Use and Cost of Low-Value Services Among Veterans Dually Enrolled in VA and Medicare.

BACKGROUND: Over half of veterans enrolled in the Veterans Health Administration (VA) are also enrolled in Medicare, potentially increasing their opportunity to receive low-value health services within and outside VA. OBJECTIVES: To characterize the use and cost of low-value services delivered to dually enrolled veterans from VA and Medicare. DESIGN: Retrospective cross-sectional. PARTICIPANTS: Veterans enrolled in VA and fee-for-service Medicare (FY 2017-2018). MAIN MEASURES: We used VA and Medicare administrative data to identify 29 low-value services across 6 established domains: cancer screening, diagnostic/preventive testing, preoperative testing, imaging, cardiovascular testing, and surgery. We determined the count of low-value services per 100 veterans delivered in VA and Medicare in FY 2018 overall, by domain, and by individual service. We applied standardized estimates to determine each service's cost. KEY RESULTS: Among 1.6 million dually enrolled veterans, the mean age was 73, 97% were men, and 77% were non-Hispanic White. Overall, 63.2 low-value services per 100 veterans were delivered, affecting 32% of veterans; 22.9 services per 100 veterans were delivered in VA and 40.3 services per 100 veterans were delivered in Medicare. The total cost was $226.3 million (M), of which $62.6 M was spent in VA and $163.7 M in Medicare. The most common low-value service was prostate-specific antigen testing at 17.3 per 100 veterans (VA 55.9%, Medicare 44.1%). The costliest low-value service was percutaneous coronary intervention (VA $10.1 M, Medicare $32.8 M). CONCLUSIONS: Nearly 1 in 3 dually enrolled veterans received a low-value service in FY18, with twice as many low-value services delivered in Medicare vs VA. Interventions to reduce low-value services for veterans should consider their substantial use of such services in Medicare.

Autophagic degradation of DHCR7 activates AKT3 and promotes sevoflurane-induced hippocampal neuroinflammation in neonatal mice.

Repeated sevoflurane exposure in neonatal mice triggers neuroinflammation with detrimental effects on cognitive function. Yet, the mechanism of the sevoflurane-induced cytokine response is largely unknown. In this study, we reveal that 3-MA, an autophagy inhibitor, attenuated the sevoflurane-induced neuroinflammation and cognitive dysfunction, including the decreased freezing time and fewer platform crossings, in the neonate mice. 3-Methyladenine (3-MA) suppressed sevoflurane-induced expression of interleukin-6 and tumor necrosis factor-alpha in vitro. Moreover, sevoflurane activates IRF3, facilitating cytokine transcription in an AKT3-dependent manner. Mechanistically, sevoflurane-induced autophagic degradation of dehydrocholesterol-reductase-7 (DHCR7) resulted in accumulations of its substrate 7-dehydrocholesterol (7-DHC), mimicking the effect of sevoflurane on AKT3 activation and IRF3-driven cytokine expression. 3-MA significantly reversed sevoflurane-induced DHCR7 degradation, AKT phosphorylation, IRF3 activation, and the accumulation of 7-DHC in the hippocampal CA1 region. These findings pave the way for additional investigations aimed at developing novel strategies to mitigate postoperative cognitive impairment in pediatric patients.

Care cascades following low-value cervical cancer screening in dually enrolled Veterans.

BACKGROUND: Veterans dually enrolled in the Veterans Health Administration (VA) and Medicare commonly experience downstream services as part of a care cascade after an initial low-value service. Our objective was to characterize the frequency and cost of low-value cervical cancer screening and subsequent care cascades among Veterans dually enrolled in VA and Medicare. METHODS: This retrospective cohort study used VA and Medicare administrative data from fiscal years 2015 to 2019. The study cohort was comprised of female Veterans aged >65 years and at low risk of cervical cancer who were dually enrolled in VA and Medicare. Within this cohort, we compared differences in the rates and costs of cascade services related to low-value cervical cancer screening for Veterans who received and did not receive screening in FY2018, adjusting for baseline patient- and facility-level covariates using inverse probability of treatment weighting. RESULTS: Among 20,972 cohort-eligible Veterans, 494 (2.4%) underwent low-value cervical cancer screening with 301 (60.9%) initial screens occurring in VA and 193 (39%) occurring in Medicare. Veterans who were screened experienced an additional 26.7 (95% CI, 16.4-37.0) cascade services per 100 Veterans compared to those who were not screened, contributing to $2919.4 (95% CI, -265 to 6104.7) per 100 Veterans in excess costs. Care cascades consisted predominantly of subsequent cervical cancer screening procedures and related outpatient visits with low rates of invasive procedures and occurred in both VA and Medicare. CONCLUSIONS: Veterans dually enrolled in VA and Medicare commonly receive related downstream tests and visits as part of care cascades following low-value cervical cancer screening. Our findings demonstrate that to fully capture the extent to which individuals are subject to low-value care, it is important to examine downstream care stemming from initial low-value services across all systems from which individuals receive care.

The impact of dual VA-Medicare use on a data-driven clinical management tool for older Veterans with multimorbidity.

BACKGROUND: Healthcare systems are increasingly turning to data-driven approaches, such as clustering techniques, to inform interventions for medically complex older adults. However, patients seeking care in multiple healthcare systems may have missing diagnoses across systems, leading to misclassification of resulting groups. We evaluated the impact of multi-system use on the accuracy and composition of multimorbidity groups among older adults in the Veterans Health Administration (VA). METHODS: Eligible patients were VA primary care users aged ≥65 years and in the top decile of predicted 1-year hospitalization risk in 2018 (n = 558,864). Diagnoses of 26 chronic conditions were coded using a 24-month lookback period and input into latent class analysis (LCA) models. In a random 10% sample (n = 56,008), we compared the resulting model fit, class profiles, and patient assignments from models using only VA system data versus VA with Medicare data. RESULTS: LCA identified six patient comorbidity groups using VA system data. We labeled groups based on diagnoses with higher within-group prevalence relative to the average: Substance Use Disorders (7% of patients), Mental Health (15%), Heart Disease (22%), Diabetes (16%), Tumor (14%), and High Complexity (10%). VA with Medicare data showed improved model fit and assigned more patients with high accuracy. Over 70% of patients assigned to the Substance, Mental Health, High Complexity, and Tumor groups using VA data were assigned to the same group in VA with Medicare data. However, 41.9% of the Heart Disease group and 14.7% of the Diabetes group were reassigned to a new group characterized by multiple cardiometabolic conditions. CONCLUSIONS: The addition of Medicare data to VA data for older high-risk adults improved clustering model accuracy and altered the clinical profiles of groups. Accessing or accounting for multi-system data is key to the success of interventions based on empiric grouping in populations with dual-system use.

Bcl-xL mediates interferon-beta secretion by protease-activated receptor 2 deficiency through the mitochondrial permeability transition pore in colorectal cancer metastasis.

Cellular plasticity and immune escape are synergistic drivers of tumor colonization in metastatic organs. Activation of protease-activated receptor 2 (PAR2) signaling promotes metastasis of colorectal carcinoma (CRC). The role of PAR2 in regulating the immune microenvironment and cancer progression remains unclear. We demonstrated that the regulation of liver metastasis by PAR2 requires a competent immune system. PAR2 knockdown enhanced liver infiltration of activated CD8+ T cells prior to metastatic foci formation in an interferon receptor-dependent manner. PAR2 depletion increased interferon (IFN)-ß production via the cGAS-STING and RIG-1 pathways. PAR2 inhibition increased mitochondrial permeability and cytosolic accumulation of mitochondrial DNA, which was reversed by Bcl-xL expression. Strikingly, shRNA against PAR2 with an immune checkpoint blocker (ICB) acted synergistically to suppress liver metastasis. Analysis of single-cell sequence data and 24 paired samples confirmed the regulatory effect of PAR2 on the metastatic immune environment in human CRC. Therefore, PAR2 signaling is involved in stabilizing the mitochondrial membrane and regulating the immune microenvironment through IFN-ß during liver metastasis in CRC. The synergistic effect of the PAR2 inhibitor and ICB provides a potential therapeutic strategy for metastatic CRC treatment.

Diagnostic value of circRNA in coronary heart disease: a meta-analysis.

Aim: Studies have indicated that circRNAs have diagnostic value for coronary heart disease (CHD), but the efficacy varies greatly; therefore, a meta-analysis was conducted to assess the diagnostic value of circRNAs in CHD. Materials & methods: 16 studies with 3962 subjects (2239 cases and 1723 controls) were included by searching PubMed, Web of Science and MEDLINE. The pooled sensitivity and specificity, summary receiver operating characteristic and area under the curve, positive likelihood ratio and negative likelihood ratio were calculated. Results: The pooled area under the curve of circRNAs for the diagnosis of CHD was 0.80 (sensitivity and specificity were 0.77 and 0.68, respectively), and more indexes were calculated. Conclusion: circRNAs may be good biomarkers for diagnosing CHD.

FBL promotes cancer cell resistance to DNA damage and BRCA1 transcription via YBX1.

Fibrillarin (FBL) is a highly conserved nucleolar methyltransferase responsible for methylation of ribosomal RNA and proteins. Here, we reveal a role for FBL in DNA damage response and its impact on cancer proliferation and sensitivity to DNA-damaging agents. FBL is highly expressed in various cancers and correlates with poor survival outcomes in cancer patients. Knockdown of FBL sensitizes tumor cells and xenografts to DNA crosslinking agents, and leads to homologous recombination-mediated DNA repair defects. We identify Y-box-binding protein-1 (YBX1) as a key interacting partner of FBL, and FBL increases the nuclear accumulation of YBX1 in response to DNA damage. We show that FBL promotes the expression of BRCA1 by increasing the binding of YBX1 to the BRCA1 promoter. Our study sheds light on the regulatory mechanism of FBL in tumorigenesis and DNA damage response, providing potential therapeutic targets to overcome chemoresistance in cancer.

Two-dimensional Aluminum Oxide Nanosheets Decorated with Palladium Oxide Nanodots for Highly Stable and Selective Hydrogen Sensing.

Hydrogen (H2 ) sensing materials such as semiconductor metal oxides may suffer from poor long-term stability against humidity and unsatisfactory selectivity against other interfering gases. To address the above issues, highly stable and selective H2 sensing built with palladium oxide nanodots decorating aluminum oxide nanosheets (PdO NDs//Al2 O3 NSs) has been achieved via combined template synthesis, photochemical deposition, and oxidation. Typically, the PdO NDs//Al2 O3 NSs are observed with thin NSs (≈17 nm thick) decorated with nanodots (≈3.3 nm in diameter). Beneficially, the sensor prototypes built with PdO NDs//Al2 O3 NSs show excellent long-term stability for 278 days, high selectivity against interfering gases, and outstanding stability against humidity at 300 °C. Remarkably, the sensor prototypes enable detection of a wide-range of 20 ppm - 6 V/V% H2 , and the response and recovery times are ≈5 and 16 s to 1 V/V% H2 , respectively. Theoretically, the heterojunctions of PdO NDs-Al2 O3 NSs with a large specific surface ratio and Al2 O3 NSs as the support exhibit excellent stability and selective H2 sensing. Practically, a sensing device integrated with the PdO NDs//Al2 O3 NSs sensor prototype is simulated for detecting H2 with reliable sensing response.

Variation in Low-Value Service Use Across Veterans Affairs Facilities.

BACKGROUND: It is unclear whether extensive variation in the use of low-value services exists even within a national integrated delivery system like the Veterans Health Administration (VA). OBJECTIVE: To quantify variation in the use of low-value services across VA facilities and examine associations between facility characteristics and low-value service use. DESIGN: In this retrospective cross-sectional study of VA administrative data, we constructed facility-level rates of low-value service use as the mean count of 29 low-value services per 100 Veterans per year. Adjusted rates were calculated via ordinary least squares regression including covariates for Veteran sociodemographic and clinical characteristics. We quantified the association between adjusted facility-level rates and facility geographic/operational characteristics. PARTICIPANTS: 5,242,301 patients across 139 VA facilities. MAIN MEASURES: Use of 29 low-value services within six domains: cancer screening, diagnostic/preventive testing, preoperative testing, imaging, cardiovascular testing and procedures, and surgery. KEY RESULTS: The mean rate of low-value service use was 20.0 services per 100 patients per year (S.D. 6.1). Rates ranged from 13.9 at the 10th percentile to 27.6 at the 90th percentile (90th/10th percentile ratio 2.0, 95% CI 1.8‒2.3). With adjustment for patient covariates, variation across facilities narrowed (S.D. 5.2, 90th/10th percentile ratio 1.8, 95% CI 1.6‒1.9). Only one facility characteristic was positively associated with low-value service use percent of patients seeing non-VA clinicians via VA Community Care, p < 0.05); none was associated with total low-value service use after adjustment for other facility characteristics. There was extensive variation in low-value service use within categories of facility operational characteristics. CONCLUSIONS: Despite extensive variation in the use of low-value services across VA facilities, we observed substantial use of these services across facility operational characteristics and at facilities with lower rates of low-value service use. Thus, system-wide interventions to address low-value services may be more effective than interventions targeted to specific facilities or facility types.

Prevalence and Cost of Care Cascades Following Low-Value Preoperative Electrocardiogram and Chest Radiograph Within the Veterans Health Administration.

BACKGROUND: Low-value care cascades, defined as the receipt of downstream health services potentially related to a low-value service, can result in harm to patients and wasteful healthcare spending, yet have not been characterized within the Veterans Health Administration (VHA). OBJECTIVE: To examine if the receipt of low-value preoperative testing is associated with greater utilization and costs of potentially related downstream health services in Veterans undergoing low or intermediate-risk surgery. DESIGN: Retrospective cohort study using VHA administrative data from fiscal years 2017-2018 comparing Veterans who underwent low-value preoperative electrocardiogram (EKG) or chest radiograph (CXR) with those who did not. PARTICIPANTS: National cohort of Veterans at low risk of cardiopulmonary disease undergoing low- or intermediate-risk surgery. MAIN MEASURES: Difference in rate of receipt and attributed cost of potential cascade services in Veterans who underwent low-value preoperative testing compared to those who did not KEY RESULTS: Among 635,824 Veterans undergoing low-risk procedures, 7.8% underwent preoperative EKG. Veterans who underwent a preoperative EKG experienced an additional 52.4 (95% CI 47.7-57.2) cascade services per 100 Veterans, resulting in $138.28 (95% CI 126.19-150.37) per Veteran in excess costs. Among 739,005 Veterans undergoing low- or intermediate-risk surgery, 3.9% underwent preoperative CXR. These Veterans experienced an additional 61.9 (95% CI 57.8-66.1) cascade services per 100 Veterans, resulting in $152.08 (95% CI $146.66-157.51) per Veteran in excess costs. For both cohorts, care cascades consisted largely of repeat tests, follow-up imaging, and follow-up visits, with low rates invasive services. CONCLUSIONS: Among a national cohort of Veterans undergoing low- or intermediate-risk surgeries, low-value care cascades following two routine low-value preoperative tests are common, resulting in greater unnecessary care and costs beyond the initial low-value service. These findings may guide de-implementation policies within VHA and other integrated healthcare systems that target those services whose downstream effects are most prevalent and costly.

Anesthetic propofol inhibits ferroptosis and aggravates distant cancer metastasis via Nrf2 upregulation.

The impact of anesthetic management on the prognosis of patients with cancer undergoing surgery is controversial. Circulating tumor cells (CTCs) play critical roles during cancer metastasis and can be released in large quantities during surgery. The ferroptosis of CTCs is related to metastasis. Whether anesthetics affect distant metastasis by increasing the survival of CTCs is unknown. To test this hypothesis, mice were inoculated with cancer cells via tail vein injection before treatment with propofol or sevoflurane for 2 h. After 2 weeks, more metastases were observed in the propofol group compared with the sevoflurane and vehicle groups. Then, we used the ferroptosis inhibitor ferrostatin-1 to explore the effect of ferroptosis on metastasis. Similar to propofol, pretreatment with ferrostatin-1 significantly increased CTC survival in mouse lungs at 24 h and the tumor burden at 10 weeks post-inoculation. Moreover, propofol protected cancer cells from RSL3-induced ferroptosis in vitro, as evidenced by decreases in intracellular levels of reactive oxygen species (ROS), lipid peroxide, and ferroptosis markers. Further studies showed that propofol treatment upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes, including HO-1, NQO1, and SLC7A11. Finally, the targeted knockdown of Nrf2 abolished the anti-ferroptosis effect of propofol. Collectively, we demonstrated the risk of a specific type of anesthetic, propofol, in promoting cancer cell metastasis through Nrf2-mediated ferroptosis inhibition. These findings may guide the choice of anesthetic for surgical removal of tumors.

Nootkatone Improves Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors by Repressing NF-κB/NLRP3-Mediated Neuroinflammation.

OBJECTIVE: To explore the effect of nootkatone (NKT) on chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors and the mechanism underlying NKT improving the depressive-like behaviors. METHODS: The CUMS-induced depression model was established in mice. Fifty mice were randomized into 5 groups (n=10) in accordance with a random number table: control group, CUMS group, CUMS + NKT (6 mg/kg) group, CUMS + NKT (12 mg/kg) group, and CUMS + ketamine group. From the 22th day, NKT (6 or 12 mg/kg) or ketamine (0.5 mg/kg) was given with intragastric administration every day for 21 days. Behavioral tests including forced swimming test (FST), tail suspension test (TST), sucrose preference test (SPT) and open-field test (OFT) were carried out. The mRNA and protein expressions of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α in hippocampus were assessed using quantitative realtime polymerase chain reaction (PCR), Western blot analysis, and enzyme linked immunosorbent assay. The nuclear factor-κB (NF-κB)/NOD-like receptor 3 (NLRP3) inflammasome pathway was analyzed using Western blot and immunofluorescence analysis. RESULTS: NKT treatment improved CUMS-induced depressive-like behaviors in mice (P<0.05 or P<0.01). NKT significantly decreased the mRNA and protein levels of IL-1ß, IL-18, IL-6, and TNF-α in hippocampus of CUMS mice (P<0.05 or P<0.01). Furthermore, NKT repressed CUMS-induced activation of NF-κB signaling and NLRP3 inflammasome (P<0.01). More important, Nigericin, a NLRP3 activator, destroyed the effect of NKT on repressing neuroinflammation and improving depressive-like behaviors (P<0.05 or P<0.01). CONCLUSION: NKT ameliorates the depressive-like symptoms, in part by repressing NF-κB/NLRP3-mediated neuroinflammation.

Conservative Treatments for Lumbar Disc Herniation at L3-4 or L4-5 Were More Likely to Fail When Ipsilateral Foraminal Stenosis Was Present at the Caudally Adjacent Segment.

BACKGROUND: Conservative treatments are important in lumbar disc herniation (LDH), but predictors for poor outcomes are unclear. METHODS: Consecutive patients with unilateral single-level LDH at L3-4 or L4-5 were enrolled. Baseline clinical data were collected, and lumbar spine magnetic resonance imaging was evaluated. Foraminal stenosis was evaluated using Lee's approach and further categorized as absence (grade 0 and 1) or presence (grade 2 or 3). Each patient underwent conservative treatments (oral meloxicam and dexamethasone, corset, back extension exercise, physiotherapy, and manual therapy) for 6 weeks. Conservative treatments were defined as failed if a patient underwent surgery within 6 weeks or reported poor recovery at 6-week follow-up. Multivariate logistic regressions were used to examine the associations of failed conservative treatments with baseline characteristics and magnetic resonance imaging findings. RESULTS: The study included 222 patients (mean age 45.5 ± 9.8 years). Of patients, 48 (21.6%) had concurrent ipsilateral foraminal stenosis at the caudal segment, and conservative treatments failed in 39 (17.6%). At baseline, patients with LDH and caudal foraminal stenosis were older (50.79 ± 6.14 years vs. 44.10 ± 10.13 years, P < 0.001), had greater leg pain (7.06 ± 1.17 vs. 6.39 ± 1.40, P = 0.003), and had a higher rate of positive straight leg raising test (54.2% vs. 33.3%, P = 0.008) than patients without caudal foraminal stenosis. In multivariate regression, failure of conservative treatments was associated with positive straight leg raising test (odds ratio 2.26, P = 0.046), and caudal foraminal stenosis (odds ratio 3.20, P = 0.007). CONCLUSIONS: In the presence of caudal foraminal stenosis and positive SLR test, conservative treatments were more likely to fail in patients with LDH.

Assessment of Care Cascades Following Low-Value Prostate-Specific Antigen Testing Among Veterans Dually Enrolled in the US Veterans Health Administration and Medicare Systems.

Importance: Older US veterans commonly receive health care outside of the US Veterans Health Administration (VHA) through Medicare, which may increase receipt of low-value care and subsequent care cascades. Objective: To characterize the frequency, cost, and source of low-value prostate-specific antigen (PSA) testing and subsequent care cascades among veterans dually enrolled in the VHA and Medicare and to determine whether receiving a PSA test through the VHA vs Medicare is associated with more downstream services. Design, Setting, and Participants: This retrospective cohort study used VHA and Medicare administrative data from fiscal years (FYs) 2017 to 2018. The study cohort consisted of male US veterans dually enrolled in the VHA and Medicare who were aged 75 years or older without a history of prostate cancer, elevated PSA, prostatectomy, radiation therapy, androgen deprivation therapy, or a urology visit. Data were analyzed from December 15, 2020, to October 20, 2022. Exposures: Receipt of low-value PSA testing. Main Outcomes and Measures: Differences in the use and cost of cascade services occurring 6 months after receipt of a low-value PSA test were assessed for veterans who underwent low-value PSA testing in the VHA and Medicare compared with those who did not, adjusted for patient- and facility-level covariates. Results: This study included 300 393 male US veterans at risk of undergoing low-value PSA testing. They had a mean (SD) age of 82.6 (5.6) years, and the majority (264 411 [88.0%]) were non-Hispanic White. Of these veterans, 36 459 (12.1%) received a low-value PSA test through the VHA, which was associated with 31.2 (95% CI, 29.2 to 33.2) additional cascade services per 100 veterans and an additional $24.5 (95% CI, $20.8 to $28.1) per veteran compared with the control group. In the same cohort, 17 981 veterans (5.9%) received a PSA test through Medicare, which was associated with 39.3 (95% CI, 37.2 to 41.3) additional cascade services per 100 veterans and an additional $35.9 (95% CI, $31.7 to $40.1) per veteran compared with the control group. When compared directly, veterans who received a PSA test through Medicare experienced 9.9 (95% CI, 9.7 to 10.1) additional cascade services per 100 veterans compared with those who underwent testing within the VHA. Conclusions and Relevance: The findings of this cohort study suggest that US veterans dually enrolled in the VHA and Medicare commonly experienced low-value PSA testing and subsequent care cascades through both systems in FYs 2017 and 2018. Care cascades occurred more frequently through Medicare compared with the VHA. These findings suggest that low-value PSA testing has substantial downstream implications for patients and may be especially challenging to measure when care occurs in multiple health care systems.

Genome-wide association study reveals that GhTRL1 and GhPIN8 affect cotton root development.

KEY MESSAGE: Two regions located at chromosome A05 and D04 were found to be significantly associated with 0-0.5 mm and 0.5-2 mm diameter roots, respectively, and two candidate genes related to root development were identified. Roots absorb water and nutrients, and play an important role in plant growth. However, there are few genetic developmental studies on cotton root structural traits. In this study, we used 200 upland cotton (Gossypium hirsutum L.) varieties to analyze the phenotypic variation of 43 traits. A total of 2001 related single-nucleotide polymorphism (SNP) sites located within or near 1046 genes were detected through a genome-wide association study (GWAS). The 32 root traits were linked to SNPs that corresponded to 317 nonrepetitive genes. For SNPs associated with root length and 0-0.5 mm diameter root traits, a significant peak appeared on chromosome A05 (between 21.91 and 22.24 Mb). For SNPs associated with root surface area, root volume and 0.5-2 mm diameter root traits, a significant peak appeared on chromosome D04 (between 7.35 and 7.70 Mb). Within these two key regions, SNPs were detected in the promoter and coding regions of two candidate genes, GhTRL1-A05 and GhPIN8-D04. The expression levels of these two genes also changed significantly according to transcriptome sequencing and quantitative real-time PCR (qRT-PCR). After silencing the GhTRL1 and GhPIN8 genes via virus-induced gene silencing (VIGS), we found that the plants expressing TRV2::GhTRL1 and TRV2::GhPIN8 had a reduced root length, surface area. Moreover, the contents of cis-12-oxo-phytodienoic acid (cis-OPDA), isopentenyl adenosine (iPR) and cis-zeatin (cZ) in the roots of the plants expressing TRV2::GhTRL1 decreased. This study contributes to the cultivation and improvement of cotton varieties.

Helicobacter bilis Contributes to the Occurrence of Inflammatory Bowel Disease by Inducing Host Immune Disorders.

Gut microbiota coevolve with humans to achieve a symbiotic relationship, which ultimately leads to physiological homeostasis. A variety of diseases can occur once this balance is disrupted. Helicobacter bilis (H. bilis) is an opportunistic pathogen in humans, triggering multiple diseases, including inflammatory bowel disease (IBD). IBD is a chronic immunologically mediated inflammation of the human gastrointestinal tract, and its occurrence is closely related to the gut microbiota. Several studies have demonstrated that H. bilis colonization is associated with IBD, and its mechanism is related to host immunity. However, few studies have investigated these mechanisms of action. Therefore, this article is aimed at reviewing these studies and summarizing the mechanisms of H. bilis-induced IBD from two perspectives: adaptive immunity and innate immunity. Furthermore, this study provides a preliminary discussion on treating H. bilis-related IBD. In addition, we also demonstrated that H. bilis played an important role in promoting the carcinogenesis of IBD and discussed its mechanism.

Perceived Contraceptive Counseling Quality Among Veterans Using VA Primary Care: Data from the ECUUN Study.

BACKGROUND: High-quality contraceptive counseling is critical to support Veterans' reproductive autonomy and promote healthy outcomes. OBJECTIVE: To describe perceived quality of contraceptive counseling in Veterans Health Administration (VA) primary care and assess factors associated with perceived high- and low-quality contraceptive counseling. DESIGN: Cross-sectional study using data from the Examining Contraceptive Use and Unmet Need in women Veterans (ECUUN) national telephone survey. PARTICIPANTS: Veterans aged 18-44 who received contraceptive services from a VA primary care clinic in the past year (N=506). MAIN MEASURES: Perceived quality of contraceptive counseling was captured by assessing Veterans' agreement with 6 statements regarding provider counseling adapted from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. High-quality counseling was defined as a top score of strongly agreeing on all 6 items; low-quality counseling was defined as not agreeing (neutral, disagreeing, or strongly disagreeing) with >3 items. We constructed two multivariable models to assess associations between patient-, provider-, and system-level factors and perceived high-quality (Model 1) and perceived low-quality counseling (Model 2). KEY RESULTS: Most participants strongly agreed that their providers listened carefully (74%), explained things clearly (77%), and spent enough time discussing things (71%). Lower proportions strongly agreed that their provider discussed more than one option (54%), discussed pros/cons of various methods (44%), or asked which choice they thought was best for them (62%). In Model 1, Veterans who received care in a Women's Health Clinic (WHC) had twice the odds of perceiving high-quality counseling (aOR=1.99; 95%CI=1.24-3.22). In Model 2, Veterans who received care in a WHC (aOR=0.49; 95%CI=0.25-0.97) or from clinicians who provide cervical cancer screening (aOR=0.49; 95%CI=0.26-0.95) had half the odds of perceiving low-quality counseling. CONCLUSIONS: Opportunities exist to improve the quality of contraceptive counseling within VA primary care settings, including more consistent efforts to seek patients' perspectives with respect to contraceptive decisions.

Predictive Potentials of ZEB1-AS1 in Colorectal Cancer Prognosis and Their Correlation with Immunotherapy.

Background: CRC is the third most common cancer globally. The tumor immune microenvironment is closely associated with the overexpressed lncRNA ZEB1-AS1. However, in individuals with CRC, the ZEB1-AS1 gene's ability to predict immune response is a mystery. Materials and Methods: The ZEB1-AS1 gene's prognostic potential was thoroughly investigated. We analyzed and included into the TCGA database all ZEB1-AS1 and ZEB1-AS1-related genes using LASSO-Cox regression. Researchers examined the link among ZEB1-AS1 and the tumor immune microenvironment, immune checkpoint, and tumor mutation burden (TMB) in CRC through the TCGA database. Using a predictive model, researchers were able to determine the link between ZEB1-AS1 and NUDT3 and CRC prognosis. Result: According to our findings, individuals with reduced ZEB1-AS1 expression had a better prognosis in CRC. Based on the expression of two genes in the TCGA database, patients were divided into two cohorts. The B lymphocytes and macrophages are less likely to be recruited by tissues with a low-risk score. TMB and immunological checkpoints were shown to have a connection. Based on these genes, a predictive nomogram was built and confirmed, with a C-index of 0.78. Conclusion: Prognostic models based on ZEB1-AS1 and ZEB1-AS1-related genes are more accurate for CRC patients when it comes to the prognosis and immune checkpoint responsiveness.

Use and Cost of Low-Value Health Services Delivered or Paid for by the Veterans Health Administration.

Importance: Within the Veterans Health Administration (VA), the use and cost of low-value services delivered by VA facilities or increasingly by VA Community Care (VACC) programs have not been comprehensively quantified. Objective: To quantify veterans' overall use and cost of low-value services, including VA-delivered care and VA-purchased community care. Design, Setting, and Participants: This cross-sectional study assessed a national population of VA-enrolled veterans. Data on enrollment, sociodemographic characteristics, comorbidities, and health care services delivered by VA facilities or paid for by the VA through VACC programs were compiled for fiscal year 2018 from the VA Corporate Data Warehouse. Data analysis was conducted from April 2020 to January 2022. Main Outcomes and Measures: VA administrative data were applied using an established low-value service metric to quantify the use of 29 potentially low-value tests and procedures delivered in VA facilities and by VACC programs across 6 domains: cancer screening, diagnostic and preventive testing, preoperative testing, imaging, cardiovascular testing and procedures, and other procedures. Sensitive and specific criteria were used to determine the low-value service counts per 100 veterans overall, by domain, and by individual service; count and percentage of each low-value service delivered by each setting; and estimated cost of each service. Results: Among 5.2 million enrolled veterans, the mean (SD) age was 62.5 (16.0) years, 91.7% were male, 68.0% were non-Hispanic White, and 32.3% received any service through VACC. By specific criteria, 19.6 low-value services per 100 veterans were delivered in VA facilities or by VACC programs, involving 13.6% of veterans at a total cost of $205.8 million. Overall, the most frequently delivered low-value service was prostate-specific antigen testing for men aged 75 years or older (5.9 per 100 veterans); this was also the service with the greatest proportion delivered by VA facilities (98.9%). The costliest low-value services were spinal injections for low back pain ($43.9 million; 21.4% of low-value care spending) and percutaneous coronary intervention for stable coronary disease ($36.8 million; 17.9% of spending). Conclusions and Relevance: This cross-sectional study found that among veterans enrolled in the VA, more than 1 in 10 have received a low-value service from VA facilities or VACC programs, with approximately $200 million in associated costs. Such information on the use and costs of low-value services are essential to guide the VA's efforts to reduce delivery and spending on such care.

High-fat diet alleviates colitis by inhibiting ferroptosis via solute carrier family seven member 11.

A high-fat diet (HFD) is reported to exacerbate ulcerative colitis by inducing obesity, which conceals the effect of the diet itself. Ferroptosis, a type of regulated cell death induced by lipid hydroperoxides, has recently been reported in colitis. Here, we aimed to determine whether HFD affects ferroptosis and colitis progression in an obesity-independent manner. We subjected male C57BL/6J mice to either an HFD (60% fat diet) or isocaloric control diet (10% fat diet) for 4 weeks, followed by inducing colitis with 2.5% dextran sulfate sodium (DSS). Compared with the isocaloric control diet, non-obesogenic HFD reduced DSS-induced colonic mucosal injury, as shown by disease activity index, colon thickness, inflammatory infiltrations, and mucosal damage index; however, there were no differences in body weight, Lee's index, and omental fat weight between the two groups. HFD mice exhibited decreased lipid peroxidation and ferroptosis markers expression in colon tissues. Furthermore, a lipid mixture protected gut organoids and normal colonic epithelial cells from RSL3-induced ferroptosis. Mechanistically, the lipid mixture prevented glutathione deficiency by upregulating the cysteine transporter, solute carrier family seven member 11. Collectively, these findings suggest that an HFD ameliorates DSS-induced colitis through ferroptosis repression in an obesity-independent manner and provide new evidence to evaluate the effects of an HFD on colitis.