To bite the hand that feeds you: A case of thrombotic microangiopathy due to Tiger snake bite.

This report details the case of a 51-year-old man with a Tiger snake bite who developed systemic envenomation, coagulopathy and thrombotic microangiopathy (TMA) requiring renal replacement therapy. He received plasma exchange as additional therapy while awaiting confirmation of the cause of the TMA. We discuss clinical decision making in detection of systemic envenomation and management of the rare complication of TMA, as well as current Australian guidelines around antivenom administration.

Case report of a pan-cytokeratin negative NUT midline carcinoma of pulmonary origin, a BRD3-NUT variant: Challenges in cytomorphologic presentation.

NUT carcinoma is an aggressive malignancy defined genetically by a balanced translocation of the NUT gene on chromosome 15q14, most commonly associated with the bromodomain-containing protein 4 (BRD4) gene on 19p13.1 but less frequently with variant genes, including BRD3 and NSD-3. We present a case report of a metastatic pulmonary NUT carcinoma found to have a BRD3-NUT fusion and to have only focal pan-cytokeratin staining.

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma.

Zanubrutinib (BGB-3111) is a next-generation Bruton tyrosine kinase inhibitor designed to be more selective with fewer off-target effects. We conducted a phase 1 study to assess the safety of its combination with obinutuzumab and evaluate early efficacy in 81 patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or relapsed/refractory (R/R) follicular lymphoma (FL). In this phase 1b study, zanubrutinib was tolerable at 160 mg twice daily or 320 mg once daily combined with IV obinutuzumab in patients with CLL/SLL (n = 45) and FL (n = 36).

Biochemical and Structural Characterization of XoxG and XoxJ and Their Roles in Lanthanide-Dependent Methanol Dehydrogenase Activity.

Lanthanide (Ln)-dependent methanol dehydrogenases (MDHs) have recently been shown to be widespread in methylotrophic bacteria. Along with the core MDH protein, XoxF, these systems contain two other proteins, XoxG (a c-type cytochrome) and XoxJ (a periplasmic binding protein of unknown function), about which little is known. In this work, we have biochemically and structurally characterized these proteins from the methyltroph Methylobacterium extorquens AM1.

Structures of Class Id Ribonucleotide Reductase Catalytic Subunits Reveal a Minimal Architecture for Deoxynucleotide Biosynthesis.

Class I ribonucleotide reductases (RNRs) share a common mechanism of nucleotide reduction in a catalytic α subunit. All RNRs initiate catalysis with a thiyl radical, generated in class I enzymes by a metallocofactor in a separate β subunit. Class Id RNRs use a simple mechanism of cofactor activation involving oxidation of a Mn cluster by free superoxide to yield a metal-based MnMn oxidant.

Brain-wide cellular resolution imaging of Cre transgenic zebrafish lines for functional circuit-mapping.

Decoding the functional connectivity of the nervous system is facilitated by transgenic methods that express a genetically encoded reporter or effector in specific neurons; however, most transgenic lines show broad spatiotemporal and cell-type expression. Increased specificity can be achieved using intersectional genetic methods which restrict reporter expression to cells that co-express multiple drivers, such as Gal4 and Cre. To facilitate intersectional targeting in zebrafish, we have generated more than 50 new Cre lines, and co-registered brain expression images with the Zebrafish Brain Browser, a cellular resolution atlas of 264 transgenic lines.

Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis with a tyrosine-derived dihydroxyphenylalanine radical.

All cells obtain 2'-deoxyribonucleotides for DNA synthesis through the activity of a ribonucleotide reductase (RNR). The class I RNRs found in humans and pathogenic bacteria differ in () use of Fe(II), Mn(II), or both for activation of the dinuclear-metallocofactor subunit, β; () reaction of the reduced dimetal center with dioxygen or superoxide for this activation; () requirement (or lack thereof) for a flavoprotein activase, NrdI, to provide the superoxide from O; and () use of either a stable tyrosyl radical or a high-valent dimetal cluster to initiate each turnover by oxidizing a cysteine residue in the α subunit to a radical (Cys•). The use of manganese by bacterial class I, subclass b-d RNRs, which contrasts with the exclusive use of iron by the eukaryotic Ia enzymes, appears to be a countermeasure of certain pathogens against iron deprivation imposed by their hosts.

Genome Plasticity of -Defective Staphylococcus aureus during Clinical Infection.

Therapy for bacteremia caused by is often ineffective, even when treatment conditions are optimal according to experimental protocols. Adapted subclones, such as those bearing mutations that attenuate -mediated virulence activation, are associated with persistent infection and patient mortality. To identify additional alterations in -defective mutants, we sequenced and assembled the complete genomes of clone pairs from colonizing and infected sites of several patients in whom demonstrated a within-host loss of function.

Evaluating the effectiveness of trematocides against Fasciola gigantica and amphistomes infections in cattle, using faecal egg count reduction tests in Iringa Rural and Arumeru Districts, Tanzania.

Background: Fasciolosis, caused by the liver fluke Fasciola gigantica, and paramphistomosis are widespread in cattle in Tanzania, and the use of trematocides is encouraged by the Government livestock extension officers. However, reduced efficacy of oxyclozanide against Fasciola gigantica and amphistomes (rumen flukes), and albendazole against F. gigantica, has been reported in some regions.

Structural Basis for Superoxide Activation of Flavobacterium johnsoniae Class I Ribonucleotide Reductase and for Radical Initiation by Its Dimanganese Cofactor.

A ribonucleotide reductase (RNR) from Flavobacterium johnsoniae ( Fj) differs fundamentally from known (subclass a-c) class I RNRs, warranting its assignment to a new subclass, Id. Its β subunit shares with Ib counterparts the requirements for manganese(II) and superoxide (O) for activation, but it does not require the O-supplying flavoprotein (NrdI) needed in Ib systems, instead scavenging the oxidant from solution. Although Fj β has tyrosine at the appropriate sequence position (Tyr 104), this residue is not oxidized to a radical upon activation, as occurs in the Ia/b proteins.

Opportunistic screening for alcohol use problems in adolescents attending emergency departments: an evaluation of screening tools.

Objective: To estimate and compare the optimal cut-off score of Alcohol Use Disorders Identification Test (AUDIT) and AUDIT-C in identifying at-risk alcohol consumption, heavy episodic alcohol use, ICD-10 alcohol abuse and alcohol dependence in adolescents attending ED in England.

Design: Opportunistic cross-sectional survey.

Setting: 10 emergency departments across England.

Alcohol Consumption, Early-Onset Drinking, and Health-Related Consequences in Adolescents Presenting at Emergency Departments in England.

Purpose: Globally, alcohol use is the leading cause of ill health and life years lost in adolescents, although its clinical impact is often overlooked, particularly in England where most research is based in schools. This study aims to examine the prevalence of alcohol consumption and the association between alcohol consumption and age of onset with health and social consequences among adolescents presenting to emergency departments (EDs).

Methods: Consecutive attenders (n = 5,576) aged 10-17 years at 10 EDs were included.

Cattle and Nematodes Under Global Change: Transmission Models as an Ally.

Nematode infections are an important economic constraint to cattle farming. Future risk levels and transmission dynamics will be affected by changes in climate and farm management. The prospect of altered parasite epidemiology in combination with anthelmintic resistance requires the adaptation of current control approaches.

Modelling Cooperia oncophora: Quantification of key parameters in the parasitic phase.

Cooperia oncophora is one of the most common intestinal nematodes in cattle. It is also the dose-limiting species for the most frequently used anthelmintics, and consequently, the species usually involved in reports of anthelmintic resistance. However, little information is available on its population dynamics, hindering the parameterisation of transmission models to support understanding of the impact of anthelmintic resistance, climate change and alternative control strategies on nematode epidemiology.

Climate-driven changes to the spatio-temporal distribution of the parasitic nematode, Haemonchus contortus, in sheep in Europe.

Recent climate change has resulted in changes to the phenology and distribution of invertebrates worldwide. Where invertebrates are associated with disease, climate variability and changes in climate may also affect the spatio-temporal dynamics of disease. Due to its significant impact on sheep production and welfare, the recent increase in diagnoses of ovine haemonchosis caused by the nematode Haemonchus contortus in some temperate regions is particularly concerning.

Asynchrony in host and parasite phenology may decrease disease risk in livestock under climate warming: Nematodirus battus in lambs as a case study.

Mismatch in the phenology of trophically linked species as a result of climate warming has been shown to have far-reaching effects on animal communities, but implications for disease have so far received limited attention. This paper presents evidence suggestive of phenological asynchrony in a host-parasite system arising from climate change, with impacts on transmission. Diagnostic laboratory data on outbreaks of infection with the pathogenic nematode Nematodirus battus in sheep flocks in the UK were used to validate region-specific models of the effect of spring temperature on parasite transmission.

The basic reproduction quotient (Q0) as a potential spatial predictor of the seasonality of ovine haemonchosis.

Haemonchus contortus is a gastrointestinal nematode parasite of small ruminants, which feeds on blood and causes significant disease and production loss in sheep and goats, especially in warmer parts of the world. The life cycle includes free-living immature stages, which are subject to climatic influences on development, survival and availability, and this species therefore exhibits spatio-temporal heterogeneity in its infection pressure based on the prevailing climate. Models that better explain this heterogeneity could predict future epidemiological changes.