Synchronous Occurrence of Mycosis Fungoides, Diffuse Large B Cell Lymphoma and Acute Myeloid Leukemia.

Patients with mycosis fungoides (MF), the most common subtype of primary cutaneous T-cell lymphoma, have an increased risk of developing secondary malignancies. We herein report two rare cases of MF concurring with diffuse large B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage) in two otherwise healthy elderly patients. Potential etiologic factors, including the impact of the therapy-associated inflammatory response on the development of secondary tumors in patients with MF, are discussed. Further clinical, experimental and genetic studies are needed to elucidate possible physiopathogenic associations among the three concurrent malignancies occurring in the cases presented here.

A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT.

IL-17 has an important role in the host defense against extracellular pathogens and the pathophysiology of autoimmune diseases. This study retrospectively examined the impact of a single-nucleotide polymorphism (rs2275913, G197A) in the IL-17 gene of a total 510 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in HLA-matched myeloablative (discovery study) and nonmyeloablative (validation study) BMT through the Japan Marrow Donor Program (JMDP). In the discovery study, the presence of a 197A genotype in the recipient resulted in a higher incidence of grades II-IV acute GVHD (hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.23-2.85; P=0.004). The donor IL-17A genotype did not significantly influence the transplant outcomes. The validation study showed a trend toward an association of the recipient 197A genotype with an increased risk of grades III-IV acute GVHD (HR, 5.84; 95% CI, 0.75-45.72; P=0.09), as well as a significantly increased risk for chronic GVHD (HR, 3.86; 95% CI, 1.29-11.59; P=0.02). These results suggest an association of the 197A genotype in the recipient side with the development of acute GVHD.

A single-nucleotide polymorphism of the Fcγ receptor type IIIA gene in the recipient predicts transplant outcomes after HLA fully matched unrelated BMT for myeloid malignancies.

Fcγ receptor type IIIA (FCGR3A) has a functional single-nucleotide polymorphism (rs396991), at which a G-to T-point mutation results in an amino acid substitution at position 158 (valine to phenylalanine; V158F). This study examined the effect of the FCGR3A polymorphism in donors and recipients on the clinical outcomes in unrelated HLA fully matched myeloablative BMT. The FCGR3A-V158F genotype was retrospectively analyzed in a total of 99 recipients with myeloid malignancies, and their unrelated donors. The presence of the 158V genotype in recipients showed a statistically better OS (adjusted hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.26-0.93; P=0.03) and TRM (HR 0.30; 95% CI 0.14-0.67; P=0.003) without significant influence on the relapse rate. The recipient 158V genotype was also associated with a significantly reduced risk of chronic GVHD (HR 0.45; 95% CI 0.20-0.99; P=0.049) and a trend toward a reduced risk of grade II-IV acute GVHD (HR 0.55; 95% CI 0.27-1.10; P=0.09), leading to a significantly reduced GVHD-related mortality (HR 0.22; 95% CI 0.06-0.77; P=0.02). The donor FCGR3A polymorphism did not have any effect on the transplant outcomes. These results suggest an association between the recipient FCGR3A genotype and the clinical outcomes after BMT.

Effects of calcium soaps of fatty acids on postpartum reproductive activity in beef cows and growth of calves.

Beef cows were used to determine the influence of calcium soaps of fatty acids (CSFA) incorporated in a range supplement on postpartum reproductive characteristics and growth of calves. Cows were assigned randomly to receive 0 (C, n = 68) or 125 g/d of CSFA (M, n = 66). Diets were isonitrogenous (23%) and were used during 105 d, beginning at 61 +/- 36 d (range) precalving. Two blood samples were collected monthly (7-d intervals). Weights of calves at 35, 50, and 90 d of age and weaning weight adjusted to 200 d of age were greater in M than in C (46.8 vs 43.8 kg, P < .05; 56.0 vs 50.6 kg, P< .01; 98.8 vs 91.8 kg, P < .01; and 186 vs 173 kg, P < .01, respectively). Body weights at 35 and 50 d postcalving were greater in M than in C cows (334 and 310 kg, P < .01; 329 and 300 kg, P < .01, respectively). A similar tendency was observed in body condition scores in the same postpartum periods (4.1 vs 3.4, P < .01 and 3.6 vs 2.5, P < .01 for M and C, respectively). Concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and triglycerides were greater (P < .01) in M than in C cows. Percentage of cycling (progesterone > 1 ng/mL) cows at 30 to 90 d postpartum was 38% in M and 22% in C (P < .02). Percentage of pregnant cows during the first half of the breeding season was greater (P < .02) in M (62.5%) than in C cows (35.5%). We concluded that CSFA incorporated in a range supplement during pre- and postpartum periods improved reproductive efficiency and growth of calves.

[Treatment of bronchial asthma in winter using controlled-release salbutamol]. / Tratamiento del asma bronquial en el periodo invernal con salbutamol de liberación controlada.

This paper presents results about comparative study in winter season, in a statistics design AB and BA on 20 patients that were treated with salbutamol (Group B) and with salbutamol of controlled liberation (Group B) at random. Results showed that patients of Group B had improvement in symptomatology and had less exacerbations than those patients of group A with statistical significance. It was concluded that salbutamol tablets of controlled liberation is a therapeutic method adequate to control chronic phase of asthmatic patients in winter season.