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Rotavirus is a leading cause of diarrhea among children but less known as a cause among adults. We describe clinical, epidemiologic, and genotype characteristics of a rotavirus outbreak among adults in King County, Washington occurring January-June 2023. Adult rotavirus incidence in 2023 was ten times higher than the same period in 2022 (5% versus 0.5% samples). Disease severity was mild. G9P[4], an uncommon, non-vaccine strain in USA, was the predominant genotype. Genotyping suggested spillover from children with subsequent spread among adults. Our study highlights benefits of routine testing and genotyping during outbreaks for surveillance, tracking, and understanding implications on vaccination., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Breastfeeding is vital for infant nutrition, bonding, and overall health. However, challenges can arise with the presence of tethered oral tissues, commonly known as labial (lip) tie or lingual (tongue) tie, otherwise known as ankyloglossia. This case study explores the differential resolution of breastfeeding symptoms in a one-month-old infant with both labial and lingual ties. It outlines the diagnostic process, surgical interventions, and postoperative care, emphasizing the importance of detailed characterization of symptom resolution associated with a lingual and labial frenectomy. Case Presentation: The one-month-old male presented with 11 symptoms of feeding difficulties. Sequential surgical releases were performed for the labial and lingual ties, with a ranula also addressed. Detailed symptom assessments were conducted at one, two, and 4 weeks postsurgery, revealing differential responses to labial and lingual releases. Results: The results show that 81.8% of symptoms resolved after labial and lingual surgeries, with some symptoms responding specifically to either labial or lingual release. The study suggests that surgical intervention can significantly improve breastfeeding outcomes, including for patients who may not have access to sufficient lactation counseling resources. Conclusion: This single case study provides a valuable starting point for the exploration of which dysfunctional breastfeeding symptoms are associated with a labial tie versus lingual tie. Further research with larger samples is warranted to explore optimal treatment strategies for diverse parent-baby dyads experiencing breastfeeding difficulties, or whose access to lactation support services is limited., Competing Interests: All authors serve as directors on the board of the International Consortium of oral Ankylofrenula Professionals (ICAP). Raymond J. Tseng and Sharon Smart co-chair the Committee for Interprofessional Research, Education, and Ankyloglossia Science (CIREAS) committee for ICAP. Sharon Smart also serves as chair of the Australasian Society of Tethered Oral Tissues (ASTOT)., (Copyright © 2024 Raymond J. Tseng et al.)

Purpose: The rapid adoption of telepractice services by health professionals was necessary to maintain service continuity for children with paediatric feeding disorders during the COVID-19 pandemic, during periods where in-person therapy was restricted. The aim of this study was to explore clinical perspectives and reflections on the use of telepractice for managing paediatric feeding disorders during the pandemic., Method: A post-positivist qualitative approach using thematic analysis was adopted. This study seeks to understand participants' experiences and thoughts from allied health professionals from speech-language pathology, occupational therapy, and dietetics working with paediatric feeding in Western Australia. All participants delivered at least 10 telepractice sessions to children from birth to 12 years with a paediatric feeding disorder. Braun and Clarke's six-step thematic analysis process was used to analyse the data inductively., Result: Eleven allied health professionals representing eight clinical settings in Western Australia, including speech-language pathology, occupational therapy, and dietetics, working with paediatric feeding were recruited. The results revealed four themes: families becoming the catalyst of change, clinician comfort over confidence, insights into authentic mealtimes, and the paradox of choice., Conclusion: This study highlighted the need to build clinicians' confidence and competence, and the provision of service guidelines and training. Although many clinicians had positive experiences with telepractice, most returned to in-person delivery once COVID-19 restrictions were lifted, emphasising the importance of comfort in service delivery selection. We recognise that the findings of this study are constrained by the fact that it was conducted in a single geographical region and utilised a small qualitative sample. While telepractice was successful in managing paediatric feeding disorders, further development and implementation of telepractice guidelines are needed for telepractice to be a viable service delivery option for families and children with feeding disorders.

Background: Surgical intervention for tongue-tie, or ankyloglossia performed by paediatric dentists can alleviate symptoms and improve functional abilities in infants and children. Despite widespread practice, there are currently no established clinical guidelines or consistent approaches for pre- and post-operative care of children., Aim: The aim of this study was to explore approaches to pre- and post-operative care for children with ankyloglossia having frenum surgery., Design: A scoping review of peer-reviewed articles in four electronic databases was conducted. Intervention studies that reported on pre- or post-operative regimens for infants, children and adolescents (0 to 18 years) with a diagnosis of tongue-tie or ankyloglossia, who had surgical intervention such as frenotomy or frenectomy, were included and quality assessments performed., Results: Twenty-three studies were identified, with seven studies incorporating both pre- and post-operative care, and 16 studies focussing solely on post-operative care. Tongue exercises were commonly prescribed, and only three studies examined the relationship between post-operative care and recovery outcomes. Considerable variability existed in study design, prescribed care and outcome measures., Conclusion: There was substantial variability in pre- and post-operative care protocols, including dosage, frequency and duration of exercises and other care regimens for infants and children having frenum surgery. Further research is needed to determine the most effective course of pre- and post-operative care for children undergoing frenum surgery., (© 2024 The Author(s). International Journal of Paediatric Dentistry published by BSPD, IAPD and John Wiley & Sons Ltd.)

Objective: COVID-19 has been associated with myocardial involvement in collegiate athletes. The first report from the Big Ten COVID-19 Cardiac Registry (Registry) was an ecological study that reported myocarditis in 37 of 1597 athletes (2.3%) based on local clinical diagnosis. Our objective was to assess the relationship between athlete and clinical characteristics and myocardial involvement., Design: Cross-sectional study., Setting: We analyzed data from 1218 COVID-19 positive Big Ten collegiate athletes who provided informed consent to participate in the Registry., Participants: 1218 athletes with a COVID-19-positive PCR test before June 1, 2021., Assessment of Independent Variables: Demographic and clinical characteristics of athletes were obtained from the medical record., Main Outcome Measures: Myocardial involvement was diagnosed based on local clinical, cardiac magnetic resonance (CMR), electrocardiography, troponin assay, and echocardiography. We assessed the association of clinical factors with myocardial involvement using logistic regression and estimated the area under the receiver operating characteristic (ROC) curve., Results: 25 of 1218 (2.0%) athletes met criteria for myocardial involvement. The logistic regression model used to predict myocardial involvement contained indicator variables for chest pain, new exercise intolerance, abnormal echocardiogram (echo), and abnormal troponin. The area under the ROC curve for these indicators was 0.714. The presence of any of these 4 factors in a collegiate athlete who tested positive for COVID-19 would capture 55.6% of cases. Among noncases without missing data, 86.9% would not be flagged for possible myocardial involvement., Conclusion: Myocardial involvement was infrequent. We predicted case status with good specificity but deficient sensitivity. A diagnostic approach for myocardial involvement based exclusively on symptoms would be less sensitive than one based on symptoms, echo, and troponin level evaluations. Abnormality of any of these evaluations would be an indication for CMR., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Much of the ecological discourse surrounding the polarising theropod Spinosaurus has centred on qualitative discussions. Using a quantitative multivariate data analytical approach on size-adjusted linear measurements of the skull, we examine patterns in skull shape across a range of sauropsid clades and three ecological realms (terrestrial, semi-aquatic, and aquatic). We utilise cluster analyses to identify emergent properties of the data which associate properties of skull shape with ecological realm occupancy. Results revealed terrestrial ecologies to be significantly distinct from both semi- and fully aquatic ecologies, the latter two were not significantly different. Spinosaurids (including Spinosaurus ) plotted away from theropods in morphospace and close to both marine taxa and wading birds. The position of nares and the degree of rostral elongation had the greatest effect on categorisation. Comparisons of supervised (k-means) and unsupervised clustering demonstrated categorising taxa into three groups (ecological realms) was inappropriate and suggested instead that cluster division is based on morphological adaptations to feeding on aquatic versus terrestrial food items. The relative position of the nares in longirostrine taxa is associated with which skull bones are elongated. Rostral elongation is observed by either elongating the maxilla and the premaxilla or by elongating the maxilla only. This results in the nares positioned towards the orbits or towards the anterior end of the rostrum respectively, with implications on available feeding methods. Spinosaurids, especially Spinosaurus , show elongation in the maxilla-premaxilla complex, achieving similar functional outcomes to elongation of the premaxilla seen in birds, particularly large-bodied piscivorous taxa. Such a skull construction would bolster "stand-and-wait" predation of aquatic prey to a greater extent than serving other proposed feeding methods., Competing Interests: The authors declare that they have no competing interests., (© 2024 Smart and Sakamoto.)

Background: Nonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and are often perceived as their most bothersome symptoms. However, these remain poorly understood with suboptimal clinical management. These unmet needs are an important determinant of health-related quality of life (QoL) in PD., Objective: The aim of this study was to gain insights into the experience of living with the NMS of PD in real-time using participatory action methodology., Method: Using the photovoice method, 14 people with PD took photographs to document their experiences of living with the NMS of PD. They composed corresponding written narratives to capture the impact of NMS on their daily activities and QoL. In total, 152 photographs and corresponding narratives were analysed using thematic analysis with an inductive approach., Results: Four interrelated themes were identified. Emotional well-being and sense of self encompassed a process of adjustment to living with PD. Engaging in valued activities, adopting a positive mindset and utilising coping strategies were thought to enhance confidence and self-esteem. Social support and societal awareness highlighted the importance of supportive relationships and socialising to aid participation and avoid isolation. Barriers to social engagement included the unpredictability of NMS and nonvisible NMS being neglected or misunderstood., Conclusion: Findings demonstrated the far-reaching impact of nonmotor aspects of PD on emotional, occupational and social dimensions. These needs could be addressed through person-centred and comprehensive approaches to care., Patient or Public Contribution: This study utilised a participatory research approach allowing participants to choose the subjects that mattered to them and how to present their results. Additionally, a group workshop was held with people with PD, their family members and healthcare professionals to guide theme development., (© 2024 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Purpose: Few assessment tools objectively measure chewing skills in the paediatric population. There is a need for assessment tools that use consistent foods so comparisons can be made between typically developing children and children with paediatric feeding disorders, and to measure the efficacy of treatment. The Test of Masticating and Swallowing Solids for adults (TOMASS) and children (TOMASS-C) are assessments that use a cracker as a consistent measure to assess chewing skills. Normative data exist for children over 4 years, however, no data are available for younger children. This study investigated age and gender-related differences in mastication skills in typically developing children aged 2-3 years when eating a cracker., Method: Thirty participants aged 2;0-3;10 were assessed using an adapted version of the TOMASS-C. Participants were required to eat a single Arnott's Salada cracker, and the number of bites, masticatory cycles, swallows, and duration of time to finish the cracker were measured., Result: Two-year-old children used more masticatory cycles and took longer to finish the cracker than 3-year-old children. There were no significant effects of age on the number of swallows and number of bites, and no significant differences between boys and girls., Conclusion: This study provides preliminary normative data for chewing skills in children aged 2 and 3 years and confirms that the TOMASS-C is sensitive to developmental changes in mastication within this younger age range. These results expand our understanding of oral motor and chewing development in children.

Metabolic disease is increasing in people with HIV (PWH) in South Africa, but little is known about self-perceptions of body size, health, and nutritional behavior in this population. We performed a cross-sectional analysis of individual-level data from the 2016 South Africa Demographic and Health Survey. This survey measured HIV serostatus and body mass index (BMI). We categorized participants into six BMI groups: 18.5-22 kg/m 2 , 22-25 kg/m 2 , 25-27.5 kg/m 2 , 27.5-30 kg/m 2 , 30-35 kg/m 2 , and ≥ 35 kg/m 2 and stratified them by HIV serostatus. Our outcomes were self-reported (1) body size and (2) health status among all participants, and intake of (3) chips and (4) sugar-sweetened beverages (SSB) in PWH. We described these metrics and used multivariable regression to evaluate the relationship between the nutritional behaviors and BMI ≥ 25 kg/m 2 in PWH only, adjusting for age, sex, educational attainment, and household wealth quintile. Of 6138 participants, 1163 (19.7%) were PWH. Among PWH, < 10% with a BMI 25-30 kg/m 2 , < 20% with a BMI 30-35 kg/m 2 and < 50% with a BMI ≥ 35 kg/m 2 self-reported as overweight or obese. PWH reported being in poor health at higher rates than those without HIV at each BMI category except ≥ 35 kg/m 2 . In adjusted models, SSB consumption was associated with BMI ≥ 25 kg/m 2 (1.13 [1.01-1.25], t-statistic = 2.14, p = 0.033) in PWH. Perceptions of body size may challenge efforts to prevent weight gain in PWH in South Africa. SSB intake reduction should be further explored as a modifiable risk factor for obesity., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Prostate cancer accounts for 20.3% of all cancers in men in sub-Saharan Africa. Early screening among at-risk groups is challenging in Uganda, with limited data on prostate cancer screening uptake in most districts, including newly established ones. The purpose of this study was to determine factors influencing the uptake of prostate cancer screening among men aged ≥ 40 in Kazo Town Council, Kazo District, a newly created district. We used a descriptive cross-sectional study design that employed both quantitative and qualitative data collection methods. Participants were recruited through simple random sampling between November 2020 and January 2021. Structured questionnaires were used for quantitative data ( n = 300). Statistical analyses to determine associations were carried out using inferential and chi-square tests followed by logistic regression. In-depth interviews were conducted with 10 key informants and analyzed thematically to explore a range of perceptions related to prostate cancer screening. Only 10 (3.33%; 95% CI: 0.018-0.60) respondents had ever screened for prostate cancer. Lack of privacy ( p < 0.033), access to prostate cancer information ( p < 0.014), and distance to health facilities ( p < 0.001) were significantly associated with the uptake of prostate cancer screening. Marital status (OR = 7.93; 95% CI: 1.85-33.99; p = 0.005), positive health worker attitudes (OR = 0.002; 95% CI: 0.000-0.023, p < 0.001), and perceived affordability (OR = 0.001; 95% CI: 0.000-0.011, p < 0.001) were independently associated with uptake of prostate cancer screening. Key barriers included lack of information, access to screening centres, and fear of screening. The level of uptake of prostate cancer screening was considerably low among men aged 40 and above in the Kazo District. Targeted community interventions to improve access to prostate cancer information, screening, sensitization, and addressing perceived and actual barriers are needed in newly created districts to bolster the uptake of prostate cancer screening. This has implications for prioritizing research evaluating district resource allocation to support optimized and integrated evidence-based service delivery in primary healthcare centres, especially for specialized services in newly created districts., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Smart Mwebembezi et al.)

Objectives: The study sought to assess the prognostic significance of nonischemic myocardial fibrosis (MF) on cardiovascular magnetic resonance (CMR)-both macroscopic MF assessed by late gadolinium enhancement (LGE) and diffuse microscopic MF quantified by extracellular volume fraction (ECV)-in patients with structurally normal hearts., Background: The clinical relevance of tissue abnormalities identified by CMR in patients with structurally normal hearts remains unclear., Methods: Consecutive patients undergoing CMR were screened for inclusion to identify those with LGE imaging and structurally normal hearts. ECV was calculated in patients with available T1 mapping. The associations between myocardial fibrosis and the outcomes of all-cause mortality, new-onset heart failure [HF], and an arrhythmic outcome were evaluated., Results: In total 525 patients (mean age 43.1±14.2 years; 30.5% males) were included. Over a median follow-up of 5.8 years, 13 (2.5%) patients died and 18 (3.4%) developed new-onset HF. Nonischemic midwall /subepicardial LGE was present in 278 (52.9%) patients; isolated RV insertion fibrosis was present in 80 (15.2%) patients. In 276 patients with available T1 mapping, the mean ECV was 25.5 ± 4.4%. There was no significant association between LGE and all-cause mortality (HR: 1.36, CI: 0.42-4.42, p = 0.61), or new-onset HF (HR: 0.64, CI: 0.25-1.61, p = 0.34). ECV (per 1% increase) correlated with all-cause mortality (HR: 1.19, CI: 1.04-1.36, p = 0.009), but not with new-onset HF (HR: 0.97, CI: 0.86-1.10, p = 0.66). There was no significant association between arrhythmic outcomes and LGE (p = 0.60) or ECV (p = 0.49). In a multivariable model after adjusting for covariates, ECV remained significantly associated with all-cause mortality (HR per 1% increase in ECV: 1.26, CI: 1.06-1.50, p = 0.009)., Conclusion: Nonischemic LGE in patients with structurally normal hearts is common and does not appear to be associated with adverse outcomes, whereas elevated ECV is associated with all-cause mortality and may be an important risk stratification tool., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Combining histology and ex vivo MRI from the same mouse brain is a powerful way to study brain microstructure. Mouse brains prepared for ex vivo MRI are often kept in storage solution for months, potentially becoming brittle and showing reduced antigenicity. Here, we describe a protocol for mouse brain dissection, tissue processing, paraffin embedding, sectioning, and staining. We then detail registration of histology to ex vivo MRI data from the same sample and extraction of quantitative histological measurements., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with cardiac amyloidosis (CA), left ventricular ejection fraction (LVEF) is frequently preserved, despite commonly reduced global longitudinal strain (GLS). We hypothesized that nonlongitudinal contraction may initially serve as a mitigating mechanism to maintain cardiac output and studied the relationship between global circumferential (GCS) and radial (GRS) strain with LVEF and extracellular volume (ECV), a marker of amyloid burden., Methods: Patients with CA who underwent cardiac magnetic resonance (CMR; n = 140, 70.7 ± 11.5 years, 66% male) or echocardiography (n = 67, 71 ± 13 years, 66% male) and normal controls (CMR, n = 20; echocardiography, n = 45) were retrospectively identified, and GCS, GLS, and GRS were quantified using feature-tracking CMR or speckle-tracking echocardiography and compared between CA patients with preserved and reduced LVEF (CA HFpEF , CA HFrEF ) and controls. The prevalence of impaired strain (magnitudes <2.5th percentile of the controls) was compared between CA HFpEF and CA HFrEF and between ECV quartiles., Results: While echocardiography-derived GLS was impaired in both CA HFpEF (-13.4% ± 3.1%, P < .003) and CA HFrEF (-9.1% ± 3.2%, P < .003), compared with controls (-20.8% ± 2.4%), GCS was more impaired in CA HFrEF compared with both controls (-15.6% ± 5.0% vs -32.3% ± 3.3%, P < .003) and CA HFpEF (-30.4% ± 5.7%, P < .003) and did not differ between CA HFpEF and controls (P = .24). The prevalence of abnormal CMR-derived GCS (P < .0001) and GRS (P < .0001) but not GLS (P = .054) varied significantly across ECV quartiles., Conclusions: Among CA patients with preserved LVEF, preserved GCS and GRS, despite near-universally impaired GLS, may be explained by an initial predominantly subendocardial involvement, where mostly longitudinal fibers are located. If confirmed in future studies, these findings may facilitate identification of patients with early stages of CA, when treatments may be most effective., (Copyright © 2023 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

The microtubule (MT) cytoskeleton and its dynamics play an important role in cell migration. Depletion of the microtubule-severing enzyme Fidgetin-like 2 (FL2), a regulator of MT dynamics at the leading edge of migrating cells, leads to faster and more efficient cell migration. Here we examine how siRNA knockdown of FL2 increases cell motility. Förster resonance energy transfer biosensor studies shows that FL2 knockdown decreases activation of the p21 Rho GTPase, RhoA, and its activator GEF-H1. Immunofluorescence studies reveal that GEF-H1 is sequestered by the increased MT density resulting from FL2 depletion. Activation of the Rho GTPase, Rac1, however, does not change after FL2 knockdown. Furthermore, FL2 depletion leads to an increase in focal adhesion kinase activation at the leading edge, as shown by immunofluorescence studies, but no change in actin dynamics, as shown by fluorescence recovery after photobleaching. We believe these results expand our understanding of the role of MT dynamics in cell migration and offer new insights into RhoA and Rac1 regulation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. Simulations showed that the proposed model was robust to perturbations in T 1 , transmit B 1 , and k PL . A significant difference in ipsilateral vs contralateral pyruvate derived cerebral blood flow (CBF) was detected in rats (140 ± 2 vs 89 ± 6 mL/100 g/min, p < 0.01, respectively) and pigs (139 ± 12 vs 95 ± 5 mL/100 g/min, p = 0.04, respectively), along with an increase in fractional metabolism (26 ± 5 vs 4 ± 2%, p < 0.01, respectively) in the rodent brain. In addition, a significant increase in ipsilateral vs contralateral MCR (0.034 ± 0.007 vs 0.017 ± 0.02/s, p = 0.03, respectively) and a decrease in mean transit time (31 ± 8 vs 60 ± 2 s, p = 0.04, respectively) was observed in the porcine brain. In conclusion, MCR mapping is a simple and robust approach to the post-processing of hyperpolarized magnetic resonance imaging., (© 2023. The Author(s).)

Objectives: This prospective cohort study tested for associations between baseline cognitive performance in individuals early within their first episode and antipsychotic treatment of psychosis. We hypothesised that poorer cognitive functioning at the initial assessment would be associated with poorer antipsychotic response following the subsequent 6 weeks., Design: Prospective cohort ., Setting: National Health Service users with a first-episode schizophrenia diagnosis, recently starting antipsychotic medication, recruited from two UK sites (King's College London, UK and University of Manchester, UK). Participants attended three study visits following screening., Participants: Eighty-nine participants were recruited, with 46 included in the main analysis. Participants required to be within the first 2 years of illness onset, had received minimal antipsychotic treatment, have the capacity to provide consent, and be able to read and write in English. Participants were excluded if they met remission criteria or showed mild to no symptoms., Primary and Secondary Outcome Measures: Antipsychotic response was determined at 6 weeks using the Positive and Negative Syndrome Scale (PANSS), with cognitive performance assessed at each visit using the Brief Assessment of Cognition in Schizophrenia (BACS). The groups identified (responders and non-responders) from trajectory analyses, as well as from >20% PANSS criteria, were compared on baseline BACS performance., Results: Trajectory analyses identified 84.78% of the sample as treatment responsive, and the remaining 15.22% as treatment non-responsive. Unadjusted and adjusted logistic regressions observed no significant relationship between baseline BACS on subscale and total performance (BACS t-score: OR=0.98, p=0.620, Cohen's d=0.218) and antipsychotic response at 6 weeks., Conclusions: This investigation identified two clear trajectories of treatment response in the first 6 weeks of antipsychotic treatment. Responder and non-responder groups did not significantly differ on performance on the BACS, suggesting that larger samples may be required or that an association between cognitive performance and antipsychotic response is not observable in the first 2 years of illness onset., Trial Registration Number: REC: 17/NI/0209., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objective: Oxygen-loaded nanobubbles have shown potential for reducing tumour hypoxia and improving treatment outcomes, however, it remains difficult to noninvasively measure the changes in partial pressure of oxygen (PO 2 ) in vivo. The linear relationship between PO 2 and longitudinal relaxation rate (R 1 ) has been used to noninvasively infer PO 2 in vitreous and cerebrospinal fluid, and therefore, this experiment aimed to investigate whether R 1 is a suitable measurement to study oxygen delivery from such oxygen carriers., Methods: T 1 mapping was used to measure R 1 in phantoms containing nanobubbles with varied PO 2 to measure the relaxivity of oxygen (r 1Ox ) in the phantoms at 7 and 3 T. These measurements were used to estimate the limit of detection (LOD) in two experimental settings: preclinical 7 T and clinical 3 T MRI., Results: The r 1Ox in the nanobubble solution was 0.00057 and 0.000235 s -1 /mmHg, corresponding to a LOD of 111 and 103 mmHg with 95% confidence at 7 and 3 T, respectively., Conclusion: This suggests that T 1 mapping could provide a noninvasive method of measuring a > 100 mmHg oxygen delivery from therapeutic nanobubbles., (© 2022. The Author(s).)

Purpose of Review: Paravalvular leak (PVL) is a relatively uncommon complication associated with prosthetic valve implantation. PVL can occasionally lead to serious adverse consequences such as congestive heart failure, infective endocarditis, and hemolytic anemia. Surgical re-operation carries a high mortality risk., Recent Findings: Transcatheter closure therapy provides a viable alternative for the treatment of this disorder with reasonable procedural and clinical success. The recent advent of hybrid imaging modalities has increased procedural success. This article summarizes the pathophysiology, clinical characteristics, and treatment modalities surroundings prosthetic paravalvular leak., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The effect of radiation therapy on tumor vasculature has long been a subject of debate. Increased oxygenation and perfusion have been documented during radiation therapy. Conversely, apoptosis of endothelial cells in irradiated tumors has been proposed as a major contributor to tumor control. To examine these contradictions, we use multiphoton microscopy in two murine tumor models: MC38, a highly vascularized, and B16F10, a moderately vascularized model, grown in transgenic mice with tdTomato-labeled endothelium before and after a single (15 Gy) or fractionated (5 × 3 Gy) dose of radiation. Unexpectedly, even these high doses lead to little structural change of the perfused vasculature. Conversely, non-perfused vessels and blind ends are substantially impaired after radiation accompanied by apoptosis and reduced proliferation of their endothelium. RNAseq analysis of tumor endothelial cells confirms the modification of gene expression in apoptotic and cell cycle regulation pathways after irradiation. Therefore, we conclude that apoptosis of tumor endothelial cells after radiation does not impair vascular structure., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Purpose: To determine the effect of altering anesthetic oxygen protocols on measurements of cerebral perfusion and metabolism in the rodent brain., Methods: Seven rats were anesthetized and underwent serial MRI scans with hyperpolarized [1- 13 C]pyruvate and perfusion weighted imaging. The anesthetic carrier gas protocol used varied from 100:0% to 90:10% to 60:40% O 2 :N 2 O. Spectra were quantified with AMARES and perfusion imaging was processed using model-free deconvolution. A 1-way ANOVA was used to compare results across groups, with pairwise t tests performed with correction for multiple comparisons. Spearman's correlation analysis was performed between O 2 % and MR measurements., Results: There was a significant increase in bicarbonate:total 13 C carbon and bicarbonate: 13 C pyruvate when moving between 100:0 to 90:10 and 100:0 to 60:40 O 2 :N 2 O % (0.02 ± 0.01 vs. 0.019 ± 0.005 and 0.02 ± 0.01 vs. 0.05 ± 0.02, respectively) and (0.04 ± 0.01 vs. 0.03 ± 0.01 and 0.04 ± 0.01 vs. 0.08 ± 0.02, respectively). There was a significant difference in 13 C pyruvate time to peak when moving between 100:0 to 90:10 and 100:0 to 60:40 O 2 :N 2 O % (13 ± 2 vs. 10 ± 1 and 13 ± 2 vs. 7.5 ± 0.5 s, respectively) as well as significant differences in cerebral blood flow (CBF) between gas protocols. Significant correlations between bicarbonate: 13 C pyruvate and gas protocol (ρ = -0.47), mean transit time and gas protocol (ρ = 0.41) and 13 C pyruvate time-to-peak and cerebral blood flow (ρ = -0.54) were also observed., Conclusions: These results demonstrate that the detection and quantification of cerebral metabolism and perfusion is dependent on the oxygen protocol used in the anesthetized rodent brain., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Introduction and Objectives: Surgeons should aim for continuous quality improvement. The aim of this study was to evaluate the impact of incremental changes to Robot Assisted Radical Prostatectomy (RARP) technique on intra-operative and early post-operative outcomes., Patients and Methods: All cases of RARP performed by a single surgeon in a tertiary institution over a 2-year period were included in this evaluation. Routine clinical data were collected. Cases were retrospectively allocated to four groups depending on key technical steps (1 = standard anterior approach; 2 = anterior approach with preservation of endopelvic fascia, puboprostatic fascia and urachus; 3 = posterior approach for nerve spare, with preservation of endopelvic fascia, puboprostatic fascia and urachus; 4 = Retzius-sparing posterior approach)., Results: 187 patients were allocated to groups: 1 = 22, 2 = 53, 3 = 90, 4 = 22. There were no significant differences in pre-operative characteristics, except age: 1 = 62.5, 2 = 62, 3 = 62.5, 4 = 58.5 (p = 0.02). Intra-operative differences were found in console time: 1 = 195, 2 = 167, 3 = 195 4 = 136.5 min (p < 0.001); and proportion of non-nerve sparing cases: 1 = 36%, 2 = 17%, 3 = 13%, 4 = 0% (p = 0.044). No significant differences were found in lymph node dissections, blood loss or complications. Post-operatively, no differences were found in length of stay, pathological characteristics, margin status, lymph node yield, complications or PSA levels. Significant differences were seen in pad-free continence at 6 weeks: 1 = 23%, 2 = 23%, 3 = 34%, 4 = 73% (p < 0.01); and social continence (using 1 pad) at 6-weeks: 1 = 59%, 2 = 87%, 3 = 81%, 4 = 95% (p = 0.01). Significant differences in pad-free continence persisted at 12 months: 1 = 63%, 2 = 81%, 3 = 78%, 4 = 100% (p = 0.019)., Conclusion: Our results suggest that aggregated marginal gains from incremental modification of RARP leads to significantly improved continence outcomes without compromising patient safety or oncological control., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Chronotropic incompetence (CI) is an inability to adequately raise heart rate during physiological stress. We established CI prevalence and exercise capacity in heart failure versus healthy age-matched controls. We conducted a systematic search (1966-July 1, 2020) and meta-analysis of studies reporting peak VO 2 in people with heart failure with reduced (HFrEF) and preserved (HFpEF) left ventricular ejection fraction and controls. Seventeen studies of 4410 participants were included, 4167 with heart failure and 243 age-matched controls. In both heart failure phenotypes, CI was more prevalent in HFrEF (51.7%) and HFpEF (55.8%) than in healthy controls (9%). Mortality was 24% higher in people with HFrEF and CI versus those with HFrEF and without CI; OR -1.24 (95% CI -2.20 to -0.28; p = 0.01). People with heart failure and CI had lower peak VO 2 than those without CI (MD) -3.30 ml kg -1  min -1 (95% CI -4.25 to -2.35, p < 0.01), and this was primarily driven by the HFrEF sub-population (MD) -3.86 ml kg -1  min -1 (95% CI -4.83 to -2.89, p < 0.01). Maximum heart rate MD -37.51 beats min -1 (95% CI -41.99 to -33.03, p < 0.01) and maximum-resting heart rate were lower MD -29.44 beats min -1 (95% CI -34.55 to -24.33, p < 0.01) in people with heart failure with CI vs without CI. People with heart failure and CI demonstrated similar respiratory exchange ratios (RER) to people with heart failure but without CI; (MD) -0.02 (95% CI -0.03 to -0.01), p < 0.01, suggesting that poor effort was unlikely to explain CI. CI is more prevalent in heart failure than in age-matched controls and although it is associated with lower peak VO 2 in HFrEF, it is unrelated to the lower peak VO 2 in HFpEF. RER values suggest poor effort is unlikely to explain these findings., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The practical applications of metal-organic frameworks (MOFs) usually require their assembly into mechanically robust structures, usually achieved via coating onto various types of substrates. This paper describes a simple, scalable, and versatile mechanochemical technique for producing MOF nanocrystal coatings on various non-prefunctionalised substrates, including ZrO 2 , carbon cloth, porous polymer, nickel foam, titanium foil and fluorine-doped tin oxide glass. We revealed the detailed mechanisms that ensure the coating's stability, and identified the coating can facilitate the interfacial energy transfer, which allowed the electrocatalysis application of the MOF coating on conductive substrates. We further demonstrated that coatings can be directly generated in a one-pot fashion by ball milling MOF precursors with substrates.

To assess whether the timing of post-operative Phosphodiesterase Inhibitor (PDE5i) therapy after Robot-Assisted Radical Prostatectomy (RARP) is associated with a change in early erectile function (EF) outcomes, continence or safety outcomes. Data were prospectively collected from a single surgeon in one tertiary centre. 158 patients were treated with PDE5i therapy post RARP over a 2-year period. PDE5i therapy was started: immediately (day 1-2) post-op in 29%, early (day 3-14) post-op in 37% and late (after day 14) post-op in 34%. EPIC-26 EF scores were collected pre-op and post-op. There were no significant differences in pre-operative characteristics between the therapy groups. Drop in EF scores and percentage return to baseline for unilateral nerve sparing was, respectively, 9 and 11.1% of immediate therapy, 7 and 14.8% of early therapy and 9.7 and 9.5% of late therapy (p = 0.9 and p = 0.6). For bilateral nerve sparing, this was, respectively, 3.5 and 42.9% immediate therapy, 5.5 and 35.5% early therapy and 7.3 and 25% late therapy (p = 0.017 and p = 0.045). Pad free and social continence were achieved in 54% and 37% of those receiving immediate therapy, 60% and 33% for early therapy and 26% and 54% for late therapy. There were no differences in compliance, complication or readmission outcomes. In patients with bilateral nerve sparing RARP, immediate post-operative PDE5i therapy can protect EF and improve early continence outcomes. Therefore, immediate PDE5i therapy should be considered in patients following nerve sparing RARP to maximise functional outcomes., (© 2021. Crown.)

Forward osmosis membrane bioreactors (FOMBRs) are currently gaining attention from the wastewater treatment industry, for their potential to produce high effluent quality and a relatively better flux stability against fouling. However, only using physical cleaning methods is not sufficient to recover the water flux performance satisfactorily under a long-term operation. This study comprehensively investigated the efficiency of a hybrid, environmentally-friendly cleaning strategy involving a combination of physical and free nitrous acid (FNA) cleanings under a long-term FOMBR operation. During 92 days of FOMBR operation, physical cleaning recovered the water flux by 85%, whilst FNA cleaning contributed to an additional 5% of the recovery. In addition, FNA cleaning also offered a retardation of fouling deposition by maintaining the water flux 18-30% more than that obtained by only the physical cleaning. A possible mechanism for FNA's role as the cleaning reagent was proposed for the first time in this study based on the water flux performance and membrane autopsy analysis. The results showed FNA cleaning broke down the residual fouling layer, preferencing protein-based substances. A lower ratio of protein to polysaccharides of the residual fouling layer contributed to a more negatively charged membrane surface (- 42.34 ± 0.30 mV) compared to the virgin one (- 17.54 ± 0.81 mV). This resulted in a stronger electrostatic repulsion between the foulants and the membrane surface, and thus slowed down the biofouling deposition process. This study suggested FNA solution has the great potential not only to recover the membrane performance, also as a strategy to slow down fouling deposition., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The melting behaviour of metal-organic frameworks (MOFs) has aroused significant research interest in the areas of materials science, condensed matter physics and chemical engineering. This work first introduces a novel method to fabricate a bimetallic MOF glass, through melt-quenching of the cobalt-based zeolitic imidazolate framework (ZIF) [ZIF-62(Co)] with an adsorbed ferric coordination complex. The high-temperature chemically reactive ZIF-62(Co) liquid facilitates the formation of coordinative bonds between Fe and imidazolate ligands, incorporating Fe nodes into the framework after quenching. The resultant Co-Fe bimetallic MOF glass therefore shows a significantly enhanced oxygen evolution reaction performance. The novel bimetallic MOF glass, when combined with the facile and scalable mechanochemical synthesis technique for both discrete powders and surface coatings on flexible substrates, enables significant opportunities for catalytic device assembly., (© 2021 Wiley-VCH GmbH.)

Objectives: High rates of depression, anxiety and stress are reported in tertiary health students. Mindfulness-based programs have been included in the training of health students to help them manage depression, anxiety and stress; however, to date, there has been no review of best practice implementation of mindfulness for health students. The aim of this review was to evaluate the outcomes of mindfulness-based practice for health students to inform best practice with this population., Methods: A comprehensive search was conducted of three electronic databases (PsychINFO, Medline and Embase) guided by the five-step systematic process for conducting scoping reviews to investigate mindfulness-based intervention programs for students enrolled in a tertiary institution in a health-related course., Results: Twenty-four papers met the eligibility criteria and were reviewed in detail. Findings suggested that mindfulness-based intervention approaches are useful in decreasing depression, anxiety and stress in health students; however, challenges exist in student engagement and retention. Generalization of results was limited by the heterogeneous population, intervention designs and delivery methods, as well as a lack of standardized outcome measures., Conclusion: The inclusion of mindfulness-based programs within tertiary curricula can be an effective approach to assist with managing depression, stress and anxiety in health students. Providing academic credit to students, improving translation of skills to working with future clients, and embedding mindfulness-based programs within the curriculum could improve engagement and retention., Supplementary Information: The online version contains supplementary material available at 10.1007/s12671-021-01740-3., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

Background Transcatheter aortic valve replacement (TAVR) is increasingly utilized for most patients with symptomatic severe aortic stenosis. TAVR is linked to enhanced long-term cardiac hemodynamics, reversal of left ventricle (LV) hypertrophy, and improved aortic valve gradients. We present a retrospective observational study assessing cardiac remodeling and valvular flow patterns post-TAVR. Methods Retrospective echocardiographic data were collected, evaluating cardiac function and valvular flow patterns before and after TAVR at a single institution. Data was compiled and statistically analyzed using a paired t-test evaluating variations at approximately 30 days and one-year post-TAVR. Results On echocardiogram 30 days and one-year post-TAVR, there was a reduction in LV mass index from 132 g/m² to 110 g/m² (95%CI: 98-122; p=0.01) and 118 g/m² (95%CI: 102-133; p=0.03), and a reduction in relative wall thickness from 0.54 to 0.49 (95%CI: 0.46-0.52; p=0.05) and 0.44 (95%CI: 0.38-0.49; p=0.03), respectively. Doppler velocity indices (DVI) increased from 0.24 to 0.61 (95%CI: 0.49-0.73; p<0.001) and 0.57 (95%CI: 0.48-0.65; p<0.001). Expected improvement in aortic valve velocities and gradients were observed post-TAVR. Conclusions Following TAVR, LV remodeling can be observed as early as 30 days. This is demonstrated by a reduction in LV mass index and relative wall thickness in conjugation with an anticipated improvement in valvular flow patterns and flow across the aortic valve., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Feghaly et al.)

A major problem with longitudinal studies is the bias generated due to attrition, particularly apparent amongst patients suffering from psychotic disorders. Factors associated with study-participation were investigated as part of a larger research collaboration (STRATA). Out of 479 eligible participants, only 50 (10,4%) were successfully followed up. The present study investigated whether study participation differed depending on baseline characteristics. Results indicated that individuals who did not participate were more likely to report an alcohol use disorder while those who did respond were more likely to have been in full-time education for longer and be of white ethnicity. Participation did not differ depending on diagnosis, symptoms, GAF, age of onset or depression., (Copyright © 2021. Published by Elsevier B.V.)

Only one study among U.S. prison staff has explored the effects of work-family conflict and job burnout. To replicate the research to determine whether the results vary by nation, this study examined the effects of four types of work-family conflict (strain-based, time-based, behavior-based and family-based conflict) on three dimensions of job burnout (emotional exhaustion, depersonalization and feeling ineffective at work) among Nigerian correctional staff. Strain- and behavior-based conflict had significant positive effects on emotional exhaustion, but time- and family-based conflict did not. Family-based conflict was the only type of domain spillover with significant positive effects on depersonalization. Behavior-based conflict was the only type of work-family conflict with significant positive effects on feeling ineffective at work. Time-based and strain-based conflict were highly related to one another, which was attributed to time-based conflict being a contributor to strain-based conflict for Nigerian prison staff., (© 2021 The Australian and New Zealand Association of Psychiatry, Psychology and Law.)

Treatment options for patients with pancreatic cancer are limited and survival prospects have barely changed over the past 4 decades. Chemoradiation treatment (CRT) has been used as neoadjuvant therapy in patients with borderline resectable disease to reduce tumour burden and increase the proportion of patients eligible for surgery. Antimetabolite drugs such as gemcitabine and 5-fluorouracil are known to sensitise pancreatic tumours to radiation treatment. Likewise, photodynamic therapy (PDT) has also been shown to enhance the effect of radiation therapy. However, PDT is limited to treating superficial lesions due to the attenuation of light by tissue. The ability of the related technique, sonodynamic therapy (SDT), to enhance CRT was investigated in two murine models of pancreatic cancer (PSN-1 and BxPC-3) in this study. SDT uses low intensity ultrasound to activate an otherwise non-toxic sensitiser, generating toxic levels of reactive oxygen species (ROS) locally. It is applicable to greater target depths than PDT due to the ability of ultrasound to propagate further than light in tissue. Both CRT and the combination of CRT plus SDT delayed tumour growth in the two tumour models. In the PSN-1 model, but not the BxPC-3 model, the combination treatment caused an increase in survival relative to CRT alone (p = 0.038). The improvement in survival conferred by the addition of SDT in this model may be related to differences in tumour architecture between the two models. MRI and US images showed that PSN-1 tumours were less well perfused and vascularised than BxPC-3 tumours. This poor vascularisation may explain why PSN-1 tumours were more susceptible to the effects of vascular damage exerted by SDT treatment., (Copyright © 2021. Published by Elsevier B.V.)

Prospective cardiac gating during MRI is hampered by electromagnetic induction from the rapidly switched imaging gradients into the ECG detection circuit. This is particularly challenging in small animal MRI, as higher heart rates combined with a smaller myocardial mass render routine ECG detection challenging. We have developed an open-hardware system that enables continuously running MRI scans to be performed in conjunction with cardio-respiratory gating such that the relaxation-weighted steady state magnetisation is maintained throughout the scan. This requires that the R-wave must be detected reliably even in the presence of rapidly switching gradients, and that data previously acquired that were corrupted by respiratory motion re-acquired. The accurately maintained steady-state magnetisation leads to an improvement in image quality and removes alterations in intensity that may otherwise occur throughout the cardiac cycle and impact upon automated image analysis. We describe the hardware required to enable this and demonstrate its application and robust performance using prospectively cardio-respiratory gated CINE imaging that is operated at a single, constant TR. Schematics, technical drawings, component listing and assembly instructions are made publicly available., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Agri-environment schemes (AES) are key mechanisms to deliver conservation policy, and include management to provide resources for target taxa. Mobile species may move to areas where resources are increased, without this necessarily having an effect across the wider countryside or on populations over time. Most assessments of AES efficacy have been at small spatial scales, over short timescales, and shown varying results. We developed a survey design based on orthogonal gradients of AES management at local and landscape scales, which will enable the response of several taxa to be monitored. An evidence review of management effects on butterflies, birds and pollinating insects provided data to score AES options. Predicted gradients were calculated using AES uptake, weighted by the evidence scores. Predicted AES gradients for each taxon correlated strongly, and with the average gradient across taxa, supporting the co-location of surveys across different taxa. Nine 1 × 1 km survey squares were selected in each of four regional blocks with broadly homogenous background habitat characteristics. Squares in each block covered orthogonal contrasts across the range of AES gradients at local and landscape scales. This allows the effects of AES on species at each scale, and the interaction between scales, to be tested. AES options and broad habitats were mapped in field surveys, to verify predicted gradients which were based on AES option uptake data. The verified AES gradient had a strong positive relationship with the predicted gradient. AES gradients were broadly independent of background habitat within each block, likely allowing AES effects to be distinguished from potential effects of other habitat variables. Surveys of several mobile taxa are ongoing. This design will allow mobile taxa responses to AES to be tested in the surrounding countryside, as well as on land under AES management, and potentially in terms of population change over time. The design developed here provides a novel, pseudo-experimental approach for assessing the response of mobile species to gradients of management at two spatial scales. A similar design process could be applied in other regions that require a standardized approach to monitoring the impacts of management interventions on target taxa at landscape scales, if equivalent spatial data are available., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Therapeutic antibodies blocking PD-1-/PD-L1 interaction have achieved remarkable clinical success in cancer. In addition to blocking a target molecule, some isotypes of antibodies can activate complement, NK cells or phagocytes, resulting in death of the cell expressing the antibody's target. Human anti-PD-1 therapeutics use antibody isotypes designed to minimize such antibody-dependent lysis. In contrast, anti-PD-1 reagents used in mice are derived from multiple species, with different isotypes, and are not engineered to reduce target cell death: few studies analyze or discuss how antibody species and isotype may impact data interpretation. We demonstrate here that anti-PD-1 therapy to promote activation and proliferation of murine PD-1-expressing CD8 T cells sometimes led instead to a loss of antigen specific cells. This phenomenon was seen in two tumor models and a model of virus infection, and varied with the clone of anti-PD-1 antibody. Additionally, we compared competition among anti-PD-1 clones to find a combination that allows detection of PD-1-expressing cells despite the presence of blocking anti-PD1 antibodies in vivo. These data bring attention to the possibility of unintended target cell depletion with some commonly used anti-mouse PD-1 clones, and should provide a valuable resource for the design and interpretation of anti-PD-1 studies in mice., (© 2021 Wiley-VCH GmbH.)

Changes in composition of the intestinal microbiota are linked to the development of obesity and can lead to endothelial cell (EC) dysfunction. It is unknown whether EC can directly influence the microbiota. Insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) are critical for coupling nutritional status and cellular growth; IGF-1R is expressed in multiple cell types including EC. The role of ECIGF-1R in the response to nutritional obesity is unexplored. To examine this, we use gene-modified mice with EC-specific overexpression of human IGF-1R (hIGFREO) and their wild-type littermates. After high-fat feeding, hIGFREO weigh less, have reduced adiposity and have improved glucose tolerance. hIGFREO show an altered gene expression and altered microbial diversity in the gut, including a relative increase in the beneficial genus Akkermansia. The depletion of gut microbiota with broad-spectrum antibiotics induces a loss of the favourable metabolic differences seen in hIGFREO mice. We show that IGF-1R facilitates crosstalk between the EC and the gut wall; this crosstalk protects against diet-induced obesity, as a result of an altered gut microbiota., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model., Methods: To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology., Results: Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity., Conclusions: The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.

Nanodiamonds (ND) have recently emerged as excellent candidates for various applications including membrane technology due to their nanoscale size, non-toxic nature, excellent mechanical and thermal properties, high surface areas and tuneable surface structures with functional groups. However, their non-porous structure and strong tendency to aggregate are hindering their potential in gas separation membrane applications. To overcome those issues, this study proposes an efficient approach by decorating the ND surface with polyethyleneimine (PEI) before embedding it into the polymer matrix to fabricate MMMs for CO 2 /N 2 separation. Acting as both interfacial binder and gas carrier agent, the PEI layer enhances the polymer/filler interfacial interaction, minimising the agglomeration of ND in the polymer matrix, which is evidenced by the focus ion beam scanning electron microscopy (FIB-SEM). The incorporation of PEI into the membrane matrix effectively improves the CO 2 /N 2 selectivity compared to the pristine polymer membranes. The improvement in CO 2 /N 2 selectivity is also modelled by calculating the interfacial permeabilities with the Felske model using the gas permeabilities in the MMM. This study proposes a simple and effective modification method to address both the interface and gas selectivity in the application of nanoscale and non-porous fillers in gas separation membranes.

Purpose: Chemoradiation therapy is the standard of care in muscle-invasive bladder cancer (MIBC). Although agents such as gemcitabine can enhance tumor radiosensitivity, their side effects can limit patient eligibility and treatment efficacy. This study investigates ultrasound and microbubbles for targeting gemcitabine delivery to reduce normal-tissue toxicity in a murine orthotopic MIBC model., Materials and Methods: CD1-nude mice were injected orthotopically with RT112 bladder tumor cells. Conventional chemoradiation involved injecting gemcitabine (10 mg/kg) before 6 Gy targeted irradiation of the bladder area using the Small Animal Radiation Research Platform (SARRP). Ultrasound-mediated gemcitabine delivery (10 mg/kg gemcitabine) involved either coadministration of microbubbles with gemcitabine or conjugating gemcitabine onto microbubbles followed by exposure to ultrasound (1.1 MHz center frequency, 1 MPa peak negative pressure, 1% duty cycle, and 0.5 Hz pulse repetition frequency) before SARRP irradiation. The effect of ultrasound and microbubbles alone was also tested. Tumor volumes were measured by 3D ultrasound imaging. Acute normal-tissue toxicity from 12 Gy to the lower bowel area was assessed using an intestinal crypt assay in mice culled 3.75 days posttreatment., Results: A significant delay in tumor growth was observed with conventional chemoradiation therapy and both microbubble groups (P < .05 compared with the radiation-only group). Transient weight loss was seen in the microbubble groups, which resolved within 10 days posttreatment. A positive correlation was found between weight loss on day 3 posttreatment and tumor growth delay (P < .05; R 2 = 0.76). In contrast with conventional chemoradiation therapy, ultrasound-mediated drug delivery methods did not exacerbate the acute intestinal toxicity using the crypt assay., Conclusions: Ultrasound and microbubbles offer a promising new approach for improving chemoradiation therapy for muscle-invasive bladder cancer, maintaining a delay in tumor growth but with reduced acute intestinal toxicity compared with conventional chemoradiation therapy., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Nutrition education is central to pediatric type 1 diabetes management. Dietary management guidelines for type 1 diabetes are evidence based, but implementation may be challenging and inconsistent. We describe variation in the practice of nutrition education across pediatric diabetes centers globally and explore associations with A1c and BMI., Methods: In 2018, 77 pediatric diabetes clinics in the SWEET network received a survey about nutrition education. Using data submitted to the registry, regression analysis corrected for age, diabetes duration, BMI, and sex was used to compare survey parameters with A1c and BMI., Results: Fifty-three centers who collectively cared for 22,085 patients aged 0 to 18 with type 1 diabetes responded. Median A1c was 7.68% [IQR 7.37-8.03], age 13.13 y [12.60-13.54], insulin pump use 39.1%, and continuous glucose monitor use 37.3%. 34% reported screening for disordered eating, but only 15.1% used validated screening tools. Recommending insulin boluses for snacks in patients taking insulin via injection varied, with 23% of the clinics giving this recommendation to half or fewer patients. In regression analysis, instructing patients to take insulin for snacks was the only survey parameter associated with the percent of clinic percent of patients attaining A1c <7.5% (<58 mmol/mol, P = 0.018) and < 7.0% (<53 mmol/mol, P = 0.026)., Conclusions: There is considerable variation in nutrition education for pediatric patients with type 1 diabetes across this international registry. Consistently recommending independent of treatment modality (insulin pump or injections) that patients take insulin for snacks and more uniformity in screening for disordered eating are improvement opportunities., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This research involved carrying out a unique micro-mesoporous carbon particle incorporation into P84 co-polyimide membrane for improved gas separation performance. The carbon filler was prepared using a hard template method from zeolite and known as zeolite-templated carbon (ZTC). This research aims to study the loading amount of ZTC into P84 co-polyimide toward the gas separation performance. The ZTC was prepared using simple impregnation method of sucrose into hard template of zeolite Y. The SEM result showing a dispersed ZTC particle on the membrane surface and cross-section. The pore size distribution (PSD) of ZTC revealed that the particle consists of two characteristics of micro and mesoporous region. It was noted that with only 0.5 wt% of ZTC addition, the permeability was boosted up from 4.68 to 7.06 and from 8.95 to 13.15 barrer, for CO 2 and H 2 respectively when compared with the neat membrane. On the other hand, the optimum loading was at 1 wt%, where the membrane received thermal stability boost of 10% along with the 62.4 and 35% of selectivity boost of CO 2 /CH 4 and H 2 /CH 4 , respectively. It was noted that the position of the filler on the membrane surface was significantly affecting the gas transport mechanism of the membrane. Overall, the results demonstrated that the addition of ZTC with proper filler position is a potential candidate to be applicable in the gas separation involving CO 2 and H 2 ., (© 2021 The Authors.)

Ultrasound and microbubbles (MBs) offer a noninvasive method of temporarily enhancing blood-brain barrier (BBB) permeability to therapeutics. To reduce off-target effects, it is desirable to minimize the ultrasound pressures required. It has been shown that a new formulation of MBs containing lysolipids (Lyso-MBs) can increase the cellular uptake of a model drug in vitro. The aim of this study is to investigate whether Lyso-MBs can also enhance BBB permeability in vivo. Female BALB/c mice are injected with either Lyso-MBs or control MBs and gadolinium-DTPA (Gd-DTPA) and exposed to ultrasound (500 kHz, 1 Hz pulse repetition frequency, 1 ms pulse length, peak-negative pressures 160-480 kPa) for 2 min. BBB permeabilization is measured via magnetic resonance imaging (7.0 T) of Gd-DTPA extravasation and subsequent histological examination of brain tissue to assess serum immunoglobulin G (IgG) extravasation (n = 8 per group). An approximately twofold enhancement in BBB permeability is produced by the Lyso-MBs at the highest ultrasound pressure compared with the control. These findings indicate that modifying the composition of phospholipid-shelled MBs has the potential to improve the efficiency of BBB opening, without increasing the ultrasound pressure amplitude required. This is particularly relevant for delivery of therapeutics deep within the brain., (© 2020 Wiley-VCH GmbH.)

Treatment-resistant schizophrenia, affecting approximately 20-30% of patients with schizophrenia, has a high burden both for patients and healthcare services. There is a need to identify treatment resistance earlier in the course of the illness, in order that effective treatment, such as clozapine, can be offered promptly. We conducted a systemic literature review of prospective longitudinal studies with the aim of identifying predictors of treatment-resistant schizophrenia from the first episode. From the 545 results screened, we identified 12 published studies where data at the first episode was used to predict treatment resistance. Younger age of onset was the most consistent predictor of treatment resistance. We discuss the gaps in the literature and how future prediction models can identify predictors of treatment response more robustly.

According to several studies, obesity increases rates of metabolic syndrome plus other comorbidities like diabetes and cardiovascular diseases. However, little evidence exists as to whether obesity assists in the prolongation of COVID-19 and seasonal flu-like symptoms especially among African American 55-74-year age groups. The purpose of this study is to show that COVID-19 symptoms can prolong recovery times and symptoms of seasonal flu-infected obese African Americans. The aim of the study is to investigate risk factors which include modifiable (i.e., obesity) and non-modifiable (i.e., age, race) effect on prolongation and recovery times for some inpatient COVID-19 and seasonal flu-infected African American from a single hospital in Detroit, MI., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021.)

Aims: Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 and usually die in the second to third decades of life from cardiac and respiratory failure. Symptomatic treatment includes the use of anti-inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, and increased risk of cardiovascular disease. Novel treatment options include blockade of the renin-angiotensin-aldosterone system, because angiotensin as well as aldosterone contribute to persistent inflammation and fibrosis, and aldosterone blockade represents an efficacious anti-fibrotic approach in cardiac failure. Recent preclinical findings enabled successful clinical testing of a combination of steroidal mineralocorticoid receptor antagonists (MRAs) and angiotensin converting enzyme inhibitors in DMD boys. The efficacy of MRAs alone on dystrophic skeletal muscle and heart has not been investigated. Here, we tested efficacy of the novel non-steroidal MRA finerenone as a monotherapy in a preclinical DMD model., Methods and Results: The dystrophin-deficient, utrophin haploinsufficient mouse model of DMD was treated with finerenone and compared with untreated dystrophic and wild-type controls. Grip strength, electrocardiography, cardiac magnetic resonance imaging, muscle force measurements, histological quantification, and gene expression studies were performed. Finerenone treatment alone resulted in significant improvements in clinically relevant functional parameters in both skeletal muscle and heart. Normalized grip strength in rested dystrophic mice treated with finerenone (40.3 ± 1.0 mN/g) was significantly higher (P = 0.0182) compared with untreated dystrophic mice (35.2 ± 1.5 mN/g). Fatigued finerenone-treated dystrophic mice showed an even greater relative improvement (P = 0.0003) in normalized grip strength (37.5 ± 1.1 mN/g) compared with untreated mice (29.7 ± 1.1 mN/g). Finerenone treatment also led to significantly lower (P = 0.0075) susceptibility to limb muscle damage characteristic of DMD measured during a contraction-induced injury protocol. Normalized limb muscle force after five lengthening contractions resulted in retention of 71 ± 7% of baseline force in finerenone-treated compared with only 51 ± 4% in untreated dystrophic mice. Finerenone treatment also prevented significant reductions in myocardial strain rate (P = 0.0409), the earliest sign of DMD cardiomyopathy. Moreover, treatment with finerenone led to very specific cardiac gene expression changes in clock genes that might modify cardiac pathophysiology in this DMD model., Conclusions: Finerenone administered as a monotherapy is disease modifying for both skeletal muscle and heart in a preclinical DMD model. These findings support further evaluation of finerenone in DMD clinical trials., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Forward osmosis membrane bioreactor (FOMBR) is an integrated physical-biological treatment process that has received increased awareness in treating municipal wastewater for its potential to produce high effluent quality coupled with its low propensity for fouling formation. However, reverse salt diffusion (RSD) is a major issue and so far limited studies have reported long-term FOMBR operation under the elevated salinity conditions induced by RSD. This study investigated the performance of a FOMBR in treating municipal wastewater under a controlled saline environment (6-8 g L -1 NaCl) using two separate sodium chloride draw solution (NaCl DS) concentrations (35 and 70 g L -1 ) over 243 days. At 35 g L -1 NaCl DS, the water flux performance dropped from 6.75 L m -2 h -1 (LMH) to 2.07 LMH after 72 days of operation in the first experimental stage, when no cleaning procedure was implemented. In the subsequent stage, the DS concentration was increased to 70 g L -1 and a weekly physical cleaning regime introduced. Under stable operation, the water flux performance recovery was 67% after 21 cycles of physical cleaning. For the first time in FOMBR studies, a shortcut nitrogen removal via the nitrite pathway was also achieved under the elevated salinity conditions. At the end of operation (day 243), the ammonia-oxidising bacteria (Nitrosomonas sp.) was the only nitrifier species in the system and no nitrite oxidising bacteria was detected. The above study proves that a FOMBR system is a feasible process for treating municipal wastewater., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Tobacco-free 'modern' oral nicotine pouches (MOPs), are similar in appearance and use to Swedish-style snus, but without tobacco. There are few identified methods to create test samples for toxicologically assessment of MOPs in vitro. In this study we present a simple method for the extraction of pouch material in cell culture media, providing consistent nicotine concentration and easy in vitro assessment. A series of contemporary in vitro screening assays (viability, cell health markers, oxidative stress and genotoxicity) using human oral fibroblasts (HGF) and human lung epithelial cells (H292) were employed. Extracts were generated from LYFT and compared to snus (CRP1.1) and cigarette (1R6F) reference products. MOP and CRP1.1 extracts were generated by incubating one pouch in 20 ml of cell culture media, while 1R6F AqE was prepared by smoking 1 cigarette into 20 ml of cell culture media. 1R6F demonstrated toxicological responses in most assays; CRP1.1 had minimal to moderate effects while MOP demonstrated little or no response in all assays. This study demonstrated the generation of MOPs extracts and their toxicological evaluation using in vitro screening approaches. Future product usage, pharmacokinetics and clinical studies will further substantiate the reduced risk potential of MOPs., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Magnetic resonance imaging (MRI) and computed tomography (CT) imaging with X-rays are crucial diagnostic techniques in medicine, especially in oncology for evaluating the response to treatment. Body movement causes image blurring and synchronized gating to the respiratory and cardiac cycles is required. Degradation of MRI and CT imaging by the presence of metal in electronic respiratory sensors has limited their use, with a preference for pressure balloons for detecting respiration, but these are cumbersome and insensitive. Here, graphene's role is studied as an electromagnetically transparent electrode in a piezoelectric graphene respiratory sensor (GRS) device designed specifically for dual gated MRI and CT imaging of small animals. The GRS is integrated into a 3D-printed cradle with all-carbon-based device life support (heating pad) and monitoring of small animals (electrocardiogram), enabling both heartbeat and respiration detection, significant improvements to throughput and reproducibility, and reduced animal suffering. This shows graphene's potential for a wide range of electromagnetic transparent electronics for medical imaging and diagnostics, beyond conventional metal electrodes., (© 2020 Wiley-VCH GmbH.)

Objective measures of tongue strength and endurance are used to assess lingual weakness and fatigue, and may have significant clinical value for dysphagia management. Recent studies investigating age and gender effects on tongue strength in children are limited by small sample sizes. The current study investigated age and gender effects on tongue strength with a larger sample size, and collected preliminary normative data for a paediatric population. This study also investigated the reliability of tongue endurance measures in children using a modified method, which has not previously been investigated. Using a cross-sectional design, this study examined tongue strength and endurance in 119 children aged 6 to 11 years, with no history of speech sound disorders, oro-motor deficits, dysphagia or cognitive impairment. Measures were collected using the Iowa Oral Performance Instrument. Children participated in two sessions, 45 min and 10 min in duration. Tongue strength was found to significantly increase with age (p < 0.001), while no gender effects were found. Modified tongue endurance measures involved using only one measure of maximal tongue strength to set parameters for tongue endurance scores. Despite this modification, data did not reach acceptable test-retest reliability, ICC = 0.68, p < 0.001; however, reliability improved from previous studies. These findings provide normative data for tongue strength, as a basis to compare individuals, and highlights the need for more reliable protocols for measuring tongue endurance. Normative data was collected from city-dwelling Australian children.

Background: Despite striking successes, immunotherapies aimed at increasing cancer-specific T cell responses are unsuccessful in most patients with cancer. Inactivating regulatory T cells (Treg) by inhibiting the PI3Kδ signaling enzyme has shown promise in preclinical models of tumor immunity and is currently being tested in early phase clinical trials in solid tumors., Methods: Mice bearing 4T1 mammary tumors were orally administered a PI3Kδ inhibitor (PI-3065) daily and tumor growth, survival and T cell infiltrate were analyzed in the tumor microenvironment. A second treatment schedule comprised PI3Kδ inhibitor with anti-LAG3 antibodies administered sequentially 10 days later., Results: As observed in human immunotherapy trials with other agents, immunomodulation by PI3Kδ-blockade led to 4T1 tumor regressor and non-regressor mice. Tumor infiltrating T cells in regressors were metabolically fitter than those in non-regressors, with significant enrichments of antigen-specific CD8 + T cells, T cell factor 1 (TCF1) + T cells and CD69 - T cells, compatible with induction of a sustained tumor-specific T cell response. Treg numbers were significantly reduced in both regressor and non-regressor tumors compared with untreated tumors. The remaining Treg in non-regressor tumors were however significantly enriched with cells expressing the coinhibitory receptor LAG3, compared with Treg in regressor and untreated tumors. This striking difference prompted us to sequentially block PI3Kδ and LAG3. This combination enabled successful therapy of all mice, demonstrating the functional importance of LAG3 in non-regression of tumors on PI3Kδ inhibition therapy. Follow-up studies, performed using additional cancer cell lines, namely MC38 and CT26, indicated that a partial initial response to PI3Kδ inhibition is an essential prerequisite to a sequential therapeutic benefit of anti-LAG3 antibodies., Conclusions: These data indicate that LAG3 is a key bottleneck to successful PI3Kδ-targeted immunotherapy and provide a rationale for combining PI3Kδ/LAG3 blockade in future clinical studies., Competing Interests: Competing interests: BV is a consultant for Karus Therapeutics (Oxford, UK), iOnctura (Geneva, Switzerland) and Venthera (Palo Alto, USA) and has received speaker fees from Gilead., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Commercial mouse chow is designed to provide a complete, nutrient-rich diet, and it can contain upwards of 100 mg/kg manganese, an essential mineral. Manganese acts as a relaxation time-shortening contrast agent for both T 1 and T 2 , and where standard chow is hydrated in the gastrointestinal tract, bright signals are produced when using T 1 -weighted imaging (T 1 WI). As a result of peristalsis, gastrointestinal hyperintensities result in temporally unstable signals, leading to image ghosting and decreased resolution from that prescribed. To avoid the problem, various methods of gastrointestinal tract modulation, including the use of intestinal cleansing with laxatives and dietary modulation, have been reported. Here, dietary modulation has been extended to the use of a biologically innocuous, long-term change of diet. In this study, we report on the use of a commercially available manganese-free chow to improve the image quality of the gastrointestinal tract. This manganese-free chow, apart from the omitted manganese which is available in tap water, is a complete diet and readily available. We investigated the time-dependent, diet-related gastrointestinal intensities on short-TR T 1 WI magnetic resonance imaging; monitored body mass, food and water consumption and standard blood biochemistry analysis following diet change; and determined manganese concentration in blood plasma following a five-day change to manganese-free chow. We show that the manganese-free chow presents a refinement to other gastrointestinal tract modulation, as it avoids the need for invasive procedures for gut voiding and can be provided ad libitum so that animals can be maintained with no need for prescribed diet change before imaging.