Projecting Changes in Expected Annual Damages From Riverine Flooding in the United States.

Inland flood risk in the United States is most often conveyed through maps of 1% annual exceedance probability (AEP) or "100-year" floodplains. However, monetary damages from flooding arise from a full distribution of events, including floods both larger and smaller than the 1% AEP event. Furthermore, floodplains are not static, since both the frequency and magnitude of flooding are likely to change in a warming climate. We explored the implications of a changing frequency and magnitude of flooding across a wide spectrum of flood events, using a sample of 376 watersheds in the United States where floodplains from multiple recurrence intervals have been mapped. Using an inventory of assets within these mapped floodplains, we first calculated expected annual damages (EADs) from flooding in each watershed under baseline climate conditions. We find that the EAD is typically a factor of 5-7 higher than the expected damages from 100-year events alone and that much of these damages are attributable to floods smaller than the 1% AEP event. The EAD from flooding typically increases by 25-50% under a 1 °C warming scenario and in most regions more than double under a 3 °C warming scenario. Further increases in EAD are not as pronounced beyond 3 °C warming, suggesting that most of the projected increases in flood damages will have already occurred, for most regions of the country, by that time. Adaptations that protect against today's 100-year flood will have increasing benefits in a warmer climate by also protecting against more frequent, smaller events.

Spontaneous Intracranial Hypotension: A Systematic Imaging Approach for CSF Leak Localization and Management Based on MRI and Digital Subtraction Myelography.

BACKGROUND AND PURPOSE: Localization of the culprit CSF leak in patients with spontaneous intracranial hypotension can be difficult and is inconsistently achieved. We present a high yield systematic imaging strategy using brain and spine MRI combined with digital subtraction myelography for CSF leak localization. MATERIALS AND METHODS: During a 2-year period, patients with spontaneous intracranial hypotension at our institution underwent MR imaging to determine the presence or absence of a spinal longitudinal extradural collection. Digital subtraction myelography was then performed in patients positive for spinal longitudinal extradural CSF collection primarily in the prone position and in patients negative for spinal longitudinal extradural CSF collection in the lateral decubitus positions. RESULTS: Thirty-one consecutive patients with spontaneous intracranial hypotension were included. The site of CSF leakage was definitively located in 27 (87%). Of these, 21 were positive for spinal longitudinal extradural CSF collection and categorized as having a ventral (type 1, fifteen [48%]) or lateral dural tear (type 2; four [13%]). Ten patients were negative for spinal longitudinal extradural CSF collection and were categorized as having a CSF-venous fistula (type 3, seven [23%]) or distal nerve root sleeve leak (type 4, one [3%]). The locations of leakage of 2 patients positive for spinal longitudinal extradural CSF collection remain undefined due to resolution of spontaneous intracranial hypotension before repeat digital subtraction myelography. In 2 (7%) patients negative for spinal longitudinal extradural CSF collection, the site of leakage could not be localized. Nine of 21 (43%) patients positive for spinal longitudinal extradural CSF collection were treated successfully with an epidural blood patch, and 12 required an operation. Of the 10 patients negative for spinal longitudinal extradural CSF collection (8 localized), none were effectively treated with an epidural blood patch, and all have undergone (n = 7) or are awaiting (n = 1) an operation. CONCLUSIONS: Patients positive for spinal longitudinal extradural CSF collection are best positioned prone for digital subtraction myelography and may warrant additional attempts at a directed epidural blood patch. Patients negative for spinal longitudinal extradural CSF collection are best evaluated in the decubitus positions to reveal a CSF-venous fistula, common in this population. Patients with CSF-venous fistula may forgo further epidural blood patch treatment and go on to surgical repair.

A synbiotic mixture of scGOS/lcFOS and Bifidobacterium breve M-16V increases faecal Bifidobacterium in healthy young children.

Little is known about the impact of nutrition on toddler gut microbiota. The plasticity of the toddler gut microbiota indicates that nutritional modulation beyond infancy could potentially impact its maturation. The objective of this study was to determine the effect of consuming Young Child Formula (YCF) supplemented with short chain galactooligosaccharides and long chain fructooligosaccharides (scGOS/lcFOS, ratio 9:1) and Bifidobacterium breve M-16V on the development of the faecal microbiota in healthy toddlers. A cohort of 129 Thai children aged 1-3 years were included in a randomised controlled clinical study. The children were assigned to receive either YCF with 0.95 g/100 ml of scGOS/lcFOS and 1.8×107 cfu/g of B. breve M-16V (Active-YCF) or Control-YCF for 12 weeks. The composition and metabolic activity of the faecal microbiota, and the level of secretory immunoglobulin A were determined in the stool samples. The consumption of Active-YCF increased the proportion of Bifidobacterium (mean 27.3% at baseline to 33.3%, at week 12, P=0.012) with a difference in change from baseline at week 12 between the Active and Control of 7.48% (P=0.030). The consumption of Active-YCF was accompanied with a more acidic intestinal milieu compared to the Control-YCF. The pH value decreased statistically significantly in the Active-YCF group from a median of 7.05 at baseline to 6.79 at week 12 (P<0.001). The consumption of Active-YCF was associated with a softer pudding-like stool consistency compared to the Control-YCF. At week 6 and week 12, the between-group difference in stool consistency was statistically significant (P=0.004 and P<0.001, respectively). A Young Child Formula supplemented with scGOS/lcFOS and B. breve M-16V positively influences the development of the faecal microbiota in healthy toddlers by supporting higher levels of Bifidobacterium. The synbiotic supplementation is also accompanied with a more acidic intestinal milieu and softer stools.

Emergency Department Visits and Ambient Temperature: Evaluating the Connection and Projecting Future Outcomes.

The U.S. Global Climate Change Research Program has identified climate change as a growing public health threat. We investigated the potential effects of changes in ambient daily maximum temperature on hyperthermia and cardiovascular emergency department (ED) visits using records for patients age 64 and younger from a private insurance database for the May-September period for 2005-2012. We found a strong positive relationship between daily maximum temperatures and ED visits for hyperthermia but not for cardiovascular conditions. Using the fitted relationship from 136 metropolitan areas, we calculated the number and rate of hyperthermia ED visits for climates representative of year 1995 (baseline period), as well as years 2050 and 2090 (future periods), for two climate change scenarios based on outcomes from five global climate models. Without considering potential adaptation or population growth and movement, we calculate that climate change alone will result in an additional 21,000-28,000 hyperthermia ED visits for May to September, with associated treatment costs between $6 million and $52 million (2015 U.S. dollars) by 2050; this increases to approximately 28,000-65,000 additional hyperthermia ED visits with treatment costs between $9 million and $118 million (2015 U.S. dollars) by 2090. The range in projected additional hyperthermia visits reflects the difference between alternative climate scenarios, and the additional range in valuation reflects different assumptions about per-case valuation.

Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy.

Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.

Lethal and sub-lethal effects of Deepwater Horizon slick oil and dispersant on oyster (Crassostrea virginica) larvae.

In April 2010, crude oil was spilled from the Deepwater Horizon (DWH) oil platform for 87 days, coincident with the spawning season and recruitment of the oyster, Crassostrea virginica, in the Gulf of Mexico. Impacts of acute exposures to surface-collected DWH oil (HEWAF), dispersed oil (CEWAF) and dispersant alone (Corexit 9500A(®)) on planktonic larval stages of C. virginica (veliger, umbo and pediveliger) were tested in the laboratory. Exposures to HEWAF, CEWAF and dispersant were toxic to larvae impairing growth, settlement success and ultimately survival. Larval growth and settlement were reduced at concentrations of tPAH50 ranging from 1.7 to 106 µg L(-1) for HEWAF and 1.1-35 µg L(-1) for CEWAF, concentrations well within the range of water sampled during the DWH oil spill. Sublethal effects induced by oil and dispersant could have significant ecological implications on oyster populations and on the whole estuarine ecosystem.

Global MLST of Salmonella Typhi Revisited in Post-genomic Era: Genetic Conservation, Population Structure, and Comparative Genomics of Rare Sequence Types.

Typhoid fever, caused by Salmonella enterica serovar Typhi, remains an important public health burden in Southeast Asia and other endemic countries. Various genotyping methods have been applied to study the genetic variations of this human-restricted pathogen. Multilocus sequence typing (MLST) is one of the widely accepted methods, and recently, there is a growing interest in the re-application of MLST in the post-genomic era. In this study, we provide the global MLST distribution of S. Typhi utilizing both publicly available 1,826 S. Typhi genome sequences in addition to performing conventional MLST on S. Typhi strains isolated from various endemic regions spanning over a century. Our global MLST analysis confirms the predominance of two sequence types (ST1 and ST2) co-existing in the endemic regions. Interestingly, S. Typhi strains with ST8 are currently confined within the African continent. Comparative genomic analyses of ST8 and other rare STs with genomes of ST1/ST2 revealed unique mutations in important virulence genes such as flhB, sipC, and tviD that may explain the variations that differentiate between seemingly successful (widespread) and unsuccessful (poor dissemination) S. Typhi populations. Large scale whole-genome phylogeny demonstrated evidence of phylogeographical structuring and showed that ST8 may have diverged from the earlier ancestral population of ST1 and ST2, which later lost some of its fitness advantages, leading to poor worldwide dissemination. In response to the unprecedented increase in genomic data, this study demonstrates and highlights the utility of large-scale genome-based MLST as a quick and effective approach to narrow the scope of in-depth comparative genomic analysis and consequently provide new insights into the fine scale of pathogen evolution and population structure.

Impacts of Deepwater Horizon oil and associated dispersant on early development of the Eastern oyster Crassostrea virginica.

The explosion of the Deepwater Horizon (DWH) oil platform resulted in large amounts of crude oil and dispersant Corexit 9500A® released into the Gulf of Mexico and coincided with the spawning season of the oyster, Crassostrea virginica. The effects of exposing gametes and embryos of C. virginica to dispersant alone (Corexit), mechanically (HEWAF) and chemically dispersed (CEWAF) DWH oil were evaluated. Fertilization success and the morphological development, growth, and survival of larvae were assessed. Gamete exposure reduced fertilization (HEWAF: EC201h=1650µg tPAH50L(-1); CEWAF: EC201h=19.4µg tPAH50L(-1); Corexit: EC201h=6.9mgL(-1)). CEWAF and Corexit showed a similar toxicity on early life stages at equivalent nominal concentrations. Oysters exposed from gametes to CEWAF and Corexit experienced more deleterious effects than oysters exposed from embryos. Results suggest the presence of oil and dispersant during oyster spawning season may interfere with larval development and subsequent recruitment.

Medical service redesign shares the load saving 6000 bed days and improving morale.

BACKGROUND AND AIMS: In 2010, demand on the Auckland City Hospital general medical service exceeded capacity. A review by the Royal Australasian College of Physicians was critical of training offered to registered medical officers, and low morale was a problem across the service. Management offered support for an improved model that would solve these problems. METHODS: A project to redesign the general medical service was undertaken. Baseline analysis found uneven workload and insufficient capacity at peak times for patient presentations. Workshops involving the entire service led to a new model that splits workload and teams into patients likely to have a short stay from those requiring longer, ward-based care. Admissions are now distributed over 12 teams on weekdays and 4 on the weekends. There was an increase of approximately 2.5 in consultant full time equivalents but no change in registrar or house officer staffing. RESULTS: Since the introduction of the new model, the average length of stay has fallen from 3.7 to 3.2 days (14%) and the median length of stay by 28%, resulting in a saving of 6000 bed days per year. Readmission, inpatient and 30-day mortality rates are unchanged. These results have been sustained over 18 months with signs of continuing improvement. CONCLUSION: This project owes its success to the following factors - management support; iterative engagement of a range of staff; provision of timely data analysis; increases in senior medical officer staffing and reorganisation leading to more predictable and fair work practices. One challenge is discontinuity, whether between doctors and patients or within the medical team.

The effect of infections on the mortality of cirrhotic patients with hepatic encephalopathy.

Cirrhotic patients are prone to having infections, which may aggravate hepatic encephalopathy (HE). However, the effect of infections on mortality in HE cirrhotic patients is not well described. The National Health Insurance Database, derived from the Taiwan National Health Insurance Programme, was used to identify 4150 adult HE cirrhotic patients hospitalized between 1 January 2004 and 31 December 2004. Nine hundred and eighty-five patients (23.7%) had one or more co-existing infections during their hospitalization. After Cox proportional hazard regression modelling adjusted by the patients' gender, age, and medical comorbidity disorders, the hazard ratios (HRs) in HE patients with infections for 30-day, 30- to 90-day, and 90-day to 1-year mortalities were 1.66 [95% confidence interval (CI) 1.42-1.94], 1.51 (95% CI 1.23-1.85) and 1.34 (95% CI 1.13-1.58), respectively. Compared to the non-infection group, the HRs of pneumonia, spontaneous bacterial peritonitis, urinary tract infection, sepsis without specific focus (SWSF), cellulitis, and biliary tract infection were 2.11, 1.48, 1.06, 2.21, 1.06, and 0.78, respectively, for 30-day mortality; 1.82, 1.22, 0.93, 2.24, 0.31, and 2.82, respectively, for 30- to 90-day mortality; and 2.03, 0.82, 1.24, 1.64, 1.14, and 0.60, respectively, for 90-day to 1-year mortality for HE cirrhotic patients. We conclude that infections increase the mortality of HE cirrhotic patients, especially pneumonia and SWSF.

Growth, acid production and bacteriocin production by probiotic candidates under simulated colonic conditions.

AIMS: The aim of this study is to evaluate the capacity of three bacteriocin producers, namely Lactococcus lactis subsp. lactis biovar diacetylactis UL719 (nisin Z producer), L. lactis ATCC 11454 (nisin A producer) and Pediococcus acidilactici UL5 (pediocin PA-1 producer), and to grow and produce their active bacteriocins in Macfarlane broth, which mimics the nutrient composition encountered in the human large intestine. METHODS AND RESULTS: The three bacteriocin-producing strains were grown in Macfarlane broth and in De Man-Rogosa-Sharpe (MRS) broth. For each strain, the bacterial count, pH drop and production of organic acids and bacteriocins were measured for different period of time. The ability of the probiotic candidates to inhibit Listeria ivanovii HPB 28 in co-culture in Macfarlane broth was also examined. Lactococcus lactis subsp. lactis biovar diacetylactis UL719, L. lactis ATCC 11454 and Ped. acidilactici UL5 were able to grow and produce their bacteriocins in MRS broth and in Macfarlane broth. Each of the three candidates inhibited L. ivanovii HPB 28, and this inhibition activity was correlated with bacteriocin production. The role of bacteriocin production in the inhibition of L. ivanovii in Macfarlane broth was confirmed for Ped. acidilactici UL5 using a pediocin nonproducer mutant. CONCLUSIONS: The data provide some evidence that these bacteria can produce bacteriocins in a complex medium with carbon source similar to those found in the colon. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the capacity of lactic acid bacteria to produce their bacteriocins in a medium simulating the nutrient composition of the large intestine.

Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres (pattern 1) shows superior survival to patterns 2 and 3: a meta-analysis of 56 cases.

AIMS: Angioimmunoblastic T-cell lymphoma (AITL) may present in patterns 1, 2 or 3, representing those with hyperplastic, regressed or effaced germinal centres (GCs), respectively, but the prognostic utility of this subclassification has not been previously validated. METHODS AND RESULTS: Twenty-five cases of AITL were reviewed immunohistologically and with in-situ hybridization for Epstein-Barr virus-encoded RNA and polymerase chain reaction for T-cell receptor gamma and immunoglobulin heavy chain clonality and followed for up to 120 months. Four cases had conventional hyperplastic GCs, two had floral GCs, and one had progressively transformed GCs, consistent with pattern 1 and one additional case had hyalinized GCs, consistent with pattern 2. The remaining 17 (pattern 3) cases lacked morphologically discernible GCs. The Kaplan-Meier survival distribution of pattern 1 cases (5-year survival 83%) was superior to that of pattern 2 and 3 cases [5-year-survival 36% (P = 0.0417)] only when combined with the 31 cases, seven of which were pattern 1, that Attygalle et al. had followed for up to 247 months and previously published. Furthermore, the development of B-lineage (classical Hodgkin or diffuse large-cell) lymphoma was associated exclusively with pattern 3 (P = 0.0057). CONCLUSIONS: Pattern 1 represents an indolent phase/grade of AITL, unassociated with the development of secondary B-lineage lymphoma and uninfluenced by treatment regimen.

Enhancement of anaerobic biohydrogen/methane production from cellulose using heat-treated activated sludge.

Anaerobic digestion is an effective technology to convert cellulosic wastes to methane and hydrogen. Heat-treatment is a well known method to inhibit hydrogen-consuming bacteria in using anaerobic mixed cultures for seeding. This study aims to investigate the effects of heat-treatment temperature and time on activated sludge for fermentative hydrogen production from alpha-cellulose by response surface methodology. Hydrogen and methane production was evaluated based on the production rate and yield (the ability of converting cellulose into hydrogen and methane) with heat-treated sludge as the seed at various temperatures (60-97 degrees C) and times (20-60 min). Batch experiments were conducted at 55 degrees C and initial pH of 8.0. The results indicate that hydrogen and methane production yields peaked at 4.3 mmol H2/g cellulose and 11.6 mmol CH4/g cellulose using the seed activated sludge that was thermally treated at 60 degrees C for 40 min. These parameter values are higher than those of no-treatment seed (HY 3.6 mmol H2/g cellulose and MY 10.4 mmol CH4/g cellulose). The maximum hydrogen production rate of 26.0 mmol H2/L/d and methane production rate of 23.2 mmol CH4/L/d were obtained for the seed activated sludge that was thermally treated at 70 degrees C for 50 min and 60 degrees C for 40 min, respectively.

The good, the bad and the flexible: plant interactions with pollinators and herbivores over space and time are moderated by plant compensatory responses.

BACKGROUND AND AIMS: Plants are sessile organisms that face selection by both herbivores and pollinators. Herbivores and pollinators may select on the same traits and/or mediate each others' effects. Erysimum capitatum (Brassicaceae) is a widespread and variable plant species with generalized pollination that is attacked by a number of herbivores. The following questions were addressed. (a) Are pollinators and herbivores attracted by similar plant traits? (b) Does herbivory affect pollinator preferences? (c) Do pollinators and/or herbivores affect fitness and select on plant traits? (d) Do plant compensatory responses affect the outcome of interactions among plants, pollinators and herbivores? (e) Do interactions among E. capitatum and its pollinators and herbivores differ among sites and years? METHODS: In 2005 and 2006, observational and experimental studies were combined in four populations at different elevations to examine selection by pollinators and herbivores on floral traits of E. capitatum. KEY RESULTS: Pollinator and herbivore assemblages varied spatially and temporally, as did their effects on plant fitness and selection. Both pollinators and herbivores preferred plants with more flowers, and herbivory sometimes reduced pollinator visitation. Pollinators did not select on plant traits in any year or population and E. capitatum was not pollen limited; however, supplemental pollen resulted in altered plant resource allocation. Herbivores reduced fitness and selected for plant traits in some populations, and these effects were mediated by plant compensatory responses. CONCLUSIONS: Individuals of Erysimum capitatum are visited by diverse groups of pollinators and herbivores that shift in abundance and importance in time and space. Compensatory reproductive mechanisms mediate interactions with both pollinators and herbivores and may allow E. capitatum to succeed in this complex selective environment.

Dynamics of maternal and paternal effects on embryo and seed development in wild radish (Raphanus sativus).

BACKGROUND AND AIMS: Variability in embryo development can influence the rate of seed maturation and seed size, which may have an impact on offspring fitness. While it is expected that embryo development will be under maternal control, more controversial hypotheses suggest that the pollen donor and the embryo itself may influence development. These latter possibilities are, however, poorly studied. Characteristics of 10-d-old embryos and seeds of wild radish (Raphanus sativus) were examined to address: (a) the effects of maternal plant and pollen donor on development; (b) the effects of earlier reproductive events (pollen tube growth and fertilization) on embryos and seeds, and the influence of embryo size on mature seed mass; (c) the effect of water stress on embryos and seeds; (d) the effect of stress on correlations of embryo and seed characteristics with earlier and later reproductive events and stages; and (e) changes in maternal and paternal effects on embryo and seed characteristics during development. METHODS: Eight maternal plants (two each from four families) and four pollen donors were crossed and developing gynoecia were collected at 10 d post-pollination. Half of the maternal plants experienced water stress. Characteristics of embryos and seeds were summarized and also compared with earlier and later developmental stages. KEY RESULTS: In addition to the expected effects of the maternal plants, all embryo characters differed among pollen donors. Paternal effects varied over time, suggesting that there are windows of opportunity for pollen donors to influence embryo development. Water-stress treatment altered embryo characteristics; embryos were smaller and less developed. In addition, correlations of embryo characteristics with earlier and later stages changed dramatically with water stress. CONCLUSIONS: The expected maternal effects on embryo development were observed, but there was also evidence for an early paternal role. The relative effects of these controls may change over time. Thus, there may be times in development when selection on the maternal, paternal or embryo contributions to development are more and less likely.

Prevalence and quantification of Vibrio parahaemolyticus in raw salad vegetables at retail level.

The purpose of this study was to investigate the biosafety of Vibrio parahaemolyticus in raw salad vegetables at wet market and supermarket in Malaysia. A combination of Most Probable Number - Polymerase Chain Reaction (MPN-PCR) method was applied to detect the presence of V. parahaemolyticus and to enumerate their density in the food samples. The study analyzed 276 samples of common vegetables eaten raw in Malaysia (Wild cosmos = 8; Japanese parsley = 21; Cabbage = 30; Lettuce = 16; Indian pennywort = 17; Carrot = 31; Sweet potato = 29; Tomato = 38; Cucumber = 28; Four winged bean = 26; Long bean = 32). The samples were purchased from two supermarkets (A and B) and two wet markets (C and D). The occurrence of V. parahaemolyticus detected was 20.65%, with higher frequency of V. parahaemolyticus in vegetables obtained from wet markets (Wet market C = 27.27%Wet Market D = 32.05%) compared to supermarkets (Supermarket A = 1.64%; Supermarket B = 16.67%). V. parahaemolyticus was most prevalent in Indian pennywort (41.18%). The density of V. parahaemolyticus in all the samples ranged from <3 up to >2400 MPN/g, mostly <3 MPN/g concentration. Raw vegetables from wet markets contained higher levels of V. parahaemolyticus compared to supermarkets. V. parahaemolyticus were present in raw vegetables although in low numbers. The results suggest that raw vegetables act as a transmission route for V. parahaemolyticus. This study will be the first biosafety assessment of V. parahaemolyticus in raw vegetables in Malaysia.

In vitro efficacy of nisin Z against Candida albicans adhesion and transition following contact with normal human gingival cells.

AIM: To investigate the nisin Z innocuity using normal human gingival fibroblast and epithelial cell cultures, and its synergistic effect with these gingival cells against Candida albicans adhesion and transition from blastospore to hyphal form. METHODS AND RESULTS: Cells were cultured to 80% confluence and infected with C. albicans in the absence or presence of various concentrations of nisin Z. Our results indicate that only high concentrations of nisin Z promoted gingival cell detachment and differentiation. Determination of the LD(50) showed that the fibroblasts were able to tolerate up to 80 microg ml(-1) for 24 h, dropping thereafter to 62 mug ml(-1) after 72 h of contact, compared to 160 microg ml(-1) after 24 h, and 80 microg ml(-1) after 72 h recorded by the gingival epithelial cells which displayed a greater resistance to nisin Z. The use of nisin Z even at low concentration (25 microg ml(-1)) at appropriate concentrations with gingival cells significantly reduced C. albicans adhesion to gingival monolayer cultures and inhibited the yeast's transition. CONCLUSION: These findings show that when used at non-toxic levels for human cells, nisin Z can be effective against C. albicans adhesion and transition and may synergistically interact with gingival cells for an efficient resistance against C. albicans. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests the potential usefulness of nisin Z as an antifungal agent, when used in an appropriate range.

Nisin Z inhibits the growth of Candida albicans and its transition from blastospore to hyphal form.

AIMS: To investigate the efficacy of nisin Z, an antimicrobial peptide produced by certain strains of Lactococcus lactis against Candida albicans growth and transition. METHODS AND RESULTS: Candida albicans was cultured in the presence of various concentrations of nisin Z (1000, 500, and 100 microg ml(-1)) for different time points. Candida albicans growth was determined using the Alamar Blue assay. The yeast's transition from blastospore to hyphal form was assessed through optical microscope observations. The effect of nisin Z on C. albicans ultrastructure was followed by scanning and transmission electron microscopy. Our results show that nisin Z inhibited C. albicans growth beginning at 500 microg ml(-1). This inhibition was both time- and dose-dependent. Nisin Z was also active against C. albicans transition by significantly inhibiting the transformation of C. albicans from the blastospore to hyphal form. Treatments with nisin Z lead to ultrastructural disturbances of C. albicans. CONCLUSION: Our findings indicate that nisin Z significantly reduced C. albicans growth and transition. These effects may have occurred through ultrastructural modifications of this yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, effect of nisin Z on C. albicans was investigated. These results therefore suggest that nisin Z may have antifungal properties, and could be used as an antifungal molecule.

Post-traumatic headache: emphasis on chronic types following mild closed head injury.

The syndrome known as chronic post-traumatic headache (CPTH) is controversial, particularly when it occurs following mild closed head injury or "whiplash". Problems with the diagnosis include issues related to classification, epidemiology, pathophysiology (psychogenic vs. organic) and treatment. In addition, there are cultural differences that may influence prevalence and diagnosis, as in some countries with little medico-legal recourse the disorder is virtually unknown. In this paper we review some of these controversies clinicians are left to formulate their own understanding based on available evidence and clinical experience. This is perhaps as it should be given that the best practice combines knowledge of the evidence with individual clinical experience.

Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib.

BACKGROUND: Evidence suggests that both selective cyclooxygenase (COX)-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events. However, evidence from prospective studies of currently available COX-2 inhibitors and non-selective NSAIDs is lacking in patients at high cardiovascular risk who are taking aspirin. OBJECTIVE: To determine the cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. METHODS: The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) of 18 325 patients with osteoarthritis comprised two parallel substudies, comparing lumiracoxib (COX-2 inhibitor) with either ibuprofen or naproxen. A post hoc analysis by baseline cardiovascular risk, treatment assignment, and low-dose aspirin use was performed. The primary composite end point was cardiovascular mortality, non-fatal myocardial infarction, and stroke at 1 year; a secondary end point was the development of congestive heart failure (CHF). RESULTS: In high risk patients among aspirin users, patients in the ibuprofen substudy had more primary events with ibuprofen than lumiracoxib (2.14% vs 0.25%, p = 0.038), whereas in the naproxen substudy rates were similar for naproxen and lumiracoxib (1.58% vs 1.48%, p = 0.899). High risk patients not taking aspirin had fewer primary events with naproxen than with lumiracoxib (0% vs 1.57%, p = 0.027), but not for ibuprofen versus lumiracoxib (0.92% vs 0.80%, p = 0.920). Overall, CHF developed more often with ibuprofen than lumiracoxib (1.28% vs 0.14%; p = 0.031), whereas no difference existed between naproxen and lumiracoxib. CONCLUSIONS: These data suggest that ibuprofen may confer an increased risk of thrombotic and CHF events relative to lumiracoxib among aspirin users at high cardiovascular risk. The study indicates that naproxen may be associated with lower risk relative to lumiracoxib among non-aspirin users. This study is subject to inherent limitations, and therefore should be interpreted as a hypothesis-generating study.