High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers.

BACKGROUND: Germline BRCA2 mutations are associated with poorer outcome prostate cancer (PCa) compared with sporadic tumours but this association remains to be characterised. In this study, we aim to assess if there is a signature set of copy number alterations (CNA) that could aid to the identification of BRCA2-mutated tumours and would assist us to understand their aggressive clinical behaviour. METHODS: High-resolution array comparative genomic hybridisation profiling of DNA from PCa and matched morphologically normal prostate samples from 9 BRCA2 germline mutation carriers and 16 non-carriers in combination with unsupervised analysis was used to define copy number features. RESULTS: PCa from BRCA2 germline mutation carriers (B2T) harbour significantly more CNA than non-carrier tumours (NCTs) (P = 14 × 10(-6)). A hundred and sixteen regions had a significantly different distribution with both false discovery rate (FDR) and P value <0.01, including CNA in the genomic region containing c-MYC that was present in 89% B2T versus 12.5% NCT (P = 3 × 10(-4)). Loss of heterozygosity (LOH) at the BRCA2 locus was observed in 67% of B2T. Elevated CNA are already present in 50% of the morphologically normal prostate tissue from BRCA2 carriers. CONCLUSION: The relative high amount of CNAs in morphologically normal prostate tissue of BRCA2 carriers implies a field effect and together with the observed LOH could be used as a marker of PCa risk in these men. Several features previously associated with poor PCa outcome have been found to be significantly more common in BRCA2-mutated PCa than in sporadic tumours and may help to explain their adverse prognosis and be of relevance for targeted therapies.

Energy requirements for maintenance and growth of male saanen goat kids.

The aim of study was to determine the energy requirements for maintenance and growth of forty-one Saanen, intact male kids with initial body weight (BW) of 5.12±0.19 kg. The baseline (BL) group consisted of eight kids averaging 5.46±0.18 kg BW. An intermediate group consisted of six kids, fed for ad libitum intake, that were slaughtered when they reached an average BW of 12.9±0.29 kg. The remaining kids (n = 27) were randomly allocated into nine slaughter groups (blocks) of three animals distributed among three amounts of dry matter intake (DMI; ad libitum and restricted to 70% or 40% of ad libitum intake). Animals in a group were slaughtered when the ad libitum-treatment kid in the group reached 20 kg BW. In a digestibility trial, 21 kids (same animals of the comparative slaughter) were housed in metabolic cages and used in a completely randomized design to evaluate the energetic value of the diet at different feed intake levels. The net energy for maintenance (NEm) was 417 kJ/kg(0.75) of empty BW (EBW)/d, while the metabolizable energy for maintenance (MEm) was 657 kJ/kg(0.75) of EBW/d. The efficiency of ME use for NE maintenance (km) was 0.64. Body fat content varied from 59.91 to 92.02 g/kg of EBW while body energy content varied from 6.37 to 7.76 MJ/kg of EBW, respectively, for 5 and 20 kg of EBW. The net energy for growth (NEg) ranged from 7.4 to 9.0 MJ/kg of empty weight gain by day at 5 and 20 kg BW, respectively. This study indicated that the energy requirements in goats were lower than previously published requirements for growing dairy goats.

Integrated ecotoxicological assessment of marine sediments affected by land-based marine fish farm effluents: physicochemical, acute toxicity and benthic community analyses.

An integrated ecotoxicological assessment of marine sediments affected by land-based marine fish farm effluents was developed using physicochemical and benthic community structure analyses and standardised laboratory bioassays with bacteria (Vibrio fischeri), amphipods (Ampelisca brevicornis) and sea urchin larvae (Paracentrotus lividus). Intertidal sediment samples were collected at five sites of the Rio San Pedro (RSP) creek, from the aquaculture effluent to a clean site. The effective concentration (EC50) from bacterial bioluminescence and A. brevicornis survival on whole sediments and P. lividus larval developmental success on sediment elutriates were assessed. Numbers of species, abundance and Shannon diversity were the biodiversity indicators measured in benthic fauna of sediment samples. In parallel, redox potential, pH, organic matter and metal levels (Cd, Cu, Ni, Pb and Zn) in the sediment and dissolved oxygen in the interstitial water were measured in situ. Water and sediment physicochemical analysis revealed the exhibition of a spatial gradient in the RSP, evidenced by hypoxia/anoxia, reduced and acidic conditions, high organic enrichment and metal concentrations at the most contaminated sites. Whereas, the benthic fauna biodiversity decreased the bioassays depicted decreases in EC50, A. brevicornis survival, P. lividus larval success at sampling sites closer to the studied fish farms. This study demonstrates that the sediments polluted by fish farm effluents may lead to alterations of the biodiversity of the exposed organisms.

Application of CMO (capacity, motivation, and opportunity) methodology in pharmaceutical care to optimize the pharmacotherapy in older people living with HIV. DISPIMDINAC project.

OBJECTIVE: To determine the effectiveness of a pharmaceutical intervention, based on the CMO methodology (capacity, motivation and opportunity), to decrease the prevalence of the PIMDINAC concept (potentially inappropriate medication+drug interactions+non-adherence to concomitant medication) in people living with HIV infection. METHODS: Longitudinal prospective multicenter study, conducted between October 2021 and October 2022. Patients living with HIV older than 65 years, on antiretroviral treatment and concomitant drug prescription were included. Demographic, clinical, and pharmacotherapeutic variables were collected. Pharmaceutical care was provided for6 months according to the CMO model in each patient. The main variable was the percentage of patients who simultaneously fulfilled the PIMDINAC concept, comparing the baseline value with the same value at the end of the study. In addition, the percentage of patient's adherent to concomitant and antiretroviral treatment and the percentage of patients meeting the pharmacotherapeutic targets established for the prescribed medicationat 24 weeks of follow-up were compared. RESULTS: Sixty-eight patients were included. Seventy-two percent were men, with a median age of 68 years. The median number of concomitant drugs was 7. A 60.6% of the patients had polypharmacy. The prevalence of the presence of the PIMDINAC concept decreased significantly (10.3 vs. 0%). In isolation, each of the aspects also decreased significantly (p<0.031). The percentage of patients who met the objectives improved significantly from 48,5 at baseline to 88.2 (p<0.001). CONCLUSIONS: The pharmaceutical intervention based onarmaceutical intervention based on the CMO methodology significantly decreased the prevalence of the PIMDINAC concept and increased the number of patients who achieved the objectives, optimising their pharmacotherapy.

Evaluation of the effect of 1,3-bis-(4-phenyl-[1,2,3] triazole-1-il)2-propanol in comparison with metronidazole in an in vitro culture of Blastocystis in samples of patients with irritable bowel syndrome.

Metronidazole is the most-used pharmaceutical for the treatment of infection by Blastocystis. However, studies have reported resistance of the microorganism towards this pharmaceutical. In Mexico, studies concerning the prevalence of this parasite and its relationship to Irritable Bowel Syndrome have been carried out. To evaluate the in vitro effect of metronidazole and the compound 1,3-bis-(4-phenyl-[1,2,3] triazole-1-il)2-propanol over Blastocystis, as well as the prevalence of Blastocystis in patients with Irritable Bowel Syndrome. A prospective, transversal design study (April 2016-April 2017) of 51 samples of patients with Irritable Bowel Syndrome, obtained from the ISSEMyM Medical Center in Toluca, Mexico. For the identification of Blastocystis was done in three serial stool samples through direct microscopic examination and the Ritchie technique. The in vitro susceptibility test towards metronidazole and the triazolic compound was done through a microculture in concentrations of 1 to 1000 µg/mL, each one in triplicate. A 31.3% prevalence of Blastocystis was observed in the population, with greater prevalence in women (30.2%) than in men (25%). In the susceptibility test, a CL50 of 64 µg/mL was obtained for metronidazole, in comparison to the CL50 of 250 µg/mL for 1,3-bis-(4-phenyl-[1,2,3] triazole-1-il)2-propanol. This molecule in development has an effect for the treatment of infection by Blastocystis in vitro in patients with IBS and therefore, more studies should be performed.

Estrategia de captación para vacunación en una zona de transformacion social / Recruitment strategy for vaccination in a social transformation area

En zona de transformación social del sur de España, se realiza una estrategia de captación para vacunación COVID-19 de personas que cumplen con los requisitos establecidos. Se realiza captación en zona de 360 personas de etnia gitana, mediante un equipo de asistencia social apoyado por Protección Civil. Se reparten mascarillas como reclamo para entablar contacto y dar información del proceso de vacunación. Posteriormente, se procede a la vacunación. Se consiguió vacunar al 40% de la población. Un 14% correspondían a aquellos con enfermedad reciente o vacunados; el resto eran menores. Se recogió, el argumento que tenían para rechazar vacunarse. La organización, y buena integración de los servicios sociales en programas de Salud Pública, ha tenido un importante papel en la creación y aceptación de programas específicos con, resultados evaluables. Tanto la estrategia de captación como la respuesta obtenida se consideraron buenas. Encontramos necesarias este tipo de intervenciones en determinados colectivos.(AU)

In an area of social transformation in southern Spain, a recruitment strategy for COVID-19 vaccination of people who meet the established requirements. A social assistance team, supported by Civil Protection, is recruiting 360 gypsy people in the area. Masks are distributed as a lure to establish contact and provide information on the vaccination process. Subsequently, vaccination is carried out. We managed to vaccinate 40% of the population. Some 14% corresponded to those with recent disease or vaccinated; the rest were minors. The argument they had for refusing to be vaccinated was collected. The organization and good integration of social services in Public Health programs has played an important role in the creation and acceptance of specific programs with evaluable results. Both the recruitment strategy and the response obtained were considered good. We found this type of intervention necessary in certain groups.(AU)

Non-genomic mechanism of action of delta-4 and 5-reduced androgens and progestins on the contractility of the isolated rat myometrium.

Effective concentrations50 of androgens, i.e. testosterone, androsterone, androstanediol, 5 beta-dihydrotestosterone and progestins: progesterone, pregnanolone, pregnanedione, epipregnanolone, allopregnanolone and allopregnanedione were assayed on the tonic contractions of the isolated rat myometrium induced by calcium in high-potassium calcium-free depolarizant solutions. Steroids showed their relaxant effect by fadding the sustained contraction induced by calcium in a depolarized state. Also, the addition of the calcium ionophores A-23187 and X-537A reversed the steroid relaxant effect by increasing sharply the tonic contraction. The possibility of steroid-induced relaxation through release of noradrenaline or histamine was discarded by blocking their specific receptors. From the results it is concluded that delta-4 and 5-reduced androgens and progestins produce relaxation by a myogenic mechanism acting on the smooth muscle cell, most likely by directly blocking the calcium channels they causing modulation of: the contraction-relaxation cycle.

Preoperative chemoradiotherapy in the treatment of gallbladder cancer.

Gallbladder cancer is generally associated with a poor prognosis, with local recurrence being the main pattern of failure. In an attempt to improve on the present status of management, we evaluated a prospective Phase II study involving preoperative 5-fluorouracil and radiation. Among 27 eligible patients with a potentially resectable gallbladder cancer detected after cholecystectomy, 18 were treated with preoperative radiation (4500 cGy; 180 cGy/fraction, 5 days/week) concurrent with a continuous infusion of 5-fluorouracil (350 mg/m2/day, days 1-5 and 21-25). Toxicity included leukopenia (8 patients) and thrombocytopenia (7 patients). Delay in surgery due to hematological toxicity was seen in 6 patients. Of the 18 patients, 15 underwent a reoperation. Resection was performed in 13 (86%). Pathologic findings after reoperation revealed residual tumor in both liver and lymph nodes in 3 patients. At a median follow-up of 24 months, 7 patients are alive. Among the patients who died after curative resection, local recurrence was demonstrated in only 1. This is the first report concerning preoperative chemoradiation in gallbladder cancer. To assess its effect on survival, a prospective randomized trial will be necessary.

Safety evaluation of sweet lupine (Lupinus albus cv. Multolupa). II. Nine-month feeding and multigeneration study in rats.

Sweet lupine Lupinus albus cv. Multolupa) flour containing 41.7% protein and 0.025% lupanine was fed for 9 months to two generations of rats (F1 and F2) at a level that provided 20% dietary protein. The diets were supplemented with 0.2% DL-methionine. The control diet provided the same dietary protein level from defatted soya-bean flour, fish meal and dried skimmed milk. The lupine diet had no effect on the general condition, mortality or behaviour of the animals. The growth rate of males fed sweet lupine was significantly higher than that of the controls. Haematological parameters and tests of liver function were normal in all treatment groups. At autopsy there were no significant changes in the weight of the heart, kidney, spleen, brain and gonads. However, the relative weight of the liver of lupine-fed rats was significantly lower than that in the controls. The histology of the liver, like that of the other organs examined, was normal. The reproduction study did not reveal any adverse effect on fertility or lactation that could be attributed to ingestion of sweet lupine. This investigation did not disclose any deleterious effects through two generations of rats that were fed sweet lupine at a level that provided 20% dietary protein for 9 months.

[Fat substitutes in human diet]. / Sustitutos de grasa en la alimentación humana.

Fat consumption in developed countries has increased steadily during this century reaching values higher than 40% of the daily total calorie intake. This situation has resulted in a high prevalence of obesity, cardiovascular disease, diabetes and some types of cancer. The health agencies in these countries have made strong recommendations for the population to reduce dietary fat intake in order to reduce total fat intake to les than 30% of the total calories, with a maximum of 10% calories derived from saturated fats. The food industry has taken a very active role developing a number of low fat foods and opening a new area of products called fat substitutes in order to help the consumers reduce their fat consumption. One of these substitutes is a synthetic product obtained by reacting fatty acids from natural sources and sucrose. The product is a polyester of sucrose and has been named olestra. Olestra has been approved by the US Food and Drug Administration (FDA) to be used in snacks and fried chips. Due to its lipophilic nature olestra has a negative effect on the absorption of fat soluble vitamins and nutrients. However, this problem may be solved by supplementation of the nutrients affected. In addition, olestra may cause gastrointestinal effects such as abdominal cramping and stool softening. The Company that developed olestra claims to have solved this problem by modifying the composition of fatty acids of the product. Olestra is being marketed in the USA under the name of Olean.

[Nutritive value of lupine and its potential as human food]. / Valor nutritivo del lupino y su potencial como alimento humano.

The chemical composition and some indices of protein quality were measured in two species of sweet lupine Lupinus albus and Lupinus luteus grown at the Experimental Station in Gorbea, Chile: both samples showed a high protein content (39.5 and 44.6%). The protein efficiency ratio (PER) was measured in the rat and found to be 0.48 and 0.71, respectively, as compared to 2.57 for casein. Supplementation with 0.3% DL-methionine increased significantly those values, thus indicating that lupine protein is deficient in said amino acid. In another experiment the effect of cooking-extrusion on lupine flour (L. albus) was investigated and the chemical composition, protein efficiency ratio, methionine supplementation and digestibility of the protein were measured. The chemical composition was not changed but PER increased from 0.50 for raw lupine to 0.76 for processed lupine (P less than 0.05). Both values increased significantly with the addition of 0.3% DL-methionine. The protein digestibility of the supplemented lupine was not affected by the cooking extrusion process (76.5 and 77.8%, respectively). Supplementation of wheat flour with 5, 10, 15 and 20% lupine flour increased the PER of wheat flour from 0.92, to 1.39 for wheat flour supplemented with 10% lupine flour, and to 1.60 for the 15% level of the supplement. These studies seem to support the conclusion that sweet lupine is an interesting protein resource for human nutrition.

[Fortification of bread with bean flour (Phaseolus vulgaris, L.). I. Flour and bread aspects]. / Fortificación del pan con harina de frejoles (Phaseolus vulgaris L.). I. aspectos farinologicos y de panificación.

This paper deals with the incorporation of bean flour (Phaseolus vulgaris, var. Tórtola) (BF) made at laboratory scale in bread enrichment, by substituting 2, 4, 6, 8 and 10% wheat flour by bean flour. First, wheat and bean flours blends were prepared to study the farinological properties of these combinations. Then, breads containing bean flour in the above-mentioned proportions were made. At the 6, 8 and 10% levels, a deterioration in farinological properties of the blends, such as water absorption, developing time, weakening and W value were evident. Baking tests showed that no significant changes occurred with respect to water absorption, mixing time, weight and volume of breads, and color and texture of crumb in BF levels of 2, 4 and 6%. However, overall qualities of the breads were significantly impaired at the 8 and 10% levels.

[Formulation and nutritive value of 2 milk substitutes based on sweet lupine (Lupinus albus, var. multolupa)]. / Formulación y valor nutritivo de dos sustitutos lácteos en base a lupino dulce.

Two protein mixtures, A and B, based on sweet lupine, wheat flour and dried skim milk powder were formulated, bearing in mind the chemical and nutritional standards set by the National System of Health Services for protein mixtures used through the National Program of Complementary Feeding (PNAC) for preschool children. Both formulas contained 12% of sweet lupine flour, but they differed in their skim milk content, which was 15% in mixture A, and 10% in mixture B. Taking as reference value a content of 2% moisture, formula A contains 17.6% protein and mixture B, 16.4%, with a caloric content of 420 kcal/100 g for both of them. The amino acid score was 0.80 for both mixtures. The biological quality of the proteins of A and B, measured as protein efficiency ratio (PER), was 2.2 and 2.1, respectively. These values are not statistically different, although they are lower than the value of 2.5 obtained for casein (p less than 0.01).

[Sensory evaluation and acceptability study, at the consumer level, of bread supplemented with sweet lupine flour]. / Evaluación sensorial y estudio de aceptabilidad, a nivel de consumidor, de pan suplementado con harina de lupino dulce.

The purpose of this study was to determine the effect of incorporating sweet lupine flour (SLF) to bread, upon the organoleptic characteristics and acceptability of the product. The substitution levels were 3, 6, 9 and 12%. The sensory evaluation test was done by 25 trained judges using the hedonic scaling method (9 to 1 scoring). Internal and external characteristics of appearance, color, aroma, texture, bitterness and flavor, as well as general acceptability, were measured. Sensory evaluation results of the external characteristics were significant at the 9 and 12% SLF levels for color (p less than 0.05) while the other parameters did not show significant differences. In regard to the internal characteristics, a significant difference for color was found at the 3% level of SLF (p less than 0.05); and at 6, 9 and 12% SLF levels, for appearance (p less than 0.05). The general acceptability was good at all the levels tested, with no significant differences among them. An acceptability study at the consumer level for 9% lupine flour bread was carried out in a group of 90 girls, aged 10-12 years, during a 10-day period. The results showed a very good acceptability of the product (p less than 0.01). The results of this study indicate that the incorporation of 6% SLF to the bread, did not affect adversely its sensory properties. Moreover, the acceptability of bread containing up to 12% SLF was excellent.

[Sensory evaluation of bread with potato flour]. / Evaluación sensorial de pan con harina de papa.

A sensory evaluation test was conducted in breads containing 2, 4, 6, 8 and 10% potato flour. The samples were sliced into equally sized pieces and served as coded randomized duplicates. All-wheat bread was used as a standard. The comparative preferences were rated on a 7-point hedonic scale (7 = very good, 1 = very bad) for appearance, flavor, texture and overall quality. The scores were statistically analyzed by the analysis of variance and the Chi square test. No significant differences were found in regard to flavor between the standard bread and bread containing from 2-10% potato flour. In the test of organoleptic quality, the bread containing 8% potato flour was rated as "good", as compared to "very good" for the all-wheat bread. However, this difference was not statistically significant. The values obtained in this study show that the incorporation of 6-8% potato flour in bread is perfectly feasible. This was obtained from a local food industry that in manufacturing the flour, used the Spartan variety potato produced in the southern region of Chile.

[Enrichment of bread with soy flour]. / Enriquecimiento de pan con harina de soya.

A series of laboratory studies was conducted to test the effect of the inclusion of soy flour in bread at the levels of 2, 4, 6, 8, 10 and 12%. The farinographic tests showed that several changes occurred with the incorporation of soy flour to the wheat flour, such as an increase in water absorption and weakening of the dough, and a decrease in the dough developing time. The mixing time remained unchanged up to the level of 8% substitution. Higher levels produced an increasing stickiness of the dough that made its handling more difficult. Soy-containing breads were slightly darker than wheat bread with a score of 71 points (scale 100) for the 12% level of substitution. The texture became coarser with increasing substitution of soy flour. Starting with the level of 4% of soy flour a volume decrease was observed, but this was corrected by the addition of 0.5% sodium stearoyl-2-lactylate (SSL). At the levels of 10 and 12% of soy flour, SSL was not effective in preventing the reduction of volume. The chemical composition of bread showed a regular increase in its protein content from 13.4, to 18% in the bread containing 12% soy flour. The protein efficiency ratio of bread improved from 1.17 for the wheat bread, to 2.13 for the bread containing 6% soy flour (casein, 2.54). Our results confirm the observation made by other workers in that the inclusion of soy flour in bread improves both the protein concentration and quality of this basic food.

[Chemical evaluation and determination of the nutritive value of a variety of Opaque-2 corn in the initial diet of broilers]. / Evaluación química y determinación del valor nutritivo de una variedad de maíz Opaco-2 en la ración inicial del broiler.

Chemical and amino acidic composition of Opaque-2 corn, cultivar CIMMYT-TL 81-A (Hungarian compound) locally produced were determined. In addition, the productive performance of broiler chicks fed Opaque-2 corn or normal corn (Pioneer) for the first 28 days of age was evaluated. The chemical and amino acid content results obtained for the Opaque-2 corn studied, compared well ranges previously reported. The productive performance at the end of the experiment was similar between the two treatments assayed.

[Cereal bars with peanut and puffed amaranthus: chemical composition and stability in accelerated storage]. / Barras de cereales maní y amaranto dilatado: composición química y estabilidad en almacenamiento acelerado.

Three different cereal bars, CM3A-CM3B and CM3C were prepared following the flow sheat of Escobar et al: different amount of oat, wheat germ, and puffed amaranthus were used: to stick them together, natural sweeteners and fats were added. Proximate analysis, were run on raw materials and snack bars. They were evaluated organoleptically to know their quality and acceptability. Bars were kept in accelerated storage at 37 degrees C during 15 days to know their stability. Every 5 days were measured the water activity (Aw), moisture, and peroxides development; also appearance of organoleptic randicity. Acceptability of bar CM3B was 91.67% with 0.0% of rejection; CM3A and CM3C got the same acceptability (66.67%) and 8.33% of rejection. In accelerate storage, Aw and moisture content decreased until reaching a value of 0.48 and 5.9 in the CM3B bar, respectively. Peroxide content of CM3B and CM3C increased gradually up to 12 and 17 meq/kg respectively at 15 days. Rancyd aroma appearance was not the same in the bars, CM3A and CM3B had a decreasing at 15 days, while CM3C showed an increasing at the same time. In brief, CM3B showed the best sensory quality, the higher acceptability and the greater stability in accelerated storage.

[Chemical and nutritional characterization of amaranthus (Amaranthus cruentus)]. / Caracterización química y nutricional del amaranto (Amaranthus cruentus).

Two samples of Amaranthus cruentus harvested in 1987 (sample A) and 1990 (sample B) were studied. Whole and refined flours were obtained. The whole flours contained 14.6 and 12.6% protein and 6.6 and 7.3 ether extraction, respectively. Both samples contained significant levels of Ca, P, Mg and K. Amaranth oil contained 19% palmitic acid, 3.4% stearic acid, 3.4% stearic acid, 34% oleic acid and 33% linoleic acid. Docosaenoic acid (C22:1) was present at the level of 9%. The ratio of saturated to unsaturated fatty acids was approximately 1:3. The level of crude fiber was 3.7% in the whole flours and 2.4% in the refined ones. Biological protein quality of flours was measured in the rat by the net protein ratio (NPR) method. The NPR values of the four materials tested ranged from 3.04 to 3.20 (NS), as compared with 4.08 for casein. These values are equivalent to 75-78% of the standard protein. Blends of raw wheat flour and whole amaranth flour fed to rats produced a good complementary effect between proteins, as shown by PER test. Wheat flour gave a poor PER value of 0.54. However, this figure increased with every increment of amaranth flour reaching a value of 2.15 for the blend 25:75. The PER for the amaranth diet (0:100) was 1.94 (casein 2.77). As expected, the extrusion process applied to the wheat/amaranth and corn/amaranth mixtures improved the biological quality of the protein. The wheat flour diet (100:0) gave a PER value of 1.64. Mixture 90:10 produced a low non significant increase in the protein quality.(ABSTRACT TRUNCATED AT 250 WORDS)