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Introduction: This study aimed to prospectively investigate magnetic resonance (MR)-guided radiotherapy (MRgRT) for post-prostatectomy prostate cancer and report preliminary clinical outcomes., Methods: All included patients underwent salvage or adjuvant adaptive MRgRT on a 1.5T MR integrated linear accelerator (MR-LINAC). Gastrointestinal and genitourinary toxicities were assessed. The primary endpoint was the progression-free survival (PFS) rate estimated by Kaplan-Meier (KM) survival analysis. A progression event was defined as the first occurrence of biochemical failure, radiological progression, or death. Secondary endpoints were biochemical failure-free survival (bFFS) rate, radiological PFS (rPFS) rate, and ≥G2 adverse events., Results: Thirty post-prostatectomy patients were enrolled and followed (median follow-up: 32.0 months; 3.0-48.1 months). Three patients had biochemical failure during follow-up. One patient developed pelvic node metastases. All patients were alive. The estimated PFS rates were 96.4% (95% confidence interval [95%CI]: 89.8%-100.0%) at 2 years and 78.8% (95%CI: 61.3%-100%) at 3 years. The estimated bFFS rates were 96.4% (95%CI: 89.8%-100%) /86.6%(95%CI: 73.4%-100%) at 2/3 years, respectively. The corresponding rPFS rates were 100% at 2 years and 92.3% (95%CI: 78.9%-100%) at 3 years, respectively. There was only one acute G2 GI adverse event (1/30, 3.33%) of abdominal pain occurred. Two late G2 events (one rectal bleeding and one urinary frequency) were scored (2/30, 6.67%). No ≥G3 events were observed., Conclusion: Our findings suggest the feasibility, excellent patient tolerance, and encouraging efficacy of post-prostatectomy MRgRT, extending our knowledge of the clinical outcomes of MRgRT and serving as a benchmark for future investigation., (© 2024 The Author(s). Asia‐Pacific Journal of Clinical Oncology published by John Wiley & Sons Australia, Ltd.)

Background: Right ventricular pseudoaneurysms are extremely rare and there is no precise recommendation for their management., Case Summary: We present the case of a successful coil embolization of a right ventricular pseudoaneurysm in a woman with chronic kidney disease due to perinuclear antineutrophil cytoplasmic antibody vasculitis and a history of difficult placement of a hemodialysis catheter., Discussion: Ventricular pseudoaneurysm is a contained rupture of the ventricular wall that can occur due to several causes. Our case describes a right ventricular pseudoaneurysm after dialysis catheter placement in a patient with vasculitis. Optimal management strategies for pseudoaneurysms remain highly variable, but the primary goal is to reduce the incidence of cardiac rupture., Take-Home Message: The percutaneous exclusion of this type of lesion is an innovative technique that can be considered in high-risk surgical patients., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2025 The Authors.)

XK disease is a very rare, multi-system disease, which can present with a wide spectrum of symptoms. This disorder can also be identified pre-symptomatically with the incidental detection of serological abnormalities when typing erythrocytes in peripheral blood, or on other routine laboratory testing. Increasing awareness of this disorder and improved access to genetic testing are resulting in increasing identification of affected patients and families. Here we provide updates to some previously-reported families and patients and provide additional clinical details. We also report four new cases with a variety of presentations, one of whom had a novel mutation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Walker, Barreto, Bateman, Bustamante, Chiu, Feitell, Frey, Guerra, Guerrero, Jung, Maldonado, Meyer, Miranda, McFarland, Oates, Ochoa, Olsson, Paucar, Proschle, Sammler, Troncoso, Wu-Wallace, Young, Vege, Westhoff and Danek.)

Purpose: Diffusion-weighted imaging (DWI) holds promise for image-guided radiotherapy (MRgRT) in prostate cancer. However, challenges persist due to image distortion, artifacts, and apparent diffusion coefficient (ADC) reproducibility issues. This study aimed to assess DWI image quality and ADC reproducibility on both a 1.5 T MR-simulator and a 1.5 T MR-Linac, employing measurements from both an ACR MRI phantom and prostate cancer patients undergoing MRgRT., Methods: DW-MRI scans were conducted on 19 patients (mean age = 69 ± 8 years, with 23 MR-visible intra-prostatic lesions) and an ACR MRI phantom using a 1.5 T MR-simulator (b-values = 0, 800, 1400s/mm 2 ) and a 1.5 T MR-Linac (b-values = 50, 500, 800 s/mm 2 ). ADC homogeneity in the phantom was evaluated via 1D profile flatness (FL) in three directions. Image quality was assessed through qualitative 5-point Likert scale ratings and quantitative ADC and signal-to-noise ratio (SNR) measurements. Intra-observer reproducibility of image quality scores was evaluated using ICC(1, 2). Geometric distortion was measured by comparing landmark sizes on the ACR phantom against the ground truth. Mean ADC and reproducibility were assessed using Bland-Altman plots., Results: Both MR-simulator and MR-Linac demonstrated high ADC homogeneity (FL > 87.5% - MR-simulator: 97.23 ± 0.62%, MR-Linac: 94.75 ± 0.62%, p < 0.05) in the phantom. Image quality scores revealed acceptable ratings (≥3) for capsule demarcation, image artifacts, and geometric distortion in patients. However, intra-prostatic lesions were barely discernible in b800 images for both MR-simulator (average score = 2.37 ± 1.33) and MR-Linac (average score = 2.16 ± 1.28). While MR-Linac DWI scans exhibited significantly more severe geometric distortion than MR-simulator scans (p < 0.01), most phantom measurements fell within the image in-plane resolution of 3 mm. Significant differences were noted in MR-simulator ADC (CTV: 1.20 ± 0.14 × 10 -3  mm 2 /s (MR-simulator) vs 1.06 ± 0.10 × 10-3 mm 2 /s (MR-Linac); GTV: 1.05 ± 0.21 × 10 -3  mm 2 /s vs 0.91 ± 0.16 × 10 mm 2 /s, all p < 0.05), with a small non-zero bias observed in the Bland-Altman analysis (CTV: 12.3%; GTV: 14.5%)., Conclusion: The significantly larger MR-simulator ADC and the small non-zero bias hint at potential systematic differences in ADC values acquired from an MR-simulator and an MR-Linac, both at 1.5 T. Although acceptable ADC homogeneity was noted, caution is warranted in interpreting MR-Linac DWI images due to occasional severe artifacts. Further studies are essential to validate DWI and ADC as reliable imaging markers in prostate cancer MRgRT., Competing Interests: Declaration of competing interest All authors confirm that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Intention offloading involves using external reminders such as diaries, to-do lists, and digital alerts to help us remember delayed intentions. Recent studies have provided evidence for various cognitive and metacognitive factors that guide intention offloading, but little research has investigated the physical cost of reminder-setting itself. Here, we present two pre-registered experiments investigating how the cost of physical effort associated with reminder-setting influences strategic intention offloading under different levels of memory load. At all memory loads, reminder-setting was reduced when it was more effortful. The ability to set reminders allowed participants to compensate for the influence of memory load on accuracy in the low-effort condition; this effect was attenuated in the high-effort condition. In addition, there was evidence that participants with less confidence in their memory abilities were more likely to set reminders. Contrary to prediction, physical effort had the greatest effect on reminder-setting at intermediate memory loads. We speculate that the physical costs of reminder-setting might have the greatest impact when participants are uncertain about their strategy choice. These results demonstrate the importance of physical effort as one of the factors relevant to cost-benefit decision-making about cognitive offloading strategies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: This prospective study aimed to investigate adaptive magnetic resonance (MR)-guided stereotactic body radiation therapy (MRgSBRT) with rectal spacer for localized prostate cancer (PC) and report 1-year clinical outcomes., Materials and Methods: Thirty-four consecutive patients with low- to high-risk localized PC that underwent 5-fraction adaptive MRgSBRT with rectal spacer were enrolled. The dosimetric comparison was performed on a risk- and age-matched cohort treated with MRgSBRT but without a spacer at a similar timepoint. Clinician-reported outcomes were based on Common Terminology Criteria for Adverse Events. Patient-reported outcomes were based on the Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline, acute (1-3 months), subacute (4-12 months), and late (> 12 months) phases., Results: The median follow-up was 390 days (range 28-823) and the median age was 70 years (range 58-82). One patient experienced rectal bleeding soon after spacer insertion that subsided before MRgSBRT. The median distance between the midline of the prostate midgland and the rectum after spacer insertion measured 7.8 mm (range 2.6-15.3), and the median length of the spacer was 45.9 mm (range 16.8-62.9) based on T2-weighted MR imaging. The use of spacer resulted in significant improvements in target coverage (V100% > 95% = 98.6% [range 93.4-99.8] for spacer vs. 97.8% [range 69.6-99.7] for non-spacer) and rectal sparing (V95% < 3 cc = 0.7 cc [range 0-4.6] for spacer vs. 4.9 cc [range 0-12.5] for non-spacer). Nine patients (26.5%) experienced grade 1 gastrointestinal toxicities, and no grade ≥ 2 toxicities were observed. During the 1-year follow-up period, EPIC scores for the bowel domain remained stable and were the highest among all other domains., Conclusions: MRgSBRT with rectal spacer for localized PC showed exceptional tolerability with minimal gastrointestinal toxicities and satisfactory patient-reported outcomes. Improvements in dosimetry, rectal sparing, and target coverage were achieved with a rectal spacer. Randomized trials are warranted for further validation., (© 2024. The Author(s).)

Many materials have been explored for the purpose of creating structures with high radiative cooling potential, such as nanocellulose-based structures and nanoparticle-based coatings, which have been reported with environmentally friendly attributes and high solar reflectance in current literature. They each have their own advantages and disadvantages in practice. It is worth noting that nanocellulose-based structures have an absorption peak in the UV wavelengths, which results in a lower total solar reflectance and, consequently, reduce radiative cooling capabilities. However, the interwoven-fiber structure of cellulose gives high mechanical strength, which promotes its application in different scenarios. The application of nanoplatelet-based coatings is limited due to the need for high volume of nanoparticles to reach their signature high solar reflectance. This requirement weakens the polymer matrix and results in more brittle structures. This work proposes a dual-layer system, comprising of a cellulose-based substrate as the bottom layer and a thin nanoparticle-based radiative cooling paint as the top layer, where both radiative cooling potential and mechanical strength can be maximized. Experimental and theoretical studies are conducted to investigate the relationship between thickness and reflectance in the top coating layer with a consistent thickness of the bottom layer. The saturation point is identified in this relationship and used to determine the optimal thickness for the top-layer to maximize material use efficiency. With the use of cotton paper painted with a 125 μm BaSO 4 -based layer, the cooling performance is enhanced to be 149.6 W/m 2 achieved by the improved total solar reflectance from 80 % to 93 %., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Lung cancer in never smokers (LCINS) represents a growing and distinct entity within the broader landscape of lung malignancies. This review provides a comprehensive overview of LCINS, encompassing its epidemiologic trends, risk factors, distinct genomic alterations, clinical outcomes and the ongoing initiative aimed at formulating screening guidelines tailored to this unique population. As LCINS continues to gain prominence, understanding its intricate genomic landscape has become pivotal for tailoring effective therapeutic strategies. Moreover, LCINS does not meet the criteria for lung cancer screening as per the current guidelines. Hence, there is an urgent need to explore its heterogeneity in order to devise optimal screening guidelines conducive to early-stage detection. This review underscores the vital importance of detailed research to elucidate the multifaceted nature of LCINS, with the potential to shape future clinical management and screening recommendations for this unique and growing patient cohort., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To determine whether the level of inspiratory volume affect the extent to which active breathing control (ABC) reduces intrafraction motion and the dose coverage of target volumes in patients receiving external beam radiation therapy (EBRT) to the thoracic region MATERIALS/METHODS: 20 patients undergoing thoracic radiotherapy enrolled in a prospective study using ABC for respiratory motion management and volumetric-modulated arc therapy (VMAT) as the treatment technique. They were randomized to one of two groups, the control group of 80% inspiratory volume and the other test group of 70%. At least one set of repeated CBCTs was done weekly. All images including CBCTs and Planning CTs were sent to MIM software TM for analysis of intrafraction motion using Dice Similarity Coefficient (DSC). The target dose conformality was assessed using conformation number (CN). Intention-to-treat analysis was employed for statistical purpose., Results: The DSC for the 70% and 80% inspiratory volume group were 0.93 and 0.92, respectively. For the 70% group, there was a significant negative correlation (p < 0.05) between DSC and time between two CBCTs, but not for the 80% group. The average percentage change in CN for the 70% and 80% group was 10.91% and 8.14%, respectively, and their difference was significant (p < 0.05). Furthermore, the actual change in volume had a significant positive correlation (p < 0.05) with the percentage change in CN for the 70% inspiratory volume group but not the 80% group., Conclusion: More evidence suggests that the target volumes from the 80% inspiratory volume group have less intrafraction motion compared to the 70% group. The findings from the percentage change in CN suggest that there could potentially be less tumor motion for higher levels of inspiratory volume and this could possibly contribute to why intrafraction motion is less for the 80% inspiratory volume group., (Copyright © 2023. Published by Elsevier Inc.)

Orthognathic surgery typically contraindicates standard oral intubation techniques. Nasal intubation may distort the nasal profile thus complicating orthognathic surgery involving the midface. Using silicone putty to stabilise the tube in a custom position may minimise these changes. A prospective analysis was undertaken of patients undergoing nasal intubation with and without silicone putty stabilisation. Pre- and post-intubation measurements were made of nasolabial angle and interalar width. Silicone putty significantly reduced the changes of nasal intubation on nasolabial angle (p < 0.001) but did not affect interalar distance (p > 0.05). Silicone putty should be considered to stabilise the nasotracheal tube in orthognathic surgery., (Copyright © 2023 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation 1,2 . Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid 1-3 . A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation 1 . NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft 4 . Although past missions have utilized impactors to investigate the properties of small bodies 5,6 , those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos 7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary., (© 2023. The Author(s).)

Purpose: To analyze and characterize the online plan adaptation of 1.5T magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) of prostate cancer (PC)., Methods: PC patients (n = 107) who received adaptive 1.5 Tesla MRgSBRT were included. Online plan adaptation was implemented by either the adapt-to-position (ATP) or adapt-to-shape (ATS) methods. Patients were assigned to the ATS group if they underwent ≥ 1 ATS fraction (n = 51); the remainder were assigned to the ATP group (n = 56). The online plan adaptation records of 535 (107 × 5) fractions were retrospectively reviewed. Rationales for ATS decision-making were determined and analyzed using predefined criteria. Statistics of ATS fractions were summarized. Associations of patient characteristics and clinical factors with ATS utilization were investigated., Results: There were 87 (16.3%) ATS fractions and 448 ATP fractions (83.7%). The numbers of ATS adoptions in fractions 1-5 were 29 (29/107, 27.1%), 18 (16.8%), 15 (14.0%), 16 (15.0%), and 9 (8.4%), respectively, with significant differences in adoption frequency between fractions (p = 0.007). Other baseline patient characteristics and clinical factors were not significantly associated with ATS classification (all p > 0.05). Underlying criteria for the determination of ATS implementation comprised anatomical changes (77 fractions in 50 patients) and discrete multiple targets (15 fractions in 3 patients). No ATS utilization was determined using dosimetric or online quality assurance criteria., Conclusions: This study contributes to facilitating the establishment of a standardized protocol for online MR-guided adaptive radiotherapy in PC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Precision livestock farming (PLF) offers a strategic solution to enhance the management capacity of large animal groups, while simultaneously improving profitability, efficiency, and minimizing environmental impacts associated with livestock production systems. Additionally, PLF contributes to optimizing the ability to manage and monitor animal welfare while providing solutions to global grand challenges posed by the growing demand for animal products and ensuring global food security. By enabling a return to the "per animal" approach by harnessing technological advancements, PLF enables cost-effective, individualized care for animals through enhanced monitoring and control capabilities within complex farming systems. Meeting the nutritional requirements of a global population exponentially approaching ten billion people will likely require the density of animal proteins for decades to come. The development and application of digital technologies are critical to facilitate the responsible and sustainable intensification of livestock production over the next several decades to maximize the potential benefits of PLF. Real-time continuous monitoring of each animal is expected to enable more precise and accurate tracking and management of health and well-being. Importantly, the digitalization of agriculture is expected to provide collateral benefits of ensuring auditability in value chains while assuaging concerns associated with labor shortages. Despite notable advances in PLF technology adoption, a number of critical concerns currently limit the viability of these state-of-the-art technologies. The potential benefits of PLF for livestock management systems which are enabled by autonomous continuous monitoring and environmental control can be rapidly enhanced through an Internet of Things approach to monitoring and (where appropriate) closed-loop management. In this paper, we analyze the multilayered network of sensors, actuators, communication, networking, and analytics currently used in PLF, focusing on dairy farming as an illustrative example. We explore the current state-of-the-art, identify key shortcomings, and propose potential solutions to bridge the gap between technology and animal agriculture. Additionally, we examine the potential implications of advancements in communication, robotics, and artificial intelligence on the health, security, and welfare of animals., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Sodium restriction is recommended for patients with heart failure (HF) despite the lack of solid clinical evidence from randomized controlled trials. Whether or not sodium restrictions provide beneficial cardiac effects is not known., Methods: The present study is a randomized, double-blind, controlled trial of stable HF patients with ejection fraction ≤ 40%. Patients were allocated to sodium restriction (2 g of sodium/day) vs. control (3 g of sodium/day). The primary outcome was change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 20 weeks. Secondary outcomes included quality of life and adverse safety events (HF readmission, blood pressure or electrolyte abnormalities)., Results: Seventy patients were enrolled. Median baseline sodium consumption was 3268 (2225-4537) mg/day. Adherence to the intervention based on 24-hour urinary sodium was 32%. NT-proBNP and quality of life did not significantly change between groups (p > 0.05 for both). Adverse safety events were not significantly different between the arms (p > 0.6 for all). In the per protocol analysis, patients who achieved a sodium intake < 2500 mg/day at the intervention conclusion showed improvements in NT-proBNP levels (between-group difference: -55%, 95% confidence interval -27 to -73%; p = 0.002) and quality of life (between-group difference: -11 ± 5 points; p = 0.04). Blood pressure decreased in patients with lower sodium intake (between-group difference: -9 ± 5 mmHg; p = 0.05) without significant differences in symptomatic hypotension or other safety events (p > 0.3 for all)., Conclusions: Adherence assessed by 24-hour natriuresis and by the nutritionist was poor. The group allocated to sodium restriction did not show improvement in NT-proBNP. However, patients who achieved a sodium intake < 2500 mg/day appeared to have improvements in NT-proBNP and quality of life without any adverse safety signals., Clinicaltrials: gov Identifier: NCT03351283.

A helical fan-beam kilovoltage computed tomography (kVCT) was recently introduced into Tomotherapy units. This study aims to share the initial experience of kVCT in clinical workflow, compare its performance with that of the existing megavoltage computed tomography (MVCT), and explore its potential in adaptive planning. We retrospectively enrolled 23 patients who underwent both MVCT and kVCT scans. The clinical performance data regarding image acquisition time, nominal dose length product (DLP), registration time and registration corrections were extracted and compared. Image quality was scored by six experienced radiation therapists and quantified based on phantom measurements. CT number stability and the implementation of adaptive radiotherapy were dosimetrically evaluated by performing the dose recalculation on kVCT. Compared to MVCT, kVCT significantly reduced DLP (except the highest kVp protocol), image acquisition and registration time. KVCT obtained higher scores than MVCT on all criteria except artifacts. Phantom measurements also revealed a better image performance characterization of kVCT except for image uniformity. The CT number variation could lead to a dose difference of 0.5% for D95% of target and D mean of organ-at-risk. For the treatment planning with kVCT, a systematic dose difference (> 1%) in PTV dose metrics was observed at regions with large longitudinal density discontinuities compared to the reference plans. The new kVCT imaging provides enhanced soft-tissue visualization. The improved efficiency with kVCT-guided treatment will allow more patients to be treated each day. In most cases, the dose calculation accuracy of kVCT images is acceptable except for regions with severe artifacts., (© 2022. Australasian College of Physical Scientists and Engineers in Medicine.)

Background: Conventionally fractionated whole-pelvic nodal radiotherapy (WPRT) improves clinical outcome compared to prostate-only RT in high-risk prostate cancer (HR-PC). MR-guided stereotactic body radiotherapy (MRgSBRT) with concomitant WPRT represents a novel radiotherapy (RT) paradigm for HR-PC, potentially improving online image guidance and clinical outcomes. This study aims to report the preliminary clinical experiences and treatment outcome of 1.5 Tesla adaptive MRgSBRT with concomitant WPRT in HR-PC patients. Materials and methods: Forty-two consecutive HR-PC patients (72.5 ± 6.8 years) were prospectively enrolled, treated by online adaptive MRgSBRT (8 Gy(prostate)/5 Gy(WPRT) × 5 fractions) combined with androgen deprivation therapy (ADT) and followed up (median: 251 days, range: 20−609 days). Clinical outcomes were measured by gastrointestinal (GI) and genitourinary (GU) toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) Scale v. 5.0, patient-reported quality of life (QoL) with EPIC (Expanded Prostate Cancer Index Composite) questionnaire, and prostate-specific antigen (PSA) responses. Results: All MRgSBRT fractions achieved planning objectives and dose specifications of the targets and organs at risk, and they were successfully delivered. The maximum cumulative acute GI/GU grade 1 and 2 toxicity rates were 19.0%/81.0% and 2.4%/7.1%, respectively. The subacute (>30 days) GI/GU grade 1 and 2 toxicity rates were 21.4%/64.3% and 2.4%/2.4%, respectively. No grade 3 toxicities were reported. QoL showed insignificant changes in urinary, bowel, sexual, and hormonal domain scores during the follow-up period. All patients had early post-MRgSBRT biochemical responses, while biochemical recurrence (PSA nadir + 2 ng/mL) occurred in one patient at month 18. Conclusions: To our knowledge, this is the first prospective study that showed the clinical outcomes of MRgSBRT with concomitant WPRT in HR-PC patients. The early results suggested favorable treatment-related toxicities and encouraging patient-reported QoLs, but long-term follow-up is needed to confirm our early results.

Background: Immunotherapy and targeted therapy treatments are novel treatments available for patients with metastatic and adjuvant melanoma. As recently approved treatments, information surrounding the patients' and caregivers' experience with these therapies, perceptions of treatments, and the effect the treatments have on their day-to-day life are lacking. Such insights would be valuable for any future decision-making with regard to treatment options., Objective: This study aims to use health-related social media data to understand the experience of patients with adjuvant and metastatic melanoma who are receiving either immunotherapy or targeted therapies. This study also included caregivers' perspectives., Methods: Publicly available social media forum posts by patients with self-reported adjuvant or metastatic melanoma (and their caregivers) between January 2014 to October 2019 were programmatically extracted, deidentified, cleaned, and analyzed using a combination of natural language processing and qualitative data analyses. This study identified spontaneously reported symptoms and their impacts, symptom duration, and the impact of treatment for both treatment groups., Results: Overall, 1037 users (9023 posts) and 114 users (442 posts) were included in the metastatic group and adjuvant group, respectively. The most identified symptoms in both groups were fatigue, pain, or exanthema (identified in 5%-43% of patients dependent on the treatment group). Symptom impacts reported by both groups were physical impacts, impacts on family, and impacts on work. Positive treatment impacts were reported in both groups and covered the areas of work, social and family life, and general health and quality of life., Conclusions: This study explored health-related social media to better understand the experience and perspectives of patients with melanoma receiving immunotherapy or targeted therapy treatments as well as the experience of their caregivers. This exploratory work uncovered the most discussed concerns among patients and caregivers on the forums including symptoms and their impacts, thus contributing to a deeper understanding of the patient/caregiver experience., (©Guy Faust, Alison Booth, Evie Merinopoulou, Sonia Halhol, Heena Tosar, Amir Nawaz, Magdalena Szlachetka, Gavin Chiu. Originally published in JMIR Cancer (https://cancer.jmir.org), 13.05.2022.)

The principal signals that drive memory and cognitive impairment in Alzheimer's disease (AD) remain elusive. Here, we revealed brain-wide cellular reactions to type I interferon (IFN-I), an innate immune cytokine aberrantly elicited by amyloid β plaques, and examined their role in cognition and neuropathology relevant to AD in a murine amyloidosis model. Using a fate-mapping reporter system to track cellular responses to IFN-I, we detected robust, Aβ-pathology-dependent IFN-I activation in microglia and other cell types. Long-term blockade of IFN-I receptor (IFNAR) rescued both memory and synaptic deficits and resulted in reduced microgliosis, inflammation, and neuritic pathology. Microglia-specific Ifnar1 deletion attenuated the loss of post-synaptic terminals by selective engulfment, whereas neural Ifnar1 deletion restored pre-synaptic terminals and decreased plaque accumulation. Overall, IFN-I signaling represents a critical module within the neuroinflammatory network of AD and prompts concerted cellular states that are detrimental to memory and cognition., Competing Interests: Declaration of interests W.C. received honorarium as an invited speaker in a symposium sponsored by AstroZeneca. H.Z. is a member of the Scientific Advisory Board of the Tau Consortium, Rainwater Charitable Foundation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The incidence and management of maxillofacial trauma was compared between the first and third lockdowns in the United Kingdom due to the COVID-19 pandemic. From 6 January, 2021 to 8 March 2021, the units that had participated in the collection of data during the first lockdown were asked to update their information into the same database for the third. Nine units participated with 929 entries. Compared to the first lockdown, the number of patients whose treatment had been changed due to the pandemic reduced from 7.6% to 0.4% in the third lockdown. In the UK during the third lockdown there were higher numbers infected with COVID-19 and admitted to hospital than in the first lockdown. Despite this OMFS units that participated in the second study were able to continue the management of maxillofacial trauma without the pandemic affecting care., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom., Methods: The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment., Discussion: Two hundred patients were included (63% [ n  = 126/200] with primary MF; 37% [ n  = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. 'Watch and wait' was the first management strategy for 53.5% ( n  = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0-350); patients with higher risk disease were prescribed active treatment sooner., Conclusion: These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients., Plain Language Summary: Background: Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient's daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently. Methods: We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK. Results: The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was 'watch and wait', which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner. Conclusion: The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AJM has consulted for Novartis, Bristol Myers Squibb/Celgene, and AbbVie, has received research funding from Novartis, Bristol Myers Squibb/Celgene, and CTI BioPharma, has received honoraria from Novartis and CTI BioPharma, and has served on the speaker’s bureau for Novartis. NB has received speaker fees, advisory board and sponsored meeting attendance fees from Novartis. AW has received consulting fees and an educational grant from Novartis. JE has received speaker fees, advisory board and sponsored meeting attendance fees from Novartis. JM has received speaker fees and advisory board fees from Novartis. RB and GC are employees of Novartis. JH is an employee of OPEN VIE. TS has received consulting fees and an educational grant from Novartis. All other authors have no conflict of interest to declare., (© The Author(s), 2022.)

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class of retrotransposons is particularly enriched. We show that protein encoded by Intracisternal A-particle, a highly active mouse ERV, is elevated in brains of tau transgenic mice. Using two complementary approaches, we find that brains of tau transgenic mice contain increased DNA copy number of transposable elements, raising the possibility that these elements actively retrotranspose in the context of tauopathy. Taken together, our study lays the groundwork for future mechanistic studies focused on transposable element regulation in the aging mouse brain and in mouse models of tauopathy and provides support for ongoing therapeutic efforts targeting transposable element activation in patients with Alzheimer's disease., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We assess the effect of coronavirus disease 2019 (COVID-19) on UK oral and maxillofacial (OMF) trauma services and patient treatment during the first wave of the pandemic. From 1 April 2020 until 31 July 2020, OMF surgery units in the UK were invited to prospectively record all patients presenting with OMF trauma. Information included clinical presentation, mechanism of injury, how it was managed, and whether or not treatment included surgery. Participants were also asked to compare the patient's care with the treatment that would normally have been given before the crisis. Twenty-nine units across the UK contributed with 2,229 entries. The most common aetiology was mechanical fall (39%). The most common injuries were soft tissue wounds (52%) and, for hard tissues, mandibular fractures (13%). Of 876 facial fractures, 79 patients' treatment differed from what would have been normal pre-COVID, and 33 had their treatment deferred. Therefore the care of 112 (14%) patients was at variance with normal practice because of COVID restrictions. The pattern of OMFS injuries changed during the first COVID-19 lockdown. For the majority, best practice and delivery of quality trauma care continued despite the on-going operational challenges, and only a small proportion of patients had changes to their treatment. The lessons learnt from the first wave, combined with adequate resources and preoperative testing of patients, should allow those facial injuries in the second wave to receive best-practice care., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

On 25 March 2020, the Chief Dental Officer issued national guidance restricting the provision of all routine, non-urgent dental services in response to the spread of COVID-19. We analysed odontogenic cervicofacial infections (CFI) presenting to oral and maxillofacial surgery (OMFS) departments during the first wave of COVID-19 in the United Kingdom. From 1 April 2020 until 31 July 2020 a database was used to prospectively collect records for all patients with CFI who presented to oral and maxillofacial teams. Information gathered included clinical presentation, location/origin of infection, and how this was managed. The OMFS units were asked to compare the patient's care with the treatment that would usually have been given prior to the crisis. A total of 32 OMFS units recorded 1381 cases of CFI in the UK. Most of the infections were referred via the emergency department (74%). Lower first or second molars were the most common origin, contributing 40% of CFI. Collaborators reported that patients' treatments were modified as a response to COVID in 20% of cases, the most frequently cited reason being the application of COVID-19 hospital policy (85%). The impact of the first wave of COVID modified the management of a significant number of patients presenting with CFI, and there was a proactive move to avoid general anaesthetics where possible. Some patients who presented to secondary care were given no treatment, suggesting they could have been managed in primary dental care if this had been available. We recommend that OMFS units and urgent dental care centres (UDCCs) build strong communication links not only to provide the best possible patient care, but to minimise COVID exposure and the strain on emergency departments during the pandemic., (Copyright © 2021 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) offers the potential for achieving better prostate cancer (PC) treatment outcomes. This study reports the preliminary clinical results of 1.5T MRgSBRT in localized PC, based on both clinician-reported outcome measurement (CROM) and patient-reported outcome measurement (PROM)., Methods: Fifty-one consecutive localized PC patients were prospectively enrolled with a median follow-up of 199 days. MRgSBRT was delivered in five fractions of 7.25-8 Gy with daily online adaptation. Clinician-reported gastrointestinal (GI) and genitourinary (GU) adverse events based on the Common Terminology Criteria for Adverse Events (CTCAE) Scale v. 5.0 were assessed. The Expanded Prostate Cancer Index Composite Questionnaire was collected at baseline, 1 month, and every 3 months thereafter. Serial prostate-specific antigen measurements were longitudinally recorded., Results: The maximum cumulative clinician-reported grade ≥ 2 acute GU and GI toxicities were 11.8% (6/51) and 2.0% (1/51), respectively, while grade ≥ 2 subacute GU and GI toxicities were 2.3% (1/43) each. Patient-reported urinary, bowel, and hormonal domain summary scores were reduced at 1 month, then gradually returned to baseline levels, with the exception of the sexual domain. Domain-specific subscale scores showed similar longitudinal changes. All patients had early post-MRgSBRT biochemical responses., Conclusions: The finding of low toxicity supports the accumulation of clinical evidence for 1.5T MRgSBRT in localized PC.

The BAOMS QOMS pilot was developed and run in six England OMFS units between December 2019 - April 2020. The aims of this pilot project were: to evaluate feasibility of the questionnaires developed for the audit and how effective they were with regards to quality improvement, to test the processes associated with the data collection system and finally, to provide baseline data to support patient data collection without the requirement of prospective consent. The pilot included a series of six audits (oral and dentoalveolar [ODA], oncology, orthognathic, reconstruction, trauma, and skin). Data entry was clinician-led in five OMFS units and in one unit (EKHU), it was additionally supported by members of the clinical coding team. One hundred and twenty-eight REDCap account user details were issued and of these, 45 (35%) completed registration and 22 (17%) were active users who participated in the pilot data entry. Disproportionate focus on individual audits within QOMS was seen, though not all units offered the full range of service audited. Users suggest the skin and ODA audits were sufficiently clear, but improvement is required in the oncology and reconstruction questionnaire particularly. The pilot was successful in aiding the project team identify areas of weaknesses and strength in the design of the REDCap registry and implementation of the next phase of the initiative. The information and experience gained has to date enabled a successful application for section 251 approval from the HRA and progress for the next phase of national data collection., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

We report the first New Zealand case of Anncaliia algerae myositis in a 55-year-old man with a history of psoriatic arthritis, treated with long-term immunosuppressive therapy. He resided in the city of Rotorua, which is famous for geothermal hot springs. A vastus lateralis muscle biopsy was performed to investigate the cause of an unexplained myositis. Light microscopy demonstrated a necrotizing myositis with scattered clusters of ovoid spores within the myocyte cytoplasm resembling microsporidia. DNA analysis by PCR and electron microscopy confirmed microsporidial myositis with features characteristic of A. algerae. Immunosuppressive drugs were stopped and the patient was treated with cholestyramine wash and albendazole. The patient deteriorated with involvement of bulbar and respiratory muscles requiring intensive care and ventilation. He died 3 weeks after diagnosis. Post-mortem examination of skeletal muscle from tongue and intercostal muscles also revealed numerous organisms confirming disseminated disease., 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 © 2021 Elsevier B.V. All rights reserved.)

It is often said that medicine could learn a lot from aviation. Human and system errors affect all complex organisations including healthcare, and there is increasing awareness of the role of non-technical skills in the safe practice of surgery. Comparisons are often drawn between the way in which the aviation industry learns from errors and the paucity of learning from errors in situational judgement in medical practice. Although many of us travel on planes, very few of us fly them, but most surgeons drive regularly. We review a series of motoring incidents that demonstrate poor situational awareness and judgement, and discuss the incidents, predisposing causes, and their relevance to medical practice. These errors are transferrable to medical practice, and perhaps we can learn from them., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Nasopharyngeal carcinoma (NPC) patients treated with Helical Tomotherapy (HT) are commonly set up in an extended neck (EN) or a flexed neck (FN) position. This study investigated the dosimetric and set-up accuracy differences between these 2 set-up positions. Twenty NPC patients treated with HT from each set-up position were retrospectively recruited. HT plans were computed using the same target prescription and organs at risks (OARs) constraints for both set-up positions. The doses parameters of the target volumes and OARs were assessed. Daily megavoltage CT images were retrieved to obtain the set-up errors at 4th (C4) and 7th (C7) cervical levels. The mean values of these parameters were compared between the 2 set-up positions. The dose to NP target in FN group was more conformal than EN group, while the conformity of the neck targets in FN group were significantly lower. For the OARs, the temporal lobe, cerebellum, and hippocampus in FN group received significantly lower doses than the EN. However, the optic structures, brain stem, spinal cord, and parotid glands received higher doses in FN group. The systematic errors at C4 and C7 levels in FN group were larger in all translational directions except the ML direction at C7 level. With regard to radiotherapy of NPC patient using helical tomotherapy, FN position reduced doses to intracranial structures but increased doses to optic structures and other structures when compared with the EN position. In terms of set-up accuracy at the neck region, EN position was relatively better., (Copyright © 2020 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated a potent IFN immunogenicity of nucleic acid-containing (NA-containing) amyloid fibrils in the periphery. Here, we investigated whether IFN is associated with β-amyloidosis inside the brain and contributes to neuropathology. An IFN-stimulated gene (ISG) signature was detected in the brains of multiple murine Alzheimer disease (AD) models, a phenomenon also observed in WT mouse brain challenged with generic NA-containing amyloid fibrils. In vitro, microglia innately responded to NA-containing amyloid fibrils. In AD models, activated ISG-expressing microglia exclusively surrounded NA+ amyloid β plaques, which accumulated in an age-dependent manner. Brain administration of rIFN-β resulted in microglial activation and complement C3-dependent synapse elimination in vivo. Conversely, selective IFN receptor blockade effectively diminished the ongoing microgliosis and synapse loss in AD models. Moreover, we detected activated ISG-expressing microglia enveloping NA-containing neuritic plaques in postmortem brains of patients with AD. Gene expression interrogation revealed that IFN pathway was grossly upregulated in clinical AD and significantly correlated with disease severity and complement activation. Therefore, IFN constitutes a pivotal element within the neuroinflammatory network of AD and critically contributes to neuropathogenic processes.

This survey of expert opinion regarding the management of mandibular third molar (M3M) impaction and its clinical sequelae was circulated to all members of the British Association of Oral and Maxillofacial Surgeons (BAOMS). It was completed by 289 clinicians who reported treating 60003 patients annually. Respondents included 199 (69%) specialists and 58 (20%) primary care clinicians. Most (99%) of the clinicians treated at least one M3M with complete surgical removal (CSR) annually. Only 69% performed one or more coronectomies (COR). Advocates of coronectomy reported lower rates of inferior alveolar nerve (IAN) injury, but IAN, lingual nerve, and adjacent second molar damage were rare, occurring in less than 0.5% of cases, with small differences between the COR and CSR groups. Although these differences are not statistically significant, they are likely to be clinically important. Also, the COR group would have comprised mainly high-risk teeth, while the CSR group would include many teeth at low risk of complications. This might have skewed the results. Those clinicians performing no coronectomies cited three main reasons for being low adopters of COR: the lack of irrefutable evidence to support its benefit, the increased need for a second operation, and more non-IAN complications. Although COR may prevent permanent IAN damage in high-risk cases, this paper highlights clinicians' views that there is a gap in evidence and knowledge to support COR. As a result, 47% of the clinicians surveyed recommended, and were prepared to participate in, further studies to determine the effectiveness and safety of COR., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The recommendations in which the Mexican Society of Cardiology (SMC) in conjunction with the National Association of Cardiologists of Mexico (ANCAM) as well as different Mexican medical associations linked to cardiology are presented, after a comprehensive and consensual review and analysis of the topics related to cardiovascular diseases in the COVID-19 pandemic. Scientific positions are analyzed and responsible recommendations on general measures are given to patients, with personal care, healthy eating, regular physical activity, actions in case of cardio-respiratory arrest, protection of the patient and health personnel as well as precise indications in the use of non-invasive cardiovascular imaging, prescription of medications, care in specific topics such as systemic arterial hypertension, heart failure, arrhythmias and acute coronary syndromes, in addition to emphasizing electrophysiology, interventionism, cardiac surgery and in cardiac rehabilitation. The main interest is to provide the medical community with a general orientation on what to do in daily practice and patients with cardiovascular diseases in the setting of this unprecedented epidemiological crisis of COVID-19., (Copyright: © 2020 Permanyer.)

Objective: In radiotherapy of nasopharyngeal carcinoma (NPC) patients, the brachial plexus (BP) situated at both sides of the neck is often irradiated to high dose. This study was to evaluate different BP delineation methods and analyse the dosimetric consequences when applying BP dose constraints in radiotherapy planning of NPC., Methods: 15 NPC cases radically treated with helical tomotherapy were recruited. Apart from the original treatment plan (Plan A), two new plans (Plans B and C) with additional BP dose constraints were computed using the same planning CT images, structures and planning parameters. Plan B consisted of BP contours based on Radiation Therapy Oncology Group (RTOG)-endorsed atlas; while those in Plan C were based on MR images registered with the planning CT images., Results: The mean BP volume by RTOG method was 19.04 ± 3.50 cm 3 vs 10.44 ± 2.00 cm 3 by CT/MRI method. The mean BP overlapping volume between the two contouring methods was 1.9 cm 3 (0.38-4.03 cm 3 ). There was significant difference between two methods ( p < 0.001). The average D max , D mean , D 5% , D 10% and D 15% of both sides of BP in Plan A were significantly higher than those in both Plan B and Plan C. There were no significant dose differences in the targets and organs at risk (OARs) after applying dose constraints in Plan B and Plan C., Conclusion: RTOG method was recommended since larger BP volume provided better protection. Applying BP dose constraints during tomotherapy plan optimisation for NPC patients could significantly reduce the BP dose ( p < 0.05) without compromising the doses to the targets and other OARs., Advances in Knowledge: This is the first study comparing the delineation method based on RTOG-endorsed atlas with the conventional CT/MRI delineation method for BP in tomotherapy of NPC patients. Our results showed that BP dose could be significantly reduced after applying the dose constraints without compromising the doses to the target volumes and other OARs. The RTOG method was more favoured as it gave a relatively larger BP volume and therefore offered better organ sparing.

This paper shows the importance of the guideline clinical practice as well as the centers for comprehensive care of pulmonary arterial hypertension. The current treatment of pulmonary arterial hypertension is analyzed according to its severity, stratified through the evaluation of the multiple parameters of risk and its mortality to 1 year. The prognosis of the disease is considered and the place of the combined treatment indicated in sequential manner or from the beginning.

Purpose: Significance of intracardiac echogenic focus (ICEF) in the fetal heart remains controversial. We aimed to investigate whether the location of ICEF is associated with fetal cardiac structure defects (CSDs) in low-risk pregnant women. Materials and Methods: A retrospective cohort study was conducted. Singleton pregnancies with normal values of triple fetal serum markers were included. 758 of 9782 fetuses with ICEF were reviewed for involvement of three ICEF locations (left, right, and bilateral ventricles (BVs)) in CSDs. χ 2 or Fisher's exact test was performed for statistical analysis. Results: ICEF prevalence was 7.7% and its location was most frequently in the left ventricle (LV) (84.8%), followed by the BV (11.6%) and the right ventricle (RV) (3.6%). No statistically significant difference was found between the ICEF location and maternal age ( χ 2  = 3.92, p- value = .1409). There were cardiac defects with an isolated echogenic focus in 24 of 758 fetuses (3.2%). Significant difference for CSDs was observed among groups of RV, LV, and BV ( p -fisher = .0146). Conclusions: Significantly more CSDs cases were identified in fetuses with ICEF in RV. Further investigation is warranted to examine the histological characteristics of fetal echogenic focus in the RV.

Hematopoietic stem progenitor cells (HSPCs) reside in the bone marrow (BM) hematopoietic "niche," a special 3-dimensional (3D) microenvironment that regulates HSPC self-renewal and multipotency. In this study, we evaluated a novel 3D in vitro culture system that uses components of the BM hematopoietic niche to expand umbilical cord blood (UCB) CD34 + cells. We developed this model using decellularized Wharton jelly matrix (DWJM) as an extracellular matrix (ECM) scaffold and human BM mesenchymal stromal cells (MSCs) as supporting niche cells. To assess the efficacy of this model in expanding CD34 + cells, we analyzed UCB CD34 + cells, following culture in DWJM, for proliferation, viability, self-renewal, multilineage differentiation, and transmigration capability. We found that DWJM significantly expanded UCB HSPC subset. It promoted UCB CD34 + cell quiescence, while maintaining their viability, differentiation potential with megakaryocytic differentiation bias, and clonogenic capacity. DWJM induced an increase in the frequency of c-kit + cells, a population with enhanced self-renewal ability, and in CXCR4 expression in CD34 + cells, which enhanced their transmigration capability. The presence of BM MSCs in DWJM, however, impaired UCB CD34 + cell transmigration and suppressed CXCR4 expression. Transcriptome analysis indicated that DWJM upregulates a set of genes that are specifically involved in megakaryocytic differentiation, cell mobility, and BM homing. Collectively, our results indicate that the DWJM-based 3D culture system is a novel in vitro model that supports the proliferation of UCB CD34 + cells with enhanced transmigration potential, while maintaining their differentiation potential. Our findings shed light on the interplay between DWJM and BM MSCs in supporting the ex vivo culture of human UCB CD34 + cells for use in clinical transplantation., (© 2019 by The American Society of Hematology.)

Objective: To evaluate the quality of the care pathway for adult patients being referred to the East Lancashire Blackburn with Darwen Oral Surgery Service using the referral management system between 2013 and 2014., Results: In the 2013–14 financial year, of the 5,285 referrals that were made to the Oral Surgery Service, 1,962 (37%) were directed to a primary care location for management. After being referred to a primary care location, 92% of patients had been seen within eight weeks. In total, £232,320 was paid to the providers for their service., Conclusion: The East Lancashire Blackburn with Darwen Oral Surgery Services delivered in primary care was found to be effective, with a good standard of quality care. There is ease of access in the community, and reduced waiting times for treatment. It is cost effective with a decreased spend to secondary care. However, there were no cost savings to the commissioners, as overall secondary care activity has not reduced.

Right ventricular (RV) systolic dysfunction due to acute myocardial infarction is associated with serious complications in the short-term. Acute kidney injury (AKI) is a frequent and unrecognized complication. This study aimed to assess whether RV longitudinal strain predicts AKI and short-term prognosis in patients with RV infarction. Prospective cohort of patients with RV infarction. RV function was evaluated with global and free wall right ventricular longitudinal strain (GRVLS and FWRVLS), tricuspid annular plane systolic excursion, and tricuspid S' wave. The primary endpoint was AKI defined as an increase ≥ 50% in serum creatinine and/or a decrease ≥ 25% in glomerular filtration rate during follow-up at 7 days. The secondary endpoint was death from any cause at 30 days. We included 101 patients with RV infarction (male 67%, age 66 ± 11 years). During follow-up at 7 days, 40% of patients developed AKI. At 30 days, 8% of patients died. At univariate analysis, FWRVLS was significantly associated with AKI (Hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.20, p = 0.006). At multivariate analysis, only age, temporary pacemaker implant, and FWRVLS remained as independent predictors of AKI (HR 1.05, 95% CI 1.02-1.08, p = 0.002; HR 2.12, 95% CI 1.11-4.07, p = 0.023; HR 1.10, 95% CI 1.02-1.19, p = 0.018, respectively). At 30 days, patients with FWRVLS ≥ - 15.5% showed a lower survival rate than those with lower strain (84 ± 6 vs. 97 ± 2%, p = 0.021). In patients with RV infarction, FWRVLS was an independent predictor of AKI and was associated with higher mortality in the short-term.

Introduction: Mexico is the country with the highest mortality due to acute myocardial infarction in adults older than 45 years old according to the OECD (28 vs. 7.5% of the average). The first real-world study, RENASCA IMSS, showed a high-risk population at 65%, but 50% without reperfusion strategies. The aim was to describe the clinical presentation, treatment, and outcomes of acute coronary syndromes at the IMSS., Methods: RENASCA IMSS is a nation-wide, prospective, longitudinal-cohort study. We include consecutive patients with an Acute Coronary Syndrome diagnosis (ACC/AHA/ESC) admitted in 177 representative hospitals of the IMSS (166 of second level and 11 of third level of attention). In an electronic database clinical, paraclinical, times, reperfusion treatment, complications, and other variables were assessed. Confidentiality was maintained in data and informed consent was obtained. Registrer calibration was performed with more than 80% of the variables and 80% of the cases., Results: From March 1, 2014 to December 25, 2017; 21,827 patients were enrolled presenting an average age 63.2 ± 11.7, 75% men (16,259) and 25% women (5,568). The most frequent risk factors were: hypertension (60.5%), smoking (46.8%), diabetes (45.5%), dyslipidemia (35.3%) and metabolic syndrome (39.1%). STEMI diagnosis was established in 73.2% of the patients and NSTEMI in 26.8%. The STEMI group within the Code Infarction showed an improvement in the reperfusion therapy (34.9% before vs. 71.4% after, p ≤0.0001) and reduction of mortality (21.1 vs. 9.4%, p ≤0.0001); while the NSTEMI group showed high risk set by a GRACE score of 131.5 ± 43.7 vs. 135.9 + 41.7, p ≤0.0001. Mortality was more frequent within the STEMI group (14.9 vs. 7.6%, p ≤0.0001)., Conclusions: RENASCA IMSS study represents the largest Acute Coronary Syndromes real-world study in Mexico, demonstrating that the Mexican population has a high risk. Patients with a STEMI diagnosis were more frequently enrolled and were associated with higher mortality and complications; however, there is improvement in the reperfusion therapy and in mortality with the Code Infarction strategy., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

Objective: A previous multidisciplinary pilot study based on computer simulations for the geriatric population showed that a dose of 0.5 mg/kg/h of propofol could sedate patients older than 65 for pacemaker implantation. The present study validates that the pacemaker implantation can be done in the elderly using 0.5-1 mg/kg/h of propofol with hemodynamic stability., Methods: 66 patients from 65 to 88 years old scheduled for pacemaker implantation were randomly assigned one of three doses of propofol. The first group received 2 mg/kg/h of propofol (P2) that is within normal range of the sedation dose. The second group received 1 mg/kg/h (P1) dose and the third group received the dose of 0.5 mg/kg/h (P0.5) according to the simulation-predicted dose for geriatric populations., Results: All patients kept MAP between 76 and 85 mmHg, with no hypotension episodes in any of the groups; therefore, they were all hemodynamically stable during the procedure. BIS was between 80 and 65 during the pacemaker implantation for the three groups, BIS of group P2 was significantly lower than the other groups. BIS in groups P1 and P0.5 was within the appropriated range for moderate sedation. Brice was positive for auditory recalls only when there was arousing noise in the operating room., Conclusions: Moderate sedation, adequate for pacemaker implantation, can be achieved infusing 0.5-1 mg/kg/h of propofol in elderly patients when the patient has proper analgesia management at the device implantation site. The second important condition is to avoid unnecessary and alerting auditory and mechanical stimuli in the operating room, so that the patient will remain calm.

A 36-year-old woman with good periodontal health sought treatment for a compensated Class II partially edentulous malocclusion associated with a steep mandibular plane (SN-MP, 45°), 9 missing teeth, a 3-mm midline discrepancy, and compromised posterior occlusal function. She had multiple carious lesions, a failing fixed prostheses in the mandibular right quadrant replacing the right first molar, and a severely atrophic edentulous ridge in the area around the mandibular left first and second molars. After restoration of the caries, the mandibular left third molar served as anchorage to correct the mandibular arch crowding. The mandibular left second premolar was retracted with a light force of 2 oz (about 28.3 cN) on the buccal and lingual surfaces to create an implant site between the premolars. Modest lateral root resorption was noted on the distal surface of the mandibular left second premolar after about 7 mm of distal translation in 7 months. Six months later, implants were placed in the mandibular left and right quadrants; the spaces were retained with the fixed appliance for 5 months and a removable retainer for 1 month. Poor cooperation resulted in relapse of the mandibular left second premolar back into the implant site, and it was necessary to reopen the space. When the mandibular left fixture was uncovered, a 3-mm deep osseous defect on the distobuccal surface was found; it was an area of relatively immature bundle bone, because the distal aspect of the space was reopened after the relapse. Subsequent bone grafting resulted in good osseous support of the implant-supported prosthesis. The relatively thin band of attached gingiva on the implant at the mandibular right first molar healed with a recessed contour that was susceptible to food impaction. A free gingival graft restored soft tissue form and function. This severe malocclusion with a discrepancy index value of 28 was treated to an excellent outcome in 38 months of interdisciplinary treatment. The Cast-Radiograph Evaluation score was 13. However, the treatment was complicated by routine relapse and implant osseous support problems. Retreatment of space opening and 2 additional surgeries were required to correct an osseous defect and an inadequate soft tissue contour. Orthodontic treatment is a viable option for creating implant sites, but fixed retention is required until the prosthesis is delivered. Bone augmentation is indicated at the time of implant placement to offset expected bone loss. Complex restorative treatment may result in routine complications that are effectively managed with interdisciplinary care., (Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Vitamin D deficiency is endemic in the United Kingdom (UK), particularly in high-risk groups. We report the outcomes of patients with low concentrations of the vitamin who had complications after reduction of mandibular fractures or osteotomy, and those who were screened preoperatively. A deficiency can be diagnosed with a simple and inexpensive blood test, and in the UK the cost of a vitamin D tablet is about £0.04/tablet/day. Patients at risk of a deficiency should be screened before mandibular operations, and those listed for orthognathic surgery or replacement of the temporomandibular joint should be asked to take a supplement before operation., (Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Pulmonary hypertension in chronic kidney disease is included in the group 5 of the pulmonary hypertension classification of the World Health Organization. Its mechanism is multifactorial and little known. Its importance has increased due to its impact on survival according to whether they received a kidney transplant, the greater risk of early renal graft loss and major hospital stays. In this review, we analyze the panorama of chronic renal disease in Mexico and Latin America, the epidemiology, pathophysiological mechanisms, the diagnostic process and the treatment of pulmonary hypertension in chronic kidney disease.

Perceptions of asthma control often vary between patients and physicians. This cross-sectional survey provided UK-specific data on actual and perceived asthma control in patients (18-75 years) attending routine asthma reviews in primary, secondary and tertiary settings. Differences between healthcare professionals' (HCP) and patients' perceptions of asthma control were evaluated via an online questionnaire and compared to a control-the validated asthma control test (ACT)-which patients completed. Treated patients (at least a short acting ß-agonist) with a documented diagnosis of asthma were enroled and consented within a month of their last appointment. Patients were grouped according to the British Thoracic Society (BTS)/Scottish Intercollegiate Guidelines Network (SIGN) 2014 treatment guidelines (BTS/SIGN steps 1-5). A total of 260 patients were screened: 234 were eligible for enrolment: 33, 52, 50, 49 and 50 patients in steps 1-5, respectively. Seventy per cent (164) were women. The percentage of patients aged 45-64 years was 47.4%. HCPs classed 70% (164) as non-smokers. 84.2% of patients and 73.9% of HCPs perceived that asthma was controlled but ACT results suggest that asthma was only controlled in 54.7% of patients (ACT score ≥20). Patients in steps 4 and 5 had the highest levels of uncontrolled asthma. Correct agreement between ACT score with perceptions of controlled or uncontrolled asthma occurred in 67.9% of patients and 68.8% of HCPs; the poorest levels of agreement occurred in patients in steps 4 and 5. Uncontrolled asthma is common in UK patients. High proportions of patients and HCPs have incorrect perceptions of asthma control, especially in relation to patients with asthma in steps 4 and 5., Asthma: MISPERCEPTIONS OF CONTROL ABOUND AMONG UK PATIENTS AND DOCTORS: Asthma patients and their doctors often misperceive whether the disease is under control, according to a British study. Andrew Menzies-Gow from Royal Brompton Hospital in London and Gavin Chiu from Boehringer Ingelheim UK in Bracknell used an online questionnaire to assess perceptions of asthma control among 234 patients and their healthcare providers. All participants had at least intermittent asthma that required occasional treatment; many had more severe disease. The researchers found that 84% of patients and 74% of doctors thought the asthma was well controlled, but results of the Asthma Control Test indicated only 55% of patients objectively achieved disease control. Correct agreement between the validated test and more subjective perceptions occurred in only 68 % of patients and 69% of doctors. Addressing this mismatch could go a long way to improving asthma control among British patients.

To find out if the devolution of some dentoalveolar services into primary care in 2007 was having an effect on the workload of oral and maxillofacial units, I reviewed the workload of two units in 2011-13., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

The ultimate goal of adaptive radiotherapy (ART) is to deliver truly customized radiation treatments. Currently, the quality of cone-beam computed tomography (CBCT) images is still inferior to that of conventional CT images in contour delineations and dose calculations for replanning purposes. This retrospective study aims to evaluate the dosimetric accuracy of using deformed conventional CT images for dose calculations, in the hope of inferring the feasibility of ART using planning CT (PCT) images that deformed to up-to-date CBCT images for patients with nasopharyngeal carcinoma (NPC). Thirty consecutive patients with NPC who had undergone 1 replan in their radiotherapy treatments were selected. The pretreatment PCT images were deformed to match the mid-treatment PCT images by deformable image registration. The same volumetric modulated arc therapy plan was then calculated on the deformed PCT images. The resulting dose distributions and dose volume histograms of the tumors and organs at risk (OARs) were compared with the original plan. Five dose levels, D 98% , D 95% , D 50% , D 5% , and D 2% , were recorded for 9 NPC targets. Four dose levels, D max , D 10% , D 50% , and D mean , were recorded for 15 OARs. The greatest percentage difference in observed dose for D 98% , D 95% , D 50% , D 5% , and D 2% of the targets were 1.71%, 1.55%, 0.64%, 0.97%, and 1.13%, respectively. The greatest percentage difference in observed dose for D max , D 10% , D 50% , and D mean of the OARs were -26.51% (left optic nerve), -17.06% (left optic nerve), 56.70% (spinal cord), and 18.97% (spinal cord), respectively. In addition, 29 of 45 (64%) dosimetric end points of the targets showed statistically significant dose differences (p < 0.05) between the original plan and the plan calculated on deformed images. Forty-nine of 60 (82%) dosimetric end points of the OARs also showed statistically significant dose differences (p < 0.05). Dose calculations using deformed PCT images could result in significant dose uncertainties in target volumes and OARs. Larger dose deviations were found in OARs in comparison with target volumes. The spinal cord and optic nerve showed the greatest percentage dose differences and the clinical significance has yet to be determined. Deformable registration error was believed to be the problem causing the dose deviations. Owing to unknown clinical significanceof dose deviation results obtained from this study, a conventional CT scan is still required for replanning in patients with NPC who are experiencing significant anatomical changes during the course of radiation treatment., (Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Background: This study characterized a cohort of chronic obstructive pulmonary disease (COPD) patients on maintenance bronchodilator monotherapy for ≥6 months to establish their disease burden, measured by health care utilization., Methods: Data were extracted from the UK Clinical Practice Research Datalink and linked to Hospital Episode Statistics. The monotherapy period spanned the first prescription of a long-acting β 2 -adrenergic agonist or a long-acting muscarinic antagonist until the end of the study (December 31, 2013) or until step up to dual/triple therapy, for example, addition of another long-acting bronchodilator, an inhaled corticosteroid, or both. A minimum of four consecutive prescriptions and 6 months on continuous monotherapy were required. Patients <50 years old at first COPD diagnosis or with another significant respiratory disease before starting monotherapy were excluded. Disease burden was evaluated by measuring patients' rate of face-to-face interactions with a health care professional (HCP), COPD-related exacerbations, hospitalizations, and referrals., Results: A cohort of 8,811 COPD patients (95% Global initiative for chronic Obstructive Lung Disease stage A/B) on maintenance monotherapy was identified between 2002 and 2013; 45% of these patients were still on monotherapy by the end of the study. Median time from first COPD diagnosis to first monotherapy prescription was 56 days, while the median time on maintenance bronchodilator monotherapy was 2 years. The median number of prescriptions was 14. On average, patients had 15 HCP interactions per year, and one in ten patients experienced a COPD exacerbation (N=8,811). One in 50 patients were hospitalized for COPD per year (n=4,848)., Conclusion: The average monotherapy-treated patient had a higher than average HCP interaction rate. We also identified a large cohort of patients who were stepped up to triple therapy despite a low rate of exacerbations. The use of the new class of long-acting muscarinic antagonist/long-acting β 2 -adrenergic agonist fixed-dose combinations may provide a useful step-up treatment option in such monotherapy patients, before the use of inhaled corticosteroids., Competing Interests: SE and SF are former employees of Boehringer Ingelheim Ltd., and AS, GC, and AT are currently employed by Boehringer Ingelheim Ltd. BJL has received payments for consulting and advisory boards from BI, Chiesi, Cipla, Dr Reddys, Sandoz, and Teva; support to attend educational meetings from BI, Teva, and Chiesi; and payment for talks from Meda and Teva. The Scottish Centre for Respiratory Research has received unrestricted research grant support from Teva, Chiesi, and Almirral and payment for multicenter trials from AstraZeneca, Janssen, Teva, and Roche. The authors report no other conflicts of interest in this work.

Li-ion hybrid supercapacitors (LIHSs) have recently attracted increasing attention as a new and promising energy storage device. However, it is still a great challenge to construct novel LIHSs with high-performance due to the majority of battery-type anodes retaining the sluggish kinetics of Li-ion storage and most capacitor-type cathodes with low specific capacitance. To solve this problem, 3D graphene-wrapped MoO 3 nanobelt foam with the unique porous network structure has been designed and prepared as anode material, which delivers high capacity, improved rate performance, and enhanced cycle stability. First-principles calculation reveals that the combination of graphene dramatically reduces the diffusion energy barrier of Li + adsorbed on the surface of MoO 3 nanobelt, thus improving its electrochemical performance. Furthermore, 3D graphene-wrapped polyaniline nanotube foam derived carbon is employed as a new type of capacitor-type cathode, demonstrating high specific capacitance, good rate performance, and long cycle stability. Benefiting from these two graphene foam-enhanced materials, the constructed LIHSs show a wide operating voltage range (3.8 V), a long stable cycle life (90% capacity retention after 3000 cycles), a high energy density (128.3 Wh·kg -1 ), and a high power density (13.5 kW·kg -1 ). These encouraging performances indicate that the obtained LIHSs may have promising prospect as next-generation energy-storage devices.