Identification and molecular epidemiology of methicillin resistant Staphylococcus pseudintermedius strains isolated from canine clinical samples in Argentina

Staphylococcus pseudintermedius is the leading cause of pyoderma in dogs and the frequent use of antimicrobial treatment is associated to the development of resistance to nearly all classes of antibiotics. Despite S. pseudintermedius significance, our understanding of the molecular mechanism of β-lactam resistance and its genetic diversity remains limited. We aimed to: i) determine the phenotypic resistance profile of methicillin resistant Staphylococcus pseudintermedius (MRSP) isolated from infected dogs in three different veterinary hospitals in Buenos Aires, Argentina; ii) identify the SCCmec elements and resistance genes; and iii) analyze the clonal relationship between isolates and in regard of dominant lineages found in the world. In addition to the differential levels of β-lactam resistance, MRSP isolates (n = 10) showed resistance to 5–6 families of antibiotics, and were therefore categorized as multidrug-resistant. All the isolates were variant of SCCmec V homologous to S. aureus; additional SCCmecFinder analysis classified five of the genomes as SCCmec type V (5C2&5) with mecA (encodes for PBP2a), mecRI and mecI and all the genes closely related to the reference SCCmec type V S. aureus TSGH17 strain. In the remaining five strains, mecA was present, although other genes associated with SCCmec V including mecR1 and mecI were missing. PBP2a was inducible in low level resistance strains (MRSP 8151), and constitutively expressed in MRSP 8150, suggesting different mecA regulatory mechanisms. MRSP isolates showed significant genetic diversity: eight PFGE clonal types and six multilocus-sequence typing (MLST) sequence types (STs) (339, 649, 919, 920, 921 and 922), including four new STs genetically distinct from STs reported in other geographic areas. Comparative genomics and phylogenetic analyses of the MRSP showed a correlation between the genetic content and the phenotypes, and established the genetic relationship between the isolates. MRSP could be a threat to animal health due to it concerning level of antimicrobial resistance. Our study highlights genetic and epidemiological aspects of multidrug-resistant MRSP strains from Argentina showing high degree of correlation between the resistance genes and the phenotype of the isolates and, furthermore, they appeared evolutionary closer to major worldwide reported ST68 and ST71.Facultad de Ciencias Veterinaria

Adjuvant treatment for elderly patients with colon cancer. An observational study

Background: Adjuvant. 5-fluoruracil-based chemotherapysignificantly reduces mortality in. patients with: stage II-III colon cancer, but is less prescribed with rising age. In this study we were interested in the pattern of adjuvant treatment and possible effects on survival among elderly patients. Patients and methods: From January to December 2004, 63 questionnaires on the management of stage II-III resected colon cancer patients aged over 70 years, collected from 10 Italian Centres, were retrospectively examined. Determinants of receipt of adjuvant chemotherapy and their relation to survival were considered. Results: The proportion of elderly patients receiving adjuvant chemotherapy was 79.4%, distinct of age, gender, educational level and comorbidities. Grade 3-4 toxicities were the following: haematological in 4 (8.5.%) patients, mucositis in 4 (8.5%), diarrhoea in 2 (4.2%) and nausea in 1 (2.1%). The disease-free survival (DFS) and overall survival (OS) at two years were 79.9% and 95.6%, respectively. Due to the paucity of events, the impact of prognostic factors (patient's age and comorbidity, tumour stage and grade) on DFS and OS could not be assessed. Conclusion: An increasing proportion of elderly patients with colon cancer may be treated with a tolerability and OS similar to those observed in the younger population. Development of age-based guidelines and increased awareness of both physicians and patients through education is important to prevent undertreatment of those elderly patients who are eligible for chemotherapy

Dioxin Exposure, from Infancy through Puberty, Produces Endocrine Disruption and Affects Human Semen Quality

BACKGROUND: Environmental toxicants are allegedly involved in decreasing semen quality in recent decades; however, definitive proof is not yet available. In 1976 an accident exposed residents in Seveso, Italy, to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). OBJECTIVE: The purpose of this study was to investigate reproductive hormones and sperm quality in exposed males. METHODS: We studied 135 males exposed to TCDD at three age groups, infancy/prepuberty (1-9 years), puberty (10-17 years), and adulthood (18-26 years), and 184 healthy male comparisons using 1976 serum TCDD levels and semen quality and reproductive hormones from samples collected 22 years later. RESULTS: Relative to comparisons, 71 men (mean age at exposure, 6.2 years; median serum TCDD, 210 ppt) at 22-31 years of age showed reductions in sperm concentration (53.6 vs. 72.5 million/mL; p = 0.025); percent progressive motility (33.2% vs. 40.8%; p < 0.001); total motile sperm count (44.2 vs. 77.5 x 10(6); p = 0.018); estradiol (76.2 vs. 95.9 pmol/L; p = 0.001); and an increase in follicle-stimulating hormone (FSH; 3.58 vs. 2.98 IU/L; p = 0.055). Forty-four men (mean age at exposure, 13.2 years; median serum TCDD, 164 ppt) at 32-39 years of age showed increased total sperm count (272 vs. 191.9 x 10(6); p = 0.042), total motile sperm count (105 vs. 64.9 x10(6); p = 0.036), FSH (4.1 vs. 3.2 UI/L; p = 0.038), and reduced estradiol (74.4 vs. 92.9 pmol/L; p < 0.001). No effects were observed in 20 men, 40-47 years of age, who were exposed to TCDD (median, 123 ppt) as adults (mean age at exposure, 21.5 years). CONCLUSIONS: Exposure to TCDD in infancy reduces sperm concentration and motility, and an opposite effect is seen with exposure during puberty. Exposure in either period leads to permanent reduction of estradiol and increased FSH. These effects are permanent and occur at TCDD concentrations < 68 ppt, which is within one order of magnitude of those in the industrialized world in the 1970s and 1980s and may be responsible at least in part for the reported decrease in sperm quality, especially in younger men

The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia in an Italian population sample

Programmed cell death and alterations in intracellular G-protein signaling may be involved in the pathophysiology of schizophrenia. The Galphas subunit of heterotrimeric G-proteins, encoded by the gene GNAS1, may play a role in both of these processes. Additionally, transgenic mice expressing a constitutively active form of Galphas provide a reliable model of certain endophenotypes of schizophrenia. To investigate whether the functional single nucleotide polymorphism T393C in GNAS1 gene could affect risk of schizophrenia, we examined its distribution in Italian subjects with (n=383) and without (n=400) schizophrenia. We also evaluated whether a specific association could exist between the deficit (n=108) and nondeficit (n=275) forms of the disorder. The alleles and genotypes frequency in the entire cohort of schizophrenic patients did not differ from that of controls. However, the frequency of the homozygous 393TT genotype was significantly higher in deficit schizophrenic patients (37.1%) compared to both nondeficit schizophrenic (22.5%, p=0.011) and controls (22.8%, p=0.015). This association with deficit schizophrenia persisted even after allowance for potential confounders [adjusted odds ratio (OR) for deficit schizophrenia: 2.06 (95% confidence interval (CI): 1.21-3.47), p=0.007]. Altogether, our data suggest that the GNAS1 T393C status could influence susceptibility for deficit schizophrenia in Italian subjects

Caracterización fenotípica y genotípica de la resistencia enzimática a las cefalosporinas de tercera generación en Enterobacter spp. Phenotypic and genotypic characterization of resistance to third-generation cephalosporins in Enterobacter spp.

Enterobacter spp. es un patógeno intrahospitalario que presenta múltiples mecanismos de resistencia a los antibióticos b-lactámicos. Se caracterizaron fenotípica y genotípicamente las diferentes b-lactamasas presentes en 27 aislamientos consecutivos e ininterrumpidos de Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes). También se evaluó la habilidad de diferentes métodos fenotípicos para detectar b-lactamasas de espectro extendido (BLEE) en estos microorganismos. En 15/27 aislamientos (63%) se observó resistencia a las cefalosporinas de tercera generación. En 12 de los aislamientos resistentes se detectó un alto nivel de producción de cefalosporinasa cromosómica, siendo 6 de ellos también productores de PER-2. Dicha resistencia en los 3 aislamientos restantes se debió exclusivamente a la presencia de BLEE, PER-2 en 2 de ellos y CTX-M-2 en un caso. Sólo CTX-M-2 se detectó con todas las cefalosporinas probadas en los ensayos de sinergia, utilizando el método de difusión, mientras que cefepima mejoró la detección de PER-2 en 7/8 aislamientos productores de esta BLEE, 4/8 utilizando la prueba de doble disco y 7/8 comparando discos de cefepima con y sin el agregado de ácido clavulánico. El método de dilución empleado solo detectó 1/9 BLEE al comparar las cefalosporinas con y sin el agregado de inhibidor.<br>Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to b-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum b-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63%) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC b-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor aproximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers