Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

The Gut Microbiome and Symptom Burden After Kidney Transplantation: An Overview and Research Opportunities.

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study.

An evaluation of a healthy participant laboratory model of epidural hyperthermia: a physiological study.

BACKGROUND: Hyperthermia complicates 21% of cases of intrapartum epidural analgesia, but the mechanism is unclear. One hypothesis is that blockade of cholinergic sympathetic nerves prevents active vasodilation and sweating, thus limiting heat loss. Because labour increases heat production, this could create a situation in which heat production exceeds loss, causing body temperature to rise. This physiological study tested a novel laboratory model of epidural-related hyperthermia, using exercise to simulate the increased heat production of labour and surface insulation to simulate the effect of epidural analgesia. METHODS: Twelve healthy non-pregnant participants (six female) cycled an ergometer for two hours at 20 Watts (W) on two occasions: once with surface insulation (intervention) and once without (control). Core temperature, skin temperature (eight sites), and heat loss (eight sites) were recorded. Mean body temperature and heat production were calculated. Values are mean (SD). RESULTS: Exercise increased heat production on both visits (intervention 38 (18) W; control 37 (31) W; P = 0.94). Total heat loss was less on the intervention visit (intervention 115 (19) W; control 129 (23) W; P = 0.002). Core temperature increased on both visits (intervention 0.21 (0.37)°C; control 0.19 (0.27)°C; P < 0.001). The increase in mean body temperature was greater on the intervention visit (intervention 0.47 (0.41)°C; control 0.25 (0.19)°C; P = 0.007). CONCLUSIONS: This laboratory model predicts that labour epidural analgesia limits heat loss by >14 W. Once the model is validated, it could be used to test the efficacy of potential interventions to prevent and treat epidural-related maternal hyperthermia.

Feasibility Study to Compare Oxytocin Function Between Body Mass Index Groups at Term Labor Induction.

OBJECTIVE: To determine the feasibility of a protocol to examine the association between oxytocin system function and birth outcomes in women with and without obesity before induction of labor. DESIGN: Prospective descriptive. SETTING: Academic medical center in the U.S. Midwest. PARTICIPANTS: Pregnant women scheduled for induction of labor at 40 weeks of gestation or greater (n = 15 normal weight; n = 15 obese). METHODS: We collected blood samples and abstracted data by chart review. We used percentages to examine adherence to protocol. We used t tests and chi-square tests to describe differences in sample characteristics, oxytocin system function variables, and birth outcomes between the body mass index groups. RESULTS: The recruitment rate was 85.7%, protocol adherence was 97.1%, and questionnaire completion was 80.0%. Mean plasma oxytocin concentration was higher in the obese group (M = 2774.4 pg/ml, SD = 797.4) than in the normal weight group (M = 2193.5 pg/ml, SD = 469.8). Oxytocin receptor DNA percentage methylation (CpG -934) was higher in the obese group than in the normal weight group. CONCLUSION: Our protocol was feasible and can serve as a foundation for estimating sample sizes in forthcoming studies investigating the diversity in oxytocin system measurements and childbirth outcomes among pregnant women in different body mass index categories.

Factors associated with mental health among undergraduate nursing students early in the COVID-19 pandemic: an integrative review.

OBJECTIVES: We aimed to synthesize research findings identifying factors associated with mental health in undergraduate nursing students early in the COVID-19 pandemic. METHODS: Seven electronic databases were searched using key terms and subject headings. JBI Critical Appraisal Checklists were used to evaluate research report quality. RESULTS: Among 23 reports (19 quantitative and four qualitative) meeting inclusion criteria, negative emotional responses to COVID-19 (fear of infection, perceived risk, uncertainty about care/future), negative behavioral responses to COVID-19 (eating behaviors, problematic internet use, insomnia), and negative coping strategies were associated with more adverse mental health symptoms. Conversely, social support, professional identity, preventive behaviors, sufficient personal protective equipment (PPE), and positive coping strategies were related to fewer symptoms. CONCLUSIONS: During a pandemic, undergraduate nursing students require educational support to promote their ability to avoid severe mental health disorders. Also, educators should strengthen students' professional identity, provide infection prevention knowledge and skills, and supply sufficient PPE.

[High-fat intake alleviates lung injury induced by Paragonimus proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues].

OBJECTIVE: To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments. METHODS: SD rats were randomly assigned into three groups, including the normal control group (n = 10), the infection and normal diet group (n = 12) and the infection and high-fat diet group (n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1ß (IL-1ß) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays. RESULTS: Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1ß [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1ß: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1ß: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05). CONCLUSIONS: High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Natural products for treatment of premature ovarian failure: a narrative review.

Premature ovarian failure (POF) is a female reproductive system disease caused by many factors and systems, which has seriously affected the quality of life of women of childbearing age. Clinically, the disease is difficult to treat while its incidence rate shows an increasing trend. In recent years, natural products used as multi-pathway, multi-target and efficient drugs, have become the focus of many research and clinical studies in China and abroad, and the effect of phytochemicals derived from edible plants and Chinese medicine herbs on POF were investigated in several papers. Using "premature ovarian failure" or "ovary" and related natural products as keywords, we retrieved and reviewed research articles from China National Knowledge Infrastructure Database, Wanfang, PubMed, Web of Science and other literature databases. Up to October, 2021, natural compounds with prophylactic or interference inhibition effects on POF mainly included flavonoids, polysaccharides, saponins, and polyphenols. Their effect on POF and ovarian function was closely related to their antioxidant, antiapoptotic, antiaging, immunoregulatory and estrogen-like activities.

Shift work domains and their interactions with empty calorie food/beverage consumption: A 14-day intensive longitudinal study.

BACKGROUND/OBJECTIVES: Shift work has been linked to unhealthy eating behaviors such as imbalanced diet, or increased empty calorie food/beverage consumption. However, most research has focused on the impact of shift timing. The concept of shift work is complex, and it contains several domains such as shift timing, intensity, and speed. Previous studies have suggested that greater shift intensity and quicker shift speed may contribute to adverse health effects. However, evidence regarding associations between other domains of shift work and empty calorie food/beverage consumption has been relatively lacking. Therefore, the purpose of this study was to evaluate how other shift work domains related to empty calorie food/beverage consumption and whether different shift work domains interacted to influence the intake of foods or beverages. DESIGN: A 14-day intensive longitudinal study employing ecological momentary assessment. SETTINGS AND PARTICIPANTS: Eighty registered nurses working in 24 accredited Taiwanese hospitals (i.e., 9 medical centers, 12 regional hospitals, and 3 district hospitals) were recruited. METHODS: During the study period, a convenience sample of 77 participants completed 2444 momentary surveys about empty calorie food/beverage consumption on a smartphone. Three shift work domains (shift timing, intensity, and speed) were evaluated based on registry-based work schedules. To study how these shift work domains influenced empty calorie food/beverage consumption, we employed three-level mixed-effects regression models for data analyses. RESULTS: Findings suggested that greater night shift intensity increased the likelihood of sugar-sweetened beverage intake (odds ratio = 1.64, 95% confidence interval [1.01, 2.68]). The impacts of work shift intensity and shift timing on sugar-sweetened beverage consumption varied by shift speed. Among participants assigned a schedule with either medium or rapid shift speed, higher work shift intensity was associated with a higher probability of sugar-sweetened beverage consumption. Compared to day shifts, those who were assigned a quicker shift speed on evening shifts were more likely to consume sugar-sweetened beverages. However, associations between night shift intensity and sugar-sweetened beverage intake did not change by shift speed. Furthermore, shift intensity and shift timing did not interact to affect empty calorie food/beverage consumption. CONCLUSIONS: This study demonstrated assignments of shift schedules (i.e., high night shift intensity, more changes in shift timings) might influence workers' consumption of empty calorie foods/beverages. Therefore, identifying and mitigating hazardous shift schedules may help to improve shift workers' eating behaviors and benefit their overall health.

Decision Delay Is a Significant Contributor to Prehospital Delay for Stroke Symptoms.

Prehospital delay after stroke symptom onset is a primary barrier to eligibility for reperfusion therapies. Decision delay is an understudied contributor to prehospital delay. We aimed to explore decision delay as a component of prehospital delay. For this correlational study, 170 Thai acute stroke patients were interviewed to explore their treatment-seeking decision factors: prior stroke knowledge, onset context, and cognitive, emotional, and behavioral factors. Participants' mean age was 61.2 years, and 46% were women. Median decision delay and prehospital delay times were 120 and 372 minutes. Decision delay represented 49% of prehospital delays. Factors shortening decision delay were atrial fibrillation, prior stroke knowledge, perceived cause of symptoms as stroke, perceived severity of symptoms, and advice from bystanders to seek treatment. In contrast, seeking support from others and self-treatment affected prolonged decision delay. Shortening decision delay, often under the patient or bystander control, can reduce overall prehospital delay.

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.

BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation. DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital & Health Sciences System. PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients. METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R = .306, p = .022), and between pain interference groups at posttransplant (R = .249, p = .041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain.

Associations between sleep variability and cardiometabolic health: A systematic review.

This review explored the associations between sleep variability and cardiometabolic health. It was performed following PRISMA guidelines. We identified 63 studies. Forty-one studies examined the association between sleep variability and body composition, with 29 examined body mass index (BMI). Thirteen studies used social jet lag (SJL), n = 30,519, with nine reporting a null association. Eight studies used variability in sleep duration (n = 33,029), with five reporting a correlation with BMI. Fourteen studies (n = 133,403) focused on overweight/obesity; significant associations with sleep variability were found in 11 (n = 120,168). Sleep variability was associated with weight gain (seven studies; n = 79,522). Twenty-three studies examined glucose outcomes. The association with hemoglobin A1c (16 studies, n = 11,755) differed depending on populations, while associations with diabetes or glucose were mixed, and none were seen with insulin resistance (five studies; n = 6416). Sixteen studies examined cardiovascular-related outcomes, with inconsistent results. Overall significant associations were found in five studies focusing on metabolic syndrome (n = 7413). In summary, sleep variability was likely associated with obesity, weight gain, and metabolic syndrome. It might be associated with hemoglobin A1c in people with type 1 diabetes. The associations with other outcomes were mixed. This review highlighted the possible association between sleep variability and cardiometabolic health.

[Analysis of prognosis factors of postoperative cardiac complications in colorectal cancer patients with comorbid coronary artery disease].

Objective: To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease. Methods: Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results: After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years(OR=3.195, 95%CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes (OR=2.551, 95%CI: 1.294 to 5.025, P=0.007), emergency surgery (OR=4.717, 95%CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio (OR=1.114, 95%CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions: Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

Effects of residual feed intake divergence on growth performance, carcass traits, meat quality, and blood biochemical parameters in small-sized meat ducks.

Feed efficiency (FE) is a major economic trait of meat duck. This study aimed to evaluate the effects of residual feed intake (RFI) divergence on growth performance, carcass traits, meat quality, and blood biochemical parameters in small-sized meat ducks. A total of 500 healthy 21-day-old male ducks were housed in individual cages until slaughter at 63 d of age. The growth performance was determined for all the ducks. The carcass yield, meat quality, and blood biochemical parameters were determined for the selected 30 high-RFI (HRFI) and 30 low-RFI (LRFI) ducks. In terms of growth performance, the RFI, feed conversion ratio (FCR), and average daily feed intake (ADFI) were found to be significantly lower in the LRFI group (P < 0.01), whereas no differences were observed in the BW and body weight gain (P > 0.05). For slaughter performance, no differences were observed in the carcass traits between the LRFI and HRFI groups (P > 0.05). For meat quality, the shear force of breast muscle was significantly lower in the LRFI group (P < 0.05), while the other meat quality traits of breast and thigh muscles demonstrated no differences (P > 0.05). For blood biochemical parameters, the serum concentrations of triglycerides (TG) and glucose (GLU) were significantly lower in the LRFI group (P < 0.05), while the other parameters showed no differences (P > 0.05). The correlation analysis demonstrated a high positive correlation between RFI, FCR, and ADFI (P < 0.01). The RFI demonstrated a negative effect on the breast muscle and lean meat yields, but a positive effect on the shear force of breast muscle (P < 0.05). Further, the RFI demonstrated a positive effect on the TG and GLU levels (P < 0.05). These results indicate that the selection for low RFI could improve the FE of small-sized meat ducks without affecting the production performance. This study provides valuable insight into the biological processes underlying the variations in FE in small-sized meat ducks.

Psychometric properties of the Insomnia Severity Index for people with chronic obstructive pulmonary disease.

OBJECTIVE/BACKGROUND: Insomnia is one of the most commonly reported symptoms among people with chronic obstructive pulmonary disease (COPD). Prior research evaluated the psychometric properties of the Insomnia Severity Index (ISI) with various populations, but no studies have examined the measurement properties of the instrument in the COPD population. This study aimed to determine the reliability and validity of the ISI for the COPD population. PATIENTS/METHODS: This study included 96 people with COPD and insomnia. As psychometric properties, the ISI's internal consistency, factor structure, and criterion validity were examined with this sample. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to evaluate construct validity. Correlations between scores for the ISI and for measures of depression, anxiety, fatigue, and dyspnea were examined to determine criterion validity. RESULTS: The Cronbach's alpha value for the ISI was 0.79, indicating good internal consistency. In the EFA, a single ISI factor with an eigenvalue of 3.19 accounted for 45.6% of the variance. CFA indicated adequate construct validity, and interference of sleep problems with daytime functioning and level of distress caused by sleep difficulties showed the highest factor loadings (both 0.78). Criterion validity was supported by significant, weak to moderate correlations between scores for the ISI and for measures of depression, anxiety, fatigue, and dyspnea. CONCLUSIONS: The results provide evidence that the ISI has good reliability and validity for measuring insomnia severity in the COPD population.

A high-concentrate diet induces an inflammatory response and oxidative stress and depresses milk fat synthesis in the mammary gland of dairy cows.

Although high-concentrate diet feeding can temporarily increase milk production, it can cause a series of metabolic diseases, such as subacute ruminal acidosis (SARA) and milk fat depression. The main purpose of this experiment was to study the effects of a high-concentrate diet on the inflammatory response, oxidative stress, and milk fat synthesis in the mammary gland of dairy cows. Twelve Holstein cows equipped with rumen fistulas were randomly divided into 2 groups, each with 6 cows, fed a low-concentrate diet (LC) and a high-concentrate diet (HC). On d 20 and 21 of the experiment, rumen fluid was collected to measure pH, and milk samples were collected for milk component analysis and lipopolysaccharide (LPS) concentration testing. On d 21, mammary vein blood was collected to detect the LPS concentration. At the end of the 21-d experimental period, mammary gland tissue was collected, and the expression of inflammatory response-, oxidative stress-, and milk fat synthesis-related genes and proteins in the mammary gland was analyzed by real-time quantitative PCR and western blot. The pH of rumen fluid in the HC group was significantly lower than that in the LC group, and the pH of 2 time points in the HC group was lower than 5.6, indicating that a high-concentrate diet induced SARA. The LPS concentration of the peripheral blood in HC group increased significantly compared with that in the LC group. For the inflammatory response, the proinflammatory cytokines (IL-6 and IL-1α) and innate immune factors (lingual antimicrobial peptide and tracheal antimicrobial peptide) in the mammary gland of the HC group were significantly increased, and the TLR4-NF-κB signaling pathway was activated. For oxidative stress, after HC diet feeding, the content of malondialdehyde in mammary vein blood and mammary gland tissue increased, the content of glutathione in mammary vein blood decreased, the activity of superoxide dismutase and the total antioxidant capacity in mammary gland tissue and mammary vein blood decreased, and the expression of antioxidant enzymes and antioxidant transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2) in mammary gland decreased. For milk fat metabolism, HC diet feeding reduced the milk fat content in milk samples and the triacylglycerol content in the mammary gland and inhibited the expression of de novo synthase (ACACA and FASN), long-chain fatty acid converting enzymes (ACSL1 and SCD), fatty acid transporters (CD36, FATP, FABP3, and LPL), triacylglycerol synthase (AGPAT6, DGAT1, and LPIN1), lipid droplet releasing enzyme (PLIN1), and transcription factors sterol regulatory element binding protein (SREBP1) and peroxisome proliferator activated receptor gamma (PPARG). In summary, a HC diet can induce SARA with increased concentration of LPS in the peripheral vein, stimulate inflammatory reactions and oxidative stress, and inhibit milk fat synthesis in the mammary gland of dairy cows.

[The value of color doppler ultrasonography in the diagnosis of endograft infections following endovascular aneurysm repair].

Objective: To study the value of color doppler ultrasonography (CDU) in the diagnosis of endograft infections following endovascular aneurysm repair (EVAR). Methods: The retrospective analysis of post-EVAR stent infections identified by computed tomography angiography (CTA) was conducted at the First Affiliated Hospital of Sun Yat-sen University from January 2010 to December 2020. There were 16 males and 4 females, aged from 49 to 86 years. All the patients were detected by CDU. The endoleak, bubbles, abscess, hematoma, aortic intestinal fistula (AEF) and occlusion of stent detected by CTA and CDU were analyzed and compared. Results: Among 20 patients, 9 cases with endoleak were detected by CTA, while CDU showed 8 cases with endoleak. The rate of missed diagnosis was 1/9. The misdiagnosis rate was 0, and the Youden index was 0.89. CDU detected 3 cases with type Ⅱ endoleak, and 1 case was missed when compared with CTA. Three cases with type Ⅰa and 2 cases with type Ⅰb were detected by CDU, which were consistent with those of CTA. CDU and CTA showed that there were no cases with type Ⅲ and type Ⅳ endoleaks. CDU detected 8 cases with bubbles in the sac. Compared with CTA, the rate of missed diagnosis was 2/10. The misdiagnosis rate was 0, and the Youden index was 0.80. The cases with abscess, hematoma, increasing size of the aneurysm, occlusion of stent and fluid sonolucent area in the sac detected by CDU were 8/20, 2/20, 4/20, 1/20, 2/20, which were consistent with CTA. CDU did not detect the 3 cases with aortoenteric fistula(AEF) which were identified by CTA. The follow-up of CDU showed that the extra-anatomic bypasses remained their patency in 5 cases, 1 case occurred bypass occlusion. The range of infectious area and bubbles reduced in 2 cases. There was no change of endoleak in 1 case. All the follow-up results were consistent with those of CTA. Conclusion: CDU can comprehensively evaluate the infection in and around the aneurysm in patients with stentinfection after EVAR, with a high auuraly, and has important clinical significance for the early diagnosis, treatment and prognosis of patients.

Feasibility of sleep extension and its effect on cardiometabolic parameters in free-living settings: a systematic review and meta-analysis of experimental studies.

AIMS: Inadequate sleep is a global health issue and has been associated with an increased risk for cardiovascular diseases. As a part of sleep hygiene, intentional lengthening of night-time sleep duration (i.e. sleep extension) might be a behavioural intervention to improve cardiometabolic health. To examine the feasibility of sleep extension and its effects on cardiometabolic parameters in free-living settings. METHODS AND RESULTS: This review was registered in PROSPERO (CRD42019146174). Five databases were searched. Only experimental studies conducted in adults without a diagnosis of sleep disorder were included. The pooled mean difference was calculated by the inverse variance method. Narrative summaries were also used. Thirteen studies from 11 trials were included. The intervention ranged from 3 days to 6 weeks. Sleep extension increased total sleep time by 51 min [95% confidence interval (CI) 39-63]. Overall, sleep extension did not result in significant changes in blood pressure. However, sub-group analysis revealed that when 24 h mean blood pressure was obtained among those with pre-hypertension or Stage 1 hypertension, sleep extension reduced systolic (weighted mean difference = -7.8 mm/Hg; 95% CI -10.6 to -4.9), and diastolic blood pressure (weighted mean difference = -4.2 mm/Hg; 95% CI -6.7 to -1.8). The pooled effects on fasting glucose and insulin resistance were not significant. The effect of sleep extension on other parameters (e.g. heart rate) was not consistent. CONCLUSION: Sleep extension is feasible and could increase sleep in free-living settings. Sleep extension shows promise for reducing 24 h mean blood pressure among those with pre-hypertension or hypertension. More large-scale studies are needed to examine its long-term effects.

Research Note: Effects of cage and floor rearing systems on growth performance, carcass traits, and meat quality in small-sized meat ducks.

This study was performed to evaluate the effects of different rearing methods on the growth performance, carcass yield, and meat quality of small-sized meat ducks. A total of 420 healthy 21-day-old birds was randomly allocated to 2 treatment groups (6 replicates per treatment, sex ratio 1/1) and subjected to 2 rearing methods (furnished cage and plastic wire-floor) until d 63. Growth performance was measured in all birds. Three males and 3 females from each replicate were randomly selected and evaluated to determine the carcass yield and meat quality. In terms of growth performance, the rearing method affected the final body weight, average daily feed intake, and average daily gain, which were higher in the cage group (P < 0.05) than in the floor group, with a similar feed/gain in both groups. For slaughter performance, ducks in the cage group showed a higher abdominal fat yield and lower gizzard yield than those in the floor group (P < 0.05). For meat quality, the L* value of the breast muscle was higher in the cage group than in the floor group (P < 0.05). The pH recorded at 1 h was lower and pH recorded at 24 h was higher in the cage group (P < 0.05). The shear force and water loss rate were both lower in the cage group (P < 0.05). Additionally, the moisture content was lower and intramuscular fat content was higher in ducks fed in cages (P < 0.05). Our results indicate that the cage rearing system improved the growth performance and meat quality of ducks, which is appropriate for small-sized meat ducks.

[Efficacy of endovenous microwave ablation in treating primary varicose veins of the lower extremities].

Objective: To explore the efficacy of endovenous microwave ablation in treating primary varicose veins of the lower extremities. Methods: A total of 214 patients with primary varicose veins of the lower extremities in the First Affiliated Hospital of Sun Yat-sen University from January 2017 to November 2019 were included and divided into microwave ablation group (n=128) and high ligation with microwave ablation group (n=86) according to surgical approach. Further subgroups including subgroup S (diameter<10 mm) and subgroup L (diameter≥10 mm) were established. The surgical success rate, postoperative incidence and recovery of local skin numbness and ecchymosis, and the postoperative recovery of active skin ulcer were compared between the two groups and subgroups. Results: The surgical success rate was 96% (136/141) in microwave ablation group, 100% in subgroup S (116/116), and 80% in subgroup L (20/25), respectively. In addition, the surgical success rate in high ligation with microwave ablation group, subgroup S, and subgroup L was all 100% (90/90, 73/73, and 17/17). In subgroup L of microwave ablation group, the diameter of 5 great saphenous veins in patients who failed the microwave ablation was 13.0-17.1 mm. The mean follow-up time was (24±4) months in microwave ablation group and (36±6) months in high ligation with microwave ablation group, respectively. In the microwave ablation group and high ligation with microwave ablation group, the incidence of postoperative skin numbness was 15.6% and 14.4%, respectively, and the incidence of skin ecchymosis was 5.7% and 3.3%, respectively, with no statistically significant difference between the two groups (both P>0.05). The rate of active skin ulcer in the two groups was 6.4% and 15.6%, respectively, and the difference was statistically significant (P=0.020). Local skin ecchymosis in the two groups recovered within 1 month after operation. Local skin numbness in both groups recovered within the maximum 2 years of follow-up, and active skin ulcer in both groups recovered within the maximum 1 years of follow-up. Conclusion: The endovenous microwave ablation is safe and effective, especially combining with high ligation of great saphenous vein. Good follow-up results can be achieved for great saphenous vein with diameter smaller than 10 mm. However, for those with diameter greater than 10 mm, the surgical success rate of endovenous microwave ablation decreases.

THF co-solvent pretreatment prevents lignin redeposition from interfering with enzymes yielding prolonged cellulase activity.

BACKGROUND: Conventional aqueous dilute sulfuric acid (DSA) pretreatment of lignocellulosic biomass facilitates hemicellulose solubilization and can improve subsequent enzymatic digestibility of cellulose to fermentable glucose. However, much of the lignin after DSA pretreatment either remains intact within the cell wall or readily redeposits back onto the biomass surface. This redeposited lignin has been shown to reduce enzyme activity and contribute to rapid enzyme deactivation, thus, necessitating significantly higher enzyme loadings than deemed economical for biofuel production from biomass. RESULTS: In this study, we demonstrate how detrimental lignin redeposition on biomass surface after pretreatment can be prevented by employing Co-solvent Enhanced Lignocellulosic Fractionation (CELF) pretreatment that uses THF-water co-solvents with dilute sulfuric acid to solubilize lignin and overcome limitations of DSA pretreatment. We first find that enzymatic hydrolysis of CELF-pretreated switchgrass can sustain a high enzyme activity over incubation periods as long as 5 weeks with enzyme doses as low as 2 mg protein/g glucan to achieve 90% yield to glucose. A modified Ninhydrin-based protein assay revealed that the free-enzyme concentration in the hydrolysate liquor, related to enzyme activity, remained unchanged over long hydrolysis times. DSA-pretreated switchgrass, by contrast, had a 40% drop in free enzymes in solution during incubation, providing evidence of enzyme deactivation. Furthermore, measurements of enzyme adsorption per gram of lignin suggested that CELF prevented lignin redeposition onto the biomass surface, and the little lignin left in the solids was mostly integral to the original lignin-carbohydrate complex (LCC). Scanning electron micrographs and NMR characterization of lignin supported this observation. CONCLUSIONS: Enzymatic hydrolysis of solids from CELF pretreatment of switchgrass at low enzyme loadings was sustained for considerably longer times and reached higher conversions than for DSA solids. Analysis of solids following pretreatment and enzymatic hydrolysis showed that prolonged cellulase activity could be attributed to the limited lignin redeposition on the biomass surface making more enzymes available for hydrolysis of more accessible glucan.