Skistodiaptomus pallidus (Copepoda: Diaptomidae) establishment in New Zealand natural lakes, and its effects on zooplankton community composition

The North American calanoid copepod Skistodiaptomus pallidus is an emerging invader globally, with non-indigenous populations recorded from constructed waters in New Zealand, Germany and Mexico since 2000. We examined the effects of S. pallidus establishment on the zooplankton community of a natural lake, Lake Kereta, where it was first recorded in late-2008, coincident with releases of domestically cultured grass carp (Ctenopharyngodon idella). Although not present in any of our samples prior to August 2008, S. pallidus was found in all samples collected in the subsequent five years. ANOSIM indicated zooplankton community composition significantly differed between samples collected before and after S. pallidus invasion, whether the invader was included in the analysis or not. Zooplankton species affected most greatly were the copepods Calamoecia lucasi and Mesocyclops sp., which decreased in their relative importance, and the cladocerans Bosmina meridionalis and Daphnia galeata, which increased. Rotifer species were relatively unaffected. As the length of grass carp released were >6.5 cm, direct predatory effects by this species on the zooplankton community are unlikely. Associated reductions in macrophyte biomass could explain increases in the relative abundances of planktonic cladocerans (B. meridionalis and D. galeata). However, the effect of macrophyte reduction by grass carp on zooplankton communities is considered to be limited elsewhere, while the reduced macrophyte biomass cannot explain the decrease in relative abundance of the native planktonic calanoid copepod C. lucasi. Competition between C. lucasi and S. pallidus is the most compelling explanation for the reduction in importance of the native calanoid copepod species. Skistodiaptomus pallidus appears to have undergone a “boom-and-bust” cycle in Lake Kereta, increasing in relative abundance in the first three years following establishment, before declining in importance

Complementary transcriptomic and proteomic analyses reveal the cellular and molecular processes that drive growth and development of Fasciola hepatica in the host liver

Background The major pathogenesis associated with Fasciola hepatica infection results from the extensive tissue damage caused by the tunnelling and feeding activity of immature flukes during their migration, growth and development in the liver. This is compounded by the pathology caused by host innate and adaptive immune responses that struggle to simultaneously counter infection and repair tissue damage. Results Complementary transcriptomic and proteomic approaches defined the F. hepatica factors associated with their migration in the liver, and the resulting immune-pathogenesis. Immature liver-stage flukes express ~ 8000 transcripts that are enriched for transcription and translation processes reflective of intensive protein production and signal transduction pathways. Key pathways that regulate neoblast/pluripotent cells, including the PI3K-Akt signalling pathway, are particularly dominant and emphasise the importance of neoblast-like cells for the parasite’s rapid development. The liver-stage parasites display different secretome profiles, reflecting their distinct niche within the host, and supports the view that cathepsin peptidases, cathepsin peptidase inhibitors, saposins and leucine aminopeptidases play a central role in the parasite’s destructive migration, and digestion of host tissue and blood. Immature flukes are also primed for countering immune attack by secreting immunomodulating fatty acid binding proteins (FABP) and helminth defence molecules (FhHDM). Combined with published host microarray data, our results suggest that considerable immune cell infiltration and subsequent fibrosis of the liver tissue exacerbates oxidative stress within parenchyma that compels the expression of a range of antioxidant molecules within both host and parasite. Conclusions The migration of immature F. hepatica parasites within the liver is associated with an increase in protein production, expression of signalling pathways and neoblast proliferation that drive their rapid growth and development. The secretion of a defined set of molecules, particularly cathepsin L peptidases, peptidase-inhibitors, saponins, immune-regulators and antioxidants allow the parasite to negotiate the liver micro-environment, immune attack and increasing levels of oxidative stress. This data contributes to the growing F. hepatica -omics information that can be exploited to understand parasite development more fully and for the design of novel control strategies to prevent host liver tissue destruction and pathology

Electronic cigarette use and risk perception in a Stop Smoking Service in England

Introduction: Electronic cigarette (e-cigarette) use rose substantially within the UK in recent years but currently, Stop Smoking Services in England do not prescribe them due to a lack of regulation. Previous research has examined e-cigarette use and attitudes within English Stop Smoking Services using samples of practitioners and managers; the current study recruited a sample of service users. Methods: Participants (N¼319) aged 18–60 years old were recruited from Roy Castle FagEnds, Liverpool, England (Stop Smoking Service). A cross-sectional questionnaire was completed, which recorded demographic variables, e-cigarette use alongside risk perception, and lastly, smoking behaviour i.e. smoking duration, cigarettes per day, and nicotine dependence. Results: Most participants were female (57.1%), current smokers (53.0%), and current or former e-cigarette users (51.7%). Participants who perceived e-cigarettes as less harmful than smoked tobacco were more likely to have smoked fewer cigarettes per day (p¼0.008). Furthermore, those who felt uncertain whether e-cigarettes were safer than smoked tobacco, were less likely to have tried them (p50.001). Conclusion: This study suggests that e-cigarette use is becoming common among users of Stop Smoking Services (despite e-cigarettes being unavailable from such services) and that e-cigarette risk perception is related to e-cigarette status. The results highlight the importance of providing smokers intending to quit smoking with current and accurate e-cigarette information. Findings may inform future Stop Smoking Services provision and the results demonstrate that further research is warranted

The effects of metformin on maternal haemodynamics in gestational diabetes mellitus: A pilot study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase AIM: To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls. METHODOLOGY: Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control. Non-invasive assessment of maternal haemodynamics, using recognised measures of arterial stiffness and central blood pressure (Arteriograph®), were undertaken under controlled conditions within four gestational windows: antenatal; AN1 (26-28 weeks), AN2 (32-34 weeks) and AN3 (37-40 weeks), and postnatal (PN) (6-8 weeks after delivery). Data were analysed using a linear mixed model incorporating gestational age and other relevant predictors, including age, blood pressure (BP), baseline bodyweight and pulse as fixed effects, and patient as a random effect. RESULTS: Fitted linear mixed models showed evidence of a two-way interaction effect between groups (GDM-D, GDM-M and Control) and stages of gestation (AN1, AN2, AN3 and PN) for maternal haemodynamic parameters: brachial artery augmentation index (AIx) (p=0.004), aortic AIx (p=0.008), and central systolic BP (p=0.001). However, differences in respect of aortic pulse wave velocity (p=0.001) and heart rate (p<0.001) were only significant for gestational stage. At AN2, we did not observe any evidence that the mean brachial Aix in the GDM-M was different from the control group (p=0.158). CONCLUSION: AIx and central systolic BP measures of arterial stiffness are adversely affected by GDM in comparison to controls during pregnancy. The possible beneficial effects of metformin therapy seen at 32 to 34 weeks of gestation require further exploration

Diurnal variation and repeatability of arterial stiffness and cardiac output measurements in the third trimester of uncomplicated pregnancy.

AIM: To investigate same day repeated measures and diurnal variation of arterial stiffness, cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) during the third trimester of normal pregnancy. METHODOLOGY: Pulse wave velocity (PWV) and augmentation index (AIx) were recorded using the Arteriograph, while CO, SV and TPR were recorded using noninvasive cardiac output monitoring. The measurements were obtained in the third trimester of pregnancy from 21 healthy pregnant women at four time points (morning, afternoon, evening and midnight) over a 24-h period. Triplicate measurements of 67 women were obtained at 5-min intervals to assess repeatability between measurements within a patient. RESULTS: Diurnal measurements of arterial stiffness for brachial AIx, aortic AIx and PWV were not statistically significantly different at any of the four time points. Estimated means (SD) for PWV at the four stated time points were 7.81 (2.05), 8.45 (1.68), 7.87 (1.74) and 7.64 m/s (1.15), respectively (P = 0.267). Estimates for AIx at those time points were 10.22 (15.62), 4.44 (10.07), 6.49 (10.92) and 8.40% (8.16), respectively (P = 0.295). Similarly, mean arterial pressure, SV, SV index and TPR did not show any evidence of diurnal variation. However, we observed that the mean CO, cardiac index (CI) and heart rate (HR) varied from morning to midnight; the mean CO, HR and CI increased significantly in the afternoon compared with the corresponding mean morning measurements in a similar fashion to HR. Mean (SD) CO estimates at the four stated time points were 5.90 (1.33), 6.38 (1.49), 6.18 (1.43) and 5.80 ml/min (1.19), respectively, (P < 0.001), whereas mean CI estimates were 3.65 (0.58), 3.93 (0.68), 3.81 (0.65), and 3.57 (0.48), respectively, (P < 0.001), and mean HR estimates were 95 (12), 98 (13), 95 (12) and 88 (12.98), respectively (P < 0.001). Triplicate measurements of 61 women in our repeatability study showed moderate-to-high correlation between observations on the same woman for all Arteriograph and noninvasive cardiac output monitoring variables (estimates of intraclass correlation ranged from 0.49 to 0.91). CONCLUSION: With the exception of CO, CI and HR which showed a diurnal variation, measurements of most haemodynamic parameters did not change significantly from morning to midnight, suggesting there was no evidence of systematic differences in the mean values of these variables at these time points. Multiple consecutive noninvasive measurements of vascular stiffness, CO, SV and TPR were highly correlated confirming repeatability of measurements in the third trimester of uncomplicated pregnancy, so these haemodynamic measurements do not need to be undertaken at a specific time period of the day

Unexpected activity of a novel kunitz-type inhibitor Inhibition of cysteine proteases but not serine proteases

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc. Kunitz-type (KT) protease inhibitors are low molecular weight proteins classically defined as serine protease inhibitors. We identified a novel secreted KT inhibitor associated with the gut and parenchymal tissues of the infective juvenile stage of Fasciola hepatica, a helminth parasite of medical and veterinary importance. Unexpectedly, recombinant KT inhibitor (rFhKT1) exhibited no inhibitory activity toward serine proteases but was a potent inhibitor of the major secreted cathepsin L cysteine proteases of F. hepatica, FhCL1 and FhCL2, and of human cathepsins L and K (Ki ô 0.4-27 nM). FhKT1 prevented the autocatalytic activation of FhCL1 and FhCL2 and formed stable complexes with the mature enzymes. Pulldown experiments from adult parasite culture medium showed that rFhKT1 interacts specifically with native secreted FhCL1, FhCL2, and FhCL5. Substitution of the unusual P1 Leu15 within the exposed reactive loop of FhKT1 for the more commonly found Arg (FhKT1Leu15 / Arg15 ) had modest adverse effects on the cysteine protease inhibition but conferred potent activity against the serine protease trypsin (Ki ô 1.5 nM). Computational docking and sequence analysis provided hypotheses for the exclusive binding of FhKT1 to cysteine proteases, the importance of the Leu15 in anchoring the inhibitor into the S2 active site pocket, and the inhibitor's selectivity toward FhCL1, FhCL2, and human cathepsins L and K. FhKT1 represents a novel evolutionary adaptation of KT protease inhibitors by F. hepatica, with its prime purpose likely in the regulation of the major parasite-secreted proteases and/or cathepsin L-like proteases of its host

Hepatitis C treatment: where are we now?

Chronic hepatitis C infection affects millions of people worldwide and confers significant morbidity and mortality. Effective treatment is needed to prevent disease progression and associated complications. Previous treatment options were limited to interferon and ribavirin regimens, which gave low cure rates and were associated with unpleasant side effects. The era of direct acting antiviral (DAA) therapies began with the development of the first-generation of NS3/4A protease inhibitors (PI) in 2011. They vastly improved outcomes for patients, particularly those with genotype 1 infection, the most prevalent genotype globally. Since then a multitude of DAAs have been licensed for use and outcomes for patients have improved further, with fewer side effects and cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, ribavirin-free and involve a combination of DAA agents. This review summarises the treatment options currently available and discusses potential barriers that may delay the global eradication of hepatitis C

Behçet's syndrome in children and young people in the United Kingdom & Republic of Ireland: a prospective epidemiological study

OBJECTIVES: To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society of Paediatric Dermatologists (BSPD). Consultants reported anonymised cases of BS seen. A follow-up study at one year examined progression of disease and treatment. RESULTS: Over a two-year period, 56 cases met International Criteria for Behçet's Disease. For children under 16 years of age, the two-year period prevalence estimate was 4.2 per million (95% CI 3.2-5.4) and the incidence was 0.96 per million person years (95% CI 0.66-1.41). Mucocutaneous disease was the most common phenotype (56/100%), with ocular (10/56; 17.9%), neurological (2/56; 3.6%) and vascular involvement (3/56; 5.4%) being less common. Median age at onset was 6.34 years and at diagnosis was 11.72 years. There were slightly more female than male children reported (32/56; 55.6%). The majority of cases (85.7%) were white Caucasian. Apart from genital ulcers, which were more common in females, there were no significant differences in frequency of manifestations between male or females, nor between ethnicities. Over 83% of cases had three or more non-primary care healthcare professionals involved in their care. CONCLUSION: BS is extremely rare in CYP in the UK and ROI and most have mucocutaneous disease. Healthcare needs are complex, and coordinated care is key

Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica: Expansion of a repertoire of virulence-associated factors

Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser ↓ His motif for autocatalytic cleavage by cathepsin Ls were preserved. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Comparative study of nonlinear properties of EEG signals of a normal person and an epileptic patient

Background: Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results: Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak \textit{et al.} [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusions: In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation.Comment: Keywords:EEG, epilepsy, Correlation dimension, Surrogate analysis, Hurst exponent. 9 page