Teratogenicity of depleted uranium aerosols: A review from an epidemiological perspective

BACKGROUND: Depleted uranium is being used increasingly often as a component of munitions in military conflicts. Military personnel, civilians and the DU munitions producers are being exposed to the DU aerosols that are generated. METHODS: We reviewed toxicological data on both natural and depleted uranium. We included peer reviewed studies and gray literature on birth malformations due to natural and depleted uranium. Our approach was to assess the "weight of evidence" with respect to teratogenicity of depleted uranium. RESULTS: Animal studies firmly support the possibility that DU is a teratogen. While the detailed pathways by which environmental DU can be internalized and reach reproductive cells are not yet fully elucidated, again, the evidence supports plausibility. To date, human epidemiological data include case examples, disease registry records, a case-control study and prospective longitudinal studies. DISCUSSION: The two most significant challenges to establishing a causal pathway between (human) parental DU exposure and the birth of offspring with defects are: i) distinguishing the role of DU from that of exposure to other potential teratogens; ii) documentation on the individual level of extent of parental DU exposure. Studies that use biomarkers, none yet reported, can help address the latter challenge. Thoughtful triangulation of the results of multiple studies (epidemiological and other) of DU teratogenicity contributes to disentangling the roles of various potentially teratogenic parental exposures. This paper is just such an endeavor. CONCLUSION: In aggregate the human epidemiological evidence is consistent with increased risk of birth defects in offspring of persons exposed to DU

Potent Phototoxicity of Marine Bunker Oil to Translucent Herring Embryos after Prolonged Weathering

Pacific herring embryos (Clupea pallasi) spawned three months following the Cosco Busan bunker oil spill in San Francisco Bay showed high rates of late embryonic mortality in the intertidal zone at oiled sites. Dead embryos developed to the hatching stage (e.g. fully pigmented eyes) before suffering extensive tissue deterioration. In contrast, embryos incubated subtidally at oiled sites showed evidence of sublethal oil exposure (petroleum-induced cardiac toxicity) with very low rates of mortality. These field findings suggested an enhancement of oil toxicity through an interaction between oil and another environmental stressor in the intertidal zone, such as higher levels of sunlight-derived ultraviolet (UV) radiation. We tested this hypothesis by exposing herring embryos to both trace levels of weathered Cosco Busan bunker oil and sunlight, with and without protection from UV radiation. Cosco Busan oil and UV co-exposure were both necessary and sufficient to induce an acutely lethal necrotic syndrome in hatching stage embryos that closely mimicked the condition of dead embryos sampled from oiled sites. Tissue levels of known phototoxic polycyclic aromatic compounds were too low to explain the observed degree of phototoxicity, indicating the presence of other unidentified or unmeasured phototoxic compounds derived from bunker oil. These findings provide a parsimonious explanation for the unexpectedly high losses of intertidal herring spawn following the Cosco Busan spill. The chemical composition and associated toxicity of bunker oils should be more thoroughly evaluated to better understand and anticipate the ecological impacts of vessel-derived spills associated with an expanding global transportation network

The 'peptide for life' initiative in the emergency department study.

AIMS: Natriuretic peptide (NP) uptake varies in Emergency Departments (EDs) across Europe. The 'Peptide for Life' (P4L) initiative, led by Heart Failure Association, aims to enhance NP utilization for early diagnosis of heart failure (HF). We tested the hypothesis that implementing an educational campaign in Western Balkan countries would significantly increase NP adoption rates in the ED. METHODS AND RESULTS: This registry examined NP adoption before and after implementing the P4L-ED study across 10 centres in five countries: Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia, and Serbia. A train-the-trainer programme was implemented to enhance awareness of NP testing in the ED, and centres without access received point-of-care instruments. Differences in NP testing between the pre-P4L-ED and post-P4L-ED phases were evaluated. A total of 2519 patients were enrolled in the study: 1224 (48.6%) in the pre-P4L-ED phase and 1295 (51.4%) in the post-P4L-ED phase. NP testing was performed in the ED on 684 patients (55.9%) during the pre-P4L-ED phase and on 1039 patients (80.3%) during the post-P4L-ED phase, indicating a significant absolute difference of 24.4% (95% CI: 20.8% to 27.9%, P < 0.001). The use of both NPs and echocardiography significantly increased from 37.7% in the pre-P4L-ED phase to 61.3% in the post-P4L-ED phase. There was an increased prescription of diuretics and SGLT2 inhibitors during the post-P4L-ED phase. CONCLUSIONS: By increasing awareness and providing resources, the utilization of NPs increased in the ED, leading to improved diagnostic accuracy and enhanced patient care

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time. This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails

Acoustic measurement of the eustachian tube function

We present a facile and versatile platform approach for the synthesis of submicrometer-sized hybrid particles based on an oil-in-water emulsion. These particles comprise organosiloxanes and/or organosilsesquioxanes formed via hydrolysis and polycondensation of alkyl- or aryltrimethoxysilane, and polystyrene or poly(methyl methacrylate) formed through radical polymerization of styrene and methyl methacrylate, respectively. In this synthesis, the alkyl- or aryltrimethoxysilane fulfills three different roles: (i) it is part of the oil phase, (ii) serves as monomer for the formation of the organosiloxane network, and (iii) forms a surface active species that stabilizes the emulsion. Size, composition and architecture of the resulting hybrid particles are programmable in this synthetic approach, as demonstrated for the combination phenyltrimethoxysilane/styrene. The versatility of the approach is demonstrated by preparing hybrid particles based on following precursor/monomer combinations: phenyltrimethoxysilane/methyl methacrylate, methyltrimethoxysilane/styrene, (3-acryloxypropyl)-trimethoxysilane/styrene and (3-mercaptopropyl)trimethoxysilane/styrene. Latter combination yields hybrid spheres with thiol groups suited for further functionalization