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This study compared dry-rolled and tempered hybrid rye when processed to a coarse or fine severity on dry matter intake (DMI), ruminal fermentation, and apparent total tract nutrient digestibility for beef cattle. Eight ruminally cannulated Simmental heifers (327 ± 33.1 kg, mean ± SD) were used in a replicated 4 × 4 Latin square (21-day periods with 16 days for adaptation and 5 d collection) balanced for carry-over effects with a 2 × 2 factorial arrangement of treatments. Feeding tempered rye increased ( P = 0.01) DMI when compared to dry-rolled rye, but there was no effect of processing severity. Cattle fed dry-rolled rye had a greater ( P = 0.04) area that pH was

Weight loss from an overweight state is associated with a disproportionate decrease in whole-body energy expenditure that may contribute to the heightened risk for weight regain. Evidence suggests that this energetic mismatch originates from lean tissue. Although this phenomenon is well documented, the mechanisms have remained elusive. We hypothesized that increased mitochondrial energy efficiency in skeletal muscle is associated with reduced expenditure under weight loss. Wildtype (WT) male C57BL6/N mice were fed with high-fat diet for 10 weeks, followed by a subset of mice that were maintained on the obesogenic diet (OB) or switched to standard chow to promote weight loss (WL) for additional 6 weeks. Mitochondrial energy efficiency was evaluated using high-resolution respirometry and fluorometry. Mass spectrometric analyses were employed to describe the mitochondrial proteome and lipidome. Weight loss promoted ~50% increase in the efficiency of oxidative phosphorylation (ATP produced per O2 consumed, or P/O) in skeletal muscle. However, Weight loss did not appear to induce significant changes in mitochondrial proteome, nor any changes in respiratory supercomplex formation. Instead, it accelerated the remodeling of mitochondrial cardiolipin (CL) acyl-chains to increase tetralinoleoyl CL (TLCL) content, a species of lipids thought to be functionally critical for the respiratory enzymes. We further show that lowering TLCL by deleting the CL transacylase tafazzin was sufficient to reduce skeletal muscle P/O and protect mice from diet-induced weight gain. These findings implicate skeletal muscle mitochondrial efficiency as a novel mechanism by which weight loss reduces energy expenditure in obesity.

SummaryReactive oxygen species (ROS) accumulation is a cardinal feature of skeletal muscle atrophy. ROS refers to a collection of radical molecules whose cellular signals are vast, and it is unclear which downstream consequences of ROS are responsible for the loss of muscle mass and strength. Here we show that lipid hydroperoxides (LOOH) are increased with age and disuse, and the accumulation of LOOH by deletion of glutathione peroxidase 4 (GPx4) is sufficient to augment muscle atrophy. LOOH promoted atrophy in a lysosomal-dependent, proteasomal-independent manner. In young and old mice, genetic and pharmacologic neutralization of LOOH or their secondary reactive lipid aldehydes robustly prevented muscle atrophy and weakness, indicating that LOOH-derived carbonyl stress mediate age- and disuse-induced muscle dysfunction. Our findings provide novel insights for the role of LOOH in sarcopenia including a therapeutic implication by pharmacologic suppression.

Thermogenesis by uncoupling protein 1 (UCP1) is one of the primary mechanisms by which brown adipose tissue (BAT) increases energy expenditure. UCP1 resides in the inner mitochondrial membrane (IMM), where it dissipates membrane potential independent of adenosine triphosphate (ATP) synthase. Here, we provide evidence that phosphatidylethanolamine (PE) modulates UCP1-dependent proton conductance across the IMM to modulate thermogenesis. Mitochondrial lipidomic analyses revealed PE as a signature molecule whose abundance bidirectionally responds to changes in thermogenic burden. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) made mice cold intolerant and insensitive to β3 adrenergic receptor agonist–induced increase in whole-body oxygen consumption. High-resolution respirometry and fluorometry of BAT mitochondria showed that loss of mitochondrial PE specifically lowers UCP1-dependent respiration without compromising electron transfer efficiency or ATP synthesis. These findings were confirmed by a reduction in UCP1 proton current in PE-deficient mitoplasts. Thus, PE performs a previously unknown role as a temperature-responsive rheostat that regulates UCP1-dependent thermogenesis.

This study was designed to evaluate dry matter intake (DMI), ruminal fermentation, ruminal digesta outflow, omasal flow of N constituents, and ruminal and total-tract digestibility in response to increasing dietary lipid content derived from high-lipid by-product-based pellets for finishing beef cattle. Five ruminally cannulated heifers were used in a 5 × 5 Latin square design. Dietary treatments were iso-nitrogenous with increasing ether extract (EE) concentrations resulting in dietary concentrations of 3.5%, 4.2%, 4.7%, 5.1%, and 5.9% of dry matter. Periods were 28 d in duration with the first 19 d used for dietary adaptation and the last 9 d for sample and data collection. Dry matter intake, ruminal pH, omasal flow of N constituents, and short-chain fatty acid concentrations were not affected by increasing dietary EE content (P ≥ 0.10). Increasing dietary EE content increased outflow of EE from the rumen (P

The objective of this study was to evaluate the use of barley (BS) or corn (CS) silage when fed with dry-rolled barley grain (BG), corn grain (CG), or an equal blend (BCG) of BG and CG for backgrounding cattle. Ruminally cannulated heifers (n = 5) were assigned to an incomplete 6 × 6 Latin square design. Treatments contained either BS or CS in combination with BG, CG, or BCG. Samples were collected to determine dry matter intake, ruminal fermentation, total-tract nutrient digestibility, and nitrogen (N) balance. Interactions between cereal silage and cereal grain sources were detected for the molar proportions of propionate and butyrate where the magnitude of change with the type of cereal grain was increased in heifers fed CS relative to BS. Feeding CS increased estimated microbial N production (silage, P = 0.022) and fecal N excretion (silage, P = 0.042) over BS. Diets containing BG had greater dry matter, organic matter, starch, and gross energy digestibility values compared with CG, but values for BCG were not different (grain, P ≤ 0.043). Based on limited silage × grain interactions, use of CS in backgrounding diets may increase microbial N production relative to BS and dry-rolled CG may reduce apparent total-tract nutrient digestibility relative to dry-rolled BG.

Corn production in Western Canada has increased with development of short-season varieties partially offsetting the use of barley as a silage and grain source. The current study evaluated effects of silage and cereal-grain source on subcutaneous fat (SCF) composition of finishing cattle. Steers (465 ± 28.0 kg) were assigned to 24 pens (12 steers per pen) in a 2 × 3 factorial design for an 89 d finishing study. Diets contained corn silage or barley silage at 8% [dry matter (DM)] combined either dry-rolled barley grain (BG; 86% of DM), corn grain (CG; 85% of DM), or an equal blend of BG and CG (85% of DM). Bone-in ribeyes were collected from four steers per pen, and subcutaneous fatty acids were analyzed by gas chromatography. Feeding dry-rolled CG increased dietary fat and 18:2n-6 concentrations, resulting in small increases in 18:2n-6, total n-6 fatty acids, and n-6/n-3 ratios in SCF (P

The objective of this study was to determine the effects of feeding barley silage (BS) or corn silage (CS) with dry-rolled barley (BG), dry-rolled corn (CG), or a blend of barley and corn grain (BCG), on growth performance and nutrient digestibility, the latter predicted using near-infrared spectroscopy for backgrounding cattle. Steers (n = 288) were stratified by body weight (BW) into 24 pens and pens were randomly assigned to one of six treatments (n = 4) in a 2 × 3 factorial design. Main factors included BS or CS in combination with BG, CG, or BCG. There were no silage × grain interactions. Dry matter intake (DMI; P = 0.018) and final BW (P = 0.004) were greater for steers fed CS than BS, but average daily gain (1.01 kg d−1) and gain-to-feed ratio (0.10 kg kg−1) were not affected by silage or grain source. Steers fed CS also had greater dry matter, organic matter, crude protein (CP), acid detergent fiber (ADF), starch, and gross energy digestibility values (P < 0.01) than BS. Feeding BG increased starch, neutral detergent fiber, ADF, and CP digestibility values (P ≤ 0.01) over CG and BCG. Relative to BS, feeding CS increased DMI, final BW, and nutrient digestibility, whereas dry-rolled BG improved nutrient digestibility when compared with CG and BCG in backgrounding diets.

Sesquitepenoids inuloxins A-D, belonging to different subgroups, were isolated from Dittrichia viscosa and showed potential biocontrol of some parasitic plants as Pelipanche, Orobanche, and Cuscuta species. The absolute configurations of the first three inuloxins A-C were previously determined by using experimental and computational chiroptical spectroscopic methods. The absolute configuration of inuloxin D remains to be established. The bioactive inuloxin E, closely related to inuloxin D, was recently isolated from the same plant organic extract. The same relative configuration of inuloxin D was assigned to inuloxin E by comparison of their NMR spectroscopic data. The absolute configurations of inuloxin D and inuloxin E are suggested in this work by analysis of the experimental and predicted chiroptical properties of the 4-O-acetyl derivative of inuloxin D.

Adult day care (ADC) centers provide community-based care (including meals) to frail, ethnically diverse older adults, many of whom are at risk for malnutrition. To support the development of interventions to benefit ADC users, the authors aimed to identify barriers and facilitators of healthy nutrition among ADC users born in Vietnam and China. Semi-structured qualitative interviews were conducted among ADC stakeholders to identify barriers and facilitators. Data were analyzed using Braun and Clarke's six-step method and organized within the framework of the Social Ecological Model. Facilitators of good nutrition included adherence to traditional diet at the ADC center, peer networks, and access to ethnic grocers. Poor health, family dynamics, and loneliness all contributed to poor nutrition, as did the restrictive nature of nutrition programs serving ADC users in the United States. Individual, relationship, organizational, community, and policy level factors play a role in ADC users' nutritional status. Targeted nutrition interventions should leverage culturally congruent relationships between ADC users and staff and include advocacy for enhancement of federal programs to support this population. [ Research in Gerontological Nursing, 13 (3), 146–157.]

Objective The objective was to evaluate the effects of drinking water sulfate concentrations on DMI, water intake, growth, and serum mineral concentrations in growing beef heifers fed a high forage diet (63% DM). Materials and Methods Two blocks of 16 Hereford-cross heifers were used in a randomized complete block design with 4 treatments. Treatments resulted in water sulfate concentrations of 292 ± 23.5, 1,245 ± 78.7, 2,305 ± 89.7, and 3,376 ± 84.9 mg/L. Heifers were housed in tiestalls, and feed and water intakes were measured daily. Body weight and serum mineral concentrations were measured on 2 consecutive days at the start and end of the 77-d study. Results and Discussion Increasing water sulfate increased and then decreased DMI (quadratic, P Implications and Applications These data suggest that water sulfate concentrations above 2,000 mg/L may decrease DMI and that increasing water sulfate concentrations linearly reduced serum copper.

We examined how convenience and financial incentives influence patient willingness to dispose of leftover prescription opioids after surgery. We also identified additional barriers and facilitators to disposal.In the United States, up to 70% of surgical patients are prescribed opioids and up to 92% will have leftover tablets. Most do not dispose of leftover opioids, increasing the risk for opioid-related harm. Current interventions promoting opioid disposal have shown mixed success.We conducted a mixed methods study using a standard gamble survey and semi-structured interviews. Participants estimated willingness to dispose in 16 scenarios with varying convenience (time requirements of5, 15, 30, and 60 minutes) and financial incentives ($0, $5, $25, $50). We estimated the likelihood of disposal using a multivariable mixed effects modified Poisson regression model. Semi-structured interviews explored how convenience, financial incentives, and other barriers and facilitators influenced decisions to dispose.Fifty-five participants were surveyed and 42 were interviewed. Most were willing to dispose when the time required was15 minutes. Few were willing to dispose if the process required 60 minutes, although a $50 financial incentive increased rates from 9% to 36%. Anxiety about future pain, opioid scarcity, recreational use, family safety, moral beliefs, addiction, theft, and environmental harm also influenced decision-making.Interventions promoting opioid disposal should focus on convenience, but the selective use of financial incentives can be effective. Tailoring interventions to individual barriers and facilitators could also increase disposal rates.

Receptor for Advanced Glycated End-products (RAGE) is highly expressed in diabetes and impairs wound healing. We proposed that administering an antibody that blocks RAGE will hasten the healing of dorsal wounds in diabetic pigs compared with a non-immune IgG. Two purpose-bred diabetic (D) Yucatan minipigs (Sinclair, Auxvasse MO) each underwent 12 2 × 2 cm full thickness dorsal wounds: four wounds received decellularized porcine skin patches (Xylyx Bio, Bklyn NY): four anti-RAGE Ab (CR-3) infused patches, four saline infused patches and four wounds were left open. One pig received anti-RAGE Ab (CR-3) 1 mg/kg IM q 10 days and other received non-immune IgG. Wounds were measured at 2 and 4 weeks followed by euthanasia and wound harvesting. At 2 weeks few of the patches appeared to be incorporated into the wound. By 4 weeks all patches in pigs treated systemically with CR-3 were detached and the wounds almost healed. For all 24 wounds for both pigs regardless of presence of patch or type of patch, the average IgG treated pig wound size at 4 weeks was 69.2 ± 14.6% of initial size and the average CR-3 treated pig wound size was 40.9 ± 11.3% of initial size (P = 0.0002). Quantitative immunohistology showed greater staining for collagen in the CR-3 treated wounds compared with IgG treated. Staining was positive for RAGE, Mac, and IL-6 in the IgG treated wounds and negative in the CR-3 treated wounds. From these pilot experiments, we conclude that a RAGE blocking antibody given parenterally improved wound healing in a diabetic pig while patches were not effective.

BACKGROUND AND AIMS. Metformin is the most commonly prescribed medication to treat diabetes. Emerging evidence suggests that metformin could have off target effects that might help promote healthy muscle aging, but these effects have not been thoroughly studied in glucose tolerant older individuals. The purpose of this study was to investigate the short-term effects of metformin consumption on skeletal muscle mitochondrial bioenergetics in healthy older adults. METHODS. We obtained muscle biopsy samples from 16 healthy older adults previously naïve to metformin and treated with metformin (METF; 3F, 5M), or placebo (CON; 3F, 5M), for two weeks using a randomized and blinded study design. Samples were analyzed using high-resolution respirometry, immunofluorescence, and immunoblotting to assess muscle mitochondrial bioenergetics, satellite cell (SC) content, and associated protein markers. RESULTS. We found that metformin treatment did not alter maximal mitochondrial respiration rates in muscle compared to CON. In contrast, mitochondrial H(2)O(2) emission and production were elevated in muscle samples from METF versus CON (METF emission: 2.59 ± 0.72 SE Fold, P=0.04; METF production: 2.29 ± 0.53 SE Fold, P=0.02). Furthermore, the change in H(2)O(2) emission was positively correlated with the change in type 1 myofiber SC content and this was biased in METF participants (Pooled: R(2)=0.5816, P=0.0006; METF: R(2)=0.674, P=0.0125). CONCLUSIONS. These findings suggest that acute exposure to metformin does not impact mitochondrial respiration in aged, glucose-tolerant muscle, but rather, influences mitochondrial-free radical and SC dynamics. CLINICAL TRIAL REGISTRATION. NCT03107884, clinicaltrials.gov

Norovirus infection causing acute gastroenteritis could lead to adverse effects on the gut microbiome. We assessed the association of microbiome diversity with norovirus infection and secretor status in patients from Veterans Affairs medical centers. Alpha diversity metrics were lower among patients with acute gastroenteritis but were similar for other comparisons.

This study evaluated the effect of processing method and severity of hybrid fall rye on dry matter intake (DMI), ruminal fermentation, and apparent total tract nutrient digestibility for beef cattle. Ruminally cannulated Simmental heifers (n = 8; 327±33 kg) were used in a replicated 4×4 Latin square (21-d periods) balanced for carry-over effects with a 2×2 factorial treatment. Tempered rye [water added to achieve 80% dry matter (DM)] was compared with dry-rolled rye. Roller gap width of 1.23-mm and 0.8-mm were used for coarse and finely processed rye, respectively. This resulted in processing index values of: 80.9% for dry-rolled and coarse; 72.7% for dry-rolled and fine; 92.9% for tempered and coarse; and 88.2% for tempered and fine processed rye. Diets (DM basis) included hybrid rye grain (86%), barley silage (15%), mineral (6%), and dry distillers’ grain plus solubles (3%). Feeding tempered rye increased (P< 0.01) DMI by 0.87 kg compared with dry-rolled rye, and feeding coarse rye increased (P=0.04) DMI by 0.33 kg compared with fine rye. Cattle fed dry-rolled and finely processed rye had greater (P< 0.04) area that pH was < 5.5 compared with tempered and coarse rye, respectively. Ruminal short-chain fatty acid concentrations and ammonia were not affected (P≥0.12). Feeding dry-rolled rye increased DM digestibility by 2.4% (P=0.02), and crude protein digestibility in 3.0% (P=0.01) compared with tempered rye. Starch digestibility was not affected by processing severity of dry-rolled rye, but increased from 92.8 to 95.9% for tempered rye with increasing severity (interaction, P=0.03). Rolling tempered rye at the same roller gap as dry-rolled rye decreases processing severity but may allow for a greater severity of processing without marked reductions in DMI and ruminal pH, while achieving similar total tract starch digestibility. When increasing processing severity (81 vs. 73%), dry-rolling hybrid rye may reduce DMI and ruminal pH.

This study evaluated the impact of naturally occurring water with a high-sulfate concentration on dry matter intake (DMI), water intake, growth, and trace mineral status of yearling beef heifers. Angus-based heifers (n = 48; 398.4 ± 22.1 kg) were randomly assigned to 1 of 12 pens (4 heifers/pen) and fed for 100 d arranged into 25 d periods. Heifers were provided water containing 350 (CON); 2,300 (MEDS); or 4,300 mg/L (HIGHS) sulfate. Concentrated water (71,482 mg/L sulfate) from natural source was collected and blended to achieve the treatments. All data were analyzed using the fixed effects of treatment, period (d 1-25, 26-50, 51-75, and 76-100), and the treatment × period interaction, with period as a repeated measure. Average daily gain, and gain-to-feed were not affected (P>0.29). Provision of HIGHS decreased (interaction, P< 0.01) DMI from d 1-25, 26-50 and 51-75, with no effect from d 76-100 compared with CON. Heifers drinking CON and MEDS during d 26-50 had greater (interaction, P< 0.01) water intake than HIGHS with no differences among treatments otherwise. Total sulfate intake (g/d) was greater for HIGHS, followed by MEDS and CON with a greater difference between treatments during d 26-50 (interaction, P< 0.01). Heifers provided MEDS and HIGHS had a greater (interaction, P< 0.01) reduction in serum copper compared with CON. Liver copper concentration did not differ at the start of the study but was 74% and 62% of CON for MEDS and HIGHS, respectively at the end of the study (interaction, P< 0.01). Serum selenium was greater for MEDS and HIGHS than CON; while liver selenium was least for HIGHS heifers at the end of the study (interaction, P< 0.01). These data highlight that beef heifers were able to tolerate 213 g/d of sulfate intake with no negative impact on growth performance; however, MEDS and HIGHS decreased liver copper and liver selenium concentrations.

Obesity alters skeletal muscle lipidome and promotes myopathy, but it is unknown whether aberrant muscle lipidome contributes to the reduction in skeletal muscle contractile force-generating capacity. Comprehensive lipidomic analyses of mouse skeletal muscle revealed a very strong positive correlation between the abundance of lysophosphatidylcholine (lyso-PC), a class of lipids that is known to be downregulated with obesity, with maximal tetanic force production. The level of lyso-PC is regulated primarily by lyso-PC acyltransferase 3 (LPCAT3), which acylates lyso-PC to form phosphatidylcholine. Tamoxifen-inducible skeletal muscle-specific overexpression of LPCAT3 (LPCAT3-MKI) was sufficient to reduce muscle lyso-PC content in both standard chow diet- and high-fat diet (HFD)-fed conditions. Strikingly, the assessment of skeletal muscle force-generating capacity ex vivo revealed that muscles from LPCAT3-MKI mice were weaker regardless of diet. Defects in force production were more apparent in HFD-fed condition, where tetanic force production was 40% lower in muscles from LPCAT3-MKI compared to that of control mice. These observations were partly explained by reductions in the cross-sectional area in type IIa and IIx fibers, and signs of muscle edema in the absence of fibrosis. Future studies will pursue the mechanism by which LPCAT3 may alter protein turnover to promote myopathy.

A novel proof-of-concept model for chiral molecular structure determination using just the molecular formula and vibrational optical activity (VOA) spectra is presented. To verify this concept, the molecular formula of a desired compound is used to generate all possible chiral structural isomers and their VOA spectra are predicted. The similarity analyses of predicted VOA spectra were then carried out in two different ways: (a) similarity between VOA spectrum of one structural isomer with those of the rest, referred to as cross-correlations; (b) similarity between VOA spectra of all chiral structural isomers with the experimental VOA spectra of the desired compound. Three different molecular formulae, C4H8O, C3H5ClO, and C6H10O, and their chiral structural isomers (6, 9, and 75 respectively), were investigated. In each case, the correct chiral molecular structure of the desired compound was identified without ambiguity. Cross-correlation analysis revealed the uniqueness of VOA spectra in deducing the chiral molecular structure solely from its molecular formula. Different chiral structural isomers associated with the molecular formula CH3NO2 were also found to have no significant cross-correlations between their VOA spectra, opening a pathway to detect and identify the elusive chiral N-hydroxyoxaziridine from its VOA spectra.

Background:Cryptococcus neoformans is an encapsulated yeast that can cause fungemia and, in rare instances, lead to endogenous fungal endophthalmitis. No standard of care has been established to treat fungal endophthalmitis when systemic antifungal treatment fails to resolve the intraocular infection. Intravitreal voriconazole has been used for the treatment of fungal endophthalmitis caused by a broad range of fungal pathogens, and a limited number of reports have shown the efficacy of using intravitreal voriconazole for C neoformans endophthalmitis. We report a case of endogenous fungal endophthalmitis caused by C neoformans that was responsive to intravitreal voriconazole. Case Report: A previously healthy 57-year-old male diagnosed with primary neuroendocrine lung tumor developed endogenous endophthalmitis from C neoformans. The endophthalmitis was resistant to intravenous amphotericin B treatment but was responsive to intravenous fluconazole in one eye and was apparently more responsive to intravitreal voriconazole in the other eye. Conclusion: Intravitreal voriconazole should be considered for the treatment of cryptococcal endophthalmitis.

The objective of this study was to evaluate the effects of the source of silage, cereal grain, and their interaction on growth performance, digestibility, and carcass characteristics of finishing beef cattle. Using a completely randomized design within an 89-d finishing study, 288 steers were randomly assigned to 1 of 24 pens (12 steers/pen) with average steer body weight (BW) within a pen of 464 kg ± 1.7 kg (mean ± SD). Diets were arranged in a 2 × 3 factorial with corn silage (CS) or barley silage (BS) included at 8% (dry matter [DM] basis). Within each silage source, diets contained dry-rolled barley grain (BG; 86% of DM), dry-rolled corn grain (CG; 85% of DM), or an equal blend of BG and CG (BCG; 85% of DM). Total tract digestibility of nutrients was estimated from fecal samples using near-infrared spectroscopy. Data were analyzed with pen as the experimental unit using the Mixed Model of SAS with the fixed effects of silage, grain, and the two-way interaction. Carcass and fecal kernel data were analyzed using GLIMMIX utilizing the same model. There were no interactions detected between silage and grain source. Feeding CG increased (P < 0.01) DM intake by 0.8 and 0.6 kg/d relative to BG and BCG, respectively. Gain-to-feed ratio was greater (P = 0.04) for BG (0.172 kg/kg) than CG (0.162 kg/kg) but did not differ from BCG (0.165 kg/kg). Furthermore, average daily gain (2.07 kg/d) and final body weight did not differ among treatments (P ≥ 0.25). Hot carcass weight (HCW) was 6.2 kg greater (372.2 vs. 366.0 kg; P < 0.01) and dressing percentage was 0.57 percentage units greater (59.53 vs. 58.96 %; P = 0.04) for steers fed CS than BS, respectively. There was no effect of dietary treatment on the severity of liver abscesses (P ≥ 0.20) with 72.0% of carcasses having clear livers, 24.4% with minor liver abscesses, and 3.6% with severe liver abscesses. Digestibility of DM, organic matter, crude protein, neutral detergent fiber, and starch were greater for BG (P < 0.01) than CG or BCG. As expected, grain source affected the appearance of grain kernels in the feces (P ≤ 0.04). Feeding CS silage increased the appearance of fractured corn kernels (P = 0.04), while feeding BS increased fiber appearance in the feces (P = 0.02). Current results indicate that when dry rolled, feeding BG resulted in improved performance and digestibility compared with CG and BCG. Even at low inclusion levels (8% of DM), CS resulted in improved carcass characteristics relative to BS.

The biophysical environment of membrane phospholipids affects structure, function, and stability of membrane-bound proteins.1,2 Obesity can disrupt membrane lipids, and in particular, alter the activity of sarco/endoplasmic reticulum (ER/SR) Ca2+-ATPase (SERCA) to affect cellular metabolism.3-5 Recent evidence suggests that transport efficiency (Ca2+ uptake / ATP hydrolysis) of skeletal muscle SERCA can be uncoupled to increase energy expenditure and protect mice from diet-induced obesity.6,7 In isolated SR vesicles, membrane phospholipid composition is known to modulate SERCA efficiency.8-11 Here we show that skeletal muscle SR phospholipids can be altered to decrease SERCA efficiency and increase whole-body metabolic rate. The absence of skeletal muscle phosphatidylethanolamine (PE) methyltransferase (PEMT) promotes an increase in skeletal muscle and whole-body metabolic rate to protect mice from diet-induced obesity. The elevation in metabolic rate is caused by a decrease in SERCA Ca2+-transport efficiency, whereas mitochondrial uncoupling is unaffected. Our findings support the hypothesis that skeletal muscle energy efficiency can be reduced to promote protection from obesity.

(1R,10bR)-1'-((R)-1,2-Dihydroxyethyl)-1-hydroxy-8,9-dimethoxy1,5,6,10b-tetrahydropyrrolo [2,1-a]isoquinolin-3(2H)-one, an analogue of (-)-crispine A, with three stereogenic centers is synthesized and its absolute configuration (AC) established using the combined information derived from the synthetic scheme and single crystal X-ray diffraction data. The experimental chiroptical spectra (namely, optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD)) and the corresponding quantum chemical (QC) predicted spectra for all diastereomers are used to evaluate the AC. The AC of the synthesized compound could be correctly established using any one of the three chiroptical spectroscopic methods (ORD, ECD, or VCD) when the relative configuration is constrained to be that derived from X-ray data or when the ACs of two of the chiral centers are constrained to be those derived from the synthetic scheme. In the absence of this outside information, the QC predicted ORD, ECD, and VCD for incorrect diastereomers are also found to satisfactorily reproduce the corresponding experimental spectra. Nevertheless, incorrect diastereomers could be eliminated when combined electronic dissymmetry factor (EDF) and vibrational dissymmetry factor (VDF) spectral analyses are included, leaving the correct diastereomer as the sole choice. Thus, the combined EDF and VDF spectral analysis is seen to be a helpful diastereomer discrimination tool.

This study evaluated in vivo effects of increasing sulfate concentrations of drinking water on dry matter intake (DMI), water intake, ruminal fermentation, and apparent total-tract digestibility, and in vitro effects of water sulfate and bismuth subsalicylate (BSS) dose. Eight ruminal-cannulated beef heifers (382 ± 45 kg) were stratified into two complete and one incomplete 3×3 Latin squares with 28 d periods. Water contained 341 ± 29 (LS), 2,785 ± 71 (MS), or 4,948 ± 163 mg/L (HS) sulfate. Feed and water intake, ruminal fermentation, and nutrient digestibility were evaluated. Ruminal gas samples were collected every 4 h on d 27 to analyze hydrogen sulfide (H2S) concentration. At the end of each period, digesta collected from heifers in the complete Latin squares were used for in vitro incubation to evaluate water sulfate and BSS dose (0.0, 0.2, 0.4, and 0.6% dry matter). Water intake was 7 L/d greater (P < 0.01) for HS than LS, while MS did not differ. Water sulfate did not affect DMI, but total sulfur intake increased with increasing water sulfate concentration (P < 0.01). Heifers drinking MS and HS had greater ruminal H2S for 10.5 h after water provision and HS continued to be greater for another 4 h relative to LS (sulfate hour, P < 0.01). Ruminal SCFA concentration, molar proportions of major acids, and nutrient digestibility were not affected (P≥0.19). There were no interactions between water sulfate and BSS in vitro. In vitro H2S production (µg/48 h) increased with increasing sulfate concentration (P < 0.01) and was reduced (P=0.05) by BSS inclusion. Neutral detergent fiber digestibility was not affected by sulfate or BSS. Increasing water sulfate concentrations did not negatively affect water or feed intake but did increase H2S concentration and production in vivo and in vitro, respectively. Bismuth subsalicylate may be a potential strategy to reduce H2S production.

BACKGROUND: Leftover pills from postoperative opioid prescriptions place patients and members of their communities at risk for opioid misuse. We aimed to better understand patients’ post-discharge opioid consumption patterns to inform new methods of postoperative opioid prescribing. METHODS: We assessed post-discharge opioid consumption of general surgery patients and assessed the adequacy of discharge opioid prescriptions. We then compared patient opioid consumption to a number of theoretical discharge prescriptions based on different opioid prescribing guidelines and a proposed discharge prescription based on the metric 24-hour predischarge opioid consumption (PDOC). RESULTS: 62/99 patients (62.6%) returned an opioid log book. Median 24-hour PDOC was 22.5 MME (IQR 5.0–45.0) and median discharge prescription size was 15 pills (IQR:10-20). Prescriptions were adequate for 83.7% of patients. The median number of pills used was 3 (IQR:0-11) and median time to opioid cessation was 3 days (IQR:0-5). Actual prescriptions were consistent with national opioid prescribing guidelines. Prescriptions based on the formula 2x 24-hour PDOC would have decreased the number of leftover pills by 7.5 per patient. CONCLUSIONS: Despite prescribing opioids consistent with national opioid prescribing guidelines, patients still receive too many pills. Improved opioid prescribing could be accomplished by use of the formula 2x 24-hour PDOC.

Resumen La transición energética es un cambio que se está llevando a cabo en todo el mundo, migrando del uso de combustibles fósiles a energías renovables. El mayor demandante de derivados del petróleo en nuestro país es el sector transporte, alimentando el 99.81% de este sector. En la presente investigación se aborda un análisis de la sustentabilidad y el impacto ambiental por emisiones en el caso particular de sustituir la gasolina por gas natural El Gas Natural Vehicular (GNV) ha demostrado ser un actor clave en el cambio hacia una economía baja en carbono y un sistema energético más sostenible que, a pesar que es de origen fósil, es un combustible más limpio, comparado con la gasolina y el diésel, aunado a esto, el ahorro en el costo de utilización economiza el 57% de los costos de operación a la fecha. El sector transporte público sin itinerario fijo es por demás atractivo para someter a un cambio de combustible, ya que el parque vehicular sigue incrementando, 1091 unidades sólo de 2017 a 2018 y más importante aún, tienen un recorrido diario mayor comparado con el sector particular, además que, por cuestiones de legislación, éstas unidades no deben tener más de 10 años de antigüedad. En México, ya existe vehículos operando con sistema dual fuel, siendo alimentados con GNV, como es el caso de Ciudad de México, Monterrey, Guadalajara y Puebla, que han sido adquiridos con planes financieros atractivos para los concesionarios, lo que ha propiciado una reducción de las emisiones y un ahorro para los usuarios. Abstract The energy transition is a change that is taking place around the world, migrating from the use of fossil fuels to renewable energy. The largest applicant for petroleum derivatives in our country is the transportation sector, feeding 99.81% of this sector. This research addresses an analysis of sustainability and the environmental impact of emissions in the particular case of replacing gasoline with natural gas. Vehicle Natural Gas (NGV) has proven to be a key player in the shift towards a low-carbon economy and a more sustainable energy system that, despite being of fossil origin, is a cleaner fuel, compared to gasoline and gasoline. Diesel, added to this, the savings in the cost of use saves 57% of the operating costs to date. The public transport sector without a fixed itinerary is extremely attractive to undergo a fuel change, since the vehicle fleet continues to increase, 1091 units only from 2017 to 2018 and more importantly, they have a longer daily route compared to the private sector, furthermore, for legislative reasons, these units must not be more than 10 years old. In Mexico, there are already vehicles operating with dual fuel system, being fed with NGV, as is the case of Mexico City, Monterrey, Guadalajara and Puebla, which have been acquired with attractive financial plans for dealers, which has led to a reduction emissions and savings for users.

Ninety steers (259.9 ± 36.18 kg BW) were used in a 56-d experiment to assess the effects of flavoring additives on feeding behavior, feed efficiency, growth performance, and temperament of newly arrived feedlot cattle. Steers were homogenously distributed by BW into six pens (15 head/pen) and pen was randomly assigned to one of 3 treatments (2 pens/treatment): a standard feedlot receiving diet (CT); or the same diet with a flavoring additive comprised of either sweeteners (SW) or a mix of basic tastes (MX) at 1 g/kg (Lucta SA, Barcelona, Spain). Pens were equipped with a feed intake monitoring system (Growsafe Systems, Airdrie, Canada), while BW and chute exit flight speed were measured bi-weekly during the study. Data were analyzed using a mixed-effects model accounting for repeated measures. There were multiple treatment × time interactions (P < 0.05), where DMI per meal was greater in SW than CT and MX on wk 3 and 5, respectively, and in MX than CT and SW on wk 3 and 7, respectively. The number of visits to the feed bunk per day was greater in MX than CT on wk 2, it was greater in SW than MX on wk 4, and it was greater in CT than in MX and SW on wk 4, and wk 7 and 8, respectively. The eating rate was greater in SW than MX on wk 4 and 5 and greater than CT and on wk 4. Although the cumulative responses for DMI, ADG and feed efficiency (FE; kg BW/kg DM) were not significant (P > 0.1), FE was greater in SW and MX than CT from 27 to 41 d. Despite these positive effects on FE, there was no feeding pattern associated with the inclusion of flavoring additives in the diet of receiving feedlot cattle.

Vijay et al. identify that phosphatidylserine exposed on dead or dying red blood cell membranes signals via Axl on B cells to promote polyclonal B cell activation and plasmablast differentiation during infections that are associated with hemolysis., Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite–infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.

To reduce cost and ease maintenance, industrial control systems (ICS) have adopted Ethernetbased interconnections that integrate operational technology (OT) systems with information technology (IT) networks. This integration has made these critical systems vulnerable to attack. Security solutions tailored to ICS environments are an active area of research. Anomalybased network intrusion detection systems are well-suited for these environments. Often these systems must be optimized for their specific environment. In prior work, we introduced a method for assessing the impact of various anomaly-based network IDS settings on security. This paper reviews the experimental outcomes when we applied our method to a full-scale ICS test bed using actual attacks. Our method provides new and valuable data to operators enabling more informed decisions about IDS configurations.

In response to the increasing awareness of the Ethernet-based threat surface of industrial control systems (ICS), both the research and commercial communities are responding with ICS-specific security solutions. Unfortunately, many of the properties of ICS environments that contribute to the extent of this threat surface (e.g. age of devices, inability or unwillingness to patch, criticality of the system) similarly prevent the proper testing and evaluation of these security solutions. Production environments are often too fragile to introduce unvetted technology and most organizations lack test environments that are sufficiently consistent with production to yield actionable results. Cost and space requirements prevent the creation of mirrored physical environments leading many to look towards simulation or virtualization. Examples in literature provide various approaches to building ICS test beds, though most of these suffer from a lack of realism due to contrived scenarios, synthetic data and other compromises. In this paper, we provide a design methodology for building highly realistic ICS test beds for validating cybersecurity defenses. We then apply that methodology to the design and building of a specific test bed and describe the results and experimental use cases.

Excess reactive oxygen species (ROS) induced by physical inactivity is associated with muscle atrophy and muscle weakness. However, the role of mitochondrial ROS on disuse-induced muscle atrophy is not fully understood. The purpose of this study was to utilize a genetic strategy to examine the effect of neutralizing mitochondrial ROS on disuse-induced skeletal muscle atrophy. This was accomplished by placing wild-type (WT) and mitochondrial-targeted catalase-expressing (MCAT) littermate mice on 7 days of hindlimb unloading. After assessment of body weight and composition, muscles were analyzed for individual muscle mass, force-generating capacity, fiber type, cross-sectional area, and mitochondrial function, including H(2)O(2) production. Despite a successful attenuation of mitochondrial ROS, MCAT mice were not protected from muscle atrophy. No differences were observed in body composition, lean mass, individual muscle masses, force-generating capacity, or muscle fiber cross-sectional area. These data suggest that neutralizing mitochondrial ROS is insufficient to suppress disuse-induced loss of skeletal muscle mass and contractile function. NEW & NOTEWORTHY The premise of this study was to examine the efficacy of genetic suppression of mitochondrial reactive oxygen species (ROS) to attenuate disuse-induced muscle atrophy and muscle weakness. Neutralization of mitochondrial ROS by MCAT expression was insufficient to rescue muscle atrophy and muscle weakness.

The biophysical environment of membrane phospholipids affects structure, function, and stability of membrane-bound proteins.1,2 Obesity can disrupt membrane lipids, and in particular, alter the activity of sarco/endoplasmic reticulum (ER/SR) Ca2+-ATPase (SERCA) to affect cellular metabolism.3–5 Recent evidence suggests that transport efficiency (Ca2+ uptake / ATP hydrolysis) of skeletal muscle SERCA can be uncoupled to increase energy expenditure and protect mice from diet-induced obesity.6,7 In isolated SR vesicles, membrane phospholipid composition is known to modulate SERCA efficiency.8–11 Here we show that skeletal muscle SR phospholipids can be altered to decrease SERCA efficiency and increase whole-body metabolic rate. The absence of skeletal muscle phosphatidylethanolamine (PE) methyltransferase (PEMT) promotes an increase in skeletal muscle and whole-body metabolic rate to protect mice from diet-induced obesity. The elevation in metabolic rate is caused by a decrease in SERCA Ca2+-transport efficiency, whereas mitochondrial uncoupling is unaffected. Our findings support the hypothesis that skeletal muscle energy efficiency can be reduced to promote protection from obesity.

Localization of the components of the cardiac conduction system (CCS) is essential for many therapeutic procedures in cardiac surgery and interventional cardiology. While histological studies provided fundamental insights into CCS localization, this information is incomplete and difficult to translate to aid in intraprocedural localization. To advance our understanding of CCS localization, we set out to establish a framework for quantifying nodal region morphology. Using this framework, we quantitatively analyzed the sinoatrial node (SAN) and atrioventricular node (AVN) in ovine with postmenstrual age ranging from 4.4 to 58.3 months. In particular, we studied the SAN and AVN in relation to the epicardial and endocardial surfaces, respectively. Using anatomical landmarks, we excised the nodes and adjacent tissues, sectioned those at a thickness of 4 μm at 100 μm intervals, and applied Masson's trichrome stain to the sections. These sections were then imaged, segmented to identify nodal tissue, and analyzed to quantify nodal depth and superficial tissue composition. The minimal SAN depth ranged between 20 and 926 μm. AVN minimal depth ranged between 59 and 1192 μm in the AVN extension region, 49 and 980 μm for the compact node, and 148 and 888 μm for the transition to His Bundle region. Using a logarithmic regression model, we found that minimal depth increased logarithmically with age for the AVN (R2 = 0.818, P = 0.002). Also, the myocardial overlay of the AVN was heterogeneous within different regions and decreased with increasing age. Age associated alterations of SAN minimal depth were insignificant. Our study presents examples of characteristic tissue patterns superficial to the AVN and within the SAN. We suggest that the presented framework provides quantitative information for CCS localization. Our studies indicate that procedural methods and localization approaches in regions near the AVN should account for the age of patients in cardiac surgery and interventional cardiology.

Peroxisomes perform essential functions in lipid metabolism, including fatty acid oxidation and plasmalogen synthesis. Here, we describe a role for peroxisomal lipid metabolism in mitochondrial dynamics in brown and beige adipocytes. Adipose tissue peroxisomal biogenesis was induced in response to cold exposure through activation of the thermogenic coregulator PRDM16. Adipose-specific knockout of the peroxisomal biogenesis factor Pex16 (Pex16-AKO) in mice impaired cold tolerance, decreased energy expenditure, and increased diet-induced obesity. Pex16 deficiency blocked cold-induced mitochondrial fission, decreased mitochondrial copy number, and caused mitochondrial dysfunction. Adipose-specific knockout of the peroxisomal β-oxidation enzyme acyl-CoA oxidase 1 (Acox1-AKO) was not sufficient to affect adiposity, thermogenesis, or mitochondrial copy number, but knockdown of the plasmalogen synthetic enzyme glyceronephosphate O-acyltransferase (GNPAT) recapitulated the effects of Pex16 inactivation on mitochondrial morphology and function. Plasmalogens are present in mitochondria and decreased with Pex16 inactivation. Dietary supplementation with plasmalogens increased mitochondrial copy number, improved mitochondrial function, and rescued thermogenesis in Pex16-AKO mice. These findings support a surprising interaction between peroxisomes and mitochondria regulating mitochondrial dynamics and thermogenesis.

Postoperative conduction block requiring lifetime pacemaker placement continues to be a considerable source of morbidity for patients undergoing repair of congenital heart defects. Damage to the cardiac conduction system (CCS) during surgical procedures is thought to be a major cause of the conduction block. Intraoperative identification and avoidance of the CCS is thus a key strategy to improve surgical outcomes. In order to avoid conduction tissue damage and mitigate morbidity a number of approaches have been developed. Here, we review the historical and contemporary approaches for identification of conduction tissue during cardiac surgery. The established approach for intraoperative identification is based on anatomical landmarks established in extensive histological studies of the normal and diseased heart. We focus on landmarks to identify the sinus and atrioventricular nodes during cardiac surgery. We also review technologies explored for intraoperative tissue identification including electrical impedance measurements and electrocardiography. We describe new optical approaches, in particular, and optical spectroscopy and fiberoptic confocal microscopy (FCM), for identification of CCS regions and working myocardium during surgery. As a template for translation of future technology developments, we describe research and regulatory pathways to translate FCM for cardiac surgery. We suggest that along with more robust approaches to surgeon training including awareness of fundamental anatomical studies, optical approaches such as FCM show promise in aiding surgeons in repairs of heart defects. In particular, for complex defects, these approaches can complement landmark-based identification of conduction tissue and thus help to avoid injury to the CCS due to surgical procedures.

Adult day service centers (ADSCs) provide community-based long-term care, including meals, to racially diverse older adults, 47% of whom have dementia and consequently experience elevated nutritional risk. We examine nutritional behaviors for Chinese and Vietnamese persons living with dementia (PLWD) in ADSCs and evaluate the extent to which ADSCs provide person-centered nutritional care. Multi-stakeholder interviews were conducted. Data were coded using Dedoose and analyzed using Braun and Clarke’s six-step method. The Model for the Provision of Good Nutritional Care in Dementia guided analysis. Barriers to food intake included distracting meal environment, rigid mealtimes, and excessively restrictive diets. Conversely, peer relationships, culturally tailored meals and celebrations, and consistent staff assisting with feeding benefited PLWD. ADSCs can support healthy nutritional behaviors and quality of life among PLWD through person-centered nutritional care. To optimize nutritional services, further exploration is needed with respect to the ADSC environment, users’ culture and ethnicity, and liberalized diets for PLWD.

Background: The goal of the US Ending the HIV Epidemic (EHE) plan is to reduce HIV incidence by 75% by 2025 and 90% by 2030. This initiative will scale-up prevention and care activities in high-need areas like the Southeast United States. It is unknown what interventions, alone or in combination, will have the greatest impact towards reaching the EHE targets. Methods: We developed a stochastic HIV transmission model for men who have sex with men (MSM), calibrated to local surveillance estimates of HIV prevalence, PrEP utilization, and HIV care continuum levels in the Atlanta area. Model scenarios varied HIV screening rates relative to empirical levels, under two assumptions of how HIV-negative persons would be linked to PrEP initiation, and also considered relative improvements to HIV care linkage and care retention for those screening positive. We estimated both the proportion of cumulative infections averted over 10 years and the reduction in incidence rates relative to EHE targets. Results: A ten-fold relative increase in HIV screening rates (to approximately biannual screening for black and Hispanic MSM and quarterly for white MSM) would lead to 41% of infections averted under the assumption of integrated linkage to PrEP, with prevention through both increased PrEP coverage and increased HIV viral suppression. At the same relative increase in screening but under the assumption of no PrEP linkage, only 9.9% of infections would be averted, with prevention only through increased viral suppression. Improvements to HIV care retention would avert 33.5% of infections if retention rates were improved 10-fold. If both screening and retention were jointly improved 10-fold, 66.6% and 48.5% of cumulative infections would be averted under assumptions of PrEP linkage and no-linkage, respectively. Under the joint 10-fold PrEP-linked scenario, it would take 7.3 years to meet the 75% EHE target and 30.4 years to meet the 90% target for MSM in Atlanta. Conclusions: Interventions to improve HIV screening linked with PrEP for those screening negative, and HIV care retention would have a substantial impact on HIV prevention through reduction of HIV acquisition and transmission rates. However, additional interventions beyond these substantial improvements to HIV screening, PrEP coverage, and HIV care retention will be necessary to reach the EHE target of a 90% reduction in incidence for Atlanta MSM by 2030.