Ambient air exposures to arsenic and cadmium and overall and prostate cancer-specific survival among prostate cancer cases in Pennsylvania, 2004 to 2014.

BACKGROUND: Exposures to arsenic (As) and cadmium (Cd) have been associated with higher prostate cancer (PC) mortality; however, these associations have been inconsistent. The authors investigated whether higher ambient air concentrations of As and Cd are associated with lower overall and PC-specific survival among PC cases in Pennsylvania. METHODS: Incident PC cases of patients, aged 40 years or older, with a clinical diagnosis and nonmetastatic disease were identified in the 2004 to 2014 Pennsylvania Cancer Registry. Demographic, clinical, and pathologic information were extracted from the Pennsylvania Cancer Registry. The 3- and 5-year average and cumulative air concentrations of As and Cd were extracted from the Environmental Protection Agency's Toxics Release Inventory database. Spatial-temporal hierarchical accelerated failure time models were used to examine the associations between air concentrations of As and Cd and overall and PC-specific survival for the total population and stratified by geographical region defined by rurality and Appalachia status, after adjusting for confounders. RESULTS: There were 78,914 PC cases included. Increasing 3- and 5-year average and cumulative air concentrations of As and Cd were significantly associated with lower overall and PC-specific survival among cases, after adjusting for confounders, for the total population, and stratified by geographical region for most of the estimates. CONCLUSIONS: Data suggest that increasing ambient air exposures to As and Cd may play a role in overall and PC-specific mortality risk among PC cases. Exposures to As and Cd are modifiable and may provide insight into potential strategies to improve PC health outcomes. LAY SUMMARY: Arsenic and cadmium exposures linked to increased prostate cancer deaths remain unclear. We investigated whether air levels of arsenic and cadmium reported to be released from industries decrease overall and prostate cancer-specific survival among prostate cancer cases identified in the 2004 to 2014 Pennsylvania Cancer Registry. Among the 78,914 prostate cancer cases, increasing air levels of arsenic and cadmium are found to be associated with lower overall and prostate cancer-specific survival for the total population and within rural and urban Appalachia and urban non-Appalachia counties in Pennsylvania. Reducing exposures to arsenic and cadmium have the potential to decrease prostate cancer deaths.

Coffee intake and trace element blood concentrations in association with renal cell cancer among smokers.

PURPOSE: To determine whether higher coffee intake may reduce the risk of renal cell cancer (RCC) associated with lead (Pb) and other heavy metals with known renal toxicity. METHODS: We conducted a nested case-control study of male smokers (136 RCC cases and 304 controls) within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Cases diagnosed with RCC at 5 or more years following cohort enrollment were matched to controls on age (± 7 years) and whole blood draw date (± 30 days). Conditional logistic regression (using two-sided tests) was used to test for main effects and additive models of effect modification. RESULTS: After a mean follow-up of 16.3 years, coffee consumption was not significantly associated with renal cell cancer risk, when adjusting for blood concentrations of Cd, Hg, and Pb and RCC risk factors (age, smoking, BMI, and systolic blood pressure) (p-trend, 0.134). The association with above median blood Pb and RCC (HR = 1.69, 95% CI 1.06, 2.85) appeared to be modified by coffee consumption, such that RCC risk among individuals with both increased coffee intake and higher blood lead concentration were more than threefold higher RCC risk (HR = 3.40, 95% CI 1.62, 7.13; p-trend, 0.003). CONCLUSION: Contrary to our initial hypothesis, this study suggests that heavy coffee consumption may increase the previously identified association between higher circulating lead (Pb) concentrations and increased RCC risk. Improved assessment of exposure, including potential trace element contaminants in coffee, is needed.

Cost evaluation of an exercise oncology intervention: The exercise in all chemotherapy trial.

BACKGROUND: There is strong evidence supporting the efficacy of exercise oncology programs to improve physical and psychosocial outcomes during active treatment. However, there is a paucity of evidence on the effect of exercise on healthcare utilization and cost analyzes of exercise oncology programs. AIMS: Our objective was to assess the effects of a pragmatic exercise oncology program (ENACT) during active chemotherapy treatment on healthcare utilization and associated costs. METHODS: We conducted post-hoc analyzes on 160 ENACT participants and 75 comparison participants matched on cancer site, stage, age range, and gender. We obtained complete healthcare utilization histories for each patient (specific to emergency department [ED] visits and hospital admissions) coinciding with their participation in ENACT. A sub-analysis was conducted for advanced stage breast, gastrointestinal, and pancreatic cancer patients. RESULTS: Healthcare costs for patients who participated in the ENACT exercise oncology intervention were numerically lower than healthcare costs for the comparison group, even after accounting for the cost of the intervention. However, the differences were not statistically significant. CONCLUSION: Our findings suggest that an exercise oncology program during active chemotherapy treatment are at least cost neutral for all cancer patients, including advanced stage cancers. Additional research is warranted to evaluate the potential for exercise oncology programs to reduce healthcare utilization, particularly in advanced cancer patients.

Examining medication adherence and preferences for a lifestyle intervention among Black and Latinx adults with hypertension: a feasibility study.

BACKGROUND: Approximately 116.4 million adults in the USA have hypertension, and the rates of uncontrolled hypertension remain higher among racial and ethnic minorities. There is a need for effective interventions that promote healthy behaviors and long-term behavioral change in the management of hypertension. The primary objective of this study was to determine the feasibility of developing a lifestyle intervention that would assess hypertension management and the use of technology among Blacks and Latinx with hypertension. The secondary objective is to explore perceptions of community-based resources for hypertension and preferences for a lifestyle intervention for hypertension among Blacks and Latinx with hypertension. METHODS: In this explanatory mixed-methods study, quantitative data were collected using surveys, participants reported their use of technology and adherence to antihypertensive medication. Participants were Black and Latinx adults with hypertension living in Central Pennsylvania, USA. Qualitative data were obtained from semi-structured interviews and focus groups, and participants were asked about managing hypertension, local resources, and preferences for a behavioral intervention. Data were examined using summary statistics for quantitative data and thematic analysis for qualitative data. RESULTS: Black and Latinx participants (n=30) completed surveys for the quantitative study. The majority (75%) of participants self-reported being confident in managing their medication without help and remembering to take their medication as prescribed. Fewer participants (54.2%) reported using technology to help manage medication. There were 12 participants in the qualitative phase of the study. The qualitative findings indicated that participants felt confident in their ability to manage hypertension and were interested in participating in a lifestyle intervention or program based online. Some participants reported a lack of resources in their community, while others highlighted local and national resources that were helpful in managing high blood pressure. CONCLUSION: This study provides important insights on barriers and facilitators for managing hypertension, current use of technology and interest in using technology to manage hypertension, and preferences for future lifestyle interventions among racial and ethnic minorities. This study also provides insights to the health needs and resources available in this community and how future behavioral interventions could be tailored to meet the needs of this community. The findings of this study will be used to inform the tailoring of future lifestyle interventions; specifically, we will include text messaging reminders for medication and to disseminate educational materials related to hypertension and provide resources to connect study participants with local and national resources.

Association between urinary arsenic, blood cadmium, blood lead, and blood mercury levels and serum prostate-specific antigen in a population-based cohort of men in the United States.

Exposures to heavy metals have been linked to prostate cancer risk. The relationship of these exposures with serum prostate-specific antigen (PSA), a marker used for prostate cancer screening, is unknown. We examined whether total urinary arsenic, urinary dimethylarsonic acid, blood cadmium, blood lead, and total blood mercury levels are associated with elevated PSA among presumably healthy U.S. men. Prostate cancer-free men, aged ≥40 years, were identified from the 2003-2010 National Health and Nutrition Examination Survey. Logistic regression analyses with survey sample weights were used to examine the association between heavy metal levels and elevated PSA for the total population and stratified by black and white race, after adjusting for confounders. There were 5,477 men included. Approximately 7% had elevated PSA. Men with an elevated PSA had statistically significantly higher levels of blood cadmium and blood lead compared to men with a normal PSA (p-values ≤ 0.02), with black men having higher levels. After adjusting for age, race/ethnicity, body mass index, smoking, and education, there was no association found between any of the heavy metal levels and elevated PSA for the total population. In addition, there was no association found when stratified by black and white race. Further investigation is warranted in a larger cohort of men who persistently are exposed to these heavy metals.

Synthesis and Pesticidal Activities of New Quinoxalines.

Natural products are a source of many novel compounds with biological activity for the discovery of new pesticides and pharmaceuticals. Quinoxaline is a fused N-heterocycle in many natural products and synthetic compounds, and seven novel quinoxaline derivatives were designed and synthesized via three steps. Pesticidal activities of title quinoxaline derivatives were bioassayed. Most of these compounds had herbicidal, fungicidal, and insecticidal activities. The compounds 2-(6-methoxy-2-oxo-3-phenylquinoxalin-1(2H)-yl)acetonitrile (3f) and 1-allyl-6-methoxy-3-phenylquinoxalin-2(1H)-one (3g) were the most active herbicides and fungicides. Mode-of-action studies indicated that 3f is a protoprophyrinogen oxidase-inhibiting herbicide. Compound 3f also possessed broad-spectrum fungicidal activity against the plant pathogen Colletotrichum species. Some of these compounds also had insecticidal activity. Molecular docking and DFT analysis can potentially be used to design more active compounds.

Novel 4-pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity.

BACKGROUND: In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure-activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity. RESULTS: Twenty-seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L-1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 µg mL-1 . In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method. CONCLUSION: It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry.

Microwave assisted synthesis, antifungal activity, DFT and SAR study of 1,2,4-triazolo[4,3-a]pyridine derivatives containing hydrazone moieties.

BACKGROUND: The increasing prevalence of multi-drug resistant fungal infections has encouraged the search for new antifungal agents. Hydrazone derivatives always exhibited diversity activities, including antifungal, anti-inflammatory, anti-oxidation, anti-cancer activity. Regarding the heterocyclic moiety, 1,2,4-triazolo[4,3-a]pyridine derivatives also display broad activities, such as antifungal activity, anticonvulsant activity, herbicidal activity, antimicrobial activity and anticancer activity. RESULTS: A series of novel 1,2,4-triazolo[4,3-a]pyridine derivatives containing hydrazone moiety were designed and synthesized from 2,3-dichloropyridine, hydrazine hydrate by multi-step reactions under microwave irradiation condition, and their structures were characterized by FT IR, (1)H NMR, (13)C NMR, (19)F NMR, MS and elemental analysis. The antifungal activities of title compounds were determined. The results indicated that some of the title compounds exhibited good antifungal activity. Furthermore, DFT calculation was carried out for studying the structure-activity relationship (SAR). CONCLUSION: A practical synthetic route to obtain 1,2,4-triazolo[4,3-a]pyridine derivatives is presented. This study suggests that the 1,2,4-triazolo[4,3-a]pyridine derivatives exhibited good antifungal activity.

pH-Dependence of the Aqueous Phase Room Temperature Brønsted Acid-Catalyzed Chemoselective Oxidation of Sulfides with H2O2.

A pH-dependence of the Brønsted acid-catalyzed oxidation of sulfides to the corresponding sulfoxides with H2O2 is reported for the first time based on our systematic investigation of the catalytic performance of a series of Brønsted acids. For all of the Brønsted acids investigated, the catalytic performances do not depend on the catalyst loading (mol ratio of Brønsted acid to substrate), but rather depend on the pH value of the aqueous reaction solution. All of them can give more than 98% conversion and selectivity in their aqueous solution at pH 1.30, no matter how much the catalyst loading is and what the Brønsted acid is. This pH-dependence principle is a very novel perspective to understand the Brønsted-acid catalysis system compared with our common understanding of the subject.

Apigenin inhibits TGF-ß1-induced proliferation and migration of airway smooth muscle cells.

It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-ß1 (TGF-ß1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-ß1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-ß1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-ß1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.

Microwave assistant synthesis, antifungal activity and DFT theoretical study of some novel 1,2,4-triazole derivatives containing pyridine moiety.

In order to investigate the biological activity of novel 1,2,4-triazole compounds, seventeen novel 1,2,4-triazole derivatives containing pyridine moiety were synthesized under microwave assistant condition by multi-step reactions. The structures were characterized by 1H NMR, MS and elemental analyses. The target compounds were evaluated for their fungicidal activities against Stemphylium lycopersici (Enjoji) Yamamoto, Fusarium oxysporum. sp. cucumebrium, and Botrytis cinerea in vivo, and the results indicated that some of the title compounds displayed excellent fungicidal activities. Theoretical calculation of the title compound was carried out with B3LYP/6-31G (d,p). The full geometry optimization was carried out using 6-31G (d,p) basis set, and the frontier orbital energy, atomic net charges were discussed, and the structure-activity relationship was also studied.