Increased Utilization of Low-Dose CT for Lung Cancer Screening at an Arkansas Community Oncology Clinic.

BACKGROUND: Low-dose CT (LDCT) is underused in Arkansas for lung cancer screening, a rural state with a high incidence of lung cancer. The objective was to determine whether offering free LDCT increased the number of high-risk individuals screened in a rural catchment area. METHODS: There were 5,402 patients enrolled in screening at Highlands Oncology, a community oncology clinic in Northwest Arkansas, from 2013 to 2020. Screenings were separated into time periods: period 1 (10 months for-fee), period 2 (10 months free with targeted advertisements and primary care outreach), and period 3 (62 months free with only primary care outreach). In all, 5,035 high-risk participants were eligible for analysis based on National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Enrollment rates, incidence densities (IDs), Cox proportional hazard models, and Kaplan-Meier curves were performed to investigate differences between enrollment periods and high-risk groups. RESULTS: Patient volume increased drastically once screenings were offered free of charge (period 1 = 4.6 versus period 2 = 66.0 and period 3 = 69.8 average patients per month). Incidence density per 1,000 person-years increased through each period (IDPeriod 1 = 17.2; IDPeriod 2 = 20.8; IDPeriod 3 = 25.5 cases). Cox models revealed significant differences in lung cancer risk between high-risk groups (P = .012) but not enrollment periods (P = .19). Kaplan-Meier lung cancer-free probabilities differed significantly between high-risk groups (log-rank P = .00068) but not enrollment periods (log-rank P = .18). CONCLUSIONS: This study suggests that eligible patients are more receptive to free LDCT screening, despite most insurances not having a required copay for eligible patients.

Maternal Periconceptional Folic Acid Supplementation and DNA Methylation Patterns in Adolescent Offspring.

BACKGROUND: Folate, including the folic acid form, is a key component of the one-carbon metabolic pathway used for DNA methylation. Changes in DNA methylation patterns during critical development periods are associated with disease outcomes and are associated with changes in nutritional status in pregnancy. The long-term impact of periconceptional folic acid supplementation on DNA methylation patterns is unknown. OBJECTIVES: To determine the long-term impact of periconceptional folic acid supplementation on DNA methylation patterns, we examined the association of the recommended dosage (400 µg/d) and time period (periconceptional before pregnancy through first trimester) of folic acid supplementation with the DNA methylation patterns in the offspring at age 14-17 y compared with offspring with no supplementation. METHODS: Two geographic sites in China from the 1993-1995 Community Intervention Program of folic acid supplementation were selected for the follow-up study. DNA methylation at 402,730 CpG sites was assessed using saliva samples from 89 mothers and 179 adolescents (89 male). The mean age at saliva collection was 40 y among mothers (range: 35-54 y) and 15 y among adolescents (range: 14-17 y). Epigenome-wide analyses were conducted to assess the interactions of periconceptional folic acid exposure, the 5,10-methylenetetrahydrofolate reductase (MTHFR)-C677T genotype, and epigenome-wide DNA methylation controlling for offspring sex, geographic region, and background cell composition in the saliva. RESULTS: In the primary outcome, no significant differences were observed in epigenome-wide methylation patterns between adolescents exposed and those non-exposed to maternal periconceptional folic acid supplementation after adjustment for potential confounders [false discovery rate (FDR) P values < 0.05]. The MTHFR-C677T genotype did not modify this lack of association (FDR P values < 0.05). CONCLUSIONS: Overall, there were no differences in DNA methylation between adolescents who were exposed during the critical developmental window and those not exposed to the recommended periconceptional/first-trimester dosage of folic acid.

The liquid Kangfuxin (KFX) has efficient antifungal activity and can be used in the treatment of vulvovaginal candidiasis in mice.

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50 ) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug-resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae-related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin-17A (IL-17A); however, the levels of interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL-17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC.

Novel variants and uncommon cases among southern Chinese children with X-linked hypophosphatemia.

PURPOSE: X-linked hypophosphatemia (XLH) is the most common inherited renal phosphate wasting disorder and is often misdiagnosed as vitamin D deficiency. This study aims to provide clinical and mutational characteristics of 65 XLH pediatric patients in southern China. METHODS: In this work, a combination of DNA sequencing and qPCR analysis was used to study the PHEX gene in 80 pediatric patients diagnosed with hypophosphatemia. The clinical and laboratory data of confirmed 65 XLH patients were assessed and analyzed retrospectively. RESULTS: In 65 XLH patients from 61 families, 51 different variants in the PHEX gene were identified, including 23 previously reported variants and 28 novel variants. In this cohort of XLH patients, the c.1601C>T(p.Pro534Leu) variant appears more frequently. Fourteen uncommon XLH cases were described, including four boys with de novo mosaic variants, eight patients with large deletions and a pair of monozygotic twins. The clinical manifestations in this cohort are very similar to those previously reported. CONCLUSION: This study extends the mutational spectrum of the PHEX gene, which will contribute to accurate diagnosis. This study also suggests a supplementary qPCR or MLPA assay may be performed along with classical sequencing to confirm the gross insertion/deletion.

Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP).

Background: Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. Objective: The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Design: Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. Results: There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Conclusions: Among both African American and European American men diagnosed with prostate cancer, a higher Ca:Mg and whole-milk intake were associated with higher odds of high-aggressive prostate cancer. This study was registered at www.clinicaltrials.gov as NCT03289130.

Longitudinal Association between Selenium Levels and Hypertension in a Rural Elderly Chinese Cohort.

OBJECTIVES: Results from previous studies have been inconsistent on the association between selenium and hypertension, and very few studies on this subject have focused on the elderly population. The purpose of this study is to examine the relationship between selenium level and hypertension in a rural elderly Chinese cohort. DESIGN: A longitudinal study was implemented and data were analyzed using logistic regression models and Cox proportional hazards regression model adjusting for potential confounders. The associations between selenium level and prevalent hypertension at baseline and between selenium and incident hypertension were examined. SETTING: Community-based setting in four rural areas in China. SUBJECTS: A total of 2000 elderly aged 65 years and over (mean 71.9±5.6 years) participated in this study. MEASUREMENTS: Nail selenium levels were measured in all subjects at baseline. Blood pressure measures and self-reported hypertension history were collected at baseline, 2.5 years and 7 years later. Hypertension was defined as systolic blood pressure 140 mmHg or higher, diastolic blood pressure 90 mmHg or higher, or reported use of anti-hypertensive medication. RESULTS: The rate of baseline hypertension was 63.50% in this cohort and the mean nail selenium level is 0.413±0.183µg/g. Multi-covariate adjusted cross-sectional analyses indicated that higher selenium level was associated with higher blood pressure measures at baseline and higher rates of hypertension. For the 635 participants with normal blood pressure at baseline, 360 had developed hypertension during follow-up. The incidence rate for hypertension was 45.83%, 52.27%, 62.50%, 70.48%, and 62.79% from the first selenium quintile to the fifth quintile respectively. Comparing to the lowest quintile group, the hazard ratios were 1.41 (95%CI: 1.03 to1.94), 1.93 (95%CI: 1.40 to 2.67), 2.35 (95%CI: 1.69 to 3.26) and 1.94 (95%CI: 1.36 to 22.77) for the second selenium quintile to the fifth quintile respectively. CONCLUSIONS: Our findings suggest that high selenium may play a harmful role in the development of hypertension. Future studies are needed to confirm our findings and to elucidate a plausible biological mechanism.

Carotenoid intake and adipose tissue carotenoid levels in relation to prostate cancer aggressiveness among African-American and European-American men in the North Carolina-Louisiana prostate cancer project (PCaP).

BACKGROUND: Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may result from combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. METHODS: Data on African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed-food frequency questionnaire (FFQ), and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analyses to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. RESULTS: Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher ß-cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR = 0.55, 95%CI: 0.34-0.89, Ptrend = 0.02), while an inverse association was observed between dietary ß-cryptoxanthin intake and high aggressive CaP among AAs (OR = 0.56, 95%CI: 0.36-0.87, Ptrend = 0.01). Adipose tissue α-carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α-carotene (Ptrend = 0.07) and lycopene (Ptrend = 0.11), and CaP aggressiveness among EAs only. CONCLUSIONS: These results suggest that diets high in lycopene and ß-cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the observed racial differences in associations. Prostate 76:1053-1066, 2016. © 2016 Wiley Periodicals, Inc.

Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study.

The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P-trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms.

Role of MnSOD in propofol protection of human umbilical vein endothelial cells injured by heat stress.

PURPOSE: Heat stress stimulation can cause various injuries in human umbilical vein endothelial cells (HUVEC), including apoptotic cell death and an increase in cell permeability. Propofol (PPF), a commonly used anesthetic, is known to have an important role in antioxidation as well as organ protection. Therefore, our aim is to evaluate the protective effects of PPF on heat stress (HS)-induced oxidative stress injury and its possible mechanism of action. METHODS: For HS + PPF, cells were treated with propofol followed by 2 h heat stress at 43 °C and then 4 h incubation under normal conditions. For propofol treatment, HUVEC were cultured in serum-free Dulbecco's modified Eagle medium supplemented with 0, 10, 25, or 50 µM propofol for 6 h under normal conditions. RESULTS: During the study, we found that, in HS-induced cellular damage, the protective effect of propofol was related closely with its antioxidation properties. We further revealed that heat stress significantly reduced the level of manganese superoxide demutase (MnSOD) and Cu/Zn SOD, but that propofol could inhibit the reduction of MnSOD only. Transfection of HUVEC with MnSOD small interfering RNA (siRNA) markedly decreased the expression of MnSOD, and the protective effect of propofol in the MnSOD siRNA clones was significantly reduced. CONCLUSION: Propofol protected the heat stress-injured cells, at least partly, through upregulating MnSOD expression, effectively reducing the direct or indirect cell damage caused by oxidative stress.

Intake of dietary antioxidants is inversely associated with biomarkers of oxidative stress among men with prostate cancer.

Prostate cancer is the most common non-cutaneous cancer and the second leading cause of cancer-related mortality among men in the USA. Growing evidence suggests that oxidative stress is involved in the development and progression of prostate cancer. In this study, the association between antioxidants from diet and supplements and biomarkers of oxidative stress in blood (n 278), urine (n 298) and prostate tissue (n 55) were determined among men from the North Carolina-Louisiana Prostate Cancer Project. The association between antioxidant intake and oxidative stress biomarkers in blood and urine was determined using linear regression, adjusting for age, race, prostate cancer aggressiveness and smoking status. Greater antioxidant intake was found to be associated with lower urinary 8-isoprostane concentrations, with a 10% increase in antioxidant intake corresponding to an unadjusted 1·1% decrease in urinary 8-isoprostane levels (95% CI -1·7, -0·3%; P value<0·01) and an adjusted 0·6% decrease (95% CI -1·4, 0·2%; P value=0·16). In benign prostate tissue, thioredoxin 1 was inversely associated with antioxidant intake (P=0·02). No significant associations were found for other blood or urinary biomarkers or for malignant prostate tissue. These results indicate that antioxidant intake may be associated with less oxidative stress among men diagnosed with prostate cancer.

Dietary, supplement, and adipose tissue tocopherol levels in relation to prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP).

BACKGROUND: Controversies remain over the safety and efficacy of vitamin E (i.e., α-tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. METHODS: This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n = 1,023) and European-American (EA, n = 1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were estimated from logistic regression comparing high-aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. RESULTS: Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95%CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17-0.69), P(trend) = 0.006; δ-tocopherol, 0.45 (0.21-0.95) P(trend) = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95%CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28-1.19), P(trend) = 0.20; supplemental α-tocopherol, 0.64 (0.31-1.21) P(trend) = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95%CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66-3.11) and AAs 0.66 (0.27-1.62)]. CONCLUSIONS: The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness.

Protection from vascular endothelial dysfunction in acute glycemic load-induced primary hypertension by vitamin C and E.

This study aimed to investigate the influence of acute glycemic load on vascular endothelial function in patients with hypertension and to evaluate the protective effect of vitamins C and E during the acute glycemic phase. We randomly selected 39 hypertensive patients and 21 normal subjects and divided them into 3 groups: 75 g oral glucose (glycemic load group), 75 g glucose+0.9 g vitamin C (VC group), 75 g glucose+2 g vitamin C+0.8 g vitamin E (VC+VE group). Extravascular color Doppler ultrasound was used to detect brachial artery flow-mediated vasodilation at 0, 1, 2, and 3 h, and, at the same time, serum anti-oxidant products were measured. Basic endothelial functions in patients with hypertension were decreased in the glycemic load group (9.48±3.33 versus 13.09±6.78%, P<0.05), and was even more depressed in the hypertensive group (9.48±3.33 versus 14.20±6.48%, P<0.05). Antioxidant vitamins played a dose-dependent protective role on acute damage of endothelial function due to glycemic load. Acute high blood sugar damaged vascular endothelial functions, especially in hypertensive patients, but this effect can be reversed by large doses of vitamin C and E.

Lycopene reduces the negative effects induced by lipopolysaccharide in breeding hens.

This study assessed the effects of lycopene on the antioxidant capacity, biochemical parameters, and immune organ index of breeding hens following lipopolysaccharide (LPS) injection. The study had a 2 × 2 factorial design. Healthy Xing-hua breeding hens (720) were divided into groups with 6 replicates per group and 30 hens per replicate. Hens were fed on a rice-soya bean basal meal supplemented with different levels of lycopene (0, 20, 40, or 80 mg/kg diet). On d 35, two hens from each replicate were injected subcutaneously with 1 mg/kg body weight of either LPS or sterile saline (control group). Blood samples were collected at 0, 6, and 24 h post-injection. At 24 h post-injection, hens were sacrificed and the thymus, spleen, and bursa of Fabricius were removed. The results revealed that LPS significantly decreased high density lipoprotein cholesterol (HDLC), triidothyronine (T3), reduced glutathione to oxidised glutathione ratio (GSH/GSSG), thymus and bursal indexes, and increased low density lipoprotein cholesterol (LDLC). Lycopene supplementation significantly increased HDLC, T3, GSH/GSSG, and immune organ index, and decreased total cholesterol, LDLC, and blood urea nitrogen (BUN). The interaction effects of lycopene and LPS were significant on BUN and T3. Lycopene supplementation affected inflammatory immune response based on increased immune organ index of breeding hens by relieving the LPS-induced stress.

Functionalized gold nanorods for thermal ablation treatment of bladder cancer.

Nanomaterial-directed, photothermal ablation is a practical future approach for the treatment of early-stage bladder cancer. Using a new PEGylation technique with bi-functional nitrophenyl carbonate PEG (bi-NPC-PEG) that promotes uniform suspension of the nanomaterial in solution, we have shown that gold nanorods conjugated to an anti-EGFR antibody (nano-alphaEGFR) bind effectively to EGFR-expressing bladder cancer cells. The subsequent application of infrared light, specifically tuned to the plasmon resonance of the nanorods used in this work, allows for the specific heating of nano-alphaEGFR to the point of localized cellular death. Such an approach, administering nano-alphaEGFR intravesically via a urinary catheter and infrared light via a modified cystoscope, represents a novel, future clinical application of this technology, which avoids the problem of systemic exposure and clearance of nanoparticles from body.

In vitro induction of tetraploid garlic with trifluralin.

Garlic (Allium sativum) is propagated asexually. Since sexual cross breeding is almost impossible, means for effective breeding are not currently available and the available production cultivars are seriously aged and degenerated. A possible alternative for breeding is chemical induction. Trifluralin, a type of herbicide, has been reported to provoke chromosome doubling. However, this chemical had not been tested on garlic. We tested various trifluralin concentrations and treatment durations for efficiency in the induction of tetraploid garlic. A clove base of garlic with a stem cv. Gailiang was used as the ex-plant to induce calluses on Murashige and Skoog (MS) medium; the calluses were then inoculated onto MS medium containing different levels of trifluralin and cultured to induce chromosome number variation in vitro. Garlic calluses were effectively induced via the ex-plant and both shoots and roots differentiated well on MS medium containing 6-benzylaminopurine at 3.0 mg/L and indole-3-acetic acid at 0.1 mg/L. However, increases in trifluralin concentration and treatment duration reduced the survival rate and differentiation rate of calluses. Garlic callus cultured for 15 days on medium containing 100 µM trifluralin gave the highest rate of chromosome doubling. Through observation of chromosome number in the root apical cells and the morphology of guard cells on the leaf epidermis of the regenerated plantlets, it was clear that chromosome number variation was induced and tetraploids were produced in vitro by trifluralin treatment.

Coffee consumption and prostate cancer aggressiveness among African and Caucasian Americans in a population-based study.

This study evaluated the relationship between caffeinated and decaffeinated coffee and prostate cancer (CaP) aggressiveness using data from a population-based incident CaP study within the North Carolina-Louisiana Prostate Cancer Project (PCaP). Classification of CaP aggressiveness at diagnosis was based on clinical criteria for 1,049 African-American (AA) and 1,083 Caucasian-American (CA) research subjects. Coffee consumption was measured using a modified NCI Dietary History Questionnaire. No significant associations were found between CaP aggressiveness and consumption of either caffeinated or decaffeinated coffee. The OR for high aggressive CaP among consumers of more than 4 cups per day was 0.92 (95%CI = 0.61, 1.39), compared to non-coffee-drinkers. Results stratified by race found no significant associations and no noticeable trends in either AAs (P for trend = 0. 62) or CAs (P for trend = 0.42). In contrast to a recent report on a select population that has less complete information on CaP aggressiveness suggesting that coffee prevents aggressive CaP, this rapid case ascertainment population-based study, in a biracial population with differing risks of CaP did not demonstrate a protective relationship between high coffee consumption and risk of high aggressive CaP.

Development of carbapenem resistance during therapy for non-typhoid Salmonella infection.

Multidrug-resistant Salmonella infection is a global problem, and carbapenems may represent the last therapeutic choice. We report a case of infection caused by ceftriaxone-resistant and ciprofloxacin-resistant Salmonella enterica serotype Typhimurium. A bla(CMY-2) -containing Tn6092, located on a self-transferable IncI1 plasmid, was found in all isolates derived from the patient. During ertapenem treatment, the strain developed carbapenem resistance. Apart from the OmpD deficiency found in all isolates, the strain further developed OmpC deficiency through a single gene mutation, and became carbapenem-resistant. Salmonella appears to be very plastic in developing antimicrobial resistance. Care must be taken by physicians when treating multidrug-resistant Salmonella infection.

Influence of angiotensin-converting enzyme insertion/deletion polymorphism on nitric oxide production in hypertensives and hypercholesterolaemics.

UNLABELLED: WHAT IS NEW AND OBJECTIVE: Some evidence suggests that angiotensin-converting enzyme insertion/deletion (I/D) polymorphism may play a role in endothelium-dependent vasodilatation. However, the impact of I/D polymorphism on endogenous nitric oxide production, which may be of great therapeutic significance, has scarcely been studied. This study aimed to investigate this in hypertensives and hypercholesterolaemics. METHODS: Adult Han subjects were recruited by cluster sampling from two communities in Shunde, Guangdong province, China. Plasma nitrite and nitrate (NO(x)) levels were determined by colorimetry assay and angiotensin II and 6-keto-prostaglandin F1-alpha by radioimmunoassay. Angiotensin-converting enzyme gene I/D polymorphism were genotyped by polymer chain reaction-amplified fragment length polymorphism. RESULTS AND DISCUSSION: Of the 779 subjects who met our inclusion criteria, 502 were with normotensive and normocholesterolaemic, 76 had hypertension only, 146 hypercholesterolaemia only, and 55 had both hypertension and hypercholesterolaemia. Among subjects with hypertension only, the plasma levels of NO(x) for genotype DD were significantly lower than those for genotype II (P = 0·034). And the plasma levels of NO(x) for genotype DD was significantly higher than those for genotype II (P = 0·040) in subjects with hypercholesterolaemia only. WHAT IS NEW AND CONCLUSION: Our results suggest that I/D polymorphism has an impact on in vivo NO production in hypertensives and hypercholesterolaemics at the population level. Hypertensives with allele D may be benefit from L-arginine supplementation and hypercholesterolaemics with allele D may respond better to statins or antioxidants.

Environmental exposure to emissions from petrochemical sites and lung cancer: the lower Mississippi interagency cancer study.

To investigate potential links between environmental exposure to petrochemical plant emissions and lung cancer, a population-based case-control study (LMRICS) was conducted in eleven Louisiana parishes bordering the Mississippi River. Cases and age, gender, and race-matched controls were interviewed regarding potential risk factors. Residential history was geocoded to provide indices of long-term proximity to industrial sites. Cases were more likely to have lived near a petrochemical site. Models adjusted for other risk factors, however, showed small or no association with lung cancer (odds ratio for residence within a half-mile of a site = 1.10, 95% confidence interval 0.58-2.08). While associations were strongest for exposures exceeding 15 years, none approached statistical significance and there was no clear dose-response across exposure duration, distance categories, or when sites were grouped according to carcinogenicity rating of chemical releases. Residential proximity to petrochemical plants along the lower Mississippi thus showed no significant association with lung cancer.