Na2S2O3 Catalyzed Three-Component Synthesis and Anti-Bacterial Activity of 3-Methyl-4-(hetero)arylmethylene isoxazole-5(4H)-ones.

An efficient and green method for synthesizing 3-methyl-4-(hetero) arylmethylene isoxazole-5(4H)-ones was developed using a recyclable and environmental-friendly catalyst, Na2S2O3, and 16 target compounds were successfully synthesized under the obtained optimal reaction condition. Using rifampicin as a positive control, the antibacterial activity of all synthesized compounds was tested by micro dilution method, among them, 3-methyl-4-[(2,4-dimethoxyphenyl) methylene]-isoxazole-5-one (4 m) presented wonderful antimicrobial activity, which may contribute to the development of anti-tuberculosis drugs.

ANKRD36 Is Involved in Hypertension by Altering Expression of ENaC Genes.

[Figure: see text].

Depression and burnout among Chinese nurses during COVID-19 pandemic: a mediation and moderation analysis model among frontline nurses and nonfrontline nurses caring for COVID-19 patients.

BACKGROUND: During the COVID-19 pandemic, nurses' workload increased dramatically, and nurses faced the risk of infection and multiple ethical dilemmas. In such a situation, nurse burnout was elevated, which tended to exacerbate depression in nurses. Although previous studies have demonstrated the relationship between burnout and depression among nurses, the exact mechanisms remain unclear. Furthermore, environmental factors are also essential to a person's psychological health. Therefore, this study intended to investigate the potential mechanisms of depression caused by nurse burnout and whether burnout among frontline nurses during the COVID-19 pandemic exacerbated its effect on depression in nurses as an environmental factor. METHODS: A total of 4517 nurses were enrolled in this study. A moderated mediation model was established to investigate the relationship between burnout and positive coping styles, interpersonal relationships, and depression utilizing the SPSS PROCESS 3.3 macro. The direct effect of burnout on depression was also investigated with the moderated mediation model. RESULTS: The indirect effects of positive coping styles (ß = 0.04, 95% CI: 0.03 to 0.04) and interpersonal relationships (ß = 0.12, 95% CI: 0.10 to 0.13) were revealed. Being a frontline nurse caring for COVID-19 patients moderated the direct effect of burnout on depression (ß = 0.12, 95% CI: 0.08 to 0.16). CONCLUSION: This study offers strong evidence for the mediating role of positive coping styles and interpersonal relationships in the relationship between nurse burnout and depression, in addition to illustrating the need for more psychological support for frontline nurses caring for COVID-19 patients.

Factors influencing parent-child relationships in chinese nurses: a cross-sectional study.

BACKGROUND: With the development of the social economy, the effective coordination of the conflict between work and family has become an urgent problem for most parents. Such conflicts are especially acute in the families of nurses with children. Therefore, a timely understanding of the status quo of the parent-child relationship and associated risk factors among nurses will assist in improving their family harmony and the healthy growth of their children. METHODS: A total of 350 nurses with children at a general tertiary hospital in Sichuan Province, China, were interviewed using a structured questionnaire between June 23 and July 9, 2022. The results were analyzed by multiple linear regression using the stepwise method. RESULTS: The results showed that the parent-child relationship received a middle-level mean score of 77.74 (SD = 10.77). The factors that influenced the parent-child relationship among nurses included the parents' character type (ß = 0.143, P = 0.002), feeling tired due to dealing with patients (ß=-0.150, P = 0.002), the nurse-patient relationship (ß = 0.137, P = 0.004), the age of older children (ß=-0.153, P = 0.001), number of children (ß=-0.093, P = 0.041), sleep quality (ß = 0.116, P = 0.014), and family adaptability (ß = 0.308, P = 0.000); these factors accounted for 31.3% of the variance in parent-child relationships among nurses. CONCLUSION: The findings of this study will help policy makers and nursing managers to better understand parent-child relationships in Chinese nurses. The results highlighted the importance of the creation of a family-oriented work environment while paying more attention to the parent-child relationships of nurses who are introverted and have more or older children. After busy workdays, nurses should also be encouraged to participate more in family decision-making and strategic parent-child interactions to avoid negative effects on children caused by work-related emotional exhaustion, physical and mental fatigue, and other reasons. The development of good parent-child relationships may help maintain both their and their children's mental health while enhancing their enthusiasm for work and their professional identity.

The factors and outcomes of stigma toward mental disorders among medical and nursing students: a cross-sectional study.

BACKGROUND: Medical and nursing students' attitudes toward mental disorders have a large impact on their working intentions in mental health settings and patients' health outcomes. However, there are few studies about the stigma toward mental disorders among medical and nursing students in China. METHODS: In this cross-sectional study, a total of 838 medical and nursing students completed questionnaires on their sociodemographic characteristics and familiarity with people diagnosed with mental disorders as well as the Community Attitudes toward Mental Illness Scale (CAMI). The stigma was compared between medical students and nursing students by ANOVA. A multiple logistic regression model was built to explore the relationships among sociodemographic characteristics, familiarity with mental disorders and stigma. RESULTS: The total mean score of the CAMI was 137.61 (SD = 15.63). The score for authoritarianism (M = 33.33, SD = 3.62) was the lowest score of the four subscales. Medical students showed more positive attitudes toward mental disorders than nursing students. However, after controlling the co-variables, the difference disappeared. Stigma was significantly associated with students' education, area of residence, marital status, economic status, history of mental disorders and familiarity with mental disorders. CONCLUSIONS: Medical and nursing students show a negative attitude toward mental illness to a certain degree, especially regarding the view that people with mental disorders are inferior. Higher education level, residence in urban areas, single marital status, better economic status, and better familiarity with mental disorders may be related to less stigma among medical and nursing students.

Different feed presentations affect subsequent feed sorting and rumen pH for a short period in weaned calves.

The objective of this study was to investigate the short- and long-term effects of different feed presentations on feed sorting and rumen pH in weaned calves. Thirty-six weaned female calves at the age of 12 wk (78 d) were raised in pairs (18 pens; n = 6/treatment) and randomly exposed to 1 of 3 feed presentation treatments: (1) concentrate ration (CON, only exposed to concentrate); (2) separate ration (CH, exposed to concentrate and hay as separate components); and (3) mixed ration (Mix, exposed to a mixed diet containing 75% concentrate and 25% hay). After 4 wk (from d 78 to 105) on different feed presentations, all weaned calves were introduced to a novel total mixed ration (TMR) for another 12 wk (from d 106 to 189). Fresh feed and orts were sampled daily before (wk 12 to 15) and after (wk 16, 17, and 28) transitioning to a TMR diet for analysis of feed sorting. Rumen fluid was sampled in wk 12, 13, 15, 16, 17, and 28 to determine rumen pH. The performance of weaned calves was affected by the different feed presentations during the pre-changing period, such that calves fed CON had a lower dry matter intake (DMI) and average daily gain than calves fed CH and Mix diets. When calves were introduced to the Mix diet, they immediately developed a higher degree of sorting behavior against the long particle fractions. Upon transition to TMR, we did not observe any differences in the performance of calves. However, the sorting behavior established in Mix calves persisted and was similar to calves previously fed the CON diet, whereas the extent of feed sorting in calves initially fed CH was less compared with that in the other 2 treatments in wk 16 and 17. Before changing the diet was transitioned to a TMR, calves fed CON had a lower rumen pH than calves fed CH and Mix. Although rumen pH in all treatments increased to the same level after the diet changed, we observed a tendency toward lower rumen pH in calves fed Mix compared with calves fed CH at wk 17, which might have resulted from the higher degree of feed sorting in these calves. However, by the end of the experiment (wk 28), feed sorting and rumen pH were similar across all treatments. These results indicated a short-term effect of previous feed presentations on subsequent feed sorting and rumen pH, but in the long term disappeared.

Interannual cycles of Hantaan virus outbreaks at the human-animal interface in Central China are controlled by temperature and rainfall.

Hantavirus, a rodent-borne zoonotic pathogen, has a global distribution with 200,000 human infections diagnosed annually. In recent decades, repeated outbreaks of hantavirus infections have been reported in Eurasia and America. These outbreaks have led to public concern and an interest in understanding the underlying biological mechanisms. Here, we propose a climate-animal-Hantaan virus (HTNV) infection model to address this issue, using a unique dataset spanning a 54-y period (1960-2013). This dataset comes from Central China, a focal point for natural HTNV infection, and includes both field surveillance and an epidemiological record. We reveal that the 8-y cycle of HTNV outbreaks is driven by the confluence of the cyclic dynamics of striped field mouse (Apodemus agrarius) populations and climate variability, at both seasonal and interannual cycles. Two climatic variables play key roles in the ecology of the HTNV system: temperature and rainfall. These variables account for the dynamics in the host reservoir system and markedly affect both the rate of transmission and the potential risk of outbreaks. Our results suggest that outbreaks of HTNV infection occur only when climatic conditions are favorable for both rodent population growth and virus transmission. These findings improve our understanding of how climate drives the periodic reemergence of zoonotic disease outbreaks over long timescales.

Anthropogenically driven environmental changes shift the ecological dynamics of hemorrhagic fever with renal syndrome.

Zoonoses are increasingly recognized as an important burden on global public health in the 21st century. High-resolution, long-term field studies are critical for assessing both the baseline and future risk scenarios in a world of rapid changes. We have used a three-decade-long field study on hantavirus, a rodent-borne zoonotic pathogen distributed worldwide, coupled with epidemiological data from an endemic area of China, and show that the shift in the ecological dynamics of Hantaan virus was closely linked to environmental fluctuations at the human-wildlife interface. We reveal that environmental forcing, especially rainfall and resource availability, exert important cascading effects on intra-annual variability in the wildlife reservoir dynamics, leading to epidemics that shift between stable and chaotic regimes. Our models demonstrate that bimodal seasonal epidemics result from a powerful seasonality in transmission, generated from interlocking cycles of agricultural phenology and rodent behavior driven by the rainy seasons.

A gastroenteritis outbreak associated with drinking water in a college in northwest China.

An acute gastroenteritis outbreak occurred at a private college in June 2014 in northwest China. This outbreak involved two teachers and 629 students (range: 17-27 years, average 21.3 years). The main symptoms included non-bloody watery diarrhea, stomach ache, nausea, and vomiting, and the duration of illness ranged from 1 to 7 days. Eight of 18 water samples were disqualified. Thirty-four norovirus (NoV) RNA-positive samples were identified from 48 stool-related samples (genotyping results: 13 GII, 13 GI and 8 GI + GII mixture). Fourteen NoV samples were successfully characterized for genotype, including two GII.6, five GI.6, four GI.3, and three GI.1. Enteropathogenic Escherichia coli (EPEC) and enteroadherent Escherichia coli (EAEC) DNA was detected from patient stool specimens and water samples from well one; two EAEC strains and one EPEC strain were isolated from patient stool specimens. The risk ratios (RRs) associated with wells one and two were 1.66 and 1.49, respectively, and the RR associated with living in north dormitory building one was 2.59. The patients' epidemiological characteristics, symptoms, and duration of illness indicated that NoV-contaminated water might be the origin of this outbreak, and RR analysis suggested that the two wells were linked to the outbreak.

Re-emerging of rabies in Shaanxi province, China, from 2009 to 2015.

To explore the epidemiological, phylogeographic, and migration characteristics of human rabies in Shaanxi province, China from 2009 to 2015. The collected data were described and the sequenced glycoprotein (G) and nucleoprotein (N) genes were implemented to estimate the evolutionary rates and phylogeographic patterns using BEAST v.1.8.2. A total of 269 rabies cases were reported and 70.26% of the cases were male and 61.71% were between the ages of 19-59. The majority of the cases were farmers (83.27%). The estimated evolutionary rate of the N genes was 2.4 × 10-4 substitutions/site/year and the G genes was 3.4 × 10-4 . The time of the most recent common ancestor (TMRCA) was estimated around 1990. We detected viral migration paths from Sichuan, Guizhou, and Hunan to Hanzhong prefecture of Shaanxi and then spreaded to Xi'an and other prefectures. The main population affected by rabies virus was male adult farmers. The evolution rate of rabies viruses in Shaanxi was similar with the prior results reported by others and the ancestor virus should be circulating in neighboring province Sichuan around 1990 and then transmitted to Shaanxi. Promptly standard wound treatment and timely post-exposure prophylaxis should be compulsory for the dog-bitten victims.

[Biomass Compositional Analysis Using Sparse Partial Least Squares Regression and Near Infrared Spectrum Technique].

Forest bio-fuel, a new type renewable energy, has attracted increasing attention as a promising alternative. In this study, a new method called Sparse Partial Least Squares Regression (SPLS) is used to construct the proximate analysis model to analyze the fuel characteristics of sawdust combining Near Infrared Spectrum Technique. Moisture, Ash, Volatile and Fixed Carbon percentage of 80 samples have been measured by traditional proximate analysis. Spectroscopic data were collected by Nicolet NIR spectrometer. After being filtered by wavelet transform, all of the samples are divided into training set and validation set according to sample category and producing area. SPLS, Principle Component Regression (PCR), Partial Least Squares Regression (PLS) and Least Absolute Shrinkage and Selection Operator (LASSO) are presented to construct prediction model. The result advocated that SPLS can select grouped wavelengths and improve the prediction performance. The absorption peaks of the Moisture is covered in the selected wavelengths, well other compositions have not been confirmed yet. In a word, SPLS can reduce the dimensionality of complex data sets and interpret the relationship between spectroscopic data and composition concentration, which will play an increasingly important role in the field of NIR application.

Mental health outcomes and their influencing factors on patients with COVID-19 in the Fangcang shelter hospital in China.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) affects physical and mental health of patients. This study aimed to investigate the psychological distress, level of hope, and the role of families of patients with COVID-19 in the Fangcang shelter hospital (FSH) and explore potential influencing factors. METHODOLOGY: We conducted an online observational cross-sectional study on 397 patients with mild to moderate COVID-19 from two FSH in Shanghai, China from 12 April to 16 May 2022. The questionnaire included demographic information, distress thermometer (DT), family adaptation, partnership, growth, affection, resolve (APGAR) index, and the Herth hope index (HHI). RESULTS: The patients reported symptoms of severe psychological distress (n = 109, 27.46%) and low levels of family care (n = 152, 38.29%). More than half of the patients (n = 244, 61.46%) exhibited high levels of hope, and around one-third of the patients (n = 151, 38.04%) reported moderate levels of hope. The study noted a significant negative correlation between the scores for psychological distress and APGAR and a significant positive correlation between the scores for APGAR and HHI (p < 0.05). The FSH living experience, diet, and symptoms of COVID-19 were closely associated with psychological distress among patients (p < 0.05). CONCLUSIONS: Patients with COVID-19 living in the FSH reported high levels of symptoms of psychological distress and low levels of family care, but relatively high levels of hope. Health care workers should improve the living and eating conditions in the FSH, strengthen family support, and alleviate the COVID-19 related symptoms of patients.

How neonatal diet affects the long-term development of rumination behavior, rumen fermentation and feed digestion in dairy calves fed a high milk level?

This study was to investigate growth performance, rumination development, rumen fermentation and feed digestion in young calves provided high volumes (about 20% of calf birth weight) of milk with or without forage inclusion and how these parameters correlate with each other. Immediately after birth, 160 newborn Holstein female calves (41.6 ± 4.2 kg of initial BW) were randomly divided into 2 treatments: 1) starter (CON, only starter) and 2) starter and hay (HAY, both starter and hay). The calves were fed their respective experimental diets from d 4 to 84, after which they were all introduced to similar diets until the end of the experiment on d 196. Treatment had no effect on growth and structural measurements throughout the experimental period. However, treatment had an effect on the other parameters, mainly during the post-weaning period. Forage supplementation tended to reduce starter dry matter intake (P = 0.05), while increasing the forage intake (P < 0.01) and the feed-to-gain ratio (P < 0.01). HAY calves had increased neutral detergent fiber (NDF) and physically effective NDF (peNDF) intakes (P < 0.05) and tended to lower (P < 0.01) starch intake compared to CON calves. The HAY calves had a higher rumination time (P < 0.01), ruminal pH (P < 0.01), and acetate-to-propionate ratio (P = 0.05) compared to the CON calves. Spearman correlation analysis showed that rumination time was positively related to the ruminal pH at d 84 (P = 0.01) and 196 (P = 0.02). The HAY calves had similar apparent total-tract digestibility of dry matter (DM), NDF and ether extract (EE), but lower digestibility of organic matter (OM, P = 0.03), crude protein (CP, P < 0.01) and starch (P < 0.01) compared to those of the CON calves at week 12. Furthermore, there were no positive relationships between rumination time and nutrient digestibility or between rumination time per kilogram DM and nutrient digestibility. In conclusion, feeding hay to calves fed a high milk level improved rumination during the post-weaning period only, without a concomitant effect on growth performance throughout the experimental period, suggesting no detrimental effect of feeding forage in calves fed high milk level.

Initial diet shapes resistance-gene composition and fecal microbiome dynamics in young ruminants during nursing.

This study was conducted to examine how colostrum pasteurization affects resistance genes and microbial communities in calf feces. Forty female Holstein calves were randomly assigned to either the control (CON) group, which received unheated colostrum, or the pasteurized colostrum (PAT) group. The calves body weight was measured weekly before morning feeding. Calf starter intake were measured and recorded daily before morning feeding. Samples of colostrum were collected before feeding. Blood was collected on d 1 and 70 before morning feeding. Ten calves were randomly selected from each group (n = 20 calves total) for fecal sampling on d 3, 28, 56 and 70 for subsequent DNA extraction and metagenomic sequencing. Total bacterial counts in the colostrum were markedly higher in the CON group than in the PAT group. Pasteurized colostrum administration substantially reduced the ARO diversity and diminishes the abundance of Enterobacteriaceae, thereby decreasing their contribution to resistance genes. Pasteurization also reduced glucoside hydrolase-66 activity in 3-day-old calves which led to an increase in the activity of aminoglycoside antibiotics, resulting in 52.63 % of PAT-enriched bacteria acquiring aminoglycoside resistance genes. However, from the perspective of overall microbial community, the proportion of aminoglycoside, beta-lactam and tetracycline resistance genes carried by microbial community in PAT group was lower than CON group (P < 0.05). Fecal samples from the PAT group contained greater abundances of Subdoligranulum (P < 0.05) and Lachnospiraceae_NK4A136_group (P < 0.05) on days 28 and 70 compared to CON. Network analysis and abundance variations of the different bacteria obtained by linear discriminant analysis effect size analysis showed that pasteurized colostrum feeding reduced the interactions among related bacteria and maintained stability of the hind-gut microbiome. In conclusion, these findings underscore the intricate interactions between early diet, calf resistance-gene transmission and microbial dynamics, which should be carefully considered in calf-rearing practices.

Unlocking the power of postbiotics: A revolutionary approach to nutrition for humans and animals.

Postbiotics, which comprise inanimate microorganisms or their constituents, have recently gained significant attention for their potential health benefits. Extensive research on postbiotics has uncovered many beneficial effects on hosts, including antioxidant activity, immunomodulatory effects, gut microbiota modulation, and enhancement of epithelial barrier function. Although these features resemble those of probiotics, the stability and safety of postbiotics make them an appealing alternative. In this review, we provide a comprehensive summary of the latest research on postbiotics, emphasizing their positive impacts on both human and animal health. As our understanding of the influence of postbiotics on living organisms continues to grow, their application in clinical and nutritional settings, as well as animal husbandry, is expected to expand. Moreover, by substituting postbiotics for antibiotics, we can promote health and productivity while minimizing adverse effects. This alternative approach holds immense potential for improving health outcomes and revolutionizing the food and animal products industries.

Outbreak of acute respiratory disease caused by human adenovirus type 7 in a military training camp in Shaanxi, China.

Outbreaks of ARD associated with HAdV have been reported in military populations in many countries. Here, we report an ARD outbreak caused by HAdV-7 in a military training camp in Shaanxi Province, China, from February to March of 2012. Epidemic data and samples from the patients were collected, and viral nucleotides from samples and viral isolations were detected and sequenced. IgG and IgA antibodies against HAdV, and the neutralization antibodies against the viral strain isolated in this outbreak, were detected. Epidemiological study showed that all personnel affected were males with an average age of 19.1 years. Two peaks appeared on the epicurve and there was an 8-day interval between peaks. Laboratory results of viral nucleotide detection carried out with clinical specimens were positive for HAdV (83.33%, 15/18). Further study through serum antibody assay, virus isolation and phylogenetic analysis showed that HAdV-7 was the etiological agent responsible for the outbreak. IgA antibody began to appear on the 4th day after the onset and showed 100% positivity on the 8th day. The virus strain in the present outbreak was highly similar to the virus isolated in Hanzhong Shaanxi in 2009. We conclude that HAdV-7 was the pathogen corresponding to the outbreak, and this is the first report of an ARD outbreak caused by HAdV-7 in military persons in China. Vaccine development, as well as enhanced epidemiological and virological surveillance of HAdV infections in China should be emphasized.

[Comparison of direct immune-fluorescent assay and real-time quantitative PCR in detecting the Hantavirus].

OBJECTIVE: To compare the differences between the direct immuno-fluorescent assay (DFA) and real-time quantitative PCR in detecting the Hantavirus (HV) in rat lungs. METHODS: From April to October in 2012, a total of 479 rats were caught by mouse-trap in residential or wild areas in Huxian, Jingyang, and Meixian of Shaanxi province, where haemorrhagic fever with renal syndrome (HFRS) was highly prevalent. The rats were dissected to take the two lungs, one was frozen and applied immuno-fluorescent assay to detect HV antigen while the other one was extracted its RNA and detected HV nucleic acid by real-time quantitative PCR. Then we compared the positive rate of the two methods. RESULTS: Out of the 479 rats, 105 were caught from residential areas and the other 374 were caught from wild areas. Among the 105 rats caught from residential areas, no HV were detected out neither by DFA nor by real-time quantitative PCR. Among the 374 wild rats, 13.1% (49/374) were detected HV positive by DFA and 14.7% (55/374) were detected HV positive by real-time quantitative PCR. The difference showed no statistical significance (χ(2) = 0.402, P = 0.526). When detecting each lung sample, the HV positive rate was 10.2% (49/479) under the detection by DFA while the HV positive rate was 11.5% (55/479) under the detection by real-time quantitative PCR. The difference had no statistical significance (χ(2) = 1.286, P = 0.257) and the consistency coefficient was 68.2% under the paired chi-square test analysis, which showed high consistency (u = 11.759, P < 0.05). The sensitivity of real-time quantitative PCR to detect HV was 77.6% (38/49) comparing with DFA as standard, and the specificity was 96.1% (413/430). Out of the 9 suspected HV positive sample detected by DFA, 6 were confirmed positive by real-time quantitative PCR and 3 were denied. CONCLUSION: Compared with the DFA, real-time quantitative PCR could also be used to detect the infection of HV in rats, and the result might be more stable.

The Death Café: Effectiveness of a hospice care educational program for nursing undergraduates based on LIFE experience-A qualitative study.

BACKGROUND: Nursing students' knowledge of hospice care is limited to textbooks due to the inadequate education and training system in China and student's willingness to participate in hospice care. OBJECTIVES: To deepen nursing students' understandings toward life and death, to improve their knowledge about hospice care, and to promote their willingness for hospice care practice. DESIGN: This study used a qualitative descriptive study design. SETTINGS: The study was conducted at a medical university in Sichuan province, China. PARTICIPANTS: 71 nursing sophomores participated in this study. METHODS: The Death Café teaching program was implemented which requires students to recall their memories about death and to imagine how they felt about dying, as if they were having a conversation in a death-themed café. During the implementation phase, a small-group interactive teaching approach was utilized. During the reflection phase, the students were asked to finish an essay answering four questions without standard right answers. The essays that students finished were used for evaluating the effectiveness of the Death Café program. The answers of the first two questions were presented as a word cloud. Graneheim and Lundman's qualitative content analysis method was used to analyze answers of the third and fourth questions. RESULTS: Word cloud analysis indicated that at the beginning of the program participants showed more negative emotions (i.e., fearful). Students' attitudes toward death changed from negative to positive through imagining death when role-playing the different stages of life. The program enhanced students' understanding of life and taught the students effective ways to cope with death. Students clarified the objectives and necessary preparation for providing hospice care and gained new understandings for improving their hospice skills. CONCLUSIONS: The Death Café program can address students' negative emotions and perceptions of death. Students gained personal benefits and professional benefits of coping with life and death from the program.

Dietary Neutral Detergent Fiber Levels Impacting Dairy Cows' Feeding Behavior, Rumen Fermentation, and Production Performance during the Period of Peak-Lactation.

This study investigated the impact of dietary neutral detergent fiber (NDF) levels (25.49%, 28.65%, 31.66%, and 34.65%, respectively) on the feeding behavior, rumen fermentation, cellulolytic bacteria, and production performance of dairy cows during peak lactation. A feeding experiment was conducted using four fistulated Holstein dairy cows (600 ± 25 kg) with days in milk (50 ± 15 days), employing a 4 × 4 Latin square design to assign the cows to four groups. The results demonstrated that increasing NDF levels in the diet had the following effects: (1) A linear decrease in dry matter intake (DMI), NDF intake, and physically effective NDF8.0 (peNDF8.0) intake; a linear increase in the average time spent eating and ruminating, as well as the time spent eating and ruminating per kilogram of dry matter (DM); a quadratic response in the time spent ruminating per kilogram of NDF and peNDF8.0. (2) A linear increase in average pH value, acetate concentration, and the proportions of Fibrobacter succinogenes and Ruminococcus flavefaciens among total bacteria; a linear decrease in ammonia nitrogen (NH3-N) concentration, microbial crude protein (MCP), total volatile fatty acid (TVFA), propionate, butyrate, and lactate. (3) A linear decrease in milk yield, milk protein percentage, and nitrogen efficiency of dairy cows; a linear increase in milk fat percentage and milk urea nitrogen (MUN) concentration. Based on the combined results, it was found that diets with 25% and 34% NDF had detrimental effects on the feeding behavior, rumen fermentation, and production performance of dairy cows. However, the diet with 28% NDF showed superior outcomes in production performance compared to the one with 31% NDF. Therefore, it is strongly recommended to include a diet containing 28% NDF during the critical peak lactation period for dairy cows.

CYP2D6 Substrate Dispensing Among Patients Dispensed Mirabegron: An Administrative Claims Analysis.

BACKGROUND: Overactive bladder (OAB) is characterized by the presence of bothersome urinary symptoms. Pharmacologic treatment options for OAB include anticholinergics and ß3-adrenergic agonists. Use of ß3-adrenergic agonists may result in similar treatment efficacy with a decreased side effect profile compared with anticholinergics because high anticholinergic burden is associated with cardiovascular and neurologic side effects. However, the ß3-adrenergic agonist mirabegron, one of two approved drugs within this class, is a moderate cytochrome P450 (CYP) 2D6 inhibitor, and coadministration of drugs that are CYP2D6 substrates with mirabegron may lead to adverse drug effects. OBJECTIVE: The aim of this study was to quantify how often CYP2D6 substrates were dispensed in patients receiving mirabegron among adults of any age and among those ≥ 65 years of age. METHODS: In this retrospective descriptive analysis, a deidentified administrative claims database in the United States, IQVIA PharMetrics® Plus, was used to identify dispensing claims for CYP2D6 substrates and mirabegron from November 2012 to September 2019. Prevalence of CYP2D6 substrate dispensing was assessed in patients dispensed mirabegron among all adults ≥ 18 years old and additionally among a cohort of those ≥ 65 years old. Patient baseline profiles at the time of mirabegron and CYP2D6 substrate codispensing and at the time of mirabegron dispensing were compared. CYP2D6 substrates were categorized as those with the potential for increased risk of QT prolongation, with anticholinergic properties, with narrow therapeutic index (NTI), contraindicated or having a black box warning when used with CYP2D6 inhibitors, or used for depression or other psychiatric disease. Dispensing data and patient profiles were summarized descriptively. RESULTS: Overall, 68.5% of adults ≥ 18 years old dispensed mirabegron had overlapping dispensings for one or more CYP2D6 substrate; 60.6% and 53.6% had overlapping dispensings for CYP2D6 substrates with anticholinergic properties or risk of QT prolongation, respectively. CYP2D6 substrates with NTI, contraindicated with CYP2D6 inhibitors, or for psychiatric use were codispensed in 17.7%, 16.6%, and 38.0% of adult mirabegron users, respectively. Mirabegron users receiving one or more concurrent CYP2D6 substrate were more likely to be older, have more comorbidities and baseline polypharmacy, and have increased healthcare resource utilization compared with those without concurrent CYP2D6 substrates. Commonly codispensed CYP2D6 substrates included hydrocodone, oxycodone, tramadol, metoprolol, and tamsulosin. Findings were similar for patients in the older cohort (≥ 65 years old), with 72.1% receiving overlapping CYP2D6 substrates. CONCLUSIONS: Codispensing of CYP2D6 substrates, especially those with anticholinergic properties or risk of QT prolongation, was common among adults and older adults receiving mirabegron. Results highlight the need for improved awareness of CYP2D6 substrate prescribing among patients receiving pharmacologic treatment for OAB that inhibits the CYP2D6 pathway.