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Black soldier fly meal in pet diets is gaining acceptance. This study aimed to assess the use of black soldier fly larvae defatted meal (BSFL) and its impact on blood parameters, biochemical markers, organic antioxidant capacity, skin barrier function and skin and coat quality. A cross-over study involved eight beagle dogs with two periods of 50 days each and a washout period of seven days in between. Two approximately iso-nutritive extruded diets were evaluated, the first containing 29.5% BSFL meal and a control diet containing 26% poultry by-product meal (PBP) as protein source. Skin and coat evaluations and blood collections were conducted before and after each period. Skin barrier function was assessed by measurement of trans epidermal water loss (TEWL) and stratum corneum hydration (SCH) in belly and pinna of the dogs on days 0, 15, 30, and 45 of each period. A trend for higher antioxidant effect significant reduction in serum scavenging capacity was found with PBP for BSFL diet trough malondialdehyde and Vitamin E measurement in dog's serum 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. When fed PBP diet dogs exhibited reduction in serum cholesterol triglycerides and decreased LDL levels after 50 days, while dogs fed BSFL presented significant reduction in ALT. TEWL was significantly reduced in belly and pinna over time when dogs were fed BSFL, and TEWL in belly was significantly lower in dogs fed BSFL in comparison to PBP. while Increased SCH was also higher for the BSFL group observed in the same along the feeding period in comparison to PBP, indicating improved ability of the dogs to retain water and keep skin moisture. Improvement skin barrier function could be related to fatty acids from BSFL and increased sebaceous lipids in skin. These are responsible for to avoid water loss and improve skin protection against microbial insults. Inclusion of BSFL as protein source did not promote negative changes in blood biochemistry and had minor antioxidant effect in healthy dogs. However, it proved effective in improving skin barrier function, making BSFL a valuable alternative protein source for dogs, particularly those with sensitive skin or allergies manifesting on the skin.

While classical in many theoretical settings-and in particular in statistical physics-inspired works-the assumption of Gaussian i.i.d. input data is often perceived as a strong limitation in the context of statistics and machine learning. In this study, we redeem this line of work in the case of generalized linear classification, also known as the perceptron model, with random labels. We argue that there is a large universality class of high-dimensional input data for which we obtain the same minimum training loss as for Gaussian data with corresponding data covariance. In the limit of vanishing regularization, we further demonstrate that the training loss is independent of the data covariance. On the theoretical side, we prove this universality for an arbitrary mixture of homogeneous Gaussian clouds. Empirically, we show that the universality holds also for a broad range of real data sets.

The number of antral follicles is considered an important fertility trait because animals with a high follicle count (HFC) produce more oocytes and embryos per cycle. Identification of these animals by genetic markers such as single nucleotide polymorphisms (SNPs) can accelerate selection of future generations. The aim of this study was to perform a genome wide association study (GWAS) on Nelore and Angus heifers with HFC and low (LFC) antral follicle counts. The groups HFC and LFC for genotyping were formed based on the average of total follicles (≥ 3 mm) counted in each breed consistently ± standard deviation. A total of 72 Nelore heifers (32 HFC and 40 LFC) and 48 Angus heifers (21 HFC and 27 LFC) were selected and the DNA was extracted from blood and hair bulb. Genotyping was done using the Illumina Bovine HD 770K BeadChip. The GWAS analysis showed 181 and 201 SNPs with genotype/phenotype association (P ≤ 0.01) in Nelore and Angus heifers, respectively. Functional enrichment analysis was performed on candidate genes that were associated with SNPs. A total of 97 genes were associated to the 181 SNPs in the Nelore heifers and the functional analysis identified genes (ROBO1 and SLIT3) in the ROBO-SLIT pathway that can be involved in the control of germ cell migration in the ovary as it is involved in lutheal cell migration and fetal ovary development. In the Angus heifers, 57 genes were associated with the 201 SNPs, highlighting Fribilin 1 (FBN1) gene, involved in regulation of growth factors directly involved in follicle activation and development. In summary, GWAS for Nelore and Angus heifers showed SNPs associated with higher follicle count phenotype. Furthermore, these findings offer valuable insights for the further investigation of potential mechanism involved in follicle formation and development, important for breeding programs for both breeds., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

The shortfin mako shark is a large-bodied pursuit predator thought to be capable of the highest swimming speeds of any elasmobranch and potentially one of the highest energetic demands of any marine fish. Nonetheless, few direct speed measurements have been reported for this species. Here, animal-borne bio-loggers attached to two mako sharks were used to provide direct measurements of swimming speeds, kinematics and thermal physiology. Mean sustained (cruising) speed was 0.90 m s -1 (±0.07 s.d.) with a mean tail-beat frequency (TBF) of 0.51 Hz (±0.16 s.d.). The maximum burst speed recorded was 5.02 m s -1 (TBF max  = 3.65 Hz) from a 2 m long female. Burst swimming was sustained for 14 s (mean speed = 2.38 m s -1 ), leading to a 0.24°C increase in white muscle temperature in the 12.5 min after the burst. Routine field metabolic rate was estimated at 185.2 mg O 2 kg -1  h -1 (at 18°C ambient temperature). Gliding behaviour (zero TBF) was more frequently observed after periods of high activity, especially after capture when internal (white muscle) temperature approached 21°C (ambient temperature: 18.3°C), indicating gliding probably functions as an energy recovery mechanism and limits further metabolic heat production. The results show shortfin mako sharks generally cruise at speeds similar to other endothermic fish - but faster than ectothermic sharks - with the maximum recorded burst speed being among the highest so far directly measured among sharks, tunas and billfishes. This newly recorded high-oxygen-demand performance of mako sharks suggests it may be particularly vulnerable to habitat loss due to climate-driven ocean deoxygenation., (© 2023 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Objectives: To establish neuropsychological profiles after high- and low-risk preterm birth (i.e., with and without neonatal brain injury) during adolescence and young adulthood and to assess the potential role of early life environmental factors in cognition., Study Design: Participants (N = 177; M age  = 20.11 years) of both sexes were evaluated when adolescent or in young adulthood. They were grouped according to their birth status: 30 high-risk preterm, 83 low-risk preterm and 64 born at full term., Results: Significant differences were found in several cognitive domains between groups. Furthermore, familial socioeconomic status (SES) moderated the relation between the degree of maturity/immaturity at birth and cognition (F (5,171)  = 11.94, p < 0.001, R 2  = 0.26)., Discussion: The findings showed different neuropsychological profiles during adolescence and young adulthood, with the high-risk preterm sample evidencing lower cognitive values. In addition, higher scores in the familial SES score in this study seem to have a protective effect on cognition., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

The most recent approaches to the initial treatment of respiratory distress syndrome (RDS)- involve non-invasive ventilation (NIV) and less-invasive surfactant (SF) administration (LISA). Combining these techniques has been proven a useful treatment option for SF-deficient neonates. The objective of this study was to explore the impact on the brain (using cerebral near infrared spectroscopy, NIRS) of different LISA methods during NIV, using nasal intermittent positive pressure ventilation (NIPPV) for treating neonatal RDS. For this, we used five groups of spontaneously breathing newborn piglets (n = 6/group) with bronchoalveolar lavage (BAL)-induced respiratory distress which received NIPPV only (controls), poractant-alfa using the INSURE-like method (bolus delivery) followed by NIPPV, or poractant-alfa using one of three LISA devices, 1) a nasogastric tube (NT), 2) a vascular catheter (VC) or 3) the LISAcath® catheter. We assessed pulmonary, hemodynamic and cerebral effects, and performed histological analysis of lung and brain tissue. Following BALs, the piglets developed severe RDS (pH<7.2, PaCO2>70 mmHg, PaO2<70 mmHg, dynamic compliance<0.5 ml/cmH2O/kg at FiO2 = 1). Poractant-alfa administration using different LISA techniques during NIPPV was well tolerated and efficacious in newborn piglets. In our study, although all groups showed normal physiological ranges of total lung injury score and biochemical lung analysis, VC and LISAcath® catheters were associated with better values of lung compliance and lower values of lung damage than NIPPV, NT or INSURE-like methods. Moreover, neither of the SF administration methods used (LISA or INSURE-like) had a significant impact on the histological neonatal brain injury score. Of note, the LISAcath® has been recently withdrawn from the market., Competing Interests: NO authors have competing interests., (Copyright: © 2023 Mielgo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to evaluate the effects of heat stress (HS) and its duration on semen quality, serum testosterone, pulsatility and resistibility index of the testicular artery of French Bulldogs. Eight male French Bulldogs, 3-7 years old, 12.63 ± 1.8 Kg were adapted and trained for two months. Room temperature was 21 °C. Semen was collected by digital stimulation. The median of four andrological evaluations was T0. Heat was applied to the scrotum using an electrical heat pad at 40 °C for 11 min. Rectal temperature (RT) and scrotum temperature were evaluated using a mercury thermometer and an infrared thermography camera before and after HS. Semen was evaluated immediately (T1) and after seven (T7), 14 (T14), 21 (T21), 28 (T28) and 60 (T60) days after HS. Semen parameters included macroscopic (volume, color and viscosity) and microscopic (sperm motility and vigor, percentage of morphologically normal or defected spermatozoa, sperm concentration and total number of sperm cells) aspects. A pulsed colored doppler ultrasound was performed on the testicular artery at the spermatic cord and epididymis region before and immediately after HS. Serum testosterone was analyzed before, 48 and 96 h after HS. Data was analyzed by ANOVA using SAS. There was a 1.23 °C increase on RT and a 4.98 °C increase on thermograph after HS. Sperm motility decreased at T1 (P < 0.05) and tended to stay lower at T7 (P = 0.056). It improved at T14, but reduced again at T21 (P < 0.05). At T28 and T60 motility was normal. Vigor was lower at T1 (P < 0.05), normal at T7 and T14, but decreased at T21 (P = 0.054), at T28 and T60 it was not different than T0. Sperm concentration was lower at T1 (P < 0.05) and not different from T0 at other timepoints. Volume color and viscosity were not different. Total sperm per ejaculate was reduced at T1 and T7 (P < 0.05) and tended to be lower at T14 (P = 0.057). T21, T28 and T60 were not different than T0. There was a decrease in normal sperm cells and an increase in defected sperm at T7. There was no difference within T14, T21, T28 and T60. The raise in pathologies at T7 was from an increase in minor defects (P < 0.05). There was no difference in serum concentration of testosterone nor pulsatility and resistivity index before and after HS. In conclusion, induction of HS directly to the testis reduces sperm quality in French Bulldog. This impairment is immediately and transitory., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The aim of our study was to validate the use of the standardized Radiological Society of North America (RSNA) reporting system in individuals with known lung cancer who presented to the emergency department with suspected COVID-19. We included patients aged 18 years or older from the Cancer Institute of the State of São Paulo (ICESP) with a confirmed diagnosis of lung cancer, admitted to the emergency department and undergoing chest computed tomography (CT) for suspicion of COVID-19. Comparison between SARS-CoV2 RT-PCR across RSNA categories was performed in all patients and further stratified by diagnosis of lung cancer progression. Among 58 individuals included in the analysis (65±9 years, 43% men), 20 had positive RT-PCR. Less than a half (43%) had no new lung findings in the CT. Positive RT-PCR was present in 75% of those with typical findings according to RSNA and in only 9% when these findings were classified as atypical or negative (P<0.001). Diagnostic accuracy was even higher when stratified by the presence or absence of progressive disease (PD). Extent of pulmonary inflammatory changes was strongly associated with higher mortality, reaching a lethality of 83% in patients with >25% of lung involvement and 100% when there was >50% of lung involvement. The lung involvement score was also highly predictive of prognosis in this population as was reported for non-lung cancer individuals. Collectively, our results demonstrated that diagnostic and prognostic values of chest CT findings in COVID-19 are robust to the presence of lung abnormalities related to lung cancer.

Objectives: The aim of this study was to describe the use of standard concentrations for continuous infusion drugs in Spanish neonatal intensive care units (NICUs)., Methods: We conducted an observational multicentre study based on a survey sent by email to 9 Spanish NICUs during January and February 2018. We collected data on intravenous drugs frequently used in neonates, and their preparation. Continuous infusion drugs with a standard concentration implemented in ≥2 NICUs were selected. An analysis of the concentrations reported was performed, and the rate of adherence to international recommendations of the Institute of Safe Medication Practice (ISMP) and Vermont Oxford Network (VON) was calculated., Results: From 69 drugs mentioned in the survey, 14 were included in the study, with all but one (furosemide) being considered high-alert medications by the ISMP. From the 9 participating NICUs, 3 had no established standard concentrations for any of the 14 drugs selected. In the other participating NICUs, dexmedetomidine was used with a standard concentration in the 3 NICUs which used the drug, whereas furosemide showed the lowest implementation rate (a standard concentration was implemented in 2 of the 7 NICUs which used the drug). In regard to concentrations adopted in the different NICUs, 80 variations were identified for the 14 drugs. The mean number of different standard concentrations for each drug per NICU was 2 (range 1-5). Adherence to ISMP/VON recommendations varied considerably depending on the drugs, from high adherence for heparin (2/3) and fentanyl (2/3) to low adherence for norepinephrine (0/4)., Conclusions: The establishment of standard concentrations is highly recommended for continuous infusion medications as an effective error-prevention strategy. Nevertheless, we detected a low implementation rate in our NICUs and a lack of consistency in the concentrations selected., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Classic infantile Pompe disease (IPD) is a rare lysosomal storage disorder characterized by severe hypertrophic cardiomyopathy and profound muscle weakness. Without treatment, death occurs within the first 2 years of life. Although enzyme replacement therapy (ERT) with alglucosidase alfa has improved survival, treatment outcome is not good in many cases and is largely dependent on age at initiation. The objective of the study was (a) to analyse the different stages in the diagnosis and specific treatment initiation procedure in IPD patients, and (b) to compare clinical and biochemical outcomes depending on age at ERT initiation (<1 month of age vs. <3 months of age). Here, we show satisfactory clinical and biochemical outcomes in two IPD patients after early treatment initiation before 3 months of life with immunomodulatory therapy in the ERT-naïve setting, with a high ERT dose from the beginning. Despite the overall good evolution, the patient who initiated treatment <1 month of life presented even better outcomes than the patient who started treatment <3 months of life, with an earlier normalization of hypertrophic cardiomyopathy, along with CK normalization, highlighting the importance of early treatment initiation in this progressive disease before irreversible muscle damage has occurred.

Objectives: Intravenous drug use in neonates is frequent and prone to medication errors. The aim of this study was to describe the intravenous drugs most frequently used in Spanish Neonatal Intensive Care Units (NICU), their preparation and the implementation rate of standardised concentration infusions., Methods: We conducted an observational multicentre study based on a survey sent by email to nine Spanish NICUs during January and February 2018. We collected data describing the intravenous drugs frequently used in neonates and their preparation. A descriptive analysis of the medicines reported (and their preparation) was performed, to assess how frequently standard concentrations were used and how medications were prepared in central pharmacies., Results: Overall, 69 different drugs were reported by participating NICUs. Of these, 33% (n=23) were not approved for use in neonates and 38% (n=26) corresponded to high-alert medications, according to the Institute for Safe Medication Practices. A mean of only 63.5% of intravenous medicines were standardised. The standard-concentration implementation rate was somewhat higher for intermittent (mean 74.1%) than continuous (mean 42.9%) infusions. Notably, infusions were more commonly prepared on wards than in hospital pharmacies., Conclusions: Intravenous drug use in NICUs has been identified as a high-risk process, and error-reduction strategies (such as concentration standardisation) have been recommended. Further data are necessary to design the most suitable intervention in our country (Spain), but institutional initiatives are needed to achieve this., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To systematically review and perform meta-analyses on the long-term neurodevelopmental outcomes of adults born moderate and late preterm (MLPT) in relation to cognitive functioning and psychiatric disorders., Study Design: A search was conducted to identify any studies that involved prematurity in adulthood. From these studies, reports that included a group of MLPT adults and included description of cognitive and/or mental health domains (including specific long-term outcomes) were selected., Results: In total, 155 publications were identified, but only 16 papers met the inclusion criteria. A small effect size (g = 0.38) was found in MLPT to demonstrate poorer intellectual performance compared with those born at term. Moreover, MLPT adults exhibited greater odds for any psychiatric (OR 1.14), substance use (OR 1.16), mood (OR 1.06), and psychotic disorders (OR 1.40)., Conclusions: Despite inconsistency due to the methodologic differences between the selected studies, MLPT showed minor long-term effects into adulthood. However, more studies are needed, because prematurity seems to confer some vulnerability to biological and environmental factors that enhance susceptibility to adverse neurodevelopment outcomes., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the prevalence of periodontal disease and alveolar bone loss in overweight/obese Brazilian adolescents.
Methods: Participants included 12- to 18-year-old adolescents who were allocated into two groups: (1) normal weight; or (2) overweight/obese. Body mass index (BMI) and waist circumference (WC) were evaluated to classify overweight/obesity. Clinical measurements included the visible plaque index (VPI) and community periodontal index (CPI). Alveolar bone loss (ABL) was also evaluated by bitewing radiographs.
Results: There were 109 subjects. There were no significant differences between the groups for VPI and CPI code two ( P >0.05). CPI code zero was more prevalent in normal weight subjects than in overweight/obese subjects ( P <0.05). CPI codes one and three were significantly more frequent in the overweight/obese group ( P <0.05). The normal weight subjects revealed a higher percentage of sites with no ABL ( P <0.05), while the overweight/obese group had a higher prevalence of incipient ABL with the number of sites greater than one and less than three ( P <0.05).
Conclusion: Overweight/obesity may affect the progression of early periodontitis in the presence of poor biofilm control in adolescents, as this group presents more bleeding on probing and pathological periodontal pockets greater than four mm as well as a higher prevalence of sites with incipient alveolar bone loss.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue., (© 2021 S. Karger AG, Basel.)

This study aimed to evaluate the effect of sodium caseinate added into freezing extender on the sperm parameters of cryopreserved bull semen and in vitro and in vivo fertility. One ejaculate of 30 bulls was used and processed using Botu-Bov (Botupharma, Botucatu, Brazil) with the addition of 20% egg yolk (EY) or 15% egg yolk with 2% sodium caseinate (EY + SC), subsequently submitted to freezing. Semen from both groups were evaluated immediately after thawing (T0) and after thermic stress at 37 °C for 90 min (T90), for sperm kinetics, by CASA method, and plasma membrane integrity (PMI), superoxide (O 2 - ) concentration and high mitochondrial potential (HMP) by flow cytometry. In vitro fertilization (IVF) was performed to assess embryo cleavage rate on day 3, and blastocyst rate on day 8. The in vivo fertility test was performed using fixed-time artificial insemination (FTAI). In sperm evaluation, trajectory velocity, linear velocity, curvilinear velocity, and lateral head movement were higher (P < 0.05) in EY + SC at T0. At T90, while rectilinearity and linearity did not differ between EY and EY + SC (P > 0.05), the other parameters evaluated were higher in EY + SC. Similarly, the integrity of the plasma and acrosomal membranes (iPAM) was higher (P < 0.05) at T90 in EY + SC, but did not differ (P > 0.05) between the groups at T0. For O 2 - and HMP, the values were lower (P < 0.05) in EY + SC group in both moments; furthermore, EY + SC showed higher cleavage and blastocyst rates in IVF. Likewise, pregnancy rates by FTAI were higher (P < 0.05) in the EY + SC group. In conclusion, the addition of sodium caseinate into freezing extender improves sperm parameters of frozen-thawed bull semen and fertility rates on during in vitro and in vivo tests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The current clinical treatment of neonates with respiratory distress syndrome includes endotracheal intubation and intratracheal instillation of exogenous surfactant. Nebulization of surfactant offers an attractive alternative. The aims of this study were to test nebulization as a noninvasive method of administering surfactant and determine the optimal dose for the treatment of respiratory distress syndrome-associated pathophysiology of the neonatal lungs., Design: Prospective, randomized, animal model study., Setting: An experimental laboratory., Subjects: Thirty-six newborn piglets., Interventions: Different doses (100, 200, 400, and 600 mg/kg) of poractant alfa were administered via a vibrating membrane nebulizer (eFlow-Neos; Pari Pharma GmbH, Starnberg, Germany) or a bolus administration using the intubation-surfactant-extubation (Insure) technique (200 mg/kg) to spontaneously breathing newborn piglets (n = 6/group) with bronchoalveolar lavage-induced respiratory distress syndrome during nasal continuous positive airway pressure (180 min)., Measurements and Main Results: Pulmonary, hemodynamic, and cerebral effects were assessed. Histologic analysis of lung and brain tissue was also performed. After repeated bronchoalveolar lavage, newborn piglets developed severe respiratory distress syndrome. Rapid improvement in pulmonary status was observed in the Insure group, whereas a dose-response effect was observed in nebulized surfactant groups. Nebulized poractant alfa was more effective at doses higher than 100 mg/kg and was associated with similar pulmonary, hemodynamic, and cerebral behavior to that in the Insure group, but improved lung injury scores., Conclusions: In newborn piglets with severe bronchoalveolar lavage-induced respiratory distress syndrome, our results demonstrate that the administration of nebulized poractant alfa using an investigational customized eFlow-Neos nebulizer is an effective and safe noninvasive surfactant administration technique.

Objectives: We have setup for the first time a long-term (72 hr) respiratory distress syndrome model in spontaneously breathing surfactant-deficient newborn piglets to investigate the continuous positive airway pressure failure rate with nebulized poractant alfa compared with that with the intubation surfactant extubation technique or continuous positive airway pressure only., Design: Prospective randomized animal study., Setting: Biocruces-Bizkaia Health Research Institute Animal Facility., Subjects-Interventions: Eighteen newborn piglets (n = 6/group) with surfactant-deficient respiratory distress syndrome were randomized to three continuous positive airway pressure-ventilated groups: 1) nebulized surfactant (poractant alfa 400 mg/kg) via a customized investigational eFlow-Neos vibrating membrane nebulizer system, 2) bolus administration using the Intubation Surfactant Extubation method (200 mg/kg), or 3) continuous positive airway pressure alone., Measurements and Main Results: Pulmonary and hemodynamic variables were assessed at 6-hour intervals for 72 hours. Lung and brain histological analyses were performed. After bronchoalveolar lavages, piglets developed respiratory distress syndrome. Over the follow-up, both surfactant-treated groups had significantly better pulmonary outcomes than the continuous positive airway pressure alone group. Furthermore, unlike in the continuous positive airway pressure group, there were no cases of respiratory failure in either of the surfactant-treated groups., Conclusions: In newborn piglets with respiratory distress syndrome, the nebulization of 400 mg/kg of poractant alfa using a customized investigational eFlow-Neos nebulizer was found to be safe and effective in reducing the risk of respiratory failure in the 72 hours after treatment.

Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation. The microbiome of the mother, the placenta and the fetus influence the fetus growth and undoubtedly plays a major role in the adequate development of the newborn infant. Hence, the microbiome modulates the inflammatory mechanisms related to physiological and pathological processes that are involved in the perinatal progress through different mechanisms. The present review summarizes the actual knowledge related to physiological changes in the microbiota occurring in the mother, the fetus, and the child, both during neonatal period and beyond. In addition, we approach some specific pathological situations during the perinatal periods, as well as the influence of the type of delivery and feeding.

Aim: To describe variations in practice between follow-up programmes for very preterm children born at less than 32 weeks' gestation or with very low birth weight of less than 1,500 g., Methods: A survey on follow-up practices was electronically distributed to level II and III units among hospitals of the Spanish National Health Service in 2016. The survey included 70 questions covering issues such as follow-up organisation and resources, routine assessments, relationships with other services and families, information management and training., Results: The response rate was 91.5% (141/154). Among respondents, 70.9% (100/141) reported that they do provide follow-up and 42% do so up to six years of age. Routine neurological and ophthalmological follow-up is not performed in 60% and 37% of hospitals, respectively, and a second hearing assessment is not given in 62%. Just 38% of units have psychologist. In 41% of hospitals, training in follow-up skills is not included in Paediatric Residency training programme., Conclusion: Although Spain has a nationwide health system that provides universal health coverage, we found that follow-up care for children born very preterm/very low birth weight is not equitable. Nearly half of paediatric residents receive no training in follow-up for this high-risk population., (©2018 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Nasal continuous-positive airway pressure (nCPAP) with the INSURE (INtubation-SURfactant-Extubation) or LISA (Less-Invasive Surfactant Administration) procedures are increasingly being chosen as the initial treatment for neonates with surfactant deficiency. Our objective was to compare the effects on cerebral oxygenation of different methods for surfactant administration: INSURE and LISA, using a nasogastric tube (NT) or a LISAcath® catheter, in spontaneously breathing SF-deficient newborn piglets., Methods: Eighteen newborn piglets with SF-deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to INSURE, LISA-NT, or LISAcath® groups. We assessed pulmonary (gas exchange, lung mechanics, lung histology) and hemodynamic (mean arterial blood pressure, heart rate) changes, cerebral oxygenation (cTOI) and cerebral fractional tissue extraction (cFTOE), with near-infrared spectroscopy, carotid blood flow and brain histology., Results: SF-deficient piglets developed respiratory distress (F iO2  = 1, pH <7.2, P aCO2 >70 mmHg, P aO2 <70 mmHg, C dyn <0.5 mL/cmH 2 O/kg). Rapid improvements in pulmonary status were observed in all surfactant-treated groups without hemodynamic alterations. In the INSURE group, a transient decrease in cTOI occurred during and immediately after surfactant administration, while cTOI only decreased during surfactant administration in the LISA-NT group and did not change significantly in the LISAcath® group. Brain injury scores were low in all surfactant-treated groups., Conclusion: In spontaneously breathing SF-deficient newborn piglets, short-lasting decreases in cerebral oxygenation are associated with surfactant administration by the INSURE method or LISA using an NT, while no cerebral oxygenation changes occurred with LISA using a LISAcath®. Notably, none of treatments studied seems to have a negative impact on the neonatal brain., (© 2019 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.)

Background: Helminth parasites cause morbidity and mortality in both humans and animals. Most anthelmintic drugs used in the treatment of parasitic nematode infections act on target proteins or regulate the electrical activity of neurons and muscles. In this way, it can lead to paralysis, starvation, immune attack, and expulsion of the worm. However, current anthelmintics have some limitations that include a limited spectrum of activity across species and the threat of drug resistance, which highlights the need for new drugs for human and veterinary medicine., Purpose: Present study has been conducted to determine the anthelmintic activity of silver nanoparticles (AgNPs) synthesized from the extract of nematophagous fungus, Duddingtonia flagrans , on the infecting larvae of Ancylostoma caninum (L 3 )., Methods: The nanoparticles were characterized by visual, ultraviolet, Fourier-transform infrared spectroscopy, transmission electron microscopy (TEM) analysis, and X-ray diffraction. The in vitro study was based on experiments to inhibit the motility of infective larvae (L 3 ), and the ultrastructural analysis of the nematode was performed by images obtained by TEM., Results: The XRD studies revealed the crystalline nature of the nanoparticles, and FTIR results implied that AgNPs were successfully synthesized and capped with compounds present in the extract. The results showed that the green synthesis of AgNPs exhibited nematicidal activity, being the only ones capable of penetrating the cuticle of the larvae, causing changes in the tegmentum, and consequently, the death of the nematode., Conclusion: The extract of the fungus D. flagrans is able to synthesize AgNP and these have a nematicidal action., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

The number of antral follicles counted (AFC) by ultrasound is associated with fertility in cattle. Cows with higher follicle count (HFC) have higher performance in reproductive-assisted technologies than cows with lower follicle count (LFC). In this study, we aimed to define the preantral follicle count by histology and to identify differentially expressed genes (DEGs) using a microarray in Nelore and Angus heifers with HFC and LFC. The ovaries of each animal were scanned with an ultrasound device 12 to 24 hr after estrus. The groups were formed based on the average number of total follicles (≥3 mm) counted in each breed consistently ± the standard deviation. For the histological analysis, preantral follicles were counted and classified under a stereo microscope, and follicle density was determined. Microarray analysis was performed on pools of three follicles dissected from the ovaries of 15 Nelore (6 HFC and 9 LFC) and 17 Angus heifers (9 HFC and 8 LFC). Angus heifers have increased total and primordial follicle density. Nelore heifers have increased antral follicle count. Different patterns of gene expression regulate follicle recruitment and development in Angus and Nelore heifers and may be associated with the different follicle densities observed in Angus versus Nelore heifers. Furthermore, HFC heifers presented increased expression of genes associated with cellular development and metabolism., (© 2018 Wiley Periodicals, Inc.)

Background and Objectives: Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence., Study Design: Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs' cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage., Results: Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 [25.9%] vs. placebo, n = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, n = 5 [9.2%] vs. placebo, n = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found., Conclusions: Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate., (© 2019 S. Karger AG, Basel.)

Introduction: Castleman disease (CD) is a rare polyclonal lymphoproliferative disorder of unknown etiology, which usually develops in the mediastinum. It can also occur in the cervical, retroperitoneal and axillary regions. Localized pancreatic CD is quite rare [1]., Presentation of Case: The authors herein present a case of a 34 years old female that was diagnosed during a symptomatic cholelithiasis evaluation. During the evaluation, an abdominal ultrasonography revealed a tumor at the head of the pancreas, which went on to generate a dilatation of the extrahepatic bile ducts. This finding was confirmed by abdominal magnetic resonance imaging (MRI). Subsequently, the patient underwent a laparotomy, where a capsulated tumor was found at the head of the pancreas with well-defined margins. The decision was made for tumor excision. The histopathology and immunohistochemistry established CD, hyaline vascular variation., Discussion: The authors of the present paper also performed a literature review concerning Pancreatic CD, where there were found only 33 cases until the time of the writing of this paper, and we have subsequently carried out a retrospective analysis of all cases. In a patient with atypical images, there might be a benefit from a preoperative diagnosis of CD, by using immunohistochemistry analysis in an image guided biopsy. Thus, avoiding unnecessary procedures and surgeries., Conclusion: Localized pancreatic CD is a very rare condition with good prognosis, but it can mimic many common diseases, such as gastrointestinal stromal tumor (GIST), pancreatic neuroendocrine tumor or pancreatic adenocarcinoma., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Little is known about the pathogenesis of cerebral sinovenous thrombosis (CSVT) in the neonate. Although thrombophilia has been described as increasing the risk of CSVT in adults, it remains controversial in pediatric patients, and prospective case-control studies regarding neonatal CSVT are lacking. From 2008 to 2017, all 26 consecutive newborn infants ≥35 weeks of gestation diagnosed with neonatal CSVT, and their mothers, were tested for factor V Leiden (FV) G1691A, FII G20210A, and methylenetetrahydrofolate reductase C677T (MTHFR C677T) mutations. Eighty-five mother-infant pairs were recruited as controls. All infants except 1 with CSVT were suspected due to clinical symptoms, mainly seizures (22/25). Magnetic resonance imaging was performed in 24/26 infants. Heterozygous FV G1691A, FII G20210A, and homozygous MTHFR C677T mutations were present in 1/26, 3/26, and 3/20 infants with CSVT, respectively. FII (odds ratio: 10.96; 95% confidence interval [CI]: 1.09-110.35) and male sex (3.93; 95% CI: 1.43-10.76) were associated with CSVT. When FII G20210A analysis was adjusted for sex, the OR for FII G20210A was 6.70 (95% CI: 0.65-69.22). No differences were found for FV G1691A or homozygous MTHFR mutations between neonates with CSVT and their mothers, compared to controls.

Background: Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) will relapse if treatment is withdrawn, but various trials have recently demonstrated that a significant proportion of patients who achieved a stable and deep molecular response (DMR) can stop therapy without relapsing. However, most information on treatment cessation was obtained from clinical trials with strict recruiting criteria., Methods: We evaluated the outcome of 25 patients with CML that discontinued TKI therapy in our institute in real-world clinical practice., Results: Of the 25 patients, 76% discontinued therapy in sustained deep molecular response (SDMR) and 24% were in unsustained DMR (UDMR). Discontinuation of therapy due to adverse effects was observed in 5 and 50% of the patients in the SDMR and UDMR groups, respectively. After TKI discontinuation, patients were followed for a median of 24 months. At the time of this analysis, 56% patients had a molecular relapse after a median of 4 months. SDMR and longer treatment duration were associated with lower probability of molecular relapse: 25% in SDMR patients with TKI treatment > 96 months and 85% in UDMR patients with TKI treatment ≤96 months. All relapsed patients promptly resumed TKI therapy and regained at least major molecular response (MMR)., Conclusions: Our results suggest that TKI discontinuation is safe outside clinical trials and particularly effective in CML patients who are in SDMR with longer TKI treatment duration.

Quantum chaos is one of the distinctive features of the Sachdev-Ye-Kitaev (SYK) model, N Majorana fermions in 0+1 dimensions with infinite-range two-body interactions, which is attracting a lot of interest as a toy model for holography. Here we show analytically and numerically that a generalized SYK model with an additional one-body infinite-range random interaction, which is a relevant perturbation in the infrared, is still quantum chaotic and retains most of its holographic features for a fixed value of the perturbation and sufficiently high temperature. However, a chaotic-integrable transition, characterized by the vanishing of the Lyapunov exponent and spectral correlations given by Poisson statistics, occurs at a temperature that depends on the strength of the perturbation. We speculate about the gravity dual of this transition.

BackgroundNasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV), forms of non-invasive ventilation (NIV) for respiratory support, are increasingly being chosen as the initial treatment for neonates with surfactant (SF) deficiency. Our objective was to compare NCPAP with NIPPV with or without SF administration as a primary mode of ventilation.MethodsTwenty-four newborn piglets with SF-deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to NCPAP or NIPPV, with or without SF administration (InSurE method). We evaluated pulmonary, systemic (hemodynamic and oxygen metabolism), and cerebral effects.ResultsSF-deficient piglets developed respiratory distress (F iO2 :1, pH<7.2, P aCO2 >70 mm Hg, P aO2 <70 mm Hg, and C dyn <0.5 ml/cmH 2 O/kg). Gradual improvements in pulmonary status were observed in both NIV groups, with NIPPV achieving lower lung inflammation markers and injury scores. Both SF-treated groups obtained significantly better respiratory outcomes than groups not treated with SF before NIV. All NIV-treated groups showed low brain injury scores.ConclusionIn spontaneously breathing SF-deficient newborn piglets, NIPPV is a suitable NIV strategy. SF administration in combination with NCPAP or NIPPV improves pulmonary status providing extra protection against pulmonary injury. No injury to the developing brain was observed to be associated with these NIV strategies, with or without SF therapy.

Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

The effects of resistant starch (RS) intake on nutrient digestibility, microbial fermentation products, faecal IgA, faecal pH, and histological features of the intestinal mucosa of old dogs were evaluated. The same formulation was extruded in two different conditions: one to obtain elevated starch cooking degree with low RS content (0.21%) and the other lower starch cooking with high RS content (1.46%). Eight geriatric Beagles (11.5 ± 0.38 years old) were fed each diet for 61 days in a crossover design. Food intake, nutrient digestibility, fermentation products, faecal pH, and faecal IgA were examined via variance analysis. Histological results of intestinal biopsies were assessed via Wilcoxon test for paired data. The morphometric characteristics of large intestine crypts were evaluated via paired t tests (p < .05). Protein, fat, and energy digestibilities were higher for the low-RS diet (p < .05). Dogs receiving the high-RS diet had lower faecal pH and higher values for propionate, butyrate, total volatile fatty acids, and lactate (p < .05). No differences between diets were found in the histological parameters of the gut mucosa, and only a tendency for deeper crypts in the descending colon was observed for dogs fed the high-RS diet (p = .083). The intake of a corn-based kibble diet manufactured with coarse ground raw material and low starch gelatinization to obtain 1.4% of RS affected microbial fermentation products and faecal pH and tended to increase crypt depth in the descending colon of old dogs., (© 2017 Blackwell Verlag GmbH.)

Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography - mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points. The analysis of plasma samples from newborns with HIE revealed a decrease of lactate, pyruvate and β-hydroxybutyrate concentrations, whereas rising malate concentrations were observed. In healthy control newborns (N = 19) significantly lower levels of pyruvate and lactate were found in comparison to age-matched newborns with HIE undergoing TH, whereas acetoacetate and β-hydroxybutyrate levels were clearly increased. Access to a validated analytical method and a controlled cohort of newborns with HIE undergoing hypothermia treatment for the first time allowed the in-depth study of the evolution of key metabolites of metabolic junctions in this special population.

Fibre is generally considered to dilute food energy, alter intestinal transit time and promote satiety; however, in cats, conflicting results have been found. In this study, two insoluble fibres were evaluated in four feline diets: control (no added fibre); diet with 10% sugar cane fibre; diet with 20% sugar cane fibre; and diet with 10% cellulose. The experiment was conducted with 32 cats, eight animals per diet, over 42 days: 1-7 for diet adaptation; 8-14 for total collection of faeces for digestibility; 15-17 for fresh faeces collection for fermentation products measurements; 18-20 for gastrointestinal transit time determination; 21 and 37 to evaluate the pattern of food intake; and 22 and 42 to assess satiety. Means were compared by analysis of variance and orthogonal contrasts, and the pattern of food intake was compared by repeated-measures analysis of variance (p < 0.05). The cats exhibited increased food intake after fibre addition to the diets (p < 0.05), achieving similar energy consumption. Cellulose and the two levels of sugar cane fibre reduced nutrient availability and energy digestibility, but only sugar cane fibre reduced fat digestibility (p < 0.05). Faecal output and the number of defecations per day increased with fibre inclusion (p < 0.05). Gastrointestinal transit time did not change with sugar cane fibre inclusion, but it was reduced with cellulose addition (p = 0.032). The pattern of food intake did not change, but cats fed fibre-supplemented diets exhibited greater consumption of a challenge meal, increasing energy intake (p < 0.01) when exposed to a palatable, energy-dense food., (Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.)

The present study determined the transcriptome profile in Nelore and Holstein oocytes subjected to heat shock during IVM and the mRNA abundance of selected candidate genes in Nelore and Holstein heat-shocked oocytes and cumulus cells (CC). Holstein and Nelore cows were subjected to in vivo follicle aspiration. Cumulus-oocyte complexes were assigned to control (38.5°C, 22h) or heat shock (41°C for 12h, followed by 38.5°C for 10h) treatment during IVM. Denuded oocytes were subjected to bovine microarray analysis. Transcriptome analysis demonstrated 127, nine and six genes were differentially expressed between breed, temperature and the breed×temperature interaction respectively. Selected differentially expressed genes were evaluated by real-time polymerase chain reaction in oocytes and respective CC. The molecular motor kinesin family member 3A (KIF3A) was upregulated in Holstein oocytes, whereas the pro-apoptotic gene death-associated protein (DAP) and the membrane trafficking gene DENN/MADD domain containing 3 (DENND3) were downregulated in Holstein oocytes. Nelore CC showed increased transcript abundance for tight junction claudin 11 (CLDN11), whereas Holstein CC showed increased transcript abundance for antioxidant metallothionein 1E (MT1E) . Moreover, heat shock downregulated antioxidant MT1E mRNA expression in CC. In conclusion, oocyte transcriptome analysis indicated a strong difference between breeds involving organisation and cell death. In CC, both breed and temperature affected mRNA abundance, involving cellular organisation and oxidative stress.

Background: Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS., Methods: Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed., Results: After delivery, lambs developed severe RDS (F IO2 :1, pH < 7.15, P aCO2  > 70 mmHg, P aO2  < 40 mmHg, C dyn  < 0.1 mL/cmH 2 O/kg). By 30 min after treatment, animals in both SF-treated groups had consistently better gas exchange and lung mechanics than controls. After CHF5633 administration, P aCO2 , carotid artery blood flow, and cerebral oxygen delivery tended to slowly decrease compared to other groups. By 2 h, SF-treated groups had similar values of all parameters studied, these remaining steady for the rest of the experiment. Lambs administered CHF5633 obtained better lung and brain injury scores than controls., Conclusion: Intratracheal administration of a bolus of CHF5633 improves pulmonary status in preterm lambs with severe RDS, obtaining better lung and brain injury scores than controls and favorable cerebral hemodynamics, comparable to those with gold standard Curosurf treatment., (© 2017 Wiley Periodicals, Inc.)

Hairball formation may induce vomiting and intestinal obstruction in predisposed cats. Some insoluble fibres as sugarcane fibre and cellulose can prevent hairball formation. The aim of this study was to evaluate the effect of beet pulp consumption, a moderate soluble and fermentable fibre source, on faecal trichobezoars excretion in adult shorthaired cats fed kibble diets. Eighteen mixed-breed shorthaired cats and three extruded diets were used as follows: a basal diet without added fibre source (PB0-8.8% dietary fibre); BP8-8% inclusion of beet pulp (17.5% of dietary fibre); BP16-16% inclusion of beet pulp (23.8% of dietary fibre). The cats were fed during 31 days and faeces quantitatively collected during three periods of 3 days each (from days 3-5; 15-17; 26-28). Gastrointestinal transit time was determined in the last 3 days of study (from days 29-31). The trichobezoars were separated from faeces, collected, dried and washed in ether for complete removal of all faecal material. The results were submitted to repeated-measure analysis of variance and means evaluated by polynomial contrast (p < 0.05). Beet pulp increased faecal production (p < 0.001) and reduced gastrointestinal transit time (p = 0.003). No alterations were found on trichobezoar faecal excretion, both as considered in number per cat per day of mg per cat per day (p > 0.05). Beet pulp intake did not reduce the number or the size of hairballs eliminated via faeces of shorthaired cats., (Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.)

The present study compared the effects of diets formulated with fibers of different fermentability and protein sources of animal or vegetable origins on old and adult dogs. The experiment was organized in a 3 (diets) × 2 (ages) factorial arrangement, totaling 6 treatments. Thirty-six Beagle dogs were used (18 old dogs [10.2 ± 1.0 yr] and 18 young adult dogs [2.6 ± 0.9 yr]), with 6 dogs per treatment. Three diets with similar compositions were used: a nonfermentable insoluble fiber source (sugarcane fiber) and chicken byproduct meal (nonfermentable fiber [NFF] diet), a fermentable fiber source (beet pulp) and chicken byproduct meal (fermentable fiber [FF] diet), and soybean meal as a protein and fiber source (soybean meal [SM] diet). Data were evaluated using the MIXED procedure and considering the effects and interactions of block, animal, diets, and age. Means were compared using Tukey's test ( < 0.05). Age × diet interactions were evaluated when < 0.1. Old dogs had a reduced coefficient of total tract apparent digestibility of DM, which was explained by the age and diet interaction of CP and fat digestibility that was lower for old than for adult dogs fed the FF diet ( < 0.05). The SM diet obtained higher DM, OM, CP, and fiber digestibility compared with the NFF diet ( < 0.05). The feces of dogs fed the NFF diet had increased DM content ( < 0.05). The short-chain fatty acids (SCFA) did not change by age group and were higher for dogs fed the FF and SM diets compared with dogs fed the NFF diet ( < 0.05). An age and diet interaction was observed for lactate and was increased in the feces of old dogs compared with adult dogs fed the FF diet ( < 0.05). Fecal putrescine, cadaverine, and spermine were increased for old dogs compared with adult dogs ( < 0.05), and the spermidine fecal concentration was increased for dogs fed the SM diet regardless of age ( < 0.05). Old dogs had reduced peripheral T and B lymphocytes ( < 0.05). An age and diet interaction was observed for fecal IgA ( < 0.001). Adult dogs fed the SM diet had increased IgA in feces compared with animals fed the NFF and FF diets ( < 0.05). However, for old dogs, both the FF and SM diets induced increased IgA compared with the NFF diet ( < 0.05). In conclusion, beet pulp may reduce digestibility and induce increased lactate in the feces of old dogs. The protein and oligosaccharides of soybean meal are digestible by dogs, induce the production of SCFA and spermidine, and increase fecal IgA. Old dogs had increased putrecine, cadaverine, and spermine fecal concentrations.

Objective: To evaluate the sedative and cardiopulmonary effects of three methadone doses, combined with acepromazine, in dogs., Study Design: Prospective, randomized, complete block study., Animals: Six healthy, adult, cross-bred dogs weighing 17.2±4.4 kg (mean±standard deviation)., Methods: Each dog was administered four treatments: acepromazine (0.05 mg kg -1 ) alone or acepromazine (same dose) in combination with methadone (0.25, 0.50 or 0.75 mg kg -1 ). All drugs were administered intramuscularly. Sedation was scored by a numeric descriptive scale (NDS, range 0-3) and a simple numerical scale (SNS, range 0-10). Heart rate, invasive blood pressure, arterial blood gases and rectal temperature were measured at 15 to 30 minute intervals for 120 minutes., Results: According to NDS scores, mild to moderate sedation (NDS=1-2) was observed in most dogs in the acepromazine treatment, with only one out of six dogs scored as exhibiting intense sedation (NDS=3). All treatments with methadone resulted in significantly higher SNS scores compared with acepromazine alone. In these treatments, most dogs exhibited intense sedation (NDS=3). Increasing the dose of methadone from 0.25 to 0.50 or 0.75 mg kg -1 prolonged sedation in a dose-related manner, but did not influence the degree of sedation. The main adverse effects following administration of acepromazine-methadone treatments were decreased blood pressure, mild respiratory acidosis and decreased rectal temperature. These effects were well tolerated and resolved without treatment., Conclusions and Clinical Relevance: In this study in six dogs, acepromazine-methadone administration resulted in intense sedation in most dogs. The results are interpreted to indicate that a low dose of methadone (0.25 mg kg -1 ) administered in combination with acepromazine (0.05 mg kg -1 ) will induce short-term sedation in dogs, whereas higher doses of methadone should be administered when prolonged sedation is desired., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Aims: To define patterns of brain injury and associated neurodevelopmental outcomes in infants with severe neonatal anaemia., Methods: We studied 20 infants with severe anaemia at birth (haemoglobin<7g/dL). Clinical details were analysed for causes of anaemia and co-morbidities. All had early brain magnetic resonance imaging (MRI) scans, which were reviewed for injury pattern. Neurodevelopmental outcomes were assessed at a median age of 24months., Results: The aetiology of the anaemia was feto-maternal haemorrhage in 17 and antepartum haemorrhage in 3 infants. The predominant site of injury was the white matter, which was affected in all infants, with differing grades of severity and with cystic evolution in 45%. Only one infant showed an injury pattern typical of an acute severe hypoxic-ischaemic insult. Outcomes correlated closely to the severity of MRI findings. Cerebral palsy was seen only with the most severe neuroimaging patterns (n=6). Global developmental delay, learning or behavioural problems and seizures were common with moderate injury. Visual impairment occurred, particularly with posterior injury. Microcephaly developed in 45%., Interpretation: Severe neonatal anaemia at birth was associated with a white matter predominant pattern of injury, the severity of which was related to neurodevelopmental outcomes. Early MRI and long-term follow-up are advisable following severe neonatal anaemia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Over the last decade, ocean sunfish movements have been monitored worldwide using various satellite tracking methods. This study reports the near-real time monitoring of fine-scale (< 10 m) behaviour of sunfish. The study was conducted in southern Portugal in May 2014 and involved satellite tags and underwater and surface robotic vehicles to measure both the movements and the contextual environment of the fish. A total of four individuals were tracked using custom-made GPS satellite tags providing geolocation estimates of fine-scale resolution. These accurate positions further informed sunfish areas of restricted search (ARS), which were directly correlated to steep thermal frontal zones. Simultaneously, and for two different occasions, an Autonomous Underwater Vehicle (AUV) video-recorded the path of the tracked fish and detected buoyant particles in the water column. Importantly, the densities of these particles were also directly correlated to steep thermal gradients. Thus, both sunfish foraging behaviour (ARS) and possibly prey densities, were found to be influenced by analogous environmental conditions. In addition, the dynamic structure of the water transited by the tracked individuals was described by a Lagrangian modelling approach. The model informed the distribution of zooplankton in the region, both horizontally and in the water column, and the resultant simulated densities positively correlated with sunfish ARS behaviour estimator (rs = 0.184, p<0.001). The model also revealed that tracked fish opportunistically displace with respect to subsurface current flow. Thus, we show how physical forcing and current structure provide a rationale for a predator's fine-scale behaviour observed over a two weeks in May 2014.

Follicle population is important when animals are used in assisted reproductive programs. Bos indicus animals have more follicles per follicular wave than Bos taurus animals. On the other hand, B taurus animals present better fertility when compared with B indicus animals. Androgens are positively related with the number of antral follicles; moreover, they increase growth factor expression in granulose cells and oocytes. Experimentation was designed to compare testosterone concentration in plasma, and follicular fluid and androgen enzymes mRNA expression (CYP11A1, CYP17A1, 3BHSD, and 17BHSD) in follicles from Angus and Nellore heifers. Heifers were assigned into two groups according to the number of follicles: low and high follicle count groups. Increased testosterone concentration was measured in both plasma and follicular fluid of Angus heifers. However, there was no difference within groups. Expression of CYP11A1 gene was higher in follicles from Angus heifers; however, there was no difference within groups. Expression of CYP17A1, 3BHSD, and 17BHSD genes was higher in follicles from Nellore heifers, and expression of CYP17A1 and 3BHSD genes was also higher in HFC groups from both breeds. It was found that Nellore heifers have more antral follicles than Angus heifers. Testosterone concentration was higher in Angus heifers; this increase could be associated with the increased mRNA expression of CYP11A1. Increased expression of androgen-producing enzyme genes (CYP17A1, 3BHSD, and 17BHSD) was detected in Nellore heifers. It can be suggested that testosterone is acting through different mechanisms to increase follicle development in Nellore and improve fertility in Angus heifers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The time at which follicles acquire LHR in bovine granulosa cells is the subject of some controversy among researchers. The main objective of the present study was to assess the mRNA expression of LHR and LRBP (mRNA protein binding), a post-transcriptional suppressor of LHR mRNA expression, in granulosa cells from the two largest follicles around the expected time of follicle deviation in Nelore heifers. First, the interval between ovulation and follicle deviation in 20 Nelore heifers was determined (2.3 ± 0.2 days after ovulation). Ovulation was hormonally synchronized, and then, heifers were slaughtered on days 2, 2.5 and 3 after ovulation (before, during and after, respectively, the expected time of follicle deviation), and granulosa cells from the two largest follicles were collected. The mRNA abundance of an LHR fragment common to all isoforms (total LHR) and LRBP was assessed by real-time RT-PCR, and LHR alternative transcripts were assessed by semiquantitative RT-PCR followed by electrophoresis. LHR mRNA expression was not detected before the expected time of deviation. Total LHR mRNA abundance was greater in the largest follicle and increased from day 2.5 to 3. In contrast, LRBP mRNA was detected starting on day 2 and was more expressed in the second largest follicle on days 2.5 and 3. The present data suggest that the expression of LHR mRNA in bovine granulosa cells is established after follicle deviation and that the lower abundance of LRBP mRNA after the expected time of deviation may contribute to greater expression of LHR in the bovine dominant follicle., (© 2015 Blackwell Verlag GmbH.)

The microenvironment of a preimplantation embryo can influence changes in development that affect postnatal phenotypes. One of the potential mediators of this effect in many species is colony-stimulating factor (CSF2), which can increase an embryo's ability to establish pregnancy after its transfer into recipients. Exposure of embryos to CSF2 during early development can also affect the pattern of development later in pregnancy in a sex-dependent manner. We therefore hypothesized that treatment of in vitro-produced embryos with CSF2 in culture would alter birth weight and postnatal growth of the resultant calf. Body weight and withers height were measured for Holstein heifer calves produced in vitro with or without 10 ng/ml CSF2 and for calves produced by artificial insemination. There were no differences in birth weight between groups; thereafter, however, calves from the CSF2-treated group experienced greater increases in body weight through 13 months of age, with only small differences in withers height. These results support the model that an embryo's postnatal characteristics can be programmed during the preimplantation period, and that CSF2 is one of the embryokines through which programming is directed. Mol. Reprod. Dev. 82: 892-897, 2015. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Fibroblast growth factor (FGF10) acts at the cumulus oocyte complex, increasing the expression of cumulus cell expansion-related genes and oocyte competency genes. We tested the hypothesis that addition of FGF10 to the maturation medium improves oocyte maturation, decreases the percentage of apoptotic oocytes and increases development to the blastocyst stage while increasing the relative abundance of developmentally important genes (COX2, CDX2 and PLAC8). In all experiments, oocytes were matured for 22 h in TCM-199 supplemented with 0, 2.5, 10 or 50 ng/ml FGF10. In Experiment 1, after maturation, oocytes were stained with Hoechst to evaluate meiosis progression (metaphase I, intermediary phases and extrusion of the first polar body) and submitted to the TUNEL assay to evaluate apoptosis. In Experiment 2, oocytes were fertilized and cultured to the blastocyst stage. Blastocysts were frozen for analysis of COX2, CDX2 and PLAC8 relative abundance. In Experiment 1, 2.5 ng/ml FGF10 increased (p < 0.05) the percentage of oocytes with extrusion of the first polar body (35%) compared to 0, 10 and 50 ng/ml FGF10 (21, 14 and 12%, respectively) and FGF10 decreased the percentage of oocytes that were TUNEL positive in all doses studied. In Experiment 2, there was no difference in the percentage of oocytes becoming blastocysts between treatments and control. Real-time RT-PCR showed a tendency of 50 ng/ml FGF10 to increase the relative abundance of COX2 and PLAC8 and of 10 ng/ml FGF10 to increase CDX2. In conclusion, the addition of FGF10 to the oocyte maturation medium improves oocyte maturation in vitro, decreases the percentage of apoptotic oocytes and tends to increase the relative abundance of developmentally important genes., (© 2014 Blackwell Verlag GmbH.)

Physiology of the adult can be modified by alterations in prenatal development driven by the maternal environment. Developmental programming, which can be established before the embryo implants in the uterus, can affect females differently than males. The mechanism by which sex-specific developmental programming is established is not known. Here we present evidence that maternal regulatory signals change female embryos differently than male embryos. In particular, actions of the maternally derived cytokine CSF2 from Day 5 to Day 7 of development affected characteristics of the embryo at Day 15 differently for females than males. CSF2 decreased length and IFNT secretion of female embryos but increased length and IFNT secretion of male embryos. Analysis of a limited number of samples indicated that changes in the transcriptome and methylome caused by CSF2 also differed between female and males. Thus, sex-specific programming by the maternal environment could occur when changes in secretion of maternally derived regulatory molecules alter development of female embryos differently than male embryos., (© 2014 by the Society for the Study of Reproduction, Inc.)

The objective was to evaluate when the LH reserve was re-established in postpartum Nellore (Bos indicus) cows by evaluating the response of the hypothalamic-pituitary axis responsiveness to exogenous GnRH or estradiol benzoate (EB). Additionally, we tested the influence of dietary supplementation (SUPL) and calf removal (CR) on the duration of postpartum anestrus. Ninety multiparous lactating Nellore cows were randomly assigned to eight groups. The EB and GnRH groups received 1.0 mg EB (N = 7), and 50 μg lecireline (N = 16), respectively. Additional cows were given the same hormones, and subjected to either nutritional supplementation (EB-SUPL, N = 9; GnRH-SUPL, N = 16), or calf removal at 72 hours after calving (EB-CR, N = 4; GnRH-CR, N = 13). The remaining two groups were the LH (12.5 mg, N = 14) and control groups (saline, N = 11). Hormones were administered weekly from 7 (±5) days postpartum to first ovulation (detection of a CL during a weekly ultrasonographic examination). Blood samples were collected just before and 2 hours (GnRH, LH, and control groups) or 18 hours (EB groups) after hormone or saline (control) administration. Ovulation occurred as early as 15 days postpartum in the GnRH group. The mean ± SEM intervals (days) from calving to first ovulation were EB, 87.7 ± 4.2; EB-CR, 20.3 ± 1.2; EB-SUPL, 60.3 ± 3.2; GnRH, 40.4 ± 2.1; GnRH-CR, 21.0 ± 1.1; GnRH-SUPL, 26.4 ± 1.1; LH, 35.6 ± 1.1; and control, 60.9 ± 2.1. We concluded that there was sufficient LH in the pituitary gland (of Nellore cows) from the second week postpartum to induce ovulation in response to exogenous GnRH. Additionally, calf removal and nutritional supplementation reduced, by 2 to 4 weeks, the interval from calving to an LH increase and ovulation induced by GnRH or EB., (Copyright © 2013. Published by Elsevier Inc.)

Heat stress is an important cause of poor development and low survival rates in bovine embryos. Experiments were conducted to test the hypothesis that Bos indicus embryos are more resistant to heat stress than are Bos taurus embryos. In experiment 1, Nelore and Jersey embryos from oocyte pick-up-derived oocytes were submitted to heat stress (96 hours post-insemination, 41 °C, 6 hours), developmental ratios were assessed at Day 7 (Day 0 = day of fertilization), and blastocysts were frozen for RNA extraction. Experiment 2 evaluated expression of COX2, CDX2, HSF1, and PLAC8 in previously frozen blastocysts. In experiment 3, Nellore and Angus embryos from oocyte pick-up-derived oocytes were submitted to heat stress (96 hours post-insemination, 41 °C, 12 hours) and transferred to recipients on Day 7. In experiment 4, embryos developed as in experiment 3 were fixed for Terminal deoxynucleotidyl transferase dUTP nick end labeling labeling and total cell counting. In experiment 1, heat stress decreased the percentage of Jersey oocytes that became blastocysts, but had no effect on Nellore embryos (34.6%, 25.0%, 39.5%, and 33.0% for Jersey control, Jersey heat-stressed, Nellore control, and Nellore heat-stressed oocytes, respectively; P < 0.05). In experiment 2, heat stress decreased (P < 0.05) expression of CDX2 and PLAC8, with higher expression of these genes in Nellore embryos than in Jersey embryos. Heat stress also decreased (P < 0.05) expression of COX2 in Jersey embryos, but had no effect on Nellore embryos. Expression of HSF1 was decreased (P < 0.05) by heat stress in both breeds, with a greater effect in Nellore embryos. In experiment 3, heat stress tended (P = 0.1) to decrease the percentage of pregnancies among cows (Day 30 to 35) that received Angus embryos. In experiment 4, heat stress increased (P < 0.05) the percentage of apoptotic blastomeres, but had no breed-specific effects. In addition, Nellore embryos had fewer (P < 0.05) Terminal deoxynucleotidyl transferase dUTP nick end labeling- positive blastomeres than did Angus embryos. We concluded that the detrimental effects of heat stress were dependent upon embryo breed and were more evident in Bos taurus embryos than in Bos indicus embryos., (Copyright © 2013 Elsevier Inc. All rights reserved.)