Evidence for causal top-down frontal contributions to predictive processes in speech perception.

Perception relies on the integration of sensory information and prior expectations. Here we show that selective neurodegeneration of human frontal speech regions results in delayed reconciliation of predictions in temporal cortex. These temporal regions were not atrophic, displayed normal evoked magnetic and electrical power, and preserved neural sensitivity to manipulations of sensory detail. Frontal neurodegeneration does not prevent the perceptual effects of contextual information; instead, prior expectations are applied inflexibly. The precision of predictions correlates with beta power, in line with theoretical models of the neural instantiation of predictive coding. Fronto-temporal interactions are enhanced while participants reconcile prior predictions with degraded sensory signals. Excessively precise predictions can explain several challenging phenomena in frontal aphasias, including agrammatism and subjective difficulties with speech perception. This work demonstrates that higher-level frontal mechanisms for cognitive and behavioural flexibility make a causal functional contribution to the hierarchical generative models underlying speech perception.

Vitamin D content and variability in fluid milks from a US Department of Agriculture nationwide sampling to update values in the National Nutrient Database for Standard Reference.

This study determined the vitamin D(3) content and variability of retail milk in the United States having a declared fortification level of 400 IU (10 µg) per quart (qt; 1 qt=946.4 mL), which is 25% daily value per 8 fluid ounce (236.6 mL) serving. In 2007, vitamin D(3) fortified milk (skim, 1%, 2%, whole, and 1% fat chocolate milk) was collected from 24 statistically selected supermarkets in the United States. Additionally, 2% milk samples from an earlier 2001 USDA nationwide collection were reanalyzed. Vitamin D(3) was determined using a specifically validated method involving HPLC with UV spectroscopic detection and vitamin D(2) as an internal standard. Quality control materials were analyzed with the samples. Of the 120 milk samples procured in 2007, 49% had vitamin D(3) within 100 to 125% of 400 IU (10 µg)/qt (label value), 28% had 501 to 600 IU (12.5-15 µg)/qt, 16% had a level below the label amount, and 7% had greater than 600 IU (15 µg)/qt (>150% of label). Even though the mean vitamin D(3) content did not differ statistically between milk types, a wide range in values was found among individual samples, from nondetectable [<20 IU (0.5 µg)/qt] for one sample to almost 800 IU (20 µg)/qt, with a trend toward more samples of whole milk having greater than 150% of the labeled content. On average, vitamin D(3) in 2% milk was higher in 2007 compared with in 2001 [473 vs. 426 IU (11.8 vs. 10.6 µg)/qt].

EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc.

The efficacy of a chelating agent in binding a given metal in a biological system depends on the binding constants of the chelator for the particular metals in the system, the concentration of the metals, and the presence and concentrations of other ligands competing for the metals in question. In this study, we make a comparison of the in vitro binding constants for the chelator, ethylenediaminetetraacetic acid, with the quantitative urinary excretion of the metals measured before and after EDTA infusion in 16 patients. There were significant increases in lead, zinc, cadmium, and calcium, and these increases roughly corresponded to the expected relative increases predicted by the EDTA-metal-binding constants as measured in vitro. There were no significant increases in urinary cobalt, chromium, or copper as a result of EDTA infusion. The actual increase in cobalt could be entirely attributed to the cobalt content of the cyanocobalamin that was added to the infusion. Although copper did increase in the post-EDTA specimens, the increase was not statistically significant. In the case of magnesium, there was a net retention of approximately 85% following chelation. These data demonstrate that EDTA chelation therapy results in significantly increased urinary losses of lead, zinc, cadmium, and calcium following EDTA chelation therapy. There were no significant changes in cobalt, chromium, or copper and a retention of magnesium. These effects are likely to have significant effects on nutrient concentrations and interactions and partially explain the clinical improvements seen in patients undergoing EDTA chelation therapy.

An effective approach to violence prevention: traditional martial arts in middle school.

This study replicated and extended the design and outcome measures of several small studies. In these studies, juveniles at high risk for violence and delinquency showed decreased violence and positive changes in psychological risk factors after being required to take a school-linked course in traditional martial arts. In the present study, 60 boys in a large urban middle school were required to take a traditional martial arts course in their school. They were paired on problematic behavior profiles and assigned to a treatment group or to a wait-list control group. Thirty classes, three per week (45 minutes each), were taught by a master of Koga Ha Kosho Shorei Ryu Kempo and his assistant (neither was a public school teacher). Results are reported here for 14 variables from the following measures: four teacher rating scales from the Sutter-Eyberg Student Behavior Inventory, five self-report scales of the Piers-Harris Self-Concept Scale, four computerized measures of attentional self-control from the Intermediate Visual and Auditory Continuous Performance Test, and a count of permanent expulsions from school. The treatment students improved over baseline on 12 variables, while the controls improved on 5 by small amounts and deteriorated from baseline on 8, including teacher-rated violence. There were significant differences between the groups on self-reported happiness and schoolwork and on one measure of attention. After controls took the course, their scores resembled the postcourse scores of the treatment group. Importantly, the control group's increase in teacher-rated violence was reversed. Both groups were then pooled to compare baseline and postcourse teacher ratings. Their scores improved significantly in the areas of resistance to rules, impulsiveness, and inappropriate social behavior. There was also improvement in regard to violence, but the change in scores was not statistically significant. Follow-up on teachers' ratings showed that improvement remained, and in some cases increased, four months after completion of the course. Interestingly, all 6 permanent expulsions were among the control group students who had not yet taken, or had only begun taking, the martial arts course.

A comparison of papaveretum-promethazine with morphine-ondansetron for patient-controlled analgesia.

BACKGROUND: Patient-controlled analgesia (PCA) with intravenous morphine is commonplace. Antiemetics are often added to reduce side-effects. In our institution an unusual combination of papaveretum-promethazine is in use. AIMS: We set out to compare this combination with a more commonly used one (morphine-ondansetron) by auditing the records of our pain-control team assessing analgesia and control of side-effects. METHODS: The records of two groups of 100 consecutive patients were studied. Pain scores were recorded 24 hours post-operatively on a scale of zero to ten. Also recorded were sedation scores, pruritus, emesis, and usage of breakthrough analgesia. The groups contained the work of a variety of anaesthetists and surgeons, though the majority were orthopaedic cases. All results were recorded by one pain-control nurse, using the same question, over a nine-month period. RESULTS: Sedation scores were identical, while side-effects were few and similar in both groups. The use of breakthrough analgesia was also similar. However, the median pain-score of zero in the papaveretum group was significantly lower than that of two in the morphine group, (p < 0.001, Mann-Whitney U). CONCLUSION: Papaveretum-promethazine appeared to be effective for PCA. This combination is also much less expensive than morphine-ondansetron. A previously described synergistic interaction between promethazine and opiates may be a factor in its success. Further evaluation of these drugs in PCA is warranted.

Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake.

We examined the validity of using the selenium level in a single biological specimen as a surrogate measure of usual intake. We used data from 77 free-living adults from South Dakota and Wyoming. Subjects provided multiple 1-day duplicate-plate food composites, repeated specimens of blood and toenails, and 24-hour urine collections. We developed a statistical calibration method that incorporated measurement error correction to analyze the data. The Pearson correlation coefficients between selenium intake and a single selenium status measure, after deattenuation to adjust for the effect of within-person variation in intake, were: 0.78 for whole blood, 0.74 for serum, 0.67 for toenails, and 0.86 for urine. We present formulas to estimate the intake of individuals, based on selenium levels in a single specimen of blood, toenails, or urine. In these data, the concentration of selenium in a single specimen of whole blood, serum, or toenails served reasonably well as a measure for ranking subjects according to long-term selenium intake but provided only a rough estimate of intake for each subject.

Utilization of two different chemical forms of selenium during lactation using stable isotope tracers: an example of speciation in nutrition.

The bioavailability and metabolism of different chemical species of mineral nutrients in the diet are receiving much attention from research nutritionists. In order to make scientifically based recommendations for mineral intakes, the chemical form of the mineral, with its specific absorption, utilization and retention, needs to be considered. Selenium is an example of an essential nutrient that is consumed in several different chemical forms, hence information is needed on the bioavailability and metabolism of each form before recommendations for dietary intakes can be made. A valuable tool for research on bioavailability and metabolism in humans is stable isotope tracers. When there are more than two stable isotopes available, as with selenium, stable isotope methodology allows the comparison of the utilization of different chemical forms of the nutrient simultaneously in in vivo studies. As an example of speciation questions addressed by nutritionists, a study is described that simultaneously evaluated utilization (absorption, retention and appearance in milk and blood) of two different chemical forms of selenium (selenite and selenomethionine) in lactating, non-lactating and never pregnant women using stable isotope tracers. All three groups of women had similar selenium status at the start of the study. Significantly more selenium from selenomethionine than from selenite was absorbed and appeared in the plasma in all groups. Milk contained more selenium from apparently absorbed selenomethionine than from selenite. All groups retained significantly more selenium from selenomethionine than from selenite; lactating women retained more selenium from selenite than did the other two groups, suggesting that milk losses may be partially compensated by enhanced retention of dietary selenium as selenite.(ABSTRACT TRUNCATED AT 250 WORDS)

Selenium in diet, blood, and toenails in relation to human health in a seleniferous area.

To determine whether high dietary selenium intake was associated with adverse effects, selenium in diet, blood, and toenails was studied in relation to human health in adults residing in western South Dakota and eastern Wyoming. Over a 2-y period 142 subjects were recruited from households selected at random and from ranches where unusually high selenium intakes were suspected. Subjects completed health questionnaires, underwent physical examinations, provided blood samples for clinical assessment, and provided blood, urine, toenails, and duplicate-plate food collections for selenium analysis. About half of the 142 free-living subjects had selenium intakes greater than 2.54 mumol/d (200 micrograms/d) (range 0.86-9.20 mumol/d, or 68-724 micrograms/d). Physical findings characteristic of selenium toxicity were not present nor were clinically significant changes in laboratory tests or frequency of symptoms related to selenium in the blood, toenails, or diet. We found no evidence of toxicity from selenium in subjects whose intake was as high as 9.20 mumol/d (724 micrograms/d).

Selenium utilization during human lactation by use of stable-isotope tracers.

We examined utilization of selenomethionine (SeMet) and selenite in six lactating (L) and six nonlactating (NL) women, 2-3 mo postpartum, and seven never-pregnant (NP) women by use of stable-isotope tracers. All groups had similar selenium status at the start of the study. Significantly more selenium from SeMet than from selenite was absorbed and appeared in plasma in all groups. Milk contained more selenium from apparently absorbed SeMet than from selenite. More selenium from apparently absorbed selenite than from SeMet appeared in urine of NP and NL subjects whereas L subjects had approximately the same amount of selenium from apparently absorbed selenite and SeMet in their urine. All groups retained significantly more selenium from SeMet than from selenite; L women retained more selenium from selenite than did the other two groups. Absorption and retention of selenium from SeMet in L women did not appear to be significantly different from that in other women, suggesting that selenium requirements during lactation are increased mainly because of milk losses.

Selenium utilization in humans--a long-term, self-labeling experiment with stable isotopes.

A stable (nonradioactive) isotope of selenium in a chemical form common in foods (selenomethionine) or inorganic selenite was taken orally (200 micrograms/d) for 3 wk to label deep body pools. By deep body pools we mean selenium compartments that are large and/or have a slow turnover (exchange) rate. Blood plasma was removed, stored for 11 mo, and later reinfused as a labeled tracer dose with the selenium label in all of the biologically significant chemical forms. Accessible tissues such as red blood cells were highly labeled (20-25%) in the subjects receiving selenomethionine. Selenium from deep body pools is excreted primarily via the urine (80%). Reexcretion of previously absorbed selenium back into the gastrointestinal tract can be measured, avoiding a major source of error in conventional balance studies used to estimate nutrient absorption.

Mild peripheral neuropathy but biochemical chromium sufficiency during 16 months of "chromium-free" total parenteral nutrition.

A 6-yr, 4-month-old boy was started on total parenteral nutrition (TPN) because of chronic diarrhea. The TPN regimen (3 liter/day) initially included supplemented Cr (3 micrograms/day) in addition to standard components (including FreAmine III). At age 8 yr, 8 months, the serum Cr level was elevated: 3.7 ng/ml (normal 0.03-0.85). A repeat level at the same time by another commercial laboratory was also high (7.0). Cr supplementation was stopped. At age 10 yr, he was noted to have mild peripheral neuropathy although glucose tolerance was excellent (alpha-linolenic acid was undetectable in the plasma). Cr status was reevaluated in a research lab. The serum level was 1.4 ng/ml (normal 0.05-0.4). The urine chromium excretion was 1.27 micrograms/day (normal 0.22). The TPN regimen (unsupplemented with Cr) provided 4 micrograms/day. Normal Cr intake is about 60 micrograms/day with 0.4% absorption (net 0.24 microgram/day). We conclude that Cr contamination of standard PN fluid may prevent biochemical evidence of low Cr status. In addition, alpha-linolenic acid-free parenteral nutrition for 46 months was not associated with clinically significant neurological dysfunction.

Adjuvant chemo-immunotherapy in stage II carcinoma of the breast.

From July of 1974 to June of 1978, 131 patients with Stage II carcinoma of the breast were randomly assigned to one of three treatment arms in order to assess the efficacy of adding immunotherapy to adjuvant chemotherapy. All patients had metastases in the axillary lymph nodes, but no clinical evidence of systemic disease. Prognostic factors were relatively equally distributed among the three treatment arms. All patients received adjuvant chemotherapy consisting of cytoxan, methotrexate, and 5-fluorouracil (CMF). In addition, patients received adjuvant immunotherapy consisting of Bacille Calmette Guerin (BCG) or BCG plus a tumor cell vaccine. This vaccine was a mixture of allogeneic breast cancer cell lines grown in tissue culture. Fourteen patients receiving tumor cell vaccine developed hepatitis B, leading to the abandonment of this arm of the study. Side effects of chemotherapy were tolerable. No statistically significant difference could be demonstrated in recurrence rate or survival. However, the two groups receiving adjuvant chemo-immunotherapy had a slightly shorter time to recurrence and lower overall survival. The use of chemo-immunotherapy as administered in this study did not improve the clinical course of patients with Stage II breast cancer and was associated with significant morbidity.

Effects of grinding and storage for one month on retention of vitamin A in premixes and mineral supplements.

Tested standardized procedures for handling premixes and mineral supplements from time of sampling to time of analysis for vitamin A have not been developed, which could account for some unexplained inconsistent and low analytical results. Grinding premix samples and storing them in a freezer for one month had little effect on amount of vitamin A found, but there was a significant loss (about 10%) after storage for one month at room temperature. Results on replicated determinations of vitamin A in unground and ground mineral supplements and on effect of storage were somewhat more variable than for premixes, but only the loss (about 12%) during storage for one month at room temperature was significant.

Effects of chromium supplementation on urinary Cr excretion of human subjects and correlation of Cr excretion with selected clinical parameters.

Daily urinary chromium (Cr) excretion of 15 healthy free-living female subjects was 0.20 +/- 0.03 microgram (mean +/- SEM) and nearly identical for 27 male subjects, 0.17 +/- 0.02 microgram. Minimum Cr absorption calculated from urinary Cr excretion was about 0.4 percent. Increasing intake fivefold by Cr supplementation led to a nearly fivefold increase in Cr excretion suggesting that the extent of absorption of supplemental inorganic chromium was similar to that from normal dietary sources. Correlations between 24-hour Cr excretion and urine volume, age, total creatinine and body weight were not found. Urinary Cr concentration of samples obtained following a morning void correlated with creatinine and Cr concentration following a glucose challenge but not with serum glucose, insulin, lipid parameters, age or body weight. Similar results were obtained for urine samples obtained from subjects during Cr supplementation. These results suggest that urinary Cr excretion does not appear to be a meaningful indicator of Cr status but is a meaningful indicator of Cr intake and that the absorption of supplemental inorganic Cr was similar to that of Cr from normal dietary sources.

Urinary chromium excretion of human subjects: effects of chromium supplementation and glucose loading.

The utilization of inorganic chromium by free-living human subjects was studied in 76 volunteers (male, 48; female, 28) who were supplemented with 200 micrograms of inorganic chromium as chromic chloride or a placebo tablet for 3 months in a double-blind, cross-over experiment. For all subjects, initial mean +/- SEM urinary chromium (Cr) level was 0.20 +/- 0.01 (range, 0.05 to 0.58) ng/ml and did not differ by sex. Initial chromium/creatinine ratio (Cr/Ct) was 0.15 +/- 0.01 (range 0.03 to 0.36) ng Cr/mg creatinine for females and was significantly lower, 0.10 +/- 0.01 (range 0.03 to 0.36) for males. Mean urinary Cr level increased to 1.0 +/- 0.12 after 2 and to 1.13 +/- 0.08 ng/ml after 3 months' supplementation. The Cr/Ct ratio increased to 0.69 +/- 0.10 for females and to 0.50 +/- 0.04 for males after 2 months' supplementation; values were similar after 3 months. An increase in urinary Cr excretion in response to a glucose load was demonstrated for nonsupplemented normal free-living subjects but not for subjects supplemented daily with trivalent chromium. Urinary Cr excretion after a glucose challenge was not predictable and did not depend on Cr status.