Erratum to: The in vitro toxicity of venoms from South Asian Hump-nosed pit vipers (Viperidae: Hypnale)

Hump-nosed pit vipers (Genus Hypnale) are venomous snakes from South India and Sri Lanka. Envenoming by Hypnale species may cause significant morbidity and is characterized by local envenoming and less commonly coagulopathy and acute renal failure. Currently there are three nominal species of this genus: H. hypnale, H. zara and H. nepa. This study investigates the biochemical and pharmacological properties of the venoms from the three Hypnale species in Sri Lanka. The three Hypnale venoms had similar chromatographic profiles using reverse phase high performance liquid chromatography and fractions with procoagulant activity were identified. Hypnale venoms had potent cytotoxicity in cultured rat aorta smooth muscle cells with similar IC50 values. The venoms had weak neurotoxic and myotoxic activity in the isolated chick biventer muscle preparation. They had mild procoagulant activity with close MCC5 values and also phospholipase activity. Locally available polyvalent antivenom did not neutralise any venom effects. The study demonstrates that the three Hypnale venoms are similar and cytotoxicity appears to be the most potent effect, although they have mild procoagulant activity. These findings are consistent with clinical reports

The role of Serum NT-proBNP for predicting left ventricular systolic dysfunction in hospitalized patients in Sri Lanka

Background/aimsOnly a few studies have addressed the role of NT-proBNP in identifying Left Ventricular Systolic Dysfunction (LVSD) in South Asian populations. Therefore, the current study was aimed at assessing the use of serum NT-proBNP in predicting LVSD in a hospitalized population in Sri Lanka.MethodsA random sample of 278 individuals referred for echocardiography at a major Teaching Hospital consented for venous blood samples to be collected for serum NT-proBNP assay by sandwich ELISA. Based on the ejection fraction (LVEF) and fractional shortening (FS), participants were differentiated as LVSD (LVEF<50%, FS≤ 29%) and non-LVSD individuals (LVEF>60%). According to inclusion/exclusion criteria, the final study sample consisted of 100 LVSD patients and 41 non-LVSD individuals.ResultsThe mean ages of the LVSD and non-LVSD groups were 69.1 (±6.2 years) and 71.4 (±2.4 years) (p=0.066) respectively. The median NT-proBNP value (with IQR) among LVSD patients (528.2 pg/mL,355.2–924.2) was comparatively higher than that of non-LVSD individuals (207.3 pg/mL,177.5–343.0). Strong correlations of NT-proBNP level with LVEF (Spearman rho= -0.84, p<0.001) and FS (rho= -0.81, p<0.001) suggested that serum NT-proBNP concentration increases in parallel to deteriorating left ventricular functions. The AUROC of serum NT-proBNP for differentiating LVSD was 0.859 (95% CI:0.79 – 0.92) and the optimal cut-off level for predicting LVSD was 265pg/mL, with 90% sensitivity and 70% specificity.ConclusionCurrent Sri Lankan study revealed a considerable correlation of serum NT-proBNP level with LVSD and utilizing such an assay for screening will facilitate adequate evidence to rule-out LVSD among high-risk residents

The identity of the Sri Lankan Amblypharyngodon (Teleostei, Cyprinidae)

Morphological and molecular analyses of specimens representative of the geographic range of the cyprinid genus Amblypharyngodon in Sri Lanka suggest the presence of only a single species in the island, for which the name Amblypharyngodon grandisquamis Jordan & Starks, 1917, is available. Amblypharyngodon grandisquamis is a species endemic to Sri Lanka, distributed across the lowlands of both of the island’s main climatic zones. It is distinguished from all other species of Amblypharyngodon, including the three species recorded from peninsular India (A. mola, A. microlepis, and A. melettinus), by a suite of characters that includes a body depth of 26.9–31.2% of the standard length (SL), 42–56 scales in the lateral series (of which usually 8–16 are pored), 20–24 circumpeduncular scales, 14–17 scale rows between the origins of the dorsal and pelvic fins, a dorsal-fin height of 21.1–27.6% SL, 18–19 caudal vertebrae and an eye diameter of 22.7–30.5% of the head length. Amblypharyngodon grandisquamis differs from A. melettinus and A. mola by uncorrected pairwise genetic distances of more than 9% and 6%, respectively, for the mitochondrial cytochrome oxidase subunit 1 (COI) gene

Filter based methods for statistical linear inverse problems

Ill-posed inverse problems are ubiquitous in applications. Understanding of algorithms for their solution has been greatly enhanced by a deep understanding of the linear inverse problem. In the applied communities ensemble-based filtering methods have recently been used to solve inverse problems by introducing an artificial dynamical system. This opens up the possibility of using a range of other filtering methods, such as 3DVAR and Kalman based methods, to solve inverse problems, again by introducing an artificial dynamical system. The aim of this paper is to analyze such methods in the context of the linear inverse problem. Statistical linear inverse problems are studied in the sense that the observational noise is assumed to be derived via realization of a Gaussian random variable. We investigate the asymptotic behavior of filter based methods for these inverse problems. Rigorous convergence rates are established for 3DVAR and for the Kalman filters, including minimax rates in some instances. Blowup of 3DVAR and a variant of its basic form is also presented, and optimality of the Kalman filter is discussed. These analyses reveal a close connection between (iterated) regularization schemes in deterministic inverse problems and filter based methods in data assimilation. Numerical experiments are presented to illustrate the theory

Paediatric snakebite envenoming: the world's most neglected 'Neglected Tropical Disease'?

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom.Revisión por pare

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming

Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom induced consumption coagulopathy (VICC). Objectives We investigated the effect of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1:1) high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4U FFP. The primary outcome was the proportion of patients with an international normalized ratio (INR)<2, 6h post-antivenom. Secondary outcomes included anaphylaxis, major haemorrhage, death and clotting factor recovery. Results From 214 eligible patients, 141 were randomized; 71 to high-dose antivenom, 70 to low-dose antivenom/FFP; five had no post-antivenom bloods. The groups were similar except for a delay of 1h in antivenom administration for FFP patients. 6h post-antivenom 23/69 (33%) patients allocated high-dose antivenom had an INR<2 compared with 28/67 (42%) allocated low-dose antivenom/FFP [absolute difference 8%;95%Confidence Interval:-8% to 25%]. 15 patients allocated FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion related acute lung injury. Three deaths occurred in low-dose/FFP patients including one intracranial haemorrhage. There was no difference in recovery rates of INR or fibrinogen, but more rapid initial recovery of factor V and X in FFP patients. Conclusion FFP post-antivenom in Russell's viper bites didn't hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting low-dose antivenom is sufficient

Haemotixic snake venoms: their functional activity, impact on snakebite victims and pharmaceutical promise

Snake venoms are mixtures of numerous proteinacious components that exert diverse functional activities on a variety of physiological targets. Because the toxic constituents found in venom vary from species to species, snakebite victims can present with a variety of life-threatening pathologies related to the neurotoxic, cytotoxic and haemotoxic effects of venom. Of the 1·8 million people envenomed by snakes every year, up to 125 000 die, while hundreds of thousands survive only to suffer with life-changing long-term morbidity. Consequently, snakebite is one of the world's most severe neglected tropical diseases. Many snake venoms exhibit strong haemotoxic properties by interfering with blood pressure, clotting factors and platelets, and by directly causing haemorrhage. In this review we provide an overview of the functional activities of haemotoxic venom proteins, the pathologies they cause in snakebite victims and how their exquisite selectivity and potency make them amenable for use as therapeutic and diagnostic tools relevant for human medicine

Two snakebite antivenoms have potential to reduce Eswatini’s dependency upon a single, increasingly unavailable product: Results of preclinical efficacy testing

Background Snakebite is a major public health concern in Eswatini, where treatment relies upon one antivenom—SAIMR Polyvalent. Although effective in treating snakebite, SAIMR Polyvalent is difficult to source outside its manufacturing country (South Africa) and is dauntingly expensive. We compared the preclinical venom-neutralising efficacy of two alternative antivenoms with that of SAIMR Polyvalent against the lethal and tissue-destructive effects of venoms from five species of medically important snakes using in vivo murine assays. The test antivenoms were ‘Panafrican’ manufactured by Instituto Clodomiro Picado and ‘PANAF’ manufactured by Premium Serums & Vaccines. Principal findings In vivo murine preclinical studies identified both test antivenoms were equally or more effective than SAIMR Polyvalent at neutralising lethal and tissue-destructive effects of Naja mossambica venom. Both test antivenoms were less effective than SAIMR Polyvalent at neutralising the lethal effects of Bitis arietans, Dendroaspis polylepis, Hemachatus haemachatus and Naja annulifera venoms, but similarly effective at neutralising tissue damage induced by B. arietans and H. haemachatus venoms. In vitro immunological assays identified that the titres and toxin-specificities of immunoglobulins (iGs) in the test antivenoms were comparable to that of SAIMR Polyvalent. Plasma clotting disturbances by H. haemachatus and N. mossambica were neutralised by the test antivenoms, whereas SAIMR Polyvalent failed to neutralise this bioactivity of N. mossambica venom. B. arietans SVMP activity was equally reduced by all three antivenoms, and H. haemachatus and N. mossambica PLA2 activities were neutralised by all three antivenoms. Conclusions While both Panafrican and PANAF antivenoms exhibited promising preclinical efficacies, both were less poly-specifically effective than SAIMR Polyvalent in these murine assays. The efficacy of these antivenoms against the lethal and tissue-destructive effects of N. mossambica venom, the most common biting species in Eswatini, identify that Panafrican and PANAF antivenoms offer effective alternatives to SAIMR Polyvalent for the treatment of snakebite in Eswatini, and potentially for neighbouring countries

Ultrasonic devulcanization of sulfur vulcanized natural rubber

The high-energy ultrasound could be used to devulcanize rubber as it can focus energy into localized sites for selective bond rupture. The research work reported to date suggests that the ultrasonic technology is more suited to convert rubber waste to a usable material efficiently, effectively and environmental friendly. The ultrasonic devulcanization reactor consisted of three main sections, namely a power source, ultrasonic transducer with sample holding unit, and a monitoring system to measure the amplitude, frequency and power. N-cyclohexyl-2-benzthiazyl sulfenamide (CBS) accelerated unfilled natural rubber vulcanized with conventional sulfur vulcanizing system and with efficient sulfur vulcanizing system were used as the model rubber compounds in these experiments. 2 mm thick vulcanized rubber sheets were directly kept on the vibrating diaphragm of the ultrasonic transducer. The frequency of ultrasonic wave was varied in a range of 20 to 50 kHz and the power level was varied up to 800 watt. The treatment time was limited to 10 minutes when treated at high power levels. The vibrating amplitudes were measured at different power levels with the variation of ultrasonic frequency. Curing behaviour, gel content and cross-link density were studied for rubber samples devulcanized at different process conditions. The increase in cross-link density and gel content of the samples treated at lower amplitudes indicated the formation of additional cross-links. However, the higher vibrational energies associated with high amplitudes resulted in lower cross-link densities and gel contents indicating a breakdown of bonds. Cure curves of virgin and devulcanized NR samples suggested that the fast initial curing of devulcanized NR was due to the presence of active sufidized rubber molecules formed due to break down of some cross-links during devulcanization. The lower maximum torque values observed in the devulcanized samples were due to the partial breakdown of C-C bonds in the main chain. The tensile properties of the revulcanized samples gave comparable results with that of virgin rubber. A theoretical process model was developed to express the extent of devulcanization in terms of cross-link density. It was based on the vibrational energy transfer mechanism. The model treated the vulcanized rubber as a pure elastic solid containing void regions. Experimental and theoretical values lied within ± 10% error limits. The model showed that the media effect on the nature of void excitation was significant and the viscoelasticity was also considerable. However, the effect due to surface tension was negligible