Disparities between perceived and true outcomes of infants born at 23-25 weeks' gestation.

BACKGROUND: Decision-making for infants born at 23-25 weeks involves counselling parents about survival and major disability risks. Accurate information is needed for parents to make informed decisions about their baby's care. AIMS: To determine if perinatal clinicians had accurate perceptions of outcomes of infants born at 23-25 weeks' gestation, and if accuracy had changed over a decade. MATERIALS AND METHODS: A web-based survey was sent to midwives, nurses, neonatologists, and obstetricians working in tertiary and non-tertiary hospitals, and the neonatal retrieval service in the state of Victoria in 2020. A similar survey had been completed in 2010. Clinicians' estimates of survival and major neurodevelopmental disability rates were compared with true rates for actively managed infants overall, and by infant birthplace and gestational age, and professional workplace and discipline. Accuracy of outcomes was compared between eras. RESULTS: Overall, 165 surveys were received. Participants underestimated survival (absolute mean difference [%] -14.4%; [95% confidence interval (CI) -16.6 to -12.3]; P < 0.001) and overestimated major disability (absolute mean difference 32.7%; [95% CI 29.7 to 35.8]; P < 0.001) rates overall, and at each week of gestation, and were worse for outborn compared with inborn infants. Perceptions of clinicians in tertiary centres were similar to those of non-tertiary clinicians. Nurses/midwives were more pessimistic, and paediatricians were more optimistic. Clinicians' perceptions of outcome were less accurate in 2020 than in 2010. CONCLUSIONS: Most perinatal clinicians underestimate survival and overestimate major disability of infants born at 23-25 weeks' gestation, which may translate into overly pessimistic counselling of parents.

Virucidal efficacy of antimicrobial surface coatings against the enveloped bacteriophage Φ6.

AIMS: Antimicrobial coatings, for use in combination with routine cleaning and disinfection, were evaluated for their effectiveness in reducing virus concentration on stainless steel surfaces. METHODS: Twenty antimicrobial coating products, predominantly composed of organosilane quaternary ammonium compounds, were applied to stainless steel coupons, dried overnight and evaluated for efficacy against Φ6, an enveloped bacteriophage. Additionally, two peel and stick polymer-based films, a copper-based film and three copper alloys were evaluated. Efficacy was determined by comparison of recoveries from uncoated (positive control) and coated (test) surfaces. RESULTS: The results indicated that some of the coating products initially demonstrated >3-log reduction of Φ6; no direct correlation of efficacy was observed with an active ingredient or its concentration. The peel and stick films and copper alloys each demonstrated efficacy in initial testing. However, none of the spray-based products retained efficacy after subjecting the coating to abrasion with either a hypochlorite or quaternary ammonium-based solution applied in accordance with EPA Interim Guidance for Evaluating the Efficacy of Antimicrobial Surface Coatings. Of the products tested for this durability, only one peel and stick polymeric film retained efficacy; the copper alloys were not tested for their durability in this study. CONCLUSIONS: These results suggest that while some organosilane quaternary ammonium compound-based products demonstrate antiviral efficacy, more research and development is needed to understand effective formulations with sufficient durability to perform as supplements to routine cleaning and disinfection.

Root and Shoot Biomass Growth of Constructed Floating Wetlands Plants in Saline Environments.

Constructed Floating Wetlands (CFWs) are increasingly being used globally in freshwater environments such as urban lakes and ponds to remove pollutants from urban stormwater runoff. However, to date there has been limited research into the use and performance of these systems in saline environments. This study compared the root and shoot biomass growth and nutrient uptake of five different plant species, Chrysopogon zizanioides, Baumea juncea, Isolepis nodosa, Phragmites australis and Sarcocornia quinqueflora, in three different saltwater treatments over a 12-week period. The aim of the study was to identify which of the plant species may be most suitable for use in CFWs in saline environments. Plant nutrient uptake testing revealed that Phragmites australis had the greatest percentage increase (1473⁻2477%) of Nitrogen mass in the shoots in all treatments. Sarcocornia quinqueflora also had impressive Nitrogen mass increase in saltwater showing an increase of 966% (0.208 ± 0.134 g). This suggests that the use of Phragmites australis and Sarcocornia quinqueflora plants in CFWs installed in saline water bodies, with regular harvesting of the shoot mass, may significantly reduce Nitrogen concentrations in the water. Isolepis nodosa had the greatest percentage increase (112% or 0.018 ± 0.020 g) of Phosphorous mass in the shoots in the saltwater treatment. Baumea juncea had the greatest percentage increase (315% or 0.026 ± 0.012 g) of Phosphorous mass in the roots in the saltwater treatment. This suggests that the use of Isolepis nodosa and Baumea juncea plants in CFWs installed in saline water bodies may significantly reduce Phosphorous concentrations in the water if there was a way to harvest both the shoots above and the roots below the CFWs. The study is continuing, and it is anticipated that more information will be available on CFW plants installed in saline environments in the near future.

Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes (Nos2, Nlrp3, Il6, and Ptgs2), were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

Phototherapy in transport for neonates with unconjugated hyperbilirubinaemia.

AIM: In Victoria, neonates with severe unconjugated hyperbilirubinaemia at risk of requiring exchange transfusion are retrieved by the Paediatric Infant Perinatal Emergency Retrieval Service and transferred to a Neonatal Intensive Care Unit where an exchange transfusion can be performed if necessary. Transfer may result in prolonged periods without phototherapy in neonates at risk of developing bilirubin encephalopathy. We aimed to describe our experience of the introduction of phototherapy using a portable phototherapy unit during transport. METHODS: Neonates with a primary diagnosis of severe unconjugated hyperbilirubinaemia were identified from the Paediatric Infant Perinatal Emergency Retrieval clinical database over an 11-year period. Demographic and clinical data including gestation, age at transport, serum bilirubin levels pre- and post-transport, use of phototherapy during transport (PTDT), likely diagnosis, and use of exchange transfusion were included. RESULTS: A total of 147 neonates were included with 104 neonates receiving PTDT and 43 who did not. Neonates who received PTDT were less likely to require exchange transfusion, 19.2% versus 34.9%, odds ratio 0.44 (95% CI 0.2-0.98), P = 0.05. However, after correction for factors appearing to be related to use of exchange transfusion, the odds ratio increased to 0.58 (95% CI 0.21-1.63), P = 0.3. There was a greater reduction in the pre- to post-transport total serum bilirubin levels (µmol/L) for the group receiving PTDT (mean 46.3, SD 64.6) versus no PTDT (mean 26.1, SD 62.5), but this did not reach significance, P = 0.08. CONCLUSIONS: Phototherapy during neonatal transport is feasible and safe and may result in a decreased requirement for subsequent exchange transfusion.

Auditory risk estimates for youth target shooting.

OBJECTIVE: To characterize the impulse noise exposure and auditory risk for youth recreational firearm users engaged in outdoor target shooting events. The youth shooting positions are typically standing or sitting at a table, which places the firearm closer to the ground or reflective surface when compared to adult shooters. DESIGN: Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage-risk criteria for unprotected adult listeners and the 120-dB peak limit suggested by the World Health Organization (1999) for children. STUDY SAMPLE: Impulses were generated by 26 firearm/ammunition configurations representing rifles, shotguns, and pistols used by youth. Measurements were obtained relative to a youth shooter's left ear. RESULTS: All firearms generated peak levels that exceeded the 120 dB peak limit suggested by the WHO for children. In general, shooting from the seated position over a tabletop increases the peak levels, LAeq8 and reduces the unprotected maximum permissible exposures (MPEs) for both rifles and pistols. Pistols pose the greatest auditory risk when fired over a tabletop. CONCLUSION: Youth should utilize smaller caliber weapons, preferably from the standing position, and always wear hearing protection whenever engaging in shooting activities to reduce the risk for auditory damage.

Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF.

Drugs that prevent the binding of VEGF to its trans-membrane cognate receptors have revolutionized the treatment of the most important chorioretinal vascular disorders: exudative age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. Pegaptanib, which binds to VEGF165 and longer isoforms, ranibizumab and bevacizumab, which bind all VEGF-A isoforms, and aflibercept, which binds VEGF-A, VEGF-B, and placental growth factor, all bind VEGF165 with high affinity. The drugs have relatively long half-lives (7 to 10 days) after intravitreal depot injections and clinical durations of action that usually exceed 4 weeks. Plasma VEGF concentrations decrease after intravitreal injections of bevacizumab and aflibercept because their systemic half-lives are extended by their Fc fragments. Extensive in vitro and in vivo testing shows that the drugs prevent VEGF-mediated activation of endothelial cells while exhibiting little evidence of toxicity. Further anti-VEGF drug development is on-going.

Functionalization-dependent induction of cellular survival pathways by CdSe quantum dots in primary normal human bronchial epithelial cells.

Quantum dots (QDs) are semiconductor nanocrystals exhibiting unique optical properties that can be exploited for many practical applications ranging from photovoltaics to biomedical imaging and drug delivery. A significant number of studies have alluded to the cytotoxic potential of these materials, implicating Cd-leaching as the causal factor. Here, we investigated the role of heavy metals in biological responses and the potential of CdSe-induced genotoxicity. Our results indicate that, while negatively charged QDs are relatively noncytotoxic compared to positively charged QDs, the same does not hold true for their genotoxic potential. Keeping QD core composition and size constant, 3 nm CdSe QD cores were functionalized with mercaptopropionic acid (MPA) or cysteamine (CYST), resulting in negatively or positively charged surfaces, respectively. CYST-QDs were found to induce significant cytotoxicity accompanied by DNA strand breakage. However, MPA-QDs, even in the absence of cytotoxicity and reactive oxygen species formation, also induced a high number of DNA strand breaks. QD-induced DNA damage was confirmed by identifying the presence of p53 binding protein 1 (53BP1) in the nuclei of exposed cells and subsequent diminishment of p53 from cytoplasmic cellular extracts. Further, high-throughput real-time PCR analyses revealed upregulation of DNA damage and response genes and several proinflammatory cytokine genes. Most importantly, transcriptome sequencing revealed upregulation of the metallothionein family of genes in cells exposed to MPA-QDs but not CYST-QDs. These data indicate that cytotoxic assays must be supplemented with genotoxic analyses to better understand cellular responses and the full impact of nanoparticle exposure when making recommendations with regard to risk assessment.

Transgenic increase in N-3/n-6 Fatty Acid ratio reduces maternal obesity-associated inflammation and limits adverse developmental programming in mice.

Maternal and pediatric obesity has risen dramatically over recent years, and is a known predictor of adverse long-term metabolic outcomes in offspring. However, which particular aspects of obese pregnancy promote such outcomes is less clear. While maternal obesity increases both maternal and placental inflammation, it is still unknown whether this is a dominant mechanism in fetal metabolic programming. In this study, we utilized the Fat-1 transgenic mouse to test whether increasing the maternal n-3/n-6 tissue fatty acid ratio could reduce the consequences of maternal obesity-associated inflammation and thereby mitigate downstream developmental programming. Eight-week-old WT or hemizygous Fat-1 C57BL/6J female mice were placed on a high-fat diet (HFD) or control diet (CD) for 8 weeks prior to mating with WT chow-fed males. Only WT offspring from Fat-1 mothers were analyzed. WT-HFD mothers demonstrated increased markers of infiltrating adipose tissue macrophages (P<0.02), and a striking increase in 12 serum pro-inflammatory cytokines (P<0.05), while Fat1-HFD mothers remained similar to WT-CD mothers, despite equal weight gain. E18.5 Fetuses from WT-HFD mothers had larger placentas (P<0.02), as well as increased placenta and fetal liver TG deposition (P<0.01 and P<0.02, respectively) and increased placental LPL TG-hydrolase activity (P<0.02), which correlated with degree of maternal insulin resistance (r = 0.59, P<0.02). The placentas and fetal livers from Fat1-HFD mothers were protected from this excess placental growth and fetal-placental lipid deposition. Importantly, maternal protection from excess inflammation corresponded with improved metabolic outcomes in adult WT offspring. While the offspring from WT-HFD mothers weaned onto CD demonstrated increased weight gain (P<0.05), body and liver fat (P<0.05 and P<0.001, respectively), and whole body insulin resistance (P<0.05), these were prevented in WT offspring from Fat1-HFD mothers. Our results suggest that reducing excess maternal inflammation may be a promising target for preventing adverse fetal metabolic outcomes in pregnancies complicated by maternal obesity.

Aflibercept for age-related macular degeneration: a game-changer or quiet addition?

PURPOSE: To describe the pharmacokinetics, preclinical studies, and clinical trials of the newly approved anti-vascular endothelial growth factor (VEGF) drug aflibercept (Eylea (VEGF Trap-Eye); Regeneron; and Bayer). DESIGN: Review with editorial commentary. METHODS: A review of the medical literature and pertinent Internet postings combined with analysis of key studies with expert opinion regarding the use of aflibercept for the treatment of exudative age-related macular degeneration. RESULTS: Aflibercept, a fusion protein with binding domains from native VEGF receptors, binds VEGF-A, VEGF-B, and placental growth factors 1 and 2 with high affinity. Preclinical ophthalmologic studies demonstrated that aflibercept suppresses choroidal neovascularization in several animal models. The results of phase 1 and 2 trials showed excellent short-term suppression of choroidal neovascularization in patients with exudative age-related macular degeneration and suggested a longer durability of aflibercept compared with other anti-VEGF drugs. The pivotal phase 3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration 1 and 2 trials showed that monthly and bimonthly aflibercept were noninferior to monthly ranibizumab at preventing vision loss (< 15-letter loss) with comparable vision gains and safety. Year 2 treatment involved monthly pro re nata injections with required injections every 3 months and maintained vision gains from the first year, with an average of 4.2 injections of aflibercept and 4.7 injections of ranibizumab. CONCLUSIONS: Aflibercept promises to deliver excellent visual outcomes for exudative age-related macular degeneration patients while undergoing fewer injections compared with ranibizumab. With a wholesale cost of $1850 per dose, the cost per patient with aflibercept treatment promises to be lower than with ranibizumab.

Early postoperative care following endoscopic sinus surgery: an evidence-based review with recommendations.

BACKGROUND: Early postoperative care following endoscopic sinus surgery (ESS) has been suggested to minimize avoidable complications and optimize long-term outcomes. Several postoperative care strategies have been proposed but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach to early postoperative care following ESS. METHODS: A systematic review of the literature was performed and the Clinical Practice Guideline Manual, Conference on Guideline Standardization (COGS), and the Appraisal of Guidelines and Research Evaluation (AGREE) instrument recommendations were followed. Study inclusion criteria were: adult population >18 years old; chronic rhinosinusitis (CRS) based on published diagnostic criteria; ESS following failed medical therapy; primary study objective was to evaluate an ESS early postoperative care strategy; and clearly defined primary clinical end-point. RESULTS: This review identified and evaluated the literature on 7 early postoperative care strategies following ESS: saline irrigations, sinus cavity debridements, systemic steroids, topical steroids, oral antibiotics, topical decongestants, and drug-eluting spacers/stents. CONCLUSION: Based on the available evidence, use of nasal saline irrigation, sinus cavity debridement, and standard topical nasal steroid spray are recommended early postoperative care interventions. Postoperative antibiotic, systemic steroid, nonstandard topical nasal steroid solution, and/or drug-eluting spacers/stents are options in postoperative management. These evidence-based recommendations should not necessarily be applied to all postoperative patients and clinical judgment, in addition to evidence, is critical to determining the most appropriate care.

Physician attitudes and practices of enteral nutrition as primary treatment of paediatric Crohn disease in North America.

BACKGROUND: The use of exclusive enteral nutrition (EEN) in children with Crohn disease has not been universally adopted by North American paediatric gastroenterologists. This is in stark contrast to their European counterparts. The present study aimed to define attitudes and practice patterns of EEN use by members of the North American Society for Paediatric Gastroenterology, Hepatology, and Nutrition. METHODS: Members were contacted by e-mail and provided with access to a Web-based survey. RESULTS: Surveys were completed by 326 of 1162 (30.7%) eligible North American Society for Paediatric Gastroenterology, Hepatology, and Nutrition members from North America (86% United States, 14% Canada). Thirty-one percent of respondents reported never using EEN, 55% reported sparse use, and 12% reported regular use. Physicians in Canada reported significantly more use than those in United States (P < 0.001). Currently working and previously working in a centre where EEN was used were highly correlated with both the perceived appropriateness of EEN and the regularity of its use (P < 0.01). More American physicians than Canadian physicians reported that concurrent medical therapy was necessary to induce remission (P < 0.001). Canadian respondents were more likely to use maintenance therapy than American respondents (P = 0.02). Compliance issues were seen as the main disadvantages of EEN and as the major barrier to increased use by nonregular users. CONCLUSIONS: There are significant variations in the patterns of use and the acceptance of EEN between Canada and the United States, with Canadian physicians showing a greater use of EEN. The use of EEN appears influenced by the extent to which physicians are exposed to its use both in their training and in their current practice setting.

Quantum dot DNA bioconjugates: attachment chemistry strongly influences the resulting composite architecture.

The unique properties provided by hybrid semiconductor quantum dot (QD) bioconjugates continue to stimulate interest for many applications ranging from biosensing to energy harvesting. Understanding both the structure and function of these composite materials is an important component in their development. Here, we compare the architecture that results from using two common self-assembly chemistries to attach DNA to QDs. DNA modified to display either a terminal biotin or an oligohistidine peptidyl sequence was assembled to streptavidin/amphiphilic polymer- or PEG-functionalized QDs, respectively. A series of complementary acceptor dye-labeled DNA were hybridized to different positions on the DNA in each QD configuration and the separation distances between the QD donor and each dye-acceptor probed with Förster resonance energy transfer (FRET). The polyhistidine self-assembly yielded QD-DNA bioconjugates where predicted and experimental separation distances matched reasonably well. Although displaying efficient FRET, data from QD-DNA bioconjugates assembled using biotin-streptavidin chemistry did not match any predicted separation distances. Modeling based upon known QD and DNA structures along with the linkage chemistry and FRET-derived distances was used to simulate each QD-DNA structure and provide insight into the underlying architecture. Although displaying some rotational freedom, the DNA modified with the polyhistidine assembles to the QD with its structure extended out from the QD-PEG surface as predicted. In contrast, the random orientation of streptavidin on the QD surface resulted in DNA with a wide variety of possible orientations relative to the QD which cannot be controlled during assembly. These results suggest that if a particular QD biocomposite structure is desired, for example, random versus oriented, the type of bioconjugation chemistry utilized will be a key influencing factor.

Preconceptional paternal exposure to depleted uranium: transmission of genetic damage to offspring.

Depleted uranium (DU) is an alpha particle emitter and radioactive heavy metal used in military applications. Due to internalization of DU during military operations and the ensuing chronic internal exposure to DU, there are concerns regarding its potential health effects. Preconceptional paternal irradiation has been implicated as a causal factor in childhood cancer and it has been suggested that this paternal exposure to radiation may play a role in the occurrence of leukemia and other cancers to offspring. Similarly, in vivo heavy metal studies have demonstrated that carcinogenic effects can occur in unexposed offspring. Using a transgenic mouse system employing a lambda shuttle vector allowing mutations (in the lacI gene) to be analyzed in vitro, we have investigated the possibility that chronic preconceptional paternal DU exposure can lead to transgenerational transmission of genomic instability. The mutation frequencies in vector recovered from the bone marrow cells of the F1 offspring of male parents exposed to low, medium, and high doses of internalized DU for 7 mo were evaluated and compared to control, tantalum, nickel, and gamma radiation F1 samples. Results demonstrate that as paternal DU-dose increased there was a trend towards higher mutation frequency in vector recovered from the DNA obtained from bone marrow of F1 progeny; medium and high dose DU exposure to P1 fathers resulted in a significant increase in mutation frequency in F1 offspring (3.57 +or - 0.37 and 4.81 + or - 0.43 x 10; p < 0.001) in comparison to control (2.28 + or - 0.31 x 10). The mutation frequencies from F1 offspring of low dose DU, Ta- or Ni-implanted fathers (2. 71 + or - 0.35, 2.38 + or - 0.35, and 2.93 + or - 0.39 x 10, respectively) were not significantly different than control levels (2.28 + or - 0.31 x 10). Offspring from Co (4 Gy) irradiated fathers did demonstrate an increased lacI mutation frequency (4.69 + or - 0.48 x 10) as had been shown previously. To evaluate the role of radiation involved in the observed DU effects, males were exposed to equal concentrations (50 mg U L) of either enriched uranium or DU in their drinking water for 2 mo prior to breeding. A comparison of these offspring indicated that there was a specific-activity dependent increase in offspring bone marrow mutation frequency. Taken together these uranyl nitrate data support earlier results in other model systems showing that radiation can play a role in DU-induced biological effects in vitro. However, since the lacI mutation model measures point mutations and cannot measure large deletions that are characteristic of radiation damage, the role of DU chemical effects in the observed offspring mutation frequency increase may also be significant. Regardless of the question of DU-radiation vs. DU-chemical effects, the data indicate that there exists a route for transgenerational transmission of factor(s) leading to genomic instability in F1 progeny from DU-exposed fathers.

Antifouling sesterterpenes from the New Zealand marine sponge Semitaspongia bactriana.

Three antifouling (AF) sesterterpenes have been isolated from the New Zealand marine sponge Semitaspongia bactriana with toxicity against the diatom Nitzschia closterium and bryozoan Bugula neritina. The three metabolites have been characterised by spectroscopic techniques as 7E,12E,20Z-variabilin (1), cavernosolide (2) and lintenolide A (3) (also called spongianolide C) and have low micromolar activity against our two test species. The gamma-hydroxybutenolide containing sesterterpenes (2 and 3) show the most promise, with relative stability and suitable lipophilicity for incorporation of either these metabolites, or synthetic analogues, as biocides to produce paints or plastics with AF properties.

DNA methylation during depleted uranium-induced leukemia.

OBJECTIVES: The radioactive heavy metal depleted uranium (DU) is used in kinetic-energy penetrators in military applications. The objective of this study was to determine involvement of DNA methylation in DU-induced leukemia. METHODS: Methylation was measured by direct analysis of 5-methylcytosine content of spleen DNA in DU leukemic mice. RESULTS: Spleen hypomethylation occurred during DU-induced leukemogenesis (chronic internal DU exposure). Aberrant gene transcription was also detected. CONCLUSIONS: Epigenetic mechanisms are implicated in DU-induced leukemia. These data are evidence of aberrant DNA hypomethylation being associated with DU leukemogenesis.

Colostrinin: a naturally occurring compound derived from mammalian colostrum with efficacy in treatment of neurodegenerative diseases, including Alzheimer's.

Neurodegenerative illnesses such as Alzheimer's disease and their debilitating effects pose a major problem as their incidence increases. Although clinical management of neurodegenerative diseases usually involves symptomatic treatment, Colostrinin() (CLN), which has efficacy in counteracting neural degradation and in stimulating neural growth, might prove to be a more effective means to deal with the causes of Alzheimer's and other neurodegenerative diseases. Evidence for the clinical efficacy of CLN is discussed and recent data examined showing the remarkable ability of CLN to reduce oxidative stress, prevent beta-amyloid aggregation and prolong the lifespan in a laboratory model of premature ageing. An increasingly important application for CLN has been as a nutraceutical product for use in the early stages of cognitive decline in humans, with licensed use in North America and Australia, and now in Europe. It might also be of considerable utility as a veterinary nutraceutical for companion animals.

Uranium concentrations in South African herbal remedies.

South Africa contains some of the world's largest mineral deposits, which include uranium. Uranium is mined as a by-product of gold production. The uranium content of the surface soil and groundwater in South Africa has been measured and shows marked variation, depending on location. Herbal remedies are collected by traditional healers from many sites, some of which may be contaminated. Thirty herbal remedies were analyzed using a sensitive adsorptive stripping voltammetry method. Eight samples had levels below the limit of detection, but in five the levels were greatly elevated, showing concentrations above 40,000 ppb. The mean uranium concentration of the remainder of the specimens was of the order of 15,000 ppb. We have attempted to put these data into context by comparison with other studies of absorption of uranium by the oral route.

Leukemic transformation of hematopoietic cells in mice internally exposed to depleted uranium.

Depleted uranium (DU) is a dense heavy metal used in military applications. During military conflicts, US military personnel have been wounded by DU shrapnel. The health effects of embedded DU are unknown. Published data from our laboratory demonstrated that DU exposure in vitro can transform immortalized human osteoblast cells (HOS) to the tumorigenic phenotype. Results from our laboratory have also shown that DU is genotoxic and mutagenic in cultured human cells. Internalized DU could be a carcinogenic risk and concurrent alpha particle and heavy metal toxic effects complicate this potential risk. Anecdotal reports have suggested that DU can cause leukemia. To better assess this risk, we have developed an in vivo leukemogenesis model. This model involves using murine hematopoietic cells (FDC-P1) that are dependent on stimulation by granulocyte-macrophage colony stimulating factor (GM-CSF) or interleukin 3 (IL-3) and injected into mice to produce myeloid leukemia. Although immortalized, these cells are not tumorigenic on subcutaneous inoculation in mice. Intravenous injection of FDC-P1 cells into DU-implanted DBA/2 mice was followed by the development of leukemias in 76% of all mice implanted with DU pellets. In contrast, only 12% of control mice developed leukemia. Karyotypic analysis confirmed that the leukemias originated from FDC-P1 cells. The growth properties of leukemic cells from bone marrow, spleen, and lymph node were assessed and indicate that the FDC-P1 cells had become transformed in vivo. The kidney, spleen, bone marrow, muscle, and urine showed significant elevations in tissue uranium levels prior to induction of leukemia. These results demonstrated that a DU altered in vivo environment may be involved in the pathogenesis of DU induced leukemia in an animal model.