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Extracellular nanovesicles (EVs) are lipid-based vesicles secreted by cells and are present in all bodily fluids. They play a central role in communication between distant cells and have been proposed as potential indicators for the early detection of a wide range of diseases, including different types of cancer. However, reliable quantification of a specific subpopulation of EVs remains challenging. The process is typically lengthy and costly and requires purification of relatively large quantities of biopsy samples. Here, we show that microcantilevers operated with sufficiently small vibration amplitudes can successfully quantify a specific subpopulation of EVs directly from a drop (0.1 mL) of unprocessed saliva in less than 20 min. Being a complex fluid, saliva is highly non-Newtonian, normally precluding mechanical sensing. With a combination of standard rheology and microrheology, we demonstrate that the non-Newtonian properties are scale-dependent, enabling microcantilever measurements with a sensitivity identical to that in pure water when operating at the nanoscale. We also address the problem of unwanted sensor biofouling by using a zwitterionic coating, allowing efficient quantification of EVs at concentrations down to 0.1 μg/mL, based on immunorecognition of the EVs’ surface proteins. We benchmark the technique on model EVs and illustrate its potential by quantifying populations of natural EVs commonly present in human saliva. The method effectively bypasses the difficulty of targeted detection in non-Newtonian fluids and could be used for various applications, from the detection of EVs and viruses in bodily fluids to the detection of molecular clusters or nanoparticles in other complex fluids.

Before the last century, societies around the globe, including Indigenous Peoples and early settlers to Canada’s west coast, relied on local procurement and preservation of seasonal food to support their food security and food sovereignty. In some instances, Indigenous Peoples and settlers shared and adopted each other’s food provisioning and preservation practices and associated values. Such cross-cultural knowledge exchanges provided wide-ranging food provisioning options for those living in the region. In this paper, we conceptualize such exchanges and varieties of provisioning options as part of Indigenous and local food systems that have been co-created through mutual interdependence, support, and food-related values. Using data from interviews and document analysis, we show that current residents of the Clayoquot Sound Biosphere Region have maintained traditional food procurement and preservation techniques, although with some new methods that have emerged in response to new technologies, innovation, and need. Indigenous and non-Indigenous residents who share food and exchange food provisioning practices simultaneously support their food needs, wellbeing, and cultural maintenance. In contrast to research that examines and conceptualizes local food systems and Indigenous food systems separately, this paper highlights the existence of an interrelated Indigenous and local food system, characterized by historical and contemporary shared food provisioning practices and cross-cultural food knowledge exchanges on Canada’s west coast. The advantage of the joint conceptualization lies in acknowledging how food systems can and do evolve to co-exist over time, and how they create opportunities for people living in remote, sometimes marginalized communities to strengthen food security and food sovereignty through shared food provisioning practices that resonate with their values.

BackgroundAutopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population.MethodsWe conducted a retrospective cohort study accessing national electronic records on death certification, hospital admissions and dispensed prescriptions for a cohort of 412 male Scottish former international rugby union players and 1236 members of the general population, matched to former players by age, sex and area socioeconomic status. Mortality and incident neurodegenerative disease diagnoses among former rugby players were then compared with the matched comparison group.ResultsOver a median 32 years follow-up from study entry at age 30 years, 121 (29.4%) former rugby players and 381 (30.8%) of the matched comparison group died. All-cause mortality was lower among former rugby players until 70 years of age with no difference thereafter. During follow-up, 47 (11.4%) former rugby players and 67 (5.4%) of the comparison group were diagnosed with incident neurodegenerative disease (HR 2.67, 95% CI 1.67 to 4.27, p<0.001).ConclusionsThis study adds to our understanding of the association between contact sports participation and the risk of neurodegenerative disease. While further research exploring this interaction is required, in the meantime strategies to reduce exposure to head impacts and head injuries in sport should be promoted.

Sexually transmitted infections, including the human immunodeficiency virus (HIV) and the human papillomavirus (HPV), disproportionally impact those in low-resource settings. Early diagnosis is essential for managing HIV. Similarly, HPV causes nearly all cases of cervical cancer, the majority (90%) of which occur in low-resource settings. Importantly, infection with HPV is six times more likely to progress to cervical cancer in women who are HIV-positive. An inexpensive, adaptable point-of-care test for viral infections would make screening for these viruses more accessible to a broader set of the population. Here, we report a novel, cost-effective electrochemical platform using gold leaf electrodes to detect clinically relevant viral loads. We have combined this platform with loop-mediated isothermal amplification and a CRISPR-based recognition assay to detect HPV. Lower limits of detection were demonstrated down to 104total copies of input nucleic acids, which is a clinically relevant viral load for HPV DNA. Further, proof-of-concept experiments with cervical swab samples, extracted using standard extraction protocols, demonstrated that the strategy is extendable to complex human samples. This adaptable technology could be applied to detect any viral infection rapidly and cost-effectively.

Estimated to be the most common non-viral sexually transmitted infection globally, Trichomonas vaginalis(TV) can lead to pelvic inflammatory disease, pregnancy complications, and increased risk of acquiring and transmitting HIV. Once diagnosed, TV infection can be treated with oral antibiotics; however, infected individuals are often asymptomatic and do not seek treatment. The WHO and others have identified a need for point-of-care tests to expand access to TV testing and screening; ideal test characteristics include high sensitivity and specificity and the ability to use urine as a sample type, rather than invasively collected swab samples. Here, we report on a proof-of-concept prototype for rapid, electrostatic enrichment of DNA from urine samples and demonstrate the use of large volumes of urine to increase sensitivity of downstream nucleic acid amplification testing. We developed an internally controlled thermophilic helicase-dependent amplification (tHDA) assay with lateral flow immunoassay readout and demonstrate that this tHDA assay can be performed directly on our DNA capture filter. We validated our method using clinical urine samples with qPCR-quantified TV loads. Using 62 clinical urine samples and a simple sample processing device, our tHDA assay displayed 96.6% sensitivity and 100% specificity. Our analytical limit of detection was found to be approximately 7 genomic equivalents of TV DNA per mL of sample when 1 mL of sample was tested, comparable to existing isothermal tests for TV. Using large-volume simulated samples (40 mL of buffered urine with spiked-in TV DNA), we also demonstrated that sensitivity could be improved 28-fold to 0.25 genomic equivalents of TV DNA per mL, with a sample processing time of only 2 minutes.

Between 2000 and 2013, over 8,000 students studied the module Reading Classical Latinat the Open University, the United Kingdom’s largest distance education provider. But while many learners attained high grades, a significant proportion withdrew from study or failed the module. In 2015, the original module was replaced with a completely new course, Classical Latin: The Language of Ancient Rome. This article details the innovative ways in which new technology and pedagogical theory from Modern Foreign Language (MFL) learning were drawn on by the team designing this new module, resulting in a learning experience which gives greater emphasis to elements such as spoken Latin, the intrinsic pleasure of reading, and cultural context. The (largely positive) effects of these pedagogical changes on student success and satisfaction are subsequently analysed using a rich mix of qualitative and quantitative data. Finally, the authors reflect on lessons learned and the possibilities for future research and enhancement.

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.

Scrotal varicoceles, which are relatively common, are sometimes caused by venous flow disturbance resulting from a renal or retroperitoneal tumour. Consequently, it is common practice to perform extended renal and retroperitoneal scans following varicocele identification. The aim of this systematic review was to determine the extent of the co-association between renal or retroperitoneal tumours and scrotal varicoceles using primary research literature. We conducted a search of 11 electronic databases; hand-searched five relevant textbooks; and conducted forward- and backward-citation searches of included articles. Articles that were included were assessed for research quality and data extracted. Twenty-four articles were found, comprising 19 case reports and five case series, reporting 35 cases in total. All cases had both a varicocele and a tumour (renal, retroperitoneal or other). We found no cohort or case–control studies. In conclusion, case reports and case series are susceptible to significant publication bias and the lack of any cohort or case–control studies meant that it was not possible to establish the extent of the co-association between renal or retroperitoneal tumours and scrotal varicoceles. It was not possible to estimate the value of conducting an extended scan in patients with scrotal varicoceles. Research is needed, particularly of a cohort or case-control design and including a robust sampling method, to examine the extent of any co-association. Meanwhile, extended renal or retroperitoneal scans should be undertaken when diagnosing all varicoceles, regardless of patient age, until this research is completed.

The growing demand for ultrasound examinations is evident, as is the incidence of work-related musculoskeletal disorders (WRMSDs) incurred by ultrasound practitioners. This paper outlines a simple ergonomic audit that all operators can complete on their ultrasound room and equipment. As a result of this audit, areas of weaknesses in room/equipment design can be highlighted, with recommendations for more ergonomically designed equipment put forward to departmental managers, with the overall aim of reducing WRMSDs among ultrasound practitioners.

Several letters to the editor are presented in response to previous articles including "Make America hate again" by Sasha Abramsky, "Out of the Ordinary" by Helen Lewis, and "None the wiser" in the October 28, 2016 issue.