Preliminary antidiarrhoeal activity of methanolic extracts of Securinega virosa (Euphorbiaceae)

Securinega virosa is used as remedy for diarrhoea in tropical Africa, but has not been investigated for its antidiarrhoeal activity. This study was therefore aimed at investigating the methanolic extracts of theleaves, stem bark and root bark for antidirrhoeal activity, using castor oil-induced diarrhoeal model in mice. The effects of these extracts on perfused isolated rabbit jejunum were also evaluated. Themethanolic leaves extract (8 x 10-5 – 1.6 x 10-3 mgml-1) produced a dose-dependent relaxation of the rabbit jejunum, while the methanolic stem bark and root bark extracts (2 x 10-5 – 3.2 x 10-3 mgml-1)produced contraction of the tissue. The methanolic root bark extract produced a dose-dependent protection against the castor oil- induced diarrhoea with the highest protection (100%), obtained at 100mgkg-1 comparable to that of loperamide (5 mgkg-1), the standard agent. The leaves extract also protected the mice but was not dose-dependent. The highest protection (60%) was obtained at thelowest dose (50 mgkg-1). The stem bark extract did not protect the animal against diarrhoea. The preliminary phytochemical analysis revealed that the three extracts contained similar phytochemicalconstituents which include alkaloids, tannins, saponins, flavonoids and cardiac glycosides. However, only the leaves extract contained anthraquinone glycosides. The acute toxicity test revealed the medianlethal dose (LD50) values for the leaves, stem bark and root bark extracts to be 1265, 288.5 and 774.6 mgkg-1 respectively. This suggests that the stem bark extract is relatively the most toxic. These results obtained revealed that the leaves and root bark extracts possess pharmacological activity against diarrhoea and may possibly explain the use of the plant in traditional medicine

International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) - the propagation of knowledge in ultrasound for the improvement of OB/GYN care worldwide: experience of basic ultrasound training in Oman.

BACKGROUND: The aim of this study is to evaluate effectiveness of a new ISUOG (International Society of Ultrasound in Obstetrics and Gynecology) Outreach Teaching and Training Program delivered in Muscat, Oman. METHODS: Quantitative assessments to evaluate knowledge and practical skills were administered before and after an ultrasound course for sonologists attending the ISUOG Outreach Course, which took place in November, 2017, in Oman. Trainees were selected from each region of the country following a national vetting process conducted by the Oman Ministry of Health. Twenty-eight of the participants were included in the analysis. Pre- and post-training practical and theoretical scores were evaluated and compared. RESULTS: Participants achieved statistically significant improvements, on average by 47% (p < 0.001), in both theoretical knowledge and practical skills. Specifically, the mean score in the theoretical knowledge test significantly increased from 55.6% (± 14.0%) to 81.6% (± 8.2%), while in the practical test, the mean score increased from 44.6% (± 19.5%) to 65.7% (± 23.0%) (p < 0.001). Performance was improved post-course among 27/28 participants (96.4%) in the theoretical test (range: 14 to 200%) and among 24/28 (85.7%) trainees in the practical skills test (range: 5 to 217%). CONCLUSION: Application of the ISUOG Basic Training Curriculum and Outreach Teaching and Training Course improved the theoretical knowledge and practical skills of local health personnel. Long-term re-evaluation is, however, considered imperative to ascertain and ensure knowledge retention

Symptoms and signs of lung cancer prior to diagnosis: case-control study using electronic health records from ambulatory care within a large US-based tertiary care centre.

OBJECTIVE: Lung cancer is the most common cause of cancer-related death in the USA. While most patients are diagnosed following symptomatic presentation, no studies have compared symptoms and physical examination signs at or prior to diagnosis from electronic health records (EHRs) in the USA. We aimed to identify symptoms and signs in patients prior to diagnosis in EHR data. DESIGN: Case-control study. SETTING: Ambulatory care clinics at a large tertiary care academic health centre in the USA. PARTICIPANTS, OUTCOMES: We studied 698 primary lung cancer cases in adults diagnosed between 1 January 2012 and 31 December 2019, and 6841 controls matched by age, sex, smoking status and type of clinic. Coded and free-text data from the EHR were extracted from 2 years prior to diagnosis date for cases and index date for controls. Univariate and multivariable conditional logistic regression were used to identify symptoms and signs associated with lung cancer at time of diagnosis, and 1, 3, 6 and 12 months before the diagnosis/index dates. RESULTS: Eleven symptoms and signs recorded during the study period were associated with a significantly higher chance of being a lung cancer case in multivariable analyses. Of these, seven were significantly associated with lung cancer 6 months prior to diagnosis: haemoptysis (OR 3.2, 95% CI 1.9 to 5.3), cough (OR 3.1, 95% CI 2.4 to 4.0), chest crackles or wheeze (OR 3.1, 95% CI 2.3 to 4.1), bone pain (OR 2.7, 95% CI 2.1 to 3.6), back pain (OR 2.5, 95% CI 1.9 to 3.2), weight loss (OR 2.1, 95% CI 1.5 to 2.8) and fatigue (OR 1.6, 95% CI 1.3 to 2.1). CONCLUSIONS: Patients diagnosed with lung cancer appear to have symptoms and signs recorded in the EHR that distinguish them from similar matched patients in ambulatory care, often 6 months or more before diagnosis. These findings suggest opportunities to improve the diagnostic process for lung cancer

Serial CT analysis in idiopathic pulmonary fibrosis: comparison of visual features that determine patient outcome

Aims: Patients with idiopathic pulmonary fibrosis (IPF) receiving antifibrotic medication and patients with non-IPF fibrosing lung disease often demonstrate rates of annualised forced vital capacity (FVC) decline within the range of measurement variation (5.0%–9.9%). We examined whether change in visual CT variables could help confirm whether marginal FVC declines represented genuine clinical deterioration rather than measurement noise. Methods: In two IPF cohorts (cohort 1: n=103, cohort 2: n=108), separate pairs of radiologists scored paired volumetric CTs (acquired between 6 and 24 months from baseline). Change in interstitial lung disease, honeycombing, reticulation, ground-glass opacity extents and traction bronchiectasis severity was evaluated using a 5-point scale, with mortality prediction analysed using univariable and multivariable Cox regression analyses. Both IPF populations were then combined to determine whether change in CT variables could predict mortality in patients with marginal FVC declines. Results: On univariate analysis, change in all CT variables except ground-glass opacity predicted mortality in both cohorts. On multivariate analysis adjusted for patient age, gender, antifibrotic use and baseline disease severity (diffusing capacity for carbon monoxide), change in traction bronchiectasis severity predicted mortality independent of FVC decline. Change in traction bronchiectasis severity demonstrated good interobserver agreement among both scorer pairs. Across all study patients with marginal FVC declines, change in traction bronchiectasis severity independently predicted mortality and identified more patients with deterioration than change in honeycombing extent. Conclusions: Change in traction bronchiectasis severity is a measure of disease progression that could be used to help resolve the clinical importance of marginal FVC declines

IACT observations of gamma-ray bursts: prospects for the Cherenkov Telescope Array

Gamma rays at rest frame energies as high as 90 GeV have been reported from gamma-ray bursts (GRBs) by the Fermi Large Area Telescope (LAT). There is considerable hope that a confirmed GRB detection will be possible with the upcoming Cherenkov Telescope Array (CTA), which will have a larger effective area and better low-energy sensitivity than current-generation imaging atmospheric Cherenkov telescopes (IACTs). To estimate the likelihood of such a detection, we have developed a phenomenological model for GRB emission between 1 GeV and 1 TeV that is motivated by the high-energy GRB detections of Fermi-LAT, and allows us to extrapolate the statistics of GRBs seen by lower energy instruments such as the Swift-BAT and BATSE on the Compton Gamma-ray Observatory. We show a number of statistics for detected GRBs, and describe how the detectability of GRBs with CTA could vary based on a number of parameters, such as the typical observation delay between the burst onset and the start of ground observations. We also consider the possibility of using GBM on Fermi as a finder of GRBs for rapid ground follow-up. While the uncertainty of GBM localization is problematic, the small field-of-view for IACTs can potentially be overcome by scanning over the GBM error region. Overall, our results indicate that CTA should be able to detect one GRB every 20 to 30 months with our baseline instrument model, assuming consistently rapid pursuit of GRB alerts, and provided that spectral breaks below 100 GeV are not a common feature of the bright GRB population. With a more optimistic instrument model, the detection rate can be as high as 1 to 2 GRBs per year.Comment: 28 pages, 24 figures, 4 tables, submitted to Experimental Astronom

Distances and ages of globular clusters using Hipparcos parallaxes of local subdwarfs

We discuss the impact of Population II and Globular Cluster (GCs) stars on the derivation of the age of the Universe, and on the study of the formation and early evolution of galaxies, our own in particular. The long-standing problem of the actual distance scale to Population II stars and GCs is addressed, and a variety of different methods commonly used to derive distances to Population II stars are briefly reviewed. Emphasis is given to the discussion of distances and ages for GCs derived using Hipparcos parallaxes of local subdwarfs. Results obtained by different authors are slightly different, depending on different assumptions about metallicity scale, reddenings, and corrections for undetected binaries. These and other uncertainties present in the method are discussed. Finally, we outline progress expected in the near future.Comment: Invited review article to appear in: `Post-Hipparcos Cosmic Candles', A. Heck & F. Caputo (Eds), Kluwer Academic Publ., Dordrecht, in press. 22 pages including 3 tables and 2 postscript figures, uses Kluwer's crckapb.sty LaTeX style file, enclose

Vocalisations of Killer Whales (Orcinus orca) in the Bremer Canyon, Western Australia

To date, there has been no dedicated study in Australian waters on the acoustics of killer whales. Hence no information has been published on the sounds produced by killer whales from this region. Here we present the first acoustical analysis of recordings collected off the Western Australian coast. Underwater sounds produced by Australian killer whales were recorded during the months of February and March 2014 and 2015 in the Bremer Canyon in Western Australia. Vocalisations recorded included echolocation clicks, burst-pulse sounds and whistles. A total of 28 hours and 29 minutes were recorded and analysed, with 2376 killer whale calls (whistles and burst-pulse sounds) detected. Recordings of poor quality or signal-to-noise ratio were excluded from analysis, resulting in 142 whistles and burst-pulse vocalisations suitable for analysis and categorisation. These were grouped based on their spectrographic features into nine Bremer Canyon (BC) "call types". The frequency of the fundamental contours of all call types ranged from 600 Hz to 29 kHz. Calls ranged from 0.05 to 11.3 seconds in duration. Biosonar clicks were also recorded, but not studied further. Surface behaviours noted during acoustic recordings were categorised as either travelling or social behaviour. A detailed description of the acoustic characteristics is necessary for species acoustic identification and for the development of passive acoustic tools for population monitoring, including assessments of population status, habitat usage, migration patterns, behaviour and acoustic ecology. This study provides the first quantitative assessment and report on the acoustic features of killer whales vocalisations in Australian waters, and presents an opportunity to further investigate this little-known population

New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.

Using a combination of exome sequencing and linkage analysis, we investigated an English family with two affected siblings in their 40s with recessive Charcot-Marie Tooth disease type 2 (CMT2). Compound heterozygous mutations in the immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) gene were identified. Further sequencing revealed a total of 11 CMT2 families with recessively inherited IGHMBP2 gene mutations. IGHMBP2 mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. The individuals with CMT2 described here, have slowly progressive weakness, wasting and sensory loss, with an axonal neuropathy typical of CMT2, but no significant respiratory compromise. Segregating IGHMBP2 mutations in CMT2 were mainly loss-of-function nonsense in the 5' region of the gene in combination with a truncating frameshift, missense, or homozygous frameshift mutations in the last exon. Mutations in CMT2 were predicted to be less aggressive as compared to those in SMARD1, and fibroblast and lymphoblast studies indicate that the IGHMBP2 protein levels are significantly higher in CMT2 than SMARD1, but lower than controls, suggesting that the clinical phenotype differences are related to the IGHMBP2 protein levels

Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues

Funding Information: This study was supported by the Latvian National Research Program BIOMEDICINE. E. Liepinsh was supported by the FP7 project InnovaBalt [grant Nr. 316149]. We would like to thank Dr. Reinis Vilskersts and Gita Dambrova for help with the isolated skeletal muscle experiments. Publisher Copyright: © 2017 The Author(s).Increased plasma concentrations of acylcarnitines (ACs) are suggested as a marker of metabolism disorders. The aim of the present study was to clarify which tissues are responsible for changes in the AC pool in plasma. The concentrations of medium- and long-chain ACs were changing during the fed-fast cycle in rat heart, muscles and liver. After 60 min running exercise, AC content was increased in fasted mice muscles, but not in plasma or heart. After glucose bolus administration in fasted rats, the AC concentrations in plasma decreased after 30 min but then began to increase, while in the muscles and liver, the contents of medium- and long-chain ACs were unchanged or even increased. Only the heart showed a decrease in medium- and long-chain AC contents that was similar to that observed in plasma. In isolated rat heart, but not isolated-contracting mice muscles, the significant efflux of medium- and long-chain ACs was observed. The efflux was reduced by 40% after the addition of glucose and insulin to the perfusion solution. Overall, these results indicate that during fed-fast cycle shifting the heart determines the medium- and long-chain AC profile in plasma, due to a rapid response to the availability of circulating energy substrates.publishersversionPeer reviewe