Striking forest revival at the end of the Roman Period in north-western Europe.

The Holocene period (last 11,700 years BP) has been marked by significant climate variability over decadal to millennial timescales. The underlying mechanisms are still being debated, despite ocean-atmosphere-land connections put forward in many paleo-studies. Among the main drivers, involving a cluster of spectral signatures and shaping the climate of north-western Europe, are solar activity, the North Atlantic Oscillation (NAO) varying atmospheric regimes and North Atlantic oceanic gyre dynamics. Over the last 2500 years BP, paleo-environmental signals have been strongly affected by anthropogenic activities through deforestation and land use for crops, grazing, habitations, or access to resources. Palynological proxies (especially pollen grains and marine or freshwater microalgae) help to highlight such anthropogenic imprints over natural variability. Palynological analyses conducted in a macro-estuarine sedimentary environment of north-western France over the last 2500 years BP reveal a huge and atypical 300 year-long arboreal increase between 1700 and 1400 years BP (around 250 and 550 years AD) that we refer to as the '1.7-1.4 ka Arboreal Pollen rise event' or '1.7-1.4 ka AP event'. Interestingly, the climatic 1700-1200 years BP interval coincides with evidence for the withdrawal of coastal societies in Brittany (NW France), in an unfavourable socio-economic context. We suggest that subpolar North Atlantic gyre strengthening and related increasing recurrence of storminess extremes may have affected long-term coastal anthropogenic trajectories resulting in a local collapse of coastal agrarian societies, partly forced by climatic degradation at the end of the Roman Period.

Foreign Plastid Sequences in Plant Mitochondria are Frequently Acquired Via Mitochondrion-to-Mitochondrion Horizontal Transfer.

Angiosperm mitochondrial genomes (mtDNA) exhibit variable quantities of alien sequences. Many of these sequences are acquired by intracellular gene transfer (IGT) from the plastid. In addition, frequent events of horizontal gene transfer (HGT) between mitochondria of different species also contribute to their expanded genomes. In contrast, alien sequences are rarely found in plastid genomes. Most of the plant-to-plant HGT events involve mitochondrion-to-mitochondrion transfers. Occasionally, foreign sequences in mtDNAs are plastid-derived (MTPT), raising questions about their origin, frequency, and mechanism of transfer. The rising number of complete mtDNAs allowed us to address these questions. We identified 15 new foreign MTPTs, increasing significantly the number of those previously reported. One out of five of the angiosperm species analyzed contained at least one foreign MTPT, suggesting a remarkable frequency of HGT among plants. By analyzing the flanking regions of the foreign MTPTs, we found strong evidence for mt-to-mt transfers in 65% of the cases. We hypothesize that plastid sequences were initially acquired by the native mtDNA via IGT and then transferred to a distantly-related plant via mitochondrial HGT, rather than directly from a foreign plastid to the mitochondrial genome. Finally, we describe three novel putative cases of mitochondrial-derived sequences among angiosperm plastomes.

Fish stomach contents in benthic macroinvertebrate assemblage assessments.

The choice of sampling gears to assess benthic macroinvertebrate communities depends on environmental characteristics, study objectives, and cost effectiveness. Because of the high foraging capacity and diverse habitats and behaviors of benthophagous fishes, their stomach contents may offer a useful sampling tool in studies of benthic macroinvertebrates, especially in large, deep, fast rivers that are difficult to sample with traditional sediment sampling gear. Our objective was to compare the benthic macroinvertebrate communities sampled from sediments with those sampled from fish stomachs. We collected benthic macroinvertebrates and fish from three different habitat types (backwater, beach, riffle) in the wet season, drying season, and dry season along a single reach of the Grande River (Paraná River Basin, southeast Brazil). We sampled sediments through use of a Petersen dredge (total of 216 grabs) and used gill nets to sample fish (total of 36 samples). We analyzed the stomach contents of three commonly occurring benthophagous fish species (Eigenmannia virescens, Iheringichthys labrosus, Leporinus amblyrhynchus). Chironomids dominated in both sampling methods. Macroinvertebrate taxonomic composition and abundances from fish stomachs differed from those from sediment samples, but less so from riffles than from backwater and beach habitats. Macroinvertebrate taxa from E. virescens stomachs were more strongly correlated with sediment samples from all three habitats than were those from the other two species. The species accumulation curves and higher mean dispersion values, compared with with sediment samples suggest that E. virescens is more efficient than sediment samples and the other fish studied at collecting benthic taxa. We conclude that by analyzing the stomach contents of benthophagous fishes it is possible to assess important characteristics of benthic communities (dispersion, taxonomic composition and diversity). This is especially true for studies that only sample fish assemblages to evaluate aquatic ecosystem impacts. Therefore, this approach can be useful to amplify assessments of human impacts, and to incorporate additional bioindicators.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

PURPOSE: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. RESULTS: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. CONCLUSIONS: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

Low-dose "metronomic chemotherapy" with oral cyclophosphamide and methotrexate in metastatic breast cancer: a case report of extraordinarily prolonged clinical benefit.

We report the case of a 34-year-old woman affected by breast cancer that had metastasized to the bone. She had been treated with oral cyclophosphamide and methotrexate (metronomic chemotherapy) and achieved 3.5 years of clinical remission. To our knowledge, this is the first description of such a prolonged response to therapy. This case report adds weight to known data on metronomic treatment and supports further investigation of this therapy.

Morphofunctional evidence of changes in principal and mitochondria-rich cells in the epidermis of the frog Rana kl. esculenta living in a polluted habitat.

The epidermis of vertebrates is the body's principal barrier against environment and its possible contaminants. The presence of keratins, as well as specific detoxifying molecules or enzyme activities, in the various epidermis layers is believed to be involved in providing protection from harmful environmental influences. Anuran integument is poorly hornified and thus permeable to some endogenous and exogenous compounds and thus serves as a good bioindicator of overall environmental conditions. In the present investigation, we studied the epidermis of Rana kl. esculenta adult specimens collected at two different rice fields, relatively unpolluted and heavily polluted, respectively. Environmental pollution was assayed by chemical analysis performed on both sediments and animals. We evaluated the structural aspects of the epidermis at both light and electron microscopy levels and the pattern of keratinization by immunohistochemistry. Furthermore, we studied the activities of some enzymes (acid and alkaline phosphatase, nitric oxide synthase-related nicotinamide adenine dinucleotide phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, catalase, nonspecific esterases, and succinic dehydrogenase) involved mainly in membrane transport, xenobiotics, and oxidative metabolism. Compared with controls, in polluted animals we found the following results: (1) an increase in pollutant levels (i.e., cadmium, mercury, and lead); (2) less keratinized superficial cells in the epidermis; and (3) changes in most enzyme activities in keratinocytes and mitochondria-rich cells (particularly glucose-6-phosphate dehydrogenase and esterases, both important to counteract oxidative and toxic stress). Taken as a whole, the present data indicate the morphofunctional plasticity of the frog epidermis in response to environmental contamination.

Little Egrets (Egretta garzetta) and trace-metal contamination in wetlands of China.

The rapidly developing Asian countries may face threatening environmental contamination, that however remains largely unassessed. We studied persistent trace elements in three wetlands, Poyang Lake, relatively unpolluted, and Tai Lake, and Pearl River Delta, selected as hotspots of pollution in Central China. We adopted as indicator the Little Egret, a widespread colonial waterbird, and during 1999 and 2000 we collected and analysed the same samples as for a parallel study we conducted in Pakistan, e.g. eggs, body feathers of chicks, prey spontaneously regurgitated by the chicks, and sediments at the areas most used by foraging egrets. The levels of trace-metals at our three study areas were similar, or within the range, of those found in the few other studies for East Asia, with few exceptions. The concentrations of the various elements were below the threshold that may affect the survival or reproduction of the birds, and even the highest concentrations relative to background, i.e. Se in eggs, and Hg in feathers at Pearl Delta, do not pose toxic hazards. In sediments, the levels of trace elements were lower than the critical levels assumed for contaminated soil, except for alarming high levels of As at Poyang. These results do not confirm our expectation, that Poyang was relatively uncontaminated, while Tai and Pearl were polluted. Although trace metal concentration differed significantly among the three study areas, these differences were minor and were not consistent among elements and samples. The bioaccumulation ratios from sediments through prey, feather and egg, were consistent with our previous findings for Pakistan. Only Hg exhibited high bioaccumulation, while Se and Zn had low accumulation, and the other elements no accumulation. This reasserts that feathers of predators such as egrets, may be more sensitive indicators of environmental contamination for the elements subject to bioaccumulation, whereas the sediments or the organisms low in the food chain are better indicators for the other elements.

Egrets as monitors of trace-metal contamination in wetlands of Pakistan.

Environments in Pakistan are subject to increasing pollution, but previous studies were very scanty. During 1999 and 2000, we assessed trace element contamination at three wetlands, Karachi Harbour (with presumed industrial-urban pollution), Taunsa Barrage (agricultural pollution), and Haleji Lake (relatively unpolluted), using as indicators the eggs and the feathers of colonial waterbirds, particularly Little Egrets, their prey, and the sediments collected within their foraging areas. The concentrations of As, Cd, Cr, Pb, Hg, Mn, Se, and Zn were generally within the normal background level, and mostly below the threshold that may affect bird survival or reproduction. However, somewhat high concentrations were found in fish from Karachi, for Pb that was at levels that may harm fish reproduction, and for Hg that was at limit concentration for human consumption. Alarming concentrations were found for Cr and Se in sediments from Karachi, that were above the critical levels for contaminated soil, and Se in eggs, that may affect egret reproduction. The differences among the three wetlands were less marked than hypothesized. The egret species within the same area differed in the concentration of certain elements in their eggs, possibly because females may have foraged in different habitats before breeding, whereas no interspecies difference was found in chick feathers, presumably because their food had been collected in similar habitats around the colony. High bioaccumulation from sediments to organic samples occurred for Hg, while Cd, Se, and Zn exhibited low accumulation; for all these elements, feathers of predatory birds such as the egrets are the best indicators of environmental contamination. On the other hand, As and Cr did not bioaccumulate, and the sediments, or the organisms low in the food chain, like fish or crustaceans, are better indicators of their presence in the environment than predatory birds.

Immobilized penicillin G acylase as reactor and chiral selector in liquid chromatography.

In this paper, the use of penicillin G acylase (PGA) as a biocatalyst and as a chiral selector is described. Penicillin G-acylase is an interesting enzyme used in the manufacture of semisynthetic antibiotics and, in particular, in the production of 6-APA by hydrolysis of penicillin G. Five PGA-based HPLC columns have been prepared by using two different silica supports by employing two immobilization methods, namely "in situ" and "in batch". The effects of the immobilization techniques and of different silica pore size on the catalytic properties of the enzyme as well as the applicability of the PGA-bonded stationary phases as chiral selectors for a number of chiral drugs have been investigated. The HPLC columns based on immobilized PGA combine the hydrolytic activity and the chiral recognition properties of PGA, therefore they have been used for the development of a combined reaction-separation system for chiral and achiral substrates.

Cardiac damage in pediatric carbon monoxide poisoning.

BACKGROUND: Cardiovascular disorders including myocardial ischemia and heart failure have been described in both laboratory animals and humans following carbon monoxide poisoning. Carbon monoxide cardiotoxicity may be clinically occult and often remains undiagnosed because of the lack of overt symptoms and specific ischemic changes in the electrocardiogram. Routine myocardial necrosis markers have low diagnostic efficiency, particularly in patients with concomitant skeletal muscle necrosis or multiple organ failure complicating carbon monoxide poisoning. Carbon monoxide-induced cardiotoxicity has been investigated rarely in children. CASE REPORT: This paper describes carbon monoxide poisoning in a 12-year-old child who suffered from occult cardiac damage despite mild symptoms and low carboxy hemoglobin concentrations. Myocardial and mitral valve dysfunctions were observed, suggesting an ischemia-like syndrome. Cardiac damage was completely reversible within 1 month. CONCLUSION: This case report supports that a prolonged carbon monoxide exposure can cause cardiac damage in children even in the absence of specific symptoms, cerebral failure and high carboxyhemoglobin concentrations.

Carbon monoxide cardiotoxicity.

Cardiac dysfunction including arrhythmias and myocardial ischemia have often been reported in carbon monoxide poisoning; scattered punctiform hemorrhages throughout the heart have been documented in autopsy samples. An appropriate diagnostic approach is crucial to assess carbon monoxide cardiac damage. This evaluation may be confounded by several factors, including the absence of overt symptoms and of specific ischemic changes in the electrocardiogram. In experimental studies, laboratory animals can develop cardiac changes similar to those seen in humans and therefore proved to be useful models to study the effects and the mechanisms of cardiac damage due to carbon monoxide. These investigations, as well as others performed in vitro, provide support for a direct action of carbon monoxide on the heart, in addition to systemic hypoxia produced by carboxyhemoglobin formation. This review focuses on the diagnostic aspects of carbon monoxide cardiotoxicity. Experimental results obtained in animals and in vitro models are also discussed.

Mild ciguatera poisoning: Case reports with neurophysiological evaluations.

Ciguatera poisoning causes mainly gastrointestinal and neurological effects of variable severity. However, symptoms of peripheral neuropathy with paresthesias and paradoxical disturbance of thermal sensation are the hallmark. Electrophysiological studies are often normal, except in severe cases. We report four people who developed mild ciguatera poisoning after barracuda ingestion. Electrophysiological studies documented normocalcemic latent tetany. These findings are consistent with ciguatoxin's mechanism of toxicity, which involves inactivation of voltage-gated Na(+) channels and eventually increases nerve membrane excitability.

[Occupational poisoning with psychiatric manifestations]. / Intossicazioni professionali con manifestazioni psichiatriche.

Numerous occupational intoxications (acute, chronic and their sequelae) may affect the central nervous system and result in a wide variety of neuropsychiatric effects, ranging from subtle behavioural disturbances to overt psychosis. Chemicals causing such manifestations include many metals and organometals (Hg, Mn, Pb, Al, Sn), pesticides (organophosphates), compounds utilised in the industrial setting as solvents or intermediates (carbon disulfide, hydrocarbons and their halogenated derivatives), and combustion products (carbon monoxide). Some types of toxic insults may not be reflected in any clinical manifestation. However, this type of damage may render the brain more vulnerable to additional insult or accelerate physiological loss of neurones with ageing. Thus, occupational exposures to chemicals (Al, Pb, organic solvents) might be involved in the causation of neurodegenerative diseases--such as Alzheimer's disease--which are usually labelled as "idiopathic". A careful occupational anamnesis is crucial to diagnose work-related psychiatric manifestations and--consequently--to interrupt the toxic exposure, to start therapy, and to promote insurance compensation.

Early acute necrosis, delayed apoptosis and cytoskeletal breakdown in cultured cerebellar granule neurons exposed to methylmercury.

Cerebellar granule cells (CGCs) are a sensitive target for methylmercury (MeHg) neurotoxicity. In vitro exposure of primary cultures of rat CGCs to MeHg resulted in a time- and concentration-dependent cell death. Within 1 hr exposure, MeHg at 5-10 microM caused impairment of mitochondrial activity, de-energization of mitochondria and plasma membrane lysis, resulting in necrotic cell death. Lower MeHg concentrations (0.5-1 microM) did not compromise cell viability, mitochondrial membrane potential and function at early time points. Later, however, the cells progressively underwent apoptosis and 100% cell death was reached by 18 hr treatment. Neuronal network fragmentation and microtubule depolymerization were detected as early as within 1.5 hr of MeHg (1 microM) exposure, long before the occurrence of nuclear condensation (6-9 hr). Neurite damage worsened with longer exposure time and proceeded to the complete dissolution of microtubules and neuronal processes (18 hr). Microtubule stabilization by taxol did not prevent MeHg-induced delayed apoptosis. Similarly ineffective were the caspase inhibitors z-VAD-fluoromethylketone and z-DEVD-chloromethylketone, the L-type calcium channel inhibitor nifedipine, the calcium chelator EGTA and BAPTA, and the NMDA receptor antagonist MK-801. On the other hand, insulin-like growth factor-I partially rescued CGCs from MeHg-triggered apoptosis. Altogether these results provide evidence that the intensity of MeHg insult is decisive in the time of onset and the mode of neuronal death that follows, i.e., necrosis vs. apoptosis, and suggest that cytoskeletal breakdown and deprivation of neurotrophic support play a role in MeHg delayed toxicity.

Association between changes in adrenal secretion and cerebral morphometric correlates in normal aging and senile dementia.

The circadian organization of adrenal secretion was studied in 23 healthy elderly subjects, 23 elderly demented patients and 10 healthy young subjects, in order to investigate the relationships between the hypothalamic-pituitary-adrenal axis and some cerebral morphometric parameters. The cerebral morphometric analysis was performed in some subjects of the three groups by MRI. A significant increase in cortisol levels during evening and nighttime was found in both groups of the aged subjects. In elderly subjects, particularly if demented, the mean serum dehydroepiandrosterone sulfate (DHEAs) levels throughout the 24-hour cycle were significantly lower than in young controls. A significant reduction of the hippocampal and temporal volume and an enlargement of the lateral ventricles were found in aged subjects, these changes being significantly related to subjects' age. Moreover, the hippocampal volume was positively correlated with the circadian mesor of DHEAs (i.e., the circadian rhythm adjusted mean) and with the cortisol nocturnal increase. Our data may suggest the existence of a link between the selective impairment of cortisol secretion and DHEAs levels, and the progression of hippocampal degeneration.

Myocardial necrosis in ICU patients with acute non-cardiac disease: a prospective study.

OBJECTIVE: To ascertain if, after an episode of hypotension, unnoticed myocardial necrosis could occur in critical care patients with acute non-cardiac illness and to search for signs of cardiac necrosis. DESIGN: A prospective observational study. SETTING: General intensive care unit (ICU) at a tertiary level hospital. PATIENTS: Thirty-one patients in two groups. Group 1 included 19 patients with severe sepsis/septic shock (ACCP/SCCM Consensus Conference). Group 2 included 12 patients with hypovolemic shock. INTERVENTIONS: Biochemical markers of myocardial necrosis (cardiac troponin I (cTnI), creatine kinase (CK), creatine kinase MB mass (CKMB) and myoglobin) were measured at 12 h (T1), 24 h (T2) and 48 h (T3) after enrollment. A standard 12-lead ECG was recorded upon enrollment (T0) and at T2. Anomalous Q-waves or ST segment depression or elevation was considered diagnostic for acute myocardial infarction (AMI). A hypotensive episode (arterial systolic pressure < 90 mmHg at heart rate > 100 bpm) was considered moderate if it lasted 30-60 min or severe if longer than 60 min. MEASUREMENTS AND RESULTS: At T0 none of the patients had AMI on ECG. At T2 a non-Q AMI developed in five patients. Increased levels of troponin I, myoglobin, CK and CKMB were found in 74.2 %, 96.8 %, 74.2 % and 67.7 % of the patients, respectively. Cardiac troponin I increased in 11 out of 19 septic patients and in all hypovolemic patients. There was a significant difference between the groups (p < 0.05). All biochemical markers increased in relationship to the degree of hypotension with cTnI again showing a significant difference. The longer the hypotensive episode was, the greater was the increase (moderate hypotension: median 1.16; quartiles 0.55-3.44 ng/ml, severe hypotension: median 8.53; quartiles 1.1-20.7 ng/ml; p < 0.05). Abnormal levels of cTnI were more frequent in non-survivors than in survivors (p < 0.05). CONCLUSIONS: Hypotension may cause cardiac damage in critically ill patients with acute non-cardiac diseases as shown by abnormal levels of cTnI. It is likely that a high number of these myocardial necroses may go unnoticed on the ECG.

Heavy metal, organochlorine pesticide, and PCB residues in eggs and feathers of herons breeding in northern Italy.

We report on organochlorine pesticide and PCB concentrations in eggs of the little egret, Egretta garzetta, and the black-crowned night-heron, Nycticorax nycticorax, collected in 1993-1994, and on mercury, cadmium, and lead concentrations in feathers of 20-day-old nestlings collected from the same nests in 1994, from heronries near Pavia, northern Italy. Organochlorine pesticide and PCB residues were lower than those commonly associated with mortality and reduced reproductive success. As population levels of the species studied are not declining, these contaminants appear to have no significant adverse effect on reproduction in the heronries studied. DDE levels have decreased markedly in heron eggs since 1978. However, the presence of both DDT and beta-HCH, albeit at low levels, is notable, given that these compounds were banned in Italy in 1978 and 1988, respectively. Relatively high levels of Hg, Cd, and Pb in feathers suggest birds in their colonies are exposed to these contaminants, although both Cd and Pb may relate more to external than to internal contamination.

[Telematics equipment for poison control surveillance. Its applications in the health management of relevant chemical incidents]. / Strumenti telematici per attività di tossicovigilanza. Applicazioni nella gestione sanitaria degli incidenti chimici rilevanti.

Health management of major chemical incidents requires a close collaboration between rescuers (on the disaster site and in the emergency department) and the poison center. The study tested telematic technologies allowing telepresence and teleconsulting, a real time and continuous connection among health care personnel and toxicologists involved in the management of the emergency. The link between the poison center (PC) and the emergency department in the local hospital is provided by a ISDN operating video conferencing system, while the data transmission from the site of the accident to the PC is achieved with a personal computer and GSM cellular data transmission. Toxicological databases and risk assessment software are integrated in the system, to support information sharing. To test such instruments in operative nearly realistic conditions, the main phase of the study has implemented simulated chemical disasters in different locations in Italy. Instruments for telepresence and teleconsulting have been effectively utilized to evaluate from a remote location the scenario and the severity of the accident, by inspecting either specific details or the whole scene, to enable PC guiding the triage of the victims before and after hospitalization, to utilize and share data, such as intervention protocols or patient records, and to document all the activities. In summary, this experience shows that the telematic link allows the toxicologists of the poison center to rapidly understand the situation, and to correctly learn about the conditions of patients with the help of images. The results of this study indicate the valuable benefits of telematic instruments for the health care in case of major chemical disasters occurring in a remote geographical location or in an area which lacks local toxicological experts, where specialized expertise can be achieved by the use of telematic technologies.

High-performance liquid chromatographic determination of alpha-tocopheryl nicotinate in cosmetic preparations.

alpha-Tocopheryl nicotinate (alpha-TN) accelerates blood circulation and stimulates hair follicle cells, hence it is an active ingredient in a broad range of cosmetic products. A reversed-phase high-performance liquid chromatographic method was developed to determine alpha-TN in cosmetic preparations with alpha-tocopheryl acetate as internal standard. The method was found to be rapid, precise and specific.