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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.)

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.

Background: In the United Kingdom, national guidance published in 2010 recommended the establishment of specialist teams to improve clinical pathways for patients presenting with malignancies of undefined primary origin (MUO) and cancer of unknown primary (CUP). This study sought to define outcomes of patients referred to a regional MUO/CUP service., Methods: Data were collected prospectively on all patients (n = 1225) referred to a regional CUP team over a 10-year period. Patient demographics, clinical, pathological and outcome data were recorded and analysed., Results: Confirmed CUP (cCUP) was diagnosed in 25% of patients. A primary metastatic cancer was identified in 36%, 5% were diagnosed with provisional CUP (pCUP), 27% retained the diagnosis of MUO and in 8% a non-cancer diagnosis was made. Median survival was low in all patients with a final malignant diagnosis: primary identified 9.0 months, cCUP 4.0 months, pCUP 1.5 months and MUO 1.5 months., Conclusions: Patients presenting with MUO have poor outcomes irrespective of the final diagnosis. These patients need a patient-centred, streamlined, rapid diagnostic pathway. There are clear benefits to primary and secondary care teams having access to a dedicated, multidisciplinary MUO/CUP service, with clinical nurse specialists supporting the patients, to help facilitate this pathway and ensure early oncology review., (© 2021. The Author(s).)

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.)

Competing Interests: Competing interests: None declared.

Background: We identified the need to modernize frostbite management in our northern centre and implemented a treatment protocol in 2015. Our aim was to describe the clinical course of patients presenting to the hospital since the implementation of the protocol., Methods: This was a retrospective case series from Whitehorse General Hospital, Whitehorse, Yukon Territory, Canada. We reviewed the charts of patients who presented to the hospital with grade 2-4 frostbite and were treated as per our protocol between Feb. 9, 2015, and Feb. 8, 2020. Patients with grade 2-4 frostbite received iloprost; in addition, those with grade 4 frostbite received alteplase and heparin. We determined the number of digits affected and salvaged, and the time from presentation to the emergency department to treatment initiation. We also examined patients' demographic characteristics, predisposing events, frostbite severity and adverse drug reactions., Results: In 22 patients treated for grade 2-4 frostbite, 142 digits were affected: 59 with grade 2 frostbite, 25 with grade 3 frostbite and 58 with grade 4 frostbite; of the 142, 113 (79.6%) were salvaged. All 29 digits amputated had grade 4 frostbite. The mean time from presentation to iloprost initiation was reduced from 32.9 hours in 2015 to 3.0 hours in 2020. Sports (10 cases [45%]) and alcohol use (6 [27%]) were the most common precipitating events, with alcohol use tending to result in more severe injury (grade 4 in 5 of 6 cases). Adverse reactions with iloprost (e.g., headache) were common but mild. Adverse reactions with alteplase (e.g., bleeding) were less common but of greater clinical significance., Interpretation: Over the study period, our protocol contributed to improvement in frostbite care at our institution, resulting in a digit salvage rate comparable to other published results. Our 5-year experience shows that advanced medical care of frostbite can be achieved, even at a rural centre., Competing Interests: Competing interests: Josianne Gauthier is employed by the Whitehorse General Hospital (Yukon Hospital Corporation). No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Age-dependent oocyte aneuploidy, a major cause of Down syndrome, is associated with declining sister chromatid cohesion in postnatal oocytes. Here we show that cohesion in postnatal mouse oocytes is regulated by Tex19.1. We show Tex19.1-/- oocytes have defects maintaining chiasmata, missegregate their chromosomes during meiosis, and transmit aneuploidies to the next generation. Furthermore, we show that mouse Tex19.1 inhibits N-end rule protein degradation mediated by its interacting partner UBR2, and that Ubr2 itself has a previously undescribed role in negatively regulating the acetylated SMC3 subpopulation of cohesin in mitotic somatic cells. Lastly, we show that acetylated SMC3 is associated with meiotic chromosome axes in mouse oocytes, and that this population of cohesin is specifically depleted in the absence of Tex19.1. These findings indicate that Tex19.1 regulates UBR protein activity to maintain acetylated SMC3 and sister chromatid cohesion in postnatal oocytes and prevent aneuploidy from arising in the female germline., (© 2020 Reichmann et al.)

Objective: This study aims to estimate the technical efficiency of health systems in Asia., Settings: The study was conducted in Asian countries., Methods: We applied an output-oriented data envelopment analysis (DEA) approach to estimate the technical efficiency of the health systems in Asian countries. The DEA model used per-capita health expenditure (all healthcare resources as a proxy) as input variable and cross-country comparable health outcome indicators (eg, healthy life expectancy at birth and infant mortality per 1000 live births) as output variables. Censored Tobit regression and smoothed bootstrap models were used to observe the associated factors with the efficiency scores. A sensitivity analysis was performed to assess the consistency of these efficiency scores., Results: The main findings of this paper demonstrate that about 91.3% (42 of 46 countries) of the studied Asian countries were inefficient with respect to using healthcare system resources. Most of the efficient countries belonged to the high-income group (Cyprus, Japan, and Singapore) and only one country belonged to the lower middle-income group (Bangladesh). Through improving health system efficiency, the studied high-income, upper middle-income, low-income and lower middle-income countries can improve health system outcomes by 6.6%, 8.6% and 8.7%, respectively, using the existing level of resources. Population density, bed density, and primary education completion rate significantly influenced the efficiency score., Conclusion: The results of this analysis showed inefficiency of the health systems in most of the Asian countries and imply that many countries may improve their health system efficiency using the current level of resources. The identified inefficient countries could pay attention to benchmarking their health systems within their income group or other within similar types of health systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mobilization of retrotransposons to new genomic locations is a significant driver of mammalian genome evolution, but these mutagenic events can also cause genetic disorders. In humans, retrotransposon mobilization is mediated primarily by proteins encoded by LINE-1 (L1) retrotransposons, which mobilize in pluripotent cells early in development. Here we show that TEX19.1, which is induced by developmentally programmed DNA hypomethylation, can directly interact with the L1-encoded protein L1-ORF1p, stimulate its polyubiquitylation and degradation, and restrict L1 mobilization. We also show that TEX19.1 likely acts, at least in part, through promoting the activity of the E3 ubiquitin ligase UBR2 towards L1-ORF1p. Moreover, loss of Tex19.1 increases L1-ORF1p levels and L1 mobilization in pluripotent mouse embryonic stem cells, implying that Tex19.1 prevents de novo retrotransposition in the pluripotent phase of the germline cycle. These data show that post-translational regulation of L1 retrotransposons plays a key role in maintaining trans-generational genome stability in mammals.

Meiosis relies on the SPO11 endonuclease to generate the recombinogenic DNA double strand breaks (DSBs) required for homologous chromosome synapsis and segregation. The number of meiotic DSBs needs to be sufficient to allow chromosomes to search for and find their homologs, but not excessive to the point of causing genome instability. Here we report that the mammal-specific gene Tex19.1 promotes Spo11-dependent recombination in mouse spermatocytes. We show that the chromosome asynapsis previously reported in Tex19.1-/- spermatocytes is preceded by reduced numbers of recombination foci in leptotene and zygotene. Tex19.1 is required for normal levels of early Spo11-dependent recombination foci during leptotene, but not for upstream events such as MEI4 foci formation or accumulation of H3K4me3 at recombination hotspots. Furthermore, we show that mice carrying mutations in Ubr2, which encodes an E3 ubiquitin ligase that interacts with TEX19.1, phenocopy the Tex19.1-/- recombination defects. These data suggest that Tex19.1 and Ubr2 are required for mouse spermatocytes to accumulate sufficient Spo11-dependent recombination to ensure that the homology search is consistently successful, and reveal a hitherto unknown genetic pathway promoting meiotic recombination in mammals.

Background: Equity in access to and utilization of healthcare is an important goal for any health system and an essential prerequisite for achieving Universal Health Coverage for any country., Objectives: This study investigated the extent to which health benefits are distributed across socioeconomic groups; and how different types of providers contribute to inequity in health benefits of Bangladesh., Methodology: The distribution of health benefits across socioeconomic groups was estimated using concentration indices. Health benefits from three types of formal providers were analysed (public, private and NGO providers), separated into rural and urban populations. Decomposition of concentration indices into types of providers quantified the relative contribution of providers to the overall distribution of benefits across socioeconomic groups. Eventually, the distribution of benefits was compared to the distribution of healthcare need (proxied by 'self-reported illness and symptoms') across socioeconomic groups. Data from the latest Household Income and Expenditure Survey, 2010 and WHO-CHOICE were used., Results: An overall pro-rich distribution of healthcare benefits was observed (CI = 0.229, t -value = 9.50). Healthcare benefits from private providers (CI = 0.237, t -value = 9.44) largely favoured the richer socioeconomic groups. Little evidence of inequity in benefits was found in public (CI = 0.044, t -value = 2.98) and NGO (CI = 0.095, t -value = 0.54) providers. Private providers contributed by 95.9% to overall inequity. The poorest socioeconomic group with 21.8% of the need for healthcare received only 12.7% of the benefits, while the richest group with 18.0% of the need accounted for 32.8% of the health benefits., Conclusion: Overall healthcare benefits in Bangladesh were pro-rich, particularly because of health benefits from private providers. Public providers were observed to contribute relatively slightly to inequity. The poorest (richest) people with largest (least) need for healthcare actually received lower (higher) benefits. When working to achieve Universal Health Coverage in Bangladesh, particular consideration should be given to ensuring that private sector care is more equitable., (© The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

The brain is made up of trillions of synaptic connections that together form neural networks needed for normal brain function and behavior. SLM2 is a member of a conserved family of RNA binding proteins, including Sam68 and SLM1, that control splicing of Neurexin1-3 pre-mRNAs. Whether SLM2 affects neural network activity is unknown. Here, we find that SLM2 levels are maintained by a homeostatic feedback control pathway that predates the divergence of SLM2 and Sam68. SLM2 also controls the splicing of Tomosyn2, LysoPLD/ATX, Dgkb, Kif21a, and Cask, each of which are important for synapse function. Cortical neural network activity dependent on synaptic connections between SLM2-expressing-pyramidal neurons and interneurons is decreased in Slm2-null mice. Additionally, these mice are anxious and have a decreased ability to recognize novel objects. Our data reveal a pathway of SLM2 homeostatic auto-regulation controlling brain network activity and behavior., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In China, there are more than 300 million male smokers. Tobacco taxation reduces smoking-related premature deaths and increases government revenues, but has been criticised for disproportionately affecting poorer people. We assess the distributional consequences (across different wealth quintiles) of a specific excise tax on cigarettes in China in terms of both financial and health outcomes., Methods: We use extended cost-effectiveness analysis methods to estimate, across income quintiles, the health benefits (years of life gained), the additional tax revenues raised, the net financial consequences for households, and the financial risk protection provided to households, that would be caused by a 50% increase in tobacco price through excise tax fully passed onto tobacco consumers. For our modelling analysis, we used plausible values for key parameters, including an average price elasticity of demand for tobacco of -0·38, which is assumed to vary from -0·64 in the poorest quintile to -0·12 in the richest, and we considered only the male population, which constitutes the overwhelming majority of smokers in China., Findings: Our modelling analysis showed that a 50% increase in tobacco price through excise tax would lead to 231 million years of life gained (95% uncertainty range 194-268 million) over 50 years (a third of which would be gained in the lowest income quintile), a gain of US$703 billion ($616-781 billion) of additional tax revenues from the excise tax (14% of which would come from the lowest income quintile, compared with 24% from the highest income quintile). The excise tax would increase overall household expenditures on tobacco by $376 billion ($232-505 billion), but decrease these expenditures by $21 billion (-$83 to $5 billion) in the lowest income quintile, and would reduce expenditures on tobacco-related disease by $24·0 billion ($17·3-26·3 billion, 28% of which would benefit the lowest income quintile). Finally, it would provide financial risk protection worth $1·8 billion ($1·2-2·3 billion), mainly concentrated (74%) in the lowest income quintile., Interpretation: Increased tobacco taxation can be a pro-poor policy instrument that brings substantial health and financial benefits to households in China., Funding: Bill & Melinda Gates Foundation and Dalla Lana School of Public Health., (Copyright © 2015 Verguet et al. Open access article distributed under the terms of CC BY-NC-SA. Published by .. All rights reserved.)

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline.

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.

Breast cancer is the most common cancer among women worldwide. Estimates suggest up to 35% of cases may be preventable through diet and lifestyle modification. Growing research on the role of fats in human health suggests that early exposure in life to specific fatty acids, when tissues are particularly sensitive to their environment, can have long-term health impacts. The present review examines the role of dietary fat in mammary gland development and breast cancer throughout the lifecycle. Overall, n-3 polyunsaturated fatty acids have promising cancer-preventive effects when introduced early in life, and warrant further research to elucidate the mechanisms of action.

Mean arterial blood pressure (BP) and heart rate (HR) during and after recovery from anesthesia in pregnant and nonpregnant ICR mice were evaluated. Mice were evaluated during mechanical ventilation, from 15 to 60 min after induction of anesthesia. The anesthetic protocols were pentobarbital (80 mg/kg, given intraperitoneally [i.p.]); two low doses of ketamine and xylazine (90 mg/kg, 7.5 mg/kg, respectively, i.p., with a second dose given 20 min after the initial dose); and a single high dose of ketamine and xylazine (150 mg/kg, 12.5 mg/kg, respectively, i.p.). The BP was measured in the right carotid artery, using a fluid-filled catheter connected to a chamber containing a solid-state pressure transducer. Mechanical ventilation was performed via tracheotomy, using a normalized minute ventilation of 3.5 ml*min-1*g-1 for nonpregnant mice and 3.0 ml*min-1*g-1 for pregnant mice. Mean BP was lower and HR was higher in pregnant than in nonpregnant mice for each anesthetic protocol. Pentobarbital induced significantly greater tachycardia and hypotension than did the other protocols. The average BP and HR were similar between two low doses and a single high dose of ketamine and xylazine. During spontaneous breathing from 30 to 180 min after recovery from anesthesia by use of a single low dose, ketamine and xylazine induced similar HR profiles, but mean BP in pregnant mice recovered earlier than did that in nonpregnant mice. These results suggest that ketamine and xylazine induced adequate anesthesia for superficial surgical procedures in pregnant and nonpregnant mice while inducing small changes in HR and BP, and pregnancy resulted in a different hemodynamic reaction in response to ketamine and xylazine. These data will be useful for the design and interpretation of physiologic protocols using pregnant and nonpregnant genetically targeted mice.

Embryonic cardiovascular function has been extensively studied in vivo in the chick embryo. However, the geometry of mammalian and avian hearts differs; the mammalian cardiovascular system is coupled to both yolk sac and placental circulations, and unique murine genetic models associated with structural and functional cardiovascular defects are now available. We therefore adapted techniques validated for the chick embryo to define cardiovascular dimensions and function in the mouse embryo. We bred C3HeB female and C57B1/J6 male mice and ICR pairs for experiments on embryonic days (EDs) 10.5 to 14.5 (n = 130 dams). After maternal anesthesia (pentobarbital, 60 mg/kg IP), laparotomy, and sequential regional hysterotomy, we exposed and then imaged individual embryos at 60 Hz (video) in the ventral and/or left anterior oblique views while maintaining uteroplacental continuity. We measured epicardial chamber dimensions and then calculated right and left ventricular elliptical volumes from ares. In addition, we measured pulsed-Doppler blood velocity across the atrioventricular cushions and ventricular outflow tract. We maintained embryonic temperature with a heated surgical platform, topical oxygenated and warmed buffer, and warming lamps. Embryonic heart rate increased from 124.7 +/- 5.2 to 194.3 +/- 13.2 bpm from EDs 10.5 to 14.5 (P < .01). Right and left ventricular end-diastolic and end-systolic dimensions increased (P < .05 by ANOVA for each). Maximal ventricular mean inflow and outflow velocities increased from 62.33 +/- 4.06 to 106.23 +/- 11.59 and from 55.79 +/- 6.11 to 91.61 +/- 6.93 mm/s, respectively (P < .05 by ANOVA for each). Thus, as has been done for chick and rat embryos, the maturation of murine embryonic cardiovascular function can be quantified in vivo, setting the stage for the investigation of structure-function relations in mouse models of cardiovascular development and disease.

Pregnancy and labour produce significant changes in salivary calcium, magnesium, phosphate and chloride when pregnant patients in labour are compared with non-pregnant patients. There is a decrease in concentration of these constituents in the 3rd trimester of pregnancy followed by a marked increase when labour occurs. Magnesium and chloride are the constituents most significantly affected and show the largest increase during labour. Changes in saliva flow rate were accounted for and are not responsible for these changes noted. Sodium and potassium follow a similar pattern. When their levels are corrected for saliva flow rate changes, both show a significant increase with the onset of labour.