Process and Outcome Evaluation of a Mindfulness-Based Cognitive Therapy Intervention for Cisgender and Transgender African American Women Living with HIV/AIDS.

There is a need for evidence-based contextualized mental health interventions for persons living with HIV/AIDS. In the current study, the primary researcher conducted open trials with African American women living with HIV/AIDS (AAWLWHA) to examine the acceptability and feasibility of Project UPLIFT, a mindfulness-based cognitive therapy intervention that has demonstrated effectiveness in persons living with epilepsy. Women were recruited for a tele-delivered phone intervention group separated by gender identity, as well as participated in pre- and post-test assessments. Additionally, data on acceptability was collected. Both cis- and transgender women were highly satisfied with the intervention and demonstrated improvement in depressive and stress symptoms. The intervention seemed to be particularly feasible for cisgender women, though more qualitative mental health research may be warranted with transgender women. The current research has implications for the utility of mindfulness-based interventions such as UPLIFT, with AAWLWHA.

Assessing the Impact of Factors that Influence the Ketogenic Response to Varying Doses of Medium Chain Triglyceride (MCT) Oil.

Objectives, Design, Setting: The ketogenic effect of medium chain triglyceride (MCT) oil offers potential for Alzheimer's disease prevention and treatment. Limited literature suggests a linear B-hyroxybutyrate (BHB) response to increasing MCT doses. This pharmacokinetic study evaluates factors affecting BHB response in three subject groups. PARTICIPANTS: Healthy subjects without cognitive deficits <65years, similarly healthy subjects >=65years, and those with Alzheimer's Disease were assessed. INTERVENTION: Different doses (0g,14g, 28g, 42g) of MCT oil (99.3% C8:0) were administered, followed by fasting during the study period. MEASUREMENTS: BHB measured by finger prick sampling hourly for 5 hours after ingestion. Each subject attended four different days for each ascending dose. Data was also collected on body composition, BMI, waist/hip ratio, grip strength, gait speed, nutrient content of pre-study breakfast and side effects. RESULTS: Twenty-five participants: eight healthy; average age of 44yr (25-61), nine healthy; 79yr (65-90) and eight with AD; 78.6yr (57-86) respectively. Compiled data showed the expected linear dose response relationship. No group differences, with baseline corrected area under the blood vs. time curve (r2=0.98) and maximum concentrations (r2=0.97). However, there was notable individual variability in maximum BHB response (42g dose: 0.4 -2.1mM), and time to reach maximum BHB response both, within and between individuals. Variability was unrelated to age, sex, sarcopenic or AD status. Visceral fat, BMI, waist/hip ratio and pretest meal CHO and protein content all affected the BHB response (p<0.001). CONCLUSION: There was a large inter-individual variability, with phenotype effects identified. This highlights challenges in interpreting clinical responses to MCT intake.

Inhibition of the growth of human dermatophytic pathogens by selected australian and asian plants traditionally used to treat fungal infections.

OBJECTIVE: Syzygium australe (H.L. Wnddl. ex. Link) B. Hyland, Syzygium luehmannii (F. Muell.) L.A.S. Johnson, Syzygium jambos L. (Alston), Terminalia ferdinandiana Exell. and Tasmannia lanceolata (Poir.) A.C.Sm. are used in traditional Australian Aboriginal and Asian healing systems to treat a variety of pathogenic diseases including fungal skin infections, yet they are yet to be examined for the ability to inhibit the growth of human dermatophytes. MATERIALS AND METHODS: The fungal growth inhibitory activity of extracts produced from selected Australian and Asian plants was assessed against a panel of human dermatophytes by standard disc diffusion and liquid dilution MIC methods. The toxicity of the extracts was evaluated by Artemia lethality and MTS HDF cell viability assays. The phytochemistry of the most promising extracts were examined by GC-MS headspace analysis and some interesting compounds were highlighted. RESULTS: The aqueous and methanolic extracts of all plant species were good antifungal agents, inhibiting the growth of all of the dematophytes tested. The methanolic S. australe (SA) and S. luehmannii (SL) extracts were particularly potent fungal growth inhibitors. MIC values of 39 and 53µg/mL were recorded for the methanolic SL fruit extract against T. mentagrophytes and T. rubrum respectively. Similar MICs were also noted for the methanolic SL leaf extract (88 and 106µg/mL respectively). The methanolic SL leaf extract was a particularly good fungal growth inhibitor, with MIC values≤100µg/mL against the reference C. albicans strain (96µg/mL), E. floccosum (53µg/mL), and T. mentagrophytes (88µg/mL). This extract also produced MICs≤200µg/mL against all other fungal species/strains tested. Similarly good activity was seen for the methanolic S. australe leaf and fruit extracts, as well as the S. lehmannii fruit and S. jambos leaf extracts, with MIC values 100-500µg/mL. Interestingly, these extracts had low toxicity and high therapeutic indices, indicating their suitability for clinical use. GC-MS headspace analysis highlighted several monoterpenoids and sesquiterpenoids in the methanolic SA and SL extracts. T. ferdinandiana and T. lanceolata extracts also had promising antifungal activity, albeit with substantially higher MICs. CONCLUSION: Whilst multiple extracts inhibited fungal growth, the methanolic S. australe and S. luehmannii leaf extracts and the S. luehmannii fruit extracts showed particularly potent activity against each of these dermatophytes, indicating that they are promising leads for the development of anti-dermatophytic therapeutics.

Bioconcentration factors for hydrocarbons and petrochemicals: Understanding processes, uncertainty and predictive model performance.

Fish bioconcentration factors (BCFs) are often used to assess substance-specific bioaccumulation. However, reliable BCF data are limited given the practical challenges of conducting such tests. The objectives of this paper are to describe nine rainbow trout studies performed in our lab using tailored dosing and test designs for obtaining empirical BCFs for 21 test substances; gain insights into the structural features and processes determining the magnitude and uncertainty in observed BCFs; and assess performance of six quantitative structure property relationships (QSPRs) for correctly categorizing bioaccumulation given current regulatory triggers. Resulting mean steady-state BCFs, adjusted to a 5% lipid content, ranged from 12 Lkg-1 for isodecanol to 15,448 Lkg-1 for hexachlorobenzene which served as a positive control. BCFs for hydrocarbons depended on aromatic and saturated ring configurations and position. Uptake clearances appeared to be modulated by gill metabolism and substance bioavailability, while elimination rates were likely influenced by somatic biotransformation. Current approaches for quantifying uncertainty in experimental BCFs, which take into account only variability in measured fish concentrations, were found to underestimate the true uncertainty in this endpoint with important implications for decision-making. The Vega (KNN/Read-Across) QSPR and Arnot-Gobas model yielded the best model performance when compared to measured BCFs generated in this study.

Resting-State Functional Magnetic Resonance Imaging Connectivity of the Brain Is Associated with Altered Sensorimotor Function in Patients with Cervical Spondylosis.

OBJECTIVE: To determine the relationship between functional connectivity (FC) using resting-state functional magnetic resonance imaging (MRI) and neurological impairment in patients with cervical spondylosis and healthy controls. METHODS: A total of 24 patients with cervical spondylosis with or without myelopathy and 17 neurologically intact, healthy volunteer subjects were prospectively enrolled in a cross-sectional study involving observational MRI and evaluation of neurological function using the modified Japanese Orthopedic Association (mJOA) score. Seed-to-seed connectivity and seed-to-voxel connectivity on functional MRI data were performed using a general linear model of connectivity with respect to age and mJOA score. RESULTS: Increased FC was observed with increasing neurological impairment in patients with cervical stenosis within sensorimotor areas, including precentral gyrus, postcentral gyrus, and supplemental motor regions, using both seed-to-seed and seed-to-voxel analyses. The anterior cingulate showed increasing connectivity with the supplemental motor area, thalamus, and cerebellum with increasing neurological function. Similarly, the thalamus, cerebellum, and putamen presented with increasing connectivity to both the bilateral precuneus and the posterior cingulate with an increasing mJOA score. CONCLUSIONS: Patients with cervical spondylosis exhibiting neurological impairment experience changes in brain connectivity similar to that of patients with chronic traumatic spinal cord injury. These results suggest an increase in FC within sensorimotor regions with increasing neurological impairment and decreased connectivity between the cerebellum, putamen, and thalamus to the anterior and posterior cingulate and frontal lobe regions.

Genomic Analyses of Dominant U.S. Clonal Lineages of Phytophthora infestans Reveals a Shared Common Ancestry for Clonal Lineages US11 and US18 and a Lack of Recently Shared Ancestry Among All Other U.S. Lineages.

Populations of the potato and tomato late-blight pathogen Phytophthora infestans are well known for emerging as novel clonal lineages. These successions of dominant clones have historically been named US1 through US24, in order of appearance, since their first characterization using molecular markers. Hypothetically, these lineages can emerge through divergence from other U.S. lineages, recombination among lineages, or as novel, independent lineages originating outside the United States. We tested for the presence of phylogenetic relationships among U.S. lineages using a population of 31 whole-genome sequences, including dominant U.S. clonal lineages as well as available samples from global populations. We analyzed ancestry of the whole mitochondrial genome and samples of nuclear loci, including supercontigs 1.1 and 1.5 as well as several previously characterized coding regions. We found support for a shared ancestry among lineages US11 and US18 from the mitochondrial genome as well as from one nuclear haplotype on each supercontig analyzed. The other nuclear haplotype from each sample assorted independently, indicating an independent ancestry. We found no support for emergence of any other of the U.S. lineages from a common ancestor shared with the other U.S. lineages. Each of the U.S. clonal lineages fit a model where populations of new clonal lineages emerge via migration from a source population that is sexual in nature and potentially located in central Mexico or elsewhere. This work provides novel insights into patterns of emergence of clonal lineages in plant pathogen genomes.

Gas formation. Formation temperatures of thermogenic and biogenic methane.

Methane is an important greenhouse gas and energy resource generated dominantly by methanogens at low temperatures and through the breakdown of organic molecules at high temperatures. However, methane-formation temperatures in nature are often poorly constrained. We measured formation temperatures of thermogenic and biogenic methane using a "clumped isotope" technique. Thermogenic gases yield formation temperatures between 157° and 221°C, within the nominal gas window, and biogenic gases yield formation temperatures consistent with their comparatively lower-temperature formational environments (<50°C). In systems where gases have migrated and other proxies for gas-generation temperature yield ambiguous results, methane clumped-isotope temperatures distinguish among and allow for independent tests of possible gas-formation models.

Evaluation of 6ß-hydroxycortisol, 6ß-hydroxycortisone, and a combination of the two as endogenous probes for inhibition of CYP3A4 in vivo.

An endogenous probe for CYP3A activity would be useful for early identification of in vivo cytochrome P450 (CYP) 3A4 inhibitors. The aim of this study was to determine whether formation clearance (CL(f)) of the sum of 6ß-hydroxycortisol and 6ß-hydroxycortisone is a useful probe of CYP3A4 inhibition in vivo. In human liver microsomes (HLMs), the formation of 6ß-hydroxycortisol and 6ß-hydroxycortisone was catalyzed by CYP3A4, and itraconazole inhibited these reactions with half maximal inhibitory concentration (IC(50))(,u) values of 3.1 nmol/l and 3.4 nmol/l, respectively. The in vivo IC(50,u) value of itraconazole for the combined CL(f) of 6ß-hydroxycortisone and 6ß-hydroxycortisol was 1.6 nmol/l. The greater inhibitory potency in vivo is probably due to circulating inhibitory itraconazole metabolites. The maximum in vivo inhibition was 59%, suggesting that f(m,CYP3A4) for cortisol and cortisone 6ß-hydroxylation is ~60%. Given the significant decrease in CL(f) of 6ß-hydroxycortisone and 6ß-hydroxycortisol after 200-mg and 400-mg single doses of itraconazole, this endogenous probe can be used to detect moderate and potent CYP3A4 inhibition in vivo.

Prevention of the recurrence of anaemia in Gambian children following discharge from hospital.

BACKGROUND: In malaria endemic countries, children who have experienced an episode of severe anaemia are at increased risk of a recurrence of anaemia. There is a need to find ways of protecting these at risk children from malaria and chemoprevention offers a potential way of achieving this objective. METHODS: During the 2003 and 2004 malaria transmission seasons, 1200 Gambian children with moderate or severe anaemia (Hb concentration <7 g/dL) were randomised to receive either monthly sulfadoxine-pyrimethamine (SP) or placebo until the end of the malaria transmission season in which they were enrolled, in a double-blind trial. All study subjects were treated with oral iron for 28 days and morbidity was monitored through surveillance at health centres. The primary endpoint was the proportion of children with moderate or severe anaemia at the end of the transmission season. Secondary endpoints included the incidence of clinical episodes of malaria during the surveillance period, outpatient attendances, the prevalence of parasitaemia and splenomegaly, nutritional status at the end of the malaria transmission season and compliance with the treatment regimen. RESULTS: The proportions of children with a Hb concentration of <7 g/dL at the end of the malaria transmission season were similar in the two study groups, 14/464 (3.0%) in children who received at least one dose of SP and 16/471 (3.4%) in those who received placebo, prevalence ratio 0.89 (0.44,1.8) P = 0.742. The protective efficacy of SP against episodes of clinical malaria was 53% (95% CI 37%, 65%). Treatment with SP was safe and well tolerated; no serious adverse events related to SP administration were observed. Mortality following discharge from hospital was low among children who received SP or placebo (6 in the SP group and 9 in the placebo group respectively). CONCLUSIONS: Intermittent treatment with SP did not reduce the proportion of previously anaemic children with moderate or severe anaemia at the end of the malaria season, although it prevented malaria. The combination of appropriate antimalarial treatment plus one month of iron supplementation and good access to healthcare during follow-up proved effective in restoring haemoglobin to an acceptable level in the Gambian setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT00131716.

Commonly used botanicals and vitamins and their impact on blood pressure and blood loss in surgical gynaecology patients.

We wanted to determine botanical and vitamin use in surgical gynaecology patients at UHWI and their effects on blood pressure and blood loss. The study was prospective and observational. Before elective surgery, we evaluated 133 patients on the use of botanicals and vitamins. We measured pre- and intraoperative blood pressure and intraoperative blood loss to determine any association with botanical use. Botanicals were used by 68.4% of patients with a 45.1% use within 2 weeks before surgery, p = 0.002). Users were older (p = 0.024) and had more chronic illnesses (p = 0.003). They also had higher mean preoperative diastolic blood pressure (p = 0.016) but no statistically significant difference in intraoperative blood pressures. Blood loss was greater with recent use of certain anticoagulant botanicals. We conclude that the use of certain botanicals may increase blood pressure or increase surgical bleeding and patients and doctors should be aware of their risk.

Total selenium and selenomethionine in pharmaceutical yeast tablets: assessment of the state of the art of measurement capabilities through international intercomparison CCQM-P86.

Results of an international intercomparison study (CCQM-P86) to assess the analytical capabilities of national metrology institutes (NMIs) and selected expert laboratories worldwide to accurately quantitate the mass fraction of selenomethionine (SeMet) and total Se in pharmaceutical tablets of selenised-yeast supplements (produced by Pharma Nord, Denmark) are presented. The study, jointly coordinated by LGC Ltd., UK, and the Institute for National Measurement Standards, National Research Council of Canada (NRCC), was conducted under the auspices of the Comité Consultatif pour la Quantité de Matière (CCQM) Inorganic Analysis Working Group and involved 15 laboratories (from 12 countries), of which ten were NMIs. Apart from a protocol for determination of moisture content and the provision of the certified reference material (CRM) SELM-1 to be used as the quality control sample, no sample preparation/extraction method was prescribed. A variety of approaches was thus used, including single-step and multiple-step enzymatic hydrolysis, enzymatic probe sonication and hydrolysis with methanesulfonic acid for SeMet, as well as microwave-assisted acid digestion and enzymatic probe sonication for total Se. For total Se, detection techniques included inductively coupled plasma (ICP) mass spectrometry (MS) with external calibration, standard additions or isotope dilution MS (IDMS), inductively coupled plasma optical emission spectrometry , flame atomic absorption spectrometry and instrumental neutron activation analysis. For determination of SeMet in the tablets, five NMIs and three academic/institute laboratories (of a total of five) relied upon measurements using IDMS. For species-specific IDMS measurements, an isotopically enriched standard of SeMet (76Se-enriched SeMet) was made available. A novel aspect of this study relies on the approach used to distinguish any errors which arise during analysis of a SeMet calibration solution from those which occur during analysis of the matrix. To help those participants undertaking SeMet analysis to do this, a blind sample in the form of a standard solution of natural abundance SeMet in 0.1 M HCl (with an expected value of 956 mg kg(-1) SeMet) was provided. Both high-performance liquid chromatography (HPLC)-ICP-MS or gas chromatography (GC)-ICP-MS and GC-MS techniques were used for quantitation of SeMet. Several advances in analytical methods for determination of SeMet were identified, including the combined use of double IDMS with HPLC-ICP-MS following extraction with methanesulfonic acid and simplified two-step enzymatic hydrolysis with protease/lipase/driselase followed by HPLC-ICP-IDMS, both using a species-specific IDMS approach. Overall, satisfactory agreement amongst participants was achieved; results averaged 337.6 mg kg(-1) (n = 13, with a standard deviation of 9.7 mg kg(-1)) and 561.5 mg kg(-1) (n = 11, with a standard deviation of 44.3 mg kg(-1)) with median values of 337.6 and 575.0 mg kg(-1) for total Se and SeMet, respectively. Recovery of SeMet from SELM-1 averaged 95.0% (n = 9). The ability of NMIs and expert laboratories worldwide to deliver accurate results for total Se and SeMet in such materials (selensied-yeast tablets containing approximately 300 mg kg(-1) Se) with 10% expanded uncertainty was demonstrated. The problems addressed in achieving accurate quantitation of SeMet in this product are representative of those encountered with a wide range of organometallic species in a number of common matrices.

Brain activity during stimulation of the trigeminal nerve with noxious heat.

OBJECTIVE: The aim of this study was to observe areas of brain activation with painful hot stimulation to the trigeminal nerve. STUDY DESIGN: Nine healthy pain-free women (mean age 26.2 +/- 6.9 yrs) with a natural, regular menstrual cycle participated in the study. Whole-brain functional magnetic resonance imaging (fMRI) data were acquired for each participant on day 2 or 3 after the onset of menses using echo-planar imaging at 1.5T with near-isotropic spatial resolution and a temporal resolution of 4 s. RESULTS: Whole-brain fMRI with a Peltier thermode inside the head coil yielded a feasible imaging protocol with little disturbance from the thermode. Painful thermal stimulation of the left trigeminal system activated discrete brain regions within the insula, cingulate gyrus, thalamus, inferior parietal lobe/postcentral gyrus, right middle and inferior frontal gyri, cuneus, precuneus, and precentral gyrus. CONCLUSION: Painful stimulation of the trigeminal nerve resulted in activation of similar brain areas generally known for pain processing of painful peripheral stimulation.

Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline.

OBJECTIVE: The study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension. STUDY DESIGN: Forty children, undergoing cardiopulmonary bypass and at risk for pulmonary hypertension, were randomized to receive 5 perioperative doses (1.9 g/m2 per dose) of either oral citrulline or placebo. Plasma citrulline and arginine concentrations were measured at 5 time points. Measurements of systemic blood pressure and presence of pulmonary hypertension were collected. RESULTS: Median citrulline concentrations were significantly higher in the citrulline group versus the placebo group immediately postoperatively (36 micromol/L vs 26 micromol/L, P = .012) and at 12 hours postoperatively (37 micromol/L vs 20 micromol/L, P = .015). Mean plasma arginine concentrations were significantly higher in the citrulline group versus the placebo group by 12 hours postoperatively (36 micromol/L vs 23 micromol/L, P = .037). Mean systemic blood pressure did not differ between groups (P = .53). Postoperative pulmonary hypertension developed in 9 patients, 6 of 20 (30%) in the placebo group and 3 of 20 (15%) in the citrulline group (P = .451), all of whom had plasma citrulline concentrations less than age-specific norms. Postoperative pulmonary hypertension did not develop in patients who demonstrated plasma citrulline concentrations in excess of 37 mumol/L (P = .036). CONCLUSIONS: Oral citrulline supplementation safely increased plasma citrulline and arginine concentrations compared with placebo after cardiopulmonary bypass. Postoperative pulmonary hypertension did not occur in children with naturally elevated citrulline levels or elevations through supplementation. Oral citrulline supplementation may be effective in reducing postoperative pulmonary hypertension.

Qigong as a psychosocial intervention for depressed elderly with chronic physical illnesses.

Literature uncovers that depression is common in elderly people. The problem is more serious in elderly with chronic physical illnesses. Although the relationship between physical problems and depression is well documented, the underlying mechanism is basically unknown. This article proposed after a comprehensive literature review that depression in elderly with chronic physical illnesses results from disability and a reduction in psychosocial resources. If depression is left untreated, suicide may be a consequence. In view of this, various forms of psychosocial interventions are developed based on mainstream western medicine. The authors argue that qigong, a form of Chinese therapeutics, has the effect of alleviating clinical depression and thus improves quality of life. A simple form of dynamic qigong, namely the Eight-Section Brocades, is suggested to serve the purpose. A theory which explains the psychosocial effect of qigong is hypothesized.

Selenium deficiency in Fisher-344 rats decreases plasma and tissue homocysteine concentrations and alters plasma homocysteine and cysteine redox status.

The purpose of the present study was to determine the effect of graded amounts of dietary selenium on plasma and tissue parameters of methionine metabolism including homocysteine. Male weanling Fisher-344 rats (n = 7-8/group) were fed a selenium-deficient, torula yeast-based diet, supplemented with 0 (selenium deficient), 0.02, 0.05 or 0.1 microg (adequate) selenium (as selenite)/g diet. After 61 d, plasma total homocysteine and cysteine were decreased (P < 0.0001) and glutathione increased (P < 0.0001) by selenium deficiency. The concentrations of homocysteine in kidney and heart were decreased (P = 0.02) by selenium deficiency. The activities of liver betaine homocysteine methyltransferase, methionine synthase, S-adenosylmethionine synthase, cystathionine synthase and cystathionase were determined; selenium deficiency affected only betaine homocysteine methyltransferase, which was decreased (P < 0.0001). The ratios of plasma free reduced homocysteine (or cysteine) to free oxidized homocysteine (or cysteine) or to total homocysteine (or cysteine) were increased by selenium deficiency, suggesting that selenium status affects the normally tightly controlled redox status of these thiols. Most differences due to dietary selenium were between rats fed 0 or 0.02 microg selenium/g diet and those fed 0.05 or 0.1 microg selenium/g diet. The metabolic consequences of a marked decrease in plasma homocysteine and smaller but significant decreases in tissue homocysteine are not known.

Manganese absorption and retention in rats is affected by the type of dietary fat.

There is evidence that manganese (Mn) metabolism may be altered by the form and amount of dietary fat. Also, iron (Fe) absorption is greater with saturated fats, as compared to polyunsaturated fatty acids (PUFAs). The absorption of Fe and Mn are interrelated in many aspects; therefore, the form of dietary fat may indirectly alter Mn absorption. The reported studies were conducted to determine whether saturated fat, as compared to unsaturated fat, affected Mn absorption, retention, and metabolism. In experiment I, adult rats were fed diets containing either 0.7 or 100.4 microg/g Mn with the fat source as high-linoleic safflower oil or stearic acid. After 2 wk of equilibration, the animals were fed a test meal of 54Mn followed by whole-body counting for 10 d. Manganese absorption was significantly (p < 0.05) lower in the stearic acid group (0.9-4.8%) than in the safflower oil group (20-33.8%); however, the biological half-life was shorter in the safflower oil group. Retention of 54Mn and total Mn was always significantly (p < 0.05) greater in the safflower oil group when dietary Mn was low, but it was the same when dietary Mn was high. In experiment II, weanling rats were fed 1.3, 39.3, or 174.6 microg Mn/g and either stearate, high-oleic safflower oil or high-linoleic safflower oil for 8 wk. Long-term feeding of the stearate and low Mn-containing diet resulted in a significant (p < 0.0001) reduction in heart superoxide dismutase activity and kidney and liver Mn concentrations compared to the other diets. These data show that stearic acid inhibitits Mn absorption, but it may not inhibit Mn retention when dietary Mn is high.

Preoperative chemoradiotherapy and radical surgery for locally advanced distal rectal adenocarcinoma: pathologic findings and clinical implications.

PURPOSE: Preoperative chemoradiotherapy followed by radical surgical resection has been the preferred treatment for patients presenting with locally advanced distal rectal carcinoma at our institutions. We postulated that chemoradiotherapy-induced pathologic response of the primary tumor would identify which patients would be candidates for local excision as definitive surgical therapy. METHODS: A retrospective analysis of 60 patients with palpable, locally advanced, distal rectal adenocarcinomas treated from 1995 to 2000 was performed. All patients received preoperative chemoradiotherapy consisting of 5-fluorouracil (325 mg/m(2)) and leucovorin (20 mg/m(2)) by bolus infusion on Days 1 through 5 and 29 through 33 delivered concurrently with at least 45.0 to 50.4 Gy of pelvic radiation, followed six to eight weeks later by radical surgery and then adjuvant chemotherapy. RESULTS: Among 60 patients (20 females) there was a mean age of 58.7 (28-84) years. Clinical staging was as follows: Stage II, 14 patients (23 percent); Stage III, 35 patients (58 percent); and Stage IV, 11 patients (18 percent). Pathologic examination revealed that negative margins were obtained in 58 patients (97 percent). Downstaging to T0-2N0 was achieved in 17 patients (28 percent), with five (8 percent) achieving a pathologically complete response. Lymph nodes were positive in 24 patients (40 percent) despite chemoradiotherapy. Pathologic node positivity was found in 0 of 5 pT0 patients, 9 (41 percent) of 22 pT1 or pT2, and 15 (45 percent) of 33 pT3. Clinical stage, tumor size, pathologic stage, and adverse histologic features could not reliably predict pN0 status, except pT0 (5 patients only). CONCLUSIONS: Preoperative chemoradiotherapy often downsizes and downstages locally advanced rectal carcinoma. Neither pretreatment clinical characteristics, response to preoperative chemoradiotherapy, or pathologic features reliably predict pN0 status. Therefore, local excision is not recommended as an alternative to radical surgery for locally advanced adenocarcinoma of the distal rectum regardless of the response of the primary tumor to preoperative chemoradiotherapy.

Selenium (Se) from high-selenium broccoli is utilized differently than selenite, selenate and selenomethionine, but is more effective in inhibiting colon carcinogenesis.

The reduction in incidence of chemically-induced colon cancer by foods high in selenium (Se) was investigated in Fisher-344 rats. The foods used were high-Se broccoli (produced in a greenhouse by addition of selenate to the media surrounding the plant roots) and a processed high-Se wheat product (made by milling high-Se wheat purchased from a seleniferous area). Weanling rats were fed diets containing different amounts of Se from these foods or from selenium salts (selenite and selenate). Early in the experiment the animals were injected with a chemical carcinogen. After 11 weeks on diets animals were killed and the colons examined for preneoplastic lesions (aberrant crypts foci, ACF). ACF were significantly reduced in animals fed supra-nutritional amounts of Se from broccoli, despite the finding that Se from broccoli was poorly bioavailable. Supra-nutritional amounts of Se from high-Se processed wheat also significantly reduced aberrant crypts (AC), although pure selenomethionine, (the predominant chemical form of Se in wheat), did not significantly reduce AC. These results emphasize the need to study Se in food forms, and not extrapolate from previous studies using pure chemical forms in cancer inhibition studies. They also demonstrate that foods with high Se bioavailability are not necessarily the most efficacious for cancer incidence reduction.

Low dietary zinc alters indices of copper function and status in postmenopausal women.

OBJECTIVES: To better define the relationship between dietary zinc and copper for humans so that sound recommendations for intakes of these elements can be made. METHODS: A study was conducted to ascertain the effect of moderately excessive and deficient intakes of zinc on copper metabolism and use in humans fed low and luxuriant amounts of copper. Twenty-one postmenopausal women housed in a metabolic unit completed the study as designed. After a 10-d equilibration period in which they were fed a diet providing 31.5 micromol (2 mg) Cu and 91.8 micromol (9 mg) Zn/8.4 MJ (2000 kcal), the women were divided into two groups. One group was fed a diet containing 15.7 micromol (1 mg) Cu/8.4 MJ (2000 kcal), and the other group was fed a diet containing 47.2 micromol (3 mg) Cu/8.4 MJ (2000 kcal). After equilibration, both groups were fed the basal diet providing 45.9 micromol (3 mg) Zn/8.4 MJ (2000 kcal) for 90 d; this was followed by another 10-d equilibration period before dietary zinc was increased to 811 micromol (53 mg)/8.4 MJ (2000 kcal) for 90 d. RESULTS: The women were in positive copper balance only when the diet provided 47.2 micromol (3 mg) Cu and 811 micromol (53 mg) Zn/d. Immunoreactive ceruloplasmin concentrations and platelet cytochrome-c oxidase activity on a platelet number basis were significantly lower and the ratio between enzymatic and immunoreactive ceruloplasmin was significantly higher during low dietary than during high dietary zinc intake. Serum cholesterol was higher in subjects fed 15.7 micromol (1 mg) Cu/d than in those fed 47.2 micromol (3 mg) Cu/d. Total and low-density lipoprotein cholesterol concentrations decreased with zinc supplementation. Whole-blood glutathione concentration and erythrocyte glutathione peroxidase activity were lower during high than during low dietary zinc intake. CONCLUSIONS: The findings indicate that an inadequate intake of zinc (45.9 micromol/d; 3 mg/d) was more effective than a moderately high intake of zinc (811 micromol/d; 53 mg/d) in inducing changes associated with a decreased copper status in postmenopausal women. Furthermore, the findings indicate that copper status indicators might be useful in evaluating changes in zinc status in humans, and an intake of 15.7 micromol (1 mg)/d of copper may be inadequate for postmenopausal women.

Patterns of fluoride intake from birth to 36 months.

OBJECTIVES: Dental fluorosis prevalence has increased in the United States, Canada, and other nations due to the widespread availability of fluoride in many forms, with fluoride ingestion during the first three years of life appearing most critical in fluorosis etiology. With few contemporary studies of fluoride ingestion in this age group, the purpose of this paper is to describe patterns of estimated fluoride ingestion from birth to 36 months of age from water, dentifrice, and dietary fluoride supplements and combined. METHODS: Repeated responses to separate series of questions about water intake, use of fluoride dentifrice, and use of fluoride supplements were collected by questionnaire as part of the longitudinal Iowa Fluoride Study and used to estimate fluoride intake. Estimated intake is reported by source and combined at different ages. Effects of subject age and other covariates on fluoride intake were assessed using regression methods appropriate for the analysis of correlated data. RESULTS: For most children, water fluoride intake was the predominant source, especially through age 12 months. Combined daily fluoride intake increased through 9 months, was lower at 12 and 16 months, and increased again thereafter. Mean intake per unit body weight (bw) was about 0.075 mg F/kg bw through 3 months of age, 0.06 mg F/kg bw at 6 and 9 months, 0.035 mg F/kg bw at 12 and 16 months, and 0.043 mg F/kg bw from 20-36 months. Depending on the threshold chosen (e.g., 0.05 or 0.07 mg F/kg bw), variable percentages of the children exceeded the levels, with percentages greatest during the first 9 months. Regression analyses showed fluoride intake (mg F/kg bw) from 1.5-9 months to decrease with increasing child's age, mother's age, and mother's education, with a complex three-way interaction among these factors. From 12-20 months, fluoride intake increased with increasing child age and decreased with increasing mother's age. No statistically significant relationships were found for fluoride intake from 24-36 months. CONCLUSIONS: There is considerable variation in fluoride intake across ages and among individuals. Longitudinal studies may be necessary to fully understand the relationships between fluoride ingestion over time and development of fluorosis.