of periostin-null mice dramatically deteriorate following tooth eruption. The purpose of this study was to determine the role of periostin in maintaining the functional integrity of the periodontium. METHODS: The periodontia from periostin-null mice were characterized followed by unloading the incisors. The effect of substrate stretching on periostin expression was evaluated using a murine PDL cell line. Real-time reverse transcription-polymerase chain reaction was used to quantify mRNA levels of periostin and TGF-beta. TGF-beta1 neutralizing antibodies were used to determine whether the effects of substrate stretching on periostin expression are mediated through TGF-beta. RESULTS: Severe periodontal defects were observed in the periostin-null mice after tooth eruption. The removal of masticatory forces in periostin-null mice rescue the periodontal defects. Periostin expression was increased in strained PDL cells by 9.2-fold at 48 hours and was preceded by a transient increase in TGF-beta mRNA in vitro. Elevation of periostin in response to mechanical stress was blocked by the addition of 2.5 ng/ml neutralizing antibody to TGF-beta1, suggesting that mechanical strain activates TGF-beta to have potential autocrine effects and to increase periostin expression. CONCLUSION: Mechanical loading maintains sufficient periostin expression to ensure the integrity of the periodontium in response to occlusal load.

Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils.

The S100 family member S100A9 and its heterodimeric partner, S100A8, are cytosolic Ca2+ binding proteins abundantly expressed in neutrophils. To understand the role of this EF-hand-containing complex in Ca2+ signalling, neutrophils from S100A9 null mice were investigated. There was no role for the complex in buffering acute cytosolic Ca2+ elevations. However, Ca2+ responses to inflammatory agents such as chemokines MIP-2 and KC and other agonists are altered. For S100A9 null neutrophils, signalling at the level of G proteins is normal, as is release of Ca2+ from the IP(3) receptor-gated intracellular stores. However MIP-2 and FMLP signalling in S100A9 null neutrophils was less susceptible than wildtype to PLCbeta inhibition, revealing dis-regulation of the signalling pathway at this level. Downstream of PLCbeta, there was reduced intracellular Ca2+ release induced by sub-maximal levels of chemokines. Conversely the response to FMLP was uncompromised, demonstrating different regulation compared to MIP-2 stimulation. Study of the activity of PLC product DAG revealed that chemokine-induced signalling was susceptible to inhibition by elevated DAG with S100A9 null cells showing enhanced inhibition by DAG. This study defines a lesion in S100A9 null neutrophils associated with inflammatory agonist-induced IP3-mediated Ca2+ release that is manifested at the level of PLCbeta.

Measurement of urinary N-acetyl-b-D-glucosaminidase in adult patients with cystic fibrosis: before, during and after treatment with intravenous antibiotics.

BACKGROUND: Patients with cystic fibrosis (CF) are at high risk from the nephrotoxic effects of intravenous antibiotics due to repeated and prolonged courses of therapy. Routine methods of monitoring renal injury are insensitive. N-acetyl-b-d-glucosaminidase (NAG) is a lysosomal enzyme present in the renal proximal tubular cells, with increased excretion an indicator of renal tubular dysfunction. METHODS: Urinary NAG, creatinine, serum creatinine, electrolytes and BUN were measured on days 1, 14 and at the first out-patient visit following treatment with tobramycin or colistin. Urinary NAG levels were corrected for urinary creatinine and expressed as a NAG ratio. Patients who received>1 course of intravenous antibiotics during the study period were included in a separate analysis of the cumulative effect of treatment. RESULTS: 88 patients (44 female, 31 with CFRD) completed a single course of intravenous antibiotics. 71 patients had urinary NAG levels at follow-up. The median time to follow-up was 50 days. Serum electrolytes, creatinine and BUN were normal throughout. A 3.5-fold increase in urinary NAG excretion was observed between day 1 and 14 and 46% of patients had an elevated NAG level at follow-up. A highly significant difference in NAG excretion was observed on day 14 for tobramycin vs. colistin (median 2.24 vs. 0.98, p<0.001). A significant difference in NAG excretion was seen in patients with CFRD at all measured time points. Patients with CFRD had a significantly worse clinical status and had received more days of intravenous antibiotics over the previous 6 years. In 20 (80%) of 25 patients who received>1 course of treatment during the study period, baseline NAG levels were significantly higher in subsequent courses (p<0.001). There was a significant correlation between previous exposure to colistin and baseline NAG levels (r=0.389, p<0.001). CONCLUSIONS: Both tobramycin and colistin cause acute renal tubular injury with a significant rise in urinary NAG excretion. Patients with CFRD seem to be at greatest risk of renal tubular damage. Cumulative damage is evident with repeated dosing. Previous exposure to nephrotoxic antibiotics, especially colistin, is associated with elevated baseline NAG levels. We recommend that colistin is reserved for patients with resistant Pseudomonas aeruginosa or those who are intolerant to tobramycin. Serial longitudinal NAG measurements may be useful in patients with CF, especially those with CFRD, to identify patients at risk of developing renal disease.