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IntroductionAfter having an acute myocardial infarction (AMI), racial and ethnic minorities have less access to care, decreased rates of invasive treatments such as percutaneous coronary intervention (PCI), and worse outcomes compared with white patients. The objective of this study was to determine whether the Affordable Care Act's expansion of Medicaid eligibility was associated with changes in racial disparities in access, treatments, and outcomes after AMI.MethodsQuasi-experimental, difference-in-differences-in-differences analysis of non-Hispanic white and minority patients with acute myocardial infarction in California and Florida from 2010-2015, using linear regression models to estimate the difference-in-differences. This population-based sample included all Medicaid and uninsured patients ages 18-64 hospitalized with acute myocardial infarction in California, which expanded Medicaid through the Affordable Care Act beginning as early as July 2011 in certain counties, and Florida, which did not expand Medicaid. The main outcomes included rates of admission to hospitals capable of performing PCI, rates of transfer for patients who first presented to hospitals that did not perform PCI, rates of PCI during hospitalization and rates of early (within 48 hours of admission) PCI, rates of readmission to the hospital within 30 days, and rates of in-hospital mortality.ResultsA total of 55,991 hospital admissions met inclusion criteria, 32,540 of which were in California and 23,451 were in Florida. Among patients with AMI who initially presented to a non-PCI hospital, the likelihood of being transferred increased by 12 percentage points (95% CI 2 to 21) for minority patients relative to white patients after the Medicaid expansion. The likelihood of undergoing PCI increased by 3 percentage points (95% CI 0 to 5) for minority patients relative to white patients after the Medicaid expansion. We did not find an association between the Medicaid expansion and racial disparities in overall likelihood of admission to a PCI hospital, hospital readmissions, or in-hospital mortality.ConclusionsThe Medicaid expansion was associated with a decrease in racial disparities in transfers and rates of PCI after AMI. We did not find an association between the Medicaid expansion and admission to a PCI hospital, readmissions, and in-hospital mortality. Additional factors outside of insurance coverage likely continue to contribute to disparities in outcomes after AMI. These findings are crucial for policy makers seeking to reduce racial disparities in access, treatment and outcomes in AMI.

The ongoing rise in antibiotic resistance, and a waning of the introduction of new antibiotics, has resulted in limited treatment options for bacterial infections, including these caused by methicillin-resistant Staphylococcus aureus, leaving the world in a post-antibiotic era. Here, we set out to examine mechanisms by which theaflavin 3,3’-digallate (TF3) might act as an anti-hemolytic compound. In the presented study, we found that TF3 has weak bacteriostatic and bactericidal effects on Staphylococcus aureus, and strong inhibitory effect towards the hemolytic activity of its α-hemolysin (Hla) including its production and secretion. A supportive SPR assay reinforced these results and further revealed binding of TF3 to Hla with KD = 4.57×10−5 M. Interestingly, TF3 was also able to protect human primary keratinocytes from Hla-induced cell death, being at the same time non-toxic for them. Further analysis of TF3 properties revealed that TF3 blocked Hla-prompting immune reaction by inhibiting production and secretion of IL1β, IL6, and TNFα in vitro and in vivo, through affecting NFκB activity. Additionally, we observed that TF3 also markedly attenuated S. aureus-induced barrier disruption, by inhibiting Hla-triggered E-cadherin and ZO-1 impairment. Overall, by blocking activity of Hla, TF3 subsequently subdued the inflammation and protected the epithelial barrier, which is considered as beneficial to relieving skin injury.

In Tennessee, populations of the state endangered Streamside Salamander (Ambystoma barbouri) are in decline as their distribution lies mostly within rapidly developing areas in the Nashville Basin. Information regarding the partitioning of genetic variation among populations of A. barbouri and the taxonomic status of these populations relative to northern populations and their congener, the Small-mouthed Salamander (A. texanum), have important implications for management and conservation of this species. Here we combined mitochondrial sequencing and genome-wide single nucleotide polymorphism (SNP) data generated using Genotyping-by-Sequencing (GBS) to investigate patterns of genetic variation within Tennessee populations of A. barbouri, to assess their relationship to populations in Kentucky, and to examine their phylogenetic relationship to the closely related A. texanum. Results from phylogenetic reconstructions reveal a complex history of Tennessee A. barbouri populations with regards to northern populations, unisexual A. barbouri, and A. texanum. Patterns of mitochondrial sequence variation suggest that A. barbouri may have originated within Tennessee and expanded north multiple times into Kentucky, Ohio, Indiana, and West Virginia. Phylogenetic reconstructions based on genome-wide SNP data contradict results based on mitochondrial DNA and correspond to geographic and taxonomic boundaries. Variation in allele frequencies at SNP genotypes, as identified by multivariate analyses and Bayesian assignment tests, identified three evolutionary significant units (ESUs) for A. barbouri within Tennessee. Collectively, these results emphasize the need for prioritizing conservation needs for Tennessee populations of A. barbouri to ensure the long-term persistence of this species.

BACKGROUND: In colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown. METHODS: We assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models. RESULTS: Patients consuming ≥ 2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04-2.68), compared with those consuming

In the pursuit of suitable and effective solutions to SARS-CoV-2 infection, we investigated the efficacy of several phenolic compounds in controlling key cellular mechanisms involved in its infectivity. The way the SARS-CoV-2 virus infects the cell is a complex process and comprises four main stages: attachment to the cognate receptor, cellular entry, replication and cellular egress. Since, this is a multi-part process, it creates many opportunities to develop effective interventions. Targeting binding of the virus to the host receptor in order to prevent its entry has been of particular interest. Here, we provide experimental evidence that, among 56 tested polyphenols, including plant extracts, brazilin, theaflavin-3,3'-digallate, and curcumin displayed the highest binding with the receptor-binding domain of spike protein, inhibiting viral attachment to the human angiotensin-converting enzyme 2 receptor, and thus cellular entry of pseudo-typed SARS-CoV-2 virions. Both, theaflavin-3,3'-digallate at 25 μg/ml and curcumin above 10 μg/ml concentration, showed binding with the angiotensin-converting enzyme 2 receptor reducing at the same time its activity in both cell-free and cell-based assays. Our study also demonstrates that brazilin and theaflavin-3,3'-digallate, and to a still greater extent, curcumin, decrease the activity of transmembrane serine protease 2 both in cell-free and cell-based assays. Similar pattern was observed with cathepsin L, although only theaflavin-3,3'-digallate showed a modest diminution of cathepsin L expression at protein level. Finally, each of these three compounds moderately increased endosomal/lysosomal pH. In conclusion, this study demonstrates pleiotropic anti-SARS-CoV-2 efficacy of specific polyphenols and their prospects for further scientific and clinical investigations.

IntroductionUninsured patients have decreased access to care, lower rates of percutaneous coronary intervention (PCI), and worse outcomes after acute myocardial infarction (AMI). The aim of this study was to determine whether expanding insurance coverage through the Affordable Care Act's expansion of Medicaid eligibility affected access to PCI hospitals, rates of PCI, 30-day readmissions, and in-hospital mortality after AMI.MethodsQuasi-experimental, difference-in-differences analysis of Medicaid and uninsured patients with acute myocardial infarction in California, which expanded Medicaid through the Affordable Care Act, and Florida, which did not, from 2010-2015. This study accounts for the early expansion of Medicaid in certain California counties that began as early as July 2011. Main outcomes included rates of admission to PCI hospitals, rates of transfer for patients who initially presented to non-PCI hospitals, rates of PCI, rates of early PCI defined as within 48 hours of hospital admission, in-hospital mortality, and 30-day readmission.Results55,991 hospital admissions between 2010-2015 met inclusion criteria. Of these, 32,540 were in California, which expanded Medicaid, and 23,451 were in Florida, which did not. 30-day readmission rates after AMI decreased by an absolute difference of 1.22 percentage points after the Medicaid expansion (95% CI -2.14 to -0.30, P < 0.01). This represented a relative decrease in readmission rates of 9.5% after AMI. No relationship between the Medicaid expansion and admission to PCI hospitals, transfer to PCI hospitals, rates of PCI, rates of early PCI, or in-hospital mortality were observed.ConclusionsHospital readmissions decreased by 9.5% after the Affordable Care Act expanded Medicaid eligibility, although there was no association found between Medicaid expansion and access to PCI hospitals or treatment with PCI. Better understanding the ways that Medicaid expansion might affect care for vulnerable populations with AMI is important for policymakers considering whether to expand Medicaid eligibility in their state.

IntroductionAfter having an acute myocardial infarction (AMI), racial and ethnic minorities have less access to care, decreased rates of invasive treatments such as percutaneous coronary intervention (PCI), and worse outcomes compared with white patients. The objective of this study was to determine whether the Affordable Care Act's expansion of Medicaid eligibility was associated with changes in racial disparities in access, treatments, and outcomes after AMI.MethodsQuasi-experimental, difference-in-differences-in-differences analysis of non-Hispanic white and minority patients with acute myocardial infarction in California and Florida from 2010-2015, using linear regression models to estimate the difference-in-differences. This population-based sample included all Medicaid and uninsured patients ages 18-64 hospitalized with acute myocardial infarction in California, which expanded Medicaid through the Affordable Care Act beginning as early as July 2011 in certain counties, and Florida, which did not expand Medicaid. The main outcomes included rates of admission to hospitals capable of performing PCI, rates of transfer for patients who first presented to hospitals that did not perform PCI, rates of PCI during hospitalization and rates of early (within 48 hours of admission) PCI, rates of readmission to the hospital within 30 days, and rates of in-hospital mortality.ResultsA total of 55,991 hospital admissions met inclusion criteria, 32,540 of which were in California and 23,451 were in Florida. Among patients with AMI who initially presented to a non-PCI hospital, the likelihood of being transferred increased by 12 percentage points (95% CI 2 to 21) for minority patients relative to white patients after the Medicaid expansion. The likelihood of undergoing PCI increased by 3 percentage points (95% CI 0 to 5) for minority patients relative to white patients after the Medicaid expansion. We did not find an association between the Medicaid expansion and racial disparities in overall likelihood of admission to a PCI hospital, hospital readmissions, or in-hospital mortality.ConclusionsThe Medicaid expansion was associated with a decrease in racial disparities in transfers and rates of PCI after AMI. We did not find an association between the Medicaid expansion and admission to a PCI hospital, readmissions, and in-hospital mortality. Additional factors outside of insurance coverage likely continue to contribute to disparities in outcomes after AMI. These findings are crucial for policy makers seeking to reduce racial disparities in access, treatment and outcomes in AMI.

In the search for novel agents against oral pathogens in their planktonic and biofilm form, we have focused our attention on 10-undecynoic acid as the representative of the acetylenic fatty acids. Using macro-broth susceptibility testing method we first established MIC value. Next, the MBC value was determined from a broth dilution minimum inhibitory concentration test by sub-culturing it to BHI agar plates that did not contain the test agent. Anti-biofilm efficacy was tested in 96-well plates coated with saliva using BHI broth supplemented with 1% sucrose as a standard approach. Based on obtained results, MIC value for 10-undecynoic acid was established to be 2.5 mg/ml and the MBC value to be 5 mg/ml. The MBIC90 showed to be 2.5 mg/ml, however completed inhibition of biofilm formation was achieved at 5.0 mg/ml. MBBC concentration revealed to be the same as MBC value, causing approximately 30% reduction at the same time in biomass of pre-existing biofilm, whereas application of 7.0 mg/ml of 10-undecynoic acid crossed the 50% eradication mark. Strong anti-adherent effect was observed upon 10-undecynoic acid application at sub-MBC concentrations as well, complemented with suppression of acidogenicity and aciduricity. Thus, we concluded that 10-undecynoic acid might play an important role in the development of alternative or adjunctive antibacterial and anti-biofilm preventive and/or therapeutic approaches.

PurposeObservational studies have demonstrated increased colon cancer recurrence and mortality in states of excess energy balance, as denoted by factors including sedentary lifestyle, diabetes, increased dietary glycemic load, and increased intake of sugar-sweetened beverages. Nonetheless, the relation between artificially sweetened beverages, a popular alternative for sugar-sweetened beverages, and colon cancer recurrence and survival is unknown.MethodsWe analyzed data from 1,018 patients with stage III colon cancer who prospectively reported dietary intake during and after chemotherapy while enrolled in a National Cancer Institute-sponsored trial of adjuvant chemotherapy. Using Cox proportional hazards regressions, we assessed associations of artificially sweetened beverage intake with cancer recurrence and mortality.ResultsPatients consuming one or more 12-ounce servings of artificially sweetened beverages per day experienced an adjusted hazard ratio for cancer recurrence or mortality of 0.54 (95% confidence interval, 0.36 to 0.80) when compared to those who largely abstained (Ptrend = .004). Similarly, increasing artificially sweetened beverage intake was also associated with a significant improvement in both recurrence-free survival (Ptrend = .005) and overall survival (Ptrend = .02). Substitution models demonstrated that replacing a 12-ounce serving of a sugar-sweetened beverage with an isovolumetric serving of an artificially sweetened beverage per day was associated with a 23% lower risk of cancer recurrence and mortality (relative risk, 0.77; 95% confidence interval, 0.63 to 0.95; P = .02).ConclusionHigher artificially sweetened beverage consumption may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer. This association may be mediated by substitution for sugar-sweetened alternatives. Further studies are needed to confirm these findings.

PURPOSE:Advanced pancreatic cancer is a highly refractory disease almost always associated with survival of little more than a year. New interventions based on novel targets are needed. We aim to identify new genetic determinants of overall survival (OS) in patients after treatment with gemcitabine using genome-wide screens of germline DNA. We aim also to support these findings with in vitro functional analysis. PATIENTS AND METHODS:Genome-wide screens of germline DNA in two independent cohorts of pancreatic cancer patients (from the Cancer and Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes associated with OS. The vitamin D receptor gene (VDR) was selected, and the interactions of genetic variation in VDR with circulating vitamin D levels and gemcitabine treatment were evaluated. Functional effects of common VDR variants were also evaluated in experimental assays in human cell lines. RESULTS:The rs2853564 variant in VDR was associated with OS in patients from both the Mayo Clinic (HR 0.81, 95% CI 0.70-0.94, p = 0.0059) and CALGB 80303 (HR 0.74, 0.63-0.87, p = 0.0002). rs2853564 interacted with high pre-treatment levels of 25-hydroxyvitamin D (25(OH)D, a measure of endogenous vitamin D) (p = 0.0079 for interaction) and with gemcitabine treatment (p = 0.024 for interaction) to confer increased OS. rs2853564 increased transcriptional activity in luciferase assays and reduced the binding of the IRF4 transcription factor. CONCLUSION:Our findings propose VDR as a novel determinant of survival in advanced pancreatic cancer patients. Common functional variation in this gene might interact with endogenous vitamin D and gemcitabine treatment to determine improved patient survival. These results support evidence for a modulatory role of the vitamin D pathway for the survival of advanced pancreatic cancer patients.

PURPOSE:Colon cancers deficient in mismatch repair (MMR) may exhibit diminished expression of the DNA repair gene, MRE11, as a consequence of contraction of a T11 mononucleotide tract. This study investigated MRE11 status and its association with prognosis, survival and drug response in patients with stage III colon cancer. PATIENTS AND METHODS:Cancer and Leukemia Group B 89803 (Alliance) randomly assigned 1,264 patients with stage III colon cancer to postoperative weekly adjuvant bolus 5-fluorouracil/leucovorin (FU/LV) or irinotecan+FU/LV (IFL), with 8 year follow-up. Tumors from these patients were analyzed to determine stability of a T11 tract in the MRE11 gene. The primary endpoint was overall survival (OS), and a secondary endpoint was disease-free survival (DFS). Non-proportional hazards were addressed using time-dependent covariates in Cox analyses. RESULTS:Of 625 tumor cases examined, 70 (11.2%) exhibited contraction at the T11 tract in one or both MRE11 alleles and were thus predicted to be deficient in MRE11 (dMRE11). In pooled treatment analyses, dMRE11 patients showed initially reduced DFS and OS but improved long-term DFS and OS compared with patients with an intact MRE11 T11 tract. In the subgroup of dMRE11 patients treated with IFL, an unexplained early increase in mortality but better long-term DFS than IFL-treated pMRE11 patients was observed. CONCLUSIONS:Analysis of this relatively small number of patients and events showed that the dMRE11 marker predicts better prognosis independent of treatment in the long-term. In subgroup analyses, dMRE11 patients treated with irinotecan exhibited unexplained short-term mortality. MRE11 status is readily assayed and may therefore prove to be a useful prognostic marker, provided that the results reported here for a relatively small number of patients can be generalized in independent analyses of larger numbers of samples. TRIAL REGISTRATION:ClinicalTrials.gov NCT00003835.

BACKGROUND:In colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown. METHODS:We assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models. RESULTS:Patients consuming ≥ 2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04-2.68), compared with those consuming