Effect of Antifibrotic Use on Mortality in Patients with Idiopathic Pulmonary Fibrosis.

Rationale: Observational studies report a significant protective effect of antifibrotics on mortality among patients with idiopathic pulmonary fibrosis (IPF). Many of these studies, however, were subject to immortal time bias because of the mishandling of delayed antifibrotic initiation. Objectives: To evaluate the antifibrotic effect on mortality among patients with IPF using appropriate statistical methods that avoid immortal time bias. Methods: Using a large administrative database, we identified 10,289 patients with IPF, of whom 2,300 used antifibrotics. Treating delayed antifibrotic initiation as a time-dependent variable, three statistical methods were used to control baseline characteristics and avoid immortal time bias. Stratified analysis was performed for patients who initiated antifibrotics early and those who initiated treatment late. For comparison, methods that mishandle immortal time bias were performed. A simulation study was conducted to demonstrate the performance of these models in a wide range of scenarios. Results: All three statistical methods yielded nonsignificant results for the antifibrotic effect on mortality, with the stratified analysis for patients with early antifibrotic initiation suggesting evidence for reduced mortality risk (for all patients, hazard ratio, 0.89; 95% confidence interval, 0.79-1.01; P = 0.08; for patients who were 65 years or older, hazard ratio, 0.85; 95% confidence interval, 0.73-0.98; P = 0.03). Methods that mishandle immortal time bias demonstrated significantly lower mortality risk for antifibrotic users. Bias of these methods was evident in the simulation study, where appropriate methods performed well with little to no bias. Conclusions: Findings in this study did not confirm an association between antifibrotics and mortality, with a stratified analysis showing support for a potential treatment effect with early treatment initiation.

Methionine Source and Level Modulate Gut pH, Amino Acid Transporters and Metabolism Related Genes in Broiler Chickens.

This study determined the effects of two methionine (Met) sources at three total sulfur amino acids (TSAA) to lysine ratios (TSAA/Lys) on gut pH, digestive enzyme activity, amino acid transporter expression, and Met metabolism of broilers. The birds were randomly assigned to a 2 × 3 factorial arrangement with Met sources (dl-Met and dl-2-hydroxy-4-(methylthio)-butanoic acid (OH-Met)) and TSAA/Lys (0.58, 0.73, and 0.88) from 1 to 21 days. The results demonstrated that dl-Met and OH-Met supported the same growth performance, but high TSAA/Lys ratio reduced the feed intake and body weight (P < 0.05). OH-Met reduced the crop chyme pH and enhanced the jejunal lipase activity (P < 0.05). ATB0,+ expression decreased with increased dl-Met levels in the duodenum; the low TSAA/Lys ratio induced a stronger mRNA expression of basolateral Met transporters. OH-Met resulted in an increase of cystathionine ß-synthase expression in the liver and a decrease in serum homocysteine levels at middle TSAA/Lys ratio compared with dl-Met treatment (P < 0.05). In conclusion, two Met sources support the same growth, but OH-Met acidified the crop chyme. The investigated transporter transcripts differed significantly along the small intestine. At the middle TSAA/Lys ratio, OH-Met showed a higher metabolic tendency of the trans-sulfuration pathway compared with dl-Met.

Multiple autoimmune disorders refractory to glucocorticoids after allogeneic hematopoietic stem cell transplantation: a case report and review of the literature.

We report here the case of a 50-year-old man who was first diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2019, resulting in complete remission. However, he was diagnosed in 2021 with several autoimmune disorders, including autoimmune hepatitis (AIH), Hashimoto's thyroiditis (HT), and autoimmune hemolytic anemia (AIHA). This is referred as multiple autoimmune syndrome (MAS), which is a rare occurrence after allo-HSCT, as previously noted in the literature. Despite being treated with glucocorticoids, cyclosporine A, and other medications, the patient did not fully recover. To address the glucocorticoid-refractory MAS, a four-week course of rituximab (RTX) at a weekly dose of 100mg was administered, which significantly improved the patient's condition. Thus, this case report underscores the importance of implementing alternative treatments in patients with post-transplant autoimmune diseases, who are glucocorticoid-refractory or glucocorticoid-dependent, and highlights the effectiveness of RTX as second-line therapy.

Variable selection for latent class analysis in the presence of missing data with application to record linkage.

The Fellegi-Sunter model is a latent class model widely used in probabilistic linkage to identify records that belong to the same entity. Record linkage practitioners typically employ all available matching fields in the model with the premise that more fields convey greater information about the true match status and hence result in improved match performance. In the context of model-based clustering, it is well known that such a premise is incorrect and the inclusion of noisy variables could compromise the clustering. Variable selection procedures have therefore been developed to remove noisy variables. Although these procedures have the potential to improve record matching, they cannot be applied directly due to the ubiquity of the missing data in record linkage applications. In this paper, we modify the stepwise variable selection procedure proposed by Fop, Smart, and Murphy and extend it to account for missing data common in record linkage. Through simulation studies, our proposed method is shown to select the correct set of matching fields across various settings, leading to better-performing algorithms. The improved match performance is also seen in a real-world application. We therefore recommend the use of our proposed selection procedure to identify informative matching fields for probabilistic record linkage algorithms.

Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study.

Background: Since the outbreak of COVID-19 in December 2019, countries around the world, including China, have been administering COVID-19 vaccines in response to the pandemic. Our center has observed that treating patients with primary immune thrombocytopenia (ITP) has become more challenging in this context. Methods: This study compared the treatment response of 25 de novo ITP patients who had received a COVID-19 vaccination (Group 1) with an equal number of de novo ITP patients randomly selected from the 2 years prior to the COVID-19 pandemic (Group 2) by using the Mann-Whitney U test and Fisher's exact. Results: Patients in both groups had predominantly female gender with similar age and baseline platelet counts. However, on Day 3, the median platelets were 22 and 49 × 109/L, and on Day 7, they were 74 and 159 × 109/L, respectively (P < 0.05). Compared to Group 2, Group 1 showed a suboptimal short-term response to glucocorticoid monotherapy, with a higher proportion of patients requiring combination therapy with other drugs including intravenous immunoglobulin, thrombopoietin receptor agonists, and rituximab. After subgroup analysis, a significant difference was observed in the proportion of patients requiring second-line therapy between the two groups. Conclusions: Our study suggests that COVID-19 vaccination may lead to a lower response rate to first-line treatment in de novo ITP patients. Nevertheless, it is crucial to acknowledge the inherent limitations in this conclusion. Further studies are needed to confirm these findings and investigate the underlying mechanisms.

Healthcare Costs of Irritable Bowel Syndrome and Irritable Bowel Syndrome Subtypes in the United States.

INTRODUCTION: Contemporaneous data on healthcare costs of irritable bowel syndrome (IBS) in the United States are lacking. We aimed to estimate all-cause and IBS-specific costs in patients with and without IBS and to compare costs across IBS subtypes. METHODS: Using Optum's deidentified Clinformatics Data Mart Database, we performed a retrospective cohort analysis of patients with and without IBS using data spanning 2016-2021. Patients with IBS were identified by ICD-10 codes. Controls were randomly selected from Clinformatics Data Mart Database participants. Primary outcomes were total all-cause and IBS-specific healthcare costs. Secondary outcomes were costs of individual services associated with any claim. Costs were compared between IBS and control groups and across IBS subtypes using propensity score weighting. Comorbidities were measured with the Elixhauser Comorbidity Index. RESULTS: Comparison of 102,887 patients with IBS (77.9% female; mean ± SD age 60.3 ± 18.4 years; 75.8% white) and 102,887 controls demonstrated higher median (interquartile range) total costs per year ( P < 0.001) for patients with IBS ($13,288 [5,307-37,071]) than controls ($5,999 [1,800-19,426]). IBS was associated with increased healthcare utilization and higher median annual costs per patient for all services. Median (interquartile range) annual IBS-specific spending was $1,127 (370-5,544) per patient. Propensity score-weighted analysis across IBS subtypes revealed differences in total all-cause and IBS-specific costs and in costs of individual services. Highest spending was observed in IBS with constipation (all-cause $16,005 [6,384-43,972]; IBS-specific $2,222 [511-7,887]). DISCUSSION: Individuals with IBS exhibit higher healthcare utilization and incur substantially higher all-cause costs than those without. Care costs differ by IBS subtype.

Manual Evaluation of Record Linkage Algorithm Performance in Four Real-World Datasets.

OBJECTIVES: Patient data are fragmented across multiple repositories, yielding suboptimal and costly care. Record linkage algorithms are widely accepted solutions for improving completeness of patient records. However, studies often fail to fully describe their linkage techniques. Further, while many frameworks evaluate record linkage methods, few focus on producing gold standard datasets. This highlights a need to assess these frameworks and their real-world performance. We use real-world datasets and expand upon previous frameworks to evaluate a consistent approach to the manual review of gold standard datasets and measure its impact on algorithm performance. METHODS: We applied the framework, which includes elements for data description, reviewer training and adjudication, and software and reviewer descriptions, to four datasets. Record pairs were formed and between 15,000 and 16,500 records were randomly sampled from these pairs. After training, two reviewers determined match status for each record pair. If reviewers disagreed, a third reviewer was used for final adjudication. RESULTS: Between the four datasets, the percent discordant rate ranged from 1.8 to 13.6%. While reviewers' discordance rate typically ranged between 1 and 5%, one exhibited a 59% discordance rate, showing the importance of the third reviewer. The original analysis was compared with three sensitivity analyses. The original analysis most often exhibited the highest predictive values compared with the sensitivity analyses. CONCLUSION: Reviewers vary in their assessment of a gold standard, which can lead to variances in estimates for matching performance. Our analysis demonstrates how a multireviewer process can be applied to create gold standards, identify reviewer discrepancies, and evaluate algorithm performance.

Lipopolysaccharide-induced intestinal inflammation on AIM2-mediated pyroptosis in the brain of rats with cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is a cerebral vascular disease with insidious onset and poor clinical treatment effect, which is related to neuroinflammation. This study investigated whether lipopolysaccharide-induced intestinal inflammation enhanced the level of pyroptosis in the brain of rats with CSVD. The bilateral carotid artery occlusion (BCAO) model was selected as the object of study. Firstly, behavioral tests and Hematoxylin-eosin staining (HE staining) were performed to determine whether the model was successful, and then the AIM2 inflammasome and pyroptosis indexes (AIM2, ASC, Caspase-1, IL-1ß, GSDMD, N-GSDMD) in the brain were detected by Western blotting and Immunohistochemistry (IHC). Finally, a single intraperitoneal injection of lipopolysaccharide (LPS) was used to induce intestinal inflammation in rats, the expression of GSDMD and N-GSDMD in the brain was analyzed by Western blotting and to see if pyroptosis caused by intestinal inflammation can be inhibited by Disulfiram, an inhibitor of pyroptosis. The results showed that the inflammatory response and pyroptosis mediated by the AIM2 inflammasome in BCAO rats were present in both brain and intestine. The expression of N-GSDMD, a key marker of pyroptosis, in the brain was significantly increased and inhibited by Disulfiram after LPS-induced enhancement of intestinal inflammation. This study shows that AIM2-mediated inflammasome activation and pyroptosis exist in both brain and intestine in the rat model of CSVD. The enhancement of intestinal inflammation will increase the level of pyroptosis in the brain. In the future, targeted regulation of the AIM2 inflammasome may become a new strategy for the clinical treatment of CSVD.

Microbiota-Short Chain Fatty Acid Relationships Underlie Clinical Heterogeneity and Identify Key Microbial Targets in Irritable Bowel Syndrome (IBS).

Background: Identifying microbial targets in irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBI) is challenging due to the dynamic nature of microbiota-metabolite-host interactions. SCFA are key microbial metabolites that modulate intestinal homeostasis and may influence IBS pathophysiology. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features varied across IBS subtypes and endophenotypes. Among 96 participants who were screened, 71 completed the study. We conducted in-depth investigations of stool microbial metagenomes, stool SCFA, and measurable IBS traits (stool bile acids, colonic transit, stool form) in 41 patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and 17 healthy controls. We used partial canonical correspondence analyses (pCCA), conditioned on transit, to quantify microbe-SCFA associations across clinical groups. To explore relationships between microbially-derived SCFA and IBS traits, we compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by their stool characteristics as well as stool microbiomes of patients with and without clinical bile acid malabsorption. Results: Overall stool microbiome composition and individual taxa abundances differed between clinical groups. Microbes-SCFA associations differed across groups and revealed key taxa including Dorea sp. CAG:317 and Bifidobacterium pseudocatenulatum in IBS-D and Akkermansia muciniphila and Prevotella copri in IBS-C that that may drive subtype-specific microbially-mediated mechanisms. Strongest microbe-SCFA associations were observed in IBS-D and several SCFA-producing species surprisingly demonstrated inverse correlations with SCFA. Fewer bacterial taxa were associated with acetate to butyrate ratios in IBS compared to health. In participants selected by stool form, we demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D patients with BAM. Conclusion: Keystone taxa responsible for SCFA production differ according to IBS subtype and traits and the IBS microbiome is characterized by reduced functional redundancy. Differences in microbial substrate preferences are also linked to bowel functions. Focusing on taxa that drive SCFA profiles and stool form may be a rational strategy for identifying relevant microbial targets in IBS and other DGBI.

Mannanase improves the growth performance of broilers by alleviating inflammation of the intestinal epithelium and improving intestinal microbiota.

This experiment aimed to discuss and reveal the effect and mechanism of mannanase on intestinal inflammation in broilers triggered by a soybean meal diet. In this experiment, 384 Arbor Acres broilers at 1 d old were randomly divided into 3 treatment groups. The broilers were fed a corn-soybean meal basal diet, a low-energy diet (metabolizable energy reduced by 50 kcal/kg), and a low-energy diet supplemented with 100 mg/kg mannanase for 42 d. The low-energy diet increased feed conversion ratio from 0 to 42 d, reduced ileal villus height and villus height-to-crypt depth ratio and upregulated the expression of nuclear factor kappa B (NF-κB) in the ileum (P < 0.05). It also reduced cecal short-chain fatty acids (SCFA), such as acetic acid (P < 0.05). Compared with low-energy diets, the addition of mannanase increased body weight at 42 d, promoted the digestibility of nutrients, and maintained the morphology and integrity of the intestinal epithelium of broilers (P < 0.05). In addition, mannanase upregulated the expression of claudin-1 (CLDN1) and zonula occludens-1 (ZO-1) in the jejunum at 21 d, downregulated the expression of ileal NF-κB, and increased the content of isobutyric acid in the cecum of broilers (P < 0.05). The results for the ileal microbiota showed that a low-energy diet led to a decrease in the relative abundance of Lactobacillus reuteri in the ileum of broilers. The addition of mannanase increased the relative abundance of Lactobacillus-KC45b and Lactobacillus johnsonii in broilers. Furthermore, a low-energy diet reduced the relative abundance of Butyricicoccus in the intestine of broilers and inhibited oxidative phosphorylation and phosphoinositol metabolism. Mannanase increased the relative abundance of Odoribacter, promoted energy metabolism and N-glycan biosynthesis, and increased the activities of GH3 and GH18. It is concluded that mannanase could improve the growth performance of broilers by reducing the expression of NF-κB in the ileum, increasing the production of SCFA in the cecum, suppressing intestinal inflammation, balancing the intestinal microbiota, reducing damage to the intestinal barrier, and improving the efficiency of nutrient utilization to alleviate the adverse effects caused by the decrease in dietary energy level.

Prediction of Sjögren's disease diagnosis using matched electronic dental-health record data.

BACKGROUND: Sjögren's disease (SD) is an autoimmune disease that is difficult to diagnose early due to its wide spectrum of clinical symptoms and overlap with other autoimmune diseases. SD potentially presents through early oral manifestations prior to showing symptoms of clinically significant dry eyes or dry mouth. We examined the feasibility of utilizing a linked electronic dental record (EDR) and electronic health record (EHR) dataset to identify factors that could be used to improve early diagnosis prediction of SD in a matched case-control study population. METHODS: EHR data, including demographics, medical diagnoses, medication history, serological test history, and clinical notes, were retrieved from the Indiana Network for Patient Care database and dental procedure data were retrieved from the Indiana University School of Dentistry EDR. We examined EHR and EDR history in the three years prior to SD diagnosis for SD cases and the corresponding period in matched non-SD controls. Two conditional logistic regression (CLR) models were built using Least Absolute Shrinkage and Selection Operator regression. One used only EHR data and the other used both EHR and EDR data. The ability of these models to predict SD diagnosis was assessed using a concordance index designed for CLR. RESULTS: We identified a sample population of 129 cases and 371 controls with linked EDR-EHR data. EHR factors associated with an increased risk of SD diagnosis were the usage of lubricating throat drugs with an odds ratio (OR) of 14.97 (2.70-83.06), dry mouth (OR = 6.19, 2.14-17.89), pain in joints (OR = 2.54, 1.34-4.76), tear film insufficiency (OR = 27.04, 5.37-136.), and rheumatoid factor testing (OR = 6.97, 1.94-25.12). The addition of EDR data slightly improved model concordance compared to the EHR only model (0.834 versus 0.811). Surgical dental procedures (OR = 2.33, 1.14-4.78) were found to be associated with an increased risk of SD diagnosis while dental diagnostic procedures (OR = 0.45, 0.20-1.01) were associated with decreased risk. CONCLUSION: Utilizing EDR data alongside EHR data has the potential to improve prediction models for SD. This could improve the early diagnosis of SD, which is beneficial to slowing or preventing complications of SD.

Results From the POINT Pragmatic Randomized Trial: An Emergency Department-Based Peer Support Specialist Intervention to Increase Opioid Use Disorder Treatment Linkage and Reduce Recurrent Overdose.

BACKGROUND: People with opioid use disorder (OUD) frequently present at the emergency department (ED), a potentially critical point for intervention and treatment linkage. Peer recovery support specialist (PRSS) interventions have expanded in US-based EDs, although evidence supporting such interventions has not been firmly established. METHODS: Researchers conducted a pragmatic trial of POINT (Project Planned Outreach, Intervention, Naloxone, and Treatment), an ED-initiated intervention for harm reduction and recovery coaching/treatment linkage in 2 Indiana EDs. Cluster randomization allocated patients to the POINT intervention (n = 157) versus a control condition (n = 86). Participants completed a structured interview, and all outcomes were assessed using administrative data from an extensive state health exchange and state systems. Target patients (n = 243) presented to the ED for a possible opioid-related reason. The primary outcome was overdose-related ED re-presentation. Key secondary outcomes included OUD medication treatment linkage, duration of medication in days, all-cause ED re-presentation, all-cause inpatient re-presentation, and Medicaid enrollment. All outcomes were assessed at 3-, 6-, and 12-months post-enrollment. Ad hoc analyses were performed to assess treatment motivation and readiness. RESULTS: POINT and standard care participants did not differ significantly on any outcomes measured. Participants who presented to the ED for overdose had significantly lower scores (3.5 vs 4.2, P < .01) regarding readiness to begin treatment compared to those presenting for other opioid-related issues. CONCLUSIONS: This is the first randomized trial investigating overdose outcomes for an ED peer recovery support specialist intervention. Though underpowered, results suggest no benefit of PRSS services over standard care. Given the scope of PRSS, future work in this area should assess more recovery- and harm reduction-oriented outcomes, as well as the potential benefits of integrating PRSS within multimodal ED-based interventions for OUD.

Dentists' Information Needs and Opinions on Accessing Patient Information via Health Information Exchange: Survey Study.

BACKGROUND: The integration of medical and dental records is gaining significance over the past 2 decades. However, few studies have evaluated the opinions of practicing dentists on patient medical histories. Questions remain on dentists' information needs; their perception of the reliability of patient-reported medical history; satisfaction with the available information and the methods to gather this information; and their attitudes to other options, such as a health information exchange (HIE) network, to collect patient medical history. OBJECTIVE: This study aims to determine Indiana dentists' information needs regarding patients' medical information and their opinions about accessing it via an HIE. METHODS: We administered a web-based survey to Indiana Dental Association members to assess their current medical information-retrieval approaches, the information critical for dental care, and their willingness to access or share information via an HIE. We used descriptive statistics to summarize survey results and multivariable regression to examine the associations between survey respondents' characteristics and responses. RESULTS: Of the 161 respondents (161/2148, 7.5% response rate), 99.5% (n=160) respondents considered patients' medical histories essential to confirm no contraindications, including allergies or the need for antibiotic prophylaxis during dental care and other adverse drug events. The critical information required were medical conditions or diagnosis, current medications, and allergies, which were gathered from patient reports. Furthermore, 88.2% (n=142) of respondents considered patient-reported histories reliable; however, they experienced challenges obtaining information from patients and physicians. Additionally, 70.2% (n=113) of respondents, especially those who currently access an HIE or electronic health record, were willing to use an HIE to access or share their patient's information, and 91.3% (n=147) shared varying interests in such a service. However, usability, data accuracy, data safety, and cost are the driving factors in adopting an HIE. CONCLUSIONS: Patients' medical histories are essential for dentists to optimize dental care, especially for those with chronic conditions. In addition, most dentists are interested in using an HIE to access patient medical histories. The findings from this study can provide an alternative option for improving communications between dental and medical professionals and help the health information technology system or tool developers identify critical requirements for more user-friendly designs.

A systematic review and meta-analysis of diet and nutrient intake in adults with irritable bowel syndrome.

BACKGROUND: Numerous individual and environmental factors including diet may play an important role in the pathophysiology of irritable bowel syndrome (IBS). It is unclear to what degree dietary intake is affected in individuals with IBS. We aimed to perform a systematic review and meta-analysis to summarize dietary intake of adults with IBS and to compare dietary intake between adults with IBS and non-IBS controls. METHODS: Ovid MEDLINE, Embase, Cochrane, CINAHL, and Scopus were searched through February 2023 for clinical trials and observational studies measuring usual diet in adults with IBS. Pooled weighted averages were estimated for total energy, macronutrient, and micronutrient data. Mean differences (MD) in nutrient intake were estimated for adults with IBS versus non-IBS controls using a random effects model. Heterogeneity was assessed by the inconsistency index (I2). KEY RESULTS: Sixty-three full-text articles were included in the review of which 29 studies included both IBS and control subjects. Nutrients not meeting the recommended intake level for any dietary reference values in the IBS population were fiber and vitamin D. Meta-regression by female proportion was positively correlated with total fat intake and negatively correlated with carbohydrate intake. Comparisons between participants with IBS and controls showed significantly lower fiber intake in participants with IBS with high heterogeneity (MD: -1.8; 95% CI: -3.0, -0.6; I2 = 85%). CONCLUSIONS AND INFERENCES: This review suggests that fiber and vitamin D intake is suboptimal in IBS; however, overall dietary intake does not appear to be comprised. Causes and consequences of reduced fiber in IBS deserve further study. Results of this systematic review and meta-analysis suggest that fiber and vitamin D intake is suboptimal in IBS. However, overall intake of other macro- and micronutrients does not appear to be compromised. Causes and consequences of reduced fiber and Vitamin D intake in IBS deserve further study.

Dietary methionine sources and levels modulate the intestinal health status of broiler chickens.

Given the key role of methionine in biological processes, adequate methionine should be provided to meet the nutritional requirements. DL-2-hydroxy-4-(methylthio)-butanoic acid (DL-HMTBA) has been considered as an important source of methionine. However, the effects of different sources and levels of methionine on the intestinal health status have not been clarified yet. An experiment was carried out to investigate the effects of different dietary sources and levels of methionine on the intestinal epithelial barrier, inflammatory cytokines expression, ileal morphology, microbiota composition, and cecal short chain fatty acids (SCFA) profiles. For this purpose, 720 male Arbor Acre broiler chicks at 1 d old were randomly assigned to a 2 × 3 factorial arrangement with 2 methionine sources (DL-methionine and DL-HMTBA) and 3 total sulfur amino acids (TSAA) levels (80%, 100%, and 120% of Arbor Acre recommendation). The results showed that DL-HMTBA supplementation promoted intestinal physical barrier at both gene expression level of claudin-1 and serum diamine oxidase level (P < 0.05), and the inflammatory cytokine IL-6 mRNA expression was down-regulated by dietary DL-HMTBA supplementation compared with the DL-methionine group (P < 0.05). Meanwhile, an upregulated gene expression of claudin-1 and zonula occluden-1 (ZO-1) were observed in the low-TSAA treatment on d 14 (P < 0.05), whereas this treatment increased the expression of IL-1ß and IL-6 (P < 0.05). Villus height to crypt depth ratio was high (P < 0.05) in the middle-level TSAA group. Furthermore, DL-HMTBA supplementation optimized the microbiota of the ileum especially the relative abundance of Lactobacillus, where the digestion and absorption were completed, and elevated the concentrations of SCFA (acetate, propionate, and butyrate) in the cecal content on d 21 (P < 0.01). In conclusion, dietary DL-HMTBA supplementation improved the intestinal barrier function, immune homeostasis and optimized the microbiota to promote intestinal health status in broiler chickens.

SAW Filters on LiNbO3/SiC Heterostructure for 5G n77 and n78 Band Applications.

The 5G communication system has experienced a substantial expansion of the spectrum, which poses higher requirements to radio frequency (RF) filters in enhancing their operating frequencies and bandwidths. To this end, this work focused on solving the filtering scheme for challenging 5G n77 and n78 bands and successfully implemented the corresponding spurious-free surface acoustic wave (SAW) filters exploiting large-coupling shear horizontal (SH) modes based on X-cut LiNbO3 (LN)/silicon carbide (SiC) heterostructure. Here, we initially investigated the suppression methods for spurious modes theoretically and experimentally and summarized an effective normalized LN thickness ( [Formula: see text] range of 0.15-0.30 for mitigating Rayleigh modes and higher order modes, as well as tilted interdigital transducers (IDT) by about 24° for eliminating transverse modes. Resonators with wavelengths ( λ) from 0.95 to [Formula: see text] were also fabricated, showing a scalable resonance from 2.48 to 4.21 GHz without any in-band ripple. Two filters completely meeting 5G n77 and n78 full bands were finally constructed, showing center frequencies ( fc) of 3763 and 3560 MHz, 3-dB fractional bandwidths (FBW) of 24.8% and 15.6%, and out-of-band (OoB) rejections of 18.7 and 28.1 dB, respectively. This work reveals that X-LN/SiC heterostructure is a promising underpinning material for SAW filters in 5G commercial applications.

Effects of Tannic Acid Supplementation on the Intestinal Health, Immunity, and Antioxidant Function of Broilers Challenged with Necrotic Enteritis.

Clostridium perfringens causes necrotic enteritis (NE) after proliferation in the intestine of poultry, resulting in considerable losses to the poultry industry. This study aimed to investigate the impact of tannic acid on the antioxidant, immunity, and gut health of broilers with NE. In the experiment, 630 one-day-old Cobb500 male chicks were randomly divided into six treatment groups, with seven replicate cages and with fifteen birds in each cage. The treatment groups were as follows: control group (NC), challenged group (PC), and challenged NE chickens treated with 250, 500, 750, and 1000 mg/kg tannic acid (PTA1, PTA2, PTA3, and PTA4, respectively). To induce NE, coccidia vaccine and Clostridium perfringens were administered on day 19 and days 22-28, respectively. Indexes related to antioxidant, immune, and intestinal health were measured on days 28 and 35. During the infection period, we observed significant increases in fecal water content, D-LA, TNF-α, and malondialdehyde concentrations (p < 0.05). Conversely, significant decreases were noted in chyme pH and in T-AOC, IL-4, and IL-10 concentrations (p < 0.05). The addition of tannic acid exhibited a linear decrease in fecal water content and TNF-α concentration (p < 0.05). Furthermore, tannic acid supplementation resulted in a quadratic curve decrease in D-LA concentration and linear increases in T-AOC, IL-4, and IL-10 (p < 0.05). Cecal microbiological analysis revealed that Ruminococcaceae and Butyricimona were dominant in PTA3. In conclusion, the dietary addition of tannic acid may reduce the negative effects of NE by increasing antioxidant and anti-inflammatory capacity, improving the intestinal barrier, and regulating the intestinal flora.

Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation.

The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association are poorly understood. Short-chain fatty acids and carboxylic acids (SCCA) produced by the intestinal microbiota cross the blood brain barrier and have been proposed to contribute to gut-brain communication. We hypothesized that changes in serum SCCA measured before and after successful FMT for rCDI influences the inflammatory response of microglia, the resident immune cells of the central nervous system. Serum SCCA were quantified using gas chromatography-mass spectroscopy from 38 patients who participated in a randomized trial comparing oral capsule-vs colonoscopy-delivered FMT for rCDI, and quality of life was assessed by SF-36 at baseline, 4, and 12 weeks after FMT treatment. Successful FMT was associated with improvements in mental and physical health, as well as significant changes in a number of circulating SCCA, including increased butyrate, 2-methylbutyrate, valerate, and isovalerate, and decreased 2-hydroxybutyrate. Primary cultured microglia were treated with SCCA and the response to a pro-inflammatory stimulus was measured. Treatment with a combination of SCCA based on the post-FMT serum profile, but not single SCCA species, resulted in significantly reduced inflammatory response including reduced cytokine release, reduced nitric oxide release, and accumulation of intracellular lipid droplets. This suggests that both levels and diversity of SCCA may be an important contributor to gut-brain communication.

Design and baseline characteristics of the Cognitive and Aerobic Resilience for the Brain (CARB) study.

BACKGROUND: Treatments that delay progression of cognitive impairment in older adults are of great public health significance. This manuscript outlines the protocol, recruitment, baseline characteristics, and retention for a randomized controlled trial of cognitive and aerobic physical training to improve cognition in individuals with subjective cognitive dysfunction, the "Cognitive and Aerobic Resilience for the Brain" (CARB) study. METHODS: Community-dwelling, older adults with self-reported memory loss were randomly assigned to receive either computer-based cognitive training, aerobic physical training, combined cognitive and physical training, or education control. Treatment was delivered 2- to 3-times per week in 45- to 90-min sessions for 12 weeks by trained facilitators videoconferencing into subject's home. Outcome assessments of were taken at the baseline, immediately following training, and 3-months after training. RESULTS: 191 subjects were randomized into the trial (mean age, 75.5 years; 68% female; 20% non-white; mean education, 15.1 years; 30% with 1+ APOE e4 allele). The sample was generally obese, hypertensive, and many were diabetic, while cognition, self-reported mood, and activities of daily living were in the normal range. There was excellent retention throughout the trial. Interventions were completed at high rates, participants found the treatments acceptable and enjoyable, and outcome assessments were completed at high rates. CONCLUSIONS: This study was designed to determine the feasibility of recruiting, intervening, and documenting response to treatment in a population at risk for progressive cognitive decline. Older adults with self-reported memory loss were enrolled in high numbers and were well engaged with the intervention and outcome assessments.

Effects of tannic acid on the immunity and intestinal health of broiler chickens with necrotic enteritis infection.

BACKGROUND: In broiler chickens, necrotic enteritis (NE) infection can reduce production performance. Tannic acid has shown great potential as a treatment of NE in broilers. However, the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear. In this study, we aimed to investigate the effects of different doses of tannic acid on the production performance, immunity, and intestinal health of broilers by constructing an NE model with C. perfringens infection and determining the appropriate dosage of tannic acid with regard to NE. RESULTS: Challenged birds showed significant reduction in body weight, villus height, and the ratio of villus height to crypt depth (P < 0.05) and increase in the feed consumption gain ratio, intestinal lesion score, and crypt depth (P < 0.05). The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance (P < 0.05) and increased the ratio of Firmicutes/Bacteroidota and cecal content of C. perfringens (P < 0.05). Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels (P < 0.05). Addition of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C. perfringens in the cecum. Specifically, tannic acid reduced the serum levels of C reactive protein, myeloperoxidase, and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds. NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna, Thermoanaerobacterium, and Thermosinus abundance (P < 0.05); their microbial composition and functional predictions were similar to those of the NC group. CONCLUSIONS: Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function. The recommended dietary tannic acid additive level is 500-750 mg/kg. Our study findings would be useful in reducing related economic losses in the broiler industry.