Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Effect of mineral supplementation on live weight of nelore heifers

Brazilian soils generally suffer from mineral deficiency, so that pasture alone cannot supply the mineral requirements of beef cattle, mainly during the animals’ growth phase, after weaning, when there is a high need for mineral salt supplementation. The objective of this study was to evaluate the effect of two types of mineral supplements on the weight of Nellore heifers, from weaning until 22 months of age. The research project was developed at the APTA Beef Cattle Center of the Institute of Zootechnics. Eighty-four Nellore heifers from the Traditional and Selected herds belonging to the Animal Science Institute, Sertãozinho, SP, were used, with average age of eight months at the beginning of the experiment in May 2016. Half of the heifers were kept in pastures receiving a commercial mineral supplement (TEST), while another 46 heifers were kept in pastures receiving blocks of mineral supplement with molasses from Caltech-Crystalyx (CRY), an English company. Both supplements were formulated for the dry season or wet season. The mineral supplement intake of each group was recorded weekly, by weighing the total product offered and left over. The animals were weighed every 28 days and afterwards the animals switched from one pasture to the other. The intake of the supplement varied greatly during the experiment. The animals that received supplementation in the form of CRY blocks presented average consumption levels of 189; 214 and 225 g animal-1 day-1 , while the consumption levels of the TEST group were 100; 67 and 87 g animal-1, day-1, from June to November 2016; from November 2016 to April 2017 and from May to August 2017, respectively. The CRY group had significantly higher weights (P0.05) between the supplements. The weights found for CRY heifers were 249.0 ± 4.61; 264.9 ± 5.04; 298.5 ± 5.25; 358.54 ± 6.03 kg animal-1, and for TEST heifers were 233.84 ± 4.65; 251.56 ± 5.07; 282.42 ± 5.28 and 339.32 ± 5.98 kg animal-1, for the ages of 14, 15, 17 and 20 months, respectively. In conclusion, the CRY group obtained better results regarding weight gain and maintenance than the animals in the TEST group

Effect of mineral supplementation on the performance of the nellore breed

Brazil is one of the biggest beef producers in the world, and several factors of the productive chain are important, among them animal nutrition because of the impact of its costs. The objective of this study was to evaluate primiparous Nellore cows’ weight loss due to delivery and body condition score (BCS) of three groups with different initial weight, receiving two different mineral supplementations. The research project was developed at the APTA Beef Cattle Center of the Institute of Zootechnics during 180 days, beginning in the dry season and ending in the wet season. The animals were divided into two treatments, one receiving mineral blocks with addition of molasses from Caltech-Crystalyx (CRY), an English company, and the other, the control, receiving mineral supplement mix (CONTROL). Both treatments had additional protein included during the dry season. Initially, the pregnant cows were classified into three groups, with initial weight between 350 and 400 kg (G1), 401 and 500 kg (G2), and 501 and 590 kg (G3). Seventeen 17 primiparous cows of the Nellore breed were in the CRY group and 19 primiparous cows in CONTROL group. During the experiment, the  were weighed twice, 30 days before and 30 days after parturition, to calculate the lost weight. The BSC was assigned at parturition and 150 days after parturition (1 = extremely slim, 9 = extremely fat). A 3x2 factorial The experimental design was used. The SAS program was used through the Mixed command, considering as fixed effects the supplement, group of cows by weight and the interaction between them. The animal was considered a random effect. The supplement intake was controlled weekly and no statistical analysis was performed. The average of CRY supplement intake varied from 0.077 to 0.821 kg/animal/day. The CONTROL supplement intake varied from 0.055 to 0.370 kg/animal/day. The loss of weight was affected by the supplement (P = 0.0384), group of cow (P = 0.009) and interaction between supplement and group(P = 0.0221). No difference was found for delivery weigh loss only for the group of lightest cows (67 ± 1.23 kg for G1 CRY x 67 ± 1.09 kg for G1 CONTROL). The heaviest cows lost more weight in the CONTROL (G3 = 113 ± 1.83 kg) compared to the CRY group (G3 = 78 ± 1.64 kg). Regarding parturition, no effect was found for BSC between CRY and CONTROL (P = 0.3120) or interaction between treatments and group (P = 0.0722), but there was an effect of the group of cows (P = 0.0272). The BSC was 4.9 ± 0.25 for G1, 5.9 ± 0.21 for G2 and 5.9 ± 0.23 for G3. A significant effect was also observed of supplementation for BSC at 150 days after delivery (P = 0.0198) and group of cows (P = 0.0021), but no effect was observed for the interaction between treatment and group (P = 0.3750). The results were 5.52 ± 0.18 and 4.90 ± 0.16 for CRY and CONTROL and 4.6 ± 0.25; 5.0 ± 0.19 and 6.0 ± 0.23 for G1, G2 and G3, respectively. The CRY supplementation minimized the loss of weight because of parturition and improved the BSC, resulting in the best performance for primiparous Nellore cows

Efficacy of educational intervention to improve awareness of the importance of iodine, use of iodized salt, and dietary iodine intake in northeastern Italian schoolchildren

OBJECTIVE: An educational program was conducted among school-aged children to improve their knowledge about iodine prophylaxis, their iodine status, and their dietary habits. METHODS: At the baseline (T0) and after 6\u2009mo (T1), participants (970 at T0 and 949 at T1) answered questionnaires testing their knowledge about iodine prophylaxis and their eating habits. Urine samples were collected from a randomly selected subgroup of participants (313 at T0 and 312 at T1). RESULTS: From T0 to T1 there was a significant improvement in respondents' knowledge about iodine prophylaxis (from 44% to 70%), iodized salt consumption (from 78% to 84%), and median urine iodine concentrations (from 70\u2009\ub5g/L to 91\u2009\ub5g/L). Milk and iodized salt intakes were associated with a better iodine status per se, and more so when used simultaneously. Girls drank milk less often than boys did (daily in 52% and 59% of cases, respectively). Children of foreign origin ate sodium-rich food more often than Italians did. CONCLUSION: Educational intervention improved the children's knowledge about iodine prophylaxis and use of iodized salt. Consuming salt in addition to milk improves iodine status. Children of foreign origin have different eating habits

Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer

A hallmark of prostate cancer progression is dysregulation of lipid metabolism via overexpression of fatty acid synthase (FASN), a key enzyme in de novo fatty acid synthesis. Metastatic castration-resistant prostate cancer (mCRPC) develops resistance to inhibitors of androgen receptor (AR) signaling through a variety of mechanisms, including the emergence of the constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective FASN inhibition antagonizes CRPC growth through metabolic reprogramming and results in reduced protein expression and transcriptional activity of both full-length AR (AR-FL) and AR-V7. Activation of the reticulum endoplasmic stress response resulting in reduced protein synthesis was involved in IPI-9119-mediated inhibition of the AR pathway. In vivo, IPI-9119 reduced growth of AR-V7-driven CRPC xenografts and human mCRPC-derived organoids and enhanced the efficacy of enzalutamide in CRPC cells. In human mCRPC, both FASN and AR-FL were detected in 87% of metastases. AR-V7 was found in 39% of bone metastases and consistently coexpressed with FASN. In patients treated with enzalutamide and/or abiraterone FASN/AR-V7 double-positive metastases were found in 77% of cases. These findings provide a compelling rationale for the use of FASN inhibitors in mCRPCs, including those overexpressing AR-V71162631640sem informaçãosem informaçãoThis work was supported by Department of Defense (DoD) IMPACT Grant PC160357 (to M.L., S.M.D., and S.R.P.), DoD synergistic Grant W81XWH1410405 (to M.L. and U.M.), NIH Grants R01-CA131945 and P50 CA90381, and the Prostate Cancer Foundation (PCF) (M.L.). G.Z. is a recipient of the DoD Idea Development Award for New Investigators (PC150263) and a Claudia Adams Barr Award in Innovative Cancer Research from the Dana-Farber Cancer Institute. The rapid autopsy material is the result of work supported by resources by the DoD (Award W81XWH-14-2-0183), the Pacific Northwest Prostate Cancer Specialized Programs of Research Excellence (SPORE) (Grant P50CA97186), and the Institute for Prostate Cancer Research. L. M.B. is supported by a Future Fellowship from the Australian Research Council (Fellowship FT130101004) and grant support from the Movember Foundation/ PCF of Australi

Adventitious rooting and xylogenesis are enhanced by methyl jasmonate in tobacco thin cell layers

Adventitious roots (ARs) are induced by auxins. Jasmonic acid (JA) and methyl jasmonate (MeJA) are also plant growth regulators with many effects on development, but their role on ARs needs investigation. To this aim, we analyzed AR formation in tobacco thin cell layers (TCLs) cultured with 0.01–10 μM MeJA, either under root-inductive conditions, i.e., on medium containing 10 μM indole-3-butyric acid (IBA) and 0.1 μM kinetin, or without hormones. The explants were excised from the cultivars Samsun, Xanthii and Petite Havana, and from genotypes with altered AR-forming ability in response to auxin, namely the non-rooting rac mutant and the over-rooting Agrobacterium rhizogenes rolB transgenic line. Results show that NtRNR1 (G1/S) and Ntcyc29 (G2/M) gene activity, cell proliferation and meristemoid formation were stimulated in hormone-cultured TCLs by submicromolar MeJA concentrations. The meristemoids developed either into ARs and xylogenic nodules, or into xylogenic nodules only (rac TCLs). MeJA-induced meristemoid over-production characterized rolB TCLs. No rooting or xylogenesis occurred under hormone-free conditions, independently of MeJA and genotype. Endogenous JA progressively (days 1–4) increased in hormone-cultured TCLs in the absence of MeJA. JA levels were enhanced by 0.1 μM MeJA, on both days 1 and 4. Endogenous IBA was the only auxin detected, both in the free form and as IBA-glucose. Free IBA increased up to day 2, remaining constant thereafter (day 4). Its level was enhanced by 0.1 μM MeJA only on day 1, while IBA conjugation was not affected by MeJA. Taken together, these results show that an interplay between jasmonates and auxins regulates AR formation and xylogenesis in tobacco TCLs