Dietary Milk Phospholipids Increase Body Fat and Modulate Gut Permeability, Systemic Inflammation, and Lipid Metabolism in Mice.

The study aimed at how dietary milk polar lipids affect gut permeability, systemic inflammation, and lipid metabolism during diet-induced obesity (DIO). C57BL/6J mice (n = 6x3) were fed diets with 34% fat as energy for 15 weeks: (1) modified AIN-93G diet (CO); (2) CO with milk gangliosides (GG); (3) CO with milk phospholipids (MPL). Gut permeability was assessed by FITC-dextran and sugar absorption tests. Intestinal tight junction proteins were evaluated by Western blot. Plasma cytokines were measured by immunoassay. Body composition was assessed by magnetic resonance imaging. Tissue lipid profiles were obtained by thin layer chromatography. Hepatic expression of genes associated with lipid metabolism was assessed by RT-qPCR. MPL increased the efficiency of converting food into body fat and facilitated body fat accumulation compared with CO. MPL and GG did not affect fasting glucose or HOMA-IR during DIO. MPL increased while GG decreased plasma TG compared with CO. MPL decreased phospholipids subclasses in the muscle while increased those in the liver compared with CO. GG and MPL had little effect on hepatic expression of genes associated with lipid metabolism. Compared with CO, MPL decreased polar lipids content in colon mucosa. Small intestinal permeability decreased while colon permeability increased and then recovered during the feeding period. High-fat feeding increased plasma endotoxin after DIO but did not affect plasma cytokines. MPL and GG did not affect plasma endotoxin, adipokines and inflammatory cytokines. After the establishment of obesity, MPL increased gut permeability to large molecules but decreased intestinal absorption of small molecules while GG tended to have the opposite effects. MPL and GG decreased mannitol and sucralose excretions, which peaked at d 45 in the CO group. MPL decreased occludin in jejunum mucosa compared with CO. GG and MPL did not affect zonula occludens-1 in gut mucosa. In conclusion, during DIO, milk GG decreased gut permeability, and had little effect on systemic inflammation and lipid metabolism; MPL facilitated body fat accumulation, decreased gut permeability, did not affect systemic inflammation.

An Azide-Free Synthesis of Metallodiazomethanes Using Nitrous Oxide.

Diazo compounds are valuable reagents in synthesis but usually require the use of potentially explosive or toxic starting materials. Here, we report the synthesis and isolation of alkali metal diazomethanides by the reaction of metalated ylides with nitrous oxide, resulting in a formal exchange of the phosphine ligand by dinitrogen. The reaction proceeds through a Wittig-like mechanism via a [3 + 2] cycloaddition of N2O across the ylide bond with release of phosphine oxide. The metalated diazomethanes exhibit an increased thermal stability due to the stronger binding of N2 compared to neutral diazomethanes. This is reflected in short C-N distances and red-shifted N-N vibrations and enables versatile applications such as for the preparation of transition metal diazomethanide complexes and the synthesis of 1,2,3-triazoles from nitriles, diazoacetates from carbon dioxide, or alkynes from aldehydes.

Pasture-finishing of cattle in Western U.S. rangelands improves markers of animal metabolic health and nutritional compounds in beef.

As environmental and health concerns of beef production and consumption mount, there is growing interest in agroecological production methods, including finishing beef cattle on pastures with phytochemically diverse grasses, forbs, and/or shrubs. The goal of this metabolomics, lipidomics, and fatty acid methyl ester profiling study was to compare meat (pectoralis profundus) of Black Angus cattle from two commercial US beef finishing systems (pasture-finished on Western U.S. rangeland; n = 18 and grain-finished in a Midwest U.S. feedlot; n = 18). A total of 907 out of 1575 compounds differed in abundance between pasture-finished and grain-finished beef samples (all, false discovery rate adjusted P < 0.05). Pasture-finished beef contained higher levels of phenolic antioxidants (2.6-fold), alpha-tocopherol (3.1-fold), nicotinate/vitamin B3 (9.4-fold), choline (1.2-fold), myo-inositol (1.8-fold), and omega-3 fatty acids (4.1-fold). Grain-finished beef contained higher levels of gamma-tocopherol (14.6-fold), nicotinamide/vitamin B3 (1.5-fold), pantothenate/vitamin B5 (1.3-fold), and pyridoxine/vitamin B6 (1.3-fold); indicating that feeding some grain (by-products) could be beneficial to increase levels of certain B-vitamins. Pasture-finished beef samples also displayed lower levels of oxidative stress (homocysteine, 0.6-fold; and 4-hydroxy-nonenal-glutathione, 0.4-fold) and improved mitochondrial function (1.3-fold) compared to grain-finished animals. Two potential metabolites of fluoroquinolone antibiotics, 2,8-quinolinediol and 2,8-quinolinediol sulfate, were only observed in grain-finished beef, though the source remains unknown. While pasture-finished cattle displayed improved markers of metabolic health and concentrated additional, potentially health-promoting compounds in their meat, our findings should not be interpreted as that grain-finished beef is unhealthy to consume. Randomized controlled trials in humans are required to further assess whether observed differences between pasture-finished and feedlot-finished beef have an appreciable effect on human health.

Quantum Enhanced Balanced Heterodyne Readout for Differential Interferometry.

Conventional heterodyne readout schemes are now under reconsideration due to the realization of techniques to evade its inherent 3 dB signal-to-noise penalty. The application of high-frequency, quadrature-entangled, two-mode squeezed states can further improve the readout sensitivity of audio-band signals. In this Letter, we experimentally demonstrate quantum-enhanced heterodyne readout of two spatially distinct interferometers with direct optical signal combination, circumventing the 3 dB heterodyne signal-to-noise penalty. Applying a high-frequency, quadrature-entangled, two-mode squeezed state, we show further signal-to-noise improvement of an injected audio band signal of 3.5 dB. This technique is applicable for quantum-limited high-precision experiments, with application to searches for quantum gravity, searches for dark matter, gravitational wave detection, and wavelength-multiplexed quantum communication.

Analysis of the immunomodulatory properties of mycobacterium cell wall fraction on the cytokine production of peripheral blood mononuclear cells of healthy dogs.

BACKGROUND: Mycobacterium cell wall fraction (MCWF) is derived from nonpathogenic Mycobacterium phlei and is used as an immunomodulatory compound in clinical practice, yet its mode-of-action requires further research. OBJECTIVE: To evaluate the host response to MCWF in canine peripheral blood mononuclear cells (PBMCs) by using enzyme-linked immunosorbent assays (ELISA) and quantitative reverse transcription (qRT)-PCR for assessment of cytokines. ANIMALS: Eight healthy Labrador retrievers. MATERIALS AND METHODS: PBMCs were isolated from whole blood using density centrifugation. The cells were cultured with different concentrations of MCWF or a potent stimulator of cytokine production, phorbol 12-myristate 13-acetate/ionomycin, or left in cell culture medium for 24, 48 and 72 h. Cytokines were measured by ELISA for interleukin (IL)-4, IL-10 and interferon-gamma (IFN-γ), and by qRT-PCR for IL-4, IL-10, IL-13, IFN-γ, tumour necrosis factor alpha (TNF-α) and transforming growth factor-beta. RESULTS: A significant increase of IL-10 messenger ribonucleic acid (mRNA) was detected at all time points for all concentrations of MCWF (p < 0.05). Protein analysis reflected this finding, with a maximum IL-10 concentration of 300.6 ± 38.3 µg/mL. Compared to the negative control, post-stimulation elevation of IFN-γ mRNA was noted at 24 h with all concentrations of MCWF (p < 0.01), and TNF-α mRNA was increased for 0.5 µg/dL MCWF only at 72 h (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: MCWF stimulation of PBMCs results in the elevation of both proinflammatory and regulatory cytokine mRNA. Further research into the role of MCWF as a systemically administered regulatory immunomodulator or adjuvant to allergen-specific immunotherapy should be considered.

Role of Interventional Radiology in Managing Primary and Metastatic Breast Cancer.

Percutaneous image-guided locoregional therapies are emerging in the treatment of primary and metastatic breast cancer. Cryoablation has emerged as the dominant ablative approach as an alternative to surgery for primary breast cancer in patients who do not wish to have surgery or are poor surgical candidates. Cryoablation is well tolerated and provides excellent local control and cosmesis. Thermal ablation may also be used in the treatment of oligometastatic breast cancer, allowing patients to achieve long disease-free intervals. Transarterial therapies have been studied in the treatment of oligoprogressive hepatic metastasis, though further supportive data would be helpful to demonstrate its efficacy.

Cryoablation of Primary Breast Cancer in Patients Ineligible for Clinical Trials: A Multiinstitutional Study.

Background: Breast cancer cryoablation clinical trials have strict inclusion criteria that exclude patients with potentially treatable disease. Objective: This study's purpose was to evaluate the safety and outcomes of breast cancer cryoablation without surgical excision in patients ineligible for prospective cryoablation clinical trials due to unfavorable patient or tumor characteristics. Methods: This retrospective study included women who underwent cryoablation of biopsy-proven unifocal primary breast cancer with locally curative intent, without surgical excision, despite being ineligible for (and thus excluded from) cryoablation clinical trials, across seven institutions between January 1, 2000 and August 26, 2021. Adverse events (AEs) were recorded. Cryoablation procedures were classified as technically successful if they were not prematurely terminated and achieved intended treatment parameters and the first imaging follow-up showed no evidence of residual disease. Results of follow-up biopsies were recorded. Ipsilateral breast tumor recurrences (IBTR) diagnosed during follow-up were identified and classified as true recurrence or new primary disease. A competing-risk model was used to estimate the cumulative incidence of IBTR accounting for death before IBTR. Results: The final study sample included 112 patients (median age, 71 years). A total of 7/112 (6.3%) patients had a minor AE; no moderate or major AE occurred. A total of 110/112 (98.2%) cryoablation procedures were technically successful. During median follow-up of 2.0 years, 22/110 (20.0%) patients underwent biopsy for suspicious imaging findings in the ipsilateral breast, yielding benign concordant findings in 9/22 (40.9%) and IBTR in 12/22 (54.5%). Overall, 12/110 (10.9%) patients experienced IBTR, including 7 with true recurrence and 5 with new primary disease; 3/12 (25.0%) patients with IBTR had received earlier adjuvant or neoadjuvant therapy. When accounting for death as a competing risk, the cumulative incidence of IBTR was 5.3%, 12.2%, and 18.2% at 1, 2, and 3 years, respectively. Conclusion: In select individuals with unfavorable patient or tumor characteristics, breast cancer cryoablation provides a safe alternative to surgery with good outcomes. These findings may be particularly relevant in patients who are also poor surgical candidates. Clinical Impact: Breast cancer cryoablation can be safely applied in a larger patient population than defined by clinical trial inclusion criteria.

Dietary milk polar lipids modulate gut barrier integrity and lipid metabolism in C57BL/6J mice during systemic inflammation induced by Escherichia coli lipopolysaccharide.

The focus of this work is the role milk polar lipids play in affecting gut permeability, systemic inflammation, and lipid metabolism during acute and chronic inflammation induced by a single subcutaneous injection of lipopolysaccharide. Three groups of C57BL/6J mice were fed: modified AIN-93G diet with moderate level of fat (CO); CO with milk gangliosides (GG); CO with milk phospholipids (MPL). The MPL did not prevent a gut permeability increase upon LPS stress but increased the expression of tight junction proteins zonula occludens-1 and occludin in colon mucosa. The GG prevented the gut permeability increase upon LPS stress. The MPL decreased absolute and relative liver mass and decreased hepatic gene expression of acetyl-CoA carboxylase 2 and 3-hydroxy-3-methylglutaryl-CoA reductase. The GG increased hepatic gene expression of acetyl-CoA acyltransferase 2. In conclusion, milk GG protected the intestinal barrier integrity but had little effect on systemic inflammation and lipid metabolism; milk MPL, conversely, had complex effects on gut permeability, did not affect systemic inflammation, and had beneficial effect on hepatic lipid metabolism.

Breast Cryoablation, From the AJR "How We Do It" Special Series.

Breast cryoablation is a minimally invasive image-guided percutaneous procedure to treat fibroadenomas and early-stage breast cancer utilizing liquid nitrogen or argon gas to create extremely cold temperatures that devitalize targeted tissue. Although more long term data are needed, this outpatient procedure is well tolerated and carries minimal risks, including non-target thermal injury that can be mitigated by careful planning and proper technique. Building a sustainable breast cryoablation service in a radiology practice poses several practical considerations, such as training proceduralists, purchasing equipment, recruiting patients, and understanding the revenue cycle. This article describes aspects of the radiologist's role in this procedure, including implementation of a breast ablation program, patient selection, technical details related to intervention, and expected postprocedural outcomes.

Publication Recommendations to Report Laboratory Data of Neonates - a Modified Delphi Approach.

BACKGROUND: Clinical and analytical information on laboratory data of neonates in scientific publications is sparse and incomplete. Furthermore, interpreting neonatal laboratory data can be complex due to their time-dependent and developmental physiology, and paucity of well-established age-appropriate reference ranges for neonates. This study aims to develop publication recommendations to report laboratory data of neonates to enhance the quality of these data in research and clinical care. METHODS: A modified Delphi approach was used to develop recommendations in cooperation with the International Neonatal Consortium. A Core Group, including different stakeholders, was responsible for developing the recommendations, in collaboration with a Reflection Group, responsible for providing additional input. RESULTS: The recommendations were classified into three categories: 'Clinical Characteristics', 'Bio-analytical Information' and 'Data-analytical Information'. These were each divided into 'Core Data' (always to be reported) and 'Supplemental Considerations' (to be reported when considered relevant to the study). CONCLUSION: Our recommendations provide guidance on standardization of neonatal laboratory data in publications. This will enhance the comparison, replication, and application of study results in research initiatives and clinical practice. Furthermore, these recommendations also serve as foundational work to develop reference ranges for neonatal laboratory values by standardizing the quality of information needed for such efforts. IMPACT: Standardized reporting of neonatal laboratory data in scientific publications will enhance the comparison, replication, and application of study results in research initiatives and clinical practice, as well as improve reporting to regulatory agencies. To integrate multistakeholder perspectives, a modified Delphi approach was used to develop publication recommendations which strengthens the applicability of the recommendations. Implementation of standardization will likely improve the overall quality of neonatal clinical research and neonatal healthcare. In addition, these recommendations are foundational to develop reference ranges for neonatal laboratory values by standardizing the quality of information needed for such efforts.

First-in-man report of transsubclavian venous implantation of the Aveir leadless cardiac pacing system.

INTRODUCTION: Transsubclavian venous implantation of the Aveir leadless cardiac pacemaker (LCP) has not been previously reported. METHODS AND RESULTS: Three cases of transsubclavian implantation of the Aveir LCP are reported. Two cases were postbilateral orthotopic lung transplant, without appropriate femoral or jugular access due to recent ECMO cannulation and jugular central venous catheters. In one case, there was strong patient preference for same-day discharge. Stability testing confirmed adequate fixation and electrical testing confirmed stable parameters in all cases. All patients tolerated the procedure well without significant immediate complications. CONCLUSIONS: We demonstrate the feasibility of transsubclavian implantation of the Aveir LCP.

Effects of Dietary Fiber on Short Chain Fatty Acid Receptor mRNA in Microglia and Serotonergic Neurons in the Mouse Brain.

Short-chain fatty acids (SCFAs) are bioactive lipids that are released into the colon as a metabolite of bacterial fermentation of dietary fibers. Beyond their function in the gastrointestinal tract, SCFAs can also have effects inthe brain, as a part of the gut-brain axis. Recent investigations into potential therapeutic interventions via the manipulation of the gut microbiome-and thus their SCFA metabolites-has been emerging as a new branch of personalized medicine,especially for mental health conditions. The current study sought to measure and localize SCFA receptors in the mouse brain. Two cell types have been implicated in the gut-brain axis: microglia and serotonergic neurons. We used fluorescentin situhybridization in brain sections from mice fed diets with different compositions of fat and fiber to quantify the mRNA levels of known gene markers of these two cell types and colocalize each with mRNA for free fatty acid receptors that bind SCFAs. We focused onmicroglia in the hippocampus and the serotonergic neurons of the dorsal raphe. We found high colocalization of SCFA receptors in both microglia and serotonergic neurons and discovered that SCFA receptor expression in the dorsal raphe is driven by fiber solubility, while SCFA receptor expression in the hippocampus is driven by fiber amount. Higher dietary fiber was associated with decreased tyrosine hydroxylase expression. Thus, our results indicate that the amount and solubility of dietary fiber can change gene expression in the brain's microglia and serotonin neurons, potentially via sensitivity to circulating levels of SCFAs produced in the gut.

The Cyanoketenyl Anion [NC3O].

Cumulenes and heterocumulenes with three or more cumulative multiple bonds are usually reactive species that serve as valuable building blocks for more complex molecules but tend to isomerize or cyclize and therefore are difficult to isolate. Using a mild ligand exchange reaction at the carbon in α-metalated ylides, we have now succeeded in the synthesis and gram-scale isolation of the elusive cyanoketenyl anion [NC3O]-. Despite its assumed cumulene-like structure and the delocalization of the negative charge across the whole 5-atom molecule, it features a bent geometry with a nucleophilic central carbon atom. Computational studies reveal an ambiguous bonding situation in the anion, which can be illustrated only by a combination of different resonance structures. Nonetheless, the anion features remarkable stability, thus allowing the storage of its potassium-crown ether salt and its application as a highly functional synthetic building block. The cyanoketenyl anion readily reacts with a series of small molecules to form more complex organic compounds, including industrially valuable compounds such as cyanoacetate. This work demonstrated that reactive species can be generated by novel synthesis methods and open up atom-economic pathways to complex compounds from small abundant molecules.

The effects of including sprouted barley with alfalfa hay in the diet on ruminal health and performance of cow-calf pairs.

The world population is growing exponentially, increasing demand to produce high-quality protein for human consumption. Changes in weather patterns, drought, and decreased land resources due to urbanization have increased the strain on the agriculture sector to meet world demands. An alternative method to combat these issues and continue to produce high-quality livestock feed would be through a controlled environment vertical farming system. Commonly, cereal grains, such as barley, are used in these systems to produce livestock feed. However, there is little information on the viability of feeding sprouted grains to beef cattle. Two diets of either feeder-quality alfalfa hay (n = 10 pairs; ALF) or the same alfalfa hay and sprouted barley (SB; 12.6% dry matter [DM]; n = 10 pairs) were fed for 90 d to Angus pairs with a steer calf during mid to late lactation. On days 0 and 90, body weight (BW), milk, rumen fluid, and body condition score were collected from cows and hip height and BW were recorded for calves. On day 10, BW was recorded for cows and calves and rumen fluid was collected from cows. Rumen fluid was also collected from cows on day 45. On day 55, BW was collected for both cows and calves and milk from cows. Intake was recorded throughout the trial via bunks with Vytelle technology. The PROC MIXED procedure of SAS was used to analyze all data with the day as a repeated measure to determine the main effect of diet. Individual volatile fatty acids (VFA) were measured as a percent of total VFA. No differences (P ≥ 0.16) were observed in calf BW, hip height, milk protein, fat, lactose, calf DM intake (DMI), or cow DMI. Cows fed SB tended (P = 0.08) to have a decreased somatic cell count compared to ALF. Percent butyrate was impacted by diet × day (P = 0.02), but no difference (P > 0.09) at any time points were detected. Additionally, a diet × day effect (P = 0.001) on rumen pH demonstrated that both groups stayed consistent until day 45 and then SB pH decreased the last 45 d. There was a day effect for total VFA (P = 0.0009), acetate:propionate (Ac:Pr; P < 0.0001), acetate (P < 0.0001), and propionate (P < 0.0001) demonstrating that total VFA, acetate, and Ac:Pr all increased throughout the trial, while propionate decreased. These results indicate that SB can be a potential alternative feed at this stage of production as it does not negatively impact health or production, but does affect the rumen pH and proportion of some VFA.

Climate variability and uncertainty associated with weather patterns can greatly impact feed security for cattle producers. Flooding, drought, and temperature extremes can reduce a farmer's ability to produce a consistent crop, resulting in feed prices that can fluctuate greatly. Vertical farming systems that sprout cereal grains in a controlled environment, using precision irrigation, may alleviate the effects of external factors such as climate and resulting feed prices. The objective of this study was to determine if sprouted barley (SB) could be used as an effective alternative feed source for cow-calf pairs. Two diets were fed to 20 cow-calf pairs, a control diet consisting of 100% feeder-quality alfalfa hay, or an experimental diet comprised of feeder-quality alfalfa hay and a 12.6% dry matter inclusion of SB for 90 d. Body weight, feed intake, and feeding behavior were analyzed in the cows and calves. Ruminal health was also assessed in cows by analyzing the ruminal fluid for pH and volatile fatty acid composition. When health and performance metrics were analyzed, no differences were found between the two diets that were administered to the cattle.

A type 4 resistant potato starch alters the cecal microbiome and gene expression in mice fed a western diet based on NHANES data.

Four major types of resistant starch (RS1-4) are present in foods, all of which can alter the microbiome and are fermented in the cecum and colon to produce short-chain fatty acids (SCFAs). Type 4 RSs are chemically modified starches, not normally found in foods, but have become a popular food additive as their addition increases fiber content. Multiple studies, in humans and rodents, have explored how different RS4 affect post-prandial glucose metabolism, but fewer studies have examined the effects of RS4 consumption on the microbiome. In addition, many RS studies conducted in rodents use high-fat diets that do not approximate what is typically consumed by humans. To address this, mice were fed a Total Western Diet (TWD), based on National Health and Nutrition Examination Survey (NHANES) data that mimics the macro and micronutrient composition of a typical American diet, for six weeks, and then supplemented with 0, 2, 5, or 10% of the RS4, Versafibe 1490™ (VF), a phosphorylated and cross-linked potato starch, for an additional three weeks. The cecal contents were analyzed for SCFA content and microbiota composition. Butyrate production was increased while branched chain SCFA production decreased. The alpha-diversity of the microbiome decreased in mice fed the TWD with 10% VF 1490 added while the beta-diversity plot showed that the 5% and 10% VF groups were distinct from mice fed the TWD. Similarly, the largest changes in relative abundance of various genera were greatest in mice fed the 10% VF diet. To examine the effect of VF consumption on tissue gene expression, cecal and distal colon tissue mRNA abundance were analyzed by RNASeq. Gene expression changes were more prevalent in the cecum than the colon and in mice fed the 10% VF diet, but the number of changes was substantially lower than we previously observed in mice fed the TWD supplemented with native potato starch (RPS). These results provide additional evidence that the structure of the RS is a major factor determining its effects on the microbiome and gene expression in the cecum and colon.

Integrating Social Cognition Into Domain-General Control: Interactive Activation and Competition for the Control of Action (ICON).

Social cognition differs from general cognition in its focus on understanding, perceiving, and interpreting social information. However, we argue that the significance of domain-general processes for controlling cognition has been historically undervalued in social cognition and social neuroscience research. We suggest much of social cognition can be characterized as specialized feature representations supported by domain-general cognitive control systems. To test this proposal, we develop a comprehensive working model, based on an interactive activation and competition architecture and applied to the control of action. As such, we label the model "ICON" (interactive activation and competition model for the control of action). We used the ICON model to simulate human performance across various laboratory tasks. Our simulations emphasize that many laboratory-based social tasks do not require socially specific control systems, such as those that are argued to rely on neural networks associated with theory-of-mind. Moreover, our model clarifies that perceived disruptions in social cognition, even in what appears to be disruption to the control of social cognition, can stem from deficits in social representation instead. We advocate for a "default stance" in social cognition, where control is usually general, but representation is specific. This study underscores the importance of integrating social cognition within the broader realm of domain-general control processing, offering a unified perspective on task processing.