Emergent hydrodynamics in a strongly interacting dipolar spin ensemble.

Conventional wisdom holds that macroscopic classical phenomena naturally emerge from microscopic quantum laws1-7. However, despite this mantra, building direct connections between these two descriptions has remained an enduring scientific challenge. In particular, it is difficult to quantitatively predict the emergent 'classical' properties of a system (for example, diffusivity, viscosity and compressibility) from a generic microscopic quantum Hamiltonian7-14. Here we introduce a hybrid solid-state spin platform, where the underlying disordered, dipolar quantum Hamiltonian gives rise to the emergence of unconventional spin diffusion at nanometre length scales. In particular, the combination of positional disorder and on-site random fields leads to diffusive dynamics that are Fickian yet non-Gaussian15-20. Finally, by tuning the underlying parameters within the spin Hamiltonian via a combination of static and driven fields, we demonstrate direct control over the emergent spin diffusion coefficient. Our work enables the investigation of hydrodynamics in many-body quantum spin systems.

Energy requirement for primiparous Holstein × Gyr crossbred dairy cows.

Our objective was to estimate the requirements of metabolizable energy (ME) and net energy for the maintenance (NEm) of lactating and dry cows, the efficiency of ME utilization for milk production (kl) and tissue gain (kg), and the use of body energy mobilization for milk production (kt) throughout the lactation of primiparous crossbred Holstein × Gyr cows, using open-circuit respiration chambers. Twenty-nine primiparous Holstein × Gyr crossbred cows with an initial BW averaging 563 ± 40.1 kg and 2.5 ± 0.09 years old were used throughout lactation and dry periods. The cows were kept non-pregnant throughout the study to eliminate possible confounding factors. Apparent digestibility assays, followed by calorimeter measurements, were performed 6 times throughout the lactation period. In the dry-off period, the cows were also evaluated but fed with restricted intake (DMI = 1.1% BW/d) to achieve heat production close to maintenance. After 21 d of diet adaptation, an apparent digestibility assay followed by calorimeter measurements was performed. Parameter estimates for lactation period were obtained by mixed models including lactation stage as repeated measures. For restricted feeding at dry-off and fasting period assays, the requirements were estimated by exponential regression. For whole lactation, the values of MEm and NEm were 0.588 and 0.395 MJ/BW0.75, respectively. The efficiencies klkgkt were 0.672, 0.771, and 0.814, respectively. However, MEm and NEm were higher in early and mid-lactation than late, while kl was higher in early than other lactation stages. Dry and non-pregnant cows had MEm of 0.434 MJ/BW0.75 and NEm of 0.351 MJ/BW0.75 for maintenance level, and MEm of 0.396 MJ/BW0.75 and NEm of 0.345 MJ/BW0.75 for fasting metabolism level and efficiency of ME utilization for maintenance was 0.80. Our findings confirmed that F1 crossbred Holstein × Gyr dairy cows have differences in energy requirement and efficiency throughout the lactation stages, suggesting the use of different values in each stage. The estimated values of energy requirement for maintenance and efficiencies for primiparous lactating crossbred Holstein × Gyr were similar to those reported in the literature in specific studies and requirements systems.

Effects of bulk tank milk, waste milk, and pasteurized waste milk on the nutrient utilization, gastrointestinal tract development, and antimicrobial resistance to Escherichia coli in pre-weaned dairy calves.

This study aimed to assess the impact of bulk tank milk (BTM), waste milk (WM), and pasteurized waste milk (PWM) on nutrient digestibility, ruminal and cecal fermentation, gastrointestinal tract (GIT) development, and antimicrobial resistance of fecal Escherichia coli from dairy calves at 2 periods (30 and 60 d of age). Calves were grouped according to body weight, serum protein levels, and breed composition. Three treatments were included: BTM (n = 21), WM from cows under antibiotic treatment (n = 21), and PWM (waste milk submitted to high-temperature, short-time pasteurization; n = 21). A total of 63 calves were used, of which: 18 animals (n = 6 per treatment) evaluated in the period of 4 - 30 d and 45 (n = 15 per treatment) from 4 - 60 d. During the experimental period, a daily intake of 6 L of milk was divided into 2 equal meals, with ad libitum access to water and starter. Milk and feed intakes were recorded daily. Apparent total-tract digestibility and nitrogen balance were conducted from 25 to 29 d of age (n = 6) and from 53 to 57 d of age (n = 15). Animals were euthanized at 30 ± 1 and 60 ± 1 d of age for the assessment of ruminal and cecal fermentation and GIT development. Antimicrobial susceptibility testing was conducted at 1, 30, and 60 d of age (n = 15/treatment). Statistical analysis utilized a linear mixed-effects model for continuous outcomes and generalized linear models for single measurements (R software). Treatments WM and PWM had lower rumen pH, higher ruminal acetate concentration, larger reticulorumen and liver, and a higher prevalence of fecal-resistant E. coli compared with BTM at both 30 and 60 d. Up to 60 d, both BTM and WM treatments exhibited higher digestibility of ether extract and gross energy compared with the PWM, whereas WM and PWM treatments showed increased nitrogen intake and retention compared with the BTM. These findings suggest that pasteurization of waste milk negatively affects nutrient digestibility and calf performance, while also impacting rumen development. Additionally, the use of milk containing antibiotic residue leads to the selection of resistant E. coli in the GIT over time.

Protein requirements for pregnant dairy cows.

We aimed to estimate the protein requirements of pregnant Holstein × Gyr cows. A total of 61 Holstein × Gyr (HG) cows were used, with an average initial body weight (BW) of 480 ± 10.1 kg and age 5 ± 0.5 yr. Cows were divided into 3 groups: pregnant (n = 43), nonpregnant (n = 12), and baseline (n = 6). Baseline animals were slaughtered before starting the experiment to estimate the initial body composition of the remaining animals. Pregnant and nonpregnant cows received 2 diets: maintenance and ad libitum. Pregnant cows were slaughtered at 139, 199, 241, and 268 gestation days (GD). First, we used data only from nonpregnant cows to determine the requirements for maintenance and growth in adult cows. The requirements of metabolizable protein for maintenance (MPm; grams of empty metabolic BW [EBW0.75] per day) were estimated using a linear regression between the metabolizable protein intake (MPI, g/d) and average daily gain (g/d), and the MPm was defined as the intercept divided by the average metabolic BW. Net protein requirements for gain (NPg; g/d) were estimated by the first derivative of the allometric equation between final crude protein in the body (kg) and the final empty BW (EBW; kg). The efficiency of use of metabolizable protein for gain (k) was calculated from the regression between the retained protein (g EBW0.75/d) and the MPI (g EBW0.75/d), and k was the slope of this regression. The MPI was estimated by combining microbial protein synthesis (purine derivatives) with the digestible rumen undegradable protein [(total protein intake - rumen-degradable protein) × intestinal digestibility]. Second, an exponential model was used to fit the protein accumulation in the gestational components in the function of GD. The first derivative of that model was considered the net requirement for gestation (NPgest). The efficiency of protein utilization for gestation (kgest) was calculated by the iterative method using the equation Δ = MPI - (MPm + NPg/kg + NPgest/kgest), where kg is efficiency of protein utilization for gain. The iteration was performed aiming at a zero deviation between observed MPI and metabolizable protein (MP) estimated by the requirements determined herein. We obtained a value of 3.88 g EBW0.75/d for MPm. The estimation of NPg can be calculated according to the following equation: NPg = 0.716 × (EBWopen-0.308) × EBGc, where EBWopen is the EBW (kg) for nonpregnant animals and EBGc is the empty body gain (kg/d) corrected for the gestational component. The k was determined as 0.347. The NPgest requirements were determined as NPgest (g/d) = 0.0008722 × exp(0.01784 × GD) × (calf weight/35). The kgest was 0.625. It is important to highlight that different methods of MP estimates should not be mixed and that the proposed method requires the estimation of microbial protein (estimated via urinary estimates), which might limit practical application. In conclusion, new studies should be conducted to validate our results and the methodology adopted to determine protein requirements for pregnancy in dairy cows. Due to the pattern of protein accumulation in the gestational components, we suggest an exponential model to describe protein requirements for pregnancy for dairy cows.

Increased H2O2 levels and p53 stabilization lead to mitochondrial dysfunction in XPC-deficient cells.

XPC deficiency is associated with mitochondrial dysfunction, increased mitochondrial H2O2 production and sensitivity to the Complex III inhibitor antimycin A (AA), through a yet unclear mechanism. We found an imbalanced expression of several proteins that participate in important mitochondrial function and increased expression and phosphorylation of the tumor suppressor p53 in Xeroderma pigmentosum complementation group C (XP-C) (XPC-null) cells compared with an isogenic line corrected in locus with wild-type XPC (XPC-wt). Interestingly, inhibition of p53 nuclear import reversed the overexpression of mitochondrial proteins, whereas AA treatment increased p53 expression more strongly in the XP-C cells. However, inhibition of p53 substantially increased XP-C cellular sensitivity to AA treatment, suggesting that p53 is a critical factor mediating the cellular response to mitochondrial stress. On the other hand, treatment with the antioxidant N-acetylcysteine increased glutathione concentration and decreased basal H2O2 production, p53 levels and sensitivity to AA treatment in the XPC-null back to the levels found in XPC-wt cells. Thus, the results suggest a critical role for mitochondrially generated H2O2 in the regulation of p53 expression, which in turn modulates XP-C sensitivity to agents that cause mitochondrial stress.

Clinical influence of calcium hydroxide and N-acetylcysteine on the levels of resolvins E1 and D2 in apical periodontitis.

AIM: To investigate the presence of resolvins E1 (RvE1) and D2 (RvD2) in teeth with primary endodontic infections and apical periodontitis, and to assess the influence of calcium hydroxide medication [Ca(OH)2 ], in association with 2% chlorhexidine gel (2% CHX gel), and N-acetylcysteine (NAC) on the levels of RvE1 and RvD2 in periapical tissues. METHODOLOGY: Thirty-six single-rooted teeth with primary endodontic infections and apical periodontitis were selected and randomly divided into three groups according to the medication: [Ca(OH)2 ] + saline solution (SSL) [Ca(OH)2  + SSL group] (n = 12), Ca(OH)2  + 2% chlorhexidine gel [Ca(OH)2  + 2% CHX gel group] (n = 12) and NAC [NAC group] (n = 12). Samples were collected from the periapical interstitial fluid at two different sampling times: before (S1) and after 14 days of intracanal medications (S2). Resolvins were measured using the enzyme-linked immunosorbent assay. Data were analysed using paired t-test, Wilcoxon test and Kruskal-Wallis test, followed by Dunn's post hoc test; all statistical tests were performed at a significance level of 5%. RESULTS: RvE1 and RvD2 were detected in 100% of the samples (36/36) at S1 and S2. Ca(OH)2 medication did not increase the levels of RvE1 or RvD2 (both P > 0.05); however, NAC significantly increased the levels of RvE1 and RvD2 after 14 days of treatment (P < 0.05). CONCLUSIONS: RvE1 and RvD2 were detected in periapical tissues from teeth with root canal infections. Moreover, calcium hydroxide medication did not increase the levels of resolvins in apical periodontitis. In contrast, the use of NAC intracanal medication significantly increased the levels of RvE1 and RvD2 after 14 days of treatment.

Acute lower gastrointestinal bleeding: are STRATE and BLEED scores valid in clinical practice?

AIM: Acute lower gastrointestinal bleeding (ALGIB) is a common gastroenterological emergency. Despite this, outcomes are difficult to predict. Only STRATE and BLEED scores are readily available. The aim of this study was to identify risk factors for severe ALGIB and access the validity of available scores. METHODS: Emergency consecutive admissions for ALGIB in the last 7 years were retrospectively reviewed. Severe ALGIB was defined as transfusion of ≥ 2 units of blood and/or a haematocrit decrease of ≥ 20% within the first 24 h and/or recurrent bleeding after 24 h of stability. STRATE and BLEED scores were calculated and concordance between score and respective severity outcome was accessed. RESULTS: A total of 132 patients were identified. Bleeding presented as haematochezia in 94.7% and was severe in 36.4% of cases. ALGIB was significantly more severe in patients with lower systolic (P = 0.02) and diastolic blood pressures on admission (P < 0.01), lower admission haemoglobin (P < 0.01), diverticular bleeding (P < 0.01), angioectasias (P = 0.02) and radiation colitis (P < 0.02). Severe ALGIB was associated with admission intermediate care units (P < 0.01), increased length of stay (P < 0.01) and volume of blood transfused (P < 0.01). We identified no significant association between outcomes with either the STRATE (P = 0.72) or BLEED scores (P = 0.05). CONCLUSIONS: Severe ALGIB is associated with greater length of stay, volume of blood transfusions and admission to greater level of care units. In our cohort, STRATE and BLEED scores were poor predictors of outcome.

Imaging the Local Charge Environment of Nitrogen-Vacancy Centers in Diamond.

Characterizing the local internal environment surrounding solid-state spin defects is crucial to harnessing them as nanoscale sensors of external fields. This is especially germane to the case of defect ensembles which can exhibit a complex interplay between interactions, internal fields, and lattice strain. Working with the nitrogen-vacancy (NV) center in diamond, we demonstrate that local electric fields dominate the magnetic resonance behavior of NV ensembles at a low magnetic field. We introduce a simple microscopic model that quantitatively captures the observed spectra for samples with NV concentrations spanning more than two orders of magnitude. Motivated by this understanding, we propose and implement a novel method for the nanoscale localization of individual charges within the diamond lattice; our approach relies upon the fact that the charge induces a NV dark state which depends on the electric field orientation.

Short communication: Tick-borne disease is associated with changes in feeding behavior in automatically fed weaned dairy calves.

Tick-borne disease is a hemolytic disease complex that causes extensive losses to the dairy industry in tropical regions. Its timely diagnosis is challenging and labor intensive. Our objective was to investigate whether tick-borne disease was associated with changes in ingestive behavior of weaned dairy calves. Weaned calves (n = 35) enrolled at 108 ± 8 d of age were group housed (n = 12, 12, and 11/group) for 4 wk in the experimental pen, which had 12 electronic feed bins and 2 electronic water bins. Data were automatically collected at each feed or water bin visit via radio frequency identification ear tags. Water and total mixed ration were provided ad libitum. Calves were examined weekly for tick-borne disease detection. A disease bout was confirmed if packed cell volume was ≤25% at any exam. Diseased calves received antimicrobial and antipyretic treatment. Data were summarized by day within bin type (feed or water) as intake (kg/d; as-fed basis), frequency of visits (visits/d), and total duration of visits (min/d). Day of detection was set as d 0; a 9-d behavioral screening period for evaluation of behavioral changes was set according to d 0 (d -4 to +4). A within-calf mean was calculated for the healthy period (HP; mean of all days between 2 consecutive negative exams) for each response variable. Data were analyzed as within-calf differences between HP and each day of the behavioral screening period. Tick-borne disease was detected in 12 calves; thus, only data referent to these animals were included in the analyses. Compared with HP, daily feed intake was reduced on d -1, 0, and +1, and daily frequency and total duration of feed bin visits were reduced from d -3 to d +4. Daily feed intake was reduced by 35% on d -1 (3.5 ± 0.4 vs. 5.4 ± 0.5 kg/d for HP), and daily frequency and duration of visits were reduced by 27% (56.3 ± 7.8 vs. 76.7 ± 8.1 visits/d for HP) and 24% (27.0 ± 3.8 vs. 35.4 ± 3.9 min/d for HP) on d -3, respectively. Daily water intake on d 0 (9.1 ± 1.4 kg/d) was lower than at HP (12.9 ± 1.6 kg/d), but other drinking behaviors were not different from healthy means during the screening period. Feeding behavior, but not drinking behavior, was different from HP means before detection at weekly exams. Therefore, feeding behavior could be further explored for the development of algorithms for tick-borne disease detection.

Effects of methionine plus cysteine inclusion on performance and body composition of liquid-fed crossbred calves fed a commercial milk replacer and no starter feed.

This experiment aimed to evaluate the effects of supplying 4 different inclusion levels of Met + Cys to crossbred liquid-fed calves on animal performance and body composition. Thirty-six Holstein-Gyr male calves were separated into 2 age groups: 16 calves, slaughtered at an age of 30 d, representing the physiological phase from 8 to 30 d, and 20 calves, slaughtered at an age of 60 d, representing the physiological phase from 30 to 60 d. At 8 d of age, the animals were randomly distributed among the experimental treatments: 4 Met + Cys inclusion levels (Met + Cys: 8.0, 8.7, 9.4, and 10.2 g/d), provided by an AA supplement added to 1.0 kg (as fed) of commercial milk replacer containing soy protein concentrate and wheat protein isolate reconstituted at 13.8% (dry matter basis). The diet was supplied without allowing leftovers and no starter feed was provided. The experimental diets were supplied without allowing orts, so that the dry matter, crude protein, and ether extract intakes were the same for all animals, independent of Met + Cys level. Total weight gain, average daily gain, gain composition, and body composition were evaluated for both age groups separately. Digestibility of organic matter, crude protein, and ether extract was lower for 8 to 30 d than for 30 to 60 d. The effect of Met + Cys levels on the digestibility of nutrients was not observed; there also was no significant interaction between physiological phase and Met + Cys levels. For the 8 to 30 d group, no responses in performance were observed according to the different Met + Cys levels, which indicates that 8.0 g/d of Met + Cys met the requirements for this physiological phase. The 30 to 60 d group responded positively to higher Met + Cys inclusion in the diet. In conclusion, an optimal Met + Cys dietary level to ensure best performance and protein gain ranges from 8.41 to 9.81 g/d.

Phenotypically divergent classification of preweaned heifer calves for feed efficiency indexes and their correlations with heat production and thermography.

The aims of this study were (1) to assess if there is phenotypical divergence for feed efficiency (FE) during the preweaning phase; (2) if FE is correlated with heat production (HP) measured by the face mask method or (3) by surface skin temperature via thermography, and (4) whether these methods are applicable to preweaned calves. Holstein × Gyr heifer calves (n = 36, birth body weight = 32.4 ± 6.6 kg) were enrolled and on trial between 4 and 12 wk of age and were classified into 2 residual feed intake (RFI) and residual body weight gain (RG) groups: high efficiency (HE; RFI, n = 10; and RG, n = 9) and low efficiency (LE; RFI, n = 10; and RG, n = 8). Calves were fed milk (6 L/d) and solid feed (95% starter and 5% chopped Tifton 85 hay, as fed). Growth was monitored weekly and feed intake (milk and solid feed) daily, during the whole period. Gas exchanges (O2 consumption and production of CO2 and CH4) were obtained using a face mask at 45 ± 5 d of age and HP was estimated. Maximum temperatures were measured at 7 sites with an infrared camera at 62 ± 7 d of age. There was divergence in RFI and RG. Respectively, HE and LE calves had RFI of -0.14 and 0.13 kg/d, and RG of 0.05 and -0.07 kg/d. Dry matter intake was 15% lower in HE-RFI compared with LE-RFI, but no differences were observed in average daily weight gain. Within the RG test, no differences were observed in dry matter intake or average daily gain. The HE-RFI calves consumed less O2 (L/d) and produced less CO2 (L/d). Heart rate and HP were lower for HE-RFI calves compared with LE-RFI. Residual feed intake was correlated with HP (r = 0.48), O2 consumption (r = 0.48), CO2 production (r = 0.48), and heart rate (r = 0.40). No differences were observed in HP and gas exchanges between RG groups. Methane production was null in both groups. Eye temperature measured by thermography was 0.5°C greater in HE-RG than LE-RG calves. Differences in skin temperature between HE and LE calves were not observed at the other sites. These results support the hypothesis that calves are divergent for RFI, RG, and FE during preweaning and divergence tests are applicable during this phase. The face mask method described here is a useful tool for estimating differences in HP among phenotypically divergent RFI calves. Eye temperature measured by infrared thermography may have potential to screen phenotypically divergent RG calves.

Performance and methane emissions in dairy cows fed oregano and green tea extracts as feed additives.

Plant extracts have been proposed as substitutes for chemical feed additives due to their potential as rumen fermentation modifiers and because of their antimicrobial and antioxidant activities, possibly reducing methane emissions. This study aimed to evaluate the use of oregano (OR), green tea extracts (GT), and their association as feed additives on the performance and methane emissions from dairy between 28 and 87 d of lactation. Thirty-two lactating dairy cows, blocked into 2 genetic groups: 16 Holstein cows and 16 crossbred Holstein-Gir, with 522.6 ± 58.3 kg of body weight, 57.2 ± 20.9 d in lactation, producing 27.5 ± 5.0 kg/cow of milk and with 3.1 ± 1.8 lactations were evaluated (means ± standard error of the means). Cows were allocated into 4 treatments: control (CON), without plant extracts in the diet; oregano extract (OR), with the addition of 0.056% of oregano extract in the dry matter (DM) of the diet; green tea (GT), with the addition of 0.028% of green tea extract in the DM of the diet; and mixture, with the addition of 0.056% oregano extract and 0.028% green tea extract in the DM of the diet. The forage-to-concentrate ratio was 60:40. Forage was composed of corn silage (94%) and Tifton hay (6%); concentrate was based on ground corn and soybean meal. Plant extracts were supplied as powder, which was previously added and homogenized into 1 kg of concentrate in natural matter, top-dressed onto the total mixed diet. No treatment by day interaction was observed for any of the evaluated variables, but some block by treatment interactions were significant. In Holstein cows, the mixture treatment decreased gross energy and tended to decrease the total-tract apparent digestibility coefficient for crude protein and total digestible nutrients when compared with OR. During the gas measurement period, GT and OR increased the digestible fraction of the ingested DM and decreased CH4 expressed in grams per kilogram of digestible DMI compared with CON. The use of extracts did not change rumen pH, total volatile fatty acid concentration, milk yield, or most milk traits. Compared with CON, oregano addition decreased fat concentration in milk. The use of plant extracts altered some milk fatty acids but did not change milk fatty acids grouped according to chain length (short or long), saturation (unsaturated or saturated), total conjugated linoleic acids, and n-3 and n-6 contents. Green tea and oregano fed separately reduced gas emission in cows during the first third of lactation and have potential to be used as feed additives for dairy cows.

The effects of increasing amounts of milk replacer powder added to whole milk on mammary gland measurements using ultrasound in dairy heifers.

The aim of this study was to determine the effect of increasing total solids (TS) in the liquid diet during the preweaning phase on mammary gland development in dairy heifers. The increase in TS was obtained with the addition of milk replacer powder to whole milk. Crossbreed Holstein-Gyr heifers (n = 60) were distributed in 4 treatments with different TS concentrations: 13.5% (n = 15), 16.1% (n = 15), 18.2% (n = 15), and 20.4% (n = 15). The liquid diets were provided from 5 to 55 d of age. From 56 to 59 d of age, the total amount of liquid feed was reduced by half. Heifers were weaned at 60 d and monitored until 90 d of age. Ultrasound mammary gland evaluations were performed weekly between 5 to 11 wk of age, using a B-mode ultrasound equipped with microconvex transducer at a frequency of 6 MHz. In those same weeks, the manual palpation of mammary parenchyma (PAR) was performed. Increased TS concentration of liquid diet during the preweaning period increased body weight of heifers, but did not alter PAR growth and the deposition of adipose tissue in the mammary gland evaluated by ultrasonography. The oval-shaped structure of PAR was altered after 2 mo of age. In the evaluated period, PAR growth was isometric with respect to the body growth rate. Palpation scoring of PAR had a strong correlation with the ultrasound evaluation of the PAR.

Adsorption of anti-inflammatory nimesulide by graphene materials: a combined theoretical and experimental study.

Interactions of anti-inflammatory nimesulide (NM) with different graphene material species were explored employing both ab initio calculations, based on Density Functional Theory (DFT), and a batch adsorption process. The adsorption of NM onto graphene, with and without a vacancy, reduced graphene oxide (rGO) and functionalized graphene nanoribbons was simulated, providing a good understanding of the adsorption process of the NM molecule onto graphene material surfaces. The theoretical results indicate a physisorption interaction between NM and all of the evaluated adsorbents. Based on batch adsorption experiments, it was found that rGO, obtained via a modified Hummers method, is a good nanoadsorbent for the removal of the anti-inflammatory NM from aqueous solutions. The general-order kinetic equation displays the best fit to the experimental data compared with pseudo-first order and pseudo-second order kinetics. The equilibrium data fitted well into the Liu isotherm equation, and the maximum sorption capacity for the adsorption of NM by rGO was 82.4 mg g-1 at 25 °C. Our results of the first principle calculations and the batch adsorption experiments point out that graphene materials are promising nanomaterials for extracting NM from aqueous solutions.

Position Paper from the Portuguese Association of Hospital Pharmacists for biosimilar therapeutic antibodies.

WHAT IS KNOWN AND OBJECTIVE: Biopharmaceuticals are an important class of drugs for the treatment of autoimmune/inflammatory and oncologic diseases. With patent expiries, biotechnological manufacturers can now develop biosimilar drugs. Due to timeliness of introducing new and more complex biosimilars, the Portuguese Association of Hospital Pharmacists gathered to develop a common positioning on the use of biosimilar monoclonal antibodies. MAIN ISSUES: The European pathway to biosimilar approval was developed to improve affordability and access to biological therapies, but it remains a work in progress because unresolved issues remain. Due to the present reality of biosimilar monoclonal antibodies, hospital pharmacists must play an important role in ensuring the safe, effective and cost-effective use of biosimilars in health systems; and educating healthcare administrators, providers, legislators, policymakers, payors and patients about these products. WHAT IS NEW AND CONCLUSION: The conclusions presented in this work focused on the proposal for optimal biosimilar prescription criteria, the preparation of original biologics and biosimilars in the pharmacy, the management and selection of suppliers, extrapolation issues, the specific role of pharmacovigilance and risk management for the optimal use of biosimilar monoclonal antibodies.

Energy and protein requirements of crossbred (Holstein × Gyr) growing bulls.

The objective of this study was to estimate the energy and protein requirements of crossbred (Holstein × Gyr) growing bulls. Twenty-four 10-mo-old bulls [initial body weight (BW) = 184 ± 23.4 kg] were used in a comparative slaughter trial. Six bulls were slaughtered at the beginning of the experiment as the reference group, to estimate initial empty body weight (EBW) and energy and protein contents of the remaining animals. The remaining bulls were assigned to a completely randomized design with 3 levels of dry matter intake and 6 replicates. The levels of dry matter intake were 1.2% of BW, 1.8% of BW, and ad libitum to target orts equal to 5% of the total amount that was fed. The remaining bulls were slaughtered at the end of the experiment. The bulls were fed a diet consisting of 59.6% corn silage and 40.4% concentrate on a dry matter basis. The equation that determined the relationship between EBW and BW was EBW = (0.861 ± 0.0031) × BW. The relationship between empty body gain (EBG) and average daily gain (ADG) was demonstrated by the following equation: EBG = (0.934 ± 0.0111) × ADG. Net energy for maintenance (NEM) was 74.8 ± 2.89 kcal/kg of EBW0.75 per day, and metabolizable energy for maintenance (MEM) was 120.8 kcal/kg of EBW0.75 per day. The detected efficiency of use of metabolizable energy for maintenance (km) was 61.9%. The equation used to estimate net energy for gain (NEG) was as follows: NEG = (0.049 ± 0.0011) × EBW0.75 × EBG0.729 ± 0.0532. The efficiency of use of metabolizable energy for gain (kg) was 35.7%. The metabolizable protein for maintenance (MPM) was 3.05 g/kg of BW0.75. The equation used to estimate net protein requirements for gain (NPG) = (87.138 ± 65.1378 × EBG) + [(40.436 ± 21.3640) × NEG]. The efficiency of use of metabolizable protein for gain (k) was 35.7%. We concluded that the estimates of energy and protein requirements presented herein are more appropriate than the National Research Council dairy cattle model and the Brazilian BR-CORTE system to balance the diets of crossbred (Holstein × Gyr) growing bulls.

Determination of energy and protein requirements for crossbred Holstein × Gyr preweaned dairy calves.

The objective was to quantify the energy and protein nutritional requirements of Holstein × Gyr crossbred preweaned dairy calves until 64 d of age. Thirty-nine Holstein × Gyr crossbred male calves with an average initial live weight (mean ± SEM; for all next values) of 36 ± 1.0 kg were used. Five calves were slaughtered at 4 d of life to estimate the animals' initial body composition (reference group). The remaining 34 calves were distributed in a completely randomized design in a 3 × 2 factorial arrangement consisting of 3 levels of milk (2, 4, or 8 L/d) and 2 levels of starter feed (presence or absence in diet). At 15 and 45 d of life, 4 animals from each treatment were subjected to digestibility trials with total collection of feces (for 72 h) and urine (for 24 h). At 64 d of age, all animals were slaughtered, their gastro-intestinal tract was washed to determine the empty body weight (EBW; kg), and their body tissues were sampled for subsequent analyses. The net energy requirement for maintenance was estimated using an exponential regression between metabolizable energy intake and heat production (both in Mcal/EBW0.75 per d) and was 74.3 ± 5.7 kcal/EBW0.75 per d, and was not affected by inclusion of starter feed in the diet. The metabolizable energy requirement for maintenance was determined at the point of zero energy retention in the body and was 105.2 ± 5.8 kcal/EBW0.75 per d. The net energy for gain was estimated using the EBW and the empty body gain (EBG; kg/d) as 0.0882 ± 0.0028 × EBW0.75 × EBG0.9050±0.0706. The metabolizable energy efficiency for gain (kg) of the milk was 57.4 ± 3.45%, and the kg of the starter feed was 39.3 ± 2.09%. The metabolizable protein requirement for maintenance was 3.52 ± 0.34 g/BW0.75 per d. The net protein required for each kilogram gained was estimated as 119.1 ± 32.9 × EBW0.0663±0.059. The metabolizable protein efficiency for gain was 77 ± 8.5% and was not affected by inclusion of starter feed in the diet. In conclusion, the energy efficiency for gain of milk is higher than that of starter and the net protein required per unit protein gain increases with empty body weight.

Effect of increasing amounts of milk replacer powder added to whole milk on postweaning performance, reproduction, glucose metabolism, and mammary fat pad in dairy heifers.

The aim of this study was to evaluate the effects of increasing the total solids (TS) content of liquid feed, by adding increasing amounts of milk replacer powder to whole milk, on age at puberty and postweaning performance, glucose metabolism, and mammary fat pad of dairy heifers. Crossbreed Holstein × Gyr heifers (n = 58) were distributed into 4 different treatments during the preweaning period. Treatments consisted of liquid feeds with TS content of 12.5 (actual TS = 13.5 ± 0.53%; n = 15), 15.0 (actual TS = 16.1 ± 0.03%; n = 15), 17.5 (actual TS = 18.2 ± 0.14%; n = 13), or 20.0% (actual TS = 20.4 ± 0.24%; n = 15), which were provided up to 59 d old. From 60 to 89 d old, the animals received the same starter offered during the preweaning period in addition to corn silage ad libitum starting at 70 d old. From 90 to 104 d old, the animals were adapted to a total mixed ration. At 105 d old, the animals were distributed in 4 paddocks equipped with electronic feed and water bins and were fed the same total mixed ration ad libitum. A period of adaptation to the electronic feed bins occurred from 105 to 119 d old. Feed and water intake and body weight and body frame development were assessed until puberty. Mammary gland evaluations were performed monthly by ultrasonography from 120 d of age until puberty onset. Puberty onset was determined as plasma progesterone concentration greater than 1 ng/mL in 2 consecutive samples collected 7 d apart. The date of puberty onset was recorded as the collection day of the first of these samples. A glucose tolerance test was performed at 280 d of age. The increased TS content of the liquid feed fed during the preweaning period did not affect dry matter intake, performance, age at puberty, glucose metabolism, or mammary gland fat pad at later stages of rearing process. Conversely, hip width and heart girth increased linearly up to 150 and 240 d of age, respectively, as a result of the increased TS concentration of the liquid feed during the preweaning period.

Immune response of toddlers with history of prematurity.

BACKGROUND: It is not quite well established how immune responses differ in term and preterm infants beyond the first year of life. This study aimed to evaluate aspects of the innate and adaptive immune responses in a group of preterm infants in comparison with their term peers. METHODS: In this cross-sectional study peripheral blood mononuclear cells (PBMC) were isolated from preterm and term children at age three years. Innate immune response was evaluated by the analysis of TLR receptors expression on CD11c+HLADRhigh cells and inflammatory cytokine production after PBMC stimulation with Toll like receptors (TLR) ligands. Adaptive immune response was evaluated by T cells' phenotyping and function after stimulation with polyclonal conventional T cell stimulus. CONCLUSION: We have found that the patterns of innate and adaptive immune responses at 3 years of age were not affected by the fact of the children having being born preterm or at term.

Redescription and range extension of the endangered Paiva's blenny Lupinoblennius paivai (Perciformes: Blenniidae).

The Paiva's blenny Lupinoblennius paivai is redescribed and its range redefined along the Brazilian coast. It differs from its congeners by the presence of three cephalic pores between the dorsal-fin base and lateral line, dorsal-fin elements XII, 12, anal-fin elements II, 16, pectoral-fin rays 14 and 10 + 20 vertebrae. It is here reported from Amazon estuaries (Marajó and Mosqueiro islands, Pará State), increasing its range by c. 3000 km. Lupinoblennius paivai is one of the few blenniid species able to tolerate low salinities. New data about its meristics and morphometrics are presented, as well as a new habitat type.