A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients.

BACKGROUND: Currently, no vaccine against Pseudomonas is available. IC43 is a new, recombinant, protein (OprF/I)-based vaccine against the opportunistic pathogen, Pseudomonas aeruginosa, a major cause of serious hospital-acquired infections. IC43 has proven immunogenicity and tolerability in healthy volunteers, patients with burns, and patients with chronic lung diseases. In order to assess the immunogenicity and safety of IC43 in patients who are most at risk of acquiring Pseudomonas infections, it was evaluated in mechanically ventilated ICU patients. METHODS: We conducted a randomized, placebo-controlled, partially blinded study in mechanically ventilated ICU patients. The immunogenicity of IC43 at day 14 was determined as the primary endpoint, and safety, efficacy against P. aeruginosa infections, and all-cause mortality were evaluated as secondary endpoints. Vaccinations (100 µg or 200 µg IC43 with adjuvant, or 100 µg IC43 without adjuvant, or placebo) were given twice in a 7-day interval and patients were followed up for 90 days. RESULTS: Higher OprF/I IgG antibody titers were seen at day 14 for all IC43 groups versus placebo (P < 0.0001). Seroconversion (≥4-fold increase in OprF/I IgG titer from days 0 to 14) was highest with 100 µg IC43 without adjuvant (80.6%). There were no significant differences in P. aeruginosa infection rates, with a low rate of invasive infections (pneumonia or bacteremia) in the IC43 groups (11.2-14.0%). Serious adverse events (SAEs) considered possibly related to therapy were reported by 2 patients (1.9%) in the group of 100 µg IC43 with adjuvant. Both SAEs resolved and no deaths were related to study treatment. Local tolerability symptoms were mild and rare (<5% of patients), a low rate of treatment-related treatment-emergent adverse events (3.1-10.6%) was observed in the IC43 groups. CONCLUSION: This phase II study has shown that IC43 vaccination of ventilated ICU patients produced a significant immunogenic effect. P. aeruginosa infection rates did not differ significantly between groups. In the absence of any difference in immune response following administration of 100 µg IC43 without adjuvant compared with 200 µg IC43 with adjuvant, the 100 µg dose without adjuvant was considered for further testing of its possible benefit of improved outcomes. There were no safety or mortality concerns. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00876252 . Registered on 3 April 2009.

Expression of calpastatin isoforms in three skeletal muscles of Angus steers and their association with fiber type composition and proteolytic potential.

This study aimed to evaluate the expression of calpastatin (CAST) isoforms and their potential associations with fiber type composition (%RA), calpastatin activity (CA) and myofibril fragmentation index (MFI) in three muscles with known differences in tenderness (infraspinatus, triceps brachii and semitendinosus) of Angus steers. Expression of total CAST (CAST-T) and CAST isoforms I, II, III (2-3) and III (2-4) (including or not exon 3) was evaluated by qRT-PCR. CAST expression and CA were significantly higher and MFI was lower in semitendinosus, the muscle with the highest %RA of IIX fibers. Differential expression of isoforms defined the variability in CAST-T among muscles. Semitendinosus had a higher expression of isoforms II and III (2-3), but lower expression of III (2-4) compared to the other two muscles. Relative expression of isoforms II and III that were defined by promoter preference linked to alternative splicing, seem to be the main factors explaining differences in CAST expression and ultimately in MFI among muscles.

Two methods for genotyping a 4-base deletion in the canine ABCB1 gene.

A 4-bp deletion (c.230_233delATAG) of the ABCB1 gene, frequently found in various dog breeds, results in intolerance to certain drugs routinely used in veterinary medicine, including many chemotherapeutic agents and macrocyclic lactones. The use of rapid and reliable genetic testing is fundamental for early detection of the mutation and prevention of undesirable toxicoses. We developed and compared 2 genotyping tests: PCR-high-resolution melting (PCR-HRM) and PCR-restriction-fragment length polymorphism (PCR-RFLP) to identify the 4-bp deletion in the ABCB1 gene of canine breeds. Amplified PCR products were sequenced in order to confirm different genotypes. Both techniques were efficient in discriminating homozygous wild-type, homozygous mutated, and heterozygous ABCB1 genotypes, and proved to be reproducible and economical methods. The HRM analysis, a sensitive and specific method for the molecular detection of genetic disorders, does not require labeled probes, processing, or separations after PCR.

Thirty years of land-cover change in Bolivia.

Land-cover change in eastern lowland Bolivia was documented using Landsat images from five epochs for all landscapes situated below the montane tree line at approximately 3000 m, including humid forest, inundated forest, seasonally dry forest, and cloud forest, as well as scrublands and grasslands. Deforestation in eastern Bolivia in 2004 covered 45,411 km2, representing approximately 9% of the original forest cover, with an additional conversion of 9042 km2 of scrub and savanna habitats representing 17% of total historical land-cover change. Annual rates of land-cover change increased from approximately 400 km2 y(-1) in the 1960s to approximately 2900 km2 y(-1) in the last epoch spanning 2001 to 2004. This study provides Bolivia with a spatially explicit information resource to monitor future land-cover change, a prerequisite for proposed mechanisms to compensate countries for reducing carbon emissions as a result of deforestation. A comparison of the most recent epoch with previous periods shows that policies enacted in the late 1990s to promote forest conservation had no observable impact on reducing deforestation and that deforestation actually increased in some protected areas. The rate of land-cover change continues to increase linearly nationwide, but is growing faster in the Santa Cruz department because of the expansion of mechanized agriculture and cattle farms.

Eficacia y seguridad clínica del itolizumab en fase de inducción en pacientes con psoriasis grave / Efficacy and clinical safety of Itolizumab in the induction phase in patients with severe psoriasis

Introducción: La psoriasis, enfermedad inflamatoria sistémica de la piel, tiene consecuencias adversas serias para el bienestar físico, mental y social de las personas; sus tratamientos son costosos y con marcados efectos adversos. El itolizumab, anticuerpo monoclonal anti CD6 humanizado, actúa como inmunomodulador de las células T y desempeña un importante papel en su patogénesis. Objetivo: Evaluar la eficacia y la seguridad clínica del itolizumab en 80 pacientes con psoriasis vulgar grave. Métodos: Se realizó un programa de uso clínico expandido, promovido por el Centro de Inmunología Molecular. La respuesta clínica se midió por el índice de gravedad y área de afectación de psoriasis, y para la eficacia se conjugaron estos elementos con los de seguridad, mediante un análisis clínico complementario de los datos generados durante la fase de inducción. Se emplearon como medidas de resumen los números absolutos, el porciento, el promedio y estadísticas de asociación: las pruebas de correlación de de Pearson, de Friedman y la prueba de Lambda. Resultados: El análisis del área de afectación de psoriasis arrojó un rápido y sostenido descenso de sus valores; prevalecieron los eventos adversos relacionados con la administración del producto en investigación, de aparición inmediata, ligeros, muy probables y no serios. Conclusiones: El itolizumab es seguro y eficaz en el 96 por ciento de los pacientes psoriásicos graves durante los esquemas de inducción(AU)

Introduction: Psoriasis, systemic inflammatory skin disease, has serious adverse consequences for the physical, mental and social well-being of people; its treatments are expensive and with marked adverse effects. Itolizumab, a humanized anti-CD6 monoclonal antibody, acts as an immunomodulator of T cells and plays an important role in its pathogenesis. Objective: To evaluate the efficacy and clinical safety of itolizumab in 80 patients with severe psoriasis vulgaris. Methods: An expanded clinical use program was carried out, promoted by the Molecular Immunology Center. The clinical response was measured by the severity index and area of psoriasis involvement and for effectiveness these elements were combined with safety, through a complementary clinical analysis of the data generated during the induction phase. Absolute numbers, percent and average and association statistics such as Pearson's correlation tests or Lambda's test were used as summary measures. Results: The area of psoriasis involvement analysis showed a rapid and sustained decrease in its values; adverse events related to the administration of the product under investigation prevailed, light onset, very probable and not serious. Conclusions: Itolizumab is safe and effective in 96 percent of severe psoriatic patients during the induction phase(AU)

Presentación clínica atípica del carcinoma epidermoide cutáneo / Atypical Clinical Presentation of Cutaneous Squamous Cell Carcinoma

Se presenta el caso de un hombre de 75 años de edad, de piel negra y con antecedentes de salud hasta hace dos años en que sufre caída y recibe un trauma en la región sacra, donde apareció una lesión pequeña e indolora, la cual meses después aumentó de tamaño. El paciente fue atendido en varios centros asistenciales con el diagnóstico de exulceración traumática. Recibió diversos tratamientos sin mejoría. En el Hospital Militar de Santiago de Cuba se le realizó biopsia de piel cuyo resultado fue carcinoma epidermoide. Constituyó un caso poco frecuente por las características clínicas y la localización de la lesión(AU)

The case of a 75-year-old black man with a health history is presented in this paper. Two years ago he suffered a fall and was injured traumatized in the sacral region, with a small, painless lesion, which increased in size months later. This patient was treated in several care centers with the diagnosis of traumatic exulceration. He received various treatments with no improvement. A skin biopsy was performed at Santiago de Cuba Military Hospital, the result was epidermoid carcinoma. It was a rare case due to the clinical characteristics and location of the lesion(AU)

Effect of ageing and µ-calpain markers on meat quality from Brangus steers finished on pasture.

Brangus steers (n=247) finished on pasture were used to evaluate the effects of post-mortem ageing and polymorphism CAPN1 316 and CAPN1 4751 markers on meat tenderness and objective colour measurements (CIEL*a*b*) of m. Longissimus dorsi. Ageing meat for 7 days decreased shear force (SF) by 13.7% and improved a* (8.4%) and b* (10%) compared to ageing for 1 day. No difference between 7 and 14 days of ageing was found for SF, a* and b*. However, L* increased markedly with ageing. Fitting both markers simultaneously, CAPN1 316 showed association with SF and L* and CAPN1 4751 with a* and b*. Fitting the markers individually, CAPN1 4751 affected all traits and CAPN1 316 showed association with SF and L*. Post-mortem ageing and the use of markers represent two independent and alternative tools that could be used for improving quality of meat from Brangus cattle.

The association of CAPN1 316 marker genotypes with growth and meat quality traits of steers finished on pasture.

The objective of this paper was to determine the association of a SNP in the µ-calpain gene at position 316 with growth and quality of meat traits of steers grown on pasture. Fifty-nine Brangus and 20 Angus steers were genotyped for CAPN1 316. Warner Bratzler shear force was measured in l. lumborum samples after a 7-day aging period. A multivariate analysis of variance was performed, including shear force (WBSF), final weight (FW), average daily gain (ADG), backfat thickness (BFT), average monthly fat thickness gain (AMFTG), rib-eye area (REA), and beef rib-eye depth (RED) as dependent variables. The CAPN1 316 genotype was statistically significant. Univariate analyses were done with these variables. The marker genotype was statistically significant (p < 0.05) for WBSF (kg: CC: 4.41 ± 0.57; CG: 5.58 ± 0.20; GG: 6.29 ± 0.18), FW (kg: CC: 360.23 ± 14.71; CG: 381.34 ± 5.26; GG: 399.23 ± 4.68), and ADG (kg/d: CC: 0.675 ± 0.046; CG: 0.705 ± 0.016; GG: 0.765 ± 0.014) Shear force, final weight and average daily gain were significantly different according to the CAPN1 316 marker genotypes. The marker genotype was statistically significant in the multivariate analysis (p = 0.001). The first characteristic root explained 89% of the differences among genotypes. WBSF, FW and ADG were the most important traits in the first vector, indicating that animals with the marker genotype for lowest WBSF also have the lowest FW and ADG.

Fibroma Odontogénico Periférico: a propósito de 2 casos clínicos / Peripheral odontogenic fibroma (POF): a rare clinical lesion

Se presentan dos casos clínicos de fibroma odontogénico periférico (FOP) entidad poco frecuente. Fueron diagnosticados tratados y seguidos en las Cátedras de Patología, Semiología y Clínica Estomatológica y de Anatomía Patológica Buco-máxilo-facial de la Facultad de Odontología (UDELAR). La baja frecuencia de esta lesión en la literatura y el diagnóstico diferencial que plantea con otras lesiones hace interesante su publicación. Ambos afectaron a mujeres de 6 y 57 años respectivamente.

The association of CAPN1 316 marker genotypes with growth and meat quality traits of steers finished on pasture

The objective of this paper was to determine the association of a SNP in the µ-calpain gene at position 316 with growth and quality of meat traits of steers grown on pasture. Fifty-nine Brangus and 20 Angus steers were genotyped for CAPN1 316. Warner Bratzler shear force was measured in l. lumborum samples after a 7-day aging period. A multivariate analysis of variance was performed, including shear force (WBSF), final weight (FW), average daily gain (ADG), backfat thickness (BFT), average monthly fat thickness gain (AMFTG), rib-eye area (REA), and beef rib-eye depth (RED) as dependent variables. The CAPN1 316 genotype was statistically significant. Univariate analyses were done with these variables. The marker genotype was statistically significant (p < 0.05) for WBSF (kg: CC: 4.41 ± 0.57; CG: 5.58 ± 0.20; GG: 6.29 ± 0.18), FW (kg: CC: 360.23 ± 14.71; CG: 381.34 ± 5.26; GG: 399.23 ± 4.68), and ADG (kg/d: CC: 0.675 ± 0.046; CG: 0.705 ± 0.016; GG: 0.765 ± 0.014) Shear force, final weight and average daily gain were significantly different according to the CAPN1 316 marker genotypes. The marker genotype was statistically significant in the multivariate analysis (p = 0.001). The first characteristic root explained 89 percent of the differences among genotypes. WBSF, FW and ADG were the most important traits in the first vector, indicating that animals with the marker genotype for lowest WBSF also have the lowest FW and ADG.

Association of CAPN1 and CAST gene polymorphisms with meat tenderness in Bos taurus beef cattle from Argentina

The activity of the calpains/calpastatin proteolytic system is closely related to the postmortem tenderization of meat. We investigated the association between beef tenderness and single nucleotide polymorphism (SNP) markers on the CAPN1 gene (SNP316, alleles C/G; SNP530 alleles A/G) and the CAST gene 3' untranslated region (SNP2870, alleles A/G). We sampled nine slaughter groups comprising 313 steers which had been reared in beef production systems in Argentina between 2002 and 2004 from crosses between Angus, Hereford and Limousin cattle. Minor allele frequencies for the markers were 0.27 to 0.46 (C), 0.02 to 0.18 (A), and 0.24 to 0.53 (A), respectively. The presence of CAPN1 markers had significant effects on meat shear force but no detectable effects were demonstrated for the CAST marker. The shear force of meat from steers with the SNP316 CC genotype was 11 percent lower than for the SNP316 CG genotype and 17 percent lower than for the SNP316 GG genotype. There were very few steers with the SNP530 AA genotype and, contrary to previous studies, meat from steers with the SNP530 GG genotype showed an 11.5 percent higher shear force than that from steers with the SNP530 GA genotype. Final body weight, carcass weight and rib eye area were not affected by any of the markers. These results support the concept that CAPN1 variants are associated with tenderness across a wide range of beef production systems.