Ice core records of atmospheric CO2 around the last three glacial terminations

Air trapped in bubbles in polar ice cores constitutes an archive for the reconstruction of the global carbon cycle and the relation between greenhouse gases and climate in the past. High-resolution records from Antarctic ice cores show that carbon dioxide concentrations increased by 80 to 100 parts per million by volume 600 ± 400 years after the warming of the last three deglaciations. Despite strongly decreasing temperatures, high carbon dioxide concentrations can be sustained for thousands of years during glaciations; the size of this phase lag is probably connected to the duration of the preceding warm period, which controls the change in land ice coverage and the buildup of the terrestrial biosphere.</jats:p

Holocene carbon-cycle dynamics based on CO2 trapped in ice at Taylor Dome, Antarctica

A high-resolution ice-core record of atmospheric CO2 concentration over the Holocene epoch shows that the global carbon cycle has not been in steady state during the past 11,000 years. Analysis of the CO2 concentration and carbon stable-isotope records, using a one-dimensional carbon-cycle model,uggests that changes in terrestrial biomass and sea surface temperature were largely responsible for the observed millennial-scale changes of atmospheric CO2 concentrations

Peptidylarginine Deiminase Inhibitors Reduce Bacterial Membrane Vesicle Release and Sensitize Bacteria to Antibiotic Treatment

Outer membrane and membrane vesicles (OMV/MV) are released from bacteria and participate in cell communication, biofilm formation and host-pathogen interactions. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that catalyze post-translational deimination/citrullination of proteins, causing structural and functional changes in target proteins. PADs also play major roles in the regulation of eukaryotic extracellular vesicle release. Here we show phylogenetically conserved pathways of PAD-mediated OMV/MV release in bacteria and describe deiminated/citrullinated proteins in E. coli and their derived OMV/MVs. Furthermore, we show that PAD inhibitors can be used to effectively reduce OMV/MV release, both in Gram-negative and Gram-positive bacteria. Importantly, this resulted in enhanced antibiotic sensitivity of both E. coli and S. aureus to a range of antibiotics tested. Our findings reveal novel strategies for applying pharmacological OMV/MV-inhibition to reduce antibiotic resistance

Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles

Membrane vesicles (MVs) released from bacteria participate in cell communication and host-pathogen interactions. Roles for MVs in antibiotic resistance are gaining increased attention and in this study we investigated if known anti-bacterial effects of cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, could be in part attributed to effects on bacterial MV profile and MV release. We found that CBD is a strong inhibitor of MV release from Gram-negative bacteria (E. coli VCS257), while inhibitory effect on MV release from Gram-positive bacteria (S. aureus subsp. aureus Rosenbach) was negligible. When used in combination with selected antibiotics, CBD significantly increased the bactericidal action of several antibiotics in the Gram-negative bacteria. In addition, CBD increased antibiotic effects of kanamycin in the Gram-positive bacteria, without affecting MV release. CBD furthermore changed protein profiles of MVs released from E. coli after 1 h CBD treatment. Our findings indicate that CBD may pose as a putative adjuvant agent for tailored co-application with selected antibiotics, depending on bacterial species, to increase antibiotic activity, including via MV inhibition, and help reduce antibiotic resistance

Factors Associated with the Lack of Adherence to Drug Therapy in Diabetic Patients

According to the World Health Organization, there are more than 347 million people living with diabetes, being one of theleading causes of death in our days. Diabetes mellitus is a chronic metabolic disorder characterized by an increase in glycemiavalues above normal, which is accompanied by late complications derived from progressive damage in kidney, retina, vessels,heart, and nervous system. The best way to avoid these complications is adherence to treatment. However, the lack of treatmentcontinuity is very frequent. This paper demonstrated that in 76% of the cases, patients with diabetes do not accomplish theprescribed treatment. The main causes of this situation are related to the patient?s habits (since diabetes has no symptoms,the patients skip doses) and to the health system (due to the lack of free drug provision, patients do not have access to thetreatment). From this data, health country authorities initiated a program to aware patients of the importance to accomplish thetreatment and provided free drug for those patientsFil: Rivas, Alba. Universidad Nacional de Asunción; ParaguayFil: Vera, Zully. Universidad Nacional de Asunción; ParaguayFil: Marin, Gustavo Horacio. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Lugo, Gladys B.. Universidad Nacional de Asunción; ParaguayFil: Domenech, María Gloria. Universidad Nacional de Asunción; ParaguayFil: Samaniego, Lourdes. Universidad Nacional de Asunción; ParaguayFil: Mastroianni, Patricia. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Maidana, Gladys Mabel. Universidad Nacional de Asunción; Paragua

3D GRID-based pharmacophore and Metadynamics approaches for the rational design of N-Methyl β-sheet breaker peptides as inhibitors of the Alzheimer's Aβ-amyloid fibrillogenesis

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the loss of the cognitive functions and dementia. Several scientific evidences report that a central role in the pathogenesis of AD is played by the brain deposition of insoluble aggregates of β-amyloid protein (Aβ) proteins, thus causing neuronal cell death [1]. For this reason, one of the promising approach is to inhibit the aggregation of Aβ peptides. Because Aβ is self-assembling, one possible strategy to prevent this process is to use short peptide fragments homologous to the full-length wild-type Aβ protein. From this consideration, several short synthetic peptides were designed as beta-sheet breakers (BSB) [2]. In particular, the pentapetide Ac-LPFFD-NH2 (iAβ5p) exhibited a certain capability to inhibit Aβ fibrillogenesis [3]. iAβ5p analogs [4] were, then, designed by introducing N-Methylation at the amide bond nitrogen were also promising BSB. Here, we describe the methodological approach, which combines 3D GRID-based pharmacophore peptide screening with Well-Tempered Metadynamics simulations aimed to the discovery of novel N-Methylated BSB. This approach led us to identify two promising, cell permeable, N-Methylated peptides that were further evaluated for their BSB properties showing a significant improvement of the fibrillogenesis inhibition with respect to the lead iAβ5p

Estimation of glomerular filtration rate from serum creatinine and cystatin C in octogenarians and nonagenarians

Background: Equations to estimate GFR have not been well validated in the elderly and may misclassify persons with chronic kidney disease (CKD). We measured GFR and compared the performance of the Modification of Diet in Renal Disease (MDRD), the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi) and the Berlin Initiative Study (BIS) equations based on creatinine and/or cystatin C in octogenarians and nonagenarians.Methods: Using cross-sectional analysis we assessed 95 very elderly persons (mean 85 years) living in the community. GFR was measured by iohexol (mGFR) and compared with estimates using six equations: MDRD, CKD-Epi_creatinine, CKD-Epi_cystatin, CKD-Epi_creatinine-cystatin, BIS_creatinine and BIS_creatinine-cystatin.Results: Mean mGFR was 55 (range, 19-86) ml/min/1.73 m(2). Bias was smaller with the CKD-Epi_creatinine-cystatin and the CKD-Epi_creatinine equations (-4.0 and 1.7 ml/min/1.73 m2). Accuracy (percentage of estimates within 30% of mGFR) was greater with the CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and BIS_creatinine equations (85%, 83% and 80%, respectively). Among the creatinine-based equations, the BIS_creatinine had the greatest accuracy at mGFR < 60 ml/min/1.73 m(2) and the CKD-Epi_creatinine was superior at higher GFRs (79% and 90%, respectively). the CKD-Epi_creatinine-cystatin, BIS_creatinine-cystatin and CKD-Epi_cystatin equations yielded the greatest areas under the receiver operating characteristic curve at GFR threshold = 60 ml/min/1.73 m(2) (0.88, 0.88 and 0.87, respectively). in participants classified based on the BIS_creatinine, CKD-Epi_cystatin, or BIS_creatinine-cystatin equations, the CKD-Epi_creatinine-cystatin equation tended to improve CKD classification (net reclassification index: 12.7%, p = 0.18; 6.7%, p = 0.38; and 15.9%; p = 0.08, respectively).Conclusions: GFR-estimating equations CKD-Epi_creatinine-cystatin and BIS_creatinine-cystatin showed better accuracy than other equations using creatinine or cystatin C alone in very elderly persons. the CKD-Epi_creatinine-cystatin equation appears to be advantageous in CKD classification. If cystatin C is not available, both the BIS_cr equation and the CKD-Epi_cr equation could be used, although at mGFR < 60 ml/min/1.73 m(2), the BIS_cr equation seems to be the best alternative.Brazilian Research CouncilUniversidade Federal de São Paulo, Sch Med, São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, Geriatr Div, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Sch Med, São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, Geriatr Div, BR-04023900 São Paulo, BrazilBrazilian Research Council: 472115/2010-3Web of Scienc

Structural and ultrastructural evaluation of the effects induced by IL-22 alone or in combination with psoriatic cytokines in an ex-vivo human skin model

IL-22 is a pro-inflammatory cytokine playing a crucial role in the pathogenesis of psoriasis, an autoimmune chronic inflammatory skin disease. The immunological activation during the progression of the psoriatic lesion is driven by IL-22 together with other cytokines, such as (TNF)-alpha and interleukin (IL)-17 [1]. The aim of our study was to evaluate the early, direct, and specific effect of IL-22 alone or in combination with TNF-alpha and IL-17 by immunofluorescence on i) the molecular composition of intercellular junctions (desmocollin (DSC)1, E-cadherin, and occludin), ii) keratin(K) 10 and 17 expression, iii) keratinocyte proliferation, and, by transmission electron microscopy (TEM), on the ultrastructural morphology of the skin. An innovative model of human skin culture standardized in our laboratory, in which a psoriatic microenvironment was reproduced, was used [2]. Skin explants obtained from plastic surgery of healthy 20-40 year-old women (n = 7) after informed consent were cultured overnight in Dulbecco's modified Eagle's medium, divided before adding IL-22 or a combination of the three cytokines, and harvested 24, 48, and 72 hours after cytokine incubation. Interestingly, keratinocyte proliferation was inhibited after exposure to the combination of cytokines while was not affected by IL-22 incubation. In both experimental groups, starting from T24, occludin immunostaining was non homogeneously distributed, K10 immunostaining gradually decreased in scattered clusters in the spinous layer, while K17 expression was induced and progressively increased with time in the suprabasal layers of epidermis. By TEM, after IL-22 incubation we observed keratin aggregates in the perinuclear cytoplasm of cells, while the combination of the three cytokines induced an enlargement of intercellular spaces. Altogether, our results suggest that IL-22 mainly affects keratinocyte terminal differentiation, whereas, for inducing an impairment in cell proliferation, a more complex psoriatic-like microenvironment is needed

Prevalence of arterial hypertension and its risk factors in young adults of Paraguay

Early detection of arterial hypertension is critical for preventing the occurrence of cardiovascular diseases. A cross-sectional, observational, descriptive study was performed in order to determine the prevalence of arterial hypertension and cardiovascular risk factors among young university students in Paraguay. WHO hypertension parameters were used to classify the hypertension status. The research demonstrated that 18.6% of the students were classified in the prehypertension and 2.2% of the population had already a hypertension stage I status. 25.8% of the students had exceed the normal body mass index and 67.4% had a family history of hypertension. The values of blood pressure and family history were very unusual among youth population and in relation to similar population around the world.Fil: Lugo, Gladys B.. Universidad Nacional de Asunción; ParaguayFil: Vera de Molinas, Zully. Universidad Nacional de Asunción; ParaguayFil: Marin, Gustavo Horacio. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Samaniego, Lourdes Raquel. Universidad Nacional de Asunción; ParaguayFil: Toledo, Jonny. Universidad Nacional de Asunción; ParaguayFil: Lial, Nilsa. Universidad Nacional de Asunción; ParaguayFil: Acosta, Patricia. Universidad Nacional de Asunción; ParaguayFil: Mastroianni, Patricia. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Maidana de Larroza, Gladys M.. Universidad Nacional de Asunción; Paragua

Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir with or without Ribavirin in Patients with HIV-HCV Coinfection. Real Life Interim Analysis of an Italian Multicentre Compassionate Use Program

Background and Aims: An HCV cure is now possible in a large proportion of HIV-HCV patient. We present real life results of a compassionate use program promoted by SIMIT (Infectious and Tropical Diseases Italian Society) of Dasabuvir and Ombitasvir/Paritaprevir/Ritonavir ± Ribavirin for 12 weeks in 213 HIV-HCV genotype 1 patients. Data on efficacy and tolerability of this strategy in HIV patients have been reported until now only in 43 non cirrhotic HIV subjects