Two new notocotylid trematodes from birds in Tasmania and their life histories

Paramonostomum caeci n. sp., adults of which occur mainly in the intestinal caeca of Anas supereiliosa, Cygnus atratus and Polioeephalus polioeephalus, is described. It is considered to closely resemble P. malerisehi from which it differs in being only one-third the size, having a spinose tegument and a cirrus covered with tubercles. P. bursae n.sp., adults of which have been found inhabiting the bursa of Fabricius of Anas supereiliosa is described and considered to be most similar to P. alveatum and P. parvum but to differ from them in the distribution of its vitellaria, the position of its ovary relative to the testes and in having a greater number of uterine loops. The domestic duck, Anas platyrhynehos, was found to serve as an experimental host for both new species. A brackish water snail, Coxiella badgerensis, inhabiting Calverts Lagoon in southeast Tasmania serves as a natural intermediate host for P. caeci n.sp. and P. bursae n.sp. and also for two other undescribed notocotylids. Developmental stages (rediae, cercariae and metacercariae) of both new Paramonostomum species are described. The cercaria of P. caeci n. sp. belongs to the Imbricata group, and that of P. bursae n.sp. to the Yenchingensis group

Two strigeoid trematodes, Apatemon (Apatemon) gracilis (Rudolphi, 1819) and Diploetomum (Dolichorchis)galaxiae n. sp., which encyst in the freshwater fish Galaxias auratus Johnston in Lake Crescent, Tasmania.

The metacercaria and adult of Apatemon (Apatemon) gracilis (Rudolphi) and Diplostomum (Dolichorchis) galaxiae n.sp. are described and figured. Metacercarial cysts of these species occur in different parts of the endemic fish Galaxias auratus: A. gracilis in the body cavity, orbit and vitreous humour, and D. galaxiae n.sp. visible as black spots ('black-spot disease') in the musculature of the body and head. A gracilis which has not previously been recorded from Australia occurs in the black duck, Anas superciliosa, while D. galaxiae n.sp. infects the white-faced heron, Ardea novaehollandiae. The domestic duck, Anas platyrhynchos, is much more susceptible to experimental infection by Apatemon gracilis than by D. galaxiae n.sp. Both flukes inhabit the upper small intestine of their bird hosts. The reproductive system of D. galaxiae n.sp. is amphitypic. D. galaxiae n.sp. most closely resembles D. heronei Srivastava, 1954 and D. ketupanensis Vidyarthi, 1937; a key to species in the sub-genus Dolichorchis is given

Update on Optic Neuritis: An International View

Previously, optic neuritis was thought to be typical, i.e. idiopathic or multiple sclerosis (MS) related, associated with a good visual prognosis, or atypical, i.e. not associated with MS and requiring corticosteroids or plasma exchange for vision to recover. More recently, the importance of optic neuritis in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein (MOG) antibody disease has become more appreciated. The results of the Optic Neuritis Treatment Trial (ONTT) has influenced how optic neuritis is treated around the world. For this review we surveyed the international literature on optic neuritis in adults. Our aims were first to find the reported incidence of optic neuritis in different countries and to ascertain what percentage of cases were seropositive for anti-aquaporin 4 and anti-MOG antibodies, and second, to document the presenting features, treatment, and outcomes from a first episode of the different types of optic neuritis from these countries, and to compare the results with the outcomes of the ONTT cohort. From these data we have sought to highlight where ambiguities currently lie in how to manage optic neuritis and have made recommendations as to how future treatment trials in optic neuritis should be carried out in the current antibody testing era

Massive Liver Cell Necrosis Induced in the Pig with Carbon Tetrachloride

An attempt was made to induce massive liver necrosis in the pig by the injection of varying doses of carbon tetrachloride into the afferent vessels of the liver. The optimal route and dose of injection were assessed as well as the effect of prior phenobarbitone administration. Survival, and biochemical and histological changes were noted. A preliminary trial of exchange transfusion showed that the model could be used, but a number of variables complicates evaluation in this biological system. A large number of animals would be needed under strictly paired conditions in order to draw significant conclusions.S. Afr. Med. J., 48, 1201 (1974)

Gating of TonB-dependent transporters by substrate-specific forced remodelling

Membrane proteins play vital roles in inside-out and outside-in signal transduction by responding to inputs that include mechanical stimuli. Mechanical gating may be mediated by the membrane or by protein(s) but evidence for the latter is scarce. Here we use force spectroscopy, protein engineering and bacterial growth assays to investigate the effects of force on TonB-TonB dependent transporter (TBDT) complexes of Gram-negative bacteria. We confirm the feasibility of protein-only mediated mechanical gating by demonstrating that the interaction between TonB and BtuB (a TBDT) is sufficiently strong under force to create a channel through the TBDT. In addition, by comparing the dimensions of the force-induced channel in BtuB and a second TBDT (FhuA) we show that the mechanical properties of the interaction are perfectly tuned to their function by inducing formation of a channel whose dimensions are tailored to the ligand

Addressing a system failure to diagnose COPD and asthma

To provide high-quality guideline-based care for patients with asthma or chronic obstructive pulmonary disease (COPD) we must first establish the correct diagnosis. The National Asthma and COPD Audit Programme (NACAP) has highlighted an important issue across England, Scotland, and Wales that potentially undermines care for many people with airways disease

Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis

Background: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses. Methods: Eighty-six acute ON cases were randomized to receive phenytoin (4–6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL). Results: Sixty-four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo – phenytoin was −44 pg/ml at 3 months (P = 0.019) and −27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and −1.6 pg/ml at 6 months (P = 0.766). Conclusions: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized

Ethanol reversal of tolerance to the respiratory depressant effects of morphine

Opioids are the most common drugs associated with unintentional drug overdose. Death results from respiratory depression. Prolonged use of opioids results in the development of tolerance but the degree of tolerance is thought to vary between different effects of the drugs. Many opioid addicts regularly consume alcohol (ethanol), and post-mortem analyses of opioid overdose deaths have revealed an inverse correlation between blood morphine and ethanol levels. In the present study, we determined whether ethanol reduced tolerance to the respiratory depressant effects of opioids. Mice were treated with opioids (morphine, methadone, or buprenorphine) for up to 6 days. Respiration was measured in freely moving animals breathing 5% CO(2) in air in plethysmograph chambers. Antinociception (analgesia) was measured as the latency to remove the tail from a thermal stimulus. Opioid tolerance was assessed by measuring the response to a challenge dose of morphine (10 mg/kg i.p.). Tolerance developed to the respiratory depressant effect of morphine but at a slower rate than tolerance to its antinociceptive effect. A low dose of ethanol (0.3 mg/kg) alone did not depress respiration but in prolonged morphine-treated animals respiratory depression was observed when ethanol was co-administered with the morphine challenge. Ethanol did not alter the brain levels of morphine. In contrast, in methadone- or buprenorphine-treated animals no respiratory depression was observed when ethanol was co-administered along with the morphine challenge. As heroin is converted to morphine in man, selective reversal of morphine tolerance by ethanol may be a contributory factor in heroin overdose deaths

Evaluating the cost-effectiveness of existing needle and syringe programmes in preventing Hepatitis C transmission in people who inject drugs

Aim To evaluate the cost-effectiveness of needle and syringe programmes (NSPs) compared to no NSPs on hepatitis C virus (HCV) transmission in the United Kingdom.Design Cost-effectiveness analysis from NHS/ health-provider perspective, utilising a dynamic transmission model of HCV infection and disease progression, calibrated using city-specific surveillance and survey data, and primary data collection on NSP costs. The effectiveness of NSPs preventing HCV acquisition was based on empirical evidence.Setting UK settings with different chronic HCV prevalence among people who inject drugs (PWID): Dundee (26%), Walsall (18%), and Bristol (45%)Population PWIDInterventions Current NSP provision is compared to a counterfactual scenario where NSPs are removed for 10 years and then returned to existing levels with effects collected for 40 years. Measurements HCV infections, and cost per quality adjusted life year (QALY) gained through NSPs over 50 years Findings Compared to a willingness-to-pay threshold of £20,000 per QALY gained, NSPs were highly cost-effective over a time-horizon of 50 years and decreased the number of HCV incident infections. The mean incremental cost-effectiveness ratio was cost-saving in Dundee and Bristol, and £596 per QALY gained in Walsall, with 78%, 46% and 40% of simulations being cost-saving in each city, respectively, with differences driven by coverage of NSP and HCV prevalence (lowest in Walsall). Over 90% of simulations were cost-effective at the willingness-to-pay threshold. Results were robust to sensitivity analyses including varying the time-horizon, HCV treatment cost and numbers of HCV treatments per year. Conclusions We projected NSPs avert HCV infections and are highly cost-effective in the UK and could be cost-saving to the NHS and other health care providers. NSPs will remain cost-effective in the UK irrespective of changes in HCV treatment cost and scale-up, meaning that NSPs will continue to be an efficient strategy for preventing HCV transmission in the future