In July 2022, Human Papillomavirus (HPV) self-collection became available as a choice to all participants in Australia's National Cervical Screening Program (NCSP). This policy change aims to facilitate equitable access to cervical screening; however, further evidence is needed to support its implementation and reach under-screened women and people with a cervix. This implementation study seeks to embed HPV self-collection into Aboriginal and Torres Strait Islander Community Controlled Health Organisations (ACCHOs) and/or primary care organisations whose context is similar to that of an ACCHO. This will be achieved by co-designing, implementing, and evaluating models of care tailored to local needs. The aim is to increase cervical screening participation, particularly among under- and never-screened, Aboriginal and Torres Strait Islander women and people with a cervix. Ultimately the aim is to achieve equity in cervical cancer elimination. Screen Your Way will use a before-and-after study design to evaluate the effectiveness, acceptability and sustainability of implemented strategies on cervical screening participation among Aboriginal and Torres Strait Islander women and people with a cervix. The study will be guided by an Indigenist implementation research approach and will employ mixed methods. Ethical approval has been obtained from the Australian Institute of Aboriginal and Torres Strait Islander Studies Research Ethics Committee (REC-0092), Aboriginal Health and Medical Research Council of New South Wales Ethics Committee (2078/23), Australian National University Human Research Ethics Committee (H/2023/1103), Northern Territory Department of Health and Menzies School of Health Research (HREC2023-4557), and Metro South Human Research Ethics Committee (HREC/2025/QMS/115155). Additional approvals will be obtained in accordance with the locally nominated governance protocols of each participating service. This may include approvals from ACCHO Boards, Community Juries, or other designated decision-making bodies. The research team will work closely with each service to ensure all required processes are respected and adhered to prior to commencing any research activities. Findings will be disseminated via workshops, reports, evidence briefs and resource creation to assist with the evidence-based scale up of self-collection in the ACCHO setting. Further dissemination will occur via conferences and peer-reviewed publications in partnership with the Screen Your Way Aboriginal and Torres Strait Islander Caucus.
Roll-your-own (RYO) tobacco sales are increasing in Latin America, with the product widely available in Argentina. We are not aware of any research in Latin America exploring adolescents' perceptions of RYO tobacco, or any research exploring how adolescents view RYO packaging and accessories. We conducted eight focus groups (n=51) in four cities in Argentina (Córdoba, Quilmes, San Salvador de Jujuy, Santa Rosa), with participants stratified by gender, age (13-14, 15-17) and smoking susceptibility (susceptible, non-susceptible). Participants were asked about RYO, RYO packaging and accessories. Participants were aware of RYO tobacco. Many had seen hand-rolled cigarettes but often associated them with marijuana joints. RYO pack colours, materials, and descriptors influenced appeal and harm perceptions, as did flavours. Packs with descriptors such as 'natural' or 'additive-free' were considered more appealing and less harmful. Some believed, based on the packaging and from listening to relatives, that RYO was less harmful than factory-made cigarettes due to the absence of additives. The general view was that the act of rolling may reduce the urge to smoke, as it requires additional effort, but that this effect would likely diminish once people became accustomed to it. Some participants suggested that it would be easier to lose track of the amount smoked when using RYO. Accessories were seen as appealing and compared to candy. Adolescents are familiar with RYO tobacco, with perceptions of harm and appeal influenced by packaging, flavour and social narratives. Like many adult RYO smokers, some participants viewed RYO as less harmful than factory-made cigarettes.
Several zona pellucida 3 (Zp3)-Cre driver mouse lines are used to enable conditional loss-of-function studies in oocytes. The Knowles Zp3-Cre line, currently maintained live at the Jackson Laboratory, is the most widely published. We recently found that the transgene expressed in the Knowles line contains a truncated metallothionein (Mt1) sequence that is expressed at high levels in oocytes from transgenic mice. This finding led us to search for an alternative Zp3-Cre line that did not express an exogenous Mt1 transcript. We tested a second transgenic Zp3-Cre line and then created our own transgenic Zp3-Cre line, neither of which was oocyte-specific as documented by crossing to the tdTomato reporter line. Similar testing confirmed the exquisite oocyte specificity of the Knowles Zp3-Cre line. An alternative to Zp3-Cre is to use the Gdf9-iCre line, which is reported to be oocyte-specific and expressed beginning at the primordial follicle stage. This line similarly showed high somatic tissue Cre expression. Reasoning that a knock-in approach would ensure oocyte specificity, we used a CRISPR/Cas9 approach to insert Cre into the endogenous Zp3 locus. However, crosses of this knock-in line with tdTomato females revealed high somatic tissue expression. Both the Zp3-Cre knock-in and Gdf9-iCre alleles, when paternally inherited, induced Cre expression by the blastocyst stage, explaining the broad tissue distribution. We conclude that the Knowles Zp3-Cre transgenic line remains the best model for generating oocyte-specific expression, though investigators should be aware of the spurious Mt1 expression from the transgene.
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Melanoma can impair patients' physical, psychological, interpersonal, and economic balance. The effects of surgical interventions and the development of skin metastases might detrimentally impact on their body image, an embodied mental representation that shapes one's identity and interpersonal relationships. This systematic review investigates the perception of body image in melanoma patients and the relationship between body image and other psychosocial variables. The literature search identified nine eligible articles, which underwent data extraction and qualitative analysis. The results are organized into five categories: body image concerns; body image and social functioning; body image and cancer-related variables; body image and sociodemographic variables; body image and correlation with other psychosocial outcomes. Despite the small number of eligible articles and the heterogeneity of emerging results, our review suggests that body image concerns are connected to other psychosocial problems such as quality of life and emotional distress and might be influenced by several tumor-related and demographic variables. Guided by progressive understanding of the specific facets of melanoma patients' suffering, multidisciplinary teams should design targeted psychological interventions to address patients' needs and improve their experience of the disease.
Tissue-resident memory T cells (TRM) are a distinct subset of memory T cells that persist long-term within non-lymphoid tissues and provide rapid, localized immune protection. The central nervous system (CNS) was among the first sites in which these TRM were detected, but only recently has their importance in brain immune surveillance been fully appreciated. Despite their relative low abundance, brain TRM can protect against reinfection, contribute to neuropathology, and participate in neurologic diseases. This review provides an overview of what is currently known about TRM in the brain, with a focus on CD8+ T cells, identifies major knowledge gaps, and highlights implications for human brain TRM biology. Addressing these gaps will help contextualize brain TRM in health and disease and guide strategies to harness or modulate them for vaccination and neuroimmune therapies.
We present a novel yet simple approach to measuring individual differences in visual imagery, in which people compare the quality of voluntarily generated visual images to the quality of (eyes-closed) negative afterimages. In laboratory testing (n = 98), many participants rated their own imagery of a face or a letter A to be similar or even stronger - on each of several experiential dimensions - than an afterimage of a face or letter. Dimensions were brightness, sharpness, detail, and two dimensions which deconstruct and challenge a simple distinction between associator-versus projector-imagers. Other participants rated their voluntary images to be weaker than afterimages, indicating qualitative differences between participants. This replicated data from a large-sample pilot, conducted under less formal conditions. Participants mostly expressed that their comparative ratings were accurate. Over the pilot and main study, ratings correlated with 3 standard self-report instruments for visual imagery, supporting the construct validity of our measure. Participants visually rendered the brightness and sharpness of their afterimages on a computer screen, allowing (a) depiction of the baseline against which voluntary images were being compared and (b) calculation that variation in afterimagery strength was independent of the strength of voluntary images, and cannot account for variance in our comparative ratings of voluntary imagery. As a method of quantifying the range of visual imagery experience from aphantasics to hyperphantasics, in healthy and clinical populations, our approach may be less metacognitively contaminated and more accurate than widely-used yet criticised self-report instruments of imagery, e.g. those comparing imagery vividness to real seeing.
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The resurgence of targeted covalent inhibitors (TCIs) has expanded the diversity of electrophilic warheads used in drug discovery. TCIs must balance efficient target engagement with resistance to rapid metabolic clearance. In drug development campaigns, intrinsic reactivity toward glutathione (GSH) is commonly used to estimate metabolic liability; however, in vivo GSH conjugation is primarily catalyzed by glutathione S-transferases (GSTs), a phase II metabolic pathway that is not captured by intrinsic reactivity measurements. Here, we establish a quantitative assay to determine GST kcat and KM values across a panel of structurally diverse warheads. We show that their intrinsic reactivities correlate poorly with GST-catalyzed conjugation rates, which are instead governed by warhead- and scaffold-dependent enzyme-substrate interactions. In contrast, GST kcat/KM values correlate closely with compound half-lives in human liver cytosol. Together, these findings establish GST susceptibility as a structurally tunable determinant of metabolic GSH conjugation and provide new principles for the optimization of TCIs.
With evolving accreditation requirements, competing demands of medical students, and the national trend toward shortening the preclerkship curriculum, management of workload hours for preclerkship medical students is essential. Although many medical schools have established policies outlining student workload expectations in the preclerkship curriculum, the mechanisms to ensure adherence to these policies are often less well defined. In 2019, the University of Cincinnati College of Medicine (UCCOM) established a scheduling workgroup, the Student Workload Advisory Group (SWAG), which evolved into a collaborative effort to monitor and manage workload. SWAG created a workload calculator that could be applied to all preclerkship courses to monitor workload hours among medical students during academic years 2021 to 2022 through 2024 to 2025. Within the first year of formal monitoring, there were 27 instances in which student workload exceeded that defined in the workload policy. SWAG identified explicit and hidden workload exceedances. Explicit workload exceedances included requirements that can be captured on a course calendar, whereas hidden workload exceedances emerged after implementation of an assignment audit self-report tool. Multiple revisions to the workload policy were incorporated to ensure scheduled activities reflected the time needed to complete the activities, which led to a reduction in workload policy exceedances. More success was seen with a proactive approach that facilitates collaboration between SWAG and course directors to anticipate and address potential workload concerns before they occur. The creation of a formal body consisting of faculty, staff, and students to monitor workload combined with a proactive monitoring plan to enforce workload policies represents a reproducible framework for other institutions seeking to create and/or enforce workload policies. The next step at UCCOM is to incorporate formal workload monitoring into clinical phases of the curriculum to monitor workload hours outside enforced duty hours to improve student wellness.
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Sex identification at early stages of development is of great interest for studies in evolutionary biology in many animals. Knowing the sex ratio, even more in offspring, allows testing hypotheses related to the cause of sex ratio biases in populations and species. Spiders born with a defined sex, mostly have an X1X20 sex chromosome system, but it is not possible to determine their sex phenotypically until the adult or near-adult stage. The wolf spider Allocosa marindia inhabits the sandy coast of Southern South America and shows sex role reversal. Laboratory and field studies suggest a strong bias in the sex ratio in favour of females in this species. Here, we analysed the 2C nuclear DNA content by flow cytometry in females and males of A. marindia to determine whether the difference between the sexes is enough to identify the sex of the individuals. The average 2C DNA content for females was 4.96 ± 0.036 pg and for males 4.72 ± 0.020 pg. Then, we tested the usefulness of the technique to sex A. marindia frozen spiderlings, in order to be able to decouple the collection time from the processing time. We analysed 59 spiderlings from four known females. Although we found greater variability in frozen samples, the difference in DNA content was enough to determine the sex of 54 frozen spiderlings (43 females and 11 males). Our results show a promising technique for sexing hatchlings of diplodiploid arthropods. In future studies, we will seek to sex spiderlings from a larger number of mothers to understand the causes of female bias in this species. La identificación del sexo en las primeras etapas del desarrollo es de gran interés para estudios de biología evolutiva en muchos animales. Conocer la proporción de sexos, especialmente en la descendencia, permite probar hipótesis relacionadas con la causa de los sesgos en la proporción de sexos en poblaciones y especies. Las arañas nacen con un sexo definido, en su mayoría tienen un sistema de cromosomas sexuales X1X20, pero no es posible determinar su sexo fenotípicamente hasta la etapa adulta o casi adulta. La araña lobo Allocosa marindia habita arenales costeros del sur de Sudamérica y muestra inversión de roles sexuales. Estudios de laboratorio y de campo sugieren un fuerte sesgo en la proporción de sexos a favor de las hembras en esta especie. Aquí, analizamos el contenido nuclear 2C de ADN por citometría de flujo en hembras y machos de A. marindia para determinar si la diferencia entre los sexos es suficiente para identificar el sexo de los individuos. El contenido de ADN 2C promedio para las hembras fue de 4,96 ± 0,036 pg y para los machos de 4,72 ± 0,020 pg. A continuación, probamos la utilidad de la técnica para determinar el sexo de crías congeladas de A. marindia, con el fin de separar el tiempo de recolección del tiempo de procesamiento. Analizamos 59 crías de cuatro hembras conocidas. Si bien encontramos mayor variabilidad en las muestras congeladas, la diferencia en el contenido de ADN fue suficiente para determinar el sexo de 54 crías congeladas (43 hembras y 11 machos). Nuestros resultados muestran una técnica prometedora para determinar el sexo de crías de artrópodos diplodiploides. En estudios futuros, buscaremos determinar el sexo de crías de un mayor número de madres para comprender las causas del sesgo hacia las hembras en esta especie.
Endoscope drying is essential to prevent outgrowth of waterborne organisms during storage, and to set the stage for effective gaseous sterilization. However, there are currently no comprehensive approaches for verifying dryness. An air test system was developed to determine the efficacy of a liquid detection method. Detection consisted of a vessel containing a humidity sensor that captured and measured air as it exited endoscope channels. The input-air parameters were controlled to determine the impact on detection in channels by recording the change in humidity as the channels dried. A design of experiments (DOE) was performed with "dry" (≤1% RH) or "wet" (≥ 30% RH) air delivered at constant pressure and flow rate to endoscope channels (1.7mm, 4.2mm and 6.0 mm inner diameter) containing either 0, 0.5 or 1 mg of water or alcohol. A second DOE was performed in test articles to determine the impact of the flow rate, pressure, and connection configuration on the method's sensitivity. Follow-up testing was conducted to verify the method's sensitivity in operational endoscopes. There was a statistically significant difference between detection of 0 mg (dry) and 0.5 or 1.0 mg. The method's sensitivity was confirmed within operational endoscopes when optimal parameters were applied. A method has been developed that assesses whether endoscope channels contain liquid. Further refinement of this method may support validation of manufacturer drying instructions and end-user drying verification.
Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may cause stress-induced transient acute cardiac dysfunction through myocardial stunning, in the form of exacerbation-triggered Takotsubo syndrome (referred to as Takotsubo stunning). Although prior studies suggest an association between AECOPD and transient cardiac dysfunction, existing evidence is limited to retrospective cohorts, case reports and expert consensus. Therefore, the incidence and clinical impact of Takotsubo stunning with acute heart failure (AHF) during AECOPD remain unknown and may be overlooked due to overlapping clinical symptoms. Cardiac Assessment and Takotsubo-stunning among COPD-exacerbations in-Hospital (CATCH study) aims to determine the incidence of Takotsubo stunning during AECOPD and to evaluate its clinical implication. CATCH is a prospective observational cohort study enrolling adults (≥18 years) admitted for AECOPD at Sahlgrenska University Hospital (Gothenburg, Sweden). Participants with chronic left ventricular systolic dysfunction (left ventricular ejection fraction <50%), pre-existing chronic regional wall motion abnormalities (RWMA) or prior type 1 myocardial infarction are excluded. Following informed consent, participants undergo echocardiographic screening for RWMA and/or systolic left ventricular dysfunction. Screening-positive patients have follow-up echocardiography at 24 hours (±6) and 30 days (±48 hours). Those with reversible dysfunction constitute the CATCH case group, while screening-negative participants serve as controls. Additional assessments include ECG, chest X-ray, N-terminal pro-B-type natriuretic peptide blood analysis and COPD severity. Primary outcomes include the incidence of reversible RWMA or left ventricular dysfunction (proxy for Takotsubo stunning) and in-hospital clinical signs of AHF (Killip class >1). A sample size of 150 patients is required for detecting AHF differences (α=0.05, 80% power). The study received ethical approval from the Swedish Ethical Review Authority. All participants provided written informed consent. Results will be disseminated through peer-reviewed journals and scientific meetings. The CATCH study is registered at ClinicalTrials.gov (NCT06597331). The reference number for ethical approval is 2024-02071-01 (with addenda 2024-05448-02 and 2025-05861-02).