The Relationship between Physical Activity, Physical Fitness, Cognition, and Academic Outcomes in School-Aged Latino Children: A Scoping Review.

This scoping review provides an overview of the relationship between physical activity, physical fitness, cognition, and academic outcomes in Latino school-aged children and identifies areas for future research. A primary search was conducted in PubMed, PsycINFO, Web of Science, and ERIC for original-research articles meeting the inclusion criteria; the search results were uploaded into PICO Portal and assessed by two independent reviewers. Of the 488 initial search results, 50 articles were eligible for full-text review, and 38 were included in this review. Most studies were cross-sectional, conducted in the United States or Chile, and included children 5-18 years old. Overall, the majority of articles reported positive associations between physical activity or physical fitness and cognitive outcomes (n = 11/12; 91.7%), and physical activity or physical fitness and academic outcomes (n = 22/28; 78.6%). In sum, this review provided consistent evidence for higher amounts of physical activity and greater physical fitness to be associated with various positive cognitive and academic outcomes in a school-aged Latino population. This scoping review also elucidated a substantial gap in the research regarding study design, with a discernible lack of interventional efforts. Future studies should test physical activity interventional strategies to optimize cognitive and academic outcomes in school-aged Latino populations.

Voriconazole-Induced Periostitis: A Case Report.

Voriconazole-induced periostitis (VIP) is an uncommon side effect typically seen in immunosuppressed patients requiring prolonged antifungal therapy. These patients can present with bone pain, fragility, and elevated alkaline phosphatase (ALP). We present a case of VIP in a 72-year-old immunocompromised female on antifungal therapy presenting with a comminuted intertrochanteric fracture after a ground-level fall. VIP, although rare, should be included as a differential diagnosis for patients presenting with bone pain and/or fractures with radiographic features of periostitis. This is particularly true when there is a history of or prior imaging suggesting a solid organ transplant. In these cases, a dedicated review of current medications noting long-term voriconazole use in the absence of underlying rheumatologic disease can result in a confident diagnosis.

The postulated innocuity of lifetime exposure to aluminium should be reappraised.

Because of its chemical versatility and abundance in nature, aluminium is employed in a myriad of frequently used products - including cosmetics and food additives - and applications - drinking water purification procedures being an example. Despite what its widespread use might suggest, aluminium's harmlessness is a matter of debate in the scientific community. In this article we trace the lines of a growing questioning about the potential mutagenic effects of this metal, due to the data produced over the recent years, and with an eye to the discussions currently underway in this regard between the scientific community, industry, and regulatory bodies.

Small mammals reduce activity during high moon illumination under risk of predation by introduced predators.

Predation influences prey survival and drives evolution of anti-predator behaviour. Anti-predator strategies by prey are stimulated by direct encounters with predators, but also by exposure to indicators of risk such as moonlight illumination and vegetation cover. Many prey species will suffer increased risk on moonlit nights, but risk may be reduced by the presence of dense vegetation. Determining the role of vegetation in reducing perceived risk is important, especially given predictions of increased global wildfire, which consumes vegetation and increases predation. We used remote cameras in southeastern Australia to compare support for the predation risk and habitat-mediated predation risk hypotheses. We examined the influence of moonlight and understorey cover on seven 20-2500 g mammalian prey species and two introduced predators, red foxes and feral cats. Activity of all prey species reduced by 40-70% with increasing moonlight, while one species (bush rat) reduced activity in response to increasing moonlight more sharply in low compared to high understorey cover. Neither predator responded to moonlight. Our findings supported the predation risk hypothesis and provided limited support for the habitat-mediated predation risk hypothesis. For prey, perceived costs of increased predation risk on moonlit nights outweighed any benefits of a brighter foraging environment.

Aluminum Enters Mammalian Cells and Destabilizes Chromosome Structure and Number.

Chromosome instability (CIN) consists of high rates of structural and numerical chromosome abnormalities and is a well-known hallmark of cancer. Aluminum is added to many industrial products of frequent use. Yet, it has no known physiological role and is a suspected human carcinogen. Here, we show that V79 cells, a well-established model for the evaluation of candidate chemical carcinogens in regulatory toxicology, when cultured in presence of aluminum-in the form of aluminum chloride (AlCl3) and at concentrations in the range of those measured in human tissues-incorporate the metal in a dose-dependent manner, predominantly accumulating it in the perinuclear region. Intracellular aluminum accumulation rapidly leads to a dose-dependent increase in DNA double strand breaks (DSB), in chromosome numerical abnormalities (aneuploidy) and to proliferation arrest in the G2/M phase of the cell cycle. During mitosis, V79 cells exposed to aluminum assemble abnormal multipolar mitotic spindles and appear to cluster supernumerary centrosomes, possibly explaining why they accumulate chromosome segregation errors and damage. We postulate that chronic aluminum absorption favors CIN in mammalian cells, thus promoting carcinogenesis.

Genomic Instability Is an Early Event in Aluminium-Induced Tumorigenesis.

Genomic instability is generally considered as a hallmark of tumorigenesis and a prerequisite condition for malignant transformation. Aluminium salts are suspected environmental carcinogens that transform mammary epithelial cells in vitro through unknown mechanisms. We report here that long-term culture in the presence of aluminium chloride (AlCl3) enables HC11 normal mouse mammary epithelial cells to form tumours and metastases when injected into the syngeneic and immunocompetent BALB/cByJ strain. We demonstrate that AlCl3 rapidly increases chromosomal structural abnormalities in mammary epithelial cells, while we failed to detect direct modulation of specific mRNA pathways. Our observations provide evidence that clastogenic activity-a well-recognized inducer of genomic instability-might account in part for the transforming abilities of aluminium in mammary epithelial cells.

Utilizing Closed Incisional Negative Pressure Therapy Reduces Peripheral Bypass Infection Rates Without Increasing Costs.

INTRODUCTION: We evaluated outcomes of closed incisional negative pressure therapy (ciNPT) on surgical site infection (SSI) rates in lower extremity bypass patients. We sought to determine whether or not the routine use of ciNPT is a cost-effective measure. METHODS: During a period from May 2018 to August 2018, our institution transitioned to the routine use of ciNPT for re-vascularization procedures. We retrospectively reviewed our outcomes before and after the initiation of ciNPT. Group A included patients from September 2017 to April 2018 without ciNPT and Group B included patients from September 2018 to April 2019 with ciNPT. Chi-squared analysis was performed and the p value was set at <0.05 to obtain statistical significance. Cost analysis was separately performed utilizing hospital metrics. RESULTS: There were a total of 102 patients in Group A and 113 patients in Group B. There was no difference in demographic information between the two groups. The overall SSI rate for Group A was 11.8% (12/102). Group B had an overall SSI rate of 3.5% (4/113; p=0.02). Deep infection rate for Group A was 7% (7/102) and for Group B was 1% (1/113; p=0.01). Cost analysis demonstrated a minimum of $62,000 in infection-related cost savings between both groups. CONCLUSIONS: ciNPT has had a profound effect on our practice and has resulted in a decrease in both deep and superficial infections. This has led to a significant cost-effective measure for our institution. We now routinely use ciNPT on all lower extremity bypass patients.

Consequences of pre-injury utilization of direct oral anticoagulants in patients with traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: The rapid adoption and widespread use of direct oral anticoagulants (DOACs) has outpaced research efforts to establish their effects in bleeding trauma patients. In patients with complicated traumatic brain injury (TBI) caused by intracranial hemorrhage, DOAC use may be associated with higher bleeding volume and potentially more disastrous sequelae than use of vitamin K antagonists (VKAs). In the current systematic review and meta-analysis we set out to evaluate the literature on the relationship between preinjury DOAC use and course of the intracranial hemorrhage. (ICH), its treatment and mortality rates in TBI patients, and to compare these outcomes to those of patients with preinjury VKA use. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched using a search strategy including three main terms: "traumatic brain injury," "direct oral anticoagulants," and "vitamin K antagonists." There were 1,446 abstracts screened, and ultimately, six included articles. Random effects modeling meta-analysis was performed on in-hospital mortality, ICH progression and neurosurgical intervention rate. RESULTS: All cohorts had similar baseline and emergency department parameters. Within individual studies surgery rate, reversal agents used, ICH progression and in-hospital mortality differed significantly between DOAC and VKA cohorts. Meta-analysis showed no significant difference in in-hospital mortality (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.23-4.06; I = 76%; p = 0.97), neurosurgical interventions (OR, 0.48; 95% CI, 0.14-1.63; p = 0.24), or ICH progression rates (OR, 1.86; 95% CI, 0.32-10.66; p = 0.49) between patients that used preinjury DOACs versus patients that used VKAs. CONCLUSION: Direct oral anticoagulant-using mild TBI patients do not appear to be at an increased risk of in-hospital mortality, nor of increased ICH progression or surgery rates, compared with those taking VKAs. LEVEL OF EVIDENCE: Systematic review, level III.

Evolution of Biomarkers of Atherogenic Risk in Liver Transplantation Recipients.

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.

Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.

BACKGROUND AND AIM: The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. METHODS AND RESULTS: We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. CONCLUSION: Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.

Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells.

Aluminium salts, present in many industrial products of frequent use like antiperspirants, anti-acid drugs, food additives and vaccines, have been incriminated in contributing to the rise in breast cancer incidence in Western societies. However, current experimental evidence supporting this hypothesis is limited. For example, no experimental evidence that aluminium promotes tumorigenesis in cultured mammary epithelial cells exists. We report here that long-term exposure to concentrations of aluminium-in the form of aluminium chloride (AlCl3 )-in the range of those measured in the human breast, transform normal murine mammary gland (NMuMG) epithelial cells in vitro as revealed by the soft agar assay. Subcutaneous injections into three different mouse strains with decreasing immunodeficiency, namely, NOD SCID gamma (NSG), NOD SCID or nude mice, revealed that untreated NMuMG cells form tumors and metastasize, to a limited extent, in the highly immunodeficient and natural killer (NK) cell deficient NSG strain, but not in the less permissive and NK cell competent NOD SCID or nude strains. In contrast, NMuMG cells transformed in vitro by AlCl3 form large tumors and metastasize in all three mouse models. These effects correlate with a mutagenic activity of AlCl3 . Our findings demonstrate for the first time that concentrations of aluminium in the range of those measured in the human breast fully transform cultured mammary epithelial cells, thus enabling them to form tumors and metastasize in well-established mouse cancer models. Our observations provide experimental evidence that aluminium salts could be environmental breast carcinogens.

Ataxia-telangiectasia mutated (ATM) silencing promotes neuroblastoma progression through a MYCN independent mechanism.

Neuroblastoma, a childhood cancer with highly heterogeneous biology and clinical behavior, is characterized by genomic aberrations including amplification of MYCN. Hemizygous deletion of chromosome 11q is a well-established, independent marker of poor prognosis. While 11q22-q23 is the most frequently deleted region, the neuroblastoma tumor suppressor in this region remains to be identified. Chromosome bands 11q22-q23 contain ATM, a cell cycle checkpoint kinase and tumor suppressor playing a pivotal role in the DNA damage response. Here, we report that haploinsufficiency of ATM in neuroblastoma correlates with lower ATM expression, event-free survival, and overall survival. ATM loss occurs in high stage neuroblastoma without MYCN amplification. In SK-N-SH, CLB-Ga and GI-ME-N human neuroblastoma cells, stable ATM silencing promotes neuroblastoma progression in soft agar assays, and in subcutaneous xenografts in nude mice. This effect is dependent on the extent of ATM silencing and does not appear to involve MYCN. Our findings identify ATM as a potential haploinsufficient neuroblastoma tumor suppressor, whose inactivation mirrors the increased aggressiveness associated with 11q deletion in neuroblastoma.

Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg-1·day-1 by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model.

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg(-1)·day(-1) by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

Work of breathing indices in infants with respiratory insufficiency receiving high-flow nasal cannula and nasal continuous positive airway pressure.

OBJECTIVE: To compare work of breathing (WOB) indices between two nCPAP settings and two levels of HFNC in a crossover study. STUDY DESIGN: Infants with a CGA 28-40 weeks, baseline of HFNC 3-5 lpm or nCPAP 5-6 cmH2O and fraction of inspired oxygen ≤40% were eligible. WOB was analyzed using respiratory inductive plethysmography (RIP) for each of the four modalities: HFNC 3 and 5 lpm, nCPAP 5 and 6 cmH2O. N=20; Study weight 1516 g (±40 g). RESULT: Approximately 12,000 breaths were analyzed indicating a high degree of asynchronous breathing and elevated WOB indices at all four levels of support. Phase angle values (means) (P<0.01): HFNC 3 lpm (114.7°), HFNC 5 lpm (96.7°), nCPAP 5 cmH2O (87.2°), nCPAP 6 cmH2O (80.5°). The mean phase relation of total breath (PhRTB) (means) (P<0.01): HFNC 3 lpm (63.2%), HFNC 5 lpm (55.3%), nCPAP 5 cmH2O (49.3%), nCPAP 6 cmH2O (48.0%). The relative labored breathing index (LBI) (means) (P≤0.001): HFNC 3 lpm (1.39), HFNC 5 lpm (1.31), nCPAP 5 cmH2O (1.29), nCPAP 6 cmH2O (1.26). Eighty-two percent of the study subjects-respiratory mode combinations displayed clustering, in which a proportion of breaths either occurred predominantly out-of-phase (relative asynchrony) or in-phase (relative synchrony). CONCLUSION: In this study, WOB indices were statistically different, yet clinically similar in that they were elevated with respect to normal values. These infants with mild-to-moderate respiratory insufficiency demonstrate a meaningful elevation in WOB indices and continue to require non-invasive respiratory support. Patient variability exists with regard to biphasic clustered breathing patterns and the level of supplemental fraction of inspired oxygen ≤40% alone does not provide guidance to the optimal matching of WOB indices and non-invasive respiratory support.

Radiation safety education in vascular surgery training.

OBJECTIVE: Endovascular volume during vascular surgery training has increased profoundly over recent decades, providing heavy exposure to ionizing radiation. The study purpose was to examine the radiation safety training and practices of current vascular surgery trainees. METHODS: An anonymous survey was distributed to all current U.S. trainees. Responses were compared according to the presence of formal radiation safety training and also the trainees' perception of their attendings' adherence to As Low As Reasonably Achievable (ALARA) strategies. RESULTS: The response rate was 14%. Forty-five percent had no formal radiation safety training, 74% were unaware of the radiation safety policy for pregnant females, 48% did not know their radiation safety officer's contact information, and 43% were unaware of the yearly acceptable levels of radiation exposure. Trained residents knew more basic radiation safety information, and more likely wore their dosimeter badges (P < .05). Trained residents found their radiation safety officer helpful in developing safety habits; untrained residents relied on other residents (P < .05). Trainees who felt their attendings consistently practiced ALARA strategies more likely practiced ALARA themselves (P < .05). CONCLUSIONS: The lack of formal radiation safety training in respondents may reflect an inadequate state of radiation safety education and practices among U.S. vascular surgery residents.

Effects of hepatitis C virus on cardiovascular risk in infected patients: a comparative study.

The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-α) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-α) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-α/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-α, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naïve and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF).

Cardiovascular effects of a PEGylated apelin.

Several studies have documented cardiovascular effects of apelin, including enhanced inotropy and vasodilation. However, these cardiovascular effects are short lived due to the predicted short circulating half-life of the apelin peptide. To address this limitation of apelin, we pursued N-terminal PEGylation of apelin and examined the cardiovascular effects of the PEGylated apelin. A 40kDa PEG conjugated apelin-36 (PEG-apelin-36) was successfully produced with N-terminal conjugation, high purity (>98%) and minimum reduction of APJ receptor binding affinity. Using an adenylate cyclase inhibition assay, comparable in vitro bioactivity was observed between the PEG-apelin-36 and unmodified apelin-36. In vivo evaluation of the PEG-apelin-36 was performed in normal rats and rats with myocardial infarction (MI). Cardiac function was assessed via echocardiography before, during a 20 min IV infusion and up to 100 min post peptide infusion. Similar increases in cardiac ejection fraction (EF) were observed during the infusion of PEG-apelin-36 and apelin-36 in normal rats. However, animals that received PEG-apelin-36 maintained significantly increased EF over the 100 min post infusion monitoring period compared to the animals that received unmodified apelin-36. Interestingly, EF increases observed with PEG-apelin-36 and apelin-36 were greater in the MI rats. PEG-apelin-36 had a prolonged circulating life compared to apelin-36 in rats. There were no changes in aortic blood pressure when PEG-apelin-36 or apelin-36 was administered. To our knowledge this is the first report of apelin PEGylation and documentation of its cardiovascular effects.

Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells.

Aluminium salts used as antiperspirants have been incriminated as contributing to breast cancer incidence in Western societies. To date, very little or no epidemiological or experimental data confirm or infirm this hypothesis. We report here that in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminium chloride (AlCl(3) ) concentrations of 10-300 µ m, i.e. up to 100 000-fold lower than those found in antiperspirants, and in the range of those recently measured in the human breast, results in loss of contact inhibition and anchorage-independent growth. These effects were preceded by an increase of DNA synthesis, DNA double strand breaks (DSBs), and senescence in proliferating cultures. AlCl(3) also induced DSBs and senescence in proliferating primary human mammary epithelial cells. In contrast, it had no similar effects on human keratinocytes or fibroblasts, and was not detectably mutagenic in bacteria. MCF-10A cells morphologically transformed by long-term exposure to AlCl(3) display strong upregulation of the p53/p21(Waf1) pathway, a key mediator of growth arrest and senescence. These results suggest that aluminium is not generically mutagenic, but similar to an activated oncogene, it induces proliferation stress, DSBs and senescence in normal mammary epithelial cells; and that long-term exposure to AlCl(3) generates and selects for cells able to bypass p53/p21(Waf1) -mediated cellular senescence. Our observations do not formally identify aluminium as a breast carcinogen, but challenge the safety ascribed to its widespread use in underarm cosmetics.