Short-term feed restriction induces inflammation and an antioxidant response via cystathionine-ß-synthase and glutathione peroxidases in ruminal epithelium from Angus steers.

Decreased intake is induced by stressors such as parturition, transportation, dietary transitions, and disease. An important function of one-carbon metabolism (OCM) is to produce the antioxidant glutathione to help reduce oxidative stress. Although various components of OCM are expressed in the bovine rumen and small intestine, the relationship among reduced feed intake, one-carbon metabolism, and antioxidant mechanisms in gut tissues is unknown. This study aimed to assess alterations in immune and antioxidant pathways in ruminal epithelium due to acute feed restriction (FR). Seven group-housed ruminally-cannulated Angus steers (663 ± 73 kg body weight, 2-year old) had ad libitum access to a finishing diet (dry-rolled corn, corn silage, modified wet distiller's grains) during 15 days of a pre-FR period (PRE). Subsequently, steers were moved to a metabolism barn with tie-stalls and individually-fed at 25% of estimated intake in PRE for 3 days (FR period, FRP). This was followed by 15-days of recovery (POST) during which steers had ad libitum access to the same diet as in PRE and FRP. Plasma and ruminal tissue biopsies were collected during each period. Plasma free fatty acid and IL1-ß concentrations were higher (P ≤ 0.03) in FRP than PRE or POST. The mRNA abundance of the pro-inflammatory genes TNF, TLR2, and TLR4 in ruminal epithelium peaked (P < 0.05) at FRP and remained higher at POST. These responses agreed with the higher (P < 0.05) abundance of phosphorylated (p)-MAPK (an inflammation activator) and p-EEF2 (translational repressor) in FRP than PRE and POST. Although ruminal GPX enzyme activity did not increase at FRP compared with PRE and POST, protein abundance of GPX1 and GPX3 along with the antioxidant response regulator NFE2L2 were highest (P < 0.01) and the activity of cystathione-beta synthase tended (P = 0.06) to be highest during FR. Although FR had minimal negative effects on tissue integrity-related genes (only filamin A was downregulated), it led to a systemic inflammatory response and triggered inflammation and antioxidant mechanisms within ruminal epithelium. Thus, deploying anti-inflammatory and antioxidant mechanisms via molecules that feed into OCM (e.g., dietary methyl donors such as methionine, choline, betaine, folate) could potentially counteract the stressors associated with FR.

Nonstatistical Unimolecular Decay of the CH2OO Criegee Intermediate in the Tunneling Regime.

Unimolecular decay of the formaldehyde oxide (CH2OO) Criegee intermediate proceeds via a 1,3 ring-closure pathway to dioxirane and subsequent rearrangement and/or dissociation to many products including hydroxyl (OH) radicals that are detected. Vibrational activation of jet-cooled CH2OO with two quanta of CH stretch (17-18 kcal mol-1) leads to unimolecular decay at an energy significantly below the transition state barrier of 19.46 ± 0.25 kcal mol-1, refined utilizing a high-level electronic structure method HEAT-345(Q)Λ. The observed unimolecular decay rate of 1.6 ± 0.4 × 106 s-1 is 2 orders of magnitude slower than that predicted by statistical unimolecular reaction theory using several different models for quantum mechanical tunneling. The nonstatistical behavior originates from excitation of a CH stretch vibration that is orthogonal to the heavy atom motions along the reaction coordinate and slow intramolecular vibrational energy redistribution due to the sparse density of states.

Collaborative artificial intelligence system for investigation of healthcare claims compliance.

Healthcare fraud, waste and abuse are costly problems that have huge impact on society. Traditional approaches to identify non-compliant claims rely on auditing strategies requiring trained professionals, or on machine learning methods requiring labelled data and possibly lacking interpretability. We present Clais, a collaborative artificial intelligence system for claims analysis. Clais automatically extracts human-interpretable rules from healthcare policy documents (0.72 F1-score), and it enables professionals to edit and validate the extracted rules through an intuitive user interface. Clais executes the rules on claim records to identify non-compliance: on this task Clais significantly outperforms two baseline machine learning models, and its median F1-score is 1.0 (IQR = 0.83 to 1.0) when executing the extracted rules, and 1.0 (IQR = 1.0 to 1.0) when executing the same rules after human curation. Professionals confirm through a user study the usefulness of Clais in making their workflow simpler and more effective.

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam / El impacto de COVID-19 y otros factores en el estado de uso de las terapias farmacológicas biológicas para la artritis reumatoide: un estudio de Vietnam

Objectives: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. Methods: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan–Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). Results: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. Conclusion: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.(AU)

Objetivos: Describir el estado del uso de fármacos antirreumáticos modificadores de la enfermedad biológica (bDMARD) para tratar la artritis reumatoide (AR) y los factores relacionados. Además, el estudio determinó el impacto de COVID-19 en el uso de bDMARD. Métodos: Este es un estudio transversal que incluyó a 219 pacientes con AR mayores de 18 años. El método Kaplan-Meier y la prueba Log-rank (p<0,05) se usaron para estimar el tiempo de retención y compararlo entre diferentes tiempos. El análisis de regresión de Cox se utilizó para determinar los factores que afectan el tiempo de retención de los medicamentos biológicos (p<0,05). Resultados: De 1.967 cursos de tratamiento, hubo 149 (7,6%) interrupciones del fármaco, 760 (38,6%) extensiones de dosis y 64 (3,3%) cambios de fármaco. Nivel de enfermedad moderado y elección del factor de necrosis tumoral (TNF) inhibidores inicialmente se asociaron con el tiempo de retención de COVID-19. Las discontinuaciones de los medicamentos y las extensiones de las dosis aumentaron después de la aparición de COVID-19. El tiempo de retención durante COVID-19 fue significativamente diferente del pre-COVID-19. Género, tipo de bDMARD de primer uso, convencional DMARD sintéticos (csDMARDs) y el estado de uso de corticoides, los niveles de actividad de la enfermedad se asociaron con el tiempo de retención. Conclusión: La presencia de COVID-19 tiene un efecto significativo en el estado de uso del medicamento biológico. Se necesitan más estudios longitudinales para aclarar la relación entre COVID-19 y el uso de fármacos, así como los factores relacionados.(AU)

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam.

OBJECTIVES: To describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. METHODS: This is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan-Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). RESULTS: Out of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. CONCLUSION: The presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

Methanediol from cloud-processed formaldehyde is only a minor source of atmospheric formic acid.

Atmospheric formic acid is severely underpredicted by models. A recent study proposed that this discrepancy can be resolved by abundant formic acid production from the reaction (1) between hydroxyl radical and methanediol derived from in-cloud formaldehyde processing and provided a chamber-experiment-derived rate constant, k1 = 7.5 × 10-12 cm3 s-1. High-level accuracy coupled cluster calculations in combination with E,J-resolved two-dimensional master equation analyses yield k1 = (2.4 ± 0.5) × 10-12 cm3 s-1 for relevant atmospheric conditions (T = 260-310 K and P = 0-1 atm). We attribute this significant discrepancy to HCOOH formation from other molecules in the chamber experiments. More importantly, we show that reversible aqueous processes result indirectly in the equilibration on a 10 min. time scale of the gas-phase reaction [Formula: see text] (2) with a HOCH2OH to HCHO ratio of only ca. 2%. Although HOCH2OH outgassing upon cloud evaporation typically increases this ratio by a factor of 1.5-5, as determined by numerical simulations, its in-cloud reprocessing is shown using a global model to strongly limit the gas-phase sink and the resulting production of formic acid. Based on the combined findings in this work, we derive a range of 1.2-8.5 Tg/y for the global HCOOH production from cloud-derived HOCH2OH reacting with OH. The best estimate, 3.3 Tg/y, is about 30 times less than recently reported. The theoretical equilibrium constant Keq (2) determined in this work also allows us to estimate the Henry's law constant of methanediol (8.1 × 105 M atm-1 at 280 K).

Effect of Fish Oil and Linseed Oil on Intake, Milk Yield and Milk Fatty Acid Profile in Goats.

This study aimed to evaluate the effect of incorporating linseed oil and fish oil in the diet on intake, ruminal fermentation, milk yield, and milk fatty acid profiles in dairy goats. Four crossbred Saanen lactating goats in mid-lactation and milking 1.30 ± 0.28 g/day were used in a 4 × 4 Latin square design. The basal diet contained concentrate and Para grass (C:F 40:60). Treatments included a basal diet without oil supplementation (Ctrl) or with 2.5% linseed oil (LO2.5), 2.5% linseed oil and fish oil (3:2, w/w, LFO2.5), and 4.16% linseed oil and fish oil (3:2, w/w, LFO4.16). Diets had no effect on intake, milk yield, milk composition, or ruminal fermentation (p > 0.05). Compared with Ctrl, lower (p < 0.05) proportions of C10:0-C14:0 in milk fat were observed with LFO4.16. Compared with the Ctrl and linseed oil added alone, feeding LFO4.16 led to a greater (p < 0.01) concentration of C18:1 t11. Compared with both the Ctrl and LO2.5 diets, milk c9,t11 CLA was 4.53 and 2.94 times greater with the LFO4.16 diet. Compared with Ctrl and LO2.5 diets (0.06% and 0.08%), goats fed LFO2.5, and LFO4.16 had greater (p < 0.001) concentrations of C22:6n-3 (0.63% and 0.87%). Overall, the combined data suggested that including 4.16% linseed oil and fish oil in the diet of dairy goats was effective in improving the concentrations of health-promoting fatty acids in milk without affecting milk production.

Alterations in skeletal muscle abundance of protein turnover, stress, and antioxidant proteins during the periparturient period in dairy cows fed ethyl-cellulose rumen-protected methionine.

Skeletal muscle turnover helps support the physiological needs of dairy cows during the transition into lactation. We evaluated effects of feeding ethyl-cellulose rumen-protected methionine (RPM) during the periparturient period on abundance of proteins associated with transport AA and glucose, protein turnover, metabolism, and antioxidant pathways in skeletal muscle. Sixty multiparous Holstein cows were used in a block design and assigned to a control or RPM diet from -28 to 60 d in milk. The RPM was fed at a rate of 0.09% or 0.10% of dry matter intake (DMI) during the prepartal and postpartal periods to achieve a target Lys:Met ratio in the metabolizable protein of ∼2.8:1. Muscle biopsies from the hind leg of 10 clinically healthy cows per diet collected at -21, 1, and 21 d relative to calving were used for western blotting of 38 target proteins. Statistical analysis was performed using the PROC MIXED statement of SAS version 9.4 (SAS Institute Inc.) with cow as random effect, whereas diet, time, and diet × time were the fixed effects. Diet × time tended to affect prepartum DMI, with RPM cows consuming 15.2 kg/d and controls 14.6 kg/d. However, diet had no effect on postpartum DMI (17.2 and 17.1 ± 0.4 kg/d for control and RPM, respectively). Milk yield during the first 30 d in milk was also not affected by diet (38.1 and 37.5 ± 1.9 kg/d for control and RPM, respectively). Diet or time did not affect the abundance of several AA transporters or the insulin-induced glucose transporter (SLC2A4). Among evaluated proteins, feeding RPM led to lower overall abundance of proteins associated with protein synthesis (phosphorylated EEF2, phosphorylated RPS6KB1), mTOR activation (RRAGA), proteasome degradation (UBA1), cellular stress responses (HSP70, phosphorylated MAPK3, phosphorylated EIF2A, ERK1/2), antioxidant response (GPX3), and de novo synthesis of phospholipids (PEMT). Regardless of diet, there was an increase in the abundance of the active form of the master regulator of protein synthesis phosphorylated MTOR and the growth-factor-induced serine/threonine kinase phosphorylated AKT1 and PIK3C3, whereas the abundance of a negative regulator of translation (phosphorylated EEF2K) decreased over time. Compared with d 1 after calving and regardless of diet, the abundance of proteins associated with endoplasmic reticulum stress (XBP1 spliced), cell growth and survival (phosphorylated MAPK3), inflammation (transcription factor p65), antioxidant responses (KEAP1), and circadian regulation (CLOCK, PER2) of oxidative metabolism was upregulated at d 21 relative to parturition. These responses coupled with the upregulation of transporters for Lys, Arg, and His (SLC7A1) and glutamate/aspartate (SLC1A3) over time were suggestive of dynamic adaptations in cellular functions. Overall, management approaches that could take advantage of this physiological plasticity may help cows make a smoother transition into lactation.

Occurrence and ecological risk assessment of organophosphate esters in surface water from rivers and lakes in urban Hanoi, Vietnam.

In this study, an investigation on the pollution status, distribution, and ecological risk to the aquatic organisms of six organophosphate tri-esters (tri-OPEs) and two organophosphate tri-esters (di-OPEs) in surface water in urban Hanoi, Vietnam were conducted. In 37 surveyed water samples (6 rivers and 17 lakes), all eight targeted OPEs were discovered with a detection frequency (DF) of 41-100% and the concentration varied largely from below the method detection limit (

Willingness and attitudes of parents towards COVID-19 vaccines for children in Vietnam.

BACKGROUND: With an increasing need for COVID-19 vaccination around the globe, we aim to investigate willingness and attitudes of parents regarding COVID-19 vaccines for children in Vietnam. METHOD: A 24-item online survey was conducted among 602 parents and legal guardians of children under 18 years of age. RESULTS: There were 82.6% of parents willing to vaccinate their children. The principal reasons for willingness were: the need for vaccination to control the COVID-19 pandemic and to reduce the risk of SARS-CoV-2 transmission when children return to school. The most common reason for refusing COVID-19 vaccine was the concern about vaccine side effects in children (73.3%), followed by perceived lack of scientific research on COVID-19 vaccines in children (31.4%). The main associated factors with increased willingness of parents towards childhood COVID-19 vaccine were: willingness to allow children to participate in a clinical vaccine trial (aOR = 3.58); possible increase in COVID-19-related mortality (aOR = 3.69); and positive media information regarding COVID-19 vaccine (aOR = 2.04). Noteworthy, higher educational status of parents was associated with decreased willingness for childhood COVID-19 vaccine (aOR = 0.26). CONCLUSION: Understanding reasons of parents to accept childhood COVID-19 vaccines will help future plans in COVID-19 vaccination program. A larger sample size study at a national level is needed to verify the results.

Polyunsaturated fatty acids and rumen undegradable protein alter ruminal fermentation and milk fatty acid profiles in dairy cows.

The present study evaluated the effects of incorporating polyunsaturated fatty acid (PUFA)- and rumen undegradable protein (RUP)-enriched feeds on ruminal fermentation, methane production, milk yield and milk FA profiles in dairy cows. Experiment 1 was carried out on 12 multiparous HF dairy cows in mid-lactation (106 ± 18.6 days in milk, 13.1 ± 1.67 kg/d of milk). Environmental conditions throughout the experiment were 34.5 ± 1.9 8°C, 58.0 ± 2.65% relative humidity and 85.7 ± 2.71 temperature-humidity index. Cows (n = 6/group) were randomly allocated to a control diet (Ctrl) consisting of corn silage and concentrate (F:C 60:40) containing 27.2% RUP in the crude protein (CP) or a treatment diet (Trt) consisting of 58.3% corn silage, 29.6% concentrate, 3.24% roasted soybean meal, 5.82% corn dried distiller grains with solubles and 3% added oil, which contained linseed, sunflower and tuna crude oil (1:1:1, wt/wt). The Trt diet contained 35.0% RUP in the CP. Experiment 2 was conducted in vitro using ruminal fluid collected from three Holstein Friesian dairy cows. The experimental design and diets were the same as in Exp. 1. Dry matter intake (DMI) tended to be lower (P = 0.06) in the Trt group. No difference in milk yield was detected, but the lower (P < 0.01) milk fat was measured in the Trt group (2.82% vs. 3.81%). Feed efficiency (milk/DMI) tended to be greater (P = 0.06) in the Trt cows (1.08 vs. 0.88). Lower 18:0 (5.73% vs. 8.29%), but greater concentrations of c9,t11 CLA (1.88% vs. 0.34%), c9,c12 18:2 (1.55% and 0.69%) 18:3n-3 (0.30% vs. 0.12%) and 22:6n-3 (0.17% vs. 0%) were detected in milk fat of cows fed Trt (P < 0.01). Atherogenicity and thrombogenic indices were lower (P < 0.01) with Trt. Concentrations of ruminal total volatile fatty acids and methane, which was assessed by production of volatile fatty acids, were 10.2% and 11.7% lower P < 0.01) in the Trt group. In conclusion, incorporating PUFA- and RUP-high feeds in lactating cow diets in the tropics causes a reduction in concentrations of ruminal VFA, methane production and milk fat while improving aspects of milk quality without affecting milk production.

Frizzled receptors and SFRP5 in lipid metabolism: Current findings and potential applications.

Lipid metabolism plays a very important role as the central metabolic process of the body. Lipid metabolism interruptions may cause many chronic diseases, for example, non-alcoholic fatty liver disease (NAFLD), diabetes, and obesity. Secreted Frizzled Related Protein 5 (SFRP5) and Frizzled receptors (FZD) are two newly discovered adipokines that are involved in lipid metabolism as well as lipogenesis. Both of these adipokines affect lipid metabolism and adipogenesis through three WNT signaling pathways (WNTSP): WNT/ß-catenin, WNT/Ca2+, and WNT/JNK. FZD consists of 10 species, which have a cysteine-rich domain (CRD) to bind to the WNT protein for signal transduction. Depending on the type of ligand or co-receptor, they can stimulate or inhibit adipogenesis. In lipid metabolism, they play a role in recognizing fatty acids. In obesity, gene expression of the WNT/FZD receptors is significantly increased. In contrast, SFPR5 serves as an antagonist that can compete with FZD for inhibition of WNTSP. It is believed to have anti-inflammatory potential in obesity and diseases related to abnormal lipid metabolism. In these cases, the expression of SFRP5 is found to be very low leading to the promoted production of proinflammatory cytokines (PICS). Some methods that include using recombinant SFRP5 to improve non-alcoholic steatohepatitis (NASH), using secreted Ly-6/uPAR-related protein 1 (Slurp1) to regulate fat accumulation in the liver through SFRP5, and dietary and lifestyle interventions to improve overweight/obesity have been studied. However, understandings of the molecular mechanisms of these two adipokines and their interactions are very limited. Therefore, more in-depth studies are needed in the future.

High-accuracy first-principles-based rate coefficients for the reaction of OH and CH3OOH.

The ˙OH-initiated oxidation of methyl hydroperoxide, which plays an important role in the atmospheric chemistry of methane, was theoretically characterized using high-accuracy composite amHEAT-345(Q) coupled-cluster calculations followed by a two-dimensional E,J resolved master equation analysis. The reaction is found to proceed through two distinct hydrogen-bonded pre-reactive complexes leading to two product channels, in accord with the experimental observations: (i) ˙OH + CH3OOH → CH3OO˙ + H2O with a yield of 0.8 ± 0.1, and (ii) ˙OH + CH3OOH → HCHO + ˙OH + H2O with a yield of 0.2 ± 0.1. The calculated reaction enthalpies are within 0.2 kcal mol-1 of the benchmark ATcT values. Overall thermal rate coefficients obtained from first principles are found to be in the low-pressure limit at atmospheric pressure; the total rate coefficient can be expressed over the T = 200-450 K range as k(T) = 5.0 × 10-12 × T-0.152 × exp(287/T) cm3 s-1, strongly supporting the experimental results of Vaghjiani and Ravishankara (J. Phys. Chem. 1989, 93, 1948), with which this expression agrees within ca. 15%. The current results show that (i) is the principal reaction channel and support the view that, due to its inherently fast transformations, CH3OOH is an important redistribution species for HOx˙ radicals in the Earth's atmosphere.

Diagnostic precision of breast MRI in prediction of pathological complete response: Is it influenced by the presence of metallic markers?

OBJECTIVE: To investigate if the presence of metallic markers (markers) influences the diagnostic accuracy of preoperative breast MRI for the prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this single-center, retrospective, observational study approved by the IRB of our institution, we included all consecutive patients that underwent preoperative breast MRI after completion of NAC (Mean 4,4 days ± 15,9). The presence or absence of markers, the type of markers, the size and type of artefact on each MRI sequence were recorded. Two radiologists blinded to histopathological results and to each other's findings evaluated all MRI examinations for presence or absence of complete response. Pathology was the standard of reference. Diagnostic performance of MRI for prediction of pCR in the presence or absence of markers and also between two most represented markers brands (O'Twist and UltraClip) were compared using Chi-squared tests or equivalents. RESULTS: Ninety-three patients (mean age 48 ± 11 years) were included in this study. Nineteen of them had no markers and 74 had 108 markers. Sensitivity and specificity of MRI for the prediction of pCR were 0.73 and 0,81 for patients with and 0.67 and 0.90 for patients without markers (p < 0.05).There was no statistical difference in the performance of MRI for the two different types of markers studied. CONCLUSION: Diagnostic performance of pre-operative MRI after NAC for the prediction of pCR did not differ statistically in the presence or absence of metallic markers nor between the two markers' brands studied.

Mechanism, thermochemistry, and kinetics of the reversible reactions: C2H3 + H2 ⇌ C2H4 + H ⇌ C2H5.

High-level coupled cluster theory, in conjunction with Active Thermochemical Tables (ATcT) and E,J-resolved master equation calculations, was used in a study of the title reactions, which play an important role in the combustion of hydrocarbons. In the set of radical/radical reactions leading to soot formation in flames, the addition of H-atoms to alkenes is likely a common reaction, triggering the isomerization of complex hydrocarbons to aromatics. The heats of formation of C2H3, C2H4, and C2H5 are established to be 301.26 ± 0.30 at 0 K (297.22 ± 0.30 at 298 K), 60.89 ± 0.11 (52.38 ± 0.11), and 131.38 ± 0.22 (120.63 ± 0.22) kJ mol-1, respectively. The calculated rate constants from first principles agree well with experiments where they are available. Under conditions typical of high temperature combustion - where experimental work is very challenging with a consequent dearth of accurate data - we provide high-level theoretical results for kinetic modeling.