Early feeding to modify digestive enzyme activity in broiler chickens

Objective. To evaluate the effect on digestive enzyme activity in broiler chickens by providing food in the first 48 hrs. after birth. Materials and methods. After incubating 300 fertile eggs from Hubbard breeding and immediately after hatching, the chicks were randomly assigned to treatments: fasting (from hatching to 48 hrs.); Hydrated Balanced Food (HBF) from birth to 48 hrs.; commercial hydrating supplement (CHS) from birth to 48 hrs. The diets were provided ad libitum. After 48 hrs. a commercial diet was fed. At birth and at 48 and 72 hrs. of age 30 chicks/treatment were sacrificed to determine the enzyme activity of maltase, sucrase, alkaline phosphatase, phytase, a-amylase, trypsin and lipase in samples of duodenal or pancreatic homogenate. Results. The supply of HBF or CHS during the first 48 hrs. of life increased the activity of maltase, sucrase and phytase in the first 3 days of life, with values between 1.2 and up to 4-fold compared to the control (p<0.05). Chickens that fasted for the first 48 hrs. had higher activity of the pancreatic enzymes a-amylase, trypsin, and lipase at 72 hrs. of life (p<0.05). Conclusions. The food supply in the first 48 hrs. after hatching increases the duodenal enzyme activity in the intestinal brush border during the first 3 days of age in broiler chickens

Lípidos sanguíneos en cerdos alimentados con pijiguao (Bactris gasipaes Kunth) y lisina sintética

RESUMENObjetivo. Evaluar el efecto de la harina de pijiguao y lisina sintética sobre los lípidossanguíneos de cerdos en crecimiento y engorde. Materiales y métodos. El estudio serealizó en dos etapas. En la primera etapa se utilizaron 72 cerdos castrados en crecimientode 30 ± 0.5 kg, en un arreglo factorial 2x3: dos niveles de lisina sintética (0 y 2.70 g/kg)y tres niveles de harina de pijiguao (0, 160 y 320 g/kg). En la segunda etapa se utilizaron16 cerdos en engorde de 67.25 ± 1.17 kg, en un arreglo factorial 2x2: dos niveles de lisinasintética (0 y 2.70 g/kg) y dos niveles de pijiguao (0 y 175 g/kg). Se determinaron lasconcentraciones séricas de triacilgliceroles, colesterol total y ácidos grasos. Resultados.Los cerdos en crecimiento que consumieron pijiguao presentaron menores (p&lt;0.001)concentraciones de colesterol que el grupo control (2.27 y 2.23 mmol/l vs 2.56 mmol/l) ytriacilgliceroles (0.34 y 0.28 mmol/l vs 0.42 mmol/l). El ácido oleico incrementó (p&lt;0.01)con el mayor nivel de pijiguao (20.78% a 28.84%), y la lisina aumentó (p&lt;0.05) el ácidolinoleico (27.83% a 31.29%). Los cerdos alimentados con pijiguao y lisina mostraronmenor (p&lt;0.001) ácido palmítico que el grupo con pijiguao sin lisina (0.23 y 0.19% vs0.45 y 0.62%, respectivamente). En la etapa de engorde los triacilgliceroles disminuyeron(p&lt;0.05) en los cerdos alimentados con pijiguao y lisina (0.46 a 0.36 mmol/l). Los cerdosalimentados con pijiguao mostraron menor ácido linoleico y mayor ácido oleico (p&lt;0.001).Conclusiones. Las dietas con pijiguao y lisina sintética no causaron efectos negativossobre los lípidos sanguíneos de cerdos

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The UN’s Sustainable Development Goals (SDGs) are grounded in the global ambition of “leaving no one behind”. Understanding today’s gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990–2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Early feeding to modify digestive enzyme activity in broiler chickens

Objetive. To evaluate the effect on digestive enzyme activity in broiler chickens by providing food in the first 48 hrs. after birth. Materials and methods. After incubating 300 fertile eggs from Hubbard breeding and immediately after hatching, the chicks were randomly assigned to treatments: fasting (from hatching to 48 hrs.); Hydrated Balanced Food (HBF) from birth to 48 hrs.; commercial hydrating supplement (CHS) from birth to 48 hrs. The diets were provided ad libitum. After 48 hrs. a commercial diet was fed. At birth and at 48 and 72 hrs. of age 30 chicks/treatment were sacrificed to determine the enzyme activity of maltase, sucrase, alkaline phosphatase, phytase, a-amylase, trypsin and lipase in samples of duodenal or pancreatic homogenate. Results. The supply of HBF or CHS during the first 48 hrs. of life increased the activity of maltase, sucrase and phytase in the first 3 days of life, with values ââbetween 1.2 and up to 4-fold compared to the control (p<0.05). Chickens that fasted for the first 48 hrs. had higher activity of the pancreatic enzymes a-amylase, trypsin, and lipase at 72 hrs. of life (p<0.05). Conclusions. The food supply in the first 48 hrs. after hatching increases the duodenal enzyme activity in the intestinal brush border during the first 3 days of age in broiler chickens.Objectivo. Evaluar el efecto sobre la actividad de enzimas digestivas en pollos de engorde al suministrar alimento en las primeras 48 h de nacidos. Materiales y métodos. Después de incubar 300 huevos fértiles provenientes de reproductoras Hubbard e inmediatamente después de la eclosión, los pollos fueron asignados al azar a los tratamientos: ayuno (desde la eclosión hasta 48 h); alimento balanceado hidratado (ABH) desde el nacimiento hasta las 48 h; suplemento hidratante comercial (SHC) desde el nacimiento hasta las 48 h. Las dietas fueron suministradas ad libitum. A partir de las 48 h se suministró una dieta comercial. Al nacer y a las 48 y 72 h de nacidos, fueron sacrificados 30 pollos/tratamiento para las determinaciones de las actividades de las enzimas maltasa, sacarasa, fosfatasa alcalina, fitasa, α-amilasa, tripsina y lipasa en muestras de homogenado duodenal o pancreático. Resultados. El suministro de ABH o SHC durante las primeras 48 h de vida aumentó la actividad de maltasa, sacarasa y fitasa en los primeros 3 días de edad, con valores entre 1.2 y hasta 4 veces en comparación con el control (p<0.05). Los pollos en ayuno durante las primeras 48 h presentaron mayor actividad de las enzimas pancreáticas α-amilasa, tripsina y lipasa a las 72 h de vida (p<0.05). Conclusiones. El suministro de alimentos en las primeras 48 h después de la eclosión aumenta la actividad de las enzimas duodenales del borde en cepillo intestinal durante los primeros 3 días de edad en pollos de engorde

Lípidos sanguíneos en cerdos alimentados con pijiguao (Bactris gasipaes Kunth) y lisina sintética

Objetive. Two experiments were designed to evaluate the effect of peach palm meal and synthetic lysine on blood lipids of growing and finishing pigs. Materials and methods. In experiment 1, 72 barrows of 30 ± 0.5 kg were randomly allotted into a 2x3 factorial design: being the main factors levels of synthetic lysine (0 and 2.70 g/kg) and levels of peach palm meal (0, 160 and 320 g/kg). In experiment 2, 16 finishing pigs of 67.25 ± 1.17 kg were used and allotted in a 2x2 factorial design arrangement of treatments: with two levels of synthetic lysine (0 and 2.70 g/kg) and two levels of peach palm meal (0 and 175 g/kg). Serum triglycerides, total cholesterol and fatty acid profile were determined. Results. In experiment 1, growing pigs fed with 160 and 320 g/kg of peach palm showed lower (p<0.001) cholesterol (2.27 and 2.23 mmol/l, respectively) than the control (2.56 mmol/l). The levels of triglycerides were also lower in pigs fed with 160 and 320 g/kg (0.34 and 0.28 mml/l) than control group (0.42 mmol/l). Oleic acid concentration increased (p<0.01) in pigs that received the highest level of peach palm (320 g/kg) with respect to the control group (20.78% to 28.84%) and synthetic lysine increased (p<0.05) linoleic acid (27.83% to 31.29%). Pigs fed peach palm and lysine had lower (p<0.001) palmitic acid concentration than the group fed pijiguao without lysine (0.23% and 0.19% vs 0.45% and 0.62%, respectively). In experiment 2, triglycerides decreased (p<0.05) in pigs that received lysine and peach palm (0.46 to 0.36 mmol/l). Pigs fed with peach palm had lower linoleic acid and higher oleic acid (p<0.001). Conclusions. Diets with peach palm and synthetic lysine do not elicit detrimental effects on blood lipid profile in pigs.Objetivo. Evaluar el efecto de la harina de pijiguao y lisina sintética sobre los lípidos sanguíneos de cerdos en crecimiento y engorde. Materiales y métodos. El estudio se realizó en dos etapas. En la primera etapa se utilizaron 72 cerdos castrados en crecimiento de 30 ± 0.5 kg, en un arreglo factorial 2x3: dos niveles de lisina sintética (0 y 2.70 g/kg) y tres niveles de harina de pijiguao (0, 160 y 320 g/kg). En la segunda etapa se utilizaron 16 cerdos en engorde de 67.25 ± 1.17 kg, en un arreglo factorial 2x2: dos niveles de lisina sintética (0 y 2.70 g/kg) y dos niveles de pijiguao (0 y 175 g/kg). Se determinaron las concentraciones séricas de triacilgliceroles, colesterol total y ácidos grasos. Resultados. Los cerdos en crecimiento que consumieron pijiguao presentaron menores (p<0.001) concentraciones de colesterol que el grupo control (2.27 y 2.23 mmol/l vs 2.56 mmol/l) y triacilgliceroles (0.34 y 0.28 mmol/l vs 0.42 mmol/l). El ácido oleico incrementó (p<0.01) con el mayor nivel de pijiguao (20.78% a 28.84%), y la lisina aumentó (p<0.05) el ácido linoleico (27.83% a 31.29%). Los cerdos alimentados con pijiguao y lisina mostraron menor (p<0.001) ácido palmítico que el grupo con pijiguao sin lisina (0.23 y 0.19% vs 0.45 y 0.62%, respectivamente). En la etapa de engorde los triacilgliceroles disminuyeron (p<0.05) en los cerdos alimentados con pijiguao y lisina (0.46 a 0.36 mmol/l). Los cerdos alimentados con pijiguao mostraron menor ácido linoleico y mayor ácido oleico (p<0.001). Conclusiones. Las dietas con pijiguao y lisina sintética no causaron efectos negativos sobre los lípidos sanguíneos de cerdos

HEMATOLOGÍA, METABOLITOS SANGUÍNEOS Y PESO DE ÓRGANOS DE CERDOS EN CRECIMIENTO ALIMENTADOS CON HARINA DE PIJIGUAO (Bactris gasipaes H.B.K.) Y LISINA

Para evaluar la hematolog&iacute;a, los metabolitos sangu&iacute;neos y el peso de &oacute;rganos de cerdos en crecimiento alimentados con harina de pijiguao (HP) y lisina sint&eacute;tica (LS), se utilizaron 72 cerdos machos castrados, del cruce de las razas Yorkshire x Landrace de 30 &plusmn; 0,5 kg. Los cerdos fueron distribuidos en seis tratamientos en un dise&ntilde;o al azar con arreglo factorial 2x3: dos niveles de LS (0 y 0,27%) y tres de HP (0, 25, y 50%), con cuatro r&eacute;plicas por tratamiento y tres cerdos por unidad experimental. El estudio se condujo durante seis semanas y se tomaron muestras sangu&iacute;neas al inicio, en la tercera y sexta semana. Se evaluaron variables hematol&oacute;gicas: hemoglobina, recuento de eritrocitos y leucocitos, f&oacute;rmula leucocitaria, hematocrito, volumen corpuscular medio (VCM) y concentraci&oacute;n de hemoglobina corpuscular media (CHCM). Los metabolitos evaluados fueron, prote&iacute;nas plasm&aacute;ticas totales, enzimas alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST), &uacute;rea, glucosa y fructosamina. Al final del experimento, se sacrificaron 24 cerdos (cuatro por tratamiento) y se pesaron los pulmones, coraz&oacute;n, est&oacute;mago, p&aacute;ncreas, intestino delgado, intestino grueso, h&iacute;gado, bazo y ri&ntilde;ones. La interacci&oacute;n HPxLS no afect&oacute; ninguna de las variables estudiadas. La LS no afect&oacute; la hematolog&iacute;a, mientras que la HP (25 y 50%) redujo el recuento de eritrocito (P&lt;0,05), el hematocrito (P&lt;0,05) y la hemoglobina (P=0,09), sin variaciones significativas sobre la VCM, CHCM y el recuento de leucocitos con respecto al grupo sin HP. Las prote&iacute;nas totales fueron menores en los cerdos alimentados con HP (P&lt;0,01) y la &uacute;rea disminuy&oacute; por efecto de la LS (P&lt;0,05). La AST fue menor (P=0,01) en los cerdos con LS con respecto al grupo sin LS. Los cerdos que consumieron dietas con 25% HP tendieron a presentar (P=0,10) est&oacute;magos m&aacute;s pesados que el&nbsp; grupo de la dieta basal y el que recibi&oacute; 50% HP (P= 0,06). El bazo result&oacute; menos pesado (P&lt;0,01) en los cerdos alimentados con 25 y 50% HP, que el grupo sin HP. La HP conjuntamente con LS en las dietas de cerdos en crecimiento no ocasionaron efectos negativos sobre la hematolog&iacute;a, los metabolitos sangu&iacute;neos y el peso de los &oacute;rganos. &nbsp; (Palabras clave: Cerdo; Bactris&nbsp; gasipaes; lisina; hematolog&iacute;a; metabolitos; peso; &oacute;rganos) &nbsp; Abstract &nbsp; To evaluate the hematology, blood metabolites, and organ weights in growing pigs fed peach-palm meal (PPM) and synthetic lysine (SL), 72 crossbred (Yorkshire x Landrace) barrows (30&plusmn;0.5 kg) were used. Pigs were allotted into six treatments in a completely randomized design with a 2 x 3 factorial arrangement, with two levels of SL (0 and 0.27%) and three levels of PPM (0, 25 and 50%), with four replications per treatment and three pigs per experimental unit. The study lasted six weeks and blood samples were collected at the onsent of the assay and at third and sixth weeks. The hematological variables evaluated were hemoglobin, erythrocytes and leukocyte count, total leukocyte count, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC). Blood metabolites evaluated were: total plasma proteins, urea, glucose, fructosamine, alanine aminotransferase (ALT), aspartate aminotransferase (AST). At the end of the trial, 24 pigs were slaughtered (four/treatment) and the lungs, heart, stomach, pancreas, small intestine, liver, spleen, and kidneys were weighed. The PPM x SL interaction did not significantly influence the variables studied. The SL did not affect hematology, while PPM (25 and 50%) significantly decreased erythrocyte count (P&lt;0,05), hematocrit (P&lt;0,05) and hemoglobin (P=0.09), without significant variations in MCV, MCHC, and leukocyte count, when compared to pigs that were fed no PPM. Pigs fed PPM had lower total proteins(P&lt;0.01) and the SL reduced urea (P&lt;0.05). The AST was lower (P=0.01) in pigs fed SL than in pigs without SL. Pigs that consumed 25% PPM tended to have (P=0.10) heavier stomachs than those fed basal diet or 50% PPM (P=0.06). Pigs fed 25 and 50% PPM exhibited the lightest spleens (P&lt;0.01), compared to those without PPM. The PPM together with SL in the diet of growing pigs had no detrimental effects on hematological variables, blood metabolites, and organ weights. &nbsp; (Key words: Pigs; Bactris gasipaes; lysine; hematology; metabolites; weight; organ