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Prior studies have described the complex interplay that exists between glioma cells and neurons; however, the electrophysiological properties endogenous to glioma cells remain obscure. To address this, we employed Patch-sequencing (Patch-seq) on human glioma specimens and found that one-third of patched cells in IDH mutant (IDHmut) tumors demonstrate properties of both neurons and glia. To define these hybrid cells (HCs), which fire single, short action potentials, and discern if they are of tumoral origin, we developed the single cell rule association mining (SCRAM) computational tool to annotate each cell individually. SCRAM revealed that HCs possess select features of GABAergic neurons and oligodendrocyte precursor cells, and include both tumor and non-tumor cells. These studies characterize the combined electrophysiological and molecular properties of human glioma cells and describe a cell type in human glioma with unique electrophysiological and transcriptomic properties that may also exist in the non-tumor brain. [Display omitted] • Patch-seq identifies spiking tumor cells in human glioma • Spiking glioma cells exhibit GABAergic and glial properties in IDH mutant gliomas • SCRAM algorithm accurately annotates tumor and non-tumor cells from Patch-seq data • Spiking glioma cells confer increased survival in IDH mutant glioma Curry et al. employ simultaneous electrophysiological and genomic profiling of single cells from human glioma to identify glioma cells that fire action potentials (APs). This study introduces single cell rule association mining (SCRAM), a computational tool that provides integrated genomic and transcriptomic profiles for each single cell. [ABSTRACT FROM AUTHOR]

A 25-year-old male presented with headaches 3 weeks after a car accident. His magnetic resonance imaging images showed a hemorrhagic vermis mass with fourth ventricle effacement. One month later, he underwent suboccipital craniotomy for removal of a pilocytic astrocytoma. A 3-month postoperative scan demonstrated a new area of medullary hyperintensity in the inferior olive, which was also present 7 months postoperatively consistent with hypertrophic olivary degeneration. This condition is caused by disruption to the dento-rubro-olivary pathway with magnetic resonance imaging enlargement of the inferior olivary nucleus and increased T2 signal. Hypertrophic olivary degeneration should be considered after cerebellar surgery and should not be mistaken for tumor recurrence. [ABSTRACT FROM AUTHOR]

Summary Several cell types experience repetitive mechanical stimuli, including vein endothelial cells during pulsating blood flow, inner ear hair cells upon sound exposure, and skin cells and their innervating dorsal root ganglion (DRG) neurons when sweeping across a textured surface or touching a vibrating object. While mechanosensitive Piezo ion channels have been clearly implicated in sensing static touch, their roles in transducing repetitive stimulations are less clear. Here, we perform electrophysiological recordings of heterologously expressed mouse Piezo1 and Piezo2 responding to repetitive mechanical stimulations. We find that both channels function as pronounced frequency filters whose transduction efficiencies vary with stimulus frequency, waveform, and duration. We then use numerical simulations and human disease-related point mutations to demonstrate that channel inactivation is the molecular mechanism underlying frequency filtering and further show that frequency filtering is conserved in rapidly adapting mouse DRG neurons. Our results give insight into the potential contributions of Piezos in transducing repetitive mechanical stimuli. [ABSTRACT FROM AUTHOR]

Acute rheumatic fever (ARF) remains a major problem in tropical regions, resource-poor countries, and minority indigenous communities. It has long been thought that group A streptococcal (GAS) pharyngitis alone was responsible for acute rheumatic fever; this belief has been supported by laboratory and epidemiological evidence gathered over more than 60 years, mainly in temperate climates where GAS skin infection is uncommon. GAS strains have been characterised as either rheumatogenic or nephritogenic based on phenotypic and genotypic properties. Primary prevention strategies and vaccine development have long been based on these concepts. The epidemiology of ARF in Aboriginal communities of central and northern Australia challenges this view with reported rates of ARF and rheumatic heart disease (RHD) that are among the highest in the world. GAS throat colonisation is uncommon, however, and symptomatic GAS pharyngitis is rare; pyoderma is the major manifestation of GAS infection. Typical rheumatogenic strains do not occur. Moreover, group C and G streptococci have been shown to exchange key virulence determinants with GAS and are more commonly isolated from the throats of Aboriginal children. We suggest that GAS pyoderma and/or non-GAS infections are driving forces behind ARF in these communities and other high-incidence settings. The question needs to be resolved as a matter of urgency because current approaches to controlling ARF/RHD in Aboriginal communities have clearly been ineffective. New understanding of the pathogenesis of ARF would have an immediate effect on primary prevention strategies and vaccine development. [Copyright &y& Elsevier]

Aims: There is increasing evidence on the role of helminth infections in modifying autoimmune and allergic diseases. These infections may have similar effect in other inflammatory processes, such as insulin resistance. This review aims to examine the literature on the effect of helminthic infections on metabolic outcomes in humans.Methods: Using the PRISMA protocol, we searched the literature using PubMed, MEDLINE, and a manual review of reference lists. Human studies published in English after 1995 were included. Four papers were included in this review. Data was extracted and a meta-analysis was conducted using a random-effects model. Heterogeneity was assessed using Tau(2) and I(2) tests.Results: The included studies found that infection was associated with lower glucose levels, less insulin resistance, and/or a lower prevalence of metabolic syndrome (MetS) or type 2 diabetes mellitus (T2DM). Meta-analysis showed that participants with a previous or current helminth infection were 50% less likely to have an endpoint of metabolic dysfunction in comparison to uninfected participants (OR 0.50; 95% CI 0.38-0.66).Conclusion: This review has shown that helminth infections can be associated with improved metabolic outcomes. Understanding of the mechanisms underlying this relationship could facilitate the development of novel strategies to prevent or delay T2DM. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular disease (CVD) is the commonest cause of death across the globe; incidence and prevalence rates are increasing. Together, CVD and diabetes mellitus are responsible for a quarter of the health gap observed between Aboriginal Australians and Torres Strait Islanders, and non-Indigenous Australians. Numerous programs have been proposed and implemented to Close the Gap; ideally, these should be evidence-based.Objective: The aim of this review is to evaluate primary prevention measures and programs that aim to reduce CVD risk in minority Indigenous populations around the world.Methods: A search of PubMed, the Cochrane Library and the Elsevier Scopus Database was initially conducted using the terms "cardiovascular disease", "population groups", "primary prevention", "health services, indigenous", "indigenous health", "risk assessment" and "risk management". Results were then assessed per inclusion/exclusion criteria. A second reviewer independently evaluated the publications and review process to ensure agreement.Results: The initial search produced 37 publications; 19 met the inclusion criteria and were incorporated into a comparative table. Most were descriptive, mixed-methods, audit or intervention studies. Heterogeneity of study design prevented statistical analysis.Conclusion: Addressing CVD risk in minority Indigenous populations is a multifactorial challenge; there is substantial room for improvement in routine risk assessment and management. Holistic approaches need to embrace local cultural perceptions of health and wellbeing. Validated risk reduction tools, individualised management plans, polypills and computer based decision support tools are promising to improve outcomes for those at risk. [ABSTRACT FROM AUTHOR]

Introduction: Knowing patients' smoking history helps guide who may benefit from preventive services such as lung cancer screening. The accuracy of smoking history electronic health records remains unclear.Methods: This was a secondary analysis of data collected from a portal-based lung cancer screening decision aid. Participants of an academically affiliated health system, aged 55-76 years, completed an online survey that collected a detailed smoking history including years of smoking, years since quitting, and smoking intensity. Eligibility for lung cancer screening was defined using the Centers for Medicare and Medicaid Services criteria. Data analysis was performed May-December 2018, and data collection occurred between November 2016 and February 2017.Results: A total of 336 participants completed the survey and were included in the analysis. Of 175 participants with self-reported smoking intensity, 72% had packs per day and 62% had pack-years recorded in the electronic health record. When present, smoking history in the electronic health records correlated well with self-reported years of smoking (r =0.78, p≤0.0001) and years since quitting (r =0.94, p≤0.0001). Self-reported smoking intensity, including pack-years (r =0.62, p<0.0001) and packs per day (r =0.65, p≤0.0001), was less correlated. Of those participants eligible for lung cancer screening by self-report, only 35% met criteria for screening by electronic health records data alone. Others were either incorrectly classified as ineligible (23%) or had incomplete data (41%).Conclusions: The electronic health records frequently misses critical elements of a smoking history, and when present, it often underestimates smoking intensity, which may impact who receives lung cancer screening. [ABSTRACT FROM AUTHOR]

Abstract: There is a high burden of disease due to group A streptococcus (GAS) in remote Northern Territory (NT) Indigenous communities. A proposed 26-valent GAS M-type vaccine covers 80–90% of pharyngeal and invasive isolates in the US. We examined the diversity and distribution of emm types in two remote Indigenous communities in the NT Top End over a 17-year period and compared them to the proposed vaccine types. Eighty emm types were identified between 1991 and 2007. Diversity in both communities was high (overall Simpson''s index 0.976), but varied between communities. Prior to 2004, 71 emm types were identified and an additional 9 emm types were identified during a period of active surveillance in 2004–2005. The proposed 26-valent vaccine would be expected to cover only 20% of emm types recovered in this study. Of the 80 emm types, 16 (20%) were new sequence types identified since the last assignment of M types in 2002. The diversity of streptococcal isolates was higher than that reported from most industrialized countries, and similar to that described in several developing countries. A vaccine based on such a variable antigen is unlikely to provide effective protection in the highest risk populations. [Copyright &y& Elsevier]

Background: The clinical profile of endocarditis has changed over the past four decades with studies showing trends towards increasing age, more nosocomial and prosthetic valve infection and increasing rates of Staphylococcus aureus infection. However, these studies have been biased by referral patterns. Methods: We reviewed data collected at three hospitals in the Barwon-South-West region in Victoria, Australia. All cases identified between 1994 and 1999 were reviewed according to the Duke criteria. Results: During this period, 58 patients were diagnosed as having endocarditis. The incidence rate during this time was 3.0 per 100 000 with a rise in the rate of admissions from 0.15 to 0.26 per 1000 from 1995 to 1999. Sixteen (28%) were nosocomial with the majority from line-related sepsis. No intravenous drug users were identified. Eighteen (31%) involved endovascular prosthetic material. S. aureus was the causative pathogen in 23 (40%), with ‘viridans’ streptococci contributing 12 (21%) and other organisms accounting for 12 (21%). Attribu­table mortality in this series was 17%. Conclusions: We have seen a rise in the rate of endocarditis during this time. The proportions of endocarditis due to S. aureus and ‘viridans’ streptococci, as well as rates of nosocomial and prosthetic valve infection, are consistent with more recent series at referral hospitals and district hospitals, representing a change since studies performed in the 1960s and 1970s. Our findings confirm a trend towards a clinical profile seen at referral centres and reinforce the emerging importance of S. aureus , nosocomial bacteraemia and prosthetic valve endocarditis. (Heart, Lung and Circulation 2002; 11: 26-31). [ABSTRACT FROM AUTHOR]

Infective aortitis and associated mycotic aneurysms are uncommon clinical entities and most reported cases are associated with Salmonella species. We report successful surgical and medical treatment of a mycotic aneurysm of the aorta which presented as acute pericarditis and may have been caused by Camplyobacter jejuni. (Heart, Lung and Circulation 2000; 9: 88–91). [ABSTRACT FROM AUTHOR]