Search

Abstract Background Polyunsaturated fatty acids (PUFA) have diverse biological effects, from promoting inflammation to preventing cancer and heart disease. Growing evidence suggests that individual PUFA may have independent effects in health and disease. The individual roles of the two essential PUFA, linoleic acid (LA) and α-linolenic acid (ALA), have been difficult to discern from the actions of their highly unsaturated fatty acid (HUFA) downstream metabolites. This issue has recently been addressed through the development of the Δ-6 desaturase knock out (D6KO) mouse, which lacks the rate limiting Δ-6 desaturase enzyme and therefore cannot metabolize LA or ALA. However, a potential confounder in this model is the production of novel Δ-5 desaturase (D5D) derived fatty acids when D6KO mice are fed diets containing LA and ALA, but void of arachidonic acid. Objective The aim of the present study was to characterize how the D6KO model differentially responds to diets containing the essential n-6 and n-3 PUFA, and whether the direct provision of downstream HUFA can rescue the phenotype and prevent the production of D5D fatty acids. Methodology Liver and serum phospholipid (PL) fatty acid composition was examined in D6KO and wild type mice fed i) 10% safflower oil diet (SF, LA rich) ii) 10% soy diet (SO, LA+ALA) or iii) 3% menhaden oil +7% SF diet (MD, HUFA rich) for 28 days (n = 3-7/group). Results Novel D5D fatty acids were found in liver PL of D6KO fed SF or SO-fed mice, but differed in the type of D5D fatty acid depending on diet. Conversely, MD-fed D6KO mice had a liver PL fatty acid profile similar to wild-type mice. Conclusions Through careful consideration of the dietary fatty acid composition, and especially the HUFA content in order to prevent the synthesis of D5D fatty acids, the D6KO model has the potential to elucidate the independent biological and health effects of the parent n-6 and n-3 fatty acids, LA and ALA.

Background: Neurosurgical cranial titanium mesh and screws are commonly encountered in postoperative radiation therapy. However, only a limited number of reports are available in the context of proton therapy, resulting in a lack of consensus among the proton centers regarding the protocol for handling the hardware., Purpose: This study is to examine the impact of the hardware in proton plans. The results serve as evidence for proton centers to generate standard operating procedures to manage the hardware in proton treatment., Methods: Plans with different gantry angles and material overrides are generated on the CT images of a phantom made of the hardware. The dose distributions of the plans with and without material override, at different depths are compared. Films and ionization chambers are used to measure the plans and the measurements are compared to the treatment planning system (TPS) calculations by gamma analysis., Results: There are some overdose and underdose regions downstream of the hardware. The overdose and underdose values are within a few percent of the prescribed dose when multiple fields with large hinge angles are used. The gamma analysis results show that the measurements agree with the TPS calculations within limits that are clinically relevant., Conclusion: The study has demonstrated the influence of the hardware on proton plans. Based on the result of this study, a standard operating procedure of managing the hardware has been implemented in our clinic., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 ., (© 2024. The Author(s).)

Background: Enabling, supporting and promoting positive health-related behaviours is critical in addressing the major public health challenges of our time, and the multifaceted nature of behaviours requires an evidence-based approach. This statement seeks to suggest how a much-needed enhanced use of behavioural and cultural science and insights for health could be advanced., Study Design and Methods: and methods: Public health authorities of Europe and Central Asia and international partner organizations in September 2023 met in Copenhagen, Denmark, to discuss the way forward. Drawing on 1) country reporting to WHO, 2) interview study with public health authorities and 3) the meeting deliberations, this meeting statement was developed., Results: The meeting statement presents a joint call for step-change accelerated use of evidence-based approaches for health behaviours. Actionable next steps for public health authorities and international and regional development partners in health are presented., Conclusions: The way forward involves increased resource allocation, integration of behavioural insights into health strategies, advocacy through case and cost-effectiveness examples and capacity building., (© 2024 Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

Abstract: MacLennan, M, Ramirez-Campillo, R, and Byrne, PJ. Self-massage techniques for the management of pain and mobility with application to resistance training: a brief review. J Strength Cond Res 37(11): 2314-2323, 2023-Fascial restrictions that occur in response to myofascial trigger points (MTrP), exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) cause soft tissue to lose extensibility, which contributes to abnormal muscle mechanics, reduced muscle length, and decrements in joint range of motion (ROM) and actively contributes to musculoskeletal pain. Resistance training and in particular, weightlifting movements have unique mobility requirements imperative for movement efficacy and safety with ROM restrictions resulting in ineffective volume and intensity tolerance and dampened force output and power, which may lead to a failed lift or injury. Self-massage (SM) provides an expedient method to promote movement efficiency and reduce injury risk by improving ROM, muscular function, and reducing pain and allows athletes to continue to train at their desired frequency with minimal disruption from MTrPs-associated adverse effects. Thus, the aim of this review was to determine the efficacy of various self-massage tools in managing pain and mobility and to explore the potential benefits of SM on resistance training performance. Many SM devices are available for athletes to manage ROM restrictions and pain, including differing densities of foam rollers, roller massagers, tennis balls, and vibrating devices. To attenuate adverse training effects, a 10-to-20-minute bout consisting of 2-minute bouts of SM on the affected area may be beneficial. When selecting a SM device, athletes should note that foam rollers appear to be more effective than roller massagers, with vibrating foam rollers eliciting an increased reduction to pain perception, and tennis balls and soft massage balls were shown to be efficacious in targeting smaller affected areas., (Copyright © 2023 National Strength and Conditioning Association.)

Introduction: This paper presents results from Cohort B (rearranged during transfection [ RET ], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing., Material and Methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated., Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients., Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose., Competing Interests: R.D: Advisory/consultancy fees from F. Hoffmann- La Roche, Ltd, Foundation Medicine, Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme, Karyopharm, and Boehringer Ingelheim. Honoraria from F. Hoffmann-La Roche, Ltd, AstraZeneca, and Amgen. Participated in data safety monitoring boards/advisory boards for F. Hoffmann-La Roche, Ltd, AstraZeneca, Amgen, and Merck Sharp & Dohme. N.P: Advisor and honorarium from, and research with, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant Health, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche, and Takeda. IP held for Volatile Organic Compounds for Detecting Cell Dysplasia and Genetic Alterations Associated With Lung Cancer; WO/2012/023138. T.M: Received fees for serving on advisory boards and consulting, and speakers fees and institutional grants and research support from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, and Pfizer. Fees for serving on advisory boards and consulting and speakers fees from ACEA Pharma, Amgen, Boehringer lngelheim, Daiichi Sankyo, Fishawack Facilitate, Ltd., Eli Lilly, OrigiMed Co. Ltd., Sanofi- Aventis; owns stock and has received fees for serving on advisory boards and board of directors/leadership roles from HutchMed; institutional grants and research support and fees for serving on advisory boards and consulting from Merck Serono and SFJ Pharmaceutical Ltd.; fees for serving on advisory boards, board of directors/leadership roles and consulting from Lunit, Inc.; fees for serving on advisory boards and for consulting from AbbVie, BerryOncology, Blueprint Medicines Corporation, C4 Therapeutics, CStone Pharmaceuticals, Curio Science, Eisai, Gilead Sciences, Inc., Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc., IQVIA, Janssen, lgnyta, Inc., lncyte Corporation, lnivata, Loxo Oncology Inc., Mirati Therapeutics Inc., Puma Biotechnology Inc., Vertex Pharmaceuticals, Yuhan Corporation; speakers fees and fees for consulting from Alpha Biopharma Co., Ltd., Amoy Diagnostics Co., Ltd., AstraZeneca (before 1 January 2019), BeiGene; fees for serving on advisory boards and institutional grants and research support from AstraZeneca, Gl Therapeutics, Inc., Takeda; institutional grants and research support from Roche, XCovery; speakers fees from Daz Group, InMed Medical Communication, Janssen, Liangyihui Network Technology Co., Ltd., Lucence Health Inc., MD Health Brazil, Medscape LLC, Merck Pharmaceuticals HK Ltd., P. Permanyer SL, PeerVoice, Physicians’ Education Resource, PrIME Oncology, Research to Practice, Roche Pharmaceuticals/Diagnostic/Foundation Medicine, Shanghai BeBirds Translation and Consulting Co., Ltd., Taiho, Takeda Oncology, touchIME; fees for consulting from Elevation Oncology, MoreHealth, Qiming Development (HK) Ltd., Roche Pharmaceuticals, Takeda Pharmaceuticals HK Ltd.; fees for serving on advisory boards for Roche/Genentech and Virtus Medical Group; fees for a board of directors/leadership role with AstraZeneca PLC; discloses serving on advisory boards (uncompensated) for geneDecode Co., Ltd.; owns stock from Act Genomics-Sanomics Group and Aurora Tele-Oncology Ltd.; declares uncompensated board of directors/leadership roles with the American Society of Clinical Oncology, Asian Thoracic Oncology Research Group, Chinese Lung Cancer Research Foundation Limited, Chinese Society of Clinical Oncology, Hong Kong Cancer Fund, Hong Kong Cancer Therapy Society, International Association for the Study of Lung Cancer (ending 30 April 2019), St. Stephen’s College and Preparatory School. S.P: Received institutional support for consulting or advising from AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, eCancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, Oncology Education, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics and Takeda; institutional fees for speaking at company-sponsored public events for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, eCancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi and Takeda; and institutional grants and research support for the conduct of clinical trials from Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, GlaxoSmithKline, Illumina, Eli Lilly, Merck Sharp & Dohme, Merck Serono, Mirati Therapeutics Inc., Novartis, Pfizer, Phosplatin Therapeutics, and Roche/Genentech. S.P.A: Nothing to disclose. J.A: Received consulting fees from F. Hoffmann-La Roche, Ltd, AstraZeneca, Takeda, and Pfizer; honorarium from F. Hoffmann-La Roche, Ltd, AstraZeneca, Takeda; and meetings and/or travel support from F. Hoffmann- La Roche, Ltd, AstraZeneca, and MSD. B.D.V: Nothing to disclose. M.M: Employment at Syneos Health and works as a Study Statistician in FSP model for F. Hoffmann- La Roche, Ltd on a full-time basis. V.B: Roche employee and shareholder. Breath Analysis of Pulmonary Nodules. US20130150261 A1; Apparatus for treating a target site of a body; WO/2015/059646. S.M.S: Genentech employee and Roche shareholder. E.S: Genentech employee and Roche shareholder. T.R: Roche employee and shareholder. M.S.M: Genentech employee and Roche shareholder. S.M.G: Received fees for consulting from Genentech/Roche, Takeda, AstraZeneca, Pfizer, Daiichi Sankyo and Eli Lilly; served on an independent data monitoring committee for AstraZeneca., (Copyright © 2023 Termedia.)

Heart rate (HR) and HR variability (HRV) can be used to infer readiness to perform exercise in athletic populations. Advancements in the photoplethysmography technology of wearable devices such as WHOOP allow for the frequent and convenient measurement of HR and HRV, and therefore enhanced application in athletes. However, it is important that the reliability of such technology is acceptable prior to its application in practical settings. Eleven elite male water polo players (age 28.8 ± 5.3 years [mean ± standard deviation]; height 190.3 ± 3.8 cm; body mass 95.0 ± 6.9 kg; international matches 117.9 ± 92.1) collected their HR and HRV daily via a WHOOP strap (WHOOP 3.0, CB Rank, Boston, MA, USA) over 16 weeks ahead of the 2021 Tokyo Olympic Games. The WHOOP strap quantified HR and HRV via wrist-based photoplethysmography during overnight sleep periods. The weekly (i.e., 7-day) coefficient of variation in lnRMSSD (lnRMSSD CV ) and HR (HR CV ) was calculated as a measure of day-to-day variability in lnRMSSD and HR, and presented as a mean of the entire recording period. The mean weekly lnRMSSD CV and HR CV over the 16-week period was 5.4 ± 0.7% (mean ± 95% confidence intervals) and 7.6 ± 1.3%, respectively. The day-to-day variability in WHOOP-derived lnRMSSD and HR is within or below the range of day-to-day variability in alternative lnRMSSD (~3-13%) and HR (~10-11%) assessment protocols, indicating that the assessment of HR and HRV by WHOOP does not introduce any more variability than that which is naturally present in these variables.

Objectives: This study aimed to confirm NeuMoDx™ SARS-CoV-2 assay (NeuMoDx assay) functionality using off-label collection media, determine assay performance versus other SARS-CoV-2 RNA assays, and assess any cross-reactivity with other respiratory viruses (human coronavirus NL63, influenza, and respiratory syncytial virus)., Methods: Nasopharyngeal swab samples in off-label collection media and external quality assessment (EQA) samples were dual-tested, first using either the RealStar® SARS-CoV-2 reverse transcriptase polymerase chain reaction assay or the QIAstat-Dx® Respiratory SARS-CoV-2 Panel and then using the NeuMoDx assay. Samples found to be positive for respiratory viruses and negative for SARS-CoV-2 were then tested using the NeuMoDx assay to assess cross-reactivity., Results: Overall, 274 samples (244 patient and 30 EQA samples) were dual-tested; 154 were SARS-CoV-2 positive and 120 were negative. No false-positive or false-negative results were identified, regardless of collection medium used. The NeuMoDx assay sensitivity was 100% (95% confidence interval [CI] 97.63-100.00) and the specificity was 100% (95% CI 96.97-100.00). The assay did not exhibit any cross-reactivity with other respiratory viruses., Conclusion: The NeuMoDx assay demonstrated high sensitivity and specificity on a platform well-suited for fully automated SARS-CoV-2 testing., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Antarctic atmospheric rivers (ARs) are driven by their synoptic environments and lead to profound and varying impacts along the coastlines and over the continent. The definition and detection of ARs over Antarctica accounts for large uncertainty in AR metrics, and consequently, impacts quantification. We find that Antarctic-specific detection tools consistently capture the AR footprint inland over ice sheets, whereas most global detection tools do not. Large-scale synoptic environments and associated ARs, however, are broadly consistent across detection tools. Using data from the Atmospheric River Tracking Method Intercomparison Project and global reanalyses, we quantify the uncertainty in Antarctic AR metrics and evaluate large-scale environments in the context of decadal and interannual modes of variability. The Antarctic western hemisphere has stronger connections to both decadal and interannual modes of variability compared to East Antarctica, and the Indian Ocean Dipole's influence on Antarctic ARs is stronger while in phase with El Nino Southern Oscillation., (© 2022. The Authors.)

Background: Unilateral agenesis of a cervical pedicle is a known rare entity that has been well described over the past 70 years. It is usually an incidental or minimally symptomatic presentation with no significant clinical repercussion. No previous report has described concurrent non-osseous developmental abnormalities alongside this unique pathology., Observations: This case reported a cervical hemangioma with associated unilateral pedicle agenesis and an incidental finding of callosal dysgenesis and lipoma. The initial presentation consisted solely of persistent neck pain, with cervical radiography illustrating significant kyphotic deformity secondary to apparent anterolisthesis of C3-C4. The patient underwent a combined approach: anterior cervical corpectomy at C4-C5 with supplemental posterior fusion. The authors provided a review of the literature concerning developmental pedicle abnormalities and vertebral hemangioma. Pedicle agenesis is known to be associated with multiple pathologies, but the authors have not found evidence of a clinical paradigm consisting of a vertebral hemangioma in the presence of cervical pedicle agenesis, callosal dysgenesis, or callosal lipoma., Lessons: Careful evaluation of radiographs with appropriate subsequent multimodal imaging is key to identifying unique pathologies in the spine that complement a patient's history and clinical findings. If multiple abnormalities are noted, a novel clinical etiology or syndrome must be considered.

Competing Interests: Intérêts concurrents : Aucun déclaré.

Mutation in the germline is the ultimate source of genetic variation, but little is known about the influence of germline chromatin structure on mutational processes. Using ATAC-seq, we profile the open chromatin landscape of human spermatogonia, the most proliferative cell type of the germline, identifying transcription factor binding sites (TFBSs) and PRDM9 binding sites, a subset of which will initiate meiotic recombination. We observe an increase in rare structural variant (SV) breakpoints at PRDM9-bound sites, implicating meiotic recombination in the generation of structural variation. Many germline TFBSs, such as NRF1, are also associated with increased rates of SV breakpoints, apparently independent of recombination. Singleton short insertions (≥5 bp) are highly enriched at TFBSs, particularly at sites bound by testis active TFs, and their rates correlate with those of structural variant breakpoints. Short insertions often duplicate the TFBS motif, leading to clustering of motif sites near regulatory regions in this male-driven evolutionary process. Increased mutation loads at germline TFBSs disproportionately affect neural enhancers with activity in spermatogonia, potentially altering neurodevelopmental regulatory architecture. Local chromatin structure in spermatogonia is thus pervasive in shaping both evolution and disease., (© 2021 Kaiser et al.; Published by Cold Spring Harbor Laboratory Press.)