Marco Vinceti

The Impact of In Vivo Reflectance Confocal Microscopy on the Diagnostic Accuracy of Lentigo Maligna and Equivocal Pigmented and Nonpigmented Macules of the Face.

Limited studies have reported the in vivo reflectance confocal microscopy (RCM) features of lentigo maligna (LM). A total of 64 RCM features were scored retrospectively and blinded to diagnosis in a consecutive series of RCM sampled, clinically equivocal, macules of the face (n=81 LM, n=203 benign macules (BMs)). In addition to describing RCM diagnostic features for LM (univariate), an algorithm was developed (LM score) to distinguish LM from BM. This comprised two major features each scoring +2 points (nonedged papillae and round large pagetoid cells > 20 microm), and four minor features; three scored +1 point each (three or more atypical cells at the dermoepidermal junction in five 0.5 x 0.5 mm(2) fields, follicular localization of atypical cells, and nucleated cells within the dermal papillae), and one (negative) feature scored -1 point (a broadened honeycomb pattern). A LM score of > or = 2 resulted in a sensitivity of 85% and specificity of 76% for the diagnosis of LM (odds ratio (OR) for LM 18.6; 95% confidence interval: 9.3-37.1). The algorithm was equally effective in the diagnosis of amelanotic lesions and showed good interobserver reproducibility (87%). In a test set of 29 LMs and 44 BMs, the OR for LM was 60.7 (confidence interval: 11.9-309) (93% sensitivity, 82% specificity).

Adverse health effects of selenium in humans

Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.

Pooled analysis of recent studies on magnetic fields and childhood leukaemia

Background:Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000.Methods:Seven studies with a total of 10 865 cases and 12 853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences.Results:In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1–0.2 μT, 0.2–0.3 μT and ⩾0.3 μT, compared with <0.1 μT, were 1.07 (95% CI 0.81–1.41), 1.16 (0.69–1.93) and 1.44 (0.88–2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model.Conclusions:Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic.

A prospective study of dietary selenium intake and risk of type 2 diabetes

BackgroundGrowing evidence raises concern about possible associations of high selenium exposure with diabetes in selenium-replete populations such as the US. In countries with lower selenium status, such as Italy, there is little epidemiological evidence on the association between selenium and diabetes. This study examined the prospective association between dietary selenium intake and risk of type 2 diabetes.MethodsThe ORDET cohort study comprised a large sample of women from Northern Italy (n = 7,182). Incident type 2 diabetes was defined as a self-report of a physician diagnosis, use of antidiabetic medication, or a hospitalization discharge. Dietary selenium intake was measured by a semi-quantitative food-frequency questionnaire at the baseline examination (1987-1992). Participants were divided in quintiles based on their baseline dietary selenium intake.ResultsAverage selenium intake at baseline was 55.7 μg/day. After a median follow-up of 16 years, 253 women developed diabetes. In multivariate logistic regression analyses, the odds ratio for diabetes comparing the highest to the lowest quintile of selenium intake was 2.39, (95% CI: 1.32, 4.32; P for linear trend = 0.005). The odds ratio for diabetes associated with a 10 μg/d increase in selenium intake was 1.29 (95% CI: 1.10, 1.52).ConclusionsIn this population, increased dietary selenium intake was associated with an increased risk of type 2 diabetes. These findings raise additional concerns about the association of selenium intake above the Recommended Dietary Allowance (55 μg/day) with diabetes risk.

Risk of Chronic Low-Dose Selenium Overexposure in Humans: Insights From Epidemiology and Biochemistry

The latest developments of epidemiologic and biochemical research suggest that current upper limits of intake for dietary selenium and for overall selenium exposure may be inadequate to protect human health. In particular, recent experimental and observational prospective studies indicate a diabetogenic effect of selenium at unexpectedly low levels of intake. Experimental evidence from laboratory studies and veterinary medicine appears to confirm previous epidemiologic observations that selenium overexposure is associated with an increased risk of amyotrophic lateral sclerosis, and a recent large trial indicated no beneficial effect in preventing prostate cancer. Moreover, the pro-oxidant properties of selenium species and the observation that the selenium-containing enzymes glutathione peroxidases are induced by oxidative stress imply that the increase in enzymatic activity induced by this metalloid may represent at least in part a compensatory response. Taken together, the data indicate that the upper safe limit of organic and inorganic selenium intake in humans may be lower than has been thought and that low-dose chronic overexposure to selenium may be considerably more widespread than supposed.

Epidemiological survey of amyotrophic lateral sclerosis in the province of Reggio Emilia, Italy: influence of environmental exposure to lead.

We carried out a retrospective incidence, prevalence and mortality survey of amyotrophic lateral sclerosis (ALS) in the province of Reggio Emilia, northern Italy. Based on 79 patients, the mean incidence per year for the period 1980 through 1992 was 1.5 cases per 100,000. On December 31st, 1992, the prevalence rate was 5.4 per 100,000. In the 10-year period of 1983-1992 the average mortality rate was 1.3 per 100,000 per year. The average age at onset was 61.3 +/- 10.2, the average survival period thereafter was 26.3 months +/- 17.7; 27.3 +/- 17.6 for classic ALS, 19.5 +/- 8.4 for progressive bulbar palsy and 36.3 +/- 41.4 for pseudopolyneuritic ALS. The incidence rate, recorded in public health district No.12, an area with documented lead pollution since the 1970s, was standardized to the sex and age of the population of the province. Its incidence and prevalence rate were comparable to the rates found in the remaining area of the province.

The need for a reassessment of the safe upper limit of selenium in drinking water

Results of recent epidemiologic studies suggest the need to reassess the safe upper limit in drinking water of selenium, a metalloid with both toxicological and nutritional properties. Observational and experimental human studies on health effects of organic selenium compounds consumed through diet or supplements, and of inorganic selenium consumed through drinking water, have shown that human toxicity may occur at much lower levels than previously surmised. Evidence indicates that the chemical form of selenium strongly influences its toxicity, and that its biological activity may differ in different species, emphasizing the importance of the few human studies on health effects of the specific selenium compounds found in drinking water. Epidemiologic studies that investigated the effects of selenate, an inorganic selenium species commonly found in drinking water, together with evidence of toxicity of inorganic selenium at low levels in from in vitro and animal studies, indicate that health risks may occur at exposures below the current European Union and World Health Organization upper limit and guideline of 10 and 40 μg/l, respectively, and suggest reduction to 1 μg/l in order to adequately protect human health. Although few drinking waters are currently known to have selenium concentrations exceeding this level, the public health importance of this issue should not be overlooked, and further epidemiologic research is critically needed in this area.

Selenium neurotoxicity in humans: Bridging laboratory and epidemiologic studies

Selenium is a metalloid of considerable interest in the human from both a toxicological and a nutritional perspective, with a very narrow safe range of intake. Acute selenium intoxication is followed by adverse effects on the nervous system with special clinical relevance, while the neurotoxicity of long-term overexposure is less characterized and recognized. We aimed to address this issue from a public health perspective, focusing on both laboratory studies and the few epidemiologic human studies available, with emphasis on their methodological strengths and limitations. The frequently overlooked differences in toxicity and biological activity of selenium compounds are also outlined. In addition to lethargy, dizziness, motor weakness and paresthesias, an excess risk of amyotrophic lateral sclerosis is the effect on the nervous system which has been more consistently associated with chronic low-level selenium overexposure, particularly to its inorganic compounds. Additional research efforts are needed to better elucidate the neurotoxic effects exerted by selenium overexposure.

Reflectance confocal microscopy and features of melanocytic lesions: An internet-based study of the reproducibility of terminology

OBJECTIVE To test the interobserver and intraobserver reproducibility of the standard terminology for description and diagnosis of melanocytic lesions in in vivo confocal microscopy. DESIGN A dedicated Web platform was developed to train the participants and to allow independent distant evaluations of confocal images via the Internet. SETTING Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy. PARTICIPANTS The study population was composed of 15 melanomas, 30 nevi, and 5 Spitz/Reed nevi. Six expert centers were invited to participate at the study. Intervention Evaluation of 36 features in 345 confocal microscopic images from melanocytic lesions. MAIN OUTCOME MEASURE Interobserved and intraobserved agreement, by calculating the Cohen kappa statistics measure for each descriptor. RESULTS High overall levels of reproducibility were shown for most of the evaluated features. In both the training and test sets there was a parallel trend of decreasing kappa values as deeper anatomic skin levels were evaluated. All of the features, except 1, used for melanoma diagnosis, including roundish pagetoid cells, nonedged papillae, atypical cells in basal layer, cerebriform clusters, and nucleated cells infiltrating dermal papillae, showed high overall levels of reproducibility. However, less-than-ideal reproducibility was obtained for some descriptors, such as grainy appearance of the epidermis, junctional thickening, mild atypia in basal layer, plump bright cells, small bright cells, and reticulated fibers in the dermis. Conclusion The standard consensus confocal terminology useful for the evaluation of melanocytic lesions was reproducibly recognized by independent observers.

Low levels of selenium compounds are selectively toxic for a human neuron cell line through ROS/RNS increase and apoptotic process activation.

Organic and inorganic selenium compounds were used to examine whether low selenium concentration is able to trigger apoptotic degeneration in a human neuron cell line in vitro and to explore changes in reactive oxygen and nitrogen species and antioxidant protein content during the apoptotic processes. The results indicated that: (1) SKNBE neuroblastoma cells treated with sodium selenite, sodium selenate and seleno-methionine (0.1, 0.5 and 0.5 μM, respectively) for 24h exhibited a viability decrease, unlike kidney or prostatic cells; (2) the PARP (poly-ADP-ribose-polymerase) degradation and caspase activation detected by Western blot and flow cytometry fluorimetric examination showed induction of apoptosis; (3) during selenium treatment, a ROS/RNS increase occurred despite the GSH increment, as revealed by fluorimetric analysis; (4) the RNS production could be blocked by a peroxynitrite scavenger; (5) after exposure to selenium compounds, the concentration of nitric oxide synthase, manganese superoxide dismutase (SOD2), P-NF-kB (phospho nuclear factor kB), glutathione reductase and glutathione peroxidase increased, whereas that of P-ERK (phospho extracellular signal-regulated kinase) decreased; (6) selenium presence induced copper/zinc superoxide dismutase (SOD1) translocation into mitochondria, in a way similar to what is observed in amyotrophic lateral sclerosis (ALS). This study supports epidemiologic studies showing the possibility that excess environmental exposure to Se represents a risk factor for a devastating human neurodegenerative disease.