Quaternary glacial history of the Mediterranean mountains

Glacial and periglacial landforms are widespread in the mountains of the Mediterranean region. The evidence for glacial and periglacial activity has been studied for over 120 years and it is possible to identify three phases of development in this area of research. First, a pioneer phase characterized by initial descriptive observations of glacial landforms; second, a mapping phase whereby the detailed distribution of glacial landforms and sediments have been depicted on geomorphological maps; and, third, an advanced phase characterized by detailed understanding of the geochronology of glacial sequences using radiometric dating alongside detailed sedimentological and stratigraphical analyses. It is only relatively recently that studies of glaciated mountain terrains in the Mediterranean region have reached an advanced phase and it is now clear from radiometric dating programmes that the Mediterranean mountains have been glaciated during multiple glacial cycles. The most extensive phases of glaciation appear to have occurred during the Middle Pleistocene. This represents a major shift from earlier work whereby many glacial sequences were assumed to have formed during the last cold stage. Glacial and periglacial deposits from multiple Quaternary cold stages constitute a valuable palaeoclimatic record. This is especially so in the Mediterranean mountains, since mountain glaciers in this latitudinal zone would have been particularly sensitive to changes in the global climate system. © 2006 Edward Arnold (Publishers) Ltd

Lakeside Cemeteries in the Sahara: 5000 Years of Holocene Population and Environmental Change

Background: Approximately two hundred human burials were discovered on the edge of a paleolake in Niger that providea uniquely preserved record of human occupation in the Sahara during the Holocene (,8000 B.C.E. to the present). CalledGobero, this suite of closely spaced sites chronicles the rapid pace of biosocial change in the southern Sahara in response tosevere climatic fluctuation.Methodology/Principal Findings: Two main occupational phases are identified that correspond with humid intervals in theearly and mid-Holocene, based on 78 direct AMS radiocarbon dates on human remains, fauna and artifacts, as well as 9 OSLdates on paleodune sand. The older occupants have craniofacial dimensions that demonstrate similarities with mid-Holocene occupants of the southern Sahara and Late Pleistocene to early Holocene inhabitants of the Maghreb. Theirhyperflexed burials compose the earliest cemetery in the Sahara dating to ,7500 B.C.E. These early occupants abandon thearea under arid conditions and, when humid conditions return ,4600 B.C.E., are replaced by a more gracile people withelaborated grave goods including animal bone and ivory ornaments.Conclusions/Significance: The principal significance of Gobero lies in its extraordinary human, faunal, and archaeologicalrecord, from which we conclude the following:(1) The early Holocene occupants at Gobero (7700–6200 B.C.E.) were largely sedentary hunter-fisher-gatherers withlakeside funerary sites that include the earliest recorded cemetery in the Sahara.(2) Principal components analysis of craniometric variables closely allies the early Holocene occupants at Gobero with askeletally robust, trans-Saharan assemblage of Late Pleistocene to mid-Holocene human populations from the Maghreband southern Sahara.(3) Gobero was abandoned during a period of severe aridification possibly as long as one millennium (6200–5200 B.C.E).(4) More gracile humans arrived in the mid-Holocene (5200–2500 B.C.E.) employing a diversified subsistence economybased on clams, fish, and savanna vertebrates as well as some cattle husbandry.(5) Population replacement after a harsh arid hiatus is the most likely explanation for the occupational sequence at Gobero.(6) We are just beginnin

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole

Background: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. Methods: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. Results: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0-67.2, n=150) when BMI was <25.0 kg m-2; 65.6 (57.8-74.6, n=154) when 25.0-29.9 kg m-2; 59.3 (47.1-74.6, n=50) when 30.0-34.9 kg m -2; and 43.3 (23.0-81.7, n=16) when 6535.0 kg m-2. No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. Conclusions: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patient

Functional Induction of the Cystine-Glutamate Exchanger System Xc- Activity in SH-SY5Y Cells by Unconjugated Bilirubin

We have previously reported that exposure of SH-SY5Y neuroblastoma cells to unconjugated bilirubin (UCB) resulted in a marked up-regulation of the mRNA encoding for the Na+ -independent cystine∶glutamate exchanger System Xc− (SLC7A11 and SLC3A2 genes). In this study we demonstrate that SH-SY5Y cells treated with UCB showed a higher cystine uptake due to a significant and specific increase in the activity of System Xc−, without the contribution of the others two cystine transporters (XAG− and GGT) reported in neurons. The total intracellular glutathione content was 2 folds higher in the cells exposed to bilirubin as compared to controls, suggesting that the internalized cystine is used for gluthathione synthesis. Interestingly, these cells were significantly less sensitive to an oxidative insult induced by hydrogen peroxide. If System Xc− is silenced the protection is lost. In conclusion, these results suggest that bilirubin can modulate the gluthathione levels in neuroblastoma cells through the induction of the System Xc−, and this renders the cell less prone to oxidative damage

Clinical Use and Therapeutic Potential of IVIG/SCIG, Plasma-Derived IgA or IgM, and Other Alternative Immunoglobulin Preparations

Intravenous and subcutaneous immunoglobulin preparations, consisting of IgG class antibodies, are increasingly used to treat a broad range of pathological conditions, including humoral immune deficiencies, as well as acute and chronic inflammatory or autoimmune disorders. A plethora of Fab- or Fc-mediated immune regulatory mechanisms has been described that might act separately or in concert, depending on pathogenesis or stage of clinical condition. Attempts have been undertaken to improve the efficacy of polyclonal IgG preparations, including the identification of relevant subfractions, mild chemical modification of molecules, or modification of carbohydrate side chains. Furthermore, plasma-derived IgA or IgM preparations may exhibit characteristics that might be exploited therapeutically. The need for improved treatment strategies without increase in plasma demand is a goal and might be achieved by more optimal use of plasma-derived proteins, including the IgA and the IgM fractions. This article provides an overview on the current knowledge and future strategies to improve the efficacy of regular IgG preparations and discusses the potential of human plasma-derived IgA, IgM, and preparations composed of mixtures of IgG, IgA, and IgM

Modifications of IGF2 and EGFR plasma protein concentrations in NAFLD patients after bariatric surgery

Background: Nonalcoholic fatty liver disease (NAFLD) is strictly associated with the epidemic of obesity and is becoming the most prevalent liver disease worldwide. In severe obesity, bariatric surgery (BS) is the most effective treatment not only for obesity but also for the associated metabolic co-morbidities, NAFLD, among others. To date, noninvasive diagnostic/prognostic methods cannot evaluate hepatic improvements following surgery. Objectives: We aimed to measure plasma level of insulin-growth factor-2 protein (IGF2) and epithermal growth factor receptor (EGFR), and to assess their relationship with clinical and biochemical parameters during the 12 months follow-up. Methods: Demographic, clinical\u2013biochemical data, and plasma IGF2 and EGFR were measured in 69 patients preoperatively (T0) and 6 and 12 months (T6M and T12M, respectively) after BS. Liver biopsy was performed at T0. Relationships between IGF2, EGFR, and several biochemical parameters were performed using Pearson or Spearman correlation analysis. Results: IGF2 plasma level increases during follow-up, passing from 2.5 (1.8\u201315.5) at baseline to 13.3 (8.6\u201319.1) at T12M, p < 0.001. Conversely, EGFR showed a not significant reduction. At T12M, the plasma level of both markers was comparable to those of lean subjects. The clinical\u2013biochemical parameters (BMI, glycated hemoglobin, HOMA-IR) also return to the normal range at T12M. Correlation analysis demonstrated that IGF2 was significantly associated with total bilirubin, direct bilirubin, and albumin at T0 while with blood glucose, ALT, GGT, and AST/ALT ratio at T6M and T12M. Conclusions: IGF2 plasma levels increase after bariatric surgery, and these changes are associated with the modification of hepatic biochemical parameters, even if other clinic or metabolic improvements cannot be excluded

Optimization of point-shear wave elastography by skin-to-liver distance to assess liver fibrosis in patients undergoing bariatric surgery

Background: Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. Materials and Methods: 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs: <5.7 kPa, F0\u20131; 5.7\u20137.99 kPa, F2; 658 kPa, F3\u20134. Results: We developed two logistic regression models using elastography\u2013histology agreement (EHA) as the dependent variable and SLD as the independent variable. The model based on the second machine showed strongly more performant discriminative and calibration metrics (AIC 38.5, BIC 44.2, Nagelkerke Pseudo-R2 0.894, AUROC 0.90). The SLD cut-off value of 34.5 mm allowed a correct EHA with a sensitivity of 100%, a specificity of 93%, negative predictive value of 100%, positive predictive value of 87%, an accuracy of 96%, and positive likelihood ratio of 3.56. Conclusion: The impact of SLD is machine-dependent and should be taken into consideration when interpreting LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in obese patients