Medications for Opioid Use Disorder after Entering Residential Treatment: Evidence from Louisiana Medicaid.

OBJECTIVE: Policies have attempted to increase the use of medication for opioid use disorder (MOUD) during an admission to a residential treatment program, but little is known about the association of residential admission with subsequent MOUD use. METHODS: In a cohort study of Louisiana Medicaid beneficiaries age 18-64 with diagnosed opioid use disorder (OUD), weekly MOUD use and overdose for 20 weeks before and after an admission to residential treatment was analyzed using comparative interrupted time series regression. Participants with residential treatment admission between January 1, 2018, and December 31, 2020 (N = 12,222) were compared against a demographically similar group of people with OUD without residential treatment during the study period. RESULTS: The samples with residential treatment were largely male (61.9%), White (47.2%), and aged 30 to 39 years (41.4%). At baseline, people admitted to residential treatment were much less likely to use MOUD than the comparison group (4.2% lower, CI: 3.8%, 4.5%, P < 0.01). After admission, use of any MOUD initially increased by 3.1% (P < 0.01) relative to the comparison group, which reverted to the counterfactual trend by 20 weeks. Post-admission MOUD use differed widely by medication. Overdose incidence was highest in the weeks right before admission, but otherwise, it did not change during the study period. CONCLUSIONS: Admission to residential treatment for OUD was associated with a temporary increase in MOUD use. Policy initiatives should focus on both boosting use of MOUD during residential treatment and sustaining access to MOUD in outpatient care in the weeks following discharge.

PCSK9 inhibitors and inclisiran with or without statin therapy on incident muscle symptoms and creatine kinase: a systematic review and network meta-analysis.

Background: Atherosclerotic cardiovascular disease (ASCVD), a leading cause of global fatalities, has inconsistent findings regarding the impact of muscle symptoms despite promising clinical trials involving PCSK9 inhibitors (PCSK9i) and siRNA as potential therapeutic options. Methods: The databases EMBASE, PubMed, Web of Science, Cochrane, and ClinicalTrials.gov were thoroughly searched without any restrictions on language. Review Manager 5.3 software was utilized to calculate relative risks with 95% confidence intervals (CIs) for dichotomous data and mean differences or standardized mean differences with 95%CIs for continuous data. To evaluate publication bias, Egger's test was employed using Stata/SE software. Results: This analysis included 26 studies comprising 28 randomized controlled trials (RCTs) involving a total of 100,193 patients, and 4 different lipid-lowering therapy combinations. For events with creatine kinase >3ULN, evolocumab and alirocumab demonstrated significant advantages compared to inclisiran. Evolocumab showed the best results in terms of both new muscle symptom events and creatine kinase >3ULN. Conclusions: Based on this network meta-analysis (NMA) results, evolocumab has emerged as a promising treatment option for patients with hyperlipidemia and muscle disorders compared to other PCSK9 inhibitors and inclisiran. Systematic Review Registration: PROSPERO [CRD42023459558].

Effects of Renal Denervation on Ouabain-Induced Hypertension in Rats.

Background: Ouabain, a Na+, K+-ATPase inhibitor, is elevated in hypertensive patients. Evidence suggests ouabain contributes to hypertension mainly through activation of the sympathetic nervous system (SNS). Renal nerves play a vital role in the regulation of SNS activity, so we hypothesize that renal denervation may attenuate the development of ouabain-induced hypertension. Methods and Results: Forty Sprague-Dawley rats were divided into following groups (n = 10 each): control group (sham surgery plus intraperitoneal saline injection), RDN group (renal denervation (RDN) plus intraperitoneal saline injection), ouabain group (sham surgery plus intraperitoneal ouabain injection), and ouabain + RDN group (RDN plus intraperitoneal ouabain injection). After eight weeks, compared with the control group, rats in the ouabain group exhibited elevated blood pressure (P < 0.05), increased plasma epinephrine, norepinephrine, angiotensin II, and aldosterone levels (P < 0.05). These indexes could be significantly ameliorated by RDN. RDN also reduced the thickening of aortic tunica media and downregulated the expression of proliferating cell nuclear antigen (PCNA) in the thoracic aorta induced by ouabain. Masson staining and echocardiography showed that myocardial fibrosis and increased left ventricular mass in the ouabain group could be attenuated by RDN. Conclusions: The present study reveals that renal nerves play an important role in the development of ouabain-induced hypertension. RDN could inhibit the pressor effect and the myocardial remodeling induced by ouabain potentially via inhibiting catecholamine release and vascular smooth muscle cell proliferation. Clinical studies are needed to explore whether RDN may exhibit better antihypertensive effects on hypertensive patients with high plasma ouabain levels as compared to those with normal plasma ouabain levels.

Structural Variations of Prions and Prion-like Proteins Associated with Neurodegeneration.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs), including Alzheimer's disease (AD) and Parkinson's disease (PD). Both amyloid-ß (Aß) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to those of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms largely focus on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and this knowledge could contribute to diagnoses and treatments for the given NDs.

Unraveling the Role of TP53 in Colorectal Cancer Therapy: From Wild-Type Regulation to Mutant.

The p53, a pivotal tumor suppressor, regulates various cellular responses, including DNA repair and apoptosis. Normally, p53 levels are low due to murine double minute clone 2 (MDM2) mediated polyubiquitination. However, stress signals disrupt p53-MDM2 interaction, stabilizing p53 and activating target genes. Dysfunctional p53 is common in cancers, especially colorectal cancer (CRC), with TP53 mutations in 43% of tumors. These mutations impair wild-type p53 function or confer novel activities, promoting cancer progression. Despite drugs targeting p53 entering trials, understanding wild-type and mutant p53 functions is crucial for novel CRC therapies. P53 mutations not only impact DNA repair and apoptosis but also play a crucial role in tumor immunotherapy. While rendering tumors resistant to chemotherapy, p53 mutations provide opportunities for immunotherapy due to neoantigen-rich tumors. Additionally, p53 mutations influence tumor microenvironment cells, such as fibroblasts and immunosuppressive cells, through p53-mediated signaling pathways. Investigating p53 mutations in tumor therapy is vital for personalized medicine and immunotherapy. In cancer treatment research, scientists explore drugs and strategies to restore or enhance p53 function. Targeting wild-type p53 aims to restore DNA repair and cell cycle control, while targeting mutant p53 seeks new drugs to inhibit its detrimental effects, advancing tumor treatment. Understanding p53 drugs and strategies is crucial for cancer therapy progress.

Improving Microcystis aeruginosa removal efficiency through enhanced sonosensitivity of nitrogen-doped nanodiamonds.

Traditional methods for algae removal in drinking water treatment, such as coagulation and sedimentation, face challenges due to the negative charge on algae cells' surfaces, resulting in ineffective removal. Ultrasonic cavitation has shown promise in enhancing coagulation performance by disrupting extracellular polymer structures and improving cyanobacteria removal through various mechanisms like shear force and free radical reactions. However, the short lifespan and limited mass transfer distance of free radicals in conventional ultrasonic treatment lead to high energy consumption, limiting widespread application. To overcome these limitations and enhance energy efficiency, advanced carbon-based materials were developed and tested. Nitrogen-doped functional groups on nanodiamond surfaces were found to boost sonosensitivity by increasing the production of reactive oxygen species at the sonosensitizer-water interface. Utilizing low-power ultrasound (0.12 W/mL) in combination with N-ND treatment for 5 min, removal rates of Microcystis aeruginosa cells in water exceeded 90 %, with enhanced removal of algal organic matters and microcystins in water. Visualization through confocal microscopy highlighted the role of positively charged nitrogen-doped nanodiamonds in aggregating algae cells. The synergy between cell capturing and catalysis of N-ND indicates that efficient mass transfer of free radicals from the sonosensitizer's surface to the microalgae's surface is critical for promoting cyanobacteria floc formation. This study underscores the potential of employing a low-intensity ultrasound and N-ND system in effectively improving algae removal in water treatment processes.

Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

OBJECTIVE: This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. METHODS: We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. RESULTS: There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. CONCLUSION: We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Risk factors associated with high-dose methotrexate induced toxicities.

INTRODUCTION: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment. AREAS COVERED: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified. EXPERT OPINION: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

Impact of fine particulate matter on liver injury: evidence from human, mice and cells.

BACKGROUND: A recently discovered risk factor for chronic liver disease is ambient fine particulate matter (PM2.5). Our research aims to elucidate the effects of PM2.5 on liver injury and the potential molecular mechanisms. METHODS AND RESULTS: A population-based longitudinal study involving 102,918 participants from 15 Chinese cities, using linear mixed-effect models, found that abnormal alterations in liver function were significantly associated with long-term exposure to PM2.5. The serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, direct bilirubin, and triglyceride increased by 2.05%, 2.04%, 0.58%, 2.99%, and 1.46% with each 10 µg/m3 increase in PM2.5. In contrast, the serum levels of total protein, albumin, and prealbumin decreased by 0.27%, 0.48%, and 2.42%, respectively. Mice underwent chronic inhalation exposure to PM2.5 experienced hepatic inflammation, steatosis and fibrosis. In vitro experiments found that hepatocytes experienced an inflammatory response and lipid metabolic dysregulation due to PM2.5, which also activated hepatic stellate cells. The down-regulation and mis-localization of polarity protein Par3 mediated PM2.5-induced liver injury. CONCLUSIONS: PM2.5 exposure induced liver injury, mainly characterized by steatosis and fibrosis. The down-regulation and mis-localization of Par3 were important mechanisms of liver injury induced by PM2.5.

Simulated impact of mobile opioid treatment program units on increasing access to methadone for opioid use disorder.

OBJECTIVE: To model the potential impact of mobile methadone unit implementation in Louisiana on net medication for opioid use disorder (MOUD) treatment rates. DATA SOURCES/STUDY SETTING: We use secondary Louisiana Medicaid claims data between 2020 and 2021. STUDY DESIGN: We simulate the impact of mobile methadone units in Louisiana using two approaches: (1) a "Poisson regression approach," which predicts the number of opioid use disorder (OUD) patients that might use methadone at mobile locations based on the underlying association between methadone use and proximity to a brick-and-mortar methadone clinic; (2) a "policy approach," which leverages local treatment uptake rates following the expansion of methadone coverage to Louisiana Medicaid beneficiaries in 2020 to estimate methadone use following mobile unit implementation. Models were run in cases where mobile methadone operators could choose their operation locations freely and in a separate instance where they were restricted to serving rural locations. DATA COLLECTION: Our analytic sample includes 43,341 Louisiana Medicaid beneficiaries with one or more primary or secondary diagnoses for opioid dependence. PRINCIPAL FINDINGS: We predict that 10 new mobile methadone units in Louisiana would increase the net MOUD treatment rate in the state by 0.54-2.39 percentage points. If these mobile units delivered Methadone exclusively to rural areas, they could increase rural MOUD treatment by 8.54-13.67 percentage points. Further, roughly 20% of all beneficiaries residing in rural areas being treated with methadone would be an average of 24 miles closer to a methadone treatment provider following mobile unit implementation. CONCLUSIONS: Mobile methadone units represent a promising innovation in the delivery of methadone that is likely to increase methadone use, especially in underserved rural locations. However, we find significant variation in their impact conditional on where they choose to operate, and so careful location planning will be required to maximize their benefit.

Medications For Opioid Use Disorder Increased Among Louisiana Medicaid Enrollees During Policy Reforms, 2018-21.

Increasing access to medications for opioid use disorder (MOUD) is a key strategy in addressing the opioid crisis. To increase MOUD access, state governments have pursued a combination of increased funding for MOUD and requirements that providers offer treatment. Louisiana has pursued multiple strategies, including a requirement that residential treatment programs offer MOUD as part of their licensure. Using Louisiana Medicaid claims data for enrollees with diagnosed OUD from the period 2018-21, we analyzed trends in MOUD between enrollees treated in residential and nonresidential settings and across demographic subgroups, and we compared trends by MOUD type. MOUD use more than tripled from 2018 to 2021 among Louisiana Medicaid enrollees diagnosed with OUD. Most of the increase in MOUD was attributable to buprenorphine use. Methadone uptake also contributed to greater MOUD use but was almost exclusively used by enrollees treated in nonresidential settings, whereas naltrexone was consistently more common in residential treatment. By 2021, differences persisted across demographic groups: MOUD use was highest among enrollees who were White, were older, had comorbidities, and lived in a metropolitan area. Policies that promote MOUD in substance use treatment programs, particularly residential programs, are critical tools for policy makers confronting a complex and unprecedented national overdose crisis.

Utilization of Medications for Opioid Use Disorder Among West Virginia Medicaid Enrollees Following Medicaid Coverage of Methadone.

BACKGROUND: West Virginia entered an institution for mental disease Section 1115 waiver with the Centers for Medicare & Medicaid Services in 2018, which allowed Medicaid to cover methadone at West Virginia's nine opioid treatment programs (OTPs) for the first time. METHODS: We conducted time trend and geospatial analyses of Medicaid enrollees between 2016 and 2019 to examine medications for opioid use disorder utilization patterns following Medicaid coverage of methadone, focusing on distance to an OTP as a predictor of initiating methadone and conditional on receiving any, longer treatment duration. RESULTS: Following Medicaid coverage of methadone in 2018, patients receiving methadone comprised 9.5% of all Medicaid enrollees with an opioid use disorder (OUD) diagnosis and 10.6% in 2019 (P < 0.01). In 2018, two-thirds of methadone patients either had no prior OUD diagnosis or were not previously enrolled in Medicaid in our observation period. Patients residing within 20 miles of an OTP were more likely to receive methadone (marginal effect [ME]: -0.041, P < 0.001). Similarly, patients residing in metropolitan areas were more likely to receive treatment than those residing in nonmetropolitan areas (ME: -0.019, P < 0.05). Metropolitan patients traveled an average of 15 miles to an OTP; nonmetropolitan patients traveled more than twice as far (P < 0.001). We found no significant association between distance and treatment duration. CONCLUSIONS: West Virginia Medicaid's new methadone coverage was associated with an influx of new enrollees with OUD, many of whom had no previous OUD diagnosis or prior Medicaid enrollment. Methadone patients frequently traveled far distances for treatment, suggesting that the state needs additional OTPs and innovative methadone delivery models to improve availability.

Regulation of Angiogenesis by Non-Coding RNAs in Cancer.

Non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, have been identified as crucial regulators of various biological processes through epigenetic regulation, transcriptional regulation, and post-transcriptional regulation. Growing evidence suggests that dysregulation and activation of non-coding RNAs are closely associated with tumor angiogenesis, a process essential for tumor growth and metastasis and a major contributor to cancer-related mortality. Therefore, understanding the molecular mechanisms underlying tumor angiogenesis is of utmost importance. Numerous studies have documented the involvement of different types of non-coding RNAs in the regulation of angiogenesis. This review provides an overview of how non-coding RNAs regulate tumor angiogenesis. Additionally, we discuss emerging strategies that exploit non-coding RNAs for anti-angiogenic therapy in cancer treatment. Ultimately, this review underscores the crucial role played by non-coding RNAs in tumor angiogenesis and highlights their potential as therapeutic targets for anti-angiogenic interventions against cancer.

Efficacy of the long-acting gonadotropin-releasing hormone agonist long protocol on IVF/ICSI outcomes of patients with repeated implantation failure.

OBJECTIVE: The present study aimed to investigate the effect of long-acting gonadotropin-releasing hormone agonist (GnRHa) long protocol on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes of patients with repeated implantation failure (RIF). METHODS: The present study was carried out from June 1, 2016 to June 30, 2021. A total of 665 patients with RIF were enrolled into the study and classified by the ovarian stimulation protocols. The outcome parameters were compared in each group. In addition, we evaluated the expression of homeobox A10 (HOXA10), integrin ß3 and leukemia inhibitory factor (LIF) in endometrial tissues between groups by quantitative RT-PCR. RESULTS: Patients who received the long-acting GnRHa long protocol had significantly higher clinical pregnancy rates (58.0%, 41.7% and 39.9%, respectively; P = 0.008 and 0.003), implantation rates (38.1%, 30.3%, and 30.1%, respectively; P = 0.001 and <0.001) and live birth rates (50.3%, 36.3%, and 31.3%, respectively; P = 0.020 and 0.002) compared with the short-acting GnRHa long protocol and GnRH antagonist protocol. In addition, we found that long-acting GnRHa could improve the expression of HOXA10 (P < 0.05). CONCLUSION: The long-acting GnRHa long protocol could improve endometrial receptivity and IVF/ICSI clinical outcomes of RIF patients compared with the short-acting GnRHa long protocol and GnRH antagonist protocol.

Strategies for Assessing Health Information Credibility Among Older Social Media Users in China: A Qualitative Study.

The fact that social media gives users easy access to online health information raises the question of what information evaluation strategies older adults use to distinguish trustworthy from unreliable health information. Identifying how older adults assess the credibility of health information that they acquire on social media is an important step toward understanding and reducing their susceptibility to health misinformation. In this study, we investigated the credibility assessment strategies used by older WeChat users in China. Following a qualitative approach, we conducted in-depth interviews with 40 WeChat users 65-85 years old (M = 71.75, SD = 6.65) in China who had acquired health information on WeChat. Results of theoretical thematic analysis revealed five source-based and content-based evaluative strategies: (1) determining the communicative orientation of the source, (2) assessing source reputation, (3) confirming content based on life experiences, (4) checking for exaggeration in claimed effects, and (5) assessing the consistency of content across sources. Older WeChat users' reliance on certain heuristic cues and their self-reliant approach to assessing information credibility provide contextual explanations for the link between heuristic processing and susceptibility to health misinformation. The findings have implications for anti-misinformation interventions targeting the older population in China and potentially beyond.

Systematic comparison of genome information processing and boundary recognition tools used for genomic island detection.

Genomic islands are fragments of foreign DNA that are found in bacterial and archaeal genomes, and are typically associated with symbiosis or pathogenesis. While numerous genomic island detection methods have been proposed, there has been limited evaluation of the efficiency of the genome information processing and boundary recognition tools. In this study, we conducted a review of the statistical methods involved in genomic signatures, host signature extraction, informative signature selection, divergence measures, and boundary detection steps in genomic island prediction. We compared the performances of these methods on simulated experiments using alien fragments obtained from both artificial and real genomes. Our results indicate that among the nine genomic signatures evaluated, genomic signature frequency and full probability performed the best. However, their performance declined when normalized to their expectations and variances, such as Z-score and composition vector. Based on our experiments of the E. coli genome, we found that the confidence intervals of the window variances achieved the best performance in the signature extraction of the host, with the best confidence interval being 1.5-2 times the standard error. Ordered kurtosis was most effective in selecting informative signatures from a single genome, without requiring prior knowledge from other datasets. Among the three divergence measures evaluated, the two-sample t-test was the most successful, and a non-overlapping window with a small eye window (size 2) was best suited for identifying compositionally distinct regions. Finally, the maximum of the Markovian Jensen-Shannon divergence score, in terms of GC-content bias, was found to make boundary detection faster while maintaining a similar error rate.

Enhancement of KMnO4 treatment on cyanobacteria laden-water via 1000 kHz ultrasound at a moderate intensity.

1000 kHz high-frequency ultrasound at 0.12 and 0.39 W/mL intensity was used to enhance the inactivation of suspensions of Microcystis aeruginosa cells using KMnO4. With 10 mg/L of KMnO4, ultrasound at 0.12 W/mL intensity was found to be effective in inactivating the cyanobacteria within 10 min. A Weibull model was found to describes the inactivation well. Its concave shape shows that some cells have a certain resistance to this treatment. Cytometry and microscopic analysis confirm that the treatment damages cell integrity. Despite that the extracellular organic matter in the water was not significantly increased. The concentration of extracellular cyanobacterial toxins even decreased. The filtered suspension of inactivated cyanobacteria was used to cultivate mung beans, and the suspension did not hinder their germination. This provides a new idea for using cyanobacteria-laden wastewater. These findings suggest a technique for speeding up the oxidation of Microcystis cells using KMnO4 with ultrasound at moderate intensity, which provide new insights into the biological effects of ultrasound.

Immunotherapy: A promising novel endometriosis therapy.

Endometriosis is a common disease of the female reproductive system and has malignant features. Although endometriosis by itself is a benign disease, its erosive growth characteristics lead to severe pelvic pain and female infertility. Unfortunately, several aspects of the pathogenesis of endometriosis are still unclear. Furthermore, the clinical therapeutic methods are unsatisfactory. The recurrence rate of endometriosis is high. Accumulating evidence suggests that the onset and development of endometriosis are closely related to the abnormal function of the female autoimmune system, especially the function of some immune cells such as the aggregation of neutrophils, abnormal differentiation of macrophages, decreased cytotoxicity of NK cells, and abnormal function of T- and B-cell lines. Therefore, immunotherapy is probably a novel therapeutic strategy for endometriosis besides surgery and hormone therapy. However, information regarding the clinical application of immunotherapy in the treatment of endometriosis is very limited. This article aimed to review the effects of existing immunomodulators on the development of endometriosis, including immune cell regulators and immune factor regulators. These immunomodulators clinically or experimentally inhibit the pathogenesis and development of endometriosis lesions by acting on the immune cells, immune factors, or immune-related signaling pathways. Thus, immunotherapy is probably a novel and effective clinical treatment choice for endometriosis. Experimental studies of the detailed mechanism of immunotherapy and large-scale clinical studies about the effectiveness and safety of this promising therapeutic method are required in the future.

Comprehensive analysis of the prognosis, tumor microenvironment, and immunotherapy response of SDHs in colon adenocarcinoma.

Background: Succinate dehydrogenase (SDH), one of the key enzymes in the tricarboxylic acid cycle, is mainly found in the mitochondria. SDH consists of four subunits encoding SDHA, SDHB, SDHC, and SDHD. The biological function of SDH is significantly related to cancer progression. Colorectal cancer (CRC) is one of the most common malignant tumors globally, whose most common histological subtype is colon adenocarcinoma (COAD). However, the correlation between SDH factors and COAD remains unclear. Methods: The data on pan-cancer was obtained from The Cancer Genome Atlas (TCGA) database. Kaplan-Meier survival analysis showed the prognostic ability of SDHs. The cBioPortal database reflected genetic variations of SDHs. The correlation analysis was conducted between SDHs and mitochondrial energy metabolism genes (MMGs) and the protein-protein interaction (PPI) network was built. Consequently, Univariate and Multivariate Cox Regression Analysis on SDHs and other clinical characteristics were conducted. A nomogram was established. The ssGSEA analysis visualized the association between SDHs and immune infiltration. Immunophenoscore (IPS) explored the correlation between SDHs and immunotherapy, and the correlation between SDHs and targeted therapy was investigated through Genomics of Drug Sensitivity in Cancer. Finally, qPCR and immunohistochemistry detected SDHs' expression. Results: After assessing SDHs differential expression in pan-cancer, we found that SDHB, SDHC, and SDHD benefit COAD patients. The cBioPortal database demonstrated that SDHA was the top gene in mutation frequency rank. Correlation analysis mirrored a strong link between SDHs and MMGs. We formulated a nomogram and found that SDHB, SDHC, SDHD, and clinical characteristics correlated with COAD patients' survival. For T helper cells, Th2 cells, and Tem, SDHA, SDHB, SDHC, and SDHD were significantly enriched in the high expression group. Moreover, COAD patients with high SDHA expression were more suitable for immunotherapy. And COAD patients with different SDHs' expression have different sensitivity to targeted drugs. Further verifying the gene and protein expression levels of SDHs, we found that the tissues were consistent with the bioinformatics analysis. Conclusions: Our study analyzed the expression and prognostic value of SDHs in COAD, explored the pathway mechanisms involved, and the immune cell correlations, indicating that SDHs might be biomarkers for COAD patients.

A Widening Divide: Cigarette Smoking Trends Among People With Substance Use Disorder And Criminal Legal Involvement.

People with substance use disorder (SUD) smoke cigarettes at a rate more than twice that of the general population. Policies and programs have focused on promoting smoking cessation among people with SUD, yet it is unclear whether interventions have adequately reached the subgroup involved in the criminal legal system, who have among the highest smoking rates. Drawing on repeated cross-sections of the National Survey on Drug Use and Health, we found that smoking rates declined by 9.4 percentage points overall among people with SUD from 2010 to 2019, but rates remained virtually unchanged among the subgroup with criminal legal involvement. In regression analyses focused on people with SUD, three-quarters of the excess smoking burden for those with criminal legal involvement at baseline (2010-13) was accounted for by controlling for sociodemographics, substance use type, health insurance, and recent SUD treatment. However, even after we controlled for these same factors, the disparity in smoking prevalence among people with SUD between those with and without criminal legal involvement remained constant over time. These findings underscore the need for smoking cessation interventions focused on the criminal legal system, including correctional facilities and SUD treatment programs that serve people in this population.