Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomaviruses types 5 and 18

Ultraviolet (UV) irradiation is a major mutagenic environmental agent, causing the appearance of DNA adducts that, if unrepaired, may give rise to mutations. Ultraviolet radiation has been indicated as a major risk factor in the development of nonmelanoma skin cancers; however, recent reports have suggested that infections with human papillomaviruses, a widespread family of epitheliotropic DNA viruses, may also contribute to the tumorigeneic process. Here, we investigated whether expression of the E6 protein from different HPV types interfere with the repair of thymine dimers caused by UV-B radiation. Results show that unrepaired DNA damage can be observed in UV-B-irradiated cells expressing the E6 protein of HPV types found in cervical and epithelial cancers. Moreover, such cells have the ability to overcome the G(1) cell cycle checkpoint induced as a result of unrepaired DNA. (C) 2004 Cancer Research UK

A case report and brief review of the literature on bilateral retinal infarction following cardiopulmonary bypass for coronary artery bypass grafting

Postoperative visual loss is a devastating perioperative complication. The commonest aetiologies are anterior ischaemic optic neuropathy (AION), posterior ischaemic optic neuropathy (PION), and central retinal artery occlusion (CRAO). These appear to be related to certain types of operation, most commonly spinal and cardiac bypass procedures; with the rest divided between: major trauma causing excessive blood loss; head/neck and nasal or sinus surgery; major vascular procedures (aortic aneurysm repair, aorto-bifemoral bypass); general surgery; urology; gynaecology; liposuction; liver transplantation and duration of surgery. The non-surgical risk factors are multifactorial: advanced age, prolonged postoperative anaemia, positioning (supine v prone), alteration of venous drainage of the retina, hypertension, smoking, atherosclerosis, hyperlipidaemia, diabetes, hypercoagulability, hypotension, blood loss and large volume resuscitation. Other important cardiac causes are septic emboli from bacterial endocarditis and emboli caused by atrial myxomata. The majority of AION cases occur during CPB followed by head/neck surgery and prone spine surgery. CPB is used to allow coronary artery bypass grafting on a motionless heart. It has many side-effects and complications associated with its use and we report here a case of bilateral retinal infarction during routine coronary artery bypass grafting in a young male patient with multiple risk factors for developing this complication despite steps to minimise its occurrence

Stampidine prevents mortality in an experimental mouse model of viral hemorrhagic fever caused by lassa virus

BACKGROUND: The potential use of microorganisms as agents of biological warfare (BW) is a growing concern. Lassa virus, a member of the Arenavirus class of Hemorrhagic fever (HF) viruses has emerged as a worldwide concern among public health officials. The purpose of the present study was to further elucidate the antiviral activity spectrum of stampidine, a novel nucleoside analog with potent anti-viral activity against the immunodeficiency viruses HIV-1, HIV-2, and FIV, by examining its effects on survival of mice challenged with Lassa virus. METHODS: We examined the therapeutic effect of Stampidine in CBA mice inoculated with intracerebral injections of the Josiah strain of Lassa virus. Mice were treated either with vehicle or nontoxic doses of stampidine administered intraperitoneally 24 hours prior to, 1 hour prior to, and 24 hours, 48 hours, 72 hours, and 96 hours after virus inoculation. RESULTS: The probability of survival following the Lassa challenge was significantly improved for stampidine treated mice (Kaplan Meier, Chi-squared = 11.7, df = 2, Log-Rank p-value = 0.003). CONCLUSION: Therefore, stampidine shows clinical potential as a new agent for treatment of viral hemorrhagic fevers caused by Lassa virus

Regulation and Role of Arabidopsis CUL4-DDB1A-DDB2 in Maintaining Genome Integrity upon UV Stress

Plants use the energy in sunlight for photosynthesis, but as a consequence are exposed to the toxic effect of UV radiation especially on DNA. The UV-induced lesions on DNA affect both transcription and replication and can also have mutagenic consequences. Here we investigated the regulation and the function of the recently described CUL4-DDB1-DDB2 E3 ligase in the maintenance of genome integrity upon UV-stress using the model plant Arabidopsis. Physiological, biochemical, and genetic evidences indicate that this protein complex is involved in global genome repair (GGR) of UV-induced DNA lesions. Moreover, we provide evidences for crosstalks between GGR, the plant-specific photo reactivation pathway and the RAD1-RAD10 endonucleases upon UV exposure. Finally, we report that DDB2 degradation upon UV stress depends not only on CUL4, but also on the checkpoint protein kinase Ataxia telangiectasia and Rad3-related (ATR). Interestingly, we found that DDB1A shuttles from the cytoplasm to the nucleus in an ATR-dependent manner, highlighting an upstream level of control and a novel mechanism of regulation of this E3 ligase

Children's and adolescents' rising animal-source food intakes in 1990-2018 were impacted by age, region, parental education and urbanicity

Animal-source foods (ASF) provide nutrition for children and adolescents physical and cognitive development. Here, we use data from the Global Dietary Database and Bayesian hierarchical models to quantify global, regional and national ASF intakes between 1990 and 2018 by age group across 185 countries, representing 93% of the worlds child population. Mean ASF intake was 1.9 servings per day, representing 16% of children consuming at least three daily servings. Intake was similar between boys and girls, but higher among urban children with educated parents. Consumption varied by age from 0.6 at <1 year to 2.5 servings per day at 1519 years. Between 1990 and 2018, mean ASF intake increased by 0.5 servings per week, with increases in all regions except sub-Saharan Africa. In 2018, total ASF consumption was highest in Russia, Brazil, Mexico and Turkey, and lowest in Uganda, India, Kenya and Bangladesh. These findings can inform policy to address malnutrition through targeted ASF consumption programmes. (c) 2023, The Author(s)

Incident type 2 diabetes attributable to suboptimal diet in 184 countries

The global burden of diet-attributable type 2 diabetes (T2D) is not well established. This risk assessment model estimated T2D incidence among adults attributable to direct and body weight-mediated effects of 11 dietary factors in 184 countries in 1990 and 2018. In 2018, suboptimal intake of these dietary factors was estimated to be attributable to 14.1 million (95% uncertainty interval (UI), 13.814.4 million) incident T2D cases, representing 70.3% (68.871.8%) of new cases globally. Largest T2D burdens were attributable to insufficient whole-grain intake (26.1% (25.027.1%)), excess refined rice and wheat intake (24.6% (22.327.2%)) and excess processed meat intake (20.3% (18.323.5%)). Across regions, highest proportional burdens were in central and eastern Europe and central Asia (85.6% (83.487.7%)) and Latin America and the Caribbean (81.8% (80.183.4%)); and lowest proportional burdens were in South Asia (55.4% (52.160.7%)). Proportions of diet-attributable T2D were generally larger in men than in women and were inversely correlated with age. Diet-attributable T2D was generally larger among urban versus rural residents and higher versus lower educated individuals, except in high-income countries, central and eastern Europe and central Asia, where burdens were larger in rural residents and in lower educated individuals. Compared with 1990, global diet-attributable T2D increased by 2.6 absolute percentage points (8.6 million more cases) in 2018, with variation in these trends by world region and dietary factor. These findings inform nutritional priorities and clinical and public health planning to improve dietary quality and reduce T2D globally. (c) 2023, The Author(s)

Risk Assessment Aflatoksin B1 pada Makanan Berbasis Jagung (Sekelan) dari Kecamatan Tretep, Kabupaten Temanggung, Propinsi Jawa Tengah

Aspergillus flavus is a species of fungus that is often found in corn that can produce mycotoxins, such as aflatoxin B1 (AFB1). Sekelan is a staple food that has potential as a substitute for rice. Sekelan raw material is corn. Corn has the potential contaminated by AFB1 when handling during harvest and post-harvest is not appropriate and when consumed by humans and animals can cause health problems. Sekelan are consume daily by the community in the Tretep Sub District. The samples consist of corn, sekelan and ready to eat sekelan, obtained from five villages in the Tretep Sub District. Fungal contamination testing, measurement of water activity (aw), AFB1 concentration analysis and risk assessment carried out on samples of corn and sekelan. Fungal contamination in corn dominated by white mycelia fungi followed by the genera Aspergillus, Penicillium, Eurotium and Trichoderma. Fungal contamination on sekelan dominated by white mycelia fungi followed by genera Aspergillus, Penicillium and Eurotium. Aflatoxigenic fungi (A. flavus) contaminate 1 of 16 samples of corn while sekelan not found aflatoxigenic fungi contamination. Aw value in corn samples ranged between 0576-0933, sekelan ranged between 0483- 0883 and ready to eat sekelan ranged between 0.96-0.98. AFB1 concentrations of all samples were below the LOD (LOD = 1.75 ppb). Half LOQ value (2.916 ppb) was used as the concentration of AFB1 in calculating exposure. AFB1 exposure amount is 0.079 μg/kg bw/day or 3.8 μg/person /day. Sekelan consumption by the community of Tretep Sub District range from 117.1-358.7 g/person/day. Sekelan in Tretep Sub District is still within safe limits for consumption