Ancient DNA from an Early Neolithic Iberian population supports a pioneer colonization by first farmers.

The Neolithic transition has been widely debated particularly regarding the extent to which this revolution implied a demographic expansion from the Near East. We attempted to shed some light on this process in northeastern Iberia by combining ancient DNA (aDNA) data from Early Neolithic settlers and published DNA data from Middle Neolithic and modern samples from the same region. We successfully extracted and amplified mitochondrial DNA from 13 human specimens, found at three archaeological sites dated back to the Cardial culture in the Early Neolithic (Can Sadurní and Chaves) and to the Late Early Neolithic (Sant Pau del Camp). We found that haplogroups with a low frequency in modern populations-N* and X1-are found at higher frequencies in our Early Neolithic population (∼31%). Genetic differentiation between Early and Middle Neolithic populations was significant (F(ST) ∼0.13, P<10(-5)), suggesting that genetic drift played an important role at this time. To improve our understanding of the Neolithic demographic processes, we used a Bayesian coalescence-based simulation approach to identify the most likely of three demographic scenarios that might explain the genetic data. The three scenarios were chosen to reflect archaeological knowledge and previous genetic studies using similar inferential approaches. We found that models that ignore population structure, as previously used in aDNA studies, are unlikely to explain the data. Our results are compatible with a pioneer colonization of northeastern Iberia at the Early Neolithic characterized by the arrival of small genetically distinctive groups, showing cultural and genetic connections with the Near East.

Epigenetic therapy of lymphoma using histone deacetylase inhibitors

In this study, we reviewed epigenetic therapy of lymphomas using histone deacetylase inhibitors (HDACi), a promising new class of antineoplastic agents. Epigenetic therapy, a new therapeutic concept, consists of the use of HDACi and or DNA methyltransferase inhibitors (DNMTi). We conducted a comprehensive review of the literature for antitumour activity of HDACi and its mechanism of action. HDACi modify the expression of several genes related to cancer development, which can result in antineoplastic activity. To elucidate the benefits of HDACi in lymphoma treatment, we discuss the crucial interplay between BCL6, p53 and STAT3. Activated B-cell (ABC) diffuse large cell lymphoma (DLCL) is increasingly being recognised as an unfavourable and frequently therapy-refractory lymphoma. We discuss the fundamental causative role of the STAT3 oncogene in ABC type DLCL. STAT3 can be effectively suppressed by several HDACi, a promising treatment for this difficult subtype of DLCL. On the other hand, various HDACi can repress the germinal-centre B Cell (GCB) type DLCL by virtue of their inhibition of the BCL6 oncogene, usually expressed in this particular subtype. We summarise the results of recent clinical trials with HDACi such as romidepsin, panobinostat, MGCD-0103, entinostat, curcumin, JAK2 inhibitor TG101348, and valproic acid that have shown preliminary activity in recurrent and refractory lymphomas. The unique mechanism of action of HDACi makes them very attractive agents to pursue in combination. Several ongoing trials are already exploring HDACi combinations in various types of cancers. Their role in front-line management remains to be determined (AU)

A clinical comparison of two formulations of tobramycin 0.3% eyedrops in the treatment of acute bacterial conjunctivitis.

PURPOSE: To compare the safety and efficacy of a new enhanced viscosity ophthalmic formulation of tobramycin, given twice daily (BID), with the existing four times daily (QID) treatment regimen in patients with acute bacterial conjunctivitis. METHODS: This was a 12-day, multicenter, observer-masked, randomized, parallel group study. Patients received one drop of tobramycin 0.3% (3 mg/mL) enhanced viscosity ophthalmic solution BID or tobramycin 0.3% (3 mg/mL) ophthalmic solution QID in the affected eyes for 7 days. The primary efficacy variable was the percentage of patients with sustained cure/presumed bacterial eradication based on clinical judgment at the test-of-cure visit (Day 12). Pretherapy bacterial isolates were obtained and tested for susceptibility to tobramycin by determination of minimum inhibitory concentrations (MIC). RESULTS: A total of 276 patients were enrolled in the study and 203 of these were culture positive and attended all follow-up examinations. In this group, 98% of those treated with tobramycin enhanced viscosity ophthalmic solution and 99% of those treated with tobramycin 0.3% ophthalmic solution were categorized as having sustained cure/presumed eradication at the test-of-cure visit (p = 0.6037). Reported adverse events were not serious, mild to moderate in severity, and generally did not prevent continuation in the study. Several pre treatment pathogens demonstrated tobramycin resistance (MIC > 4 mg/mL). However, therapy with both treatments was effective in the majority of the cases. CONCLUSIONS: Tobramycin enhanced viscosity ophthalmic solution is well tolerated and has equivalent efficacy to the established treatment regimen with a simplified posology. The formulation provides an alternative therapy for acute bacterial conjunctivitis that should improve patient compliance and satisfaction.

[Loss of antibiotic sensitivity of Pseudomonas aeruginosa strains during treatment]. / Pérdida de sensibilidad a los antibióticos de cepas de Pseudomonas aeruginosa en el curso del tratamiento.

BACKGROUND: Loss of sensitivity to betalactamic, quinolones and aminoglucoside antibiotics has been described during treatment of infections produced by strains of Pseudomonas aeruginosa. Sixteen nosocomial strains isolated over a year during which sensitivity to one or several antibiotics of the above mentioned groups had been lost during the course of treatment were studied. METHODS: The strains were identified by conventional techniques. Sensitivity to antibiotics was studied by determination of the minimum inhibitory concentration in solid medium, according to the guidelines of the National Committee for Clinical Laboratory Standards. Plasmidic beta-lactamases were identified by analytic isoelectric focusing. Hyperproduction of chromosomic lactamase was studied by a qualitative technique. The 0 antigens were studied against rabbit antisera. The pyocinetype was determined according to the Fyfe method. Plasmids were detected by alkaline lysis extraction and electrophoresis in agarose gel. RESULTS: The 16 strains in which changes in sensitivity were observed during the course of treatment represent 4.47% of all P. aeruginosa isolates during one year. Loss of sensitivity to betalactamic antibiotics was observed in 10 strains, in one to aminoglucosides, in two to ciprofloxacin, simultaneously to aminoglucosides and ciprofloxacin in one and to betalactamic and ciprofloxacin in another two. Six of the 13 patients (46%) required a change in antibiotic treatment. CONCLUSIONS: The convenience of following the sensitivity of the strains of Pseudomonas aeruginosa isolated in a patients is suggested to thereby avoid therapeutic failure and the potential danger of clonal dissemination of the strains which have lost sensitivity.

[Hardening and softening phenomena in beans: technological alternatives]. / Fenómeno de endurecimiento y ablandamiento del frijol: alternativas tecnológicas.

The effect of accelerated hardening and soaking solutions on cooking time and microstructure of common bean (Phaseolus vulgaris) was studied. Two varieties (Canario and Mayocoba) were grown in the same location. Three hardening procedures were used: 1) End A. Soaking in acetate buffer, pH = 4.0 at 37 degrees C for 5 hs, 2) End B. Storage at 37 degrees C, 100% RH for 28 days and, 3) End C storage at 13-33 degrees C, 76% RH for 120 days. The salt solutions used for soaking were: Soln 1 (1% NaCl+0.75% NaHCO3) and Soln 2 (0.75% NaHCO3). Cooking times were determined using a Mattson bean cooker. In both varieties, the three hardening procedures decreased (38-50%) cotyledons water holding capacity and increased significantly (2-4 times) cooking times. During soaking in salt solutions hardened beans reached maximum water absorption in four hours. Soaking in salt solutions decreased drastically (2.6-10.6 times) cooking times. Fresh, hardened and softened seeds were examined by light microscopy, observing ultrastructural differences among them. The methods used in this research might well represent the central components of an industrial technological procedure for the utilization of hardened beans.

Complementary activity of mezlocillin and the combination of amoxicillin with clavulanic acid on Enterobacteriaceae.

The MICs of amoxicillin, mezlocillin and BRL 25,000, a combination of two parts amoxicillin and one part clavulanic acid (2AM + 1CA), were measured for 331 Enterobacteriaceae strains which produced beta-lactamases as demonstrated by nitrocefin. The MIC values for mezlocillin and the combination 2AM + 1CA were very similar for the total number of the strains investigated. When investigated separately according to the bacterial species, three different sensitivity groups were established for the above-mentioned preparations: 1) species with the same or similar sensitivity to mezlocillin and 2AM + 1CA (Escherichia coli and Shigella spp., amoxicillin-resistant strains); 2) species which were more sensitive to mezlocillin than to the combination 2AM + 1CA (Citrobacter spp., Enterobacter cloacae, Serratia spp. and indole-positive Proteus as well as strains of E. coli and Shigella spp. which produce a cephalosporinase and are sensitive to amoxicillin); 3) species which are more sensitive to 2AM + 1CA than to mezlocillin (amoxicillin-resistant Salmonella spp., Proteus mirabilis and Klebsiella pneumoniae). This complementary activity of mezlocillin and 2AM + 1CA against Enterobacteriaceae depended on the beta-lactamases produced.