Combination of phenotype and polygenic risk score in breast cancer risk evaluation in the Spanish population: a case -control study.

BACKGROUND: In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. METHODS: This is a case control study based on a population-based cohort. We describe and evaluate a multivariable model that incorporates 92 Single-nucleotide polymorphisms (SNPs) (Supplementary Table S1) and five different phenotypic variables and which was employed in a Spanish population of 642 healthy women and 455 breast cancer patients. RESULTS: Our model allowed us to stratify two groups: high and low risk of developing breast cancer. The 9th decile included 1% of controls vs 9% of cases, with an odds ratio (OR) of 12.9 and a p-value of 3.43E-07. The first decile presented an inverse proportion: 1% of cases and 9% of controls, with an OR of 0.097 and a p-value of 1.86E-08. CONCLUSIONS: These results indicate the capacity of our multivariable model to stratify women according to their risk of developing breast cancer. The major limitation of our analysis is the small cohort size. However, despite the limitations, the results of our analysis provide proof of concept in a poorly studied population, and opens up the possibility of using this method in the routine screening of the Spanish population.

Patient's perspective in clinical practice to assess and predict disability in multiple sclerosis.

The information provided by a person with multiple sclerosis (MS) may anticipate changes in the course of the disease. To explore the role of a set of standardized patient-reported outcomes (PRO) in predicting disability progression in MS an observational study was conducted in two cohorts of 30 and 86 persons with progressive MS (pwPMS) and relapsing MS (pwRMS), respectively. The associations between baseline clinical, biochemical variables and results on MS quality of life scale (MusiQol), Modified Fatigue Impact Scale (MFIS) and Beck Depression Inventory II (BDI-II) were analyzed. The progression of disability after 2 years of follow-up in pwRMS was investigated. We show that PRO differentiated pwRMS and pwPMS cohorts with lower MusiQoL and higher MFIS and BDI-II scores in the latter. Only MFIS was correlated with disability in pwRMS and high scores in the physical MFIS domain associated with worse performance in 9HPT, and a trend in T25FW and SDMT. Instead, the cognitive MFIS domain was correlated with CHI3L1 in cerebrospinal fluid, a biomarker of progression. At the end of the study, global MFIS and BDI-II were found to be independent risk factors for disability independent of relapse. Although all PRO measures explored were altered in pwPMS, baseline MFIS discriminated current and prospective disability in pwRMS, identifying patients at risk of progression.

Molecular and biological characterization of natural variants of Citrus dwarfing viroid.

Citrus dwarfing viroid has been proposed as an agent to control tree size in high-density plantations. Thirty-three field isolates have been characterized, and the most frequent sequence/s have been identified. Five distinct variants were selected for biological characterization. Symptom expression analysis demonstrated a good correlation between leaf/stem symptoms and plant growth. The discriminating nucleotide sequence differences included two deletions and an insertion resulting in a reorganization of the base pairing of the terminal left loop, two (G42 --> A and C52 --> U) changes found in one of the variants, and as many as thirteen changes located in the right and left regions flanking the CCR.

Meat quality traits in the Greater rhea (Rhea americana) as influenced by muscle, sex and age.

Meat from the Greater rhea (Rhea americana) could compete with traditional red meats, diversifying the market of protein products of animal origin. The meat from 32 rheas was used to study quality aspects and this included ultimate pH (pHu), color, water-holding capacity (WHC%), cooking loss (CL%) and tenderness. The muscles sampled were the Gastrocnemius pars externa, Iliofibularis and Obturatorius medialis from both sexes at multiple ages (10, 12, 14, 16 months). Age at slaughter affected WHC%, CL%, and color in raw meat and tenderness in cooked meat. Muscles under study showed differences in terms of pHu, raw meat color, and tenderness of cooked meat. Sex did not have a significant effect on any of the variables studied. According to our results, rhea meat from younger animals, between 10 to 14 months old, was tender and moderately juicy and the visual color was appreciated by the consumers.

Mechanical Transmission of Citrus Viroids.

Preliminary transmission assays conducted under greenhouse conditions demonstrated that Citrus exocortis viroid (CEVd), Citrus bent leaf viroid (CBLVd), Hop stunt viroid (HSVd), Citrus viroid III (CVd-III), and Citrus viroid IV (CVd-IV) can be mechanically transmitted from citron to citron (Citrus medica) by a single slash with a knife blade. The impact of mechanical transmission of viroids by pruning and harvesting operations was also demonstrated in experimental and commercial field plots. Transmission efficiency under field conditions ranged from 4% in 'Nules' clementine to 10% in 'Navelina' sweet orange and 21% in 'Verna' lemon. Transmission efficiency varied only slightly with viroid and donor hosts. The impact of viroid transmission on tree height, canopy volume, and crop harvest was minimal. When the donor host was coinfected with several viroids, the viroids were not necessarily cotransmitted. Considerations regarding viroid transmission in other climates are discussed. Measures to control viroid spread in nurseries should be mandatory in certification programs.

A novel RT-PCR approach for detection and characterization of citrus viroids.

Citrus plants are natural hosts of five viroid species and a large number of sequence variants. Because of their small size, viroids lend themselves to various RT-PCR approaches for their detection and further characterization. The one-step RT-PCR approach proposed here is based on the synthesis of viroid-cDNA by reverse transcription at 60 degrees C using a viroid specific 27-mer primer followed by standard second strand synthesis plus PCR amplification with various primer pairs. According to the primers used, full or partial length viroid-DNA is obtained. The technique avoids amplicon contamination in routine diagnosis. The suitability of the technique has been demonstrated using several nucleic acid extraction procedures and different viroid infected host species. The homogenization of tissue inside sealed plastic bags followed by nucleic acid extraction using a SDS/potassium acetate method is recommended because of its efficiency, simplicity and low cost. This extraction procedure, when coupled to the one-step RT-PCR approach, can be useful to avoid cross-contamination during routine diagnosis. A PCR strategy capable of discriminating between mild and severe strains of CEVd and identifying cachexia-inducing isolates of HSVd, is also described.