Association Between Young Adult Characteristics and Blood Pressure Trajectories.

BACKGROUND: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample. METHODS AND RESULTS: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m2, 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m2, 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2). CONCLUSIONS: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells.

Metabolic abnormalities are one of the main hallmarks of cancer and are associated with chemoresistance. Therefore, targeting the metabolic reprogramming of cancer cells has the potential to overcome chemoresistance. Probiotic-derived extracellular vesicles (EVs) play important roles in biological function and intracellular communication. However, the inhibitory effect of Lactobacillus plantarum-derived EVs (LpEVs) on colorectal cancer (CRC) cells has not yet been elucidated. This study clearly revealed that increased glycolysis in 5-fluorouracil (5-FU)-resistant CRC cells (CRC/5FUR) is directly related to chemoresistance and that the metabolic shift reversed by LpEVs inhibits cancer cell proliferation and eventually leads to apoptosis. Pyruvate dehydrogenase kinase 2 (PDK2), one of the crucial enzymes for enhancing glycolysis, was upregulated in CRC/5FUR cells. In our study, LpEVs sensitized CRC/5FUR cells to 5-FU by attenuating PDK2 expression in p53-p21-dependent metabolic signaling, thereby circumventing 5-FU resistance. We demonstrated the effect of cellular responses to 5-FU by modifying the PDK2 expression level in both 5-FU-sensitive parental CRC and 5-FU resistant CRC cell lines. Finally, we revealed that the PDK2 signaling pathway can potentially be targeted using LpEVs treatment to overcome chemoresistant CRC, thereby providing a potential strategy for CRC treatment by intervening in tumor metabolism.

Lactobacillus plantarum-derived metabolites sensitize the tumor-suppressive effects of butyrate by regulating the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells.

A critical obstacle to the successful treatment of colorectal cancer (CRC) is chemoresistance. Chemoresistant CRC cells contribute to treatment failure by providing a mechanism of drug lethargy and modifying chemoresistance-associated molecules. The gut microbiota provide prophylactic and therapeutic effects by targeting CRC through anticancer mechanisms. Among them, Lactobacillus plantarum contributes to the health of the host and is clinically effective in treating CRC. This study confirmed that 5-fluorouracil (5-FU)-resistant CRC HCT116 (HCT116/5FUR) cells acquired butyrate-insensitive properties. To date, the relationship between 5-FU-resistant CRC and butyrate resistance has not been elucidated. Here, we demonstrated that the acquisition of butyrate resistance in HCT116/5FUR cells was strongly correlated with the inhibition of the expression and function of SMCT1, a major transporter of butyrate in colonocytes. L. plantarum-cultured cell-free supernatant (LP) restored the functional expression of SMCT1 in HCT116/5FUR cells, leading to butyrate-induced antiproliferative effect and apoptosis. These results suggest that LP has a synergistic effect on the SMCT1/butyrate-mediated tumor suppressor function and is a potential chemosensitizer to overcome dual 5-FU and butyrate resistance in HCT116 cells.

GABA-producing Lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABAB receptor signaling.

5-Fluorouracil (5-FU) is an essential drug in systemic chemotherapy treatments for colorectal cancer (CRC). Despite the development of several treatment strategies over the past decades, the patient benefits of 5-FU-based therapies have been compromised by the development of chemoresistance. Differences in treatment responses among CRC patients may be due to genetic and epigenetic factors unique to individuals. Therefore, important factors for realizing personalized medicine are to accurately understand the causes and mechanisms of drug resistance to 5-FU-based therapies and to identify and validate prognostic biomarkers. Gut microbes that interact directly with the host contribute to human health and cancer control. Lactobacillus plantarum, in particular, has the potential to be a therapeutic agent by producing bioactive compounds that may benefit the host. Here, we investigated the gamma-aminobutyric acid (GABA) and GABAB receptor (GABABR)-dependent signaling pathway as a treatment option for 5-FU-resistant HT-29 cells. GABA-producing L. plantarum activates anti-proliferative, anti-migration, and anti-invasion effects against 5-FU-resistant HT-29 cells. The inhibitory effects of GABA-producing L. plantarum are mediated via GABABR. Activated GABABR induces apoptosis through the inhibition of cAMP-dependent signaling pathways and cellular inhibitor of apoptosis protein 2 (cIAP2) expression. Thus, the GABAergic system has potential in 5-FU-resistant HT-29 cells as a predictive biomarker. In addition, GABA-producing L. plantarum is promising as an adjuvant treatment for 5-FU-resistant CRC, and its intervention in neurobiological signaling imply new possibilities for chemoprevention and the treatment of colon cancer-related diseases.

Prevalence and incidence of microvascular and macrovascular complications over 15 years among patients with incident type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) is a common condition that, if left untreated or poorly managed, can lead to adverse microvascular and macrovascular complications. We estimated the prevalence and incidence of microvascular and macrovascular complications among patients newly diagnosed with T2D within a US integrated healthcare system. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study among patients newly diagnosed with T2D between 2003 and 2014. We evaluated 13 complications, including chronic kidney disease (CKD), cardiovascular disease (CVD), and all-cause mortality through 2018. Multivariable Cox proportional hazards models were used to study factors associated with complications. RESULTS: We identified 135 199 patients with incident T2D. The mean age was 58 years, and 48% were women. The prevalence of CKD was the highest of the complications at the time of T2D diagnosis (prevalence=12.3%, 95% CI 12.2% to 12.5%), while the prevalence of CVD was among the lowest at 3.3% (95% CI 3.2% to 3.3%). The median time to incidence of a T2D complication ranged from 3.0 to 5.2 years. High incidence rates (95% CI) of T2D complications included peripheral neuropathy (26.9, 95% CI 26.5 to 27.3 per 1000 person-years (PY)), CKD (21.2, 95% CI 20.9 to 21.6 per 1000 PY), and CVD (11.9, 95% CI 11.7 to 12.2 per 1000 PY). The trend of 5-year incidence rates of T2D complications by diagnosis year decreased over time (p value<0.001). Older age, non-Hispanic white race/ethnicity, sex, higher A1C, smoking, and hypertension were associated with increased CKD and CVD incidence. CONCLUSION: Though incidence rates of T2D complications were lower in more recent years (2010-2014), a significant proportion of patients had complications at T2D diagnosis. Earlier preventive therapies as well as managing modifiable factors may help delay the development and progression of T2D complications.

Lactobacillus-derived metabolites enhance the antitumor activity of 5-FU and inhibit metastatic behavior in 5-FU-resistant colorectal cancer cells by regulating claudin-1 expression.

Lactobacillus plantarum-derived metabolites (LDMs) increase drug sensitivity to 5-FU and antimetastatic effects in 5-FU-resistant colorectal cancer cells (HCT-116/5FUR). In this study, we evaluated the effects of LDMs on the regulation of genes and proteins involved in HCT-116/5-FUR cell proliferation and metastasis. HCT-116/5-FUR cells showed high metastatic potential, significantly reduced tight junction (TJ) integrity, including increased migration and paracellular permeability, and upregulation of claudin-1 (CLDN-1). The genetic silencing of CLDN-1 increased the sensitivity of HCT-116/5FUR to 5-FU and inhibited its metastatic potential by regulating the expression of epithelial-mesenchymal transition (EMT) related genes. Co-treatment of HCT-116/5FUR with LDMs and 5-FU suppressed chemoresistant and metastatic behavior by downregulating CLDN-1 expression. Finally, we designed LDMs-based therapeutic strategies to treatment for metastatic 5-FU-resistant colorectal cancer cells. These results suggested that LDMs and 5-FU cotreatments can synergistically target 5-FU-resistant cells, making it a candidate strategy to overcome 5-FU chemoresistance improve anticancer drug efficacy.

Surface Energy of Filtration Media Influencing the Filtration Performance against Solid Particles, Oily Aerosol, and Bacterial Aerosol.

Particulate airborne pollutants are a big concern to public health, and it brings growing attention about effective filtration devices. Especially, particulate matters smaller than 2.5 µm can reach the thoracic region and the blood stream, and the associated health risk can be exacerbated when pathogenic microbials are present in the air. This study aims at understanding the surface characteristics of nonwoven media that influence filtration performance against solid particles (sodium chloride, NaCl), oily aerosol (dioctyl phthalate, DOP), and Staphylococcus aureus (S. aureus) bacteria. Nonwoven media of polystyrene (PS) fibers were fabricated by electrospinning and its pristine surface energy (38.5 mN/m) was modified to decrease (12.3 mN/m) by the plasma enhanced chemical vapor deposition (PECVD) of octafluorocyclobutane (C4F8) or to increase (68.5 mN/m) by the oxygen (O2) plasma treatment. For NaCl particles and S. aureus aerosol, PS electrospun web showed higher quality factor than polypropylene (PP) meltblown electret that is readily available for commercial products. The O2 plasma treatment of PS media significantly deteriorated the filtration efficiency, presumably due to the quick dissipation of static charges by the O2 plasma treatment. The C4F8 treated, fluorinated PS media resisted quick wetting of DOP, and its filtration efficiency for DOP and S. aureus remained similar while its efficiency for NaCl decreased. The findings of this study will impact on determining relevant surface treatments for effective particulate filtration. As this study examined the instantaneous performance within 1-2 min of particulate exposure, and the further study with the extended exposure is suggested.

Economic evaluation of patient-centered care among long-term cancer survivors.

OBJECTIVES: To evaluate the economic outcomes associated with patient perceptions of patient-centered medical home (PCMH) characteristics among long-term cancer survivors in the United States. STUDY DESIGN: A retrospective analysis of the 2008 to 2012 Medical Expenditure Panel Survey. METHODS: A nationally representative sample of adult long-term cancer survivors (≥3 years since diagnosis) was categorized into either patient-centered care (PCC) or non-PCC groups based on responses to PCMH model hallmark attributes of "comprehensive care," "whole-person orientation," and "accessible care." The positive perception of all 3 attributes was defined as PCC. The patient perceptions, as well as patient characteristics, were measured at year 1 (baseline), with a propensity score model to balance baseline characteristics. Adjusted total healthcare utilization and healthcare expenditures in 2014 US$ at year 2 (follow-up) were compared between the PCC and non-PCC groups. RESULTS: A total of 4288 long-term cancer survivors were identified, with a mean (SD) age of 65.2 (13.8) years. The PCC group was associated with a reduction in mean adjusted healthcare expenditures at follow-up (savings of $1596 per cancer survivor; P = .020). These findings are driven by lower odds of hospitalization (odds ratio, 0.81; 95% CI, 0.66-0.99; P = .035) and lower hospitalization-related healthcare expenditures (PCC: $3323; 95% CI, $2727-$3918; non-PCC: $4912; 95% CI, $4039-$5785; P = .002) associated with PCC among the population who were 65 years and older. The whole-person orientation attribute had a major impact on reduced healthcare expenditures. CONCLUSIONS: The positive patient perception of PCMH characteristics was associated with reduced healthcare expenditures in adult long-term cancer survivors.

Adherence to the American Diabetes Association retinal screening guidelines for population with diabetes in the United States.

PURPOSE: (1) To assess long-term adherence to American Diabetes Association guideline-recommended retinal screening among population with diabetes in the United States. (2) To determine factors associated with long-term adherence to routine eye screening exams. METHODS: A retrospective cohort study was conducted in adult patients with diabetes identified from January 2009 to December 2010. Patients were followed until disenrollment, death, or study end date (December 2013). A patient was defined as adherent when having at least one exam in each 12-month period if there was evidence of retinopathy, or at least one exam in each 24-month period if there was no evidence of retinopathy. Multivariate logistic regressions were used to investigate patient demographics and other baseline characteristics associated with adherence to guidelines. RESULTS: A total of 204,073 patients were identified; the mean age (SD) was 61 (13) years and 48% were female. Overall, 71.1% were adherent to the retinal screening guidelines during a median of 4.8 years of follow-up including 27.7% who received an eye exam every year. Patient socioeconomic status (younger age, black race, lower income/education), less comorbidity, insulin use, higher specialist copayment plans, and proxies for poor patient behavior (lower adherence to the oral hypoglycemic agents, less diabetes education, hemoglobin A1C >9%) were associated with nonadherence to routine eye screening exams. CONCLUSION: During nearly 5 years of follow-up, 28.9% of patients with diabetes were nonadherent to the retinal screening guidelines. Future research should focus on the development of interventions to address modifiable factors associated with nonadherence.

Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells.

Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT- 116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/ß-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.