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  • Your eyes can alert you to dementia onset 12 years in advance

    Your eyes can alert you to dementia onset 12 years in advance

    Your eyes do more than show your brain what’s happening in the world around you. They also reveal how well your brain may fare in the years ahead, including whether or not you might develop dementia.

    A long‑running study of 8,623 adults has found that a subtle slowdown in detecting a faint triangle on a computer screen can hint at Alzheimer’s disease up to 12  years before diagnosis.


    Lead author Eef Hogervorst of Loughborough University says the simple test “could slot into routine checkups without adding a single drop of blood.”

    Vision timing signals brain trouble

    Participants pressed a button when they spotted a triangle drifting amid random dots. Those who later developed dementia needed roughly two extra seconds – a gap large enough to raise their future risk by 56 percent. 

    The task measures visual processing speed, the time the brain takes to register and respond to a stimulus. Sluggish scores predicted dementia even after researchers adjusted for age, education, and cardiovascular health.

    “Visual sensitivity is related to memory performance,” noted Hogervorst. She adds that eyesight often declines quietly, leaving people unaware until memory falters.

    A similar pattern appeared in an independent analysis showing that early amyloid plaques disrupt visual signals before memory centers suffer. Taken together, the findings suggest eye‑based tests could extend the warning window for preventive care.

    Eyes offer dementia warning

    The retina is an outgrowth of the brain, so toxic proteins can accumulate there first. Researchers now examine retinal layers for thinning, abnormal blood vessels, and microscopic deposits that mirror cerebral changes.

    Damage often begins in the occipital cortex, the region that deciphers vision, before spreading to the hippocampus. That makes contrast sensitivity, color discrimination, and motion detection early casualties.

    People with Alzheimer’s also struggle to ignore distractions. “These problems could increase the risk of driving accidents,” warned Thom Wilcockson, a psychologist at Loughborough University.

    Eye-tracking research confirms the concern, showing that older drivers with dementia exhibit erratic saccades, longer fixations, and reduced scanning range – all linked to crash risk.

    What slowing detection really means

    Spotting a shape on a screen sounds trivial, yet it taps fast neural circuits shared with memory. When those circuits lag, forgetting names and appointments may follow.

    The Norfolk data showed the triangle test remained significant after standard memory exams were considered. In clinics, combining both could improve accuracy while saving time and cost.

    Slower vision also correlates with trouble recognizing faces, a social cue often missed in early dementia. Patients skim past eyes and mouths, failing to “imprint” new acquaintances and later feeling lost in familiar rooms.

    Several groups are testing whether directed eye exercises can sharpen recall. Early trials of rapid left‑right movements report modest gains, though results remain mixed.

    Smartphones join dementia fight

    High‑grade eye trackers once cost thousands of dollars. A California team has squeezed similar optics into a smartphone app that uses the front‑facing infrared camera to measure pupil changes.

    The prototype walks users through a brief pupil dilation task, then uploads data for cloud analysis. Engineers hope the approach will let families monitor brain health between clinic visits.

    Consumer wearables are also inching closer. Some virtual‑reality headsets already track gaze direction at millisecond resolution, offering another route for large‑scale screening.

    Still, technology alone is not enough. Experts stress the need for clear guidelines to avoid false alarms and protect privacy.

    Fight dementia with eye health

    Lifestyle counts, too. A 14‑year study of almost 2,000 older adults found those who read at least once a week cut cognitive decline odds by nearly half.

    Reading, watching subtitles, or knitting forces the eyes to dart and refocus, a workout for neural networks. Longer education and regular exercise add extra cognitive reserve, buffering the toll of disease.

    Optometrists recommend annual exams after people reach 60 years of age.

    Reporting new glare, color shifts, or slowed adaptation can nudge physicians to order broader cognitive checks.

    Vision‑friendly habits help, too. Good lighting, high‑contrast text, and blue‑green filters reduce strain and may delay functional loss.

    Finally, keep blood vessels healthy. Controlling blood pressure, diabetes, and cholesterol supports both retinal and cerebral circulation, tying the two organs together.

    The study is published in Scientific Reports.

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  • Will YR4 Hit the Moon? We Won’t Know Until 2028

    Will YR4 Hit the Moon? We Won’t Know Until 2028

    Why we’ll have to wait a bit to say yay or nay on a 2024 YR4 lunar impact.

    Predicting the precise path of a new asteroid or comet is a complex affair; the more observations you have, the better you know where an object will be, years hence.

    Asteroid 2024 YR4 was discovered late last year, and found to have a trajectory passing through the Earth/Moon system in 2032. The world’s telescopes focused on the potential threat and downgraded the chance to negligible for the Earth…but the asteroid still has a non-zero chance of hitting the Moon. As the asteroid became too dim to continue observing, its Moon impact chance stood at 4%. When will we update this number? Not until it does another close flyby in 2028.

    The Discovery

    Asteroid 2024 YR4 was discovered by the Asteroid Terrestrial-impact Last Alert System (ATLAS) as a +13th magnitude object moving through the constellation Hydra the Sea Serpent on the night of December 27th, 2024. The 60-meter space rock was actually discovered two days after closest Earth approach, which was on Christmas Day at 828,800 kilometers away, just over twice the Earth-Moon distance.

    As is the case with lots of asteroids approaching from the sunward direction, 2024 YR4 was outbound on discovery. The Chelyabinsk bolide that exploded over the Russian city of the same name on February 15th, 2013 snuck up on us as well… and just last week, a daytime fireball was seen over central Georgia, and showered an area with recovered fragments.

    Anatomy of a (Potential) Impact

    The asteroid immediately created a stir, as there seemed to be a slight chance of an Earth impact on December 22nd, 2032. At 60 meters across, the asteroid is smaller than an extinction triggering impact such as the 10 kilometer Chicxulub asteroid which hit off of the Yucatan peninsula 66 million years ago, and was instead dubbed a ‘city killer…’ Maps were even published showing a tentative impact swath across South America, the Atlantic, Africa and the Middle East.

    Credit: A risk level comparison for dangerous asteroids. Credit: ESA.

    It even briefly held a notable Torino scale rating of 3 during its first month of discovery—one of few new asteroid discoveries to do so. 99942 Apophis had the highest, briefly hitting a rating of 4 for its 2029 pass, after discovery in 2004. As is usually the case, further observations including ones tasked to JWST shrunk the potential for an Earth impact to zero. However, the chances of a lunar impact actually crept upward, and now stand at 4%.

    More observations are needed before we’ll know for sure. Unfortunately, we’ll have to wait to refine the orbit of 2024 YR4 further. On a 4 year orbit around the Sun, the asteroid ranges from a perihelion 0.85 AU from the Sun, out to an aphelion in the asteroid belt at 4.18 AU distant. Next aphelion for the asteroid is set for November 22nd, 2026.

    Bruno Crater; an impact from 2024 YR4 may produce a similar result. Credit: NASA/LRO Bruno Crater; an impact from 2024 YR4 may produce a similar result. Credit: NASA/LRO

    What if asteroid 2024 YR4 actually hit the Moon? The Moon phase at impact will be 70% illuminated, waning gibbous on December 22nd, 2032 around 15:20 Universal Time (UT), the approximate time that 2024 YR4 will be in the vicinity of the Moon. Viewing would favor the Pacific Ocean region… though it’s uncertain at this point just what area of the Moon the asteroid would strike, if it hits the Moon at all. Certainly, the near nighttime side would be favorable for observation. The asteroid will be approaching the Earth from the direction of Sagittarius (the same constellation the Sun crosses in late December).

    An impression of a small asteroid striking the gibbous Moon. Credit: Created by the author using ChatGPT. An impression of a small asteroid striking the gibbous Moon. Credit: Created by the author using ChatGPT.

    Protecting the Planet From Sunward Space Rocks

    Clearly there’s lots more out there to discover in terms of near-Earth asteroids. Vera Rubin revealed an amazing 2,104 new asteroids on its first run. NASA still plans to launch their NEO Surveyor mission to scout for asteroids in September 2027. The mission survived the current budget FY2026 cuts and passed its Critical Design Review phase earlier this year.

    The European Space Agency (ESA) also has plans to hunt for asteroids using space-based assets as well. ESA’s Near Earth Object Mission in the Infrared (NEOMIR) will head to the Sun-Earth L1 point. This location is the home of the Solar Heliospheric Observatory (SOHO), the Deep Space Climate Observatory (DSCOVR) and more. Launching in the 2030s, NEOMIR would use its infrared ‘eyes’ to scour the sky, detecting objects such as 2024 YR4 before they came close to the Earth.

    NEOMIR in space. Credit: ESA NEOMIR in space. Credit: ESA

    “We looked at how NEOMIR would have performed in this situation, and the simulations surprised even us,” says Richard Moissl (Head of ESA’s Defense Office) in a recent press release, referring to the expected performance of NEOMIR. “NEOMIR would have detected asteroid 2024 YR4 about a month earlier than ground-based telescopes did. This would have given astronomers more time to study the asteroid’s trajectory and allowed them to much sooner rule out any chance of Earth impact in 2032.”

    A lunar impact would give astronomers a first-ever opportunity to witness such an event first-hand…and study such an event like never before. And heck, it would put on a show for amateur astronomers as well (assuming it doesn’t hit the lunar farside). Is it wrong that I kind of want to see this happen?

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  • Acute Myocardial Infarction Due to Spontaneous Coronary Dissection in

    Acute Myocardial Infarction Due to Spontaneous Coronary Dissection in

    Introduction

    Over 33.3% of pregnancy-related deaths are due to cardiovascular diseases, with acute myocardial infarction (AMI) being a significant contributor to maternal mortality.1 While the risk of AMI during pregnancy and the early postpartum period is relatively low (6 to 10 cases per 100,000 pregnancies), it is three times higher compared to non-pregnant women of reproductive age.2,3 Pregnant women who experience AMI have a 22-fold higher in-hospital mortality risk, with a 37% mortality rate and the potential loss of both mother and child.1,4 In the past 20 years, the incidence of AMI in pregnancy has increased, likely due to the rising average maternal age and greater prevalence of risk factors.5,6 The etiology of AMI also differs significantly. In the general population, most cases result from atherosclerotic coronary artery disease. However, among pregnant women, approximately 40% of AMI cases are associated with spontaneous coronary artery dissection (SCAD). Atherosclerosis accounts for around 27% of cases, while myocardial infarction with non-obstructive coronary arteries (MINOCA) represents up to 29%.2,7,8

    The pathophysiology of SCAD remains unclear and likely multifactorial. It involves spontaneous coronary artery dissection due to an intramural hematoma, with or without intimal rupture.7,8 SCAD is often linked to arteriopathies, connective tissue disorders, and autoimmune diseases.8 Pregnant women, especially in the third trimester and postpartum, are at higher risk, particularly those who have undergone infertility treatment, including in vitro fertilisation.9–11

    Case Report

    A 28-year-old female, gravida 3, at 37 weeks of gestation, was admitted to the district central hospital via emergency medical services with complaints of a single episode of vomiting, nausea, constrictive retrosternal pain, and a sensation of rapid heartbeat. She attributed the onset of symptoms to the consumption of a low-alcohol beverage the previous evening (300 mL of light beer) along with potato chips.

    Her medical history revealed a prior smoking habit, with a four-year history of tobacco use, smoking up to 15 cigarettes per day (pack-year index: 3). She discontinued smoking upon conception of the current pregnancy. Her family history was unremarkable for cardiovascular disease, connective tissue disorders, or sudden cardiac death. The patient’s obstetric history included a spontaneous miscarriage at 11 weeks of gestation in 2015. In 2018, she had an uncomplicated full-term pregnancy, resulting in a vaginal delivery of a healthy female neonate weighing 3300 g.

    The emergency medical team administered antispasmodics with minimal effect. The time from the onset of symptoms to hospitalization was 7 hours. An electrocardiogram (ECG) was performed immediately upon arrival (Figure 1, ECG from 24.09.23), showing no signs of acute ischemia. Troponin I was measured at 0.10 ng/mL (normal value: up to 0.16 ng/mL). Routine laboratory tests showed elevated total cholesterol (TC) at 7.03 mmol/L, low-density lipoprotein cholesterol (LDL-C) at 4.70 mmol/L, high-density lipoprotein cholesterol (HDL-C) at 1.48 mmol/L, and triglycerides (TG) at 2.74 mmol/L. These findings were considered physiological for late pregnancy and not indicative of a primary lipid disorder.

    Figure 1 Initial ECG recording taken on admission. No signs of acute ischemia are seen.

    Upon admission, the patient continued to experience recurrent episodes of constricting retrosternal pain. A repeat investigation was performed, revealing a significant rise in troponin I levels, which was 14.31 ng/mL, 4 hours after hospitalization. The repeat ECG (Figure 2, ECG from 24.09.23) showed ST-segment elevation in leads I, aVL, and V4-V6, with reciprocal ST depression in leads II, III, aVF, and negative T-waves in leads I and aVL. Echocardiography demonstrated septal and anterior left ventricular wall hypokinesis with left ventricular ejection fraction of 50%. Given the patient’s clinical symptoms, ECG findings, and the increase in myocardial necrosis markers, along with input from relevant specialists, the decision was made to transfer the patient to a center capable of providing specialized care.

    Figure 2 Follow-up ECG displaying ST-segment elevation and reciprocal changes, indicating acute ischemic injury.

    Thus, the patient was admitted to the intensive care unit of the maternity hospital for further observation and continuous cardio-respiratory monitoring. An ultrasound was immediately performed in the obstetrics department to assess the fetal condition. At the time of admission, the patient did not report any complaints, and the ECG showed no abnormalities. Considering the transient, rapidly evolving changes on the ECG, which were clearly associated with retrosternal pain, and the significant rise in myocardial necrosis markers over time, a presumed diagnosis of acute type 2 myocardial infarction was made.

    A decision was reached to proceed with conservative management, and the patient was started on enoxaparin 0.4 mL twice daily subcutaneously and acetylsalicylic acid (ASA) 100 mg once daily. The following day, the patient again complained of severe retrosternal pain, which did not alleviate despite the administration of nitrates and required opioid analgesics. In response, an echocardiogram was immediately performed, revealing hypokinesis of the anterior segment of the left ventricular wall. The repeat ECG (Figure 3, ECG from 26.09.23) was registered. The aforementioned changes were interpreted as an expansion of AMI, prompting the decision to proceed with urgent coronary angiography to determine the subsequent treatment strategy. During the coronary angiography, a femoral access was used. A long dissection in the mid-distal segment of the left anterior descending artery (LAD) was noted (Figure 4A). Two Resolute Integrity (DES) stent systems were then implanted using the “stent-in-stent” technique. Follow-up angiography showed complete stent deployment in the LAD, with adequate positioning and restoration of the main blood flow through the LAD (TIMI – 3; TIMI myocardial perfusion grade – 3) (Figure 4B). No significant narrowings were identified in the left circumflex artery or the right coronary artery.

    Figure 3 ECG taken during symptom recurrence, revealing expansion of ischemic changes.

    Figure 4 (A) Coronary angiography identifying a long dissection in the left anterior descending artery (arrow). (B) Post-stenting angiography confirming restored blood flow in the affected artery (ellipse).

    Following PCI, clopidogrel (75 mg once daily) and bisoprolol (1.25 mg once daily) were added to the patient’s treatment regimen. Regarding pregnancy management, multiple consultations were held with a multidisciplinary team comprising specialists in obstetrics and cardiology. The patient remained under continuous surveillance in the high-risk obstetric intensive care unit. Given the gestational age of 37–38 weeks and the elevated risk associated with surgical delivery, adjustments were made to the antiplatelet and anticoagulant therapy. Specifically, clopidogrel was discontinued, and enoxaparin was replaced with heparin. Heparin was administered at a dose of 7,000 IU every six hours, with activated partial thromboplastin time monitoring. It was recommended that the final dose be administered no later than four hours before the planned delivery.

    At 39 weeks of gestation, due to the onset of spontaneous labor and rupture of membranes in the presence of a pure breech presentation, a decision was made to proceed with delivery via cesarean section. A female neonate was delivered, weighing 3,300 g and measuring 54 cm in length, with Apgar scores of 8/8. On postoperative day 4, the patient and her newborn were discharged home. Recommendations were provided regarding ongoing pharmacological therapy, specifically the continuation of DAPT (ASA and clopidogrel) for the next 12 months.

    The subsequent follow-up period was uneventful. At 4 months postpartum, her lipid profile had normalized: total cholesterol 4.71 mmol/L, LDL-C 2.9 mmol/L, HDL-C 1.54 mmol/L, and triglycerides 0.93 mmol/L, supporting the interpretation that the earlier elevation was related to physiological gestational changes. One year after myocardial infarction, ECG revealed persistent scarring at the apex extending to the interventricular septum, mild ST-segment elevation, and biphasic T waves in leads V3–V4 (Figure 5, ECG from 11.11.2024). Echocardiography showed a preserved left ventricular ejection fraction. No clinical evidence of a vascular or systemic connective tissue disorder has been observed during the one-year follow-up to date.

    Figure 5 Follow-up ECG one year later, showing residual non-specific ST-T abnormalities.

    Discussion

    Cardiovascular risk factors in pregnancy are consistent with those in the general population, including a family history of cardiovascular disease, dyslipidemia, diabetes, and smoking.12 Pregnancy-specific factors include polycystic ovary syndrome, early menarche, maternal age over 35, gestational diabetes, pre-eclampsia, and hormonal therapy use.13

    Although the patient had ceased smoking during pregnancy, her prior tobacco use may have contributed to vascular vulnerability. Several studies have identified smoking as a potential risk factor for SCAD, both in pregnancy-associated and non-pregnancy cases, likely due to its role in vascular inflammation and endothelial dysfunction. In particular, a meta-analysis of women with SCAD, smoking was among the most frequently reported cardiovascular risk factors, present in nearly a quarter of cases.14 Another study found a significant association between smoking and increased mortality in SCAD patients.15

    Similarly, while gestational hyperlipidemia has been proposed to influence vascular function through mechanisms such as endothelial dysfunction or oxidative stress, its direct role in SCAD remains unproven. SCAD is typically not associated with lipid deposition or coronary atherosclerotic plaque.16 During pregnancy, physiological hyperlipidemia is well recognized: total cholesterol and LDL-C typically rise by 30–50%, triglycerides by 50–100%, and HDL-C by 20–40% as gestation progresses.17 The patient’s third-trimester lipid profile was consistent with these expected changes, and normalization at follow-up supported the interpretation of a transient physiological response. These findings underscore the importance of interpreting lipid values in pregnancy within trimester-specific reference ranges, rather than assuming pathological significance in isolation.

    Pregnancy-related SCAD likely results from increased shear stress, elevated progesterone reducing arterial elasticity, and estrogen-induced hypercoagulation and collagen inhibition. Increased cardiac output and blood volume further contribute. It often affects major coronary arteries, leading to reduced ejection fraction and severe maternal-fetal complications.18–23

    Managing patients with pregnancy-related SCAD is challenging, particularly in diagnosing the condition. In 70% of cases, SCAD presents with typical ST-segment elevation on ECG.24 However, nearly one-third of patients show no ECG signs of coronary circulation impairment.10,25 In the presented clinical case, early ECG showed a transient ST elevation in the anterior-lateral wall, which resolved after pain relief, initially suggesting vasospastic angina. The key indicator of myocardial injury was the sustained rise in troponin I levels. Notably, troponin is preferred over CK-MB in pregnant women, as CK-MB can rise due to uterine contractions or cell breakdown during delivery, with lower specificity in pregnancy and postpartum.26

    Given the absence of pronounced clinical symptoms at the time of our patient’s transfer, a conservative treatment approach was initially chosen. However, this was later reassessed due to the recurrence of symptoms (angina, vomiting), accompanied by deteriorating ECG changes and severe arrhythmias. There is no consensus on the preferred management strategy for pregnant women with AMI, and each case requires an individual approach. Conservative management of SCAD not related to pregnancy has shown better outcomes than in pregnant women and the early postpartum period.9,23,24 In pregnant women with SCAD, coronary interventions were associated with a higher risk of dissection progression and the occurrence of new iatrogenic dissections during the procedure.23–25 Additionally, concern arises over the potential impact of X-ray exposure on the fetus during coronary angiography (CAG). During CAG, the patient’s radiation dose is less than 20 mGy, while the fetal radiation dose is estimated at 0.074 mGy.27 The teratogenic risk to the fetus is minimal for doses below 50 mGy and potentially fatal for doses above 150 mGy, depending on gestational age.28 Therefore, it can be concluded that the radiation dose during coronary angiography is generally safe for most pregnant patients.29 An alternative option is the use of computed tomography coronary angiography, particularly in non-ST elevation myocardial infarction patients, but it may cause delays and is not always effective in detecting small areas of dissection.30 The access route for percutaneous intervention is also crucial. Radial access, as opposed to femoral access, reduces radiation exposure to the fetus, as it avoids direct X-ray exposure, making it more often recommended for pregnant women. Moreover, radial access is associated with a lower risk of complications, such as bleeding.31 However, some studies suggest that femoral access may be more effective for pregnant women with SCAD, as it has been linked to nearly three times fewer iatrogenic dissections compared to radial access.32,33 In our patient, femoral access was used, and no expansion of the dissection zone was observed during the procedure.

    Pharmacological management, particularly dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI), has specific considerations. According to the latest European Society of Cardiology guidelines, clopidogrel is recommended as part of DAPT in pregnant women post-PCI, as it is considered safer than glycoprotein IIb/IIIa inhibitors, due to a lack of data on their use in pregnancy.10 However, there are no clear guidelines on the duration of DAPT during labour for patients at high risk of thrombosis or those with recent intervention. Some studies show positive outcomes, while others report serious side effects from prolonged DAPT use.25 A decision was made to continue long-term DAPT, with a short-term discontinuation of clopidogrel before the planned cesarean section. After discharge, the patient continued DAPT for 12 months with no complications.

    While the case highlights key aspects of diagnosis and management, it also has certain limitations. These are inherent to a single-patient observation. Intravascular ultrasound or optical coherence tomography was not performed, which might have provided more precise characterization of the arterial dissection. Additionally, no further investigations were undertaken to evaluate possible underlying vascular or connective tissue disorders. However, the case reflects real-world clinical complexity, where decisions must often be made based on evolving symptoms and limited diagnostic data.

    Conclusion

    The issue of myocardial infarction during pregnancy involves several aspects, including challenges in emergency diagnosis due to a low index of suspicion among young women without traditional risk factors, as well as the absence of clear, definitive algorithms for selecting a management strategy (conservative/invasive). Additionally, there is uncertainty regarding the volume and duration of anticoagulant and antiplatelet therapy. Since the likelihood of conducting randomized clinical trials among pregnant women is quite limited and problematic, the accumulation of sufficient clinical case reports from real-world practice will, in the future, allow for the formulation of a well-founded expert opinion and evidence-based recommendations for managing this patient cohort.

    Date and Materials Statement

    This is a case report without statistical analysis of the raw medical record data. All medical data involving the patient were documented in the patient’s medical records. If necessary, more detailed imaging data or laboratory data can be provided by the corresponding author upon reasonable request.

    Ethics Statement

    Ethical review and approval were not required for the study involving human participants in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the patient for the publication of any potentially identifiable images or data included in this report.

    Informed Consent for Publication

    The patient agreed to publish her medical data including imaging data and laboratory data, and signed the informed consent.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Funding

    This study was not supported by any external funds.

    Disclosure

    All the authors declare that they have no conflicts of interest in this medical case report and have not received any financial support.

    References

    1. Markson F, Shamaki RG, Antia A, Osabutey A, Ogunniyi MO. Trends in the incidence and in-patient outcomes of acute myocardial infarction in pregnancy: insights from the national inpatient sample. Am Heart J Plus. 2023;34:100318. doi:10.1016/j.ahjo.2023.100318

    2. Smilowitz NR, Gupta N, Guo Y, et al. Acute myocardial infarction during pregnancy and the puerperium in the United States. Mayo Clin Proc. 2018;93(10):1404–1414. doi:10.1016/j.mayocp.2018.04.019

    3. James AH, Jamison MG, Biswas MS, Brancazio LR, Swamy GK, Myers ER. Acute myocardial infarction in pregnancy: a United States population-based study. Circulation. 2006;113(12):1564–1571. doi:10.1161/CIRCULATIONAHA.105.576751

    4. Burlingame J, Horiuchi B, Ohana P, Onaka A, Sauvage LM. The contribution of heart disease to pregnancy-related mortality according to the pregnancy mortality surveillance system. J Perinatol. 2012;32(3):163–169. doi:10.1038/jp.2011.74

    5. Balgobin CA, Zhang X, Lima FV, et al. Risk factors and timing of acute myocardial infarction associated with pregnancy: insights from the national inpatient sample. J Am Heart Assoc. 2020;9(21):e016623. doi:10.1161/JAHA.120.016623

    6. Gédéon T, Akl E, D’Souza R, et al. Acute myocardial infarction in pregnancy. Curr Probl Cardiol. 2022;47(11):101327. doi:10.1016/j.cpcardiol.2022.101327

    7. Elkayam U, Jalnapurkar S, Barakkat MN, et al. Pregnancy-associated acute myocardial infarction: a review of contemporary experience in 150 cases between 2006 and 2011. Circulation. 2014;129(16):1695–1702. doi:10.1161/CIRCULATIONAHA.113.002054

    8. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al. ESC scientific document group. 2018 ESC guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165–3241. doi:10.1093/eurheartj/ehy340

    9. Saw J, Humphries K, Aymong E, et al. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol. 2017;70(9):1148–1158. doi:10.1016/j.jacc.2017.06.053

    10. Lebrun S, Bond RM. Spontaneous coronary artery dissection (SCAD): the underdiagnosed cardiac condition that plagues women. Trends Cardiovasc Med. 2018;28(5):340–345. doi:10.1016/j.tcm.2017.12.004

    11. Zeven K. Pregnancy-associated spontaneous coronary artery dissection in women: a literature review. Curr Ther Res. 2023;98:100697. doi:10.1016/j.curtheres.2023.100697

    12. Kealey A. Coronary artery disease and myocardial infarction in pregnancy: a review of epidemiology, diagnosis, and medical and surgical management. Can J Cardiol. 2010;26(6):185–189. doi:10.1016/s0828-282x(10)70397-4

    13. Nguyen AH, Murrin E, Moyo A, et al. Ischemic heart disease in pregnancy: a practical approach to management. Am J Obstet Gynecol MFM. 2024;6(3):101295. doi:10.1016/j.ajogmf.2024.101295

    14. Apostolović S, Ignjatović A, Stanojević D, et al. Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis. Front Cardiovasc Med. 2024;11:1277604. doi:10.3389/fcvm.2024.1277604

    15. Adams C, He M, Hughes I, Singh K. Mortality in spontaneous coronary artery dissection: a systematic review and meta-analysis. Catheter Cardiovasc Interv. 2021;98(7):1211–1220. doi:10.1002/ccd.29488

    16. Stanojevic D, Apostolovic S, Kostic T, et al. A review of the risk and precipitating factors for spontaneous coronary artery dissection. Front Cardiovasc Med. 2023;10:1273301. doi:10.3389/fcvm.2023.1273301

    17. Mulder JWCM, Kusters DM, Roeters van Lennep JE, Hutten BA. Lipid metabolism during pregnancy: consequences for mother and child. Curr Opin Lipidol. 2024;35(3):133–140. doi:10.1097/MOL.0000000000000927

    18. Maas AHEM, Bouatia-Naji N, Persu A, Adlam D. Spontaneous coronary artery dissections and fibromuscular dysplasia: current insights on pathophysiology, sex and gender. Int J Cardiol. 2019;286:220–225. doi:10.1016/j.ijcard.2018.11.023

    19. Yip A, Saw J. Spontaneous coronary artery dissection – a review. Cardiovasc Diagn Ther. 2015;5(1):37–48. doi:10.3978/j.issn.2223-3652.2015.01.08

    20. Giacoppo D, Capodanno D, Dangas G, Tamburino C. Spontaneous coronary artery dissection. Int J Cardiol. 2014;175(1):8–20. doi:10.1016/j.ijcard.2014.04.178

    21. Vijayaraghavan R, Verma S, Gupta N, Saw J. Pregnancy-related spontaneous coronary artery dissection. Circulation. 2014;130(21):1915–1920. doi:10.1161/CIRCULATIONAHA.114.011422

    22. Abbott JD, Curtis JP, Murad K, et al. Spontaneous coronary artery dissection in a woman receiving 5-fluorouracil: a case report. Angiology. 2003;54(6):721–724. doi:10.1177/000331970305400613

    23. Havakuk O, Goland S, Mehra A, Elkayam U. Pregnancy and the risk of spontaneous coronary artery dissection: an analysis of 120 contemporary cases. Circ Cardiovasc Interv. 2017;10(3):e004941. doi:10.1161/CIRCINTERVENTIONS.117.004941

    24. Tweet MS, Hayes SN, Codsi E, Gulati R, Rose CH, Best PJM. Spontaneous coronary artery dissection associated with pregnancy. J Am Coll Cardiol. 2017;70(4):426–435. doi:10.1016/j.jacc.2017.05.055

    25. Lindor RA, Tweet MS, Goyal KA, et al. Emergency department presentation of patients with spontaneous coronary artery dissection. J Emerg Med. 2017;52(3):286–291. doi:10.1016/j.jemermed.2016.09.005

    26. Siromakha SO, Arvanytakvy SS, Rudenko SA, Lazorishenetc VV. Coronary insufficiency during pregnancy. Epidemiology, methods of diagnosis and treatment. Ukr J Perinatol Pediatr. 2019;3:32–39. doi:10.15574/PP.2019.79.32

    27. Colletti PM, Lee KH, Elkayam U. Cardiovascular imaging of the pregnant patient. Am J Roentgenol. 2013;200(3):515–521. doi:10.2214/AJR.12.9864

    28. Kuba K, Wolfe D, Schoenfeld AH, Bortnick AE. Percutaneous coronary intervention in pregnancy: modeling of the fetal absorbed dose. Case Rep Obstet Gynecol. 2019;2019:8410203. doi:10.1155/2019/8410203

    29. Alameh A, Jabri A, Aleyadeh W, et al. Pregnancy-associated myocardial infarction: a review of current practices and guidelines. Curr Cardiol Rep. 2021;23:142. doi:10.1007/s11886-021-01579-z

    30. Joshi FR. CT rather than invasive angiography for pregnant patients with NSTEMI?: More delay and more radiation. J Am Coll Cardiol. 2016;68(24):2716–2717. doi:10.1016/j.jacc.2016.08.075

    31. Prokšelj K, Brida M. Cardiovascular imaging in pregnancy. Int J Cardiol Congenit Heart Dis. 2021;5(Suppl. 1):100235. doi:10.1016/j.ijcchd.2021.100235

    32. Prakash R, Starovoytov A, Heydari M, Mancini GB, Saw J. Catheter-induced iatrogenic coronary artery dissection in patients with spontaneous coronary artery dissection. JACC: Cardiovasc Interv. 2016;9(17):1851–1853. doi:10.1016/j.jcin.2016.06.026

    33. Hayes SN, Kim ESH, Saw J, et al. Spontaneous coronary artery dissection: current state of the science: a scientific statement from the American heart association. Circulation. 2018;137(19):e523–e557. doi:10.1161/CIR.0000000000000564

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  • Gary Lineker says BBC should ‘hold its head in shame’ for dropping Gaza film | BBC

    Gary Lineker says BBC should ‘hold its head in shame’ for dropping Gaza film | BBC

    Gary Lineker has said the BBC should “hold its head in shame” over its failure to show a documentary about the plight of medics in Gaza.

    The former Match of the Day presenter said people at “the very top of the BBC” had been failing over the conflict, following the corporation’s controversial decision to drop Gaza: Doctors Under Attack.

    It is the first time Lineker has criticised his former employer since he left the broadcaster in May. His departure came after he apologised for amplifying online material with antisemitic connotations. He had reposted a video about Gaza that contained a picture of a rat, imagery used in the Nazi era to attack Jews.

    A clearly emotional Lineker was speaking at a private viewing of the Gaza medics documentary in London on Thursday night, where he led a question and answer session with the producers after the showing.

    “It needed to be seen, it really did need to be seen – I think everyone would agree with that,” he said. “I think the BBC should hold its head in shame.

    “As someone who’s worked for the corporation for 30 years, to see the way it’s declined in the last year or two has been devastating really, because I’ve defended it and defended it against claims that it’s partial. It talks about impartiality all the time.

    “The truth is at the moment, [there is a problem] at the very top of the BBC. Not [all] the BBC because there are thousands and thousands of people that work at the BBC, that are good people, that understand what is going on here and can see it. We see it on our phones every day. The problem is they’re bowing to the pressure from the top. This is a worry and I think time’s coming where a lot of people are going to be answerable to this, and complicity is something that will come to many.”

    The BBC Radio 5 presenter Nihal Arthanayake responded to a video of Lineker’s comments by saying: “Gary Lineker is a good man. He is spot on about the BBC.”

    The BBC has been approached over his comments. It has previously said it had been attempting to find ways to use the documentary material in news coverage, but a final decision was made to drop the film entirely after talks broke down with its producers, Basement Films.

    There has been considerable internal unrest over the failure to broadcast the programme, with the director general, Tim Davie, facing questions about it at a recent virtual meeting with staff. More than 100 BBC staff signed a letter criticising the decision to drop the film.

    It ends a torrid week for the BBC, which has also been hit with the fallout from its failure to cut the live feed of Bob Vylan’s Glastonbury performance. Davie has come under significant pressure from ministers over the broadcast. During the live stream, Bobby Vylan, whose real name is Pascal Robinson-Foster, led chants of “death, death to the IDF”, referring to the Israel Defense Forces, at Glastonbury last Saturday.

    While Davie has received a vote of confidence from the BBC board and its chair, Samir Shah, more junior figures appear to be expected to take the blame for the incident. There have been unconfirmed reports that Lorna Clarke, who oversees pop music commissioning at the BBC, has stood back from her duties.

    A BBC spokesperson said: “We would urge people not to speculate, particularly in relation to any individuals.”

    BBC insiders have pointed to editorial cuts as fuelling issues around the monitoring of live streams. One said many of the BBC staff who worked on Glastonbury were volunteers from other teams, especially on digital-only streams.

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  • ‘The bubble had to burst’ – the inside story of the Lindsey oil refinery collapse | Oil

    ‘The bubble had to burst’ – the inside story of the Lindsey oil refinery collapse | Oil

    It was mid-April and the government had just finished nationalising British Steel, to prevent thousands of job losses at the Scunthorpe steelworks, when word reached Whitehall that another national infrastructure asset was wobbling.

    Prax Group, owner of the Lindsey oil refinery on the Humber estuary in northern England, was rumoured to be in financial trouble, stoking fears about jobs and disruption to critical fuel supplies.

    In a hastily arranged meeting at the department for energy security and net zero (DESNZ) on 13 May, well-placed sources said, a concerned Ed Miliband, the energy secretary, took solace from Prax’s owner and sole director, Winston Soosaipillai.

    Prax had suffered some setbacks, the seldom-seen oil boss is understood to have said, but it was not in any imminent danger and was even planning investment for the future. Within weeks, these assurances had crumbled to dust.

    By Friday of last week, ministers had been informed that Prax could not pay its debts – including sums owed to HM Revenue and Customs that the Financial Times reported had reached up to £250m – and was headed for insolvency. The shock update put 625 jobs at risk and sent officials scrambling to keep the refinery going. By Monday, administrators had been called in.

    The refinery’s main supplier, Glencore, initially agreedto provide its crude oil for free while the government began its search for a buyer, in what one person close to the situation described as a “gesture of goodwill”. A deal has since been reached that will see Glencore paid out of taxpayers’ funds.

    Winston Soosaipillai. Photograph: Prax Group

    The company’s sudden collapse blind-sided the government and even Glencore, famed for the global intelligence network that informs its trading activity. But to Prax insiders, it came as no surprise.

    Multiple sources, including former staff, described a house of cards stacked on increasingly unstable foundations due its owners’ insatiable thirst for debt-fuelled growth, building an empire which included the refinery, trading in oil and petrol stations.

    Prax’s recent woes, one former employee claimed, began to spiral out of control more than a year before the government got wind that anything was wrong.

    “They started the process of reducing costs in March 2024,” said the source. “They sold petrol station stores and made hundreds of people redundant. The strategy was to get salaries out of the company. The mood was horrible.”

    The accountancy firm Deloitte was parachuted in during 2023 to run a “performance improvement programme”, in effect taking charge of the business for about three months. One of its consultants was installed as a joint-chief executive the following year, a sharing of power that took place under the codename “Project King”.

    It was an apt choice of name, for Soosaipillai was the de facto king of Prax.

    Better known by his middle names, Sanjeev Kumar, Soosaipillai owned and ran the business alongside his wife, Arani, the company’s head of human resources, for 25 years.

    They hold 80% of the equity directly and 20% through family trusts.

    The Lindsey oil refinery in Lincolnshire. Photograph: Alamy

    That, in itself, is unusual, in an industry dominated by global corporations such as ExxonMobil and India’s Essar, overseen by teams of seasoned executives.

    Soosaipillai, in contrast, is the sole director of Lindsey and the wider Prax Group, Companies House filings show.

    Former employees said that even senior staff knew little about company strategy or dealings, with information tightly controlled among a tiny, close-knit group.

    This heavily top-down structure reflects the company’s extraordinary growth story.

    The Soosaipillais bought their first petrol station in 1999, expanding into the importing, blending and storage of fuels.

    They ran State Oil, as the business was then known, from a modest £65,000 flat in Weybridge, Surrey, building a multinational oil and gas business with billions in revenue and 1,300 staff in a little over two decades.

    Contemporary reports – and former employees – suggest the business began to take off with the recruitment in 2009 of a lawyer and oil trader called Don Camillo.

    By 2014, with Camillo’s help, the business was fuelling regular profits, not to mention a steady and increasing stream of dividends that helped the Soosaipillais move into a £4.5m mansion in St George’s Hill, the Surrey estate better known as the bolthole of Russian oligarchs.

    The business continued to grow, via the 2015 acquisition of fuel retail business Harvest Energy and later via the surprise purchase in 2021 of the Lindsey oil refinery from French oil company Total for nearly $170m (£125m).

    The deal more than tripled the group’s revenues, to nearly $10bn, but also sent debts soaring.

    Annual interest payments had rocketed from $19m to $79m by 2023, surging again to $133m in 2024. Prax recorded a $75m loss. Its total liabilities had reached $2.3bn, nearly 10 times the level immediately before the Lindsey takeover.

    A Union flag flies outside the Prax Lindsey oil refinery in North Killingholme, England. Photograph: Lindsey Parnaby/AFP/Getty Images

    In a letter to staff, sent shortly after administrators were appointed, Soosaipillai acknowledged that the cost of operating Prax Lindsey had become “increasingly unsustainable” and that this had spread into the rest of the group due to its divisions’ “interdependent” nature.

    Yet, even as the debt pile was mounting, supply deals with global oil traders – first Trafigura and then Glencore – ensured a constant flow of crude.

    The refinery is the smallest of the five that remain in the UK since Grangemouth, in Scotland, stopped processing crude earlier this year.

    But, at 5.4m tonnes annually, it still accounts for nearly 10% of national capacity, supplying everything from petrol forecourts to Heathrow airport.

    Owning such a strategically important asset has proved lucrative.

    As the Guardian revealed earlier this week, the husband and wife owners have extracted about £11.5m in pay and dividends since the Lindsey deal alone.

    Yet the couple, who are said to be extremely publicity-shy, did not flaunt their wealth.

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    “He is very quiet and studious,” said a former supplier, who asked not to be named. “There is nothing flash about them. They drive a 10-year-old Land Rover to work.”

    But the vaulting ambition that helped Prax grow came with a darker side, according to some accounts.

    The supplier fell out with Soosaipillai when Prax, he says, inexplicably refused to pay invoices worth tens of thousands. The company only coughed up after a threat of legal action, he alleges.

    Others referred to a ruthless streak in Soosaipillai, who allegedly viewed mass redundancies and severe cost-cutting as the solution to strategic missteps.

    This, two sources said, sometimes led to instability as people with operational expertise left after short tenures.

    The sun rises over Lindsey oil refinery in North Lincolnshire. Photograph: Christopher Furlong/Getty Images

    Ministers got a taste of the company’s sometimes chaotic modus operandi last month, when Prax suddenly admitted that it was at risk of insolvency after all.

    Officials asked for financial information to help them assess the scale of the problem. Despite repeated requests, Prax refused.

    The near-term cause of the collapse remains a mystery, although one source close to the situation claimed that Prax could not pay its debts to HM Revenue and Customs.

    Anyone keeping a close eye on corporate filings might have seen the warning signs.

    Even before “Project King”, Prax’s annual accounts had been restated several times in the past few years to reflect a worse position than before.

    In 2023, the company attempted to pay a dividend to the Soosaipillais, only to admit that it didn’t have enough cash in its distributable reserves. The payout had to be reversed and reclassified for accounting purposes.

    Nevertheless, industry experts were not expecting Prax Lindsey to fail.

    Long-term conditions have been tough in Europe, amid falling demand for carbon-based fuel, high electricity costs, and fierce competition from rivals in Asia, the Middle East and Africa.

    But Alan Gelder, a refining expert at global energy and mining consultancy Wood Mackenzie, said margins have been much better in the first half of 2025 due to tight capacity in the market.

    “It surprised us,” said Gelder. “[Lindsey] was an OK asset, not brilliant but probably cash positive.”

    One former employee put the failure down to a culture of relentless expansion.

    Arani Kumar. Photograph: Prax Petroleum

    As well as large takeovers of assets of questionable quality, such as Lindsey, there was an abortive venture in Nigeria and a vain attempt to buy Shell’s business in Pakistan.

    And, although Prax carried itself like a global player, it didn’t behave like one, sources said.

    “They were still working as they were when they started in a flat in Weybridge, doing things as if they had only one petrol station,” said one former employee.

    “Every few years they’d take on a bigger acquisition and eventually I think it was too much,” said the other. “The bubble had to burst at some point.”

    The government has now ordered the Insolvency Service to investigate the conduct of “directors”. In practice, that means Soosaipillai alone.

    Soosaipillai wrote in his letter to staff that he was “deeply sorry”. Those employees must now wait to see if government officials can find a buyer to secure the future of his precarious realm.

    As one current employee put it: “We’re just sitting around, waiting for the guillotine to fall.”

    The Soosaipillais did not return requests for comment.

    The Guardian approached someone believed to be Don Camillo for comment. He denied being Camillo and hung up the phone.

    Deloitte declined to comment.

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  • The existentialist philosophy of Lana Del Rey

    The existentialist philosophy of Lana Del Rey

    Speaking to Myspace as an upcoming artist in 2013, Lana Dey Rey said that the “vision of making [her] life a work of art” was what inspired her to create her music video for her breakthrough single, Video Games (2011).

    The self-made video, featuring old movies clips and webcam footage of Del Rey singing, went viral. It eventually led her to sign with a major record label. For many, the video conveyed a sense of authenticity. However, upon discovering that “Lana Del Rey” was a pseudonym (her real name is Elizabeth Grant), some fans began to have doubts. Perhaps this self-made video was just another calculated marketing scheme?

    The question of Del Rey’s authenticity has puzzled many throughout her career. Consider, for instance, the controversial Judah Smith Interlude from her latest album, Did You Know That There’s a Tunnel Under Ocean Blvd? (2023). Both fans and critics – including her sizeable LGBTQ+ fanbase – were surprised and troubled by her decision to feature the megachurch pastor Judith Smith, who’s been accused of homophobia.

    However, the meaning of Del Rey’s inclusion of Smith’s sermon soundclips, layered under a recording of Del Rey giggling, is unclear. Is this meant to mock Smith, or even Christianity itself? Or is it an authentic expression of Del Rey’s own spirituality? After all, she repeatedly makes references to her “pastor” in the same album’s opening track The Grants, about her family in real life.

    Looking for something good? Cut through the noise with a carefully curated selection of the latest releases, live events and exhibitions, straight to your inbox every fortnight, on Fridays. Sign up here.

    Before she became a singer-songwriter, Del Rey gained her philosophy degree at Fordham University. It was the mid-2000s, when the eminent existentialism scholar Merold Westphal would have been on staff, so she probably studied theories of authenticity by existentialists such as Jean-Paul Sartre (1905–80) and Martin Heidegger (1889–1976). Heidegger spoke of human existence as a “being-towards-death”. Or as Del Rey sings in the title track of her first major-label album, “you and I, we were born to die”.

    In Heidegger’s view, to pretend that we are not all bound to die is to deny the kind of finite beings which we are: it is to disown ourselves and exist inauthentically. Conversely, to exist authentically is to accept our own mortality and embrace the way we exist as finite beings.

    The music video for Video Games.

    In this understanding, to exist authentically does not mean the expression of some underlying “true self” or “human nature”. Rather, it is to accept the conditions of life in which we find ourselves.

    ‘An obsession for freedom’

    For existentialist philosophers, such conditions include not only mortality but also freedom – a theme particularly emphasised by Sartre.

    As Sartre says in his 1946 lecture Existentialism Is a Humanism, existentialism holds that “there is no human nature, because there is no God to have a conception of it … Man is nothing else but that which he makes of himself”.

    Jean-Paul Sartre in front of a window full of flowers
    Jean-Paul Sartre in Venice in 1967.
    Wiki Commons, CC BY-SA

    With no creator God or pre-established human nature to determine human destiny or purpose, Sartre teaches that human beings are “condemned to freedom”. We are free beings who are always acting freely – whether we acknowledge that we are free or not. To pretend that we are not free is to be inauthentic.

    Sartre suggests embracing our freedom means living life in a manner “comparable to the construction of a work of art”. In his view, in both art and life, we cannot decide in advance what actions ought to be taken: “No one can tell what the painting of tomorrow will be like; one cannot judge a painting until it is done.”

    Lana Del Rey with 60s beehive hair
    Lana Del Rey at Primavera in 2024.
    Wiki Commons, CC BY-SA

    Likewise, we cannot judge whether or not a life is well-lived until it is finished. We must not predetermine how someone should live according to some pre-established criterion of “human nature”.

    Instead, we can only assess someone’s life by considering whether they accept that they are free, with the freedom and responsibility to create meaning for their existence by living life as a work of art.

    Both freedom and making life a work of art are recurring themes in Del Rey’s discography. They are brought together perhaps most memorably in her much-loved monologue in the music video for Ride (2012):

    On the open road, we had nothing to lose, nothing to gain, nothing we desired anymore, to make our lives into a work of art: Live fast, die young, be wild, and have fun. I believe in the country America used to be. I believe in the person I want to become. I believe in the freedom of the open road.

    Del Rey is someone Elizabeth Grant became. As though echoing Sartre’s comparison between making art and living life, in her 2012 song Gods & Monsters, she sings of herself “posing like a real singer – cause life imitates art”.

    For Del Rey, being a public-facing “real singer” involves some kind of image-cultivation or even self-cultivation. Not unlike how her music video for Video Games is “self-made”, the very identity of Lana Del Rey is also “self-made”. The image of Lana is a work of art made by the artist, Del Rey herself.

    Ride by Lana Del Rey.

    To be an “authentic” or “real” singer is to accept that the persona of a public figure is always inevitably curated. To combine Sartre’s slogan and Del Rey’s lyrics, the real singer is always “condemned to posing”. To pretend otherwise is to disown what it is to be a “real singer” and to act inauthentically.

    If it is true that, as Del Rey sings, “life imitates art”, to render life as a work of art is the most authentic thing that a person can do. Because to live life as a work of art is nothing other than authentically accepting life as it is, something that itself “imitates art”. As she sings in Get Free (2017), this is Del Rey’s commitment, her modern manifesto.

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  • Salmonella cases are at ten-year high in England – here’s what you can do to keep yourself safe

    Salmonella cases are at ten-year high in England – here’s what you can do to keep yourself safe

    Salmonella cases in England are the highest they’ve been in a decade, according to recent UK Health Security Agency (UKHSA) data. There was a 17% increase in cases observed from 2023 to 2024 – culminating in 10,388 detected infections last year. Children and older adults accounted for around a fifth of cases.

    Although the number of infections caused by foodborne diseases such as Salmonella had broadly decreased over the last 25 years, this recent spike suggests a broader issue is at play. A concurrent increase in Campylobacter cases points to a possible common cause that would affect risk of both foodborne pathogens – such as changes in consumer behaviour or food supply chains.

    While the UK maintains a high standard of food safety, any increase in the incidence of pathogens such as Salmonella warrants serious attention.

    Salmonella is a species of bacteria that is one of the most common causes of foodborne illnesses globally. The bacteria causes salmonellosis – an infection that typically causes vomiting and diarrhoea.

    Most cases of salmonellosis don’t require medical intervention. But approximately one in 50 cases results in more serious blood infections. Fortunately, fatalities from Salmonella infections in the UK are extremely rare – occurring in approximately 0.2% of all reported infections.

    Salmonella infections are typically contracted from contaminated foods. But a key challenge in controlling Salmonella in the food supply chain lies in the diverse range of foods it can contaminate.

    Salmonella is zoonotic, meaning it’s present in animals, including livestock. This allows it to enter the food chain and subsequently cause human disease. This occurs despite substantial efforts within the livestock industry to prevent it from happening – including through regular testing and high welfare practices.

    Salmonella can be present on many retail food products – including raw meat, eggs, unpasteurised milk, vegetables and dried foods (such as nuts and spices). When present, it’s typically at very low contamination levels. This means it doesn’t pose a threat to you if the product is stored and cooked properly.

    Vegetables and leafy greens can also become contaminated with Salmonella through cross-contamination, which may occur from contaminated irrigation water on farms, during processing or during storage at home. As vegetables are often consumed raw, preventing cross-contamination is particularly critical.

    Spike in cases

    It’s premature to draw definitive conclusions regarding the causes of this recent increase in Salmonella cases. But the recent UKHSA report suggests the increase is probably due to many factors.

    Never prepare raw meat next to vegetables you intend to eat without cooking, as cross-contamination can lead to Salmonella.
    kathrinerajalingam/ Shutterstock

    One contributing factor is that diagnostic testing has increased. This means we’re better at detecting cases. This can be viewed as a positive, as robust surveillance is integral to maintaining a safe food supply.

    The UKHSA also suggests that changes in the food supply chain and the way people are cooking and storing their food due to the cost of living crisis could also be influential factors.

    To better understand why Salmonella cases have spiked, it will be important for researchers to conduct more detailed examinations of the specific Salmonella strains responsible for the infections. While Salmonella is commonly perceived as a singular bacterial pathogen, there are actually numerous strains (serotypes).

    DNA sequencing can tell us which of the hundreds of Salmonella serotypes are responsible for human infections. Two serotypes, Salmonella enteritidis and Salmonella Typhimurium, account for most infections in England.

    Although the UKHSA reported an increase in both serotypes in 2024, the data suggests that Salmonella enteritidis has played a more significant role in the observed increase. This particular serotype is predominantly associated with egg contamination.

    Salmonella enteritidis is now relatively rare in UK poultry flocks thanks to vaccination and surveillance programmes that were introduced in the 1980s and 1990s. So the important question here is where these additional S enteritidis infections are originating.

    Although the numbers may seem alarming, what the UKHSA has reported is actually a relatively moderate increase in Salmonella cases. There’s no reason for UK consumers to be alarmed. Still, this data underscores the importance of thoroughly investigating the underlying causes to prevent this short-term increase from evolving into a longer-term trend.

    Staying safe

    The most effective way of lowering your risk of Salmonella involves adherence to the “4 Cs” of food hygiene:

    1. Cleaning

    Thoroughly wash hands before and after handling any foods – especially raw meat. It’s also essential to keep workspaces, knives and utensils clean before, during and after preparing your meal.

    2. Cooking

    The bacteria that causes Salmonella infections can be inactivated when cooked at the right temperature. In general, foods should be cooked to an internal temperature above 65°C – which should be maintained for at least ten minutes. When re-heating food, it should reach 70°C or above for two minutes to kill any bacteria that have grown since it was first cooked.

    3. Chilling

    Raw foods – especially meat and dairy – should always be stored below 5°C as this inhibits Salmonella growth. Leftovers should be cooled quickly and also stored at 5°C or lower.

    4. Cross-contamination

    To prevent Salmonella passing from raw foods to those that are already prepared or can be eaten raw (such as vegetables and fruit), it’s important to wash hands and clean surfaces after handling raw meat, and to use different chopping boards for ready-to-eat foods and raw meat.

    Most Salmonella infections are mild and will go away in a few days on their own. But taking the right steps when storing and preparing your meals can significantly lower your risk of contracting it.

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  • The Toxicity of Dimethyl Sulfoxide Combined with Alkylating Agent MNU

    The Toxicity of Dimethyl Sulfoxide Combined with Alkylating Agent MNU

    Introduction

    Dimethyl sulfoxide (DMSO) is a highly polar, organic compound that is widely utilized in scientific and medical researches.1,2 Known for its unique ability to penetrate biological membranes, DMSO is often used as a solvent to facilitate the absorption of a wide variety of chemical compounds, including drugs, toxins, and other substances. This characteristic makes DMSO an invaluable tool in laboratory experiments, particularly in drug delivery systems and pharmacological studies.3 In particular, DMSO’s ability to increase the permeability of biological membranes can influence the pharmacokinetics and biodistribution of co-administered substances, potentially altering their efficacy and safety profiles. This is especially relevant in toxicological studies, where DMSO is frequently used as a vehicle solvent to solubilize poorly water-soluble compounds. However, its capacity to enhance the absorption of compounds into biological tissues also raises concerns about its potential to exacerbate the toxic effects of those compounds, as high concentrations or prolonged exposure may lead to adverse effects such as hemolysis, allergic reactions, and genotoxicity.

    One of the critical areas where DMSO’s solvent properties are frequently leveraged is in the use of chemical agents such as alkylating agents, which have been extensively studied for their ability to modify the structure and function of biological molecules, particularly DNA. Alkylating agents, including N-methyl-N-nitrosourea (MNU), one of the most commonly used alkylating agents, has been widely utilized in cancer research and retinitis pigmentosa modeling.4,5 These agents could covalently bind to DNA, leading to significant alterations in its structure and function. Specifically, they exert their effects by transferring alkyl groups to DNA, which can cause mutations, chromosomal damage, and eventually carcinogenesis or apoptosis of retinal photoreceptors. MNU, in particular, is a powerful mutagen and carcinogen that has been shown to induce a variety of cancers in laboratory animals, including lymphomas, leukemias, and solid tumors in various organs. Its high reactivity and ability to penetrate biological membranes make it an effective agent for inducing genetic damage in a wide range of cell types. Besides, the effectiveness of MNU as a research tool for studying retinitis pigmentosa has made it a cornerstone in many ocular experimental protocols.6,7 In details, by selectively targeting retinal photoreceptors, MNU allows researchers to mimic the progressive degeneration seen in human retinitis pigmentosa, providing a valuable model for testing potential therapeutic interventions.

    While DMSO is often regarded as relatively safe when used at low concentrations, its interaction with other chemicals and the subsequent effects on the health of experimental animals require careful consideration. Low levels of DMSO may interact with cellular processes or metabolic pathways in ways that are not yet fully understood. Studies involving DMSO as a vehicle solvent for chemical agents need to take into account the potential for DMSO to alter the pharmacokinetics and toxicity profiles of the compounds being studied. It may influence absorption rates, distribution within tissues, and elimination half-lives, potentially leading to unexpected outcomes. For example, DMSO was shown to increase the permeability of the blood-brain barrier and enhance the systemic distribution,8 which could result in higher concentrations reaching sensitive areas such as the central nervous system, thereby amplifying their therapeutic or toxic effects. However, despite the well-documented uses of DMSO and MNU in research,9 the combined effects of these substances on biological systems have not been fully elucidated, particularly in terms of long-term consequences or subtle interactions that may only become apparent after prolonged exposure. The potential of DMSO to enhance the absorption of MNU into biological tissues might lead to a more pronounced toxicological effect than when either agent is administered alone. This could result in increased DNA damage or oxidative stress, which are critical factors in carcinogenesis and tissue injury. Given that alkylating agents like MNU can induce significant DNA damage, it is important to assess the overall toxicity and safety of these compounds of DSMO and MNU, particularly in animal studies, to ensure that experimental protocols adequately account for potential risks and to establish safe dosage ranges for future research applications.

    The main goal of this study was to investigate the combined toxicity of DMSO and MNU in a controlled animal model. Specifically, this research aimed to assess the impact of DMSO on the toxicity and mortality associated with MNU exposure in C57BL/6J mice, which are commonly used in ocular researches. By varying the doses of MNU and administering it in combination with DMSO, this study provided preliminary data on the synergistic effects of these two compounds. Additionally, the study assessed whether DMSO, by facilitating the absorption of MNU, exacerbated the toxicological outcomes, including changes in activity levels, health status, and overall survival rates in the mice.

    Methods

    Animal Models

    A total of 12 male SPF C57BL/6J mice, aged 8–10 weeks, with an averaged body weight range of 20–25 grams, were selected for this experiment. These mice were obtained from the Laboratory Animal Center of Fuzong Clinical Medical College of Fujian Medical University (License number.: SYXK2018006) and were allowed to acclimate to the laboratory environment for a period of 3 days before the commencement of the study. The mice were housed in standard laboratory conditions, with a controlled room temperature of 22°C ± 2°C and a relative humidity of 50–60%. The animals were maintained on a 12-hour light/dark cycle, with lights on at 7:00 AM and off at 7:00 PM. The mice were provided with standard rodent chow and clean, filtered water ad libitum throughout the experiment. The cages were kept in an environmentally controlled room to minimize external stressors, and the mice were allowed unrestricted access to their environment in order to reduce potential confounding factors.

    After a period of 3 days of accommodation, the mice were randomly assigned to one of three experimental groups, with four mice per group. The groups were: the DMSO control group (D), the low-dose MNU group (L), and the high-dose MNU group (H). We confirmed that ethical and legal approval was obtained from the Experimental Animal Care and Use Committee of Fuzong Clinical Medical College of Fujian Medical University (Ethics committee number: 201923), prior to the commencement of the study. Besides, all animal experiments and procedures were performed in accordance with the ethical guidelines and regulations established by Fuzong Clinical Medical College of Fujian Medical University and our nation. The overall design of our study was showed in the Graphic Abstract of the Study.

    Group Design and Treatment Protocol

    1. DMSO Control Group (D): The D group, serving as the vehicle control, received intraperitoneal (IP) injections of pure DMSO (100% concentration). Each mouse was administered 12 mL of DMSO per kilogram of body weight. This control treatment was designed to assess the baseline effects of DMSO, ensuring that any observed effects in the other groups could be attributed specifically to the MNU treatment, rather than the vehicle itself.

    2. Low-dose MNU Group (L): The L group received a DMSO solution containing 40 mg/kg of MNU,10 the potent genotoxic agent. MNU was dissolved in DMSO to obtain the desired concentration, and the injection volume for all mice was maintained at 12 mL/kg body weight. In greater details, we firstly calculated the required amount of MNU. For example, for a dose of 40 mg/kg in 3 mice weighing 30 g each, the amount of MNU needed would be MNU = 40×10 × 0.03 = 12 mg. Then, we calculated the corresponding concentration of the MNU solution for injection at a volume of 12 mL/kg. If the MNU was administered at 40 mg/kg and injected at a volume of 12 mL/kg, the corresponding concentration of the MNU solution should be 10/3 mg/mL. Thus, 12 mg of MNU would require a volume of DMSO of 3.6 mL. The solution was then stored at 4°C for later use, and prepared immediately before use. The purpose of this group was to examine the effects of a low-dose MNU exposure on the mice, focusing on toxicological effects and any changes in behavior or general health that could result from this exposure level.

    3. High-dose MNU Group (H): The H group received a higher dose of MNU, specifically 60 mg/kg,10 in the DMSO solution. Similar to the L group, the MNU solution was prepared by dissolving MNU in DMSO, and the injection volume was 12 mL/kg of body weight. This higher dose aimed to assess the potential acute toxicity and mortality associated with a more severe exposure to MNU. This group was expected to show more pronounced toxicological effects, including possible lethality, and served as an extreme comparison for the lower dose.

    Injection Procedure

    All injections were administered via intraperitoneal injection, a standard route for delivering substances that need to be absorbed into the body quickly. The injections were carefully carried out by an experienced personnel to ensure precise and consistent dosages across all animals. The animals were weighed immediately prior to injection to ensure accurate dosing, and each mouse was handled gently to reduce stress and minimize discomfort.

    Monitoring and Observations

    Following treatment, the mice were closely monitored for any immediate or delayed signs of distress, toxicity, or adverse effects. The following parameters were tracked throughout the study:

    1. Body Weight: Mice were weighed several timepoints (Timepoint 1 (T1): at the time of purchase (ie, before the 3-day pre-adaptation feeding); T2: before injection (ie, after the 3-day pre-adaptation feeding); T3: at 24 hours post-injection; T4: at 48 hours post-injection) to monitor any significant changes in body weight, which could indicate adverse effects such as dehydration, malnutrition, or systemic toxicity. A marked decrease in body weight was considered a key indicator of toxicity,11,12 and the rate of weight loss was recorded for comparison across groups.

    2. Activity Levels and scoring: Activity levels were observed both during the light and dark cycles at several timepoints (T1: before injection; T2: at 2 hours post-injection; T3: at 24 hours post-injection; T4: at 36 hours post-injection; T5: at 48 hours post-injection). General locomotor activity was evaluated through simple observational methods, such as monitoring the frequency of walking, movement across the cage, and exploratory behavior. Mice were also monitored for signs of lethargy or reduced activity, which are common indicators of stress or illness.13 Additionally, behaviors like body stretching and body posture were noted, as these could reflect changes in the mice’s physical condition or discomfort.14,15 Besides, fur condition was examined daily to assess any signs of stress or health decline. Deterioration in fur quality, such as loss of fur, roughness (or called the ruffled fur), or lack of grooming behavior, was considered an important indicator of poor health or systemic effects of the treatment.15,16 In our study, the activity score was primarily based on three key domains: the mice’s activity alertness (or the locomotor activity), body extension or posture, and the condition of the fur. A total of 9 points were assigned, with 3 points allocated to each domain. The corresponding scores were assessed and recorded by one certain person, and then were stored for later statistical analysis.

    3. Mortality and Survival curve: Mortality was monitored at several timepoints (T1: before injection; T2: at 2 hours post-injection; T3: at 24 hours post-injection; T4: at 36 hours post-injection; T5: at 48 hours post-injection). Any deaths within this period were carefully observed and the number of mice in each group were recorded. Furthermore, the surviving time of mice in each group was recorded and the survival curves were created based on the number of surviving mice and their survival time.17 Further Kaplan-Meier survival curve analysis was then performed.18

    Statistical Analysis

    Due to the small sample size of 4 animals (less than 5 animals) per group, the non-parametric statistical method, the Bootstrap test, was employed to compare the groups.19 This special test was chosen as it does not rely on distributional assumptions, making it more appropriate for small sample sizes.20 The data were presented as mean ± standard deviation. In the Bootstrap method, the calculation of the P-value is based on the distribution of resampled data and does not directly provide a standard P-value. Although there is no direct P-value, the significance can be indirectly assessed through the following approach by examining the confidence interval. If the confidence interval of the Bootstrap results does not include zero, this typically indicates that the difference is significant. The survival analysis was conducted using the Kaplan-Meier survival curves. The statistical analysis was performed using SPSS 27.0 software, and survival curves were generated and analyzed using Log-rank tests. Figures were generated using GraphPad 5.01 software.

    Results

    Pre-Injection Status and Parameters

    Before the injection, the mice in all experimental groups were closely monitored. The 95% confidence interval of difference in the body weight of mice revealed by the Bootstrap analysis between the D and L, D and H, L and H groups, were (−3.16, 2.66), (−3.36, 2.36) and (−2.25, 1.75) respectively. No significant statistical differences were found in terms of body weight, as the confidence interval of the Bootstrap results included zero (Figure 1). The 95% confidence interval of difference in the volume of DMSO injected between the D and L, D and H, L and H groups, were (−0.019,0.012), (−0.025, 0.012) and (−0.016, 0.007) respectively. No significant statistical differences were found as the confidence interval of the Bootstrap results included zero (Figure 2). It suggested that the experimental groups were well-matched at baseline and there was no noticeable variation in these parameters before treatment.

    Figure 1 Body Weight of Each Group of Mice Before Injection. Bar graph showed the body weight of mice in the DMSO, low-dose MNU, and high-dose MNU groups before the injection. There were no significant differences in body weight between the groups (The confidence interval of the Bootstrap results included zero). D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group. N.S.: no statistical difference.

    Figure 2 Volume of DMSO Injected in Each Group of Mice. Bar graph illustrated the volume of DMSO administered to each group (DMSO, low-dose MNU, high-dose MNU). The injection volume was consistent across all groups, at 12 mL/kg body weight, with no significant differences (The confidence interval of the Bootstrap results included zero). D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group. N.S.: no statistical difference.

    Regarding the MNU injection, the dose administered to the mice in the H group was significantly higher than that given to L group (the 95% confidence interval of difference was 0.076–0.096), which was in turn higher than the dose given to the D group (the 95% confidence interval of difference was 0.160–0.166). The statistical analysis confirmed that the differences in MNU doses among the groups were highly significant, as the confidence interval of the Bootstrap results did not include zero (Figure 3). Prior to the injection, all mice in the study exhibited strong mobility, alertness, and a relaxed posture, with their fur appearing glossy and well-groomed, indicating overall good health.

    Figure 3 MNU Dose Injected in Each Group of Mice. Bar graph showed the dose of MNU injected in the DMSO (D), low-dose (L) and high-dose (H) MNU groups. The high-dose group (60 mg/kg) received a significantly higher MNU dose compared to the low-dose group (40 mg/kg) and the DMSO group (0 mg/kg) (The confidence interval of the Bootstrap results did not include zero). D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group. None: not any quality of MNU; **: a significant difference existed.

    Survival Counts and Survival Curves Analysis

    Following the injection, the survival rates varied across the different groups. Two hours after the injection, all mice in all the experimental groups, except for one mouse in the D group, displayed reduced mobility, decreased alertness, and a hunched posture. After 12 hours, mortality of the mice in all groups began to increase, with one mouse in the D group and two mice in the L group being dead. By 24 hours, the mortality rate continued to rise, as another one mouse in the D group, and two mice in both the L and H groups died. After 36 hours, another one mouse in the D group had died, while one mouse in the D group had regained increased activity. The other mice exhibited the poor mobility and the hunched posture. At this point, all mice in the L and H groups had died, leaving only two surviving individuals in D group. After 48 hours, the recovering mouse in the D group showed significant differences in the survival, which remained alive, exhibiting normal walking ability and alertness. Meanwhile the other mice in the D group had died out (Figure 4).

    Figure 4 Number of Each Group of Mice at Different Time Points and the Survival Curves. (A) Number of each group of mice at different time points. (B) The survival curves of each group of mice at different time points. The number of mice in each group with the survival curve displayed the number of surviving mice at various time points after injection in the DMSO, low-dose MNU, and high-dose MNU groups. Mortality increased over time, with the low-dose and high-dose groups experiencing complete mortality by 36 hours. The DMSO group displayed a smaller mortality, with one mouse surviving at 48 hours. T1: before injection; T2: at 12 hours post-injection; T3: at 24 hours post-injection; T4: at 36 hours post-injection; T5: at 48 hours post-injection. D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group.

    Body Weight Changes

    Throughout the course of the study, no significant differences in the changes of body weight were found in the surviving mice across all groups in all the timepoints of observation. Despite the varying mortality rates and changes in activity levels among all groups, the body weight of the surviving mice remained stable in the D, L and H groups. This might suggest that the physiological effects of the treatment did not result in substantial weight loss among the survivors during the observation period (Figure 5).

    Figure 5 Changes in Body Weight of Each Group of Mice After Injection. Line graph showed the changes in body weight over time in the DMSO, low-dose MNU, and high-dose MNU groups after injection. No significant differences in body weight changes were observed among the groups during the observation period. Timepoint 1 (T1): at the time of purchase (ie, before the 3-day pre-adaptation feeding).; T2: before injection (i.e., after the 3-day pre-adaptation feeding); T3: at 24 hours post-injection; T4: at 48 hours post-injection. D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group.

    Activity Levels Changes

    In terms of activity, two hours after the injection, all mice in the experimental groups showed a marked decline in activity levels. They appeared less alert, displayed a hunched posture, and had reduced physical activity compared to their pre-injection status. As the hours passed, the decline in activity became more pronounced. By 24 hours, some mice in all the groups exhibited trembling, and their activity levels were further reduced. At 36 hours, one mouse in the D group managed to regain increased activity, while others showed signs of poor mobility and distress. No significant differences in activity levels scores were found in the surviving mice across all groups. By the 48-hour mark, the only surviving mouse in the D group displayed the normal walking ability and alertness, while all the other mice in the D, L, and H groups had died out (Figures 6 and 7).

    Figure 6 Changes in Activity Scores of Each Group of Mice After Injection. Line graph illustrated the changes in activity scores (measuring mobility, posture, and alertness) over time in each group after injection. Significant reductions in activity were observed in the low-dose and high-dose MNU groups, with severe declines noted by 24 hours. The DMSO group showed some recovery by 36 hours, though further decline was observed at 48 hours. T1: before injection; T2: at 2 hours post-injection; T3: at 24 hours post-injection; T4: at 36 hours post-injection; T5: at 48 hours post-injection. D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group.

    Figure 7 Representative Images of the Activity Levels and Mental Status of Mice at Different Time Points in Each Group. Red arrows indicated mice with reduced activity and a hunched posture, while blue arrows highlighted mice with a good mental status, increased activity, high alertness, and the ability to move freely. Black arrows indicated the dead mice. T1: at 2 hours post-injection; T2: at 24 hours post-injection; T3: at 36 hours post-injection; T4: at 48 hours post-injection. D: the DMSO control group; L: the low-dose MNU group; H: the high-dose MNU group.

    Discussion

    In our study, male C57BL/6J mice were divided into three groups, the D, L and H groups. Mice were monitored for changes in body weight, activity levels, and mortality. Our results showed no significant differences in body weight among the groups prior to injection. Mortality rate was relative increased with injection of DMSO and MNU combination, while the DMSO alone could also led to a high mortality. All mice in the L and H groups had died out by 36 hours, while only one mouse in the D group survived, regaining a normal activity by 48 hours. All mice exhibited a reduced mobility and a hunched posture, with the activity declining progressively, after injection of either the DMSO or the DMSO-MNU combination.

    In greater details, the mice with only the DMSO injection showed a noticeable decline in activity, reduced alertness, and signs of physical distress such as, a hunched posture, the limb curling and dull fur within two hours after injection. These symptoms indicated the presence of toxic effects. Subsequently, the animal deaths were observed, with only one mouse managed to recover and regain normal vitality at the end. The above results suggested that DMSO had a clear toxic effect on animals, with the potential for lethality or mortality. The toxicity of DMSO observed in this study were consistent with findings reported in other researches.21 DMSO was shown to provoke toxic reactions in the body, which might include a variety of adverse effects.22 Several studies also highlighted the toxicological risks associated with DMSO, indicating that it could significantly alter physiological processes and lead to behavioral changes.23 In particular, the impact of 0.1–10% DMSO concentrations on behavior of aquatic model species has also been noted.24 The DMSO concentrations under 1% did not cause statistically significant mortality, but did induce clear signs of stress, reduced locomotion, and impaired responses to stimuli. Given all these observed effects, it is essential for researchers to be cautious when using DMSO in experimental settings, ensuring that proper controls and safety protocols are in place to safeguard the well-being of animal subjects. It is critical that appropriate dilution of DMSO concentrations is conducted in related studies to minimize potential harm. Interestingly, the observation that one mouse with only the DMSO injection showed activity recovery at 36 hours post-injection was noteworthy. While the DMSO solution itself at high concentration is generally considered toxic, the occurrence of such a recovery in an individual animal may point to inherent variability in the response of mice to the DMSO. It was plausible that the special mouse had a stronger immune or repair response, which allowed it to gradually recover from the toxic effects of the DMSO injection. However, this singular recovery did not diminish the overall trend of severe toxicity observed in the DMSO group, which highlighted the potent and rapid toxicity of DMSO exposure.25

    In mice with injection of the DMSO and MNU combination, the DMSO and MNU combination did not exhibit significantly aggravated toxic reactions or increased mortality in mice during the early stages. From the survival curves, it was apparent that there were no noticeable differences in the early stages compared to the DMSO injection. However, as time progressed, the mortality rate in the DMSO and MNU combination groups began to increase significantly. Upon further analysis, it was found that in the DMSO and MNU combination groups with different doses of MNU, there was no clear MNU-dose dependent increase in toxicity at the early stages. Surprisingly, the early mortality rate in the L group was slightly higher compared to H group. As the observation period extended, however, the mortality rates between the two groups became similar. The results might suggest that the relationship between the MNU dosage and the related toxicity may not always follow a straightforward, dose-dependent pattern. It implied that other factors, such as the rate of absorption, metabolism, or individual genetic responses, might influence the observed outcomes of possible toxicity. The early increased mortality in the L group might be attributed to a higher sensitivity of certain physiological systems or an accelerated onset of toxicity in those mice. As time went on, however, the toxic effects of MNU probably reached a threshold, and the overall mortality rate stabilized in both L and H groups.

    MNU was initially recognized as a potent carcinogenic agent and has been widely used to induce various types of cancer in animal models.26 Subsequent studies demonstrated that MNU at the dose 60 mg/kg could selectively induce apoptosis in retinal photoreceptor cells, which led to its use in research on retinal pigment degeneration and retinal degeneration-related diseases.7,27 However, there has been limited researches on the effects of MNU in increasing animal mortality and lethality. Some studies reported that higher doses of MNU (80, 160 or 240 mg/kg) could lead to tumor formation, leukemia, and even an increase in early mortality in mice26,28. MNU exposure was showed to impair hippocampal neurogenesis in rats,28 which might lead to toxic behaviors. Our study utilized a relatively low dose of MNU, ranging from 40 to 60 mg/kg, and the results suggested that MNU could, to some extent, enhance the toxic effects of DMSO in mice. This enhancement may be due to an increased inherent toxicity of MNU itself, or a result of MNU-mediated potentiation of the DMSO toxicity.

    Several limitations existed in our study. One limitation of this study was the relatively small sample size, which may reduce the statistical power and generalizability of the findings. As our research involved potentially severe toxicological effects and mortality endpoints of mice, we adhered to the principle of minimizing animal use while maintaining scientific validity. This approach aligned with the 3Rs (Replacement, Reduction, and Refinement) principle in animal research. Although we applied the Bootstrap method due to the small sample size, the results should be interpreted with caution and considered as preliminary observations that provided the foundation for more robust studies. Additionally, the short observation period of 48 hours post-injection in our study did not account for potential long-term toxic effects or delayed pathological changes, limiting our understanding of DMSO and MNUinduced chronic toxicity. Besides, the current study did not consider the impact of gender and age variations, which could influence the results. Furthermore, while the study focused on acute toxicity, it did not explore the underlying molecular mechanisms, such as DNA damage repair or oxidative stress. In addition, we did harvest the blood or organs for future enzymatic assays, which might extract the maximum amount of information on the toxicity mechanism. Finally, the use of mice as model organisms, though standard, might not fully represent the human responses. This limitation underscored the necessity for future studies to incorporate other animal models, cell models or human data for broader applicability.

    In conclusion, our study demonstrated that DMSO exhibited a notable toxicity, particularly when used in combination with MNU, the alkylating agents. This combination was shown to significantly reduce the activity levels and increase the mortality rate in mice. These findings highlighted the importance of closely monitoring animal’ reactions during experiments involving DMSO and similar reagents. To mitigate potential adverse effects, it is crucial to establish comprehensive research observation protocols that ensure the health and well-being of the animals. Further studies are needed to explore the underlying mechanisms of DMSO and MNU toxicity and to determine the safest concentrations and guidelines for its application in scientific research. Besides, we would include enzymatic assays of relevant serum and organs, including the heart, liver, spleen, lungs, and kidneys of mice, to further explore the possible toxicity mechanism. By advancing the understanding of DMSO and MNU toxicity, it could better inform safety practices and contribute to the broader field of chemical toxicity assessment.

    Data Sharing Statement

    The datasets used and/or analyzed during the current study were available from the corresponding author on reasonable request.

    Acknowledgments

    We are grateful to our families for their constant support and encouragement throughout this study.

    Weiming Yan, Qiurui He and Lin Xiao are Co-first author.

    Funding

    This work was supported by the grants from the National Natural Science Foundation of China (Grant number: 82301245), the Natural Science Foundation of Fujian Province, China (Grant number: 2024J011148), the Joint Funds for the innovation of science and Technology, Fujian province (Grant number: 2024Y9653), the Postdoctoral Science Foundation of the Fuzhou General Hospital (Grant number: 48678) and the Natural Science Foundation of Zhangzhou City, China (Grant number: ZZ2024J57).

    Disclosure

    The authors declared no potential conflicts of interest regarding the research, authorship, or publication of this article.

    References

    1. Kumar S, Islam R, O’Connor W, et al. A metabolomic analysis on the toxicological effects of the universal solvent, dimethyl sulfoxide. Comp Biochem Physiol C Toxicol Pharmacol. 2025;287:110073. doi:10.1016/j.cbpc.2024.110073

    2. Kligman AM. Dimethyl Sulfoxide. 2. JAMA. 1965;193:923–928. doi:10.1001/jama.1965.03090110061015

    3. Kaczor-Kaminska M, Kaszuba K, Bilska-Wilkosz A, et al. Dimethyl Sulfoxide (DMSO) as a potential source of interference in research related to sulfur metabolism-a preliminary study. Antioxidants. 2024;13(5):582. doi:10.3390/antiox13050582

    4. Sasatani M, Xi Y, Daino K, et al. Rev1 overexpression accelerates N -methyl- N -nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis. Cancer Sci. 2024;115(6):1808–1819. doi:10.1111/cas.16159

    5. Kong Q, Han X, Cheng H, et al. Lycium barbarum glycopeptide (wolfberry extract) slows N-methyl-N-nitrosourea-induced degradation of photoreceptors. Neural Regen Res. 2024;19(10):2290–2298. doi:10.4103/1673-5374.390958

    6. Tawarayama H, Uchida K, Hasegawa H, et al. Estrogen, via ESR2 receptor, prevents oxidative stress-induced Muller cell death and stimulates FGF2 production independently of NRF2, attenuating retinal degeneration. Exp Eye Res. 2024;248:110103. doi:10.1016/j.exer.2024.110103

    7. Zhu Y, Zhao X, Japhet TJ, Chen J, Zhao Q. Sampling of N-methyl-N-nitrosourea-induced rat’s retina damage and multi-index evaluation of pathological changes. J Vis Exp. 2024;(211).

    8. Delgado-Goni T, Martín‐Sitjar J, Simões RV, et al. Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors. NMR Biomed. 2013;26(2):173–184. doi:10.1002/nbm.2832

    9. Rosch S, Werner C, Müller F, et al. Photoreceptor degeneration by intravitreal injection of N-methyl-N-nitrosourea (MNU) in rabbits: a pilot study. Graefes Arch Clin Exp Ophthalmol. 2017;255(2):317–331. doi:10.1007/s00417-016-3531-7

    10. Yan W, He Q, Long P, et al. A novelly-spatiotemporal characterization of the disease course in the MNU-induced retinitis pigmentosa model. J Inflamm Res. 2024;17:9243–9254. doi:10.2147/JIR.S474102

    11. Tanaka M, Abe S. Augmented anti-tumour effect of lipopolysaccharide with G-CSF without enhancing body weight loss in mice bearing MH134 hepatoma. Eur J Pharmacol. 2022;934:175206. doi:10.1016/j.ejphar.2022.175206

    12. Zhan J, Ma X, Liu D, et al. Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice. Environ Pollut. 2020;266(Pt 3):115276. doi:10.1016/j.envpol.2020.115276

    13. Jarrar Q, Ayoub R, Jarrar Y, et al. Flumazenil pretreatment reduces mefenamic acid-induced central nervous system toxicity in mice. J Integr Neurosci. 2023;22(4):104. doi:10.31083/j.jin2204104

    14. Mohamad Shalan NAA, Mustapha NM, Mohamed S. Chronic toxicity evaluation of Morinda citrifolia fruit and leaf in mice. Regul Toxicol Pharmacol. 2017;83:46–53. doi:10.1016/j.yrtph.2016.11.022

    15. Nguyen KC, Zhang Y, Todd J, et al. Biodistribution and systemic effects in mice following intravenous administration of cadmium telluride quantum dot nanoparticles. Chem Res Toxicol. 2019;32(8):1491–1503. doi:10.1021/acs.chemrestox.8b00397

    16. Chadalavada D, Adamson TW, Burnett JC, et al. Irradiated compared with nonirradiated NSG mice for the development of a human B-cell lymphoma model. Comp Med. 2014;64(3):179–185.

    17. Suzuki H, Okada Y. Comparative toxicity of dinophysistoxin-1 and okadaic acid in mice. J Vet Med Sci. 2018;80(4):616–619. doi:10.1292/jvms.17-0377

    18. Uttekar PS, Yadav VD, Bhagwat DA. 1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE), doxorubicin and folic acid conjugated micelles for cancer management in tumor bearing BALB/c mice. Bioorg Med Chem Lett. 2021;50:128337. doi:10.1016/j.bmcl.2021.128337

    19. Dwivedi AK, Mallawaarachchi I, Alvarado LA. Analysis of small sample size studies using nonparametric bootstrap test with pooled resampling method. Stat Med. 2017;36(14):2187–2205. doi:10.1002/sim.7263

    20. Neuhauser M, Jockel K. A bootstrap test for the analysis of microarray experiments with a very small number of replications. Appl Bioinformatics. 2006;5(3):173–179. doi:10.2165/00822942-200605030-00005

    21. Swiecilo A, Januś E, Krzepiłko A, et al. The effect of DMSO on Saccharomyces cerevisiae yeast with different energy metabolism and antioxidant status. Sci Rep. 2024;14(1):21974. doi:10.1038/s41598-024-72400-4

    22. Kim K, Lee S. Combined toxicity of dimethyl sulfoxide (DMSO) and vanadium towards zebrafish embryos (Danio rerio): unexpected synergistic effect by DMSO. Chemosphere. 2021;270:129405. doi:10.1016/j.chemosphere.2020.129405

    23. Haschek WM, Baer KE, Rutherford JE. Effects of dimethyl sulfoxide (DMSO) on pulmonary fibrosis in rats and mice. Toxicology. 1989;54(2):197–205. doi:10.1016/0300-483X(89)90045-0

    24. Huang Y, Cartlidge R, Walpitagama M, et al. Unsuitable use of DMSO for assessing behavioral endpoints in aquatic model species. Sci Total Environ. 2018;615:107–114. doi:10.1016/j.scitotenv.2017.09.260

    25. Fry LJ, Querol S, Gomez SG, et al. Assessing the toxic effects of DMSO on cord blood to determine exposure time limits and the optimum concentration for cryopreservation. Vox Sang. 2015;109(2):181–190. doi:10.1111/vox.12267

    26. Da Silva Franchi CA, Bacchi MM, Padovani CR, et al. Thymic lymphomas in Wistar rats exposed to N-methyl-N-nitrosourea (MNU). Cancer Sci. 2003;94(3):240–243. doi:10.1111/j.1349-7006.2003.tb01427.x

    27. Guo D, Sun Y, Wu J, et al. Photoreceptor-targeted extracellular vesicles-mediated delivery of Cul7 siRNA for retinal degeneration therapy. Theranostics. 2024;14(13):4916–4932. doi:10.7150/thno.99484

    28. Song P, Li X, Chen S, et al. YTHDF1 mediates N -methyl- N -nitrosourea-induced gastric carcinogenesis by controlling HSPH1 translation. Cell Prolif. 2024;57(7):e13619. doi:10.1111/cpr.13619

    Continue Reading

  • Bionomics of Anopheles gambiae complex (Diptera: Culicidae) and malaria transmission pattern in a pre-elimination area in South–Western Senegal | Malaria Journal

    Bionomics of Anopheles gambiae complex (Diptera: Culicidae) and malaria transmission pattern in a pre-elimination area in South–Western Senegal | Malaria Journal

  • WHO. Guidelines for malaria vector control. Geneva: World Health Organization; 2019. p. 1–161.

    Google Scholar 

  • WHO. World Malaria Report 2022. Geneva: World Health Organization; 2022. p. 1–372.

    Google Scholar 

  • NMCP. Annual Epidemiological Newsletter 2021 on Malaria in Senegal. Dakar: Ministry of Health and Social Action; 2022.

    Google Scholar 

  • NMCP. Annual Epidemiological Newsletter 2022 on Malaria in Senegal. Dakar: Ministry of Health and Social Action; 2023.

    Google Scholar 

  • Sene S, Ozer P. Rainfall trends and relationship floods and rainy events in Senegal. Geogr Soc Newsl Liege. 2002;42:27–33.

    Google Scholar 

  • Diouf I, Deme A, Rodriguez Fonseca B, Cisse M, Ndione JA, Gaye AT. Determination of malaria parameters in Senegal using meteorological station data and reanalysis. Guayaquil: XXVIIIe Colloquium of the International Association of Climatology; 2015.

    Google Scholar 

  • Faye O, Gaye O, Fontenille D, Sy N, Konate L, Hébrard G, et al. Comparison of malaria transmission in two epidemiological facies in Senegal: the Sahelian coastal zone and the southern Sudanian zone. Dakar Med. 1995;40:201–7 (in French).

    CAS 

    Google Scholar 

  • Faye O, Konaté L, Diop A. Entomological profile of malaria in Senegal. Dakar: Ministry of Health Medical Prevention; 2011.

    Google Scholar 

  • Fleury L, Pison G, Delaunay V. Senegal-Mlomp health and population observatory (1985–ongoing). Arch Natl Data Senegal. 2019;1–12.

  • PDC. Diagnostic report for the Commune of Mlomp. Report. 2018. http://www.pouyelayese.com/ardzig/media/attachments/2020/11/23/rapport-final_pdc_mlomp-ouss.pdf.

  • CDO. Departmental land use and development plan of Oussouye. Report. 2016;1–90.

  • Diagne N, Fontenille D, Konate L, Faye O, Lamizana MT, Legros F, et al. The Anopheline of Senegal: an annotated and illustrated list. Bull Soc Path Exot. 1994;87:267–77 (in French).

    CAS 

    Google Scholar 

  • Detinova TS. Determination of the physiological age of female Anopheles from the changes of the tracheal system of the ovaries. Med Parazitol (Mosk). 1945;14:45–9 (in Russian).

    CAS 

    Google Scholar 

  • Beier JC, Perkins PV, Wirtz RA, Koros J, Diggs D, Gargan TP, et al. Bloodmeal identification by direct enzyme-linked immunosorbent assay (ELISA), tested on Anopheles (Diptera: Culicidae) in Kenya. J Med Entomol. 1988;25:9–16.

    CAS 

    Google Scholar 

  • Wirtz RA, Zavala F, Charoenvit Y, Campbell GH, Burkot TR, Schneider I, et al. Comparative testing of monoclonal antibodies against Plasmodium falciparum sporozoites for ELISA development. Bull World Health Organ. 1987;65:39–45.

    CAS 

    Google Scholar 

  • Collins FH, Mendez MA, Rasmussen MO, Mehaffey PC, Besansky NJ, Finnerty V. A ribosomal RNA gene probe differentiates member species of the Anopheles gambiae complex. Am J Trop Med Hyg. 1987;37:37–41.

    CAS 

    Google Scholar 

  • Wilkins EE, Howell PI, Benedict MQ. IMP PCR primers detect single nucleotide polymorphisms for Anopheles gambiae species identification, Mopti and Savanna rDNA types, and resistance to dieldrin in Anopheles arabiensis. Malar J. 2006;5:125.

    Google Scholar 

  • Fontenille D, Faye O, Konate L, Sy N, Collins FH. Comparison of PCR and cytogenetic techniques to identify members of the Anopheles gambiae complex in Senegal. Ann Parasitol Hum Comp. 1993;68:239–40 (in French).

    CAS 

    Google Scholar 

  • Ndiath MO, Brengues C, Konate L, Sokhna C, Boudin C, Trape JF, et al. Dynamics of transmission of Plasmodium falciparum by Anopheles arabiensis and the molecular forms M and S of Anopheles gambiae in Dielmo, Senegal. Malar J. 2008;7:136.

    Google Scholar 

  • Caputo B, Tondossoma N, Virgillito C, Pichler V, Serini P, Calzetta M, et al. Is Côte d’Ivoire a new high hybridization zone for the two major malaria vectors, Anopheles coluzzii and An. gambiae (Diptera, Culicidae)? Infect Genet Evol. 2022;98:105215.

    Google Scholar 

  • Nwakanma DC, Neafsey DE, Jawara M, Adiamoh M, Lund E, Rodrigues A, et al. Breakdown in the process of incipient speciation in Anopheles gambiae. Genetics. 2013;193:1221–31.

    Google Scholar 

  • Oliveira E, Salgueiro P, Palsson K, Vicente JL, Arez AP, Jaenson TG, et al. High levels of hybridization between molecular forms of Anopheles gambiae from Guinea Bissau. J Med Entomol. 2008;45:1057–63.

    CAS 

    Google Scholar 

  • Sougoufara S, Sokhna C, Diagne N, Doucouré S, Sembène PM, Harry M. The implementation of long-lasting insecticidal bed nets has differential effects on the genetic structure of the African malaria vectors in the Anopheles gambiae complex in Dielmo, Senegal. Malar J. 2017;16:337.

    Google Scholar 

  • Niang EHA, Konaté L, Diallo M, Faye O, Dia I. Reproductive isolation among sympatric molecular forms of An. gambiae from inland areas of South-Eastern Senegal. PLoS ONE. 2014;9: e104622.

    Google Scholar 

  • Caputo B, Nwakanma D, Jawara M, Adiamoh M, Dia I, Konate L, et al. Anopheles gambiae complex along The Gambia river, with particular reference to the molecular forms of An. gambiae s.s. Malar J. 2008;7:17.

    Google Scholar 

  • Della Torre A, Tu Z, Petrarca V. On the distribution and genetic differentiation of Anopheles gambiae s.s. molecular forms. Insect Biochem Mol Biol. 2005;35:755–69.

    CAS 

    Google Scholar 

  • Niang A, Epopa PS, Sawadogo SP, Maïga H, Konaté L, Faye O, et al. Does extreme asymmetric dominance promote hybridization between Anopheles coluzzii and Anopheles gambiae s.s. in seasonal malaria mosquito communities of West Africa. Parasit Vectors. 2015;8:586.

    Google Scholar 

  • Faye O, Konate L, Mouchet J, Fontenille D, Sy N, Hebrard G, et al. Indoor resting by outdoor biting females of Anopheles gambiae complex (Diptera: Culicidae) in the Sahel of Northern Senegal. J Med Entomol. 1997;34:285–9.

    CAS 

    Google Scholar 

  • Faye O. Malaria in Senegal. Ecology of the parasitosis and perspectives for control. Thesis, Nat Univ Cheikh Anta Diop Dakar. 1994.

  • Niang EHA, Touré A, Ngom EHM, Konaté L, Faye O, Diallo M, et al. Malaria transmission pattern in an area selected for clinical trials in the Sudanian area of Senegal (West Africa). J Trop Med. 2013;2013: 907375.

    Google Scholar 

  • Dia I, Diop T, Rakotoarivony I, Kengne P, Fontenille D. Bionomics of Anopheles gambiae Giles, An. arabiensis Patton, An. funestus Giles and An. nili (Theobald) (Diptera: Culicidae) and Transmission of Plasmodium falciparum in a Sudano-Guinean Zone (Ngari, Senegal). J Med Entomol. 2003;40:279–83.

    Google Scholar 

  • Rajaonarivelo V, Le Goff G, Cot M, Brutus L. Anopheline and malaria transmission in Ambohimena, a village on the western margin of the Malagasy Highlands. Parasite. 2004;11:75–82.

    CAS 

    Google Scholar 

  • Assouho KF, Adja AM, Guindo-Coulibaly N, Tia E, Kouadio AMN, Zoh DD, et al. Vectorial transmission of malaria in major districts of Côte d’Ivoire. J Med Entomol. 2020;57:908–14.

    Google Scholar 

  • Faye O. Contribution to the study of Anophelinae (Diptera, Culicidae) and malaria transmission in the area of the Bignona anti-salt dam (Ziguinchor, Senegal). Thesis. Univ Cheikh Anta Diop Dakar. 1987.

  • Robert V, Dieng H, Lochouarn L, Traoré SF, Trape J-F, Simondon F, et al. Malaria transmission in the Niakhar area, Senegal. Trop Med Int Health. 1998;3:667–77.

    CAS 

    Google Scholar 

  • Faye O, Gaye O, Hervé JP, Diack PA, Diallo S. Malaria in the Sahelian zone of Senegal. Ann Soc Belg Med Trop. 1993;73:21–30.

    CAS 

    Google Scholar 

  • Konate L, Diagne N, Brahimi K, Faye O, Legros F, Rogier C, et al. Vector biology and transmission of Plasmodium falciparum, P. malariae et P. ovale in a West African savannah village (Dielmo, Senegal). Parasite. 1994;1:325–33.

    CAS 

    Google Scholar 

  • Faye O, Fontenille D, Gaye O, Sy N, Molez JF, Diallo S, et al. Malaria and rice growing in the Senegal River delta (Senegal). Ann Soc Belg Med Trop. 1995;75:179–89.

    CAS 

    Google Scholar 

  • Yadouleton A, Aikpon R, Houndeton G, Aboubacar S, Ursins F, Tchibçozo C, et al. Preliminary entomological data for the implementation of large-scale indoor residual spraying in the commune of Corpargo in Northeastern Benin. Int J Biol Chem Sci. 2018;12:1993–2003.

    CAS 

    Google Scholar 

  • Carrara GC, Petrarca V, Niang M, Coluzzi M. Anopheles pharoensis and transmission of Plasmodium falciparum in the Senegal River delta, West Africa. Med Vet Entomol. 1990;4:421–4.

    CAS 

    Google Scholar 

  • Manga L, Toto JC, Carnevale P. Vectors and malaria transmission around the new Yaounde-Nsimalen international airport. Bull Liaison Doc-OCEAC. 1992;102:48–55.

    Google Scholar 

  • Diop A, Molez JF, Konaté L, Fontenille D, Gaye O, Diouf M, et al. Role of Anopheles melas Theobald (1903) in malaria transmission in the Saloum mangrove (Senegal). Parasite. 2002;9:239–46.

    CAS 

    Google Scholar 

  • Jawara M, Pinder M, Drakeley CJ, Nwakanma DC, Jallow E, Bogh C, et al. Dry season ecology of Anopheles gambiae complex mosquitoes in The Gambia. Malar J. 2008;7:156.

    Google Scholar 

  • Akogbeto M. Entomological study of coastal lagoon malaria transmission: the case of a village built on a brackish-water lake. Ann Soc Belg Med Trop. 1995;75:219–27.

    CAS 

    Google Scholar 

  • Trape JF, Pison G, Preziosi MP, Enel C, Du Loû AD, Delaunay V, et al. Impact of chloroquine resistance on malaria mortality. C R Acad Sci. 1998;III(321):689–97.

    Google Scholar 

  • Agnamey P, Brasseur P, Eldin de Pecoulas P, Vaillant M, Olliaro P. Plasmodium falciparum in vitro susceptibility to antimalarial drugs in Casamance (South-western Senegal) during the first 5 years of routine use of artesunate-amodiaquine. Antimicrob Agents Chemother. 2006;50:1531–4.

    CAS 

    Google Scholar 

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