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Katherine B Snyder,1,2 Chase L Calkins,3 Alena Golubkova,1,2 Tyler Leiva,1,2 Camille Schlegel,1 Catherine J Hunter1,2 1Division of Pediatric Surgery, Oklahoma City, OK, 73104, USA; 2Department of Surgery, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; 3College of Medicine, The University of Oklahoma College of Medicine, Oklahoma City, OK, 73104, USACorrespondence: Catherine J Hunter, Department of Pediatric Surgery, Oklahoma Children’s Hospital, 1200 Everett Drive, ET NP 2320, Oklahoma City, OK, 73104, USA, Email catherine-hunter@ouhsc.eduBackground: Necrotizing enterocolitis (NEC) is the leading gastrointestinal cause of death of premature neonates. NEC is associated with prematurity, a hyperinflammatory response, and dysregulation of intestinal barrier function. We hypothesize that patients with NEC will have, and continue to have after recovery, an increased hyperinflammatory intestinal response compared to those patients without NEC.Methods: Neonates with NEC, those that have recovered from NEC, and those without NEC undergoing intestinal resections had specimens collected and snap frozen or generated into enteroids. The enteroids were treated with 100ug/mL lipopolysaccharide (LPS) and subjected to 24 hr of hypoxia together, then compared with untreated controls. Expression of Tumor Necrosis Factor (TNF-α) and interleukin 8 (IL-8) were evaluated via RT-qPCR and ELISA to measure inflammatory response. ANOVA determined statistical significance (p< 0.05).Results: There was no difference in inflammatory markers in recovered NEC tissue compared to non-NEC tissue on RTqPCR (p=0.701 TNF-α and 0.861 IL-8). However, recovered NEC enteroids demonstrate elevated levels of inflammatory markers after treatment compared to non-NEC enteroids after treatment on RTqPCR (p=0.0485 TNF-α, p=0.0057 IL-8) and ELISA (p=0.0354 TNF-α, p=0.0011 IL-8). Recovered NEC enteroids that underwent treatment demonstrated increased inflammatory markers compared to recovered NEC enteroids without treatment on RTqPCR (p=0.0045 TNF-α, p=0.0002 IL-8) and ELISA (p=0.034 TNF-α, p=0.0002 IL-8) suggesting a heightened inflammatory response to a second hit.Conclusion: Intestinal tissue resected from neonates with NEC has an elevated hyperinflammatory response compared to neonates recovered from NEC and neonates without NEC. Enteroids generated from patients that have recovered from NEC have a heightened inflammatory response in response to NEC inducing stimuli compared to controls. This tendency towards an increased hyperinflammatory state may be correlated with an infant’s proclivity to develop NEC and demonstrates the significance of a second hit on this tissue creating a heightened inflammatory response. This could be correlated with the impact and trajectory of an illness post recovery from NEC.Keywords: necrotizing enterocolitis, recovery, hyperinflammatory, enteroids

This experiment compared insulin sensitivity, milk production, and reproductive outcomes in dairy cows consuming excessive energy during mid to late lactation and receiving in a 2 × 2 factorial design (1) concentrate based on ground corn (CRN; n = 20) or including 8% (DM basis) of Ca salts of palm oil (CSPO; n = 20), and (2) supplemented (n = 20) or not (n = 20) with 2.5 g/d of Cr-propionate. During the experiment (d 0–203), 40 multiparous, nonpregnant, lactating 3/4 Holstein × 1/4 Gir cows (initial days in milk = 81 ± 2; mean ± SE) were offered corn silage for ad libitum consumption, and individually received concentrate formulated to allow diets to provide 160% of their daily net energy for lactation requirements. From d −15 to 203, milk production was recorded daily, blood samples collected weekly, and cow body weight (BW) and body condition score (BCS) recorded on d 0 and 203. For dry matter intake evaluation, cows from both treatments were randomly divided in 5 groups of 8 cows each, and allocated to 8 individual feeding stations for 3 d. Intake was evaluated 6 times/group. Glucose tolerance tests (GTT; 0.5 g of glucose/kg of BW) were performed on d −3, 100, and 200. Follicle aspiration for in vitro embryo production was performed via transvaginal ovum pick-up on d −1, 98, and 198. Mean DMI, net energy for lactation intake, as well as BW and BCS change were similar across treatments. On average, cows gained 40 kg of BW and 0.49 BCS during the experiment. Within weekly blood samples, CRN cows had lower serum concentrations of glucose, insulin, fatty acids, and insulin-to-glucose ratio compared with CSPO cows, suggesting increased insulin sensitivity in CRN cows. During the GTT, insulin-sensitivity traits were also greater in CRN versus CSPO cows. Supplemental Cr-propionate resulted in lower serum insulin concentrations and insulin-to-glucose ratio within CRN cows only, indicating that Cr-propionate improved basal insulin sensitivity in CRN but not in CSPO cows. During the GTT, however, Cr-propionate supplementation reduced hyperinsulinemia and insulin-to-glucose ratio across CSPO and CRN cows. Milk production, as well as number of viable oocytes collected and embryos produced within each aspiration, were not affected by treatments. Hence, replacing corn by Ca salts of palm oil in the concentrate did not improve insulin sensitivity in Holstein × Gir dairy cows consuming excessive energy during mid to late lactation, whereas Cr-supplementation was effective in improving basal insulin sensitivity in cows not receiving Ca salts of palm oil. [ABSTRACT FROM AUTHOR]

Several reports suggest use of light-emitting diode (LED) lights of various colors may improve efficiency of broiler production. The objective was to compare effects of different light sources on growth and gene expression of broilers. In a subset of a larger experiment, 48 Cobb 500 strain chicks were assigned to one of six lighting treatments with 8 birds per treatment: 1) incandescent, INC); 2) fluorescent (FL); 3) white LED (WL); 4) green LED (GL); 5) blue LED (BL); or 6) green LED on days 1-9 followed by blue LED on days 10-17 (GB). Treatments were administered by using bulbs that met the above specifications. Feed and water were available ad libitum. At termination on day 17, body weight and feed intake were determined and blood and liver samples were obtained for RNA analysis. Blood RNA was used for RNAseq analysis on a subset of samples (n = 4/treatment for WL, GL and BL) to identify target genes for further analysis. Treatment effects were analyzed by orthogonal contrasts and genes were considered differentially expressed (DE) when P ≤ 0.001 and FDR ≤ 0.10. Comparing white and colored LED light (WL vs the average of GL and BL) revealed 63 DE genes. Comparing GL to BL identified 107 DE genes. Integrative analysis using DAVID software indicated: Functions including signal, secreted, blood microparticles, extracellular exosomes and plasma membrane; KEGG pathways, including PPAR signaling; and Tissue specificity, indicating liver. Based on those analyses, we selected 12 DE genes for analysis in liver RNA by qPCR. Target genes included AvBD9, APOA4, CAT, CHAC1, FOXN2, HMGCS1, IL15, SCD, SPINK5, TTR, UBAP2, XPA. Target gene expression was normalized to that of a reference gene, RPL4, and data were log2 transformed before analysis using Proc GLM of SAS. Genes were considered DE at P < 0.05. There was no effect (P > 0.05) of any lighting treatment on expression of the selected genes of interest in liver. Similar to liver gene expression, light treatments had no effect on broiler growth, feed intake or feed efficiency to day 17 (P > 0.05). In summary, different light treatments altered gene expression in blood cells but not liver and had no effect on broiler performance. Conflicting gene expression in blood and liver suggests cell type specificity in response to lighting. Similarity of broiler performance under different lighting suggests LED lights of various colors can be used to reducing operating costs without penalizing performance. [ABSTRACT FROM AUTHOR]

Pregnancy and lactation represent a complex stage from a nutritional point of view, since energy, protein and micronutrient requirements increase during these stages. The literature describes that a well-planned plant-based diet can be sufficient in energy, macronutrients and micronutrients, with the exception of vitamin B12 and n3 polyunsaturated fatty acids, mainly EPA and DHA. During the last few years, adherence to this diet has increased rapidly in the population, so the main objective of this article is to review the current evidence on the intake and concentrations of vitamin B12, EPA and DHA during pregnancy and lactation in women following a plant-based diet. A literature search was performed in PubMed, Scopus, Web of Science and Ovid MedLine using free terms and MESH. Eleven articles were selected in this review. Well-planned vegetarian and vegan diets, with adequate supplementation of vitamin B12, EPA and DHA, are compatible during pregnancy and lactation, being a positive predictor of their content in breast milk. A similar situation was observed in plasma levels in women supplemented with B12. However, it is important to continue with research in this area that considers an adequate dietary anamnesis, integral evaluation of nutritional status, estimation of nutritional requirements and an individualized nutritional plan.

This experiment compared narasin and monensin as anticoccidials for calves naturally infected with Eimeria spp. Twenty-four weaned, non-castrated male calves ( Bos indicus  ×  B. taurus cross) were assigned to this experiment (days -8 to 42). All calves were infected by Eimeria spp. according to oocyst count per gram ( OPG ) from fecal samples collected on days -8 and -7 (average 1,059 ± 101 oocysts/g). Calves were housed in individual pens, received corn silage, mineral mix, and water for ad libitum consumption, in addition to a grain-based supplement at 200 g/head daily. Fecal samples were collected on days -2 and -1 for OPG, and results averaged as initial OPG value. Calves were blocked according to initial OPG into eight blocks of three calves each, ranked within each block according to body weight ( BW ) recorded on day -1, and assigned to receive narasin ( NAR; 0.8 mg/kg of BW), monensin ( MON; 1 mg/kg of BW), or no ionophore ( CON ; negative control). Ionophores were added to the grain-based supplement, and offered from days 0 to 42 of the experiment. Calf BW was recorded on days 7, 14, 21, 28, 35, and 42. Fecal samples were collected on days 6 and 7, 13 and 14, 20 and 21, 26 and 27, 34 and 35, and 41 and 42 for OPG analysis, and results from samples collected on consecutive days were averaged. Aliquoted fecal samples were also pooled across calves from the same treatment and collection days, and used to determine the prevalence of individual species of Eimeria . No treatment effects were detected ( P  ≥ 0.51) for calf BW or growth rate. A treatment × day interaction was detected ( P  < 0.01) for OPG, as NAR and MON calves had less ( P  < 0.01) OPG compared with CON calves beginning on day 7. The OPG was also less ( P  ≤ 0.03) in MON compared with NAR calves on days 7, 14, and 28, but did not differ ( P  ≥ 0.48) on days 21, 35, and 42. The anticoccidial efficacy of NAR and MON did not differ ( P  ≥ 0.16) when calculated across all Eimeria spp., or according to prevalence of E. bovis and E. alabamensins . A treatment × day interaction was detected ( P  = 0.04) for anticoccidial efficacy to E. alabamensis , which was greater ( P  < 0.01) in MON calves on days 7 and 14 and did not differ ( P  ≥ 0.40) afterward. Collectively, both ionophores were similarly effective in controlling coccidiosis upon completion of the 42-d study, although the anticoccidial effects of monensin were noted earlier in the experiment. Nonetheless, these results corroborate narasin as an efficient anticoccidial ionophore for naturally infected calves., Competing Interests: Tiago Leiva, José Manuel Correia de Simas, Pedro V. F. Lasmar, and Rodrigo L. Valarelli are employed by the funder of this project (Elanco Saúde Animal; São Paulo, Brazil) and contributed to research design and interpretation of results. All other authors of this manuscript have no additional conflict of interest to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Meta-analyses were performed to quantitatively summarize the effects of monensin on in vivo methane (CH4) production in beef cattle, and differentiate these outcomes according to dietary management, dose of monensin, and length of monensin supplementation. Data from 11 manuscripts describing 20 individual studies were used, and CH4 was converted to g/d when required. Studies were classified according to dose of monensin (mg/kg of diet dry matter), length of monensin supplementation prior to the last CH4 measurement, feeding management (ad libitum vs. limited-fed), and diet profile (high-forage or high-concentrate diets). Variance among studies were assessed using a χ² test of heterogeneity and calculated using I² statistics. The inclusion of monensin decreased ( P  < 0.01) CH4 production by 17.5 g/d when all studies were analyzed together. A moderate ( P  < 0.01) heterogeneity ( I²  = 55%) was detected for CH4 production estimates between studies; thus, meta-analyses were performed within classes. The reduction in CH4 differed ( P  < 0.01) according to dose of monensin, as it decreased ( P  < 0.01) by 25.6 g/d when the high recommended dose range was used (32 to 44 mg/kg), and tended to decrease ( P  ≤ 0.07) by 9.7 and 13.5 g/d when the moderate (≤31 mg/kg) and above recommended (≥45 mg/kg) doses were used, respectively. The reduction in CH4 also differed ( P  < 0.01) according to the length of monensin supplementation. Monensin decreased ( P  ≤ 0.05) CH4 production by 24.3 g/d when supplemented for <15 d, by 15.4 g/d when supplemented from 23 to 33 d, by 24.3 g/d when supplemented from 52 to 79 d, and tended to decrease ( P  = 0.06) CH4 production by 3.21 g/d when supplemented from 94 to 161 d. The reduction in CH4 did not differ ( P  = 0.37) according to diet profile, despite a 30% difference in reduction when monensin was added to high-forage (20.89 g/d) compared with high-concentrate diets (14.6 g/d). The reduction in CH4 tended to differ according to feeding management ( P  = 0.08), decreasing by 22.9 g/d ( P  < 0.01) when monensin was added to diets offered ad libitum, and by 11.5 g/d ( P  = 0.05) in limit-fed diets. Collectively, this study provides novel insights and further corroborates monensin as CH4 mitigation strategy in beef cattle operations. The most effective responses were observed during the first 79 d of monensin supplementation, and when monensin was included between 32 to 44 mg/kg of diet, was added to high-forage diets, and added to diets fed ad libitum., Competing Interests: Tiago Leiva, José Manuel Correia de Simas, and Pedro V. F. Lasmar are employed by the funder of this project (Elanco Saúde Animal; São Paulo, Brazil) and contributed to research design and interpretation of results. We of this manuscript have no additional conflict of interest to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objective: Traumatic lumbar hernias are a rare entity mostly seen with high-impact, blunt abdominal trauma. This injury occurs when there is disruption of the posterior musculature along with bony structures, allowing for herniation of abdominal contents. There are minimal cases of this entity reported in adults, but even fewer in the pediatric population., Methods: We describe 3 cases of traumatic lumbar hernia at our institution as well as provide a review of the literature to elucidate the most common mechanisms, severity of injury, and associated injuries., Results: Traumatic lumbar hernia is most commonly seen in restrained passengers involved in motor vehicle collisions. A majority of cases are diagnosed using computed tomography imaging and less frequently during primary surgical exploration. The most common associated injuries were mesenteric and bowel injuries, followed by spinal and chest trauma. Traumatic lumbar hernia often leads to prolonged hospital stays and increased need for posthospital rehabilitation because of associated traumatic comorbidities., Conclusions: Traumatic lumbar hernia is a rare entity in children, and early suspicion and identification of associated injuries is necessary in the management of these patients., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Grant writing takes significant time and effort and often may be elusive, especially on a first attempt. After the rejection of a grant, many investigators face a dilemma regarding the best next steps. In this article, we discuss the options of revision versus resubmission and how to navigate these decisions., Methods: The literature was surveyed, including review articles, personal perspectives, and editorial pieces regarding the grant writing and funding processes. The National Institute of Health database was reviewed, and data were extrapolated from the past 10 years of funding percentages and rates of both R01 initial applications and resubmissions. Recommendations were then generated based on pertinent literature and experience from the authors., Results: The grant writing process involves many checkpoints between conception and funding. Only approximately 15% of R01 and R01-equivalent grants are accepted for funding on the initial submission. However, this statistic increases to >30% if the appropriate steps are taken to revise and resubmit the grant. These steps include consulting co-investigators, modifying hypotheses, drafting a succinct "Introduction" document, and many more. Knowing the options after the rejection of an original submission plays a huge role in the ultimate success of the grant., Conclusion: Although receiving funding for an original grant can be difficult, with appropriate guidance, it may seem more feasible than initially expected. Adequately responding to the critiques of the grant and revising the grant appropriately can make or break the outcome of the grant., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Necrotizing enterocolitis (NEC) is a devastating disease of premature neonates with substantial morbidity and mortality. Necrotizing enterocolitis is associated with prematurity, a hyperinflammatory response, and dysregulation of intestinal barrier function. We hypothesize that patients with NEC will have an increased hyperinflammatory intestinal response compared with those without NEC. Patients and Methods: Enteroids were generated from intestinal tissue from neonates undergoing resection. They were treated with 100 mcg/mL lipopolysaccharide (LPS), subjected to 24 hours of hypoxia inducing experimental NEC, then compared with untreated controls. Expression of tumor necrosis factor (TNF-α) and interleukin 8 (IL-8) were evaluated via reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) to measure inflammatory response. Analysis of variance (ANOVA) determined statistical significance (p < 0.05). Results: Treated NEC-derived enteroids expressed significantly higher levels of IL-8 (RT-qPCR, p = 0.003; ELISA, p = 0.0002) compared with untreated NEC-derived enteroids with an increase in inflammatory marker concentration in those with a greater degree of prematurity (ELISA, p = 0.0015). A higher level of IL-8 was seen in NEC-derived enteroids compared with control after treatment (RT-qPCR, p = 0.024). Tumor necrosis factor-α levels were elevated in treated NEC-derived enteroids compared with untreated NEC-derived enteroids (RT-qPCR, p = 0.006; ELISA, p = 0.002) and compared with treated non-NEC-derived enteroids (RT-qPCR, p = 0.025; ELISA, p < 0.0001). Conclusions: Enteroids generated from neonates with NEC have an elevated hyperinflammatory response in response to NEC-inducing stimuli compared with controls. Enteroids generated from neonates with NEC with a greater degree of prematurity have a larger increase in inflammatory markers. This tendency toward a hyperinflammatory state may be correlated with an infant's proclivity to develop NEC and further demonstrates the hyperinflammatory state of prematurity.

Necrotizing enterocolitis (NEC) is a neonatal intestinal disease associated with oxidative stress. The targets of peroxidation and the role of the innate intestinal epithelial antioxidant defense system are ill-defined. We hypothesized that oxidative stress in NEC correlates with oxidized GSH redox potentials, lipid peroxidation, and a dysfunctional antioxidant system. Methods : Intestinal samples from infants +/- NEC were generated into enteroids and incubated with lipopolysaccharide (LPS) and hypoxia to induce experimental NEC. HPLC assayed GSH redox potentials. Lipid peroxidation was measured by flow cytometry. Immunoblotting measured glutathione peroxidase 4 (Gpx4) expression. Results : GSH redox potentials were more oxidized in NEC intestinal tissue and enteroids as compared to controls. Lipid radicals in NEC-induced enteroids were significantly increased. Human intestinal tissue with active NEC and treated enteroid cultures revealed decreased levels of Gpx4. Conclusions : The ability of neonatal intestine to mitigate radical accumulation plays a role in its capacity to overcome oxidative stress. Accumulation of lipid radicals is confirmed after treatment of enteroids with NEC-triggering stimuli. Decreased Gpx4 diminishes a cell's ability to effectively neutralize lipid radicals. When lipid peroxidation overwhelms antioxidant machinery, cellular death ensues. Identification of the mechanisms behind GSH-dependent enzyme dysfunction in NEC may provide insights into strategies for reversing radical damage.

Background: Procalcitonin (PCT) is a biomarker for sepsis, but its utility has not been investigated in necrotizing enterocolitis (NEC). Necrotizing enterocolitis is a devastating multisystem disease of infants that in severe cases requires surgical intervention. We hypothesize that an elevated PCT will be associated with surgical NEC. Patients and Methods: After obtaining Institutional Review Board (IRB) approval (#12655), we performed a single institution retrospective case control study between 2010 and 2021 of infants up to three months of age. Inclusion criteria was PCT drawn within 72 hours of NEC or sepsis diagnosis. Control infants had a PCT drawn in the absence of infectious symptoms. Recursive partitioning (RP) identified PCT cutoffs. Categorical variable associations were tested using Fisher exact or χ 2 tests. Continuous variables were tested using Wilcoxon rank sum test, Student t-test, and Kruskal-Wallis test. Adjusted associations of PCT and other covariables with NEC or sepsis versus controls were obtained via multinomial logistic regression analysis. Results: We identified 49 patients with NEC, 71 with sepsis, and 523 control patients. Based on RP, we selected two PCT cutoffs: 1.4 ng/mL and 3.19 ng/ml. A PCT of ≥1.4 ng/mL was associated with surgical (n = 16) compared with medical (n = 33) NEC (87.5% vs. 39.4%; p = 0.0015). A PCT of ≥1.4 ng/mL was associated with NEC versus control (p < 0.0001) even when adjusting for prematurity and excluding stage IA/IB NEC (odds ratio [OR], 28.46; 95% confidence interval [CI], 11.27-71.88). A PCT of 1.4-3.19 ng/mL was associated with both NEC (adjusted odds ratio [aOR], 11.43; 95% CI, 2.57-50.78) and sepsis (aOR, 6.63; 95% CI, 2.66-16.55) compared with controls. Conclusions: A PCT of ≥1.4 ng/mL is associated with surgical NEC and may be a potential indicator for risk of disease progression.

AbstractBackground: Attending surgeons must maintain balance between promoting education and assuring safe, transparent patient care. This investigation aimed to define ethics that guide surgical training. We hypothesized that resident autonomy in the operating room is influenced by attending approach to patients, specifically patients considered to be vulnerable., Materials and Methods: After IRB approval, surgeons from three institutions were invited to participate in a pilot, survey, exploring how principles of patient autonomy, physician beneficence, nonmaleficence, and justice apply to participant opinions. Responses were transcribed and coded for quantitative and qualitative analysis., Results: 51 attendings and 55 residents completed the survey. We identified that patient autonomy is upheld through transparent consent practices. Intraoperative supervision is a key practice that maintains the principles of physician beneficence and nonmaleficence and mitigates the risk of resident participation. Vulnerable patients were defined by respondents as those unable to participate in their own consent and those limited by social determinants of health and barriers to medical literacy. In contrast, resident participation is not limited in the care of vulnerable patients but is restricted in cases of higher complexity and those procedures deemed to have lower error margins., Conclusions: Although residents measure the success of their training based on their level of intraoperative independence, autonomy afforded to the resident does not only depend on objective skill. There are ethical considerations that the attending must navigate as they decide on effective teaching and safe surgical management, which is especially relevant in the care of complex cases.

Introduction: Necrotizing enterocolitis (NEC) is a gastrointestinal disease of premature neonates. We previously validated a NEC enteroid model derived from human infant intestinal tissue. Typical enteroid configuration is basolateral-out (BO) without direct access to the luminal (apical) surface. Apical access is necessary to allow physiologic comparison of pathogen interaction with the intestinal epithelial barrier. We hypothesize that apical-out (AO) enteroids will provide a relevant NEC model to study this relationship., Methods: Following the institutional review board approval (#11610-11611), neonatal intestinal tissue was collected from surgical specimens. Stem cells were collected; enteroids were generated and grown to maturity in BO conformation then everted to AO. Enteroids were untreated or treated for 24 h with 100 μg/mL lipopolysaccharide and hypoxia. Protein and gene expression were analyzed for inflammatory markers, tight junction (TJ) proteins and permeability characteristic of NEC., Results: Apical TJ protein zonula occludens-1 and basolateral protein β-catenin immunofluorescence confirmed AO configuration. Treated AO enteroids had significantly increased messenger RNA (P = 0.001) and protein levels (P < 0.0001) of tumor necrosis factor-α compared to controls. Corrected total cell fluorescence of toll-like receptor 4 was significantly increased in treated AO enteroids compared to control (P = 0.002). Occludin was found to have significantly decreased messenger RNA in treated AO enteroids (P = 0.003). Expression of other TJ proteins claudins-1, -4 and zonula occludens-1 was significantly decreased in treated AO enteroids (P < 0.05)., Conclusions: AO enteroids present an innovative model for NEC with increased inflammation and gut barrier restructuring. This model allows for a biologically relevant investigation of the interaction between the pathogen and the intestinal epithelial barrier in NEC., (Copyright © 2022 Elsevier Inc. All rights reserved.)

This experiment evaluated the effects of supplementing narasin during late-gestation and lactation on productive and physiological responses of Bos indicus beef heifers and their offspring. Pregnant, nulliparous Nelore heifers ( N = 88) that conceived under the same fixed-time artificial insemination protocol and to the same sire were used. Heifers were ranked by maternal ability genomic score, body weight ( BW ) and body condition score ( BCS ) and allocated to 44 drylot pens (2 heifers per pen; 10 × 25 m). Pens were ranked by these traits and alternatively assigned to receive ( NAR ) or not ( CON ) 0.260 mg of narasin/kg of heifer BW daily (Elanco Saúde Animal, São Paulo, Brazil). Narasin was mixed into a supplement offered at 0.30% of heifer BW from day 0 until heifers weaned their calves (day 316), whereas CON heifers received the same supplement without narasin addition. Heifers received Urochloa brizantha hay and water for ad libitum consumption (days 0 to 316) and calved between days 97 to 112 of the experiment. After calving, heifers and offspring had access to hay and supplement; hence, supplements and narasin were offered according to heifer + calf BW beginning on day 162. No treatment differences were detected ( P ≥ 0.18) for heifer BW and BCS during the experiment, although BW loss from day 0 to calving was less ( P = 0.04) in NAR compared to CON heifers. Hay intake during the experiment did not differ ( P = 0.79) between treatments. Serum IGF-I concentrations were greater ( P = 0.05) for NAR heifers on day 60 of the experiment and did not differ ( P ≥ 0.28) between treatments 24 h and 30 d after calving (treatment × day interaction; P = 0.04). No treatment effects were detected ( P ≥ 0.58) for calf birth BW. Serum concentrations of total protein 24 h after birth were greater ( P = 0.04) in calves from NAR compared with CON heifers, and a tendency ( P = 0.10) for a similar outcome was noted for serum IgG concentrations. Diarrhea incidence did not differ ( P = 0.16) between treatments, although the number of total diarrhea cases per calf were greater ( P = 0.03) in the CON offspring. Growth rate of calves from NAR heifers tended ( P = 0.08) to be greater, resulting in heavier calves at weaning ( P ≤ 0.04) compared with CON offspring. Collectively, these outcomes indicate narasin supplementation to beef heifers as a nutritional alternative to improve cow-calf productivity via developmental programming effects during gestation, as well as direct consumption by their nursing offspring., Competing Interests: Rodrigo L. Valarelli, Pedro V. F. Lasmar, and Tiago Leiva are employed by the funder of this project (Elanco Saúde Animal) and contributed to interpretation of research results. All other authors of this manuscript have no additional conflict of interest to report., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Necrotizing enterocolitis (NEC) continues to be a major cause of morbidity and mortality in preterm infants. Despite decades of research in NEC, no reliable biomarkers can accurately diagnose NEC or predict patient prognosis. The recent emergence of multi-omics could potentially shift NEC biomarker discovery, particularly when evaluated using systems biology techniques. Furthermore, the use of machine learning and artificial intelligence in analyzing this 'big data' could enable novel interpretations of NEC subtypes, disease progression, and potential therapeutic targets, allowing for integration with personalized medicine approaches. In this review, we evaluate studies using omics technologies and machine learning in the diagnosis of NEC. Future implications and challenges inherent to the field are also discussed., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Necrotizing enterocolitis (NEC) is a devastating disease that primarily affects the gastrointestinal tract of premature neonates. The diagnosis and treatment of NEC remain challenging. New biomarkers and potential treatments for NEC have emerged in recent years, leading to the potential of earlier therapeutic intervention and improved outcomes. This paper aims to provide a review of the most recent diagnostic indicators and therapeutics of NEC along with a brief overview of future directions of research into this disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Ileocolic intussusception is a common gastrointestinal emergency that occurs in infancy. Many cases are caused by anatomic lead points, such as hypertrophied Peyer's patches. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), commonly presents with respiratory symptoms, however, its relation to intussusception remains unknown. Methods: Two cases are reported as well as a review of pertinent English-language literature on the topic. Results: We present two cases of intussusception in COVID-19-positive patients, including the first known case of a lead point with tissue polymerase chain reaction (PCR) confirming COVID-19 positivity, and compare these findings to a review of the recent literature. Intussusception in COVID-19-positive patients is becoming more prevalent and more often requires operative treatment. Discussion: We offer evidence that intussusception can be the presenting symptom in the absence of COVID-19-related respiratory symptoms. There also seems to be a trend toward the need for operative intervention compared with COVID-19-negative intussusception. The presence of SARS-CoV-2 can be confirmed via PCR in specific lead points (lymph nodes), directly causing the intussusception. Conclusions: Providers should have a low threshold to suspect and diagnose intussusception as operative treatment is more readily used in COVID-19-positive pediatric patients with gastrointestinal symptoms.

Enteroids are an emerging research tool in the study of inflammatory bowel diseases such as necrotizing enterocolitis (NEC). They are traditionally grown in the basolateral-out (BO) conformation, where the apical surface of the epithelial cell faces the inner lumen. In this model, access to the luminal surface of enteroids for treatment and experimentation is challenging, which limits the ability to study host-pathogen interactions. To circumvent this, a neonatal apical-out (AO) model for necrotizing enterocolitis was created. Since intestinal epithelial cell permeability changes are pathognomonic for NEC, this protocol outlines using lucifer yellow (LY) as a marker of paracellular permeability. LY traverses the intestinal epithelial barrier via all three major paracellular pathways: pore, leak, and unrestricted. Using LY in an AO model allows for a broader study of permeability in NEC. Following IRB approval and parental consent, surgical samples of intestinal tissue were collected from human preterm neonates. Intestinal stem cells were harvested via crypt isolation and used to grow enteroids. Enteroids were grown to maturity and then transformed AO or left in BO conformation. These were either not treated (control) or were treated with lipopolysaccharide (LPS) and subjected to hypoxic conditions for the induction of in vitro NEC. LY was used to assess for permeability. Immunofluorescent staining of the apical protein zonula occludens-1 and basolateral protein β-catenin confirmed AO conformation. Both AO and BO enteroids treated with LPS and hypoxia demonstrated significantly increased paracellular permeability compared to controls. Both AO and BO enteroids showed increased uptake of LY into the lumen of the treated enteroids compared to controls. The utilization of LY in an AO enteroid model allows for the investigation of all three major pathways of paracellular permeability. It additionally allows for the investigation of host-pathogen interactions and how this may affect permeability compared to the BO enteroid model.

Background: Despite the importance of social justice advocacy, surgeon attitudes toward individual involvement vary. We hypothesized that the majority of surgeons in this study, regardless of gender or training level, believe that surgeons should be involved in social justice movements., Methods: A survey was distributed to surgical faculty and trainees at three academic tertiary care centers. Participation was anonymous with 123 respondents. Chi-square and Fisher's exact test were used for analysis with significance accepted when p < 0.05. Thematic analysis was performed on free responses., Results: The response rate was 46%. Compared to men, women were more likely to state that surgeons should be involved (86% vs 64%, p = 0.01) and were personally involved in social justice advocacy (86% vs 51%, p = 0.0002). Social justice issues reported as most important to surgeons differed significantly by gender (p = 0.008). Generated themes for why certain types of advocacy involvement were inappropriate were personal choices, professionalism and relationships., Conclusions: Social justice advocacy is important to most surgeons in this study, especially women. This emphasizes the need to incorporate advocacy into surgical practice., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of motoneurons, which is preceded by loss of neuromuscular connections in a "dying back" process. Neuregulin-1 (Nrg1) is a neurotrophic factor essential for the development and maintenance of neuromuscular junctions, and Nrg1 receptor ErbB4 loss-of-function mutations have been reported as causative for ALS. Our main goal was to investigate the role of Nrg1 type I (Nrg1-I) in SOD1(G93A) mice muscles. We overexpressed Nrg1-I by means of an adeno-associated viral (AAV) vector, and investigated its effect by means of neurophysiological techniques assessing neuromuscular function, as well as molecular approaches (RT-PCR, western blot, immunohistochemistry, ELISA) to determine the mechanisms underlying Nrg1-I action. AAV-Nrg1-I intramuscular administration promoted motor axon collateral sprouting by acting on terminal Schwann cells, preventing denervation of the injected muscles through Akt and ERK1/2 pathways. We further used a model of muscle partial denervation by transecting the L4 spinal nerve. AAV-Nrg1-I intramuscular injection enhanced muscle reinnervation by collateral sprouting, whereas administration of lapatinib (ErbB receptor inhibitor) completely blocked it. We demonstrated that Nrg1-I plays a crucial role in the collateral reinnervation process, opening a new window for developing novel ALS therapies for functional recovery rather than preservation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Increasing meal frequency is commonly used in the clinical practice as part of the nutritional treatment of patients with type 2 Diabetes Mellitus (DM2), although its effect on metabolic control parameters is controversial., Aim: To evaluate the association of energy intake, meal frequency, and amount of carbohydrates with fasting plasma glucose and glycosylated hemoglobin in a group of patients with DM2 without insulin therapy., Material and Methods: Dietary intake was evaluated in 60 subjects with DM2 through three-day food records. The meal frequency was estimated establishing the main meal times considering snacks., Results: Meal frequency was 4.7 ± 1.1 times per day. There was a positive association between glycosylated and fasting blood glucose levels (p <0.01). Meal frequency was associated with energy intake (p <0.01). When meal frequency, available carbohydrates and energy intake, body mass index and fasting plasma glucose were analyzed in a multiple linear regression model, fasting blood glucose was the variable that best predicted changes in glycosylated hemoglobin (45.5%). Meal frequency had no association with glycosylated hemoglobin., Conclusions: Meal frequency showed no association with metabolic control parameters in DM2 patients.

Tuberculosis (TB), caused by the pathogen Mycobacterium tuberculosis (MTB), remains a disease of high importance to global public health. Studies into the population structure of MTB have become vital to monitoring possible outbreaks and also to develop strategies regarding disease control. Although Chile has a low incidence of MTB, the current rates of migration have the potential to change this scenario. We collected and analyzed a total of 458 M. tuberculosis isolates (1 isolate per patient) originating from all 15 regions of Chile. The isolates were genotyped using the spoligotyping method and the data obtained were analyzed and compared with the SITVIT2 database. A total of 169 different patterns were identified, of which, 119 patterns (408 strains) corresponded to Spoligotype International Types (SITs) and 50 patterns corresponded to orphan strains. The most abundantly represented SITs/lineages were: SIT53/T1 (11.57%), SIT33/LAM3 (9.6%), SIT42/LAM9 (9.39%), SIT50/H3 (5.9%), SIT37/T3 (5%); analysis of the spoligotyping minimum spanning tree as well as spoligoforest were suggestive of a recent expansion of SIT42, SIT50 and SIT37; all of which potentially evolved from SIT53. The most abundantly represented lineages were LAM (40.6%), T (34.1%) and Haarlem (13.5%). LAM was more prevalent in the Santiago (43.6%) and Concepción (44.1%) isolates, rather than the Iquique (29.4%) strains. The proportion of X lineage was appreciably higher in Iquique and Concepción (11.7% in both) as compared to Santiago (1.6%). Global analysis of MTB lineage distribution in Chile versus neighboring countries showed that evolutionary recent lineages (LAM, T and Haarlem) accounted together for 88.2% of isolates in Chile, a pattern which mirrored MTB lineage distribution in neighboring countries (n = 7378 isolates recorded in SITVIT2 database for Peru, Brazil, Paraguay, and Argentina; and published studies), highlighting epidemiological advantage of Euro-American lineages in this region. Finally, we also observed exclusive emergence of patterns SIT4014/X1 and SIT4015 (unknown lineage signature) that have hitherto been found exclusively in Chile, indicating that conditions specific to Chile, along with the unique genetic makeup of the Chilean population, might have allowed for a possible co-evolution leading to the success of these emerging genotypes.

Background: The incidence of acquired resistance to antituberculous drugs of Mycobacterium tuberculosis in Chile is approximately 23%., Aim: To analyze the mutations associated with drug resistance in drug resistant strains of Mycobacterium tuberculosis., Material and Methods: In 28 drug resistant Mycobacterium tuberculosis strains isolated in Chile, genes leading to drug resistance were studied. DNA was amplified by polymerase chain reaction (PCR) and sequencing was carried out using the ABI PRISM big dye terminator cycle sequencing ready reaction kit., Results: In rifampicin-resistant strains, the mutations in rpoβ gene were in the codons S531W/L (56%), D516Y (16%) and D516V (16%). The predominant mutation in katG gene was in the codon S315L (73%) in isoniazid-resistant strains. The mutation S95T was found in the 71% of ciprofloxacin resistant strains. Only one ethambutol resistant strain had the M306I mutation. Three unreported mutations in katG were identified., Conclusions: Drug resistance associated mutations of Mycobacterium tuberculosis isolated in Chile were similar to those reported abroad.

The aim of this paper is to evaluate the effectiveness of podometry to measure the pressure developed over the feet and the value of these findings to help in the prevention of the plantar neuropathic ulcer in patients bearing Hansen's disease. We evaluated 13 patients with impaired plantar pain and touch sensations and 17 normal patients. All the patients were submitted to static evaluation using the podometer. The system employed was the "Midcapteur" commercial podometer composed of a platform for acquisition of analogic data capable of registering the segmental pressures applied to the feet. These data are read by a 386 IBM/PC compatible computer that registers the graphic patterns obtained from the pressures developed and also calculates the modes of pressure distribution in the four quadrants of the foot. These data obtained by means of static podometry were compared to the clinical evaluation of pain and touch sensation of the feet in hansenian patients. The results demonstrate that podometery is an efficient method for evaluating the pressure in impaired feet in Hansen's disease and is a progression of neuropathic ulcer; it is sensitive in the identification of the spots of increased pressure in anesthetic and anomalous areas, asymmetries and in correlating the presence of ulcers with increased pressure.