A Case of Unintentional Isopropanol Poisoning via Transdermal Absorption Delayed by Weekly Hemodialysis

BACKGROUND Isopropanol toxicity is the most common reported toxic alcohol ingestion in the United States and is well known to emergency physicians. Most toxicities result from unintentional ingestion of rubbing alcohol; however, an under-recognized mechanism of unintentional toxicity is transdermal absorption. Additionally, hemodialysis effectively removes isopropanol and its metabolites from circulation, so that in patients receiving regular hemodialysis, the manifestation of toxicity can be delayed. CASE REPORT A 67-year-old woman with end-stage renal disease secondary to insulin-dependent type II diabetes on once-weekly hemodialysis presented to the Emergency Department via the Emergency Medical Service with acute encephalopathy, severe hypoglycemia, and hypothermia. Her daughter found her confused and lethargic, smelling of acetone, and with a bottle of rubbing alcohol in her hand. The patient had been topically applying large quantities of rubbing alcohol for several months as a home remedy for cramps and adamantly denied any oral ingestion. She had missed several hemodialysis appointments over the previous month. Upon arrival, the patient was confused, profoundly hypoglycemic, and hypothermic. Additional laboratory examination revealed an elevated plasma osmolality, osmolar gap, isopropanol level, and acetone level. She was treated supportively with glucose-containing fluids and external warming and was admitted to the Intensive Care Unit. Hemodialysis was resumed, and the patient was discharged 3 days after admission with stable blood glucose, regular body temperature, and baseline mental status. CONCLUSIONS Our report is unique as it presents both an under-recognized mechanism of isopropanol toxicity (transdermal absorption) and an uncommon presentation of chronic exposure with manifestations of toxicity delayed by regular hemodialysis

Cutibacterium (formerly Propionibacterium) acnes clavicular infection.

Cutibacterium (formerly Propionibacterium) acnes13, 16 is a slow growing, gram-positive bacteria that is naturally found in higher concentrations as skin flora on the chest and back, as well as in other areas with greater numbers of hair follicles.25, 37 Most of the reported cases of C. acnes shoulder girdle infection follow arthroplasty surgery,18, 20, 26, 27, 32, 35 which then often requires debridement, administration of intravenous antibiotics, and surgical revision of the implanted device.12, 15, 21, 28-30 In a recent study, 56% of 193 shoulder revisions had a positive culture, 70% of which grew C. acnes.30 Despite the relatively common presumed association of C. acnes humeral osteomyelitis with prosthetic infection, infection of the scapula or clavicle secondary to C. acnes is rare.4, 23, 36 Osteomyelitis of the clavicle involving any organism is also an uncommon event that can arise spontaneously via presumed hematogenous spread, or secondary to open fractures or internal fixation.6, 33 The most commonly found organism in clavicular osteomyelitis is Staphylococcus aureus.9 We here report two cases of clavicular infection secondary to C. acnes that were not associated with implants

Visualization of positive and negative sense viral RNA for probing the mechanism of direct-acting antivirals against hepatitis C virus

RNA viruses are highly successful pathogens and are the causative agents for many important diseases. To fully understand the replication of these viruses it is necessary to address the roles of both positive-strand RNA ((+)RNA) and negative-strand RNA ((-)RNA), and their interplay with viral and host proteins. Here we used branched DNA (bDNA) fluorescence in situ hybridization (FISH) to stain both the abundant (+)RNA and the far less abundant (-)RNA in both hepatitis C virus (HCV)- and Zika virus-infected cells, and combined these analyses with visualization of viral proteins through confocal imaging. We were able to phenotypically examine HCV-infected cells in the presence of uninfected cells and revealed the effect of direct-acting antivirals on HCV (+)RNA, (-)RNA, and protein, within hours of commencing treatment. Herein, we demonstrate that bDNA FISH is a powerful tool for the study of RNA viruses that can provide insights into drug efficacy and mechanism of action

Questioning policy, youth participation and lifestyle sports

Young people have been identified as a key target group for whom participation in sport and physical activity could have important benefits to health and wellbeing and consequently have been the focus of several government policies to increase participation in the UK. Lifestyle sports represent one such strategy for encouraging and sustaining new engagements in sport and physical activity in youth groups, however, there is at present a lack of understanding of the use of these activities within policy contexts. This paper presents findings from a government initiative which sought to increase participation in sport for young people through provision of facilities for mountain biking in a forest in south-east England. Findings from qualitative research with 40 young people who participated in mountain biking at the case study location highlight the importance of non-traditional sports as a means to experience the natural environments through forms of consumption which are healthy, active and appeal to their identities. In addition, however, the paper raises questions over the accessibility of schemes for some individuals and social groups, and the ability to incorporate sports which are inherently participant-led into state-managed schemes. Lifestyle sports such as mountain biking involve distinct forms of participation which present a challenge for policy-makers who seek to create and maintain sustainable communities of youth participants

Ensuring the Involvement of Children in the Evaluation of New Tuberculosis Treatment Regimens

William Burman and colleagues review the barriers to involving children in studies of new tuberculosis treatments and recommend strategies for overcoming these barriers

Uncovering Blind Spots in Urban Carbon Management: The Role of Consumption-Based Carbon Accounting in Bristol, UK

The rapid urbanisation of the twentieth century, along with the spread of high-consumption urban lifestyles, has led to cities becoming the dominant drivers of global anthropogenic greenhouse gas emissions. Reducing these impacts is crucial, but production-based frameworks of carbon measurement and mitigation—which encompass only a limited part of cities’ carbon footprints—are much more developed and widely applied than consumption-based approaches that consider the embedded carbon effectively imported into a city. Frequently, therefore, cities are left blind to the importance of their wider consumption-related climate impacts, while at the same time left lacking effective tools to reduce them. To explore the relevance of these issues, we implement methodologies for assessing production- and consumption-based emissions at the city-level and estimate the associated emissions trajectories for Bristol, a major UK city, from 2000 to 2035. We develop mitigation scenarios targeted at reducing the former, considering potential energy, carbon and financial savings in each case. We then compare these mitigation potentials with local government ambitions and Bristol’s consumption-based emissions trajectory. Our results suggest that the city’s consumption-based emissions are three times the production-based emissions, largely due to the impacts of imported food and drink. We find that low-carbon investments of circa £3 billion could reduce production-based emissions by 25% in 2035. However, we also find that this represents <10% of Bristol’s forecast consumption-based emissions for 2035 and is approximately equal to the mitigation achievable by eliminating the city’s current levels of food waste. Such observations suggest that incorporating consumption-based emission statistics into cities’ accounting and decision-making processes could uncover largely unrecognised opportunities for mitigation that are likely to be essential for achieving deep decarbonisation

Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors

Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders