How to Alleviate Cardiac Injury From Electric Shocks at the Cellular Level

Electric shocks, the only effective therapy for ventricular fibrillation, also electroporate cardiac cells and contribute to the high-mortality post-cardiac arrest syndrome. Copolymers such as Poloxamer 188 (P188) are known to preserve the membrane integrity and viability of electroporated cells, but their utility against cardiac injury from cardiopulmonary resuscitation (CPR) remains to be established. We studied the time course of cell killing, mechanisms of cell death, and protection with P188 in AC16 human cardiomyocytes exposed to micro- or nanosecond pulsed electric field (μsPEF and nsPEF) shocks. A 3D printer was customized with an electrode holder to precisely position electrodes orthogonal to a cell monolayer in a nanofiber multiwell plate. Trains of nsPEF shocks (200, 300-ns pulses at 1.74 kV) or μsPEF shocks (20, 100-μs pulses at 300 V) produced a non-uniform electric field enabling efficient measurements of the lethal effect in a wide range of the electric field strength. Cell viability and caspase 3/7 expression were measured by fluorescent microscopy 2–24 h after the treatment. nsPEF shocks caused little or no caspase 3/7 activation; most of the lethally injured cells were permeable to propidium dye already at 2 h after the exposure. In contrast, μsPEF shocks caused strong activation of caspase 3/7 at 2 h and the number of dead cells grew up to 24 h, indicating the prevalence of the apoptotic death pathway. P188 at 0.2–1% reduced cell death, suggesting its potential utility in vivo to alleviate electric injury from defibrillation

Uneven Distribution of MHC Class II Epitopes within the Influenza Virus

The identification of T cell epitopes is crucial for the understanding of the host immune response during infection. While much is known about the MHC class I-restricted response following influenza virus infection of C57BL/6 mice, with over 16 CD8 epitopes identified to date, less is known about the MHC class II-restricted response. Currently, only a few I-Ab-restricted T helper epitopes have been identified. Therefore, several important questions remain about how many class II epitopes exist in this system and whether these epitopes are evenly distributed within the most abundant viral proteins. In order to address these questions, we analyzed the repertoire of epitopes that drive the CD4b T cell response to influenza virus infection in C57BL/6 (H-2b) mice. Using a panel of overlapping peptides from each of the viral proteins we show that approximately 20–30 epitopes drive the CD4 T cell response and that the majority of these peptides are derived from the NP and HA proteins. We were also able to demonstrate that vaccination with one of the newly identified epitopes, HA211–225/Ab, resulted in increased epitope-specific T cell numbers and a significant reduction in viral titers following influenza virus challenge

Uneven Distribution of MHC Class II Epitopes within the Influenza Virus

The identification of T cell epitopes is crucial for the understanding of the host immune response during infection. While much is known about the MHC class I-restricted response following influenza virus infection of C57BL/6 mice, with over 16 CD8 epitopes identified to date, less is known about the MHC class II-restricted response. Currently, only a few I-Ab-restricted T helper epitopes have been identified. Therefore, several important questions remain about how many class II epitopes exist in this system and whether these epitopes are evenly distributed within the most abundant viral proteins. In order to address these questions, we analyzed the repertoire of epitopes that drive the CD4b T cell response to influenza virus infection in C57BL/6 (H-2b) mice. Using a panel of overlapping peptides from each of the viral proteins we show that approximately 20–30 epitopes drive the CD4 T cell response and that the majority of these peptides are derived from the NP and HA proteins. We were also able to demonstrate that vaccination with one of the newly identified epitopes, HA211–225/Ab, resulted in increased epitope-specific T cell numbers and a significant reduction in viral titers following influenza virus challenge

The SPORTSMART study: a pilot randomised controlled trial of sexually transmitted infection screening interventions targeting men in football club settings

Background: Uptake of chlamydia screening by men in England has been substantially lower than by women. Non-traditional settings such as sports clubs offer opportunities to widen access. Involving people who are not medically trained to promote screening could optimise acceptability. Methods: We developed two interventions to explore the acceptability and feasibility of urine-based sexually transmitted infection (STI) screening interventions targeting men in football clubs. We tested these interventions in a pilot cluster randomised control trial. Six clubs were randomly allocated, two to each of three trial arms: team captain-led and poster STI screening promotion; sexual health adviser-led and poster STI screening promotion; and poster-only STI screening promotion (control/comparator). Primary outcome was test uptake. Results: Across the three arms, 153 men participated in the trial and 90 accepted the offer of screening (59%, 95% CI 35% to 79%). Acceptance rates were broadly comparable across the arms: captain-led: 28/56 (50%); health professional-led: 31/46 (67%); and control: 31/51 (61%). However, rates varied appreciably by club, precluding formal comparison of arms. No infections were identified. Process evaluation confirmed that interventions were delivered in a standardised way but the control arm was unintentionally ‘enhanced’ by some team captains actively publicising screening events. Conclusions: Compared with other UK-based community screening models, uptake was high but gaining access to clubs was not always easy. Use of sexual health advisers and team captains to promote screening did not appear to confer additional benefit over a poster-promoted approach. Although the interventions show potential, the broader implications of this strategy for UK male STI screening policy require further investigation

Integrative Imaging Informatics for Cancer Research: Workflow Automation for Neuro-oncology (I3CR-WANO)

Efforts to utilize growing volumes of clinical imaging data to generate tumor evaluations continue to require significant manual data wrangling owing to the data heterogeneity. Here, we propose an artificial intelligence-based solution for the aggregation and processing of multisequence neuro-oncology MRI data to extract quantitative tumor measurements. Our end-to-end framework i) classifies MRI sequences using an ensemble classifier, ii) preprocesses the data in a reproducible manner, iii) delineates tumor tissue subtypes using convolutional neural networks, and iv) extracts diverse radiomic features. Moreover, it is robust to missing sequences and adopts an expert-in-the-loop approach, where the segmentation results may be manually refined by radiologists. Following the implementation of the framework in Docker containers, it was applied to two retrospective glioma datasets collected from the Washington University School of Medicine (WUSM; n = 384) and the M.D. Anderson Cancer Center (MDA; n = 30) comprising preoperative MRI scans from patients with pathologically confirmed gliomas. The scan-type classifier yielded an accuracy of over 99%, correctly identifying sequences from 380/384 and 30/30 sessions from the WUSM and MDA datasets, respectively. Segmentation performance was quantified using the Dice Similarity Coefficient between the predicted and expert-refined tumor masks. Mean Dice scores were 0.882 ($\pm$0.244) and 0.977 ($\pm$0.04) for whole tumor segmentation for WUSM and MDA, respectively. This streamlined framework automatically curated, processed, and segmented raw MRI data of patients with varying grades of gliomas, enabling the curation of large-scale neuro-oncology datasets and demonstrating a high potential for integration as an assistive tool in clinical practice

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: A call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, st jude global, UICC and WHPCA

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.Fil: Pritchard Jones, Kathy. University College London; Estados UnidosFil: de Abib, Simone C.V.. International Society Of Paediatric Surgical Oncology; Surinam. Universidade Federal de Sao Paulo; BrasilFil: Esiashvili, Natia. University of Emory; Estados UnidosFil: Kaspers, Gertjan J.L.. Princess Máxima Center for Pediatric Oncology; Países BajosFil: Rosser, Jon. No especifíca;Fil: van Doorninck, John A.. Rocky Mountain Hospital for Children; Estados UnidosFil: Braganca, João M.L.. No especifíca;Fil: Hoffman, Ruth I.. No especifíca;Fil: Rodriguez Galindo, Carlos. St Jude Children’s Research Hospital; Estados UnidosFil: Adams, Cary. Union for International Cancer Control; SuizaFil: Connor, Stephen R.. Worldwide Hospice Palliative Care Alliance; Estados UnidosFil: Abdelhafeez, Abdelhafeez H.. International Society of Paediatric Surgical Oncology; Suiza. St. Jude Children’s Research Hospital; Estados UnidosFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Howard, Scott C.. International Society of Paediatric Surgical Oncology; Suiza. University of Tennessee; Estados UnidosFil: Challinor, Julia M.. International Society of Paediatric Surgical Oncology; Suiza. University of California; Estados UnidosFil: Hessissen, Laila. Children Hospital of Rabat; Marruecos. International Society of Paediatric Surgical Oncology; SuizaFil: Dalvi, Rashmi B.. Bombay Hospital Institute of Medical Sciences; India. International Society of Paediatric Surgical Oncology; SuizaFil: Kearns, Pamela. International Society of Paediatric Surgical Oncology; SuizaFil: Chantada, Guillermo Luis. International Society of Paediatric Surgical Oncology; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Frazier, Lindsay A.. International Society of Paediatric Surgical Oncology; Suiza. Dana-Farber Cancer Institute; Estados UnidosFil: Sullivan, Michael J.. University of Melbourne; Australia. International Society of Paediatric Surgical Oncology; SuizaFil: Schulte, Fiona S.M.. University of Calgary; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Morrissey, Lisa K.. Boston Children’s Hospital; Estados Unidos. International Society of Paediatric Surgical Oncology; SuizaFil: Kozhaeva, Olga. European Society for Paediatric Oncology; BélgicaFil: Luna Fineman, Sandra. Children’s Hospital Colorado; Estados Unidos. International Society of Paediatric Oncology; SuizaFil: Khan, Muhammad S.. Tawam Hospital; Emiratos Arabes Unido